New Cancer Research

 1: J Nippon Med Sch. 2009 Jun;76(3):148-53.  The effect of doxazosin mesilate on cerebral blood flow in patients with hypertension and chronic cerebral infarction.  Usuda K, Katayama Y.  Department of Neurological, Nephrological and Rheumatological Science, Graduate School of Medicine, Nippon Medical School.  alpha(1)-Adrenoceptor antagonists are useful antihypertensive agents for patients with hypertension who have hyperlipidemia, benign prostatic hyperplasia, or pheochromocytoma. The purpose of this study was to evaluate the effect of the alpha(1)-adrenoceptor antagonist, doxazosin mesilate, on cerebral blood flow (CBF) and flow velocity in the common carotid artery in patients with hypertension and chronic cerebral infarction. Doxazosin mesilate (1 mg/day) was orally administered for 4 to 8 weeks to 7 patients with hypertension 4 weeks after the onset of cerebral infarction. We determined blood pressure, heart rate, CBF measured with autoradiography single photon emission computed tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine ((123)I-IMP) as a tracer, and the maximum, minimum and mean flow velocities in the common carotid arteries measured with duplex carotid ultrasonography before and 4 to 8 weeks after the beginning of treatment. Mean CBF was defined as the mean count of tracer from the 8 regions of interest (ROIs) in the frontal, parietal, occipital, and temporal cortices of the cerebral hemisphere. Values were analyzed with paired t tests. With administration of doxazosin mesilate, systolic pressure significantly decreased from 152 +/- 11 to 137 +/- 7 mmHg (p<0.01), but diastolic pressure and  heart rate were unchanged. Mean CBF was improved significantly from 32.0 +/- 4.1  to 34.7 +/- 4.1 mL/100 g brain/min (p<0.01) in the ipsilateral cerebral cortex and from 32.6 +/- 6.2 to 36.2 +/- 5.1 mL/100 g brain/min (p<0.05) in the contralateral cerebral cortex. The maximum, minimum, and mean flow velocities in  the bilateral common carotid arteries were not changed significantly. In the present study, the improvement of mean CBF in the ipsilateral and contralateral cerebral cortices was demonstrated in patients with hypertension and chronic cerebral infarction after the treatment with doxazosin mesilate. Doxazosin mesilate might be an effective antihypertensive agent for hypertensive chronic cerebral infarction.  PMID: 19602821 [PubMed - in process]  2: Int J Urol. 2009 Jun 26. [Epub ahead of print]  Comparison of photoselective vaporization and standard transurethral resection of the prostate on urodynamics in patients with benign prostatic hyperplasia.  Nomura H, Seki N, Yamaguchi A, Naito S.  Division of Urology, Harasanshin Hospital, Fukuoka, Japan.  Objectives: To compare photoselective vaporization of the prostate (PVP) and transurethral resection of the prostate (TURP) in patients with benign prostatic  hyperplasia. Methods: Patients were enrolled in a prospective non-randomized trial and underwent PVP (n = 78) and TURP (n = 51). Primary outcome variables included: International Prostate Symptom Score, quality-of-life score, urinary peak flow and post-void residual urine volume at 3, 6 and 12 months postoperatively. Secondary outcomes were urodynamic variables, including the index of bladder outlet obstruction (BOO) and detrusor contractility. Results: Improvement in all outcome variables after PVP was comparable to that after TURP  within 12 months. Outcome based on urodynamic parameters was also similar. Pre/post median value of the BOO index was 63/2 in the PVP group and 61/5 in the  TURP group. Pre/post rate of detrusor overactivity was 49%/27% in the PVP and 53%/29% in the TURP group. There was minimal change in detrusor contractility. Overall, morbidity was comparable in the two groups. Conclusions: The 12-month outcome after PVP is similar to that of TURP with an effective relief from BOO and detrusor overactivity and minimal change in detrusor contractility.  PMID: 19602003 [PubMed - as supplied by publisher]  3: Int J Urol. 2009 Jun 26. [Epub ahead of print]  Editorial comments to Comparison of photoselective vaporization and standard transurethral resection of the prostate on urodynamics in patients with benign prostatic hyperplasia.  Sugimura Y.  Mie University Graduate School of Medicine, Department of Nephro-Urologic Surgery and Andrology, Tsu, Mie, Japan sugimura@clin.medic.mie-u.ac.jp.  PMID: 19602002 [PubMed - as supplied by publisher]  4: Anticancer Agents Med Chem. 2009 Jul;9(6):642-60.  Advances in development of inhibitors of 17beta hydroxysteroid dehydrogenases.  Poirier D.  Laboratory of Medicinal Chemistry, CHUQ (CHUL) Research Center and Laval University, 2705 Laurier Boulevard, Québec (Québec) G1V4G2, Canada. donald.poirier@crchul.ulaval.ca  The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are involved in the regulation of estrogens and androgens by catalyzing the reduction of 17-ketosteroids or the oxidation of 17beta hydroxysteroids. The enzyme activities associated with the different 17beta-HSD isoforms are widespread in human tissues, not only in classic steroidogenic tissues but also in a large series of  peripheral intracrine tissues. Being involved at the end of steroidogenesis, the  numerous members of 17beta-HSD family constitute interesting therapeutic targets  for controlling the concentration of estrogens and androgens. Thus, inhibitors of reductive 17beta-HSD isoforms are attractive to block the formation of hydroxysteroids that stimulate estrogeno-sensitive pathologies (breast, ovarian,  and endometrium cancers) and androgeno-sensitive pathologies (prostate cancer, benign prostatic hyperplasia, acne, and hirsutism). The inhibitors could be used  to block the degradation of estradiol, an attractive strategy for treating osteoporosis and Alzheimer's disease. In addition to their classical use as anti-cancer agents and therapeutic agents, inhibitors of 17beta-HSDs are also useful tools to elucidate the role of these enzymes in particular biological systems. The present review article gives a description of novel inhibitors of 17beta-HSDs that were published in 2003-2006.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19601747 [PubMed - in process]  5: Neurourol Urodyn. 2009;28(3):197-201.  Analysis of the prognostic factors for overactive bladder symptoms following surgical treatment in patients with benign prostatic obstruction.  Seki N, Yuki K, Takei M, Yamaguchi A, Naito S.  Department of Urology, Graduate School of Medicine Sciences, Kyushu University, Fukuoka, Japan. narihito@uro.med.kyushu-u.ac.jp  AIMS: To identify the prognostic variables concerning the improvement of overactive bladder syndrome (OAB) related symptoms following a transurethral resection of the prostate (TURP) in patients with benign prostatic obstruction (BPO). METHODS: A retrospective review was conducted in 298 patients with BPO who had undergone TURP. All patients had completed the preoperative evaluations including OAB related symptoms and full urodynamics, as well as symptomatic assessment postoperatively. OAB related symptoms were defined by the International Prostate Symptom Score questionnaires (questions 2, 4 and 7 stand for frequency, urgency and nocturia). They were divided into three categories based on an individual score >or=3 for on urgency, frequency and nocturia in the  preoperative state. The association between the baseline variables and the improvement in each symptom score was analyzed. RESULTS: A multivariate analysis  suggested that the baseline degree of detrusor contractility was consistently associated with the improvement in each OAB symptom (The odds ratio in normal/weak detrusor: 9.5, 3.4, 3.0 for score on urgency, frequency and nocturia, respectively). Both the patient's age (Odds ratio: 0.93) and the maximum flow rate (Odds ratio: 0.20) influenced the improvement in the score on nocturia. CONCLUSION: The observation of a positive and consistent correlation between the  baseline degree of detrusor contractility and the improvement in OAB related symptoms, suggests that good detrusor contractility is essential for the symptomatic benefits after the surgical relief of bladder outlet obstruction. Aging males with good urinary flow rates appear to experience a reduced improvement of nocturia symptoms after undergoing TURP.  PMID: 18973143 [PubMed - indexed for MEDLINE] 

 1: Br J Cancer. 2009 Jul 14. [Epub ahead of print]  Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours.  Jacob K, Albrecht S, Sollier C, Faury D, Sader E, Montpetit A, Serre D, Hauser P, Garami M, Bognar L, Hanzely Z, Montes JL, Atkinson J, Farmer JP, Bouffet E, Hawkins C, Tabori U, Jabado N.  Department of Pediatrics and Human Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada.  Background:Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade astrocytomas (LGA), are common, heterogeneous and poorly understood subset of brain tumours in children. Chromosomal 7q34 duplication leading to fusion genes formed between KIAA1549 and BRAF and subsequent constitutive activation of BRAF was recently identified in a proportion of LGA, and may be involved in their pathogenesis. Our aim was to investigate additional chromosomal unbalances in LGA and whether incidence of 7q34 duplication is associated with tumour type or location.Methods and results:Using Illumina-Human-Hap300-Duo and 610-Quad high-resolution-SNP-based arrays and quantitative PCR on genes of interest, we investigated 84 paediatric LGA. We demonstrate that 7q34 duplication is specific  to sporadic JPA (35 of 53 - 66%) and does not occur in other LGA subtypes (0 of 27) or NF1-associated-JPA (0 of 4). We also establish that it is site specific as it occurs in the majority of cerebellar JPA (24 of 30 - 80%) followed by brainstem, hypothalamic/optic pathway JPA (10 of 16 - 62.5%) and is rare in hemispheric JPA (1 of 7 - 14%). The MAP-kinase pathway, assessed through ERK phosphorylation, was active in all tumours regardless of 7q34 duplication. Gain of function studies performed on hTERT-immortalised astrocytes show that overexpression of wild-type BRAF does not increase cell proliferation or baseline MAPK signalling even if it sensitises cells to EGFR stimulation.Conclusions and inte:Our results suggest that variants of JPA might arise from a unique site-restricted progenitor cell where 7q34 duplication, a hallmark of this tumour-type in association to MAPK-kinase pathway activation, potentially plays a site-specific role in their pathogenesis. Importantly, gain of function abnormalities in components of MAP-Kinase signalling are potentially present in all JPA making this tumour amenable to therapeutic targeting of this pathway.British Journal of Cancer advance online publication, 14 July 2009; doi:10.1038/sj.bjc.6605179 www.bjcancer.com.  PMID: 19603027 [PubMed - as supplied by publisher]  2: JAMA. 2009 Jul 15;302(3):276-89.  Comment in:     JAMA. 2009 Jul 15;302(3):325-6.  Monosomy of chromosome 10 associated with dysregulation of epidermal growth factor signaling in glioblastomas.  Yadav AK, Renfrow JJ, Scholtens DM, Xie H, Duran GE, Bredel C, Vogel H, Chandler  JP, Chakravarti A, Robe PA, Das S, Scheck AC, Kessler JA, Soares MB, Sikic BI, Harsh GR, Bredel M.  Department of Neurological Surgery, Northwestern Brain Tumor Institute, Lurie Center for Cancer Genetics Research, Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3015, USA.  CONTEXT: Glioblastomas--uniformly fatal brain tumors--often have both monosomy of chromosome 10 and gains of the epidermal growth factor receptor (EGFR) gene locus on chromosome 7, an association for which the mechanism is poorly understood. OBJECTIVES: To assess whether coselection of EGFR gains on 7p12 and monosomy 10 in glioblastomas promotes tumorigenic epidermal growth factor (EGF) signaling through loss of the annexin A7 (ANXA7) gene on 10q21.1-q21.2 and whether ANXA7 acts as a tumor suppressor gene by regulating EGFR in glioblastomas. DESIGN, SETTING, AND PATIENTS: Multidimensional analysis of gene, coding sequence, promoter methylation, messenger RNA (mRNA) transcript, protein data for ANXA7 (and EGFR), and clinical patient data profiles of 543 high-grade gliomas from US  medical centers and The Cancer Genome Atlas pilot project (made public 2006-2008; and unpublished, tumors collected 2001-2008). Functional analyses using LN229 and U87 glioblastoma cells. MAIN OUTCOME MEASURES: Associations among ANXA7 gene dosage, coding sequence, promoter methylation, mRNA transcript, and protein expression. Effect of ANXA7 haploinsufficiency on EGFR signaling and patient survival. Joint effects of loss of ANXA7 and gain of EGFR expression on tumorigenesis. RESULTS: Heterozygous ANXA7 gene deletion is associated with significant loss of ANXA7 mRNA transcript expression (P = 1 x 10(-15); linear regression) and a reduction (mean [SEM]) of 91.5% (2.3%) of ANXA7 protein expression compared with ANXA7 wild-type glioblastomas (P = .004; unpaired t test). ANXA7 loss of function stabilizes the EGFR protein (72%-744% increase in EGFR protein abundance) and augments EGFR transforming signaling in glioblastoma  cells. ANXA7 haploinsufficiency doubles tumorigenic potential of glioblastoma cells, and combined ANXA7 knockdown and EGFR overexpression promotes tumorigenicity synergistically. The heterozygous loss of ANXA7 in approximately 75% of glioblastomas in the The Cancer Genome Atlas plus infrequency of ANXA7 mutation (approximately 6% of tumors) indicates its role as a haploinsufficiency  gene. ANXA7 mRNA transcript expression, dichotomized at the median, associates with patient survival in 191 glioblastomas (log-rank P = .008; hazard ratio [HR], 0.667; 95% confidence interval [CI], 0.493-0.902; 46.9 vs 74.8 deaths/100 person-years for high vs low ANXA7 mRNA expression) and with a separate group of  180 high-grade gliomas (log-rank P = .00003; HR, 0.476; 95% CI, 0.333-0.680; 21.8 vs 50.0 deaths/100 person-years for high vs low ANXA7 mRNA expression). Deletion  of the ANXA7 gene associates with poor patient survival in 189 glioblastomas (log-rank P = .042; HR, 0.686; 95% CI, 0.476-0.989; 54.0 vs 80.1 deaths/100 person-years for wild-type ANXA7 vs ANXA7 deletion). CONCLUSION: Haploinsufficiency of the tumor suppressor ANXA7 due to monosomy of chromosome 10 provides a clinically relevant mechanism to augment EGFR signaling in glioblastomas beyond that resulting from amplification of the EGFR gene.  Publication Types:      Research Support, N.I.H., Extramural     Research Support, Non-U.S. Gov't  PMID: 19602687 [PubMed - in process]  3: JAMA. 2009 Jul 15;302(3):261-75.  Comment in:     JAMA. 2009 Jul 15;302(3):325-6.  A network model of a cooperative genetic landscape in brain tumors.  Bredel M, Scholtens DM, Harsh GR, Bredel C, Chandler JP, Renfrow JJ, Yadav AK, Vogel H, Scheck AC, Tibshirani R, Sikic BI.  Department of Neurological Surgery, Northwestern Brain Tumor Institute and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of  Medicine, Chicago, IL 60611-3015, USA. m-bredel@northwestern.edu  CONTEXT: Gliomas, particularly glioblastomas, are among the deadliest of human tumors. Gliomas emerge through the accumulation of recurrent chromosomal alterations, some of which target yet-to-be-discovered cancer genes. A persistent question concerns the biological basis for the coselection of these alterations during gliomagenesis. OBJECTIVES: To describe a network model of a cooperative genetic landscape in gliomas and to evaluate its clinical relevance. DESIGN, SETTING, AND PATIENTS: Multidimensional genomic profiles and clinical profiles of 501 patients with gliomas (45 tumors in an initial discovery set collected between 2001 and 2004 and 456 tumors in validation sets made public between 2006  and 2008) from multiple academic centers in the United States and The Cancer Genome Atlas Pilot Project (TCGA). MAIN OUTCOME MEASURES: Identification of genes with coincident genetic alterations, correlated gene dosage and gene expression,  and multiple functional interactions; association between those genes and patient survival. RESULTS: Gliomas select for a nonrandom genetic landscape-a consistent  pattern of chromosomal alterations-that involves altered regions ("territories")  on chromosomes 1p, 7, 8q, 9p, 10, 12q, 13q, 19q, 20, and 22q (false-discovery rate-corrected P<.05). A network model shows that these territories harbor genes  with putative synergistic, tumor-promoting relationships. The coalteration of the most interactive of these genes in glioblastoma is associated with unfavorable patient survival. A multigene risk scoring model based on 7 landscape genes (POLD2, CYCS, MYC, AKR1C3, YME1L1, ANXA7, and PDCD4) is associated with the duration of overall survival in 189 glioblastoma samples from TCGA (global log-rank P = .02 comparing 3 survival curves for patients with 0-2, 3-4, and 5-7  dosage-altered genes). Groups of patients with 0 to 2 (low-risk group) and 5 to 7 (high-risk group) dosage-altered genes experienced 49.24 and 79.56 deaths per 100 person-years (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.10-2.40; Cox regression model P = .02), respectively. These associations with survival are validated using gene expression data in 3 independent glioma studies, comprising  76 (global log-rank P = .003; 47.89 vs 15.13 deaths per 100 person-years for high risk vs low risk; Cox model HR, 3.04; 95% CI, 1.49-6.20; P = .002) and 70 (global log-rank P = .008; 83.43 vs 16.14 deaths per 100 person-years for high risk vs low risk; HR, 3.86; 95% CI, 1.59-9.35; P = .003) high-grade gliomas and 191 glioblastomas (global log-rank P = .002; 83.23 vs 34.16 deaths per 100 person-years for high risk vs low risk; HR, 2.27; 95% CI, 1.44-3.58; P<.001). CONCLUSIONS: The alteration of multiple networking genes by recurrent chromosomal aberrations in gliomas deregulates critical signaling pathways through multiple,  cooperative mechanisms. These mutations, which are likely due to nonrandom selection of a distinct genetic landscape during gliomagenesis, are associated with patient prognosis.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19602686 [PubMed - in process]  4: Neurotoxicol Teratol. 2009 Jan 24. [Epub ahead of print]  Nonenzymatic role of acetylcholinesterase in neuritic sprouting: Regional changes in acetylcholinesterase and choline acetyltransferase after neonatal 6-hydroxydopamine lesions.  Slotkin TA, Ryde IT, Wrench N, Card JA, Seidler FJ.  Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710 USA.  Acetylcholinesterase (AChE) is postulated to play a nonenzymatic role in the development of neuritic projections. We gave the specific neurotoxin, 6-OHDA to rats on postnatal day (PN) 1, a treatment that destroys noradrenergic nerve terminals in the forebrain while producing reactive sprouting in the brainstem. AChE showed profound decreases in the forebrain that persisted in males over the  entire phase of major synaptogenesis, from PN4 through PN21; in the brainstem, AChE was increased. Parallel examinations of choline acetyltransferase, an enzymatic marker for cholinergic nerve terminals, showed a different pattern of 6-OHDA-induced alterations, with initial decreases in both forebrain and brainstem in males and regression toward normal by PN21; females were far less affected. The sex differences are in accord with the greater plasticity of the female brain and its more rapid recovery from neurotoxic injury; our findings indicate that these differences are present well before puberty. These results support the view that AChE is involved in neurite formation, unrelated to its enzymatic role in cholinergic neurotransmission. Further, the results for choline acetyltransferase indicate that early depletion of norepinephrine compromises development of acetylcholine systems, consistent with a trophic role for this neurotransmitter.  PMID: 19602385 [PubMed - as supplied by publisher]  5: Eur J Pharm Biopharm. 2009 Feb 6. [Epub ahead of print]  A fluorescence-based in vitro assay for drug interactions with breast cancer resistance protein (BCRP, ABCG2).  Mahringer A, Delzer J, Fricker G.  Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.  Purpose: To establish a fluorescence-based assay for drug interactions with the ABC-export-protein BCRP (ABCG2). Methods: BCRP expression was verified by immunostaining and Western blots in intact porcine brain capillaries, isolated endothelial cells (PBCECs) and MDCKII-cells over-expressing human wild-type BCRP  (MDCKII-hBCRP). Transport of fluorescent mitoxantrone across cells was determined to assess a preferred transport direction. Sensitivity of cultured cells versus mitoxantrone in absence and in presence of transport modulators was examined at increasing concentrations of the cytostatic using the AlamarBlue(TM) assay. In addition, cells were incubated with mitoxantrone in absence and presence of increasing concentrations of different compounds with the potential to interact with BCRP. Intracellular fluorescence accumulation was measured using a flow cytometer. Results: Isolated capillaries as well as 7 day old PBCECs showed expression of BCRP. Cell sensitivity to mitoxantrone significantly increased in presence of the BCRP inhibitors KO143 and GF120918. Transport of mitoxantrone across PBCEC monolayers was directed with P(app) (apical to basolateral) 5.6 x 10(-6)cm sec(-1) and (app) (basolateral to apical) 2.8 x 10(-5) cm sec(-1). FACS  analysis revealed a different extent of fluorescence accumulation dependent on kind and concentration of BCRP modulating compounds. Conclusions: The mitoxantrone based assay can be used as a rapid FACS screening system to assess drug interactions with BCRP at the blood-brain barrier and therefore represents a useful tool in drug profiling.  PMID: 19602370 [PubMed - as supplied by publisher] 

