MedWorm: Ovarian Cancer

Expression of hepatocyte nuclear factor 4α in primary ovarian mucinous tumors

Pathology International — Sat, 11 Oct 2008 06:46:58 +0100

Hepatocyte nuclear factor 4[alpha] (HNF4[alpha]) is a member of the nuclear receptor superfamily and is expressed in several endodermal tissues. The aim of the present study was to examine the expression of HNF4[alpha] on ovarian epithelial tumors with immunocytochemistry and immunohistochemistry using mAbs recognizing P1 and P2 promoter-driven HNF4[alpha]. Ovarian mucinous adenoma, mucinous tumors of borderline malignancy, and mucinous adenocarcinoma had positive nuclear staining for HNF4[alpha] (41/45, 91%). One-third (34%) of mucinous tumors had P1-positive staining and most had P1/P2-positive staining (93%). MUC2- and MUC5AC-positive staining was observed in 34% and 95% of mucinous tumors, respectively. The histological subtype of these mucinous tumors was not correlated with HNF4[alpha] expression. On cytology it was found that cancer cells in the ascites from ovarian mucinous adenocarcinomas were HNF4[alpha] positive, but tumor cells in ascites from other types of ovarian carcinomas were negative for HNF4[alpha]. Thus, HNF4[alpha] is demonstrated to be a useful marker for histological and cytological diagnosis of ovarian mucinous tumors. (Source: Pathology International)

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Talc use in genital area linked to increased risk for ovarian cancer

Medscape Medical News Headlines — Fri, 10 Oct 2008 21:00:00 +0100

Women should avoid using talc in the genital area, say researchers reporting further evidence supporting an association between such use and an increase in the risk for ovarian cancer. Medscape Medical News (Source: Medscape Medical News Headlines)

Prognostic value of kallikrein-related peptidase 6 protein expression levels in advanced ovarian cancer evaluated by automated quantitative analysis (aqua)

Cancer Science — Fri, 10 Oct 2008 04:00:00 +0100

Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. In the present study, we sought to determine the prognostic value of kallikrein-related peptidase 6 (KLK6) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of KLK6 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred and thirty-five of 150 cases had sufficient tissue for AQUA analysis. In univariate survival analysis, low tumor KLK6 expression was associated with better outcome for overall survival over 3 years (P = 0.019). There was no association between tumor KLK6 expression and progression-free survival (P = 0.128). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor KLK6 expression level was one of the most significant predictor variable for overall survival (95% confidence interval, 1.19[ndash]3.50; P = 0.009). High tumor KLK6 protein expression is associated with inferior patient outcome in ovarian cancer. KLK6 may represent a promising disease biomarker and therapeutic target in ovarian cancer. (Cancer Sci 2008) (Source: Cancer Science)

Fda says ovarian cancer test is marketed illegally

MedPage Today Hematology/Oncology — Thu, 09 Oct 2008 22:13:52 +0100

ROCKVILLE, Md. (MedPage Today) -- The FDA has warned a company that makes a serum-based ovarian cancer test had no legal authority to put the assay on the market, which the firm did in June. (Source: MedPage Today Hematology/Oncology)

U.s. says labcorp ovarian cancer test sales illegal

Medscape Business of Medicine Headlines — Thu, 09 Oct 2008 16:54:06 +0100

Laboratory Corp of America is violating the law by selling an ovarian cancer screening test without regulatory approval, U.S. health officials said Wednesday. Reuters Health Information (Source: Medscape Business of Medicine Headlines)

Fda: labcorp’s marketing of ovarian-cancer test violates law

bizjournals.com Health Care:Pharmaceuticals headlines — Thu, 09 Oct 2008 13:22:13 +0100

The federal Food and Drug Administration has told Burlington-based Laboratory Corporation of America Holdings that it is violating the law by selling a test for ovarian cancer without regulatory approval. (LH) (Source: bizjournals.com Health Care:Pharmaceuticals headlines)

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Fda: labcorp’s marketing of ovarian-cancer test violates law

bizjournals.com Health Care:Pharmaceuticals headlines — Thu, 09 Oct 2008 12:05:04 +0100

The federal Food and Drug Administration has told Burlington-based Laboratory Corporation of America Holdings that it is violating the law by selling a test for ovarian cancer without regulatory approval. (Source: bizjournals.com Health Care:Pharmaceuticals headlines)

Women with breast cancer gene grapple with choosing surgery...now or later?

Cancercompass News: Gynecological Cancer — Thu, 09 Oct 2008 08:41:50 +0100

For Joanna Rudnick, being healthy is complicated. The 34-year-old Chicago filmmaker is one of a new group of cancer "pre-vivors" - women with a genetic mutation that scientists say puts them at a high risk of developing breast and ovarian cancer. In other words, she's cancer-free today, but may not be tomorrow. "In a bizarre way, I have a dual citizenship," said Rudnick. "I am healthy - I've never had cancer. But there's this threat always looming over my head." It's an increasingly common predicament, one Rudnick decided to feature in her directorial debut, "In the Family." The 86-minute documentary, airing Oct. 4 on KCET, examines the challenges women with the so-called "breast cancer gene" face when trying to an... (Source: Cancercompass News: Gynecological Cancer)

Fda warns labcorp about illegal sales of ovarian cancer test

Medical Devices News From Medical News Today — Thu, 09 Oct 2008 07:00:00 +0100

The US Food and Drug Administration (FDA) has written to global clinical network giant LabCorp to warn the company it is violating the law on a number of counts by selling its ovarian cancer test OvaSure. There was no suggestion that there was something clinically wrong with the test. (Source: Medical Devices News From Medical News Today)

F.d.a. says cancer test failed to get its approval

NYT > Health — Thu, 09 Oct 2008 04:43:28 +0100

The F.D.A. told LabCorp that its blood test to detect ovarian cancer, called OvaSure, requires agency approval before it can be marketed. (Source: NYT > Health)

Discrimination analysis of mass spectrometry proteomics for ovarian cancer detection1