 1: Genes Chromosomes Cancer. 2009 Jul 14. [Epub ahead of print]  Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.  Hodge JC, Park PJ, Dreyfuss JM, Assil-Kishawi I, Somasundaram P, Semere LG, Quade BJ, Lynch AM, Stewart EA, Morton CC.  Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115.  Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including interstitial deletion of 7q. To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t tests demonstrates this matched design is critical to eliminate the confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the  only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosaicism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis. (c) 2009 Wiley-Liss, Inc.  PMID: 19603527 [PubMed - as supplied by publisher]  2: Mol Nutr Food Res. 2009 Jul 14. [Epub ahead of print]  Dietary sources of lignans and isoflavones modulate responses to estradiol in estrogen reporter mice.  Penttinen-Damdimopoulou PE, Power KA, Hurmerinta TT, Nurmi T, van der Saag PT, Mäkelä SI.  Functional Foods Forum, University of Turku, FI-20014 Turku, Finland. Fax: +33-1-69361119.  Dietary phytoestrogens, such as the lignan metabolite enterolactone (ENL) and the isoflavone genistein (GEN), are suggested to modulate the risk of estrogen-dependent disease (e.g., breast cancer) through regulation of estrogen signaling. However, the effects of complex food items containing lignans or isoflavones on estrogen receptor (ER) transactivation have not been assessed so far. In this study, the modulation of ER-mediated signaling by dietary sources of lignans (cereals and flaxseed) and isoflavones (soy) was studied in vivo. Adult ovariectomized 3xERE-luciferase (luc) reporter mice received isocaloric diets supplemented with flaxseed, rye, wheat, or soy for 40 h or two weeks, and an additional group of mice was challenged with 17beta-estradiol (E(2)) following the two-week dietary intervention. In non-E(2)-treated mice, soy diet induced luc expression in liver, mammary gland, and pituitary gland while the other diets had no effects. Interestingly, all diets modulated the E(2)-induced luc expression. In particular rye diet efficiently reduced E(2)-induced luc expression as well as uterine growth, the hallmark of estrogen action in vivo. It is concluded that dietary sources of lignans and isoflavones can modulate estrogen signaling in vivo. The results suggest intriguing possibilities for the modulation of the risk of estrogen-dependent diseases by dietary means.  PMID: 19603405 [PubMed - as supplied by publisher]  3: Cytotechnology. 2009 Jul 15. [Epub ahead of print]  Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action.  Huang Y, Liu Q, Liu K, Yagasaki K, Zhang G.  Laboratory of Molecular Pharmacology, School of Pharmacy, Yantai University, No.  30, Qing Quan Lu, Lai Shan Qu, 264005, Yantai, Shandong Province, China.  The effects of norcantharidin (NCTD) on the growth of highly-metastatic human breast cancer cells were investigated by in vitro and ex vivo assays. Our results indicated that norcantharidin inhibited the in vitro growth of human breast cancer MDA-MB-231 cell line in dose- and time-dependent manners after the cancer  cells were treated with norcantharidin at the concentrations of 6, 30 and 60 mumol/L for 24, 48 and 72 h. Moreover, the sera from the NCTD-treated rabbits after intravenous injection of NCTD at 15 and 30 min significantly suppressed the growth of the cancer cells ex vivo. The analyses by Hoechst 33258 staining and flow cytometry showed that the typical apoptotic morphological changes appeared and cell cycles arrested at G2/M phase in MDA-MB-231 cells after the cells were treated for 48 h with NCTD. In addition, NCTD down-regulated the expressions of anti-apoptotic protein Bcl-2 and up-regulated the expressions of pro-apoptotic protein Bax, eventually leading to the reduction of Bcl-2/Bax ratio in MDA-MB-231 cells. Furthermore, NCTD at concentrations of 6, 30 and 60 mumol/L dose-dependently reduced the phosphorylation of Akt and NF-kappaB expression in the breast cancer cell line. Induction of apoptosis and cell cycle arrest as well as reduction of Bcl-2/Bax ratio by NCTD may be the important mechanisms of action of NCTD suppressing the growth of MDA-MB-231 cells, which are associated with inhibition of the Akt and NF-kappaB signaling. Our findings suggest that norcantharidin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer.  PMID: 19603282 [PubMed - as supplied by publisher]  4: Curr Treat Options Oncol. 2009 Jul 15. [Epub ahead of print]  Current Understanding of Risk Factors for Ovarian Cancer.  Sueblinvong T, Carney ME.  Department of Obstetrics and Gynecology, John A Burn School of Medicine, 1319 Punahou St. suite #640, Honolulu, HI, 96826, USA.  OPINION STATEMENT: Ovarian cancer is the deadliest gynecologic cancer. Unlike many cancers such as breast, cervical and colon cancers, there is no easily clinically identifiable pre-malignant phase of this malignancy making early identification difficult. Similarly, unlike lung, head and neck, and skin cancers, there is not easily identifiable risk factor making prevention short of  oophorectomy difficult. Even so, theories as to the causative factors of ovarian  cancer continue to evolve making our understanding of the genesis of ovarian cancer more clear. Genetics, parity, environment, hormonal factors, and inflammation all play an important and pivotal role in the development of ovarian cancer. The most current understanding of these elements and their respective contribution to the development of this cancer are presented in this chapter.  PMID: 19603272 [PubMed - as supplied by publisher]  5: Breast Cancer Res Treat. 2009 Jul 15. [Epub ahead of print]  Clinical evaluation of chemotherapy response predictors developed from breast cancer cell lines.  Liedtke C, Wang J, Tordai A, Symmans WF, Hortobagyi GN, Kiesel L, Hess K, Baggerly KA, Coombes KR, Pusztai L.  Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, BO Box 301439, Houston, TX, 77030-1439, USA.  The goal of this study was to develop pharmacogenomic predictors in response to standard chemotherapy drugs in breast cancer cell lines and test their predictive value in patients who received treatment with the same drugs. Nineteen human breast cancer cell lines were tested for sensitivity to paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) in vitro. Baseline gene expression data were obtained for each cell line with Affymetrix U133A gene  chips, and multigene predictors of sensitivity were derived for each drug separately. These predictors were applied individually and in combination to human gene expression data generated with the same Affymetrix platform from fine  needle aspiration specimens of 133 stage I-III breast cancers. Tumor samples were obtained at baseline, and each patient received 6 months of preoperative TFAC chemotherapy followed by surgery. Cell line-derived prediction results were correlated with the observed pathologic response to chemotherapy. Statistically robust differentially expressed genes between sensitive and resistant cells could only be found for paclitaxel. False discovery rates associated with the informative genes were high for all other drugs. For each drug, the top 100 differentially expressed genes were combined into a drug-specific response predictor. When these cell line-based predictors were applied to patient data, there was no significant correlation between observed response and predicted response either for individual drug predictors or combined predictions. Cell line-derived predictors of response to four commonly used chemotherapy drugs did  not predict response accurately in patients.  PMID: 19603265 [PubMed - as supplied by publisher] 

 1: Oncogene. 2009 Jul 13. [Epub ahead of print]  Loss of Nkx3.1 leads to the activation of discrete downstream target genes during prostate tumorigenesis.  Song H, Zhang B, Watson MA, Humphrey PA, Lim H, Milbrandt J.  [1] Department of Pathology & Immunology, School of Medicine, Washington University at St Louis, St Louis, MO, USA [2] Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.  The expression of NKX3.1, a transcriptional regulator and tumor suppressor gene in prostate cancer, is downregulated during early stages of prostate tumorigenesis. However, little is known of the alterations in gene expression that occur as a result of this event. We combined laser capture microdissection and gene expression profiling to analyse the molecular consequences of Nkx3.1 loss during prostate cancer initiation using Nkx3.1-deficient mice. This analysis identified a cohort of genes (loss-of-Nkx3.1 signature) that are aberrantly overexpressed during loss-of-Nkx3.1-driven tumor initiation. We studied the expression of these genes in independent loss-of-Pten and c-myc overexpression prostate adenocarcinoma mouse models. Nkx3.1 expression is lost in prostate epithelial proliferation in both of these mouse models. However, Nkx3.1 loss is an early event of tumor development in the loss-of-Pten model, whereas it occurs  at later stages in c-myc transgenic mice. A number of genes of the loss-of-Nkx3.1 signature, such as clusterin and quiescin Q6, are highly expressed in prostatic hyperplasia and intraepithelial neoplasia (PIN) lesions that also lack Nkx3.1 in  the Pten-deficient prostate, but not in similar lesions in the c-myc transgenic model. Meta-analysis of multiple prostate cancer gene expression data sets, including those from loss-of-Nkx3.1, loss-of-Pten, c-myc overexpression and constitutively active Akt prostate cancer models, further confirmed that genes associated with the loss-of-Nkx3.1 signature integrate with PTEN-AKT signaling pathways, but do not overlap with molecular changes associated with the c-myc signaling pathway. In human prostate tissue samples, loss of NKX3.1 expression and corresponding clusterin overexpression are co-localized at sites of prostatic inflammatory atrophy, a possible very early stage of human prostate tumorigenesis. Collectively, these results suggest that the molecular consequences of NKX3.1 loss depend on the epithelial proliferative stage at which its expression is lost, and that alterations in the PTEN-AKT-NKX3.1 axis are important for prostate cancer initiation.Oncogene advance online publication, 13  July 2009; doi:10.1038/onc.2009.181.  PMID: 19597465 [PubMed - as supplied by publisher]  2: Zhonghua Wai Ke Za Zhi. 2009 Apr 1;47(7):545-7.  [The clinical observation of bipolar transurethral plasmakinetic resection of prostate for high risk benign prostate hyperplasia.]  [Article in Chinese]  Liu DY, Gu J, Zhang CY, Wang J, Tang Q, Zhou YF, Zhou WL, Wang MW, Zhu Y, Zhao JP.  Department of Urology, Punan Hospital, Shanghai 200125, China. Email: dr.liudingyi@yahoo.com.cn.  OBJECTIVE: To evaluate therapeutic effect and reliability of bipolar transurethral plasmakinetic prostatectomy (TUPKP) for high risk level binign prostatic hyperplasia (BPH). METHODS: A total of 230 cases of high risk of BPH were treated with TUPKP. Among them, 132 cases with the residual urine of 40 to 420 ml had accepted long term but inefficient medical therapy, 98 cases were suffered with repeating acute urinary retention. One hundred and seventy-three cases with the functional capacity > 4 MET were performed the standard transurethral resection of the prostate (TURP), the other 57 cases with the functional capacity < 4 MET were accepted the minimally invasive TURP. Among them 12 cases complicated with bladder stones accepted Ho: YAG lithotripsy priory. The international prostate symptom score (IPSS), The maximal urinary flow rate (Qmax) and residual urine of the 2 groups before and after operation were analyzed. RESULTS: There was no trensurethral resection syndrome occurred in both groups. After 3 to 12 months of follow-up postoperatively, the IPSS of the two groups were reduced from (21.9 +/- 5.7) and (23.7 +/- 5.0) to (4.4 +/- 2.3) and (5.5 +/- 2.4), residual urine were reduced from (61.8 +/- 18.4) ml and (103.9 +/- 77.3) ml to (13.0 +/- 6.2) ml and (15.8 +/- 6.1) ml, respectively. The Qmax was increased  from (5.7 +/- 3.0) ml/s and (4.8 +/- 2.8) ml/s to (20.9 +/- 6.3) ml/s and (16.8 +/- 3.9) ml/s, there existed significant differences (P < 0.01). However the IPSS, Qmax and residual urine of the standard group had progressed more obviously than the minimally invasive TURP group (P < 0.05). CONCLUSIONS: It is safe and effective to use TUPKP for treating high risk patients of BPH with classic TURP and minimally invasive TURP according to different functional capacity. When the  functional capacity is more than 4 MET, the standard procedures is prefered.  Publication Types:      English Abstract  PMID: 19595217 [PubMed - in process]  3: J Endourol. 2009 Jul 13. [Epub ahead of print]  Functional Results 1 Year After Laser Vaporization of the Prostate: The Impact of Age.  Buse S, Pfitzenmaier J, Wagener N, Haferkamp A, Hohenfellner M.  Departments of Urology and Pediatric Urology, University of Heidelberg Medical School , Heidelberg, Germany .  Abstract Purpose: To test the hypothesis that age affects functional results after 80W photoselective vaporization of the prostate (PVP). Patients and Methods: In 156 patients who were undergoing PVP for benign prostatic hyperplasia (BPH), we assessed the International Prostate Symptom Score (IPSS) and Quality of Life (QoL) score preoperatively and at 12 months. We calculated the association between age and IPSS and QoL results and corrected it for prostate-specific antigen (PSA) value, whose impact on PVP functional results is well accepted. Results: Median patient age was 66 years (interquartile range [IQR] 62-75), median preoperative IPSS 20.5 (IQR 15-25) and QoL 4 (IQR 3-5). At 12 months, the  median IPSS percent decrease was 58.8% (range 33%-75%), and the median QoL percent decrease was 66.7% (range 25%-80%). Age was independently associated with both (P < 0.05). In contrast, after adjustment for age, PSA was not significantly associated with percent IPSS decrease (P = 0.561), and its association with QoL was at the limit of significance (P = 0.05). Conclusions: Age independently and strongly affects IPSS and QoL results at 12 months after 80W PVP.  PMID: 19594373 [PubMed - as supplied by publisher] 

 1: Psychooncology. 2009 Jul 14. [Epub ahead of print]  First degree relatives of women with breast cancer: who's providing information and support and who'd they prefer.  Tunin R, Uziely B, Woloski-Wruble AC.  Speciality-Oncology, Hadassah Hebrew University Medical Centers, Jerusalem, Israel.  Introduction: Mothers, sisters, and daughters of women diagnosed with breast cancer have an increased need for factual information, counseling, and emotional  support. The purpose of this exploratory, descriptive study was to identify the information and support needs of Israeli women with a family history of breast cancer; discover whether these needs have been met, by whom, and who is the preferred source for them.Methods: 128 healthy Israeli women, aged 18-65, with a  first degree relative with breast cancer completed the adapted Information and Support Needs Questionnaire (ISNQ).Results: Information needs were ranked above support needs, especially information about disease prevention. The degree to which the needs were met was generally ranked as low, with response to the information needs ranking higher than the response to the support needs. The doctor was the prime source of choice for the information and support needs.Conclusion: This study contributes to the understanding of the needs of patients' families, provides a framework for the improvement of methods of communication, and a basis for constructing information and support systems. In addition, it highlights the need for a multidisciplinary, proactive approach in health promotion for cancer patients' families. Copyright (c) 2009 John Wiley & Sons, Ltd.  PMID: 19598293 [PubMed - as supplied by publisher]  2: Int J Cancer. 2009 May 18. [Epub ahead of print]  Drug-regulatable cancer cell death induced by BID under control of the tissue-specific, lung cancer-targeted TTS promoter system.  Fukazawa T, Maeda Y, Matsuoka J, Tanaka N, Tanaka H, Durbin ML, Naomoto Y.  Department of Gastroenterological Surgery, Okayama University Graduate School of  Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.  Gene therapy and virotherapy are among the approaches currently being used to treat lung cancer. The success of cancer gene therapy depends on treatments where different types of tumors can be selectively targeted and destroyed without affecting normal cells and tissue. Previously, we described a promoter system (TTS) that we designed that is specifically targeted to lung cancer cells but which does not affect other types of cells including stem cells. In our study, we have enhanced the utility of the TTS system by inserting the pro-apoptotic gene BH3 domain interacting death agonist (Bid) into the TTS promoter system (TTS/Bid) to create a drug regulatable lung cancer-specific gene therapy. A recombinant adenoviral vector was used to introduce TTS/Bid (Ad-TTS/Bid) into lung cancer cells. BID expression and apoptosis occurred in A549 pulmonary adenocarcinoma cells but little Bid expression or apoptosis occurred in MCF7 breast cancer cells or in normal human lung fibroblasts. The use of cisplatin enhanced the processing of full length BID to t-BID which significantly increased lung cancer-specific cell death. In in vivo experiments, intraperitonal injection of cisplatin enhanced the antitumor effects of the vector in a lung cancer xeno-graft mouse model. Moreover, dexamethasone effectively suppressed exogenous BID expression and the antitumor effect of Ad-TTS/Bid both in vitro and in vivo. Here, we describe the efficacy of the use of cisplatin and dexamethasone with the anti lung cancer promoter system (Ad-TTS/Bid) for a safe and effective gene therapy against advanced lung cancer. (c) 2009 UICC.  PMID: 19598260 [PubMed - as supplied by publisher]  3: Breast Cancer Res Treat. 2009 Jul 14. [Epub ahead of print]  Oral contraceptives and postmenopausal hormones and risk of contralateral breast  cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study.  Figueiredo JC, Haile RW, Bernstein L, Malone KE, Largent J, Langholz B, Lynch CF, Bertelsen L, Capanu M, Concannon P, Borg A, Børresen-Dale AL, Diep A, Teraoka S,  Torngren T, Xue S, Bernstein JL.  Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Harlyne J Norris Cancer Research Tower, 1450 Biggy Street, Los Angeles, CA, 90033, USA, janefigu@usc.edu.  The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH) use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation carriers with a history of breast cancer. We investigated the association between OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE (Women's Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study is a population-based case-control study of 705 women with asynchronous CBC and 1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation carriers. Risk-factor information was assessed by telephone interview. Mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing in all participants. Outcomes, treatment, and tumor characteristics were abstracted from medical records. Ever use of OCs was not associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66-1.15) or BRCA2 carriers (RR = 0.82; 95% CI = 0.21-3.13). BRCA1 carriers who used OCs had a nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72-7.83). Total  duration of OC use and at least 5 years of use before age 30 were associated with a nonsignificant increased risk among mutation carriers but not among noncarriers. Few women had ever used PMH and we found no significant associations between lifetime use and CBC risk among carriers and noncarriers. In conclusion,  the association between OC/PMH use and risk of CBC does not differ significantly  between carriers and noncarriers; however, because carriers have a higher baseline risk of second primaries, even a potential small increase in risk as a result of OC use may be clinically relevant.  PMID: 19597986 [PubMed - as supplied by publisher]  4: Breast Cancer Res Treat. 2009 Jul 14. [Epub ahead of print]  Impact of obesity on diagnosis and treatment of breast cancer.  Deglise C, Bouchardy C, Burri M, Usel M, Neyroud-Caspar I, Vlastos G, Chappuis PO, Ceschi M, Ess S, Castiglione M, Rapiti E, Verkooijen HM.  Geneva Cancer Registry, Institute of Social and Preventive Medicine, Geneva University, 55 Boulevard de la Cluse, 1205, Geneva, Switzerland.  In this population-based study, we evaluated the impact of obesity on presentation, diagnosis and treatment of breast cancer. Among all women diagnosed with invasive breast cancer in the canton Geneva (Switzerland) between 2003 and 2005, we identified those with information on body mass index (BMI) and categorized them into normal/underweight (BMI <25 kg/m(2)), overweight (BMI >/=-<30 kg/m(2)) and obese (BMI >/=30 kg/m(2)) women. Using multivariate logistic regression, we compared tumour, diagnosis and treatment characteristics between groups. Obese women presented significantly more often with stage III-IV disease  (adjusted odds ratio [OR(adj)]: 1.8, 95% CI: 1.0-3.3). Tumours >/=1 cm and pN2-N3 lymph nodes were significantly more often impalpable in obese than in normal/underweight patients (OR(adj) 2.4, [1.1-5.3] and OR(adj) 5.1, [1.0-25.4],  respectively). Obese women were less likely to have undergone ultrasound (OR(adj) 0.5, [0.3-0.9]) and MRI (OR(adj) 0.3, [0.1-0.6]) and were at increased risk of prolonged hospital stay (OR(adj) 4.7, [2.0-10.9]). This study finds important diagnostic and therapeutic differences between obese and lean women, which may impair survival of obese women with breast cancer. Specific strategies are needed to optimize the care of obese women with or at risk of breast cancer.  PMID: 19597985 [PubMed - as supplied by publisher]  5: Ann Surg Oncol. 2009 Jul 14. [Epub ahead of print]  Reply to "Preoperative Chemotherapy and Potential Impact on Re-Excision for Early Breast Cancer"  Christy CJ, Grube BJ, Lannin DR.  Department of Surgery, Yale University, New Haven, USA, carlajchristy@yahoo.com.  PMID: 19597888 [PubMed - as supplied by publisher] 

 1: Mass Spectrom Rev. 2009 Jul 13. [Epub ahead of print]  A review of current applications of mass spectrometry for neuroproteomics in epilepsy.  Liu X, Wen F, Yang J, Chen L, Wei YQ.  National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.  The brain is unquestionably the most fascinating organ, and the hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In temporal lobe epilepsy (TLE), the seizure origin typically involves  the hippocampal formation. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward an improved understanding of the complex molecular mechanisms that underlie functions of the brain and hippocampus is neuroproteomics. Mass spectrometry has  been widely used to analyze biological samples, and has evolved into an indispensable tool for proteomics research. In this review, we present a general  overview of the application of mass spectrometry in proteomics, summarize neuroproteomics and systems biology-based discovery of protein biomarkers for epilepsy, discuss the methodology needed to explore the epileptic hippocampus proteome, and also focus on applications of ingenuity pathway analysis (IPA) in disease research. This neuroproteomics survey presents a framework for large-scale protein research in epilepsy that can be applied for immediate epileptic biomarker discovery and the far-reaching systems biology understanding  of the protein regulatory networks. Ultimately, knowledge attained through neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the burden of epilepsy on society. (c) 2009 Wiley Periodicals, Inc., Mass Spec Rev.  PMID: 19598206 [PubMed - as supplied by publisher]  2: Nat Rev Neurol. 2009 Jul 14. [Epub ahead of print]  Advances in the genetics of glioblastoma: are we reaching critical mass?  Purow B, Schiff D.  Neuro-Oncology Division, Neurology Department, University of Virginia, Charlottesville, VA, USA.  Glioblastoma is the most common and highest-grade brain tumor, causing over 10,000 deaths each year in the US alone. Given the resistance of this tumor to standard surgery, radiation and chemotherapy, an understanding of the underlying  genetic lesions is vital. Recent efforts to comprehensively profile glioblastomas using the latest technologies, both by The Cancer Genome Atlas (TCGA) project and by other groups, are addressing this need. Some genetic aberrations in glioblastoma have been known for decades, but early output from the new profiling initiatives has further illuminated the relevant genetics in this disease. Some genetic lesions, such as TP53 mutation, NF1 deletion or mutation, and ERBB2 amplification, have been found to be more common than was previously reported. New and unexpected discoveries have also been made, such as frequent mutations of the IDH1 and IDH2 genes in secondary glioblastoma. We might be tempted to speculate that we are approaching a comprehensive knowledge of the genetic lesions involved in glioblastoma, although other major discoveries doubtless remain to be made. In addition, the complex task of incorporating our updated knowledge into new-and possibly personalized-therapies for patients with glioblastoma still lies ahead.  PMID: 19597514 [PubMed - as supplied by publisher]  3: Keio J Med. 2009 Jun;58(2):120-3.  Stereotactic radiosurgery with an upper partial denture.  Tayama S, Kunieda E, Oku Y, Takeda A, Takeda T.  Department of Dentistry and Oral Surgery, Tokyo Metropolitan Hiroo General Hospital.  A 54-year-old male with partial denture underwent stereotactic radiosurgery with  an infrared camera-guided system for a metastatic brain tumor arising from lung cancer. Although this method utilizes a biteplate mounted on the upper jaw to detect head movement, the patient only had four teeth in his upper jaw. In order  to stabilize the biteplate, the maxillary denture was fixed to the biteplate with an autopolymerizing resin. In addition, the rest-occlusal position of the lower jaw was impressed on the inferior surface of the biteplate with an autopolymerizing resin. To assess reproducibility and stability, the distance between the left and right incus and left and right markers was measured during pre-planning, as well as before and after stereotactic irradiation. Wearing the biteplate ensures the accuracy of radiotherapy planning for the implementation of radiosurgery in patients who have many maxillary teeth missing. However, a large  degree of error was observed when the biteplate was removed.  PMID: 19597308 [PubMed - in process]  4: Anticancer Res. 2009 Jul;29(7):2793-8.  Brain metastases from epithelial ovarian cancer: overview and optimal management.  Pietzner K, Oskay-Oezcelik G, El Khalfaoui K, Boehmer D, Lichtenegger W, Sehouli  J.  Department of Gynaecology and Obstetrics, Charité-Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. sehouli@aol.com.  Central nervous system involvement is a rare finding in the management of epithelial ovarian cancer with an incidence between 1-2%. A sharp rise in the incidence has been widely and repeatedly proclaimed for nearly two decades now, but has to be treated with scepticism after a careful review of the current literature. Brain metastases from ovarian cancer are known to be related to a very poor prognosis. Since brain imaging is not part of the routine follow-up care for ovarian cancer patients, and since CA-125 - one of the standard tools -  cannot be relied upon to detect central nervous system relapse, brain lesions are mostly traced by unspecific neurological symptoms only. Several prognostic factors are still being discussed today. But only a high performance status and the absence of an extra cranial disease at the time of CNS relapse have been accepted throughout the current literature as having a highly significant positive impact on survival. In the past, therapeutic efforts have focused on symptom palliation with corticosteroids and whole-brain radiation therapy (WBRT). During the last years several other therapy options have evolved from encouraging efforts made by several study groups, including chemotherapy, neurosurgery and radiosurgery. It has been shown that a multi-modal approach, combining these strategies, promises the best prolongation of survival and in some cases even resulted in long-term remissions. The present article gives an overview of brain  metastases in epithelial ovarian cancer and discusses the current treatment options.  PMID: 19596963 [PubMed - in process]  5: Anticancer Res. 2009 Jul;29(7):2641-4.  Does distance to treatment centre influence the rate of palliative radiotherapy in adult cancer patients?  Nieder C, Norum J, Spanne O, Bilberg I, Vagstad G, Dalhaug A.  Radiation Oncology Unit, Department of Internal Medicine, Nordlandssykehuset HF,  8092 Bodø, Norway. carsten.nieder@nlsh.no.  Previous reports suggest that age, household income and travel distance from residence to treatment facility are barriers which influence access to radiotherapy. The purpose of this study was to analyse the utilisation of palliative radiotherapy in a health care system where the main goal is equal access despite place of residence. The Authors collected prospective data on the  use of palliative radiotherapy in adult cancer patients over a 12-month period in 2007/2008. All patients were treated in northern Norway and had unlimited, rapid  access to treatment. Efforts were made to account for potential overuse. The patients were divided into three groups according to travel distance. The majority of irradiated patients had bone metastases, followed by non-bony thoracic targets and brain metastases. No statistically significant differences in the utilisation rates were detected, the latter ranging from 129 annual treatment courses per 100,000 inhabitants in the region furthest away from the hospital to 142 courses in that closest to it. The median age of the irradiated patients in the three groups was similar. In conclusion, these data suggest that  the utilisation of palliative radiotherapy in a health care system without financial barriers to treatment no longer varies with distance between residence  and hospital.  PMID: 19596940 [PubMed - in process] 

 1: Proc Natl Acad Sci U S A. 2009 Jul 10. [Epub ahead of print]  ETS family transcription factors collaborate with alternative signaling pathways  to induce carcinoma from adult murine prostate cells.  Zong Y, Xin L, Goldstein AS, Lawson DA, Teitell MA, Witte ON.  Howard Hughes Medical Institute.  Chromosomal rearrangements involving erythroblast transformation specific (ETS) family transcription factors were recently defined as the most common genetic alterations in human prostate cancer. Despite their prevalence, it is unclear what quantitative role they play in either initiation or progression of the disease. Using a lentiviral transduction and dissociated cell prostate regeneration approach, we find that acutely increased expression of ETS proteins  in adult murine prostate epithelial cells is sufficient to induce the formation of epithelial hyperplasia and focal prostatic intraepithelial neoplasia (PIN) lesions, but not progression to carcinoma. However, combined expression of ERG with additional genetic alternations associated with human prostate cancer can lead to aggressive disease. Although ERG overexpression does not cooperate with loss of the tumor suppressor p53, it does collaborate with alterations in PI3K signaling, such as Pten knockdown or AKT up-regulation, to produce a well-differentiated adenocarcinoma. Most striking is our finding that overexpression of androgen receptor (AR) does not give rise to any hyperplastic lesions, but when combined with high levels of ERG, it promotes the development of a more poorly differentiated, invasive adenocarcinoma. These findings suggest  that in human prostate cancer, the most potent function of ETS gene fusions may be to synergize with alternative genetic events and provide different pathways for carcinoma production and invasive behavior. Our results provide direct evidence for selective cooperating events in ERG-induced prostate tumorigenesis and offer a rational basis for combined therapeutic interventions against multiple oncogenic pathways in prostate cancer.  PMID: 19592505 [PubMed - as supplied by publisher]  2: J Endourol. 2009 Jul 10. [Epub ahead of print]  Robot-Assisted Laparoscopic Bladder Diverticulectomy Combined with Photoselective Vaporization of Prostate: A Case Report and Review of Literature.  Kural AR, Atug F, Akpinar H, Tufek I.  1 Department of Urology, Istanbul University Cerrahpasa School of Medicine , Istanbul, Turkey .  Abstract Purpose: Open surgery, endoscopic technique, and standard laparoscopic technique are surgical options for the management of bladder diverticuli. In this article, we report robot-assisted bladder diverticulectomy (RABD) and photoselective vaporization of prostate (PVP) in the same patient sequentially. To the best of our knowledge, this is the first case report of RABD combined with PVP. Materials and Methods: A 63-year-old patient with benign prostatic hyperplasia and a secondary large bladder diverticulum underwent sequential PVP and RABD. Cystoscopic examination revealed obstructing prostate lobes and a large diverticulum at posterior wall of bladder. After completion of PVP procedure, a 16F urethral catheter was inserted into the diverticulum via outer sheath of optic urethrotome and another 16F urethral catheter was left in bladder for urinary drainage. A transperitoneal approach was preferred. The diverticulum was  distended with saline infusion via the Foley catheter inside the diverticulum. The distended diverticulum was seen easily and dissected from the surrounding tissue. The bladder was closed in two separate layers. Results: Total operative time, including diverticulectomy with PVP procedure, was 230 minutes, and console time was 90 minutes. The length of stay was 7 days. Conclusions: There has been always concern about the high intravesical pressures secondary to irrigant instillation that may disrupt the bladder repair. To avoid this problem we combined robotic diverticulectomy with PVP. Because of hemostatic properties of potassium-titanyl-phosphate laser, we did not encounter with bleeding after prostatectomy procedure. Moreover, we did not use irrigation, and the suture line of the bladder was kept safe. Therefore, we recommend to use greenlight laser in  combined prostate and RABD operations. RABD is a feasible and safe procedure. RABD and PVP can be performed safely in the same patient sequentially.  PMID: 19591613 [PubMed - as supplied by publisher]  3: Drug Saf. 2009;32(8):637-47. doi: 10.2165/00002018-200932080-00003.  Serenoa repens (Saw Palmetto): A Systematic Review of Adverse Events.  Agbabiaka TB, Pittler MH, Wider B, Ernst E.  Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, Exeter, United Kingdom.  Serenoa repens (W. Bartram) Small, also known as saw palmetto, is one of the most widely used herbal preparations for the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Although a number of randomized controlled trials (RCTs) and systematic reviews of the efficacy of S. repens for  the treatment of LUTS and BPH have been published, no systematic review on its drug interactions or adverse events currently exists. This review assesses all available human safety data of S. repens monopreparations. Systematic literature  searches were conducted from date of inception to February 2008 in five electronic databases; reference lists and our departmental files were checked for further relevant publications. Information was requested from spontaneous reporting schemes of the WHO and national safety bodies. Twenty-four manufacturers/distributors of S. repens preparations and four herbalist organizations were contacted for additional information. No language restrictions were imposed. Only reports of adverse events in humans from monopreparations of S. repens were included. Data from all articles, regardless of study design, reporting adverse events or interactions were independently extracted by the first author and validated by the second. Forty articles (26 randomized controlled trials, 4 non-randomized controlled trials, 6 uncontrolled trials and  4 case reports/series) were included. They suggest that adverse events associated with the use of S. repens are mild and similar to those with placebo. The most frequently reported adverse events are abdominal pain, diarrhoea, nausea, fatigue, headache, decreased libido and rhinitis. More serious adverse events such as death and cerebral haemorrhage are reported in isolated case reports and  data from spontaneous reporting schemes, but causality is questionable. No drug interactions were reported. Currently available data suggest that S. repens is well tolerated by most users and is not associated with serious adverse events. The majority of adverse events are mild, infrequent and reversible, and include abdominal pain, diarrhoea, nausea and fatigue, headache, decreased libido and rhinitis. We found no evidence for drug interactions with S. repens. However, higher quality reporting of adverse events is essential if safety assessments are to be improved in future.  PMID: 19591529 [PubMed - in process] 