Acta Pharmacologica Sinica — Thu, 09 Oct 2008 04:00:00 +0100

Aim: A discrimination analysis has been explored for the probabilistic classification of healthy versus ovarian cancer serum samples using proteomics data from mass spectrometry (MS). Methods: The method employs data normalization, clustering, and a linear discriminant analysis on surface-enhanced laser desorption ionization (SELDI) time-of-flight MS data. The probabilistic classification method computes the optimal linear discriminant using the complex human blood serum SELDI spectra. Cross-validation and training/testing data-split experiments are conducted to verify the optimal discriminant and demonstrate the accuracy and robustness of the method. Results: The cluster discrimination method achieves excellent performance. The sensitivity, specificity, and positive predictive values are above 97% on ovarian cancer. The protein fraction peaks, which significantly contribute to the classification, can be available from the analysis process. Conclusion: The discrimination analysis helps the molecular identities of differentially expressed proteins and peptides between the healthy and ovarian patients. (Source: Acta Pharmacologica Sinica)

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Cross-sectional analysis of germline brca1 and brca2 mutations in japanese patients suspected to have hereditary breast/ovarian cancer

Cancer Science — Thu, 09 Oct 2008 04:00:00 +0100

The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22[ndash]2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165[ndash]7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25[ndash]6.64). (Cancer Sci 2008) (Source: Cancer Science)

A case of ovarian cancer associated with hypercalcemia

Japanese Journal of Clinical Oncology — Thu, 09 Oct 2008 04:00:00 +0100

(Source: Japanese Journal of Clinical Oncology)

A joinpoint regression analysis of long-term trends in cancer mortality in japan (1958-2004)

International Journal of Cancer — Thu, 09 Oct 2008 04:00:00 +0100

Cancer is one of the major targets of disease control programs in Japan. A Joinpoint regression model was used to analyze the long-term trends of mortality related to overall cancer and the 15 most common cancers based on published data from the National Vital Statistics of Japan between 1958 and 2004. Since 1996, a decline has been seen in overall cancer for both sexes in Japan. Most of the common sites, including cancers of the stomach, colon, liver, gallbladder and lung and leukemia in both sexes, cancer of esophagus in men and rectal and ovarian cancers in women showed a decreasing trend, and cancers of the rectum, pancreas, prostate and urinary bladder and malignant lymphoma in men and cancers of the esophagus and uterus in women leveled off during the most recent period. However, an increasing trend was confirmed for cancers of the pancreas, breast and urinary bladder and malignant lymphoma in women. An effective cancer control program including prevention, early detection and treatment should be implemented to further reduce the cancer mortality, particularly for cancer sites that show higher mortality rates or increasing trends. © 2008 Wiley-Liss, Inc. (Source: International Journal of Cancer)

Fda: labcorp’s marketing of ovarian-cancer test violates law

bizjournals.com Health Care:Pharmaceuticals headlines — Wed, 08 Oct 2008 20:16:01 +0100

The federal Food and Drug Administration has told Burlington-based Laboratory Corporation of America Holdings that it is violating the law by selling a test for ovarian cancer without regulatory approval. (Source: bizjournals.com Health Care:Pharmaceuticals headlines)

F.d.a. says labcorp cancer test is illegal

NYT > Health — Wed, 08 Oct 2008 20:14:16 +0100

The F.D.A. told the company that its blood test to detect ovarian cancer, called OvaSure, requires agency approval before it can be marketed. (Source: NYT > Health)

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Talc use in genital area linked to increased risk for ovarian cancer

Medscape Medical News Headlines — Wed, 08 Oct 2008 19:50:27 +0100

Women should avoid using talc in the genital area, say researchers reporting evidence supporting the association between such use and an increase in the risk for ovarian cancer. Medscape Medical News (Source: Medscape Medical News Headlines)

Traco: angiogenesis and ovarian cancer

Videocast - All Events — Wed, 08 Oct 2008 14:13:00 +0100

TRACO: Angiogenesis and Ovarian CancerPresented by: E. Zudaire, C. AnnunziataCategory: TRACOAired date: 10/06/2008 (Source: Videocast - All Events)

Role of diffusion-weighted imaging in the diagnosis of gynecological diseases

European Radiology — Wed, 08 Oct 2008 09:50:11 +0100

Abstract Recent technical advances in diffusion-weighted imaging (DWI) greatly enhanced the clinical value of magnetic resonance imaging (MRI) of the body. DWI can provide excellent tissue contrast based on molecular diffusion and may be able to demonstrate malignant tumors. Quantitative measurement of the apparent diffusion coefficient (ADC) may be valuable in distinguishing between malignant and benign lesions. We reviewed DWI and conventional MRI of the female pelvis to study the utility of DWI in patients with gynecological diseases. Although the ADC can help to differentiate between normal and cancerous tissue in the uterine cervix and endometrium, its utility may be limited by the large overlap of the uterine myometrium and ovaries. On the other hand, the ADC may be useful for monitoring the therapeutic outcome after uterine arterial embolizati (UAE), chemotherapy and/or radiation therapy. In patients with ovarian cancer, DWI demonstrates high intensity not only at the primary cancer site but also in disseminated peritoneal implants. When added to conventional MRI findings, DWI and ADC values provide additional information and DWI may play an important role in the diagnosis of patients with gynecological diseases. Content Type Journal ArticleCategory UrogenitalDOI 10.1007/s00330-008-1185-5Authors Tomohiro Namimoto, Kumamoto University Department of Diagnostic Radiology, Graduate School of Medical Sciences 1–1–1, Honjo Kumamoto 860–8556 JapanKazuo Awai, Kumamoto University Department of Diagnostic Radiology, Graduate School of Medical Sciences 1–1–1, Honjo Kumamoto 860–8556 JapanTakeshi Nakaura, Kumamoto University Department of Diagnostic Radiology, Graduate School of Medical Sciences 1–1–1, Honjo Kumamoto 860–8556 JapanYumi Yanaga, Kumamoto University Department of Diagnostic Radiology, Graduate School of Medical Sciences 1–1–1, Honjo Kumamoto 860–8556 JapanToshinori Hirai, Kumamoto University Department of Diagnostic Radiology, Graduate School of Medical Sciences 1–1–1, Honjo Kumamoto 860–8556 JapanYasuyuki Yamashita, Kumamoto University Department of Diagnostic Radiology, Graduate School of Medical Sciences 1–1–1, Honjo Kumamoto 860–8556 Japan Journal European RadiologyOnline ISSN 1432-1084Print ISSN 0938-7994 (Source: European Radiology)