 1: Cell Motil Cytoskeleton. 2009 Jul 10. [Epub ahead of print]  Profilin-1 overexpression restores adherence junctions in MDA-MB-231 breast cancer cells in R-cadherin-dependent manner.  Zou L, Hazan R, Roy P.  Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania.  Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, is downregulated in several different types of adenocarcinoma and elicits tumor-suppressive effect on breast cancer cell lines. MDA-MB-231 (MDA-231), a breast cancer cell line that displays all the characteristics of post-epithelial-to-mesenchymal transition and does not form cell-cell adhesion, can be reverted to an epithelioid phenotype by Pfn1 overexpression. This morphological transition is caused by restoration of adherence junctions (AJ) requiring Pfn1's interaction with actin. Pfn1 overexpression increases the expression level of R-cadherin (a type of cadherin that is endogenously expressed in the parental cell line) and restores AJ in MDA-231 cells in R-cadherin-dependent manner. These findings highlight important role of Pfn1 in the regulation of epithelial cell-cell adhesion. Cell Motil. Cytoskeleton 2009. (c) 2009 Wiley-Liss, Inc.  PMID: 19593789 [PubMed - as supplied by publisher]  2: J Pathol. 2009 Jun 1. [Epub ahead of print]  MicroRNA expression profiling of human metastatic cancers identifies cancer gene  targets.  Baffa R, Fassan M, Volinia S, O'Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M,  Gomella LG, Croce CM, Rosenberg A.  Department of Urology, Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA, USA.  Small non-coding microRNAs (miRNAs) contribute to cancer development and progression, and are differentially expressed in normal tissues and cancers. However, the specific role of miRNAs in the metastatic process is still unknown.  To seek a specific miRNA expression signature characterizing the metastatic phenotype of solid tumours, we performed a miRNA microarray analysis on 43 paired primary tumours (ten colon, ten bladder, 13 breast, and ten lung cancers) and one of their related metastatic lymph nodes. We identified a metastatic cancer miRNA  signature comprising 15 overexpressed and 17 underexpressed miRNAs. Our results were confirmed by qRT-PCR analysis. Among the miRNAs identified, some have a well-characterized association with cancer progression, eg miR-10b, miR-21, miR-30a, miR-30e, miR-125b, miR-141, miR-200b, miR-200c, and miR-205. To further  support our data, we performed an immunohistochemical analysis for three well-defined miRNA gene targets (PDCD4, DHFR, and HOXD10 genes) on a small series of paired colon, breast, and bladder cancers, and one of their metastatic lymph nodes. We found that the immunohistochemical expression of these targets significantly follows the corresponding miRNA deregulation. Our results suggest that specific miRNAs may be directly involved in cancer metastasis and that they  may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets. Copyright (c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.  PMID: 19593777 [PubMed - as supplied by publisher]  3: Cell Biochem Biophys. 2009 Jul 11. [Epub ahead of print]  Altered Expression of Proliferation-Inducing and Proliferation-Inhibiting Genes Might Contribute to Acquired Doxorubicin Resistance in Breast Cancer Cells.  Saleh EM, El-Awady RA, Abdel Alim MA, Abdel Wahab AH.  Biochemistry Unit, Tumour Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt, ekramsaleh@hotmail.com.  This study was designed to investigate the molecular changes that may develop during exposure of breast cancer cells to anticancer agents and that may lead to  acquired resistance. We used two breast cancer cell lines, a parental (MCF7/WT) and a doxorubicin-resistant (MCF7/DOX) one. Cell survival, cell cycle distribution and RT-PCR expression level of genes involved in DNA damage response, MDR1, GST and TOPOIIalpha were measured. MCF7/DOX cells were five-fold  more resistant to doxorubicin (DOX) than the MCF7/WT cells. DOX treatment causes  arrest of MCF7/DOX cells in G1 and G2 phases of cell cycle whereas MCF7/WT cells  were arrested in S-phase. The molecular changes in both cell lines due to DOX treatment could be classified into: (1) the basal level of p53, p21, BRCA1, GST and TOPOIIalpha mRNA was higher in MCF7/DOX than MCF7/WT. During DOX treatment, the expression level of these genes decreased in both cell lines but the rate of  down-regulation was faster in MCF7/WT than MCF7/DOX cells. (2) The expression level of MDR1 was the same in both cell lines but 48 and 72 h of drug treatment,  MDR1 disappeared in MCF7/WT but still expressed in MCF7/DOX. (3) There was no change in the expression level of BAX, FAS and BRCA2 in both cell lines. Conclusively, after validation in clinical samples, overexpression of genes like  BRCA1, p53, p21, GST, MDR1 and TOPOIIalpha could be used as a prognostic biomarker for detection of acquired resistance in breast cancer and as therapeutic targets for the improvement of breast cancer treatment strategies.  PMID: 19593673 [PubMed - as supplied by publisher]  4: Breast Cancer Res Treat. 2009 Jul 11. [Epub ahead of print]  E-cadherin mediates the aggregation of breast cancer cells induced by tamoxifen and epidermal growth factor.  Mauro L, Pellegrino M, Lappano R, Vivacqua A, Giordano F, Palma MG, Andò S, Maggiolini M.  Department Cellular Biology, University of Calabria, Cosenza, Arcavacata-Rende (CS), 87030, Italy.  In the present study, we evaluated the ability of 4-hydroxytamoxifen (OHT) and epidermal growth factor (EGF) to regulate homotypic adhesion in MCF7 breast cancer cells. Our results demonstrate that OHT and EGF activate the E-cadherin promoter, increase E-cadherin mRNA and protein expression and enhance homotypic aggregation of MCF7 cells. Interestingly, an ERalpha and EGFR cross-talk is involved in the E-cadherin expression by OHT and EGF, as demonstrated by knocking down either receptor. On the basis of our findings, the well-established cross-talk between ERalpha and EGFR could be extended to the modulation of E-cadherin expression by OHT and EGF. Thus, the potential ability of tamoxifen to induce cell-cell aggregation may contribute to the biologic response of pharmacologic intervention in patients with breast cancer.  PMID: 19593637 [PubMed - as supplied by publisher]  5: Breast Cancer Res Treat. 2009 Jul 11. [Epub ahead of print]  Antimitotic chemotherapeutics promote adhesive responses in detached and circulating tumor cells.  Balzer EM, Whipple RA, Cho EH, Matrone MA, Martin SS.  Program in Molecular Medicine, University of Maryland School of Medicine, Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, 21201, USA.  In the clinical treatment of breast cancer, antimitotic cytotoxic agents are one  of the most commonly employed chemotherapies, owing largely to their antiproliferative effects on the growth and survival of adherent cells in studies that model primary tumor growth. Importantly, the manner in which these chemotherapeutics impact the metastatic process remains unclear. Furthermore, since dissemination of tumor cells through the systemic circulation and lymphatics necessitates periods of detached survival, it is equally important to  consider how circulating tumor cells respond to such compounds. To address this question, we exposed both nontumorigenic and tumor-derived epithelial cell lines  to two antitumor compounds, jasplakinolide and paclitaxel (Taxol), in a series of attached and detached states. We report here that jasplakinolide promoted the extension of microtubule-based projections and microtentacle protrusions in adherent and suspended cells, respectively. These protrusions were specifically enriched by upregulation of a stable post-translationally modified form of alpha-tubulin, and this occurred prior to, and independently of any reductions in cellular viability. Microtubule stabilization with Taxol significantly enhanced these effects. Additionally, Taxol promoted the attachment and spreading of suspended tumor cell populations on extracellular matrix. While the antiproliferative effects of these compounds are well recognized and clinically valuable, our findings that microfilament and microtubule binding chemotherapeutics rapidly increase the mechanisms that promote endothelial adhesion of circulating tumor cells warrant caution to avoid inadvertently enhancing metastatic potential, while targeting cell division.  PMID: 19593636 [PubMed - as supplied by publisher] 

 1: Int J Clin Oncol. 2009 Jun;14(3):219-24. Epub 2009 Jul 11.  Effective treatment of the brachial plexus syndrome in breast cancer patients by  early detection and control of loco-regional metastases with radiation or systemic therapy.  Kamenova B, Braverman AS, Schwartz M, Sohn C, Lange C, Efiom-Ekaha D, Rotman M, Yoon H.  Division of Medical Oncology-Hematology, Department of Medicine, Downstate Medical College, State University of New York, New York, USA.  BACKGROUND: In breast cancer (BC) patients the brachial plexus syndrome (BPS) has been reported to be due to loco-regional metastases or radiation plexopathy. Associated arm edema is considered more suggestive of the latter. Radiation therapy is the only effective treatment for BPS reported. METHODS: The charts of  all BC patients who presented to our clinic from 1982 to 2006 with homolateral arm pain and neurological deficits, without humerus, cervical spine, or brain metastases, were reviewed. RESULTS: There were 28 patients fulfilling these criteria for BPS. Supraclavicular, axillary or chest wall metastases developed synchronously with the BPS in 26 patients; in 21 they were recurrences, found 6-94 months (median 34 months) after primary BC treatment, while in 5 others they were progressing inoperable primary tumors and nodes. Arm edema first occurred at the same time as loco-regional metastases in 19 patients. Treatment for the BPS was administered to 22 patients; it was directed at their locoregional metastases. The BPS was initially treated with radiation (8 patients) or chemo- or endocrine therapy (14 patients); 19 (86%) had partial or complete remission of pain and neurologic deficits, with an 8-month median duration. CONCLUSION: The BPS in BC patients is due to loco-regional metastases and is often associated with arm edema. Chemoor endocrine therapy induced the remission of pain and deficits as frequently as radiation therapy.  PMID: 19593613 [PubMed - in process]  2: Epidemiology. 2009 Jul 10. [Epub ahead of print]  Epidemiologic Evidence on Mobile Phones and Tumor Risk: A Review.  Ahlbom A, Feychting M, Green A, Kheifets L, Savitz DA, Swerdlow AJ; ICNIRP (International Commission for Non-Ionizing Radiation Protection) Standing Committee on Epidemiology.  From the aDepartment of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; bEpidemiology and Public Health Unit, The Queensland Institute of Medical Research, Brisbane, Australia; cDepartment of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, CA; dEpidemiology, Biostatistics, and Disease Prevention Institute,  Mount Sinai School of Medicine, New York, NY; and eSection of Epidemiology, Institute of Cancer Research, Sutton, Surrey, United Kingdom.  This review summarizes and interprets epidemiologic evidence bearing on a possible causal relation between radiofrequency field exposure from mobile phone  use and tumor risk. In the last few years, epidemiologic evidence on mobile phone use and the risk of brain and other tumors of the head in adults has grown in volume, geographic diversity of study settings, and the amount of data on longer-term users. However, some key methodologic problems remain, particularly with regard to selective nonresponse and inaccuracy and bias in recall of phone use. Most studies of glioma show small increased or decreased risks among users,  although a subset of studies show appreciably elevated risks. We considered methodologic features that might explain the deviant results, but found no clear  explanation. Overall the studies published to date do not demonstrate an increased risk within approximately 10 years of use for any tumor of the brain or any other head tumor. Despite the methodologic shortcomings and the limited data  on long latency and long-term use, the available data do not suggest a causal association between mobile phone use and fast-growing tumors such as malignant glioma in adults (at least for tumors with short induction periods). For slow-growing tumors such as meningioma and acoustic neuroma, as well as for glioma among long-term users, the absence of association reported thus far is less conclusive because the observation period has been too short.  PMID: 19593153 [PubMed - as supplied by publisher]  3: J Immunol. 2009 Jul 10. [Epub ahead of print]  Recurrence of Intracranial Tumors following Adoptive T Cell Therapy Can Be Prevented by Direct and Indirect Killing Aided by High Levels of Tumor Antigen Cross-Presented on Stromal Cells.  Thomas DL, Kim M, Bowerman NA, Narayanan S, Kranz DM, Schreiber H, Roy EJ.  *Neuroscience Program.  Elimination of peripheral tumors by adoptively transferred tumor-specific T cells may require killing of cancer cells and tumor stromal cells. Tumor Ags are cross-presented on stromal cells, resulting in direct cytotoxic T cell (CTL) killing of both Ag-expressing cancer cells and stromal cells. Indirect killing of Ag loss variant cells also occurs. We show here that similar processes occur in a brain tumor stromal environment. We used murine cancer cell lines that express high or low levels of a peptide Ag, SIYRYYGL (SIY), recognized by transgenic 2C CD8(+) T cells. The two cell lines are killed with equivalent efficiency by 2C T  cells in vitro. Following adoptive transfer of 2C T cells into mice with established SIY-Hi or SIY-Lo brain tumors, tumors of both types regressed, but low-Ag-expressing tumors recurred. High-Ag-expressing tumors contained CD11b(+) cells cross-presenting SIY peptide and were completely eliminated by 2C T cells.  To further test the role of cross-presentation, RAG1(-/-) H-2(b) mice were infused with H-2(k) tumor cells expressing high levels of SIY peptide. Adoptively transferred 2C T cells are able to kill cross-presenting H-2(b) stromal cells but not H-2(k) tumor cells. In peripheral models, this paradigm led to a small static tumor. In the brain, activated 2C T cells were able to kill cross-presenting CD11b(+) cells and completely eliminate the H-2(k) tumors in most mice. Targeting brain tumor stroma or increasing Ag shedding from tumor cells to enhance cross-presentation may improve the clinical success of T cell adoptive therapies.  PMID: 19592642 [PubMed - as supplied by publisher]  4: J Biol Chem. 2009 Jul 10. [Epub ahead of print]  NDRG4 is required for cell cycle progression and survival in glioblastoma cells.  Schilling SH, Hjelmeland AB, Radiloff DR, Liu IM, Wakeman TP, Fielhauer JR, Foster EH, Lathia JD, Rich JN, Wang XF, Datto MB.  Duke University Medical Center, United States;  NDRG4 is a largely unstudied member of the predominantly tumor suppressive N-Myc  downstream-regulated gene (NDRG) family. Unlike its family members NDRG1-3, which are ubiquitously expressed, NDRG4 is expressed almost exclusively in the heart and brain. Given this tissue-specific expression pattern and the established tumor suppressive roles of the NDRG family in regulating cellular proliferation,  we investigated the cellular and biochemical functions of NDRG4 in the context of astrocytes and glioblastoma multiforme (GBM) cells. We show that, in contrast to  NDRG2, NDRG4 expression is elevated in GBM and NDRG4 is required for the viability of primary astrocytes, established GBM cell lines, and both CD133(+) (cancer stem cell (CSC)-enriched) and CD133(-) primary GBM xenograft cells. While NDRG4 overexpression has no effect on cell viability, NDRG4 knockdown causes G(1) cell cycle arrest followed by apoptosis. The initial G(1) arrest is associated with a decrease in cyclin D1 expression and an increase in p27(Kip1) expression,  and the subsequent apoptosis is associated with a decrease in the expression of XIAP and survivin. As a result of these effects on cell cycle progression and survival, NDRG4 knockdown decreases the tumorigenic capacity of established GBM cell lines and GBM CSC-enriched cells that have been implanted intracranially into immunocompromised mice. Collectively, these data indicate that NDRG4 is required for cell cycle progression and survival, thereby diverging in function from its tumor suppressive family member NDRG2 in astrocytes and GBM cells.  PMID: 19592488 [PubMed - as supplied by publisher]  5: Lung Cancer. 2009 Jul 8. [Epub ahead of print]  Can upfront systemic chemotherapy replace stereotactic radiosurgery or whole brain radiotherapy in the treatment of non-small cell lung cancer patients with asymptomatic brain metastases?  Kim KH, Lee J, Lee JI, Nam DH, Kong DS, Ahn YC, Park HC, Jung Kwon O, Kim H, Chang MH, Yi SY, Ji SH, Park YH, Ahn JS, Park K, Ahn MJ.  Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center,  Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu,Seoul 135-710, Republic of Korea.  BACKGROUND: The optimal treatment for non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastasis is still controversial. This study aimed to analyze the outcome for various treatment modalities including chemotherapy only, upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in NSCLC patients with asymptomatic brain metastases. METHODS: We retrospectively reviewed the medical records of patients with histopathologically proven NSCLC and synchronous asymptomatic brain metastasis between January 2003 and December 2007. RESULTS: From the database, 741 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between January 2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were identified to have synchronous brain metastasis without associated symptoms. Of the 129 patients included in the analysis, 78 (57.8%) patients received systemic  chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24 (17.8%) patients received upfront SRS and chemotherapy. There was no significant  difference in overall survival among three groups (systemic chemotherapy alone, 13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT followed by chemotherapy, 17.7 months, respectively; P=0.86). Subset analysis of  110 adenocarcinoma patients showed that the median OS for patients treated with upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7 months; P=0.01) or chemotherapy alone (29.3 months versus 14.6 months; P=0.04). CONCLUSION: This study suggested a potential role of systemic chemotherapy alone  or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal treatment modality, however, needs to be defined in prospective trials for this subset of patients.  PMID: 19592127 [PubMed - as supplied by publisher] 