[gynecologic cancer] interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients

Journal of Clinical Oncology — Wed, 08 Oct 2008 04:00:00 +0100

Purpose Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients. Patients and Methods Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP). Results Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005). Conclusion These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients. (Source: Journal of Clinical Oncology)

Limited clinical relevance of mitochondrial dna mutation and gene expression analyses in ovarian cancer

BMC Cancer — Wed, 08 Oct 2008 04:00:00 +0100

Background: In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas. Methods: We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000 750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (MT-ATP6, MT-CO1, MT-CYB, MT-ND1, MT-ND6, and MT-RNR1) were quantified in 62 cancer tissues by real-time RT-PCR. Results: Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene RNR1 might be used as a predictor of tumour sensitivity to chemotherapy. Conclusions: In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies. (Source: BMC Cancer)

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Ovarian suppression in the management of premenopausal breast cancer: methods and efficacy in adjuvant and metastatic settings.

Oncology — Wed, 08 Oct 2008 04:00:00 +0100

Ovarian Suppression in the Management of Premenopausal Breast Cancer: Methods and Efficacy in Adjuvant and Metastatic Settings.

Oncology. 2008 Oct 8;75(3-4):192-202

Authors: McDonald Wade 3rd S, Hackney MH, Khatcheressian J, Lyckholm LJ

Ovarian suppression has been used to treat hormone-responsive metastatic breast cancer in premenopausal women for over 100 years and is currently under continued evaluation for treatment in the adjuvant setting. In this article, ovarian suppression by surgery, radiation, and pharmacological therapy is discussed, including the risks, benefits, and efficacy of each strategy. The role of ovarian suppression in premenopausal women with early and advanced stages of breast cancer will be reviewed. It is hoped that this review will assist clinicians and their patients in selecting the appropriate therapy if ovarian suppression is indicated.

PMID: 18841034 [PubMed - as supplied by publisher]

(Source: Oncology)

Ovarian cancer.

Annual Review of Pathology — Wed, 08 Oct 2008 04:00:00 +0100

Ovarian Cancer.

Annu Rev Pathol. 2008 Oct 8;

Authors: Cho KR, Shih IM

Ovarian carcinomas are a heterogeneous group of neoplasms and are traditionally subclassified based on type and degree of differentiation. Although current clinical management of ovarian carcinoma largely fails to take this heterogeneity into account, it is becoming evident that each major histological type has characteristic genetic defects that deregulate specific signaling pathways in the tumor cells. Moreover, within the most common histological types, the molecular pathogenesis of low-grade versus high-grade tumors appears to be largely distinct. Mouse models of ovarian carcinoma have been developed that recapitulate many of the morphological features, biological behavior, and gene expression patterns of selected subtypes of ovarian cancer. Such models will likely prove useful for studying ovarian cancer biology and for preclinical testing of molecularly targeted therapeutics, which may ultimately lead to better clinical outcomes for women with ovarian cancer. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 4 is February 28, 2009. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

PMID: 18842102 [PubMed - as supplied by publisher]

(Source: Annual Review of Pathology)

Ovarian suppression in the management of premenopausal breast cancer: methods and efficacy in adjuvant and metastatic settings

Karger Publishers — Tue, 07 Oct 2008 15:18:45 +0100

Oncology 2008;75:192-202 (DOI:10.1159/000163059) (Source: Karger Publishers)

A phase i study of oral topotecan and pegylated liposomal doxorubicin (doxil) in platinum-resistant ovarian and peritoneal cancer.

American Journal of Clinical Oncology - Current Table Of Contents — Tue, 07 Oct 2008 11:47:26 +0100

Page: 476DOI: 10.1097/COC.0b013e31816a6221Authors: Rose, Peter G. *; Smrekar, Mary *+; Haba, Pam *++; Fusco, Nancy *[S]; Rodriguez, Michael *[//] (Source: American Journal of Clinical Oncology - Current Table Of Contents)

A phase ii trial of fixed-dosed rate gemcitabine in platinum-resistant ovarian cancer: a geico (grupo espanol de investigacion en cancer de ovario) trial.

American Journal of Clinical Oncology - Current Table Of Contents — Tue, 07 Oct 2008 11:47:26 +0100

Page: 481DOI: 10.1097/COC.0b013e31816d1c7bAuthors: Gonzalez, Belen Ojeda *; Martin, Antonio Gonzalez +; Barcelo, Isabel Bover ++; i Mayol, Xavier Fabregat [S]; Mellado, Begona [P]; Perez, Maria Jesus Rubio [//]; Carrion, Lorenzo Alonso **; Herraez, Antonio Casado ++; Garcia, Elisa Calvo ++++; Galaz, Cristina Churruca [S][S]; Lanza, Angels Arcusa [P][P]; Ibanez, Ana Herrero [//][//]; Cebrian, Encarna Adrover ***; Velasco, Andres Poveda +++ (Source: American Journal of Clinical Oncology - Current Table Of Contents)

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Green tea and ovarian cancer.

Southern Medical Journal — Tue, 07 Oct 2008 11:43:18 +0100

Page: 977DOI: 10.1097/SMJ.0b013e318185d3e3Authors: Ferguson, Lynnette R. DPhil (Oxon.), DSc (Source: Southern Medical Journal)

[news] consensus statement on ovarian cancer aims to settle dispute over symptoms

BMJ — Tue, 07 Oct 2008 04:00:00 +0100

(Source: BMJ)

Primary signet ring cell carcinoma of the appendix: a rare case report and our 18-year experience.

World Journal of Gastroenterology : WJG — Tue, 07 Oct 2008 04:00:00 +0100

Primary signet ring cell carcinoma of the appendix: A rare case report and our 18-year experience.

World J Gastroenterol. 2008 Oct 7;14(37):5763-8

Authors: Ko YH, Jung CK, Oh SN, Kim TH, Won HS, Kang JH, Kim HJ, Kang WK, Oh ST, Hong YS

Primary adenocarcinoma of the appendix is a rare malignancy that constitutes < 0.5% of all gastrointestinal neoplasms. Moreover, primary signet ring cell carcinoma of the appendix is an exceedingly rare entity. We have encountered 15 cases of primary appendiceal cancer among 3389 patients who underwent appendectomy over the past 18 years. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastases and unresectable peritoneal dissemination occurring in a 67-year-old female patient. She underwent appendectomy and bilateral salpingo-oophorectomy with a laparoscopy procedure. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-flurorouracil, and leucovorin (FOLFOX-4). The patient currently is well without progression of disease 12 mo after beginning chemotherapy.

PMID: 18837098 [PubMed - in process]

(Source: World Journal of Gastroenterology : WJG)

[immunology] generation and regulation of human cd4+ il-17-producing t cells in ovarian cancer

Proceedings of the National Academy of Sciences — Tue, 07 Oct 2008 04:00:00 +0100

Despite the important role of Th17 cells in the pathogenesis of many autoimmune diseases, their prevalence and the mechanisms by... (Source: Proceedings of the National Academy of Sciences)

Gonadotropin-releasing hormone and ovarian cancer: a functional and mechanistic overview

FEBS Journal — Mon, 06 Oct 2008 04:00:00 +0100

The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH) is well known for its role in the control of pituitary gonadotropin secretion, but the hormone and receptor are also expressed in extrapituitary tissues and tumor cells, including epithelial ovarian cancers. It is hypothesized that they may function as a local autocrine regulatory system in nonpituitary contexts. Numerous studies have demonstrated a direct antiproliferative effect on ovarian cancer cell lines of GnRH and its synthetic analogs. This effect appears to be attributable to multiple steps in the GnRH signaling cascade, such as cell cycle arrest at G0/G1. In contrast to GnRH signaling in pituitary gonadotropes, the involvement of G[alpha]q, protein kinase C and mitogen-activated protein kinases is less apparent in neoplastic cells. Instead, in ovarian cancer cells, GnRH receptors appear to couple to the pertussis toxin-sensitive protein G[alpha]i, leading to the activation of protein phosphatase, which in turn interferes with growth factor-induced mitogenic signals. Apoptotic involvement is still controversial, although GnRH analogs have been shown to protect cancer cells from doxorubicin-induced apoptosis. Recently, data supporting a regulatory role of GnRH analogs in ovarian cancer cell migration/invasion have started to emerge. In this minireview, we summarize the current understanding of the antiproliferative actions of GnRH analogs, as well as the recent observations of GnRH effects on ovarian cancer cell apoptosis and motogenesis. The molecular mechanisms that mediate GnRH actions and the clinical applications of GnRH analogs in ovarian cancer patients are also discussed. (Source: FEBS Journal)

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Knowledge-guided multi-scale independent component analysis for biomarker identification

BioMed Central — Mon, 06 Oct 2008 04:00:00 +0100

Background: Many statistical methods have been proposed to identify disease biomarkers from gene expression profiles. However, from gene expression profile data alone, statistical methods often fail to identify biologically meaningful biomarkers related to a specific disease under study. In this paper, we develop a novel strategy, namely knowledge-guided multi-scale independent component analysis (ICA), to first infer regulatory signals and then identify biologically relevant biomarkers from microarray data. Results: Since gene expression levels reflect the joint effect of several underlying biological functions, disease-specific biomarkers may be involved in several distinct biological functions. To identify disease-specific biomarkers that provide unique mechanistic insights, a meta-data "knowledge gene pool" (KGP) is first constructed from multiple data sources to provide important information on the likely functions (such as gene ontologic information) and regulatory events (such as promoter responsive elements) associated with potential genes of interest. The gene expression and biological meta data associated with the members of the KGP can then be used to guide subsequent analysis. ICA is then applied to multi-scale gene clusters to reveal regulatory modes reflecting the underlying biological mechanisms. Finally disease-specific biomarkers are extracted by their weighted connectivity scores associated with the extracted regulatory modes. A statistical significance test is used to evaluate the significance of transcription factor enrichment for the extracted gene set based on motif information. We applied the proposed method to yeast cell cycle microarray data and Rsf-1-induced ovarian cancer microarray data. The results show that our knowledge-guided ICA approach can extract biologically meaningful regulatory modes and outperform other baseline methods for biomarker identification. The proposed method significantly outperforms several baseline methods for biomarker identification. Conclusion: We have proposed a novel method, namely knowledge-guided multi-scale ICA, to identify disease-specific biomarkers. The goal is to infer knowledge-relevant regulatory signals and then identify corresponding biomarkers through a multi-scale strategy. The approach has been successfully applied to two expression profiling experiments to demonstrate its improved performance in extracting biologically meaningful and disease-related biomarkers. More importantly, the proposed approach shows promising results to infer novel biomarkers for ovarian cancer and extend current knowledge. (Source: BioMed Central)

Epigenetic regulation of cd133 and tumorigenicity of cd133+ ovarian cancer cells

Oncogene — Mon, 06 Oct 2008 04:00:00 +0100

Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells Oncogene advance online publication, October 6, 2008. doi:10.1038/onc.2008.374 Authors: T Baba, P A Convery, N Matsumura, R S Whitaker, E Kondoh, T Perry, Z Huang, R C Bentley, S Mori, S Fujii, J R Marks, A Berchuck & S K Murphy (Source: Oncogene)

The clinical evaluation of hirsutism

Dermatologic Therapy — Mon, 06 Oct 2008 04:00:00 +0100

ABSTRACT: Hirsutism is a disorder of excess growth of terminal hairs in androgen-dependent areas in women. Other cutaneous conditions associated with androgen excess are androgenetic alopecia, acanthosis nigricans, and acne. Hirsutism is often associated with measurably elevated androgen levels, but not in all cases. Androgens in women arise from the ovary and adrenal glands, and peripherally from skin and fat. The most common cause of hirsutism is polycystic ovarian syndrome. Patients with "idiopathic" hirsutism have normal ovulatory cycles and androgen levels. Other causes are late onset congenital adrenal hyperplasia, Cushing's syndrome, and the HAIR-AN syndrome. Pituitary, ovarian, and adrenal tumors are important, but rare causes of hirsutism. A thorough history and examination are important. Laboratory investigation is essential in women with moderate to severe, sudden onset or rapidly progressing hirsutism. Identification of the underlying etiology does not alter management, but detects patients at risk for infertility, diabetes, cardiovascular disease and endometrial carcinoma. (Source: Dermatologic Therapy)

Antiproliferative and apoptotic activities of tosylcyclonovobiocic acids as potent heat shock protein 90 inhibitors in human cancer cells.