 1: Stem Cell Rev Rep. 2009 Apr 23. [Epub ahead of print]  Therapeutic Window of Stem Cell Potential for Targeting Pediatric Malignant Brain Tumors: An Opportunity for Stem Cell Therapy.  Calvin Li S, Han YP, Dethlefs BA, Günter Loudon W.  Neuro-Oncology Research Laboratory, Center for Neuroscience and Stem Cell Research, CHOC Children's Research Institute, 455 S. Main Street, Orange, CA, 92868-3874, USA, sli@choc.org.  In children, cancers are the deadliest of diseases and second only to accidents as the leading cause of death. The deadliest of the brain cancers are the malignant gliomas. Approximately two-thirds of children can survive less malignant types of brain cancers, however, in ~ 67% of these survivors recurs under the current regimes of surgery followed by administration of high doses toxic drugs and exposure to high doses of radiation. Even more distressing is that fortunate survivors are generally left with life-long cognitive disabilities. A new medical approach is desperately needed. Stem cells, with their natural ability to seek out brain tumors, could be used to accurately deliver therapy directly to the cancer sparing normal tissues for suppression of  tumor growth. Despite exciting initial reports, clinical potency of stem cell therapy in animal brain tumor models has to date proven disappointing. Attempts to extrapolate the animal study results to humans are stymied by the fact that stem cells are heterogeneous, resulting in differences in their efficacy. Indeed, therapeutic success relies on an effective strategy to select for a stem cell sub-population within some particular stage of the development at which they are  competitive and capable of targeting brain tumors. To improve this during developmental path, concept of a 'therapeutic window' is proposed. The "therapeutic window" for stem cells or more specifically a "biochemical therapeutic window" can be determined from biochemical assays and a "biological therapeutic window" from biological assays or even a molecular window for genetic description. Taken together, we can use selective processes to generate more effective stem cells to treat cancers as is clearly needed today.  PMID: 19590989 [PubMed - as supplied by publisher]  2: Neurotox Res. 2009 Jul 10. [Epub ahead of print]  Anthocyanins: Are They Beneficial in Treating Ethanol Neurotoxicity?  Chen G, Luo J.  Department of Internal Medicine, College of Medicine, University of Kentucky, 124C Combs Research Building, 800 Rose Street, Lexington, KY, 40536, USA.  Heavy alcohol exposure produces profound damage to the developing central nervous system (CNS) as well as the adult brain. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation. Excessive alcohol consumption is associated with Wernicke-Korsakoff syndrome (WKS) and neurodegeneration in the adult brain. Although the cellular/molecular mechanism underlying ethanol's neurotoxicity has not been fully understood, it is generally believed that oxidative stress plays an important role. Identification  of neuroprotective agents that can ameliorate ethanol neurotoxicity is an important step for developing preventive/therapeutic strategies. Targeting ethanol-induced oxidative stress using natural antioxidants is an attractive approach. Anthocyanins, a large subgroup of flavonoids present in many vegetables and fruits, are safe and potent antioxidants. They exhibit diverse potential health benefits including cardioprotection, anti-atherosclerotic activity, anti-cancer, anti-diabetic, and anti-inflammation properties. Anthocyanins can cross the blood-brain barrier and distribute in the CNS. Recent studies indicate  that anthocyanins represent novel neuroprotective agents and may be beneficial in ameliorating ethanol neurotoxicity. In this review, we discuss the evidence and potential of anthocyanins in alleviating ethanol-induced damage to the CNS. Furthermore, we discuss possible underlying mechanisms as well as future research approaches necessary to establish the therapeutic role of anthocyanins.  PMID: 19590929 [PubMed - as supplied by publisher]  3: Environ Health Perspect. 2009 Jun;117(6):1002-6. Epub 2009 Feb 13.  Parental exposure to pesticides and childhood brain cancer: U.S. Atlantic coast childhood brain cancer study.  Shim YK, Mlynarek SP, van Wijngaarden E.  Division of Health Studies, Agency for Toxic Substances and Disease Registry, Atlanta, Georgia 30341-3737, USA. Yshim@cdc.gov  BACKGROUND: The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use. OBJECTIVES: We aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children. METHODS: We included 526 one-to-one-matched case-control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S. Atlantic Coast states. We selected controls by random digit dialing. We conducted computer-assisted telephone interviews with mothers. Using information on residential pesticide use and jobs held by fathers  during the 2-year period before the child's birth, we assessed potential exposure to insecticides, herbicides, and fungicides. For each job, two raters independently classified the probability and intensity of exposure; 421 pairs were available for final analysis. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, after adjustment for maternal education. RESULTS: A significant risk of astrocytoma was associated with exposures to herbicides from residential use (OR = 1.9; 95% CI, 1.2-3.0). Combining parental exposures to herbicides from both residential and occupational sources, the elevated risk remained significant (OR = 1.8; 95% CI, 1.1-3.1). We observed little association with primitive neuroectodermal tumors (PNET) for any of the pesticide classes or exposure sources considered. CONCLUSIONS: Our observation is consistent with a previous literature reporting suggestive associations between parental exposure to pesticides and risk of astrocytoma in offspring but not PNET. However, these findings should be viewed in light of limitations in exposure assessment and effective sample size.  Publication Types:      Research Support, U.S. Gov't, Non-P.H.S.  PMID: 19590697 [PubMed - in process]  4: Environ Health Perspect. 2009 Jun;117(6):916-22. Epub 2009 Feb 3.  Comment in:     Environ Health Perspect. 2009 Jun;117(6):A257.  Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions.  Slotkin TA, Lassiter TL, Ryde IT, Wrench N, Levin ED, Seidler FJ.  Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. t.slotkin@duke.edu  BACKGROUND: Developmental exposure to a wide variety of developmental neurotoxicants, including organophosphate pesticides, evokes late-emerging and persistent abnormalities in acetylcholine (ACh) systems. We are seeking interventions that can ameliorate or reverse the effects later in life. OBJECTIVES: We administered parathion to neonatal rats and then evaluated whether a high-fat diet begun in adulthood could reverse the effects on ACh systems. METHODS: Neonatal rats received parathion on postnatal days 1-4 at 0.1 or 0.2 mg/kg/day, straddling the cholinesterase inhibition threshold. In adulthood, half the animals were switched to a high-fat diet for 8 weeks. We assessed three indices of ACh synaptic function: nicotinic ACh receptor binding, choline acetyltransferase activity, and hemicholinium-3 binding. Determinations were performed in brain regions comprising all the major ACh projections and cell bodies. RESULTS: Neonatal parathion exposure evoked widespread abnormalities in ACh synaptic markers, encompassing effects in brain regions possessing ACh projections and ACh cell bodies. In general, males were affected more than females. Of 17 regional ACh marker abnormalities (10 male, 7 female), 15 were reversed by the high-fat diet. CONCLUSIONS: A high-fat diet reverses neurodevelopmental effects of neonatal parathion exposure on ACh systems. This points to the potential for nonpharmacologic interventions to offset the effects  of developmental neurotoxicants. Further, cryptic neurodevelopmental deficits evoked by environmental exposures may thus engender a later preference for a high-fat diet to maintain normal ACh function, ultimately contributing to obesity.  Publication Types:      Research Support, N.I.H., Extramural     Research Support, Non-U.S. Gov't  PMID: 19590683 [PubMed - in process]  5: Neurologist. 2009 Jul;15(4):208-11.  Bilateral temporal glioma presenting as a paraneoplastic limbic encephalitis with pure cognitive impairment.  Deramecourt V, Bombois S, Debette S, Delbeuck X, Ramirez C, Reyns N, Kerdraon O,  Maurage CA, Pasquier F.  Department of Neurology and Memory Clinic, University Hospital of Lille and Lille II University, France. v-deramecourt@chru-lille.fr  INTRODUCTION: Memory impairment caused by bilateral hippocampal primitive brain tumor is rarely reported. Clinical and MRI features can mimic paraneoplastic limbic encephalitis (PLE), and the differential diagnosis between these 2 entities may be difficult. CASE REPORT: We report the case of a 42-year-old woman presenting with amnesia without neurologic focal signs at clinical examination. The neuroimaging features consisted of bilateral limbic hyperintensities on T2-weighted and FLAIR brain MRI. Despite exhaustive biologic and radiologic investigations, no specific etiology was found. The diagnosis of paraneoplastic limbic encephalitis was suspected, although antineuronal antibodies were negative and no cancer was detected after the first evaluation. Eight months after onset,  the memory complaint of the patient increased along with disability in activities of the daily living, the neurologic examination slightly changed with frontal neurologic signs and the brain MRI showed a new cystic lesion in the left hippocampus with enhancement after contrast administration. The left temporal tumor was resected and the neuropathological examination was consistent with gliomatosis cerebri with a focal high grade astrocytoma. CONCLUSIONS: This case highlights the need to consider the possibility of infiltrative gliomatosis in patients presenting with features of paraneoplastic limbic encephalitis.  PMID: 19590380 [PubMed - in process] 

 1: Pediatr Blood Cancer. 2009 Jul 9. [Epub ahead of print]  Septic arthritis as the initial manifestation of fatal Vibrio vulnificus septicemia in a patient with thalassemia and iron overload.  Kuo CH, Dai ZK, Wu JR, Hsieh TJ, Hung CH, Hsu JH.  Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.  Vibrio vulnificus infection is an uncommon but potentially fatal disease in children such that prompt recognition has prognostic implications. We describe here the case of a 9-year-old female with thalassemia and iron overload who presented with septic arthritis as an atypical initial manifestation of fatal V.  vulnificus septicemia. This report underscores the possibility of septic arthritis as an early manifestation of V. vulnificus septicemia. Pediatricians should be alert to this extremely invasive disease, especially in children with iron overload. Pediatr Blood Cancer (c) 2009 Wiley-Liss, Inc.  PMID: 19591224 [PubMed - as supplied by publisher]  2: J Cell Physiol. 2009 Jul 9. [Epub ahead of print]  RAGE expression and NF-kappaB activation attenuated by extracellular domain of RAGE in human salivary gland cell line.  Chuong C, Katz J, Pauley KM, Bulosan M, Cha S.  Oral Surgery and Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, Florida.  The receptor for advanced-glycation-end-products (RAGE) has been implicated as a  pro-inflammatory factor in chronic inflammatory conditions such as diabetes mellitus and rheumatoid arthritis. The aim of this study was to investigate the inhibitory effect of the soluble-RAGE (sRAGE), the extracellular domain of RAGE,  on RAGE expression and NF-kappaB translocation in human-salivary gland-cell-lines (HSG). Cells were stimulated with agonist S100A4, fusion protein of RAGE encompassing the extracellular domain of RAGE (ex-RAGE), ex-RAGE followed by S100A4, or S100A4 followed by ex-RAGE. Our study indicates that RAGE expression was highest at 150 microg/microl of S100A4 and efficiently down-regulated by 1.8-fold (P < 0.05) when ex-RAGE was incubated prior to agonist S100A4. RAGE protein was also consistently down-regulated by 20-40% with pre-incubation of ex-RAGE. More importantly, nuclear translocation of p65 and p52 of NF-kappaB by S100A4 was inhibited in the presence of ex-RAGE, confirming anti-inflammatory function of ex-RAGE. In conclusion, ex-RAGE down-regulates RAGE expression and inhibits p65 and p52 activation in HSG, providing evidence that ex-RAGE functions as a "decoy" to RAGE-ligand interaction and thus potentially dampening inflammatory conditions. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.  PMID: 19591173 [PubMed - as supplied by publisher]  3: Free Radic Res. 2009 Jul 9:1-13. [Epub ahead of print]  Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance.  Strosova M, Karlovska J, Spickett CM, Orszagova Z, Ponist S, Bauerova K, Mihalova D, Horakova L.  Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia.  Adjuvant arthritis (AA) is a condition that involves systemic oxidative stress. Unexpectedly, it was found that sarcoplasmic reticulum Ca(2 +)-ATPase (SERCA) activity was elevated in muscles of rats with AA compared to controls, suggesting possible conformational changes in the enzyme. There was no alteration in the nucleotide binding site but rather in the transmembrane domain according to the tryptophan polar/non-polar fluorescence ratio. Higher relative expression of SERCA, higher content of nitrotyrosine but no increase in phospholipid oxidation  in AA SR was found. In vitro treatments of SR with HOCl showed that in AA animals SERCA activity was more susceptible to oxidative stress, but SR phospholipids were more resistant and SERCA could also be activated by phosphatidic acid. It was concluded that increased SERCA activity in AA was due to increased levels of  SERCA protein and structural changes to the protein, probably induced by direct and specific oxidation involving reactive nitrogen species.  PMID: 19591012 [PubMed - as supplied by publisher]  4: Climacteric. 2009 Jul 7:1-9. [Epub ahead of print]  The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus.  Holroyd CR, Edwards CJ.  Rheumatology Department, Southampton University Hospitals NHS Trust, Southampton, UK.  Autoimmune diseases are generally more common in women than men; however, there is no simple explanation for this. Sex hormones, especially estrogen (but also prolactin and testosterone), play important roles in these diseases. Estrogens are generally considered to enhance autoimmunity and have multiple effects on the immune system through various cell types and molecular pathways. There is much evidence supporting the role of estrogen in the pathogenesis of systemic lupus erythematosus (SLE): the disease occurs much more frequently in women, especially during the years of child-bearing potential, and commonly flares during pregnancy. The relationship between estrogen and the development of SLE is complex, however. Exogenous estrogens have been historically avoided in women with SLE due to the widely held view that they could activate disease and their use remains controversial. Current evidence from prospective trials suggests that there may be a small increased risk of mild/moderate flares in women with SLE taking hormone replacement therapy (HRT), but the risk of major flare does not appear to be increased. In rheumatoid arthritis, HRT does not appear to be associated with an increased risk of disease flare and may actually improve disease activity. In all individuals with autoimmune disease, the risk of venous  thrombosis associated with oral HRT is an important factor that should also be considered.  PMID: 19591008 [PubMed - as supplied by publisher]  5: Mod Rheumatol. 2009 Jul 10. [Epub ahead of print]  Japan College of Rheumatology 2009 guidelines for the use of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, in rheumatoid arthritis.  Koike R, Harigai M, Atsumi T, Amano K, Kawai S, Saito K, Saito T, Yamamura M, Matsubara T, Miyasaka N.  Department of Pharmacovigilance, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan, koike.rheu@tmd.ac.jp.  The introduction of biological agents targeting tumor necrosis factor-alpha (TNF-alpha) has brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). Although these anti-TNF agents have excellent efficacy against RA, a substantial number of patients still show inadequate responses. In Western  countries, such patients are already being treated with new classes of antirheumatic drugs such as abatacept and rituximab. Tocilizumab (TCZ) is a humanized monoclonal antibody developed in Japan against the human interleukin-6  (IL-6) receptor. TCZ does not only alleviate the signs and symptoms of RA but also seems to prevent progressive bone and joint destruction. However, there is a concern that TCZ might increase the risk of adverse events such as infections since IL-6 plays a pivotal role in the immune system. Calculating the relative risks of specific adverse outcomes with TCZ use remains difficult, due to insufficient patient numbers enrolled in clinical trials to date. This review presents tentative guidelines for the use of TCZ for RA patients prepared by the  Japan College of Rheumatology and based on results of clinical trials in Japan and Western countries. The guidelines are intended as a guide for postmarketing surveillance and clinical practice, and will be revised periodically based on the surveillance.  PMID: 19590933 [PubMed - as supplied by publisher] 