Cancer Letters — Mon, 06 Oct 2008 04:00:00 +0100

Antiproliferative and apoptotic activities of tosylcyclonovobiocic acids as potent heat shock protein 90 inhibitors in human cancer cells.

Cancer Lett. 2008 Oct 6;

Authors: Radanyi C, Bras GL, Marsaud V, Peyrat JF, Messaoudi S, Catelli MG, Brion JD, Alami M, Renoir JM

We evaluated whether inhibition of heat shock protein 90 (hsp90) function by novobiocin derivatives could induce the degradation of signal transducers that drive cancer cell growth and thereby promote apoptosis. Removal of the noviose moiety in novobiocin and introduction of a tosyl substituent at C-4 or C-7 coumarin nucleus provided derivatives 4TCNA and 7TCNA which compared favourably with novobiocin in MCF-7 breast cancer cells. Here we extend the antiproliferative and apoptotic properties of these analogues to a panel of cancer cell lines. Destabilization of hsp90 client proteins Raf-1, HER2, and cdk4 suggests inhibition of hsp90 chaperoning function. In HT29 colon and IGROV1 ovarian cancer cells, the growth inhibiting effect of 4TCNA and 7TCNA was consistent with the stimulation of cell death as assessed by the processing and activation of caspase 9, 8, 7 and 3 and the subsequent cleavage of poly(ADP-ribose) polymerase (PARP). In Ishikawa endometrial adenocarcinoma cells, 4TCNA also promoted apoptosis and the processing of PARP. These derivatives impacting multiple pathways involved in the neoplastic process may represent promising drugs for cancer therapy.

PMID: 18842335 [PubMed - as supplied by publisher]

(Source: Cancer Letters)

Implication of the akt2/survivin pathway as a critical target in paclitaxel treatment in human ovarian cancer cells.

Cancer Letters — Mon, 06 Oct 2008 04:00:00 +0100

Implication of the Akt2/survivin pathway as a critical target in paclitaxel treatment in human ovarian cancer cells.

Cancer Lett. 2008 Oct 6;

Authors: Weng D, Song X, Xing H, Ma X, Xia X, Weng Y, Zhou J, Xu G, Meng L, Zhu T, Wang S, Ma D

PURPOSE: Although multiple mechanisms have been implicated in paclitaxel (PTX)-induced resistance in ovarian cancer, recent evidence has suggested that Akt2 has an important role in the protection of cells from paclitaxel-induced apoptosis. In the present study, we investigated the role of the Akt2/survivin pathway in paclitaxel-induced resistance by a modified method to generate an effective shRNA vector. METHODS: We applied RNAi-mediated silencing techniques to investigate the mechanism of the Akt2/survivin pathway on PTX-induced resistance in ovarian cancer cells (A2780 and SKOV3). The expression of Akt2 and survivin mRNA and related protein levels were evaluated with semiquantitative real-time RT-PCR and western blot analysis, respectively. Inhibition of cell proliferation was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, and the induction of apoptosis was examined through flow cytometry (FACS) and Hoechst staining. RESULTS: Akt2 down-regulation sensitized ovarian cancer cells to paclitaxel-induced apoptosis, and inhibited survivin expression. We further demonstrated that suppressing the inhibition of survivin expression can induce the drug-resistance to paclitaxel. We introduced a modified vector to generate shRNA to induce RNA interference, which contained three U6 promoters to express different shRNAs; it severely reduced Akt2 gene expression and showed good specificity. CONCLUSION: Our findings will aid in understanding the molecular mechanism of paclitaxel-induced resistance in ovarian cancer and facilitate the development of novel anti-neoplastic strategies.

PMID: 18842333 [PubMed - as supplied by publisher]

(Source: Cancer Letters)

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Wisecare+: results of a european study of a nursing intervention for the management of chemotherapy-related symptoms.

European Journal of Oncology Nursing — Mon, 06 Oct 2008 04:00:00 +0100

WISECARE+: Results of a European study of a nursing intervention for the management of chemotherapy-related symptoms.

Eur J Oncol Nurs. 2008 Oct 6;

Authors: Kearney N, Miller M, Maguire R, Dolan S, Macdonald R, McLeod J, Maher L, Sinclair L, Norrie J, Wengström Y

While the use of chemotherapy has significantly improved survival rates, the symptoms associated with chemotherapy remain a major burden for patients. Preventing or appropriately managing side effects significantly improves patients' functional status and quality of life, ultimately leading to greater patient acceptance of chemotherapy. However, symptom assessment and management are fraught with difficulties such as poor patient recall, retrospective assessment conducted by clinicians and lack of appropriate, clinically relevant and patient friendly symptom assessment and management tools. Furthermore the differences between clinician and patient perceptions of stresses and distress during chemotherapy are well recognised. This study aimed to evaluate the impact of a nursing intervention incorporating structured symptom assessment and management, facilitated by information technology, on chemotherapy-related symptoms, nausea, vomiting, fatigue and mucositis. This pan-European study, involved 8 clinical sites from Belgium, Denmark, England, Ireland and Scotland. Adults (n=249) receiving first line chemotherapy for breast, lung, ovarian or colorectal cancer, osteosarcoma, acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoma were recruited to the study. Patients completed daily symptom assessment questionnaires for 14 days following consecutive cycles of chemotherapy. Symptom outcomes were compared before and after the introduction of the intervention with positive impact on patients' experiences of nausea, vomiting and oral problems. Fatigue was not significantly improved.

PMID: 18842457 [PubMed - as supplied by publisher]

(Source: European Journal of Oncology Nursing)

Her-2 dna versus cell vaccine: immunogenicity and anti-tumor activity

Cancer Immunology, Immunotherapy — Sat, 04 Oct 2008 09:25:44 +0100

Abstract Direct comparison and ranking of vaccine formulations in pre-clinical studies will expedite the identification of cancer vaccines for clinical trials. Two human ErbB-2 (Her-2) vaccines, naked DNA and whole cell vaccine, were tested side-by-side in wild type and Her-2 transgenic mice. Both vaccines can induce humoral and cellular immunity to the entire repertoire of Her-2 epitopes. Mice were electro-vaccinated i.m. with a mixture of pGM-CSF and pE2TM, the latter encodes Her-2 extracellular and transmembrane domains. Alternatively, mice were injected i.p. with human ovarian cancer SKOV3 cells that have amplified Her-2. In wild type mice, comparable levels of Her-2 antibodies (Ab) were induced by these two vaccines. However, T cell immunity and protection against Her-2+ tumors were superior in DNA vaccinated mice. In BALB Her-2 transgenic (Tg) mice, which were tolerant to Her-2, DNA and cell vaccines were administered after regulatory T cells (Treg) were removed by anti-CD25 mAb. Again, comparable levels of Her-2 Ab were induced, but DNA vaccines rendered greater anti-tumor activity. In B6xDR3 Her-2 Tg mice that expressed the autoimmune prone HLA-DR3 allele, higher levels of Her-2 Ab were induced by SKOV3 cell than by Her-2 DNA. But anti-tumor activity was still more profound in DNA vaccinated mice. Therefore, Her-2 DNA vaccine induced greater anti-tumor immunity than cell vaccine, whether mice were tolerant to Her-2 or susceptible to autoimmunity. Through such side-by-side comparisons in appropriate pre-clinical test systems, the more effective vaccine formulations will emerge as candidates for clinical trials. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00262-008-0599-xAuthors Paula J. Whittington, Wayne State University Department of Immunology and Microbiology, School of Medicine Detroit MI 48201 USAOlga Radkevich-Brown, Wayne State University Karmanos Cancer Institute, School of Medicine 110 E. Warren Ave. Detroit MI 48201 USAJennifer B. Jacob, Wayne State University Karmanos Cancer Institute, School of Medicine 110 E. Warren Ave. Detroit MI 48201 USARichard F. Jones, Wayne State University Karmanos Cancer Institute, School of Medicine 110 E. Warren Ave. Detroit MI 48201 USAAmy M. Weise, Wayne State University Karmanos Cancer Institute, School of Medicine 110 E. Warren Ave. Detroit MI 48201 USAWei-Zen Wei, Wayne State University Karmanos Cancer Institute, School of Medicine 110 E. Warren Ave. Detroit MI 48201 USA Journal Cancer Immunology, ImmunotherapyOnline ISSN 1432-0851Print ISSN 0340-7004 (Source: Cancer Immunology, Immunotherapy)

New chemotherapy ‘cures’ early testicular cancer

Drugs.com - Clinical Trials — Sat, 04 Oct 2008 01:56:10 +0100

BETHESDA, Md., Oct. 3, 2008-A single injection of carboplatin – a chemotherapy drug commonly used to treat ovarian and lung cancer – can replace radiotherapy to cure a common type of testicular cancer, according to results presented at... (Source: Drugs.com - Clinical Trials)

Establishment of an ovarian metastasis model and possible involvement of e-cadherin down-regulation in the metastasis

Cancer Science — Fri, 03 Oct 2008 04:00:00 +0100

Clinical observations of cases of ovarian metastasis suggest that there may be a unique mechanism underlying ovarian-specific metastasis. This study was undertaken to establish an in vivo model of metastasis to the ovary, and to investigate the mechanism of ovarian-specific metastasis. We examined the capacity for ovarian metastasis in eight different human carcinoma cell lines by implantation in female NOD/SCID mice transvenously and intraperitoneally. By transvenous inoculation, only RERF-LC-AI, a poorly differentiated carcinoma cell line, frequently demonstrated ovarian metastasis. By intraperitoneal inoculation, four of the eight cell lines (HGC27, MKN-45, KATO-III, and RERF-LC-AI) metastasized to the ovary. We compared E-cadherin expression among ovarian metastatic cell lines and others. All of these four ovarian metastatic cell lines and HSKTC, a Krukenberg tumor cell line, showed E-cadherin down-regulation and others did not. E-cadherin was then forcibly expressed in RERF-LC-AI, and inhibited ovarian metastasis completely. The capacity for metastasizing to the other organs was not affected by E-cadherin expression. We also performed histological investigation of clinical ovarian-metastatic tumor cases. About half of all ovarian-metastatic tumor cases showed loss or reduction of E-cadherin expression. These data suggest that E-cadherin down-regulation may be involved in ovarian-specific metastasis. (Cancer Sci 2008) (Source: Cancer Science)

Signet-ring stromal tumor of the testis: a case report and literature review.

Human Pathology — Fri, 03 Oct 2008 04:00:00 +0100

Signet-ring stromal tumor of the testis: a case report and literature review.