 1: Br J Surg. 2009 Jul 9;96(8):859-864. [Epub ahead of print]  Circumferential suction-assisted lipectomy for lymphoedema after surgery for breast cancer.  Damstra RJ, Voesten HG, Klinkert P, Brorson H.  Department of Dermatology, Phlebology and Lymphology, The Netherlands.  BACKGROUND:: The incidence of arm lymphoedema after treatment for breast cancer ranges from 1 to 49 per cent. Although most women can be treated by non-operative means with satisfying results, end-stage lymphoedema is often non-responsive to compression, where hypertrophy of adipose tissue limits the outcome value of compression or massage. METHODS:: This was a prospective study of 37 women with unilateral non-pitting lymphoedema. After initial conservative treatment for 2-4  days, circumferential suction-assisted lipectomy was used to remove excess volume. Limb compression was resumed after surgery with short-stretch bandages, followed by flat-knit compression garments. RESULTS:: The mean preoperative excess arm volume was 1399 ml. The total aspirate volume was 2124 ml with 93 per  cent aspirate adipose tissue content. After 12 months, the mean reduction in excess volume was 118 per cent. The percentage reduction in excess volume after 12 months was linearly related to the preoperative excess volume but showed no linear relationship with the duration of lymphoedema or surgeon experience. CONCLUSION:: Circumferential lipectomy combined with lifelong compression hose is an effective technique in end-stage lymphoedema after treatment for breast cancer. Copyright (c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.  PMID: 19591161 [PubMed - as supplied by publisher]  2: Br J Surg. 2009 Jul 9;96(8):865-869. [Epub ahead of print]  Sympathetic nerve damage as a potential cause of lymphoedema after axillary dissection for breast cancer.  Bennett Britton TM, Wallace SM, Wilkinson IB, Mortimer PS, Peters AM, Purushotham AD.  Department of Research Oncology, King's College London and Guy's and St Thomas' NHS Foundation Trust, Bermondsey Wing, Guy's Hospital, London, UK.  BACKGROUND:: The physiological disturbances leading to lymphoedema after breast cancer surgery are poorly understood. Damage to sympathetic nerves during axillary lymph node dissection (ALND), leading to increased capillary fluid filtration, was investigated as a possible contributory factor. METHODS:: The integrity of the upper limb sympathetic nervous system was tested in 36 patients  before, and 3 and 12 months after ALND. Forearm vascular resistance (FVR), calculated from forearm blood flow and mean systemic arterial pressure, was measured before and after exposure to lower-body negative pressure. Forearm venous compliance was measured using (99m)Tc-labelled autologous erythrocytes and radionuclide plethysmography before and after cold water immersion of the feet. RESULTS:: There were clear changes in FVR and venous compliance in response to sympathetic stimulation but no differences attributable to surgery or between the nine patients who developed lymphoedema and the 27 who did not; nor were there differences between the two arms. There was a trend towards lower preoperative FVR in patients who developed lymphoedema. CONCLUSION:: Lymphoedema is not the result of sympathetic nerve damage sustained during ALND. Preoperative FVR may help predict who will get lymphoedema following this surgery. Copyright (c) 2009  British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.  PMID: 19591159 [PubMed - as supplied by publisher]  3: Climacteric. 2009 Jul 7:1-12. [Epub ahead of print]  Hormone replacement therapy after breast cancer: attitudes of women eligible in a randomized trial.  Wallberg B, von Schoultz E, Bolund C, Bergh J, Wilking N.  Department of Oncology-Pathology, Cancer Centre Karolinska & Radiumhemmet, Karolinska Institutet and Karolinska University Hospital, Stockholm.  Objectives To investigate the attitudes of breast cancer patients who accepted or declined participation in a randomized trial with hormone replacement therapy that might increase their risk of recurrence (the Stockholm trial). Methods A total of 115 patients free from breast cancer recurrence were interviewed; 57 were participants and 58 were non-participants in the Stockholm trial. Patients answered five questionnaires regarding information needs (two), attitudes to participation in trials (two) and patient role in treatment decisions (one). Results Participants in the Stockholm trial had a lower risk of breast cancer recurrence (measured by node-positive disease and tumor size) and were older than non-participants. Their information needs were the same. Participants in the trial were more prepared to accept uncertainty, to have an altruistic attitude, to accept risks including an increased risk of recurrence of breast cancer, if their quality of life or general health was improved. Most patients preferred a collaborative role in relation to their physician but participants often wanted more influence than they had in treatment decisions. Conclusion A patient's decision to accept or decline participation in the Stockholm trial was influenced by her objective risk of breast cancer recurrence and reflected her attitude to risk, uncertainty and preference to be active in treatment decisions.  PMID: 19591009 [PubMed - as supplied by publisher]  4: Breast Cancer Res Treat. 2009 Jul 10. [Epub ahead of print]  The proteins FABP7 and OATP2 are associated with the basal phenotype and patient  outcome in human breast cancer.  Zhang H, Rakha EA, Ball GR, Spiteri I, Aleskandarany M, Paish EC, Powe DG, Macmillan RD, Caldas C, Ellis IO, Green AR.  Division of Pathology, School of Molecular Medical Sciences, Queen's Medical Centre, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK.  The basal-like or basal phenotype (BP) class of breast cancers have recently attracted attention as a poor prognostic form of breast cancer. However, BP appears to encompass biologically and clinically heterogeneous tumours, resulting in a lack of consensus definition of BP. We analysed 48,000 gene transcripts in 132 invasive breast carcinomas to identify two novel genes (OATP2 and FABP7) significantly associated with BP [defined by cytokeratin (CK)5/6 and/or CK14 positivity]. Using a series of invasive breast carcinoma cases (n = 899), prepared as tissue microarrays, we assessed OATP2 and FABP7 protein expression using immunohistochemistry to investigate associations with clinicopathological variables, patients' outcome and ability to refine BP classification. A total of  7.9 and 15.6% cases were OATP2 and FABP7 positive, respectively. OATP2 was associated with tumours of high histological grade (p < 0.01), ER and PgR negativity (p < 0.01) and shorter breast cancer-specific survival (p = 0.04). FABP7 expression was associated with lower lymph node stage (p < 0.01), ER and PgR negativity (p < 0.01). BP tumours which were FABP7 positive had a significantly longer BCSS (p = 0.05) and disease-free survival (p = 0.01) compared with FABP7 negative basal tumours (p < 0.01). OATP2 positive tumours were associated with adverse survival and increased risk of early recurrence. This study confirms the biological and clinical heterogeneity of the BP in breast cancer. We have identified a novel subgroup of basal tumours showing FABP7 expression that have significantly better clinical outcome. Further studies analysing the role of FABP7 are therefore warranted.  PMID: 19590950 [PubMed - as supplied by publisher]  5: Breast Cancer Res Treat. 2009 Jul 10. [Epub ahead of print]  Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis.  Economopoulos KP, Sergentanis TN.  School of Medicine, National University of Athens, Athens, Greece, economopoulos@gmail.com.  MDM2 SNP309 is a single nucleotide T > G polymorphism present in intron 1 of the  MDM2 gene. A variety of case-control studies have been published evaluating the association between MDM2 SNP309 and breast cancer risk. However, the published studies, as well as the subsequent meta-analyses, have yielded contradictory results. This meta-analysis aims to examine whether MDM SNP309 polymorphism may exert a differential effect on breast cancer risk along with race. Eligible articles were identified by a search of MEDLINE, Cochrane and EMBASE bibliographical databases for the period July 1993 to June 2009; 16 case-control  studies were eligible (12,986 breast cancer cases, 12,993 controls). Subanalyses  in case-control studies conducted on Chinese (3 studies, 892 cases, 1,435 controls) and non-Chinese populations (13 studies, 12,094 cases, 11,558 controls) were performed. All pooled odds ratios (ORs) were derived from fixed-effects models given that the between-study heterogeneity was not statistically significant. Subanalysis on Chinese subjects demonstrated that GT and GG genotype were associated with increased breast cancer risk (pooled OR = 1.272, 95% CI 1.025-1.578 and pooled OR = 1.323, 95% CI 1.034-1.694, respectively); as a result the overall effect of the G allele was statistically significant (pooled OR = 1.287, 95% CI 1.048-1.579). On the contrary, no significant associations between  MDM2 SNP309 status and breast cancer risk were demonstrated in non-Chinese populations. In conclusion, the association between MDM2 SNP309 and breast cancer is modified by race. MDM2 SNP309 represents a risk factor for breast cancer in Chinese women but not in non-Chinese women. This phenomenon is analogous to that  described in the context of lung cancer.  PMID: 19590949 [PubMed - as supplied by publisher] 

 1: Breastfeed Med. 2009 Jun;4(2):55.  Comment on:     Breastfeed Med. 2009 Jun;4(2):57-61.  Revelations about Candida albicans, a bundle of letters from our readers, and an  assault on breastfeeding.  Lawrence RA.  Publication Types:      Comment     Editorial  PMID: 19500048 [PubMed - indexed for MEDLINE]  2: Intern Med J. 2009 Jan;39(1):61-3.  Thrombolytic therapy for management of complicated catheter-related Candida albicans thrombophlebitis.  Block AA, Thursky KA, Worth LJ, Slavin MA.  Department of Infectious Diseases, Dandenong Hospital, David Street, Dandenong, Victoria 3175, Australia. andrew.block@med.monash.edu.au  In immunocompromised patients, endovascular infection due to Candida albicans is  associated with significant morbidity and mortality. Recommended management includes removal of any existing central venous catheter. Rarely, complications of endocarditis or infected mural thrombi may arise, with poorer clinical outcomes. For large endoluminal lesions, particularly of the great vessels or those that are intra-atrial, thrombolysis has been used in paediatric populations or before surgery for dissolution of infected thrombus. We describe the case of an adult patient with lung carcinoma who developed persisting candidaemia with a  large endovascular fungal lesion adherent to the tip of a peripherally inserted central venous catheter. Local urokinase infusion enabled safe removal of the catheter without embolization. As an adjunct to antifungal therapy, local thrombolysis may play a contributory role in the management of central venous catheter-related candidal septic thrombosis.  Publication Types:      Case Reports  PMID: 19290985 [PubMed - indexed for MEDLINE]  3: Int J Antimicrob Agents. 2009 Jul;34(1):95-8. Epub 2009 Feb 28.  Monotherapy with caspofungin for candidaemia in adult patients with cancer: a retrospective, single institution study.  Sipsas NV, Lewis RE, Raad II, Kontoyiannis DP.  Department of Infectious Diseases, Infection Control and Employee Health, Unit 402, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.  This study was performed to evaluate retrospectively the efficacy and safety of caspofungin monotherapy for candidaemia in patients with cancer. The medical records were reviewed of 63 consecutive adult patients with cancer who had candidaemia treated with caspofungin alone for at least 3 consecutive days at The University of Texas M.D. Anderson Cancer Center (March 2001-February 2007). Twenty patients (32%) had haematological malignancies. Most of the candidaemia cases (54%) were caused by non-albicans Candida spp. The most frequent isolates were C. albicans (38%) followed by Candidaparapsilosis (21%), Candidatropicalis (16%) and Candidaglabrata (10%). In vitro susceptibility studies showed that of 30 Candida isolates tested, only one C. parapsilosis isolate had a caspofungin minimum inhibitory concentration > 1 microg/mL. The clinical and mycological response rates after 7 days of treatment with caspofungin were 78% and 77%, respectively. The overall mortality rate was 5% on Day 7, 12% on Day 14 and 21% on Day 30. The 30-day Candida-attributable mortality rate was 11% and was significantly higher in patients with fluconazole-resistant or susceptible-dose-dependent Candida isolates. Caspofungin was well tolerated in all patients. Although selection of candidaemic patients with cancer who received caspofungin monotherapy may have accounted for the favourable outcomes, it was observed that caspofungin had efficacy and safety comparable with those in candidaemic patients without malignancy.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19251404 [PubMed - indexed for MEDLINE]  4: Eur J Clin Microbiol Infect Dis. 2009 Jun;28(6):689-92. Epub 2008 Nov 15.  Risk-based fluconazole prophylaxis of Candida bloodstream infection in a medical  intensive care unit.  Faiz S, Neale B, Rios E, Campos T, Parsley E, Patel B, Ostrosky-Zeichner L.  University of Texas Medical School at Houston, Houston, TX, USA. safaiz@mdanderson.org  Candida bloodstream infection (CBSI) accounted for 50% of bloodstream infections  in our medical intensive care unit (MICU) in 2004. Our objective was to evaluate  a risk-based fluconazole prophylaxis program. CBSI incidence, patient demographics, and unit metrics were retrospectively reviewed for 2004. Starting on January 2005, patients meeting pre-specified criteria were placed on risk-based fluconazole prophylaxis and their outcomes, adverse events, and unit metrics were prospectively collected. The inclusion criteria were based on a clinical prediction rule and included an MICU stay greater than 72 h, broad-spectrum antibiotics, and central venous catheter, along with at least two  of the following: mechanical ventilation for at least 48 h, any type of dialysis, parenteral nutrition, pancreatitis, systemic steroids, or other systemic immunosuppressive agents. For 2004, the unit had nine CBSI, corresponding to a rate of 3.4 CBSI/1,000 line-days. Four cases were caused by C. albicans, four by  C. glabrata, and one by C. tropicalis. The mean +/- standard deviation (SD) APACHE II score for these patients was 25 +/- 9. In 2005, a total of 36 patients  (2.6% of all unit admissions) received prophylaxis and the unit had two CBSI, corresponding to a rate of 0.79 CBSI/1,000 line-days. One patient had C. albicans and the other had C. tropicalis. The mean +/- SD APACHE II score for these patients was 21 +/- 8. The mean +/- SD duration of fluconazole prophylaxis was 8  +/- 6 days. Fluconazole was discontinued in two patients due to non-severe adverse events (acute eosinophilia, elevated transaminases). The attributable cost of CBSI in the unit in 2004 was $63,000 per episode. The total cost for the  36 courses of fluconazole was $6,000. When comparing the 2004 CBSI patients and the 2005 prophylaxis patients, we found similar acuity, demographics, and risk factors, with no differences in MICU or hospital mortality or length of stay. Risk-based fluconazole prophylaxis in an MICU with a high incidence of CBSI was safe and cost-effective when applied to a limited number of patients and produced a significant decrease in the incidence of this disease.  PMID: 19011913 [PubMed - indexed for MEDLINE]  5: Clin Vaccine Immunol. 2008 Dec;15(12):1868-77. Epub 2008 Oct 29.  Antibodies against glucan, chitin, and Saccharomyces cerevisiae mannan as new biomarkers of Candida albicans infection that complement tests based on C. albicans mannan.  Sendid B, Dotan N, Nseir S, Savaux C, Vandewalle P, Standaert A, Zerimech F, Guery BP, Dukler A, Colombel JF, Poulain D.  INSERM U799, Université Lille 2, Lille, France.  Antibodies against Saccharomyces cerevisiae mannan (ASCA) and antibodies against  synthetic disaccharide fragments of glucans (ALCA) and chitin (ACCA) are biomarkers of Crohn's disease (CD). We previously showed that Candida albicans infection generates ASCA. Here, we explored ALCA and ACCA as possible biomarkers  of invasive C. albicans infection (ICI). ASCA, ALCA, ACCA, and Candida mannan antigen and antibody detection tests were performed on 69 sera obtained sequentially from 18 patients with ICIs proven by blood culture, 59 sera from CD  patients, 47 sera from hospitalized subjects colonized by Candida species (CZ), and 131 sera from healthy controls (HC). ASCA, ALCA, and ACCA levels in CD and ICI patients were significantly different from those in CZ and HC subjects (P<0.0001). In ICI patients, these levels increased as infection developed. Using ASCA, ALCA, ACCA, and Platelia Candida tests, 100% of ICIs were detected, with the kinetics of the antibody response depending on the patient during the time course of infection. A large number of sera presented with more than three positive tests. This is the first evidence that the detection of antibodies against chitin and glucans has diagnostic value in fungal infections and that these tests can complement more specific tests. Future trials are necessary to assess the value of these tests in multiparametric analysis, as well as their pathophysiological relevance.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 18971303 [PubMed - indexed for MEDLINE] 

 1: Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007357.  Single dose oral etodolac for acute postoperative pain in adults.  Tirunagari SK, Derry S, Moore RA, McQuay HJ.  Anaesthesia and Critical Care, Oxford Deanery, 10, Norhaw Close, Hemel Hempstead, UK, HP2 7NH.  BACKGROUND: Etodolac is a selective cyclo-oxygenase-2 (COX-2) inhibitor, with evidence of efficacy in osteoarthritis and rheumatoid arthritis. Its analgesic efficacy in postoperative pain has not been clearly established. There are no systematic reviews on Etodolac's use in this condition. OBJECTIVES: To assess the analgesic efficacy of etodolac in single oral doses for moderate and severe postoperative pain. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials of single dose orally administered etodolac (any formulation) in adults with moderate to severe  acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. MAIN RESULTS: Nine studies (1459 participants) compared etodolac and placebo. Studies  were of adequate reporting quality, and the majority of participants had pain following dental extractions. The dose of etodolac used was 25 mg to 1200 mg, with most of the information for 100 mg and 200 mg. For at least 50% pain relief  over 4 to 6 hours compared with placebo the NNT for etodolac 100 mg (498 participants) was 4.8 (3.5 to 7.8) and for etodolac 200 mg (670 participants) it  was 3.3 (2.7 to 4.2). Very limited information with the extended release formulation did not suggest improved benefit for this outcome.The proportion of participants with at least 50% pain relief was 41% with 100 mg and 44% with 200 mg. Remedication was needed by about 60% with etodolac 200 mg or 400 mg over 6 to 8 hours, compared with almost 80% with placebo.Adverse events were uncommon, and  not significantly different form placebo. AUTHORS' CONCLUSIONS: Etodolac 200 mg may be a useful analgesic in postoperative pain, with efficacy similar to paracetamol 1000 mg and celecoxib 200 mg. Higher doses may provide analgesia equivalent to more commonly used drugs, such as ibuprofen 400 mg, naproxen 500 mg and diclofenac 50 mg.  PMID: 19588426 [PubMed - in process]  2: Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007076.  Pregabalin for acute and chronic pain in adults.  Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ.  Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.  BACKGROUND: Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. OBJECTIVES: To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified  from the reference lists of retrieved papers and on-line clinical trial databases. SELECTION CRITERIA: Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. MAIN RESULTS: There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic  nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic  neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for  central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not  affected by dose, nor was the number with a serious adverse event, which was not  more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above. AUTHORS' CONCLUSIONS: Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.  PMID: 19588419 [PubMed - in process]  3: Rheumatol Int. 2009 Jul 9. [Epub ahead of print]  Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis.  Lee YH, Woo JH, Choi SJ, Ji JD, Song GG.  Division of Rheumatology, Department of Internal Medicine, Korea University Anam  Hospital, Korea University College of Medicine, 126-1 5-ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, Korea, lyhcgh@korea.ac.kr.  The aim of this study was to determine whether the rs7574865 polymorphism of STAT4 (signal transducers and activators of transcription 4) confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. A meta-analysis was conducted on the T allele of the STAT4 rs7574865 polymorphism in 15 studies containing 16,088 RA patients and 16,509 normal control subjects. Meta-analysis revealed an association between RA and the STAT4  rs7574865 T allele in all subjects (OR = 1.271, 95% CI = 1.197-1.350, P < 0.001). Furthermore, the STAT4 rs7574865 T allele was found to be significantly associated with RA in Europeans and Asians (OR = 1.300, 95% CI = 1.195-1.414, P < 0.001; OR = 1.216, 95% CI = 1.135-1.303, P < 0.001). Stratification of RA patients according to the presence of anti-CCP antibody revealed a statistically  significant association between the T allele and RA in both anti-CCP-positive and -negative RA patients versus controls. Europeans had the lowest (21.4%) and Asians had the highest (32.0%) prevalence of the T allele among the populations studied. In conclusion, this meta-analysis confirms that the STAT4 rs7574865 polymorphism is associated with RA susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.  PMID: 19588142 [PubMed - as supplied by publisher]  4: Chem Soc Rev. 2009 Jun;38(6):1759-82. Epub 2009 Apr 21.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity.  Boisselier E, Astruc D.  Institut des Sciences Moléculaires, UMR CNRS No. 5255, Université Bordeaux I, 33405, Talence Cedex, France. d.astruc@ism.u-bordeaux1.fr.  This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and conjugation with biological and biocompatible ligands, plasmon-based labeling and imaging, optical and electrochemical sensing, diagnostics, therapy (drug vectorization and DNA/gene delivery) for various diseases, in particular cancer (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the essential in vitro and in vivo toxicity. It will interest the medicine, chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities (211 references).  PMID: 19587967 [PubMed - in process]  5: Tetrahedron Lett. 2008 Jul 7;49(28):4383-4385.  An improved synthesis of haloaceteamidine-based inactivators of protein arginine  deiminase 4 (PAD4).  Causey CP, Thompson PR.  Departent of Chemstry and Biochemistry, University of South Carolina, 631 Sumter  Street, Columbia, SC 29208.  Protein arginine deiminase 4 (PAD4) is an enzyme that hydrolyzes peptidyl arginine residues to form citrulline and ammonia. This enzyme has been implicated in several disease states, e.g. rheumatoid arthritis, and therefore represents a  unique target for the development of a novel therapeutic. A solution-phase synthesis of Cl-amidine, the most potent PAD4 inactivator described to date, has  been developed. This synthesis proceeds in 80% yield over 4 steps at a significantly (12-fold) lower cost.  PMID: 19587776 [PubMed] 