Hum Pathol. 2008 Oct 3;

Authors: Kuo CY, Wen MC, Wang J, Jan YJ

Primary signet-ring stromal tumor of the testis is extremely rare. To our knowledge, only one case has been reported in the literature. Herein, we present a case of testicular signet-ring stromal tumor with positive immunostain for CD99, which has not been reported previously. We also review the literature and discuss the clinicopathological significance of this type of tumor. The most important differential diagnosis of signet-ring stromal tumor is metastatic signet-ring cell carcinoma because of its different management and prognosis. Fortunately, signet-ring stromal tumors have a well-defined growth pattern, bland histological features, no mucin production, and immunoreaction to vimentin rather than cytokeratin, all of which help pathologists to rule out metastatic adenocarcinoma. Although ovarian signet-ring stromal tumors are categorized in the fibroma/thecoma group of sex cord stromal tumors, the cell origin of signet-ring stromal tumors is still debatable. The histological criteria for predicting clinical behavior of signet-ring stromal tumors are not clear. Fortunately, however, all reported signet-ring stromal tumors are benign tumors with excellent prognosis, and they do not recur or metastasize. We consider signet-ring stromal tumor to be a special type of sex cord stromal tumor.

PMID: 18835626 [PubMed - as supplied by publisher]

(Source: Human Pathology)

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Phase 2 study of imc-1121b for advanced ovarian cancer commences patient enrollment

Cancercompass News: Gynecological Cancer — Thu, 02 Oct 2008 08:36:48 +0100

NEW YORK -- ImClone Systems Incorporated, a global leader in the development and commercialization of novel antibodies to treat cancer, today announced that the first patient has been treated in its disease-directed Phase 2 clinical trial of IMC-1121B in patients with advanced ovarian cancer. IMC-1121B is ImClone's proprietary fully human, IgG1 anti-vascular growth factor receptor-2 (VEGFR-2) monoclonal antibody. This multicenter, open-label Phase 2 single-arm study is enrolling women with persistent or recurrent advanced ovarian, fallopian tube, and primary peritoneal epithelial cancers following at least one platinum-containing chemotherapy regimen. Approximately 55 patients are expected to be enrolled at various center... (Source: Cancercompass News: Gynecological Cancer)

Advanced ovarian cancer patient enrollment phase 2 study of imc-1121b commences

Cancer / Oncology News From Medical News Today — Thu, 02 Oct 2008 08:00:00 +0100

ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the development and commercialization of novel antibodies to treat cancer, today announced that the first patient has been treated in its disease-directed Phase 2 clinical trial of IMC-1121B in patients with advanced ovarian cancer. IMC-1121B is ImClone's proprietary fully human, IgG1 anti-vascular growth factor receptor-2 (VEGFR-2) monoclonal antibody. (Source: Cancer / Oncology News From Medical News Today)

Cryopreservation/transplantation of ovarian tissue and in vitro maturation of follicles and oocytes: challenges for fertility preservation

BioMed Central — Thu, 02 Oct 2008 04:00:00 +0100

Cryopreservation of ovarian tissue and in vitro follicle maturation are two emerging techniques for fertility preservation, especially in cancer patients. These treatment regimes are opening up more options and allow for more suitable choices to preserve fertility according to the patient's specific circumstances. If these technologies are to become widely accepted, they need to be safe, easy to perform and must obtain favorable results. The generation of healthy eggs with the normal genetic complement and the ability to develop into viable and healthy embryos requires tight regulation of oocyte development and maturation. Novel freezing techniques such as vitrification, along with whole ovary cryopreservation and three-dimensional follicle cultures, have shown favorable outcomes. The scope of this article is to take a comprehensively look at the challenges still faced in order for these novel technologies to be routinely employed with the aim of successful fertility preservation. (Source: BioMed Central)

Frozen ovaries help women with breast cancer

WDSU.com - Health — Wed, 01 Oct 2008 18:56:35 +0100

A hospital helps a woman with cancer preserve her chances of having a baby by removing one of her ovaries. (Source: WDSU.com - Health)

Usefulness of third-line chemotherapy for women with recurrent ovarian, fallopian tube, and primary peritoneal cancer who receive platinum/taxane regimens as first-line therapy

Journal of Cancer Research and Clinical Oncology — Wed, 01 Oct 2008 09:19:22 +0100

Abstract Background Limited information is available regarding the usefulness of third-line chemotherapy for recurrent ovarian, fallopian tube, and primary peritoneal cancer treated with platinum-taxane regimens as first-line therapy. Patients and methods We retrospectively reviewed the medical records of women with ovarian, fallopian tube, and primary peritoneal cancer who were treated at the National Cancer Center Hospital between 1999 and 2005 to investigate the relations of clinicopathological factors to important clinical endpoints such as the response rate (RR), time to progression (TTP) and overall survival (OS) after third-line chemotherapy. Results A total of 172 patients received first-line platinum/taxane regimens during the study period, among whom 111 had disease progression after first-line chemotherapy. Eighty-one of these 111 patients received second-line chemotherapy, and 73 had disease progression. Fifty-four of the 73 patients with disease progression received third-line chemotherapy. The RR to third-line chemotherapy was 40.7% (95% CI, 27.6–53.8%). The median TTP was 4.4 months (range 0–19.5 months), and the median OS was 10.4 months (range 1.5–44.3 months). Performance status (PS) and primary drug-free interval (DFI) were independent predictive factors for the RR to third-line chemotherapy (P = 0.04 and P = 0.009). PS and primary DFI were also independent predictive factors for TTP and OS on multivariate analysis (P = 0.006, P = 0.005 and P = 0.01, P = 0.004, respectively). Conclusions PS and primary DFI are useful predictors of the response to third-line chemotherapy in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer. In this setting, however, both of these variables are subject to several well-established potential biases and limitations; further prospective studies are thus needed. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-008-0488-xAuthors Shin Nishio, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanNoriyuki Katsumata, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanKoji Matsumoto, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanHiroshi Tanabe, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanKan Yonemori, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanTsutomu Kouno, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanChikako Shimizu, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanMasashi Ando, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanToshiharu Kamura, Kurume University School of Medicine Department Obstetrics and Gynecology 67 Asahi-machi, Kurume Fukuoka 830-0011 JapanTakahiro Kasamatsu, National Cancer Center Hospital Division of Gynecologic Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 JapanYasuhiro Fujiwara, National Cancer Center Hospital Division of Medical Oncology 5-1-1 Tsukiji, Chuo-ku Tokyo 104-0045 Japan Journal Journal of Cancer Research and Clinical OncologyOnline ISSN 1432-1335Print ISSN 0171-5216 (Source: Journal of Cancer Research and Clinical Oncology)

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Regulation of arginase i activity and expression by both pd-1 and ctla-4 on the myeloid-derived suppressor cells

Cancer Immunology, Immunotherapy — Wed, 01 Oct 2008 09:17:51 +0100

Abstract An elevated number of Gr-1+CD11b+ myeloid-derived suppression cells (MDSCs) has been described in mice and human bearing tumor and associated with immune suppression. Arginase I production by MDSCs in the tumor environment may be a central mechanism for immunosuppression and tumor evasion. In this study and before, we found that Gr-1+CD11b+ MDSCs from ascites and spleen of mice bearing ovarian 18D carcinoma express a high level of PD-1, CTLA-4, B7-H1 and CD80 while other co-stimulatory molecules, namely CD40, B7-DC and CD86 are not detected. Further studies showed that PD-1 and CTLA-4 on the Gr-1+CD11b+ MDSCs regulated the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules could significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results were also observed while their ligands B7-H1 and/or CD80 were blocked or silenced. Furthermore, CD80 deficiency also decreased the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduced the suppressive potential of PD-1+CTLA-4+MDSCs. Blockade of PD-1, CTLA-4 or both also slowed tumor growth and improved the survival rate of tumor-bearing mice. Thus, there may exist a coinhibitory and costimulatory molecules-based immuno-regulating wet among MDSCs. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00262-008-0591-5Authors Yu Liu, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaYinyan Yu, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaSuguang Yang, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaBin Zeng, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaZhuohan Zhang, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaGuohui Jiao, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaYuan Zhang, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaLimin Cai, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin ChinaRongcun Yang, Nankai University Department of Immunology, Nankai University School of Medicine 300071 Tianjin China Journal Cancer Immunology, ImmunotherapyOnline ISSN 1432-0851Print ISSN 0340-7004 (Source: Cancer Immunology, Immunotherapy)

Loehmann’s shop and share day draws lines of ocrf supporters

OCRF News — Wed, 01 Oct 2008 04:00:00 +0100

On Thursday, September 25, OCRF supporters stocked up on new fall fashions at 62 Loehmann's stores in 14 states across the country. On Thursday, September 25, OCRF supporters stocked up on new fall fashions at 62 Loehmann's stores in 14 states across the country. Loehmann's hosted Shop and Share Day where shoppers donated $5 to OCRF and instantly received 15% off their entire purchase. Loehmann's also donated 5% of all Shop and Share purchases to OCRF. CEO Elizabeth Howard visited a Manhattan store to see OCRF supporters lined up around the block, and OCRF Board Member Susan Fragnoli took part in the event at store in Los Angeles. We thank Loehmann's for their support and dedication to helping raise awareness and advance ovarian cancer research. (Source: OCRF News)

Tissue transglutaminase protects epithelial ovarian cancer cells from cisplatin-induced apoptosis by promoting cell survival signaling

Carcinogenesis — Wed, 01 Oct 2008 04:00:00 +0100

Tissue transglutaminase (TG2), an enzyme involved in protein cross-linking and overexpressed in ovarian tumors, has antiapoptotic effects in cancer cells and may play a role in response to chemotherapy. In this study, we investigated the role of TG2 in the sensitivity of ovarian cancer cells to cisplatin. By using stable knockdown and overexpression strategies, we demonstrate that the level of expression of TG2 regulates apoptosis induced by cisplatin in SKOV3 and OV-90 ovarian cancer cells. Interestingly, not only TG2 knockdown but also a TG2 enzymatic inhibitor (KCC009) sensitized SKOV3 cells to cisplatin. To understand the mechanism by which TG2 exerts its antiapoptotic role, we examined the effects of protein kinase B (Akt) and nuclear factor-kappa B (NF-B), two survival pathways commonly involved in development of drug resistance. Overexpression of the constitutively active p65 subunit of NF-B, but not constitutively active Akt, rescued cells with diminished TG2 expression from cisplatin-induced apoptosis. This implicates activation of NF-B as the main cisplatin resistance mechanism downstream of TG2. Indeed, NF-B activity is decreased and the level of the inhibitory subunit IB is increased in ovarian cancer cells engineered to express diminished levels of TG2 or treated with the enzymatic inhibitor, KCC009. Our data show that TG2 prevents apoptosis induced by cisplatin by activating the NF-B survival pathway in ovarian cancer cells. (Source: Carcinogenesis)

A functional polymorphism in the mir-146a gene and age of familial breast/ovarian cancer diagnosis

Carcinogenesis — Wed, 01 Oct 2008 04:00:00 +0100

A G to C polymorphism (rs2910164) is located within the sequence of miR-146a precursor, which leads to a change from a G:U pair to a C:U mismatch in its stem region. The predicted miR-146a target genes include BRCA1 and BRCA2, which are key breast and ovarian cancer genes. To examine whether rs2910164 plays any role in breast and/or ovarian cancer, we studied associations between this polymorphism and age of diagnosis in 42 patients with familial breast cancer and 82 patients with familial ovarian cancer. Breast cancer patients who had at least one miR-146a variant allele were diagnosed at an earlier age than with no variant alleles (median age 45 versus 56, P = 0.029) and ovarian cancer patients who had at least one miR-146a variant allele were diagnosed younger than women without any variant allele (median age 45 versus 50, P = 0.014). In further functional analysis, we found that the variant allele displayed increased production of mature miR-146a from the precursor microRNA compared with the common allele. Consistent with the target prediction, in a target in vitro assay, we observed that miR-146a could bind to the 3' untranslated regions (UTRs) of BRCA1 and BRCA2 messenger RNAs (mRNAs) and potentially modulate their mRNA expression. Intriguingly, the binding capacity between the 3' UTR of BRCA1 and miR-146a was statistically significantly stronger in variant C allele than those in common G allele (P = 0.046). Taken together, our data suggest that breast/ovarian cancer patients with variant C allele miR-146a may have high levels of mature miR-146 and that these variants predispose them to an earlier age of onset of familial breast and ovarian cancers. (Source: Carcinogenesis)