 1: Prostate. 2009 Jul 8. [Epub ahead of print]  Preliminary evaluation of the effect of dutasteride on PCA3 in post-DRE urine sediments: A randomized, open-label, parallel-group pilot study.  van Gils MP, Hessels D, Peelen WP, Vergunst H, Mulders PF, Schalken JA.  Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The  Netherlands.  BACKGROUND: Dutasteride is commonly used in patients that are also at risk for prostate cancer (PCa). Therefore, the influence of dutasteride on PCa markers has to be studied. To date, only the effect of dutasteride on serum prostate-specific antigen (PSA) has been studied. This was the first study to investigate the effect of dutasteride on the new PCa marker PCA3, longitudinally and in a dose dependent manner. METHODS: From April 25, 2005 to October 31, 2006, 16 subjects with benign prostatic hyperplasia (BPH) and 9 subjects with clinically localized  PCa were enrolled at the urological outpatient clinics of one university hospital and one community hospital. Eight subjects with BPH and five with PCa received 0.5 mg dutasteride once daily for 3 months, eight with BPH and four with PCa received 3.5 mg. No subjects were withdrawn because of adverse effects. RESULTS:  In all four groups both 0.5 and 3.5 mg dutasteride had a variable effect on the PCA3 score. In contrast, its other effects were consistent as it rapidly reduced  serum DHT by >/=90%, over time increased serum T by 20-30%, over time halved serum PSA and decreased prostate volume by 10-16%. CONCLUSIONS: In this exploratory/pilot study the effect of dutasteride on the PCA3 score was variable. This should be taken into account while using PCA3 in diagnostics. As this study  was exploratory, the influence of androgen-deprivation therapy on the PCA3 score  should be analyzed further. Prostate (c) 2009 Wiley-Liss, Inc.  PMID: 19588525 [PubMed - as supplied by publisher]  2: J Formos Med Assoc. 2009 Jul;108(7):554-9.  Cadmium concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans.  Lee JD, Wu SM, Lu LY, Yang YT, Jeng SY.  Division of Urology, Department of Surgery, Taichung Armed Forces General Hospital, and Central Taiwan University of Science and Technology, Taiwan.  Background/Purpose: Cadmium (Cd) causes various genitourinary disorders and is a  carcinogen for prostate cancer. Metallothionein (MT) is a protein that detoxifies heavy metals. We evaluated changes in Cd concentration and MT expression in human prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Our goal was to clarify the relationship between Cd concentration and MT expression in prostatic  diseases. Methods: The experimental group consisted of 18 patients who underwent  radical prostatectomy for CaP. The control group consisted of 35 patients who underwent transurethral resection of the prostate for BPH. Tissue samples were acquired from the gross tumor site and from resected chips. We determined Cd concentration by atomic absorption, MT expression by immunoblotting, and immunohistochemical staining. The significance of between-group differences for these outcomes was analyzed using Student's t tests. Results: There was no statistically significant difference in Cd concentration between the CaP and BPH  groups. Immunoblots from both groups revealed a single band. The relative intensity of the MT band was 0.58 +/- 0.09 in the BPH group and 0.17 +/- 0.03 in  the CaP group. MT expression in patients with BPH was 3.4-fold higher than in those with CaP. Conclusion: MT may bind heavy metals and protect patients from CaP. Additional studies are needed to reveal the factors that influence the expression of MT in prostate epithelial cells, and to analyze the free and compound forms of Cd at the same time.  PMID: 19586829 [PubMed - in process]  3: Urology. 2009 Jul 7. [Epub ahead of print]  Contemporary Patients With LUTS/BPH Requiring Prostatectomy Have Long-term History of Treatment With alpha(1)-Blockers and Large Prostates Compared With Past Cases.  Takeuchi M, Masumori N, Tsukamoto T.  Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.  OBJECTIVES: To retrospectively investigate the characteristics of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia for which surgery was needed during the past 20 years. In particular, the chronologic change in prostate volume at surgery and the status of alpha(1)-blocker use before surgery and its duration were studied. METHODS: The data from 371 consecutive patients with lower urinary tract symptoms/benign prostatic hyperplasia who had undergone surgery in our institute from 1987 through 2006 were retrospectively analyzed. The number of surgeries, type of surgical procedure, content and duration of medical treatment of lower urinary tract symptoms/benign prostatic hyperplasia before surgery, prostate volume on transrectal ultrasonography at baseline and at surgery, and the weight of the removed tissue were determined from the medical charts. RESULTS: The number of surgeries suddenly began to decrease between 1987 and 1990 and again from 1991 to 1994, probably owing to the introduction of 2 nonselective alpha(1)-blockers at those times in Japan. The percentage of use of alpha(1)-blockers before surgery and the duration of use increased in each period. More than 80% of recent patients had received alpha(1)-blockers before surgery, with an average duration  of 3 years. Recent patients had a large prostate volume at baseline and at surgery compared with previous patients. Corresponding to the large prostate, open subcapsular prostatectomy was indicated in 18% of the recent patients. CONCLUSIONS: Patients with surgical treatment after long-term use of alpha(1)-blockers had large prostates at baseline and at surgery. Although alpha(1)-blockers delayed the need for surgery by a few years, patients with a large prostate volume might finally need to undergo surgery.  PMID: 19586655 [PubMed - as supplied by publisher]  4: Duodecim. 2009;125(10):1119-24.  [Sexuality and sexual disorders of aging man]  [Article in Finnish]  Kaipia A, Tammela T.  TAYS, kirurgian vastuualue, PL 2000, 33521 Tampere.  Functional ability of an aging man decreases less than presumed, and sexual desire remains for long. The most common disturbances include lessened ability for erection and ejaculatory disturbances. Some men will be helped for their sexual disturbances in connection with the treatment of urinary symptoms caused by benign prostatic hyperplasia. Erectile dysfunction may be the initial symptom  of cardiovascular disease. Erectile dysfunction may also be caused by medication  used by the patient. If an aged man wants therapy for his sexual disorder, he should be individually provided with the most appropriate treatment form.  Publication Types:      English Abstract  PMID: 19585909 [PubMed - in process]  5: Phytother Res. 2009 Jul 7. [Epub ahead of print]  Eviprostat suppresses urinary oxidative stress in a rabbit model of partial bladder outlet obstruction and in patients with benign prostatic hyperplasia.  Matsumoto S, Hanai T, Matsui T, Oka M, Tanaka M, Uemura H.  Urological and Urodynamics Center, Koushinkai Hospital, Sakai, Japan.  Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity. The present study investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in a rabbit model of surgical  partial bladder outlet obstruction (PBOO) and in patients with lower urinary tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in  urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of sham-operated rabbits. When twice-daily Eviprostat was administered orally throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5-fold lower urinary 8-OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 +/- 2.74 to 13.67 +/- 2.30 and the quality of life score from 4.22 +/- 0.40 to 3.22 +/- 0.46. The findings provide evidence that the antioxidant activity of Eviprostat is responsible for its beneficial effects in the treatment of BPH. Copyright (c) 2009 John Wiley & Sons, Ltd.  PMID: 19585469 [PubMed - as supplied by publisher] 

 1: Indian J Dermatol Venereol Leprol. 2009 Jul-Aug;75(4):373-8.  Outcome of dexamethasone-cyclophosphamide pulse therapy in pemphigus: a case series.  Kandan S, Thappa DM.  Department of Dermatology and Sexually Transmitted Diseases (STD), Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India.  BACKGROUND: Pemphigus disorders are a group of serious and potentially life-threatening diseases affecting skin and/or mucus membranes. Dexamethasone-cyclophosphamide pulse (DCP) therapy has shown promising results in the management of these diseases. AIMS: The objective of the study was to assess  the outcome of DCP therapy in pemphigus. METHODS: Pemphigus patients who had been treated with DCP therapy from 2001 to 2008 were prospectively and retrospectively analyzed. RESULTS: A total of 65 pemphigus patients were enrolled. Male to female ratio was 1 : 1.82. Mean age of patients was 44.65 +/- 11.85 years with a range of 14 to 73 years. Thirty two patients completed phase I, of which 28 (9 in phase II, 7 in phase III and 12 in phase III) were maintaining remission and four patients relapsed. Relapse was observed only in patients who discontinued or took irregular treatment. Six patients were declared cured of disease. Five patients died during phase I. Dexamethasone-cyclophosphamide pulse therapy is not absolutely free from adverse effects. Most of the immediate side effects were expected, tolerable and did not pose any problem in continuing treatment. There was a slight increased incidence of weight gain, hypertension, diabetes mellitus, cataract and Cushingoid habitus, since most of our patients also received additional daily oral steroids. Also, there was a high incidence of secondary pyogenic infections of skin lesions and oral candidiasis during phase I. Staphylococcus aureus was the commonest bacteria isolated from the pus of skin lesions. Most of the alterations in laboratory parameters were transitory or correctable, and did not pose a problem in continuing therapy. CONCLUSIONS: DCP therapy was found to be effective in inducing and maintaining remission in pemphigus, provided the patients receive regular and complete treatment.  PMID: 19584462 [PubMed - in process]  2: J Antimicrob Chemother. 2009 Jul 7. [Epub ahead of print]  Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis.  Lazzell AL, Chaturvedi AK, Pierce CG, Prasad D, Uppuluri P, Lopez-Ribot JL.  Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, Texas, USA.  Objectives We sought to develop a novel model of central venous catheter (CVC)-associated candidiasis in mice and to use this model to examine the efficacy of caspofungin to treat and prevent Candida albicans biofilms in vivo. Methods We used catheterized mice, commercially available from the National Cancer Institute, to form C. albicans biofilms inside CVCs. Once the model was developed, we examined the efficacy of caspofungin for the treatment of preformed biofilms and for the prevention of C. albicans biofilm formation. Results We developed a relatively simple murine model of CVC-associated candidiasis that minimized the number of manipulations necessary for in vivo biofilm formation. C. albicans biofilms formed in vivo display structural features similar to those observed for models of in vitro- and other in vivo-formed biofilms. Following model development, 0.25 microg/mL of caspofungin was instilled in the catheter to treat preformed biofilms. The results indicated that caspofungin treatment significantly reduced biofilm fungal load in the catheters and dissemination to kidneys compared with untreated controls. In a second set of experiments catheters were pre-treated by filling with 60 microg/mL of caspofungin before challenge with C. albicans via the CVC. Again, the results indicated a significant reduction in biofilm fungal load and dissemination to kidneys compared with untreated controls. Conclusions We have developed a novel model of  CVC-associated candidiasis in mice. Using this model we demonstrate the efficacy  of caspofungin for the treatment and prevention of C. albicans biofilms in vivo.  PMID: 19584104 [PubMed - as supplied by publisher]  3: BJOG. 2009 Jul 7. [Epub ahead of print]  Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial.  Witt A, Kaufmann U, Bitschnau M, Tempfer C, Ozbal A, Haytouglu E, Gregor H, Kiss  H.  Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.  Please cite this paper as: Witt A, Kaufmann U, Bitschnau M, Tempfer C, Ozbal A, Haytouglu E, Gregor H, Kiss H. Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial. BJOG 2009; DOI: 10.1111/j.1471-0528.2009.02262.x.Objective Antimycotics effectively treat sporadic and recurrent vulvovaginal candidiasis (RVVC). Classic homeopathy  (CH) is also used to treat this condition. We compared the efficacy of CH and itraconazole in reducing the frequency of RVVC episodes. Design Single-centre, prospective, randomised trial. Sample One hundred-and-fifty patients with a history of RVVC and an acute episode of VVC. Methods Women were randomised into 3 groups: itraconazole with lactobacilli (group 1), itraconazole without lactobacilli (group 2) and CH (group 3). Itraconazole treatment of acute infection was followed by a 6-month maintenance regimen with monthly single-day itraconazole (200 mg bid). Women in group 1 were given additional vaginal lactobacilli for 6 days per month throughout the maintenance regimen Thereafter,  patients were followed without treatment for 6 months. CH treatment was performed for 12 months. Results Women in groups 1 and 2 reached a culture-free status significantly earlier than women in group 3 (log-rank test; P < 0.0001). Specifically, before the start of the maintenance regimen, 44 of 49 women (89.8%) in group 1 and 40 of 47 women (85%) in group 2 were free of Candida detectable by culture, 22 of 46 (47%) women in group 3 reached a culture-free status after the  first visit, but had a recurrence significantly earlier compared with women in groups 1 and 2 (log-rank test; P = 0.002). After 12 months, 19 of 25 (76%) women  in group 1, 18 of 23 (78%) women in group 2 and 9 of 23 (39%) women in group 3 were free of culture-detectable Candida. Assessment of RVVC-associated complaints by VAS score showed that women in group 3 had a significantly higher level of discomfort (36.8, 25.1 and 27.7 respectively; P < 0.001) and were significantly less satisfied (59.2, 68.2 and 71.7 respectively; P < 0.001) than patients in groups 1 and 2. Conclusions Monthly cycle-dependent itraconazole is more effective than CH in the treatment of RVVC. Lactobacilli do not confer an added benefit.  PMID: 19583713 [PubMed - as supplied by publisher]  4: J Reprod Med. 2009 May;54(5):281-7.  A retrospective study of relevant diagnostic procedures in vulvodynia.  Petersen CD, Kristensen E, Lundvall L, Giraldi A.  Sexological Clinic, Psychiatric Center, and Department of Gynecology, Juliane Marie Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. cdamsted@dadlnet.dk  OBJECTIVE: To identify objective clinical signs of vulvodynia and determine specific diagnostic tests for vulvodynia in women referred to a vulvar outpatient clinic for vulval complaints. STUDY DESIGN: A retrospective study was performed of the medical records of 201 consecutive Danish patients suspected of suffering  from vulvodynia who were referred to a vulvar outpatient clinic (Department of Gynecology, Rigshospitalet University Hospital) between October 2003 and January  2006. RESULTS: Of 201 women, 117 were diagnosed with vulvodynia and 84 had other  diagnoses. Of the women diagnosed with vulvodynia in the vulvar clinic, 88.9% were correctly diagnosed before referral. The women with vulvodynia were more likely to report dyspareunia (chi2 = 7.89, p = 0.005) and stinging pain (chi2 = 3.74, p = 0.05). The nonvulvodynia group was more likely to report a tendency toward fissures (chi2 = 5.94, p < 0.05). CONCLUSION: Self-reported dyspareunia and stinging pain are strongly associated with vulvodynia. Self-reported pruritus and a tendency toward fissures are not likely to be associated with vulvodynia. Whether vulvar biopsies should be performed regularly when redness and pain is present must be explored further in prospective studies.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19517691 [PubMed - indexed for MEDLINE]  5: Transplantation. 2009 Jun 15;87(11):1706-11.  Early intra-abdominal infections associated with orthotopic liver transplantation.  Reid GE, Grim SA, Sankary H, Benedetti E, Oberholzer J, Clark NM.  Section of Infectious Diseases, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA. gereid@comcast.net  BACKGROUND: Postoperative infections remain a significant problem among liver transplant recipients (LTRs). An early cause of morbidity after liver transplantation is intra-abdominal infection (IAI) about which there are limited  data. METHODS: We report a retrospective review of 169 adult LTRs from January 1, 2002 to June 9, 2006, comparing those who developed early postoperative IAI (peritonitis, biliary tract infection, abdominal abscess, or enteritis) with those who did not to identify clinical features and risk factors, analyze epidemiology, and assess graft and patient survival. RESULTS: Sixty-eight patients (40%) had 104 infections, with 148 pathogens isolated. Leukocytosis (53%) and fever (34%) were the most common clinical features, and peritonitis (43%) was the most common manifestation. Enterococcus spp., the most frequent single pathogens, comprised 26% of organisms cultured. There were significant associations of IAI with pretransplant ascites (P=0.002), posttransplant dialysis (P=0.015), and non-IAI surgical complications (P<0.001). There was a trend toward graft failure in patients with IAI (P=0.051) but increased mortality was not associated with IAI. Use of pretransplant antibiotics was significantly associated with development of multiple drug-resistant organisms in IAI (P=0.032). CONCLUSION: IAI occurred at a relatively high rate in the early postoperative period, and fever was not a major indicator. In patients receiving  antibiotics within 2 weeks before transplantation, multiple drug-resistant organisms often caused IAI. In addition, the presence of pretransplant ascites, posttransplant dialysis, and wound infection or reoperation after transplant should alert one to the increased risk of IAI in LTRs.  PMID: 19502964 [PubMed - indexed for MEDLINE] 

 1: Cancer Detect Prev. 2009;32(5-6):386-94.  Vitamin D receptor gene polymorphism(s) and breast cancer risk in north Indians.  Chakraborty A, Mishra AK, Soni A, Regina T, Mohil R, Bhatnagar D, Bhatnagar A, Chintamani C, Sharma PC, Saxena S.  Institute of Pathology, Safdarjang Hospital Campus, New Delhi 110029, India.  BACKGROUND: Vitamin D (1,25-dihydroxyVitamin D3) has shown experimentally anticarcinogenic effects and is thought to protect against breast cancer. The actions of Vitamin D are mediated via the Vitamin D receptor (VDR), and the polymorphisms at 3'UTR region of this gene are associated with the risk and progression of breast carcinoma. The current study is an attempt to examine the association of these variations with breast cancer risk in north Indians. METHODS: A total of 160 cases and 140 control subjects were studied for the polymorphisms at 3' end of the VDR gene. A polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method and fragment analysis  was performed to determine ApaI and TaqI polymorphisms and variable length poly-A microsatellite repeats. Linkage disequilibrium (LD) was calculated for each pair  of polymorphisms. Unadjusted and adjusted odds ratios for breast cancer with genotypes comprising the polymorphic sites were calculated to understand their role towards breast cancer susceptibility. RESULTS: Patient's with long poly-A repeat showed a significant association with disease (chi 2 = 9.52, df = 2, P <or= 0.01). Compared to subjects having two S alleles (SS), odds ratios (and 95%  CI) were 0.75 (0.45-1.23) and 2.49 (1.18-5.27) for subjects having genotypes SL and LL, respectively. Among matched pairs (age), the poly-A LL genotype was found significantly associated with increased risk of breast cancer among early-onset cases (P = 0.02). The unconditional logistic regression analysis demonstrated a significant association between grade and LL genotype [(unadjusted odds ratio (95% CI): 4.45 (1.87, 10.63); adjusted odds ratio: 4.66 (1.88, 11.53)]. No significant association was observed for the VDR ApaI (chi 2 = 1.00, df = 2, P =  0.60) and TaqI polymorphism (chi 2 = 0.35, df = 2, P = 0.83). Although, strong LD was not observed among these polymorphic sites, it denies the total equilibrium at the same time. Based on haplotype distribution, the most common one observed among cases and controls was ATS while, genotype AATTLL had shown a significant association with the breast cancer risk (P = 0.02). CONCLUSIONS: The results indicate that the VDR poly-A polymorphism is significantly associated with breast cancer risk in north Indians especially with early onset disease. Although, ApaI  and TaqI did not show any significant association with the disease when analyzed  in isolation, but TaqI might modulate the risk associated with L alleles. Further, understanding the functional role of these variants residing on the VDR  haplotype associated with disease susceptibility may suggest novel approaches for breast cancer prevention and therapy.  Publication Types:      Research Support, Non-U.S. Gov't  PMID: 19588543 [PubMed - in process]  2: IUBMB Life. 2009 Jul 8. [Epub ahead of print]  Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis.  Thompson HJ, Jiang W, Zhu Z.  Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO, USA.  Evidence is strong that a reduction in risk for breast cancer is associated with  moderate to vigorous physical activity (PA); however, there is limited understanding of the role of type, intensity, duration, and frequency of PA and their mechanisms in accounting for this health benefit. The objective of this review is to stimulate investigations of candidate mechanisms that may account for the effects of the intensity and duration of aerobic PA on breast cancer risk and tumor burden. Three hypotheses are considered: 1) the mTOR network hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR  signaling network in mammary carcinomas; 2) the hormesis hypothesis: the carcinogenic response to PA is nonlinear and accounted for by a physiological cellular stress response; and 3) the metabolic reprogramming hypothesis: PA limits the amount of glucose and glutamine available to mammary carcinomas thereby inducing apoptosis because tumor-associated metabolic programming is reversed. To link these hypotheses to systemic effects of PA, it is recommended that consideration be given to determining: 1) what contracting muscle releases into circulation or removes from circulation that would directly modulate the carcinogenic process in epithelial cells; 2) whether the effects of muscle contraction on epithelial cell carcinogenesis are exerted in an endocrine, paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle contraction on malignant cells differ from effects on normal or premalignant cells that do not manifest the hallmarks of malignancy. (c) 2009 IUBMB IUBMB Life, 2009.  PMID: 19588523 [PubMed - as supplied by publisher]  3: Int J Cancer. 2009 Jul 8. [Epub ahead of print]  A case-control study on hormone therapy as a risk factor for breast cancer in finland: Intrauterine system carries a risk as well.  Lyytinen HK, Dyba T, Ylikorkala O, Pukkala EI.  Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, P.O. Box 140, FI-00029 HUS, Finland.  The purpose of this study was to evaluate the association between postmenopausal  hormone therapy (HT) and the risk for breast cancer in recently postmenopausal Finnish women.All Finnish women with first invasive breast cancer diagnosed between the ages of 50-62 during 1995-2007 (n= 9956) were identified from the Finnish Cancer Registry. For each case, three controls of the same age were retrieved from the Finnish Population Register. The cases and controls were linked to the national medical reimbursement register to assess the use of HT. The odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer were calculated with conditional logistic regression analysis, adjusting for parity, age at the first birth and health care district. Oestradiol-only therapy (991 users with breast cancer, n), or oral progestagen (n=138) were not accompanied by an increased risk. Oestradiol-progestagen therapy (EPT) (n=1731) was associated with an elevated risk in the whole series (OR 1.36; 95% CI 1.27-1.46). The risk became detectable in less than 3 years of use. Continuous EPT use tended to be associated with a higher risk for breast cancer than the sequential EPT use. The  use of tibolone (n=80) (1.36; 1.15-1.96), a levonorgestrel releasing intrauterine system (LNG-IUS) alone (n=154) (1.45; 1.97-1.77) or as a complement to oestradiol (n=137) (2.15; 1.72-2.68) was also associated with an increased risk. The association between HT use and the risk for breast cancer shows a large variation between various forms of HT, and also the use of LNG-IUS may carry a risk. (c) 2009 UICC.  PMID: 19588504 [PubMed - as supplied by publisher]  4: Int J Cancer. 2009 Apr 27. [Epub ahead of print]  EGFRvIII-induced estrogen-independence, tamoxifen-resistance phenotype correlates with PgR expression and modulation of apoptotic molecules in breast cancer.  Zhang Y, Su H, Rahimi M, Tochihara R, Tang C.  Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, DC.  The tumor-specific, ligand-independent, constitutively active epidermal growth factor receptor (EGFR) variant, EGFRvIII, remains understudied in breast cancer.  Here, we report that expression of EGFRvIII in the ErbB-2-overexpressing, estrogen-dependent MDA-MB-361 breast cancer cell line resulted in significant estrogen-independent tumor growth in ovariectomized, athymic nude mice in comparison to MDA-MB-361/wt cells. MDA-MB-361/vIII breast cancer cells maintained estrogen-induced tumor growth, but were tamoxifen-resistant in the presence of estrogen, while MDA-MB-361/wt cells had a significant reduction in tumor growth in the presence of estrogen and tamoxifen. Tamoxifen alone did not have a significant effect on EGFRvIII-mediated estrogen-independent tumor growth. Constitutive signaling from the EGFRvIII receptor resulted in an increased activation of both the Akt and MAPK pathways. Compared to estrogen-dependent, tamoxifen-sensitive MCF-7/vIII breast cancer cells, which had unchanged levels of ERalpha, but an increase in progesterone receptor (PgR) in comparison to MCF-7/wt cells, MDA-MB-361/vIII cells had a reduction in ERalpha expression as well as a more pronounced reduction in PgR compared with MDA-MB-361/wt cells. EGFRvIII expression was also significantly associated with an absence of PgR protein in invasive human breast cancer specimens. Alterations of proapoptotic proteins and  antiapoptotic proteins were observed in EGFRvIII transfectants. In conclusion, constitutive signaling through EGFRvIII and its downstream effector proteins crosstalks with the ERalpha pathway, resulting in loss of PgR expression and alterations in the apoptotic pathway, which may result in the estrogen-independent, tamoxifen-resistant phenotype conferred to EGFRvIII-expressing breast cancer cells. (c) 2009 UICC.  PMID: 19588487 [PubMed - as supplied by publisher]  5: Int J Cancer. 2009 Jun 2. [Epub ahead of print]  Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer.  Kabat GC, Kim M, Caan BJ, Chlebowski RT, Gunter MJ, Ho GY, Rodriguez BL, Shikany  JM, Strickler HD, Vitolins MZ, Rohan TE.  Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.  Experimental and epidemiological evidence suggests that circulating glucose and insulin may play a role in breast carcinogenesis. However, few cohort studies have examined breast cancer risk in association with glucose and insulin levels,  and studies to date have had only baseline measurements of exposure. We conducted a longitudinal study of postmenopausal breast cancer risk using the 6% random sample of women in the Women's Health Initiative clinical trials whose fasting blood samples, provided at baseline and at years 1, 3 and 6, were analyzed for glucose and insulin. In addition, a 1% sample of women in the observational study, who had glucose and insulin measured in fasting blood samples drawn at baseline and in year 3, were included in the analysis. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of baseline and follow-up measurements of serum glucose and insulin with breast cancer risk. All statistical tests were 2-sided. Among 5,450 women with baseline serum glucose and insulin values, 190 incident cases of breast cancer were ascertained over a median of 8.0 years of follow-up. The highest tertile of baseline insulin, relative to the lowest, was associated with a 2-fold increase in risk in the total population (multivariable hazard ratio 2.22, 95% confidence interval 1.39-3.53) and with a 3-fold increase in risk in women who were not enrolled in the intervention arm of any clinical trial (multivariable hazard ratio 3.15, 95% confidence interval 1.61-6.17). Glucose levels showed no association with risk. Analysis of the repeated measurements supported the results of the baseline analysis. These data suggest that elevated serum insulin  levels may be a risk factor for postmenopausal breast cancer. (c) 2009 UICC.  PMID: 19588485 [PubMed - as supplied by publisher] 

 1: Cancer Detect Prev. 2009;32(5-6):363-71.  Epidemiology of primary brain tumors in the Middle Eastern population in California, USA 2001-2005.  Nasseri K, Mills JR.  Public Health Institute, California Cancer Registry, California, USA. qnasseri@cox.net  BACKGROUND: The fast growing Middle Eastern (ME) population has rarely been studied in the U.S.. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle  Eastern White (NHNMW) in California. METHODS: ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant,  16 uncertain) in the ME and 15,589 cases (8352 benign, 6812 malignant, 425 uncertain) in the NHNMW were available for this study. RESULTS: ME patients were  significantly (p < 0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p < 0.05). Rates for malignant  tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. CONCLUSIONS: This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to  be evaluated in future studies.  Publication Types:      Research Support, N.I.H., Extramural     Research Support, Non-U.S. Gov't     Research Support, U.S. Gov't, P.H.S.  PMID: 19588542 [PubMed - in process]  2: J Neurosci. 2009 Jul 8;29(27):8790-7.  The gad2 promoter is a transcriptional target of estrogen receptor (ER) alpha and ERbeta: a unifying hypothesis to explain diverse effects of estradiol.  Hudgens ED, Ji L, Carpenter CD, Petersen SL.  Department of Biology, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.  Estradiol (E(2)) regulates a wide range of neural functions, many of which require activation of estrogen receptor alpha (ERalpha) and/or ERbeta, ligand-gated transcriptional regulators. Surprisingly, very few neural gene targets of ERs have been identified, and these cannot easily explain the myriad effects of E(2). GABA regulates most of the same neural functions as E(2), and GABAergic neurons throughout the brain contain ER. Therefore, we examined whether E(2) directly regulates expression of glutamic acid decarboxylase 2 (gad2), the enzyme primarily responsible for GABA synthesis for synaptic release. Using dual  luciferase assays, we found that E(2), but not other gonadal steroids, stimulated the activity of a 2691 bp rat gad2 promoter reporter construct. Activation required either ERalpha or ERbeta, and ERbeta did not repress ERalpha-mediated transactivation. Site-directed mutagenesis studies identified three estrogen response elements (EREs) with cell-specific functions. An ERE at -711 upstream of the gad2 translational start site was essential for transactivation in both MCF-7 breast cancer cells and SN56.B5.G4 neural cells, but an ERE at -546 enhanced transcription only in neural cells. A third ERE at -1958 was inactive in neural cells but exerted potent transcriptional repression in E(2)-treated MCF-7 cells.  Chromatin immunoprecipitation assays in mouse GABAergic N42 cells confirmed that  E(2) induced ERalpha binding to a DNA fragment containing sequences corresponding to the -546 and -711 EREs of the rat promoter. Based on these data, we propose that direct transcriptional regulation of gad2 may explain, at least in part, the ability of E(2) to impact such a diverse array of neural functions.  Publication Types:      Research Support, N.I.H., Extramural  PMID: 19587286 [PubMed - in process]  3: J Formos Med Assoc. 2009 Jul;108(7):592-4.  Early-onset Stroke in a Patient With Nasopharyngeal Cancer Associated With Protein C Deficiency.  Chiu YN, Wang TG, Chang CW.  Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan.  We report a 47-year-old male stroke patient with nasopharyngeal cancer (NPC) and  protein C deficiency. The patient was diagnosed with NPC and received a complete  course of radiotherapy. Infarction stroke occurred 28 months after radiotherapy and magnetic resonance imaging of the brain confirmed the diagnosis. Carotid duplex sonography showed 50-79% stenosis in his left internal carotid artery. Coagulation profiles indicated protein C deficiency. After medical treatment and  rehabilitation, the patient regained the ability to walk and he could perform most of his daily activities. Radiotherapy-induced carotid stenosis is an exacerbating feature of stroke in patients with protein C deficiency. We suggest  early carotid duplex sonography and survey of the coagulation profile to prevent  a stroke in patients with NPC.  PMID: 19586834 [PubMed - in process]  4: Epidemiol Prev. 2009 Jan-Apr;33(1-2):37-44.  [Statistical analysis of the incidence of some cancers in the province of Taranto 1999-2001]  [Article in Italian]  Graziano G, Bilancia M, Bisceglia L, de Nichilo G, Pollice A, Assennato G.  Osservatorio epidemiologico regionale, Regione Puglia. graziano@dss.uniba.it  OBJECTIVE: to estimate the spatial distribution of risk, in order to assess its correlation to environmental pollution exposure around the large production facilities located in the Taranto area, and to identify high risk areas not previously reported. SETTING: Italy, Taranto province (581,508 inhabitants). DESIGN: incidence data in 29 municipalities of the Taranto province were extracted from the Jonico Salentino Cancer Registry (RTJS) for the following cancer sites: lung (ICDX C33-C34); pleura, pleuric mesothelioma (ICDX C45.0); bladder, malignancies only (ICDX C67); brain (ICDX C70-72); non-Hodgkin lymphoma  (ICDX C82-85, C96); leukaemia (ICDX C91-5). Age standardized incidence rates for  the whole province were computed. High-level risk areas were classified using a Poisson model, computing area-specific p-values associated to the null hypothesis of no increased risk (i.e. relative risk equal to 1). A hierarchical spatial Bayesian model was estimated to strengthen results: specifically two additional variance components, accounting for relative risk spatial autocorrelation and excess heterogeneity respectively, were considered in the model specification. Bayesian mapping of disease incidence allows for the drawing of regularized (smoothed) maps. To adjust for the effect of socio-economic deprivation, a five-variable index was introduced into the model as an ecological covariate. RESULTS: an increased risk of lung, pleura and bladder cancer was observed among  male residents in the city of Taranto (respectively: SIR 1.24, p-value < 0.01; SIR: 2.21, p-value < 0.01; SIR 1.28, p-value < 0.01). For non-Hodgkin lymphoma, a significant value was observed in the city of Taranto for males (SIR 1.46, p-value < 0.01), as well as in the neighbouring area of Pulsano for females (SIR  3.88, p-value < 0.01). An unexpected increased risk of brain cancer was found in  both sexe risk (especially among males) of lung, pleura and bladder cancer is likely related to the chemical pollutants and asbestos, due to the presence of many industries and shipyards in the city of Taranto.  Publication Types:      English Abstract  PMID: 19585874 [PubMed - in process]  5: Am J Ind Med. 2009 Jul 7. [Epub ahead of print]  Neurological mortality among U.S. veterans of the Persian Gulf War: 13-year follow-up.  Barth SK, Kang HK, Bullman TA, Wallin MT.  Department of Veterans Affairs, Environmental Epidemiology Service, Washington, District of Columbia.  BACKGROUND: This study focuses on long-term mortality, specifically brain cancer, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and multiple sclerosis  (MS) of 621,902 veterans who served in the 1990-1991 Persian Gulf War (GW), and 746,248 non-GW veterans. METHODS: Follow-up began with the date the veteran left  the GW theater or May 1, 1991 and ended with the date of death or December 31, 2004. Cox proportional hazard models were used for analyses. RESULTS: Adjusted mortality rate ratios (aRR) of GW veterans compared to non-GW veterans were not statistically significant for brain cancer (aRR = 0.90, 95% confidence interval (CI): 0.73, 1.11), MS (aRR = 0.61, 95% CI: 0.23, 1.63), Parkinson's disease (aRR  = 0.71, 95% CI: 0.17, 2.99), or ALS (aRR = 0.96, 95% CI: 0.56, 1.62). GW veterans potentially exposed to nerve agents for 2 or more days and GW veterans exposed to oil well fire smoke were at increased risk for brain cancer mortality (aRR = 2.71, 95% CI: 1.25, 5.87; aRR = 1.81, 95% CI: 1.00, 3.27; respectively). CONCLUSIONS: The risk of death due to ALS, MS, Parkinson's disease, and brain cancer was not associated with 1991 GW service in general. However, GW veterans potentially exposed to nerve agents at Khamisiyah, Iraq, and to oil well fire smoke had an increased risk of mortality due to brain cancer. Am. J. Ind. Med. (c) 2009 Wiley-Liss, Inc.  PMID: 19585544 [PubMed - as supplied by publisher]