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Ovarian cancer biomarker

Britton Trabert, Ronald C Eldridge, Ruth M Pfeiffer, Meredith S Shiels, Troy J Kemp, Chantal Guillemette, Patricia Hartge, Mark E Sherman, Louise A Brinton, Amanda Black, Anil K Chaturvedi, Allan Hildesheim, Sonja I Berndt, Mahboobeh Safaeian, Ligia Pinto, Nicolas Wentzensen
Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Bruce Wen, Kirby R Campbell, Karissa Tilbury, Oleg Nadiarnykh, Molly A Brewer, Manish Patankar, Vikas Singh, Kevin W Eliceiri, Paul J Campagnola
Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class...
October 21, 2016: Scientific Reports
I Nakachi, B A Helfrich, M A Spillman, E A Mickler, C J Olson, J L Rice, C D Coldren, L E Heasley, M W Geraci, R S Stearman
Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression...
October 20, 2016: Clinical and Translational Science
Tatiana Pochechueva, Alexander Chinarev, Andreas Schoetzau, André Fedier, Nicolai V Bovin, Neville F Hacker, Francis Jacob, Viola Heinzelmann-Schwarz
Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined...
2016: PloS One
Zhanzhan Xu, Yu Zhou, Yexuan Cao, Thi Lan Anh Dinh, Jing Wan, Min Zhao
Ovarian cancer is the first leading cause of mortality in gynecological malignancies. To identify key genes and microRNAs in ovarian cancer, mRNA microarray dataset GSE36668, GSE18520, GSE14407 and microRNA dataset GSE47841 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained using GEO2R. Functional and pathway enrichment analysis were performed for DEGs using DAVID database. Protein-protein interaction (PPI) network was established by STRING and visualized by Cytoscape...
November 2016: Medical Oncology
Xiaodan Meng, Volkmar Müller, Karin Milde-Langosch, Fabian Trillsch, Klaus Pantel, Heidi Schwarzenbach
In the present study, we investigated whether circulating cell-free microRNAs serve as potential biomarkers in epithelial ovarian cancer (EOC) patients. Circulating miR-373, miR-200a, miR-200b and miR-200c were quantified in a cohort of 60 EOC patients, 20 patients with benign ovarian diseases and 32 healthy women using quantitative TaqMan MicroRNA assays. The serum concentrations of cell-free miR-373, miR-200a, miR-200b and miR-200c were significantly higher in EOC patients than in healthy women (p = 0.0001)...
2016: Advances in Experimental Medicine and Biology
Zhentong Wei, Yan Liu, Yishu Wang, Yandong Zhang, Qinghua Luo, Xiaxia Man, Feng Wei, Xiaowei Yu
Ovarian cancer (OVCa) stem cells are associated with tumor growth, metastasis, and recurrence, which are driving forces behind a majority of the OVCa-related mortality. This subpopulation of cancer cells are characterized by uncontrolled proliferation, high invasiveness, and resistance against the current platinum-based therapy. Thus, targeting OVCa cancer stem cells has been focused in recent therapeutic development. Isolation and purification of cancer stem cells are, however, challenging for the lack of sensitive and specific markers...
November 2016: Medical Oncology
Ling Mao, Ai-Jun Sun, Jian-Zhong Wu, Jin-Hai Tang
The prognostic value of HER2 has been demonstrated in many human cancer types such us breast cancer, gastric cancer and ovarian cancer. Trastuzumab is the first anti-HER2 monoclonal antibody that has remarkably improved outcomes of patients with HER2-positive breast cancer. For HER2-positive metastatic gastric cancers, the addition of trastuzumab to traditional chemotherapy also significantly prolonged overall survival. However, intrinsic and acquired resistance to trastuzumab is common and results in disease progression...
October 12, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Priya Samuel, David Raul Francisco Carter
Ovarian cancer causes more than 100,000 deaths globally per year. Despite intensive research efforts, there has been little improvement in the overall survival of patients over the past three decades. Most patients are not diagnosed until the cancer is at an advanced stage, by which time their chances of still being alive after 5 years are appallingly low. Attempts to extend life in these patients have been, for the most part, unsuccessful. This owes partly to the lack of suitable biomarkers for stratifying patients at the molecular level, into responders and non-responders...
October 7, 2016: Molecular Diagnosis & Therapy
Christopher S Hughes, Melissa K McConechy, Dawn R Cochrane, Tayyebeh Nazeran, Anthony N Karnezis, David G Huntsman, Gregg B Morin
Although re-sequencing of gene panels and mRNA expression profiling are now firmly established in clinical laboratories, in-depth proteome analysis has remained a niche technology, better suited for studying model systems rather than challenging materials such as clinical trial samples. To address this limitation, we have developed a novel and optimized platform called SP3-Clinical Tissue Proteomics (SP3-CTP) for in-depth proteome profiling of practical quantities of tumour tissues, including formalin fixed and paraffin embedded (FFPE)...
October 7, 2016: Scientific Reports
Atsushi Kiba, Kouji Banno, Megumi Yanokura, Mari Asada, Yusuke Nakayama, Daisuke Aoki, Tatsuya Watanabe
AIM: Micro ribonucleic acids (miRNAs) play an important pathological role in endometriosis. Leuprolide acetate, an analog of gonadotropin-releasing hormone, is widely used to treat endometriosis; however, the molecular mechanisms involved in endometriotic tissue regression remain unclear. We performed miRNA expression profiling of clinical ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium, eight ovarian endometriotic, and 12 leuprolide acetate-treated endometriotic tissues...
October 6, 2016: Journal of Obstetrics and Gynaecology Research
Ki-Hyung Kim, Seong-Hwan Park, Kee Hun Do, Juil Kim, Kyung Un Choi, Yuseok Moon
Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in developed countries. Chronic endogenous sterile pro-inflammatory responses are strongly linked to EOC progression and chemoresistance to anti-cancer therapeutics. In the present study, the activity of epithelial NF-κB, a key pro-inflammatory transcription factor, was enhanced with the progress of EOC. This result was mechanistically linked with an increased expression of NSAID-Activated Gene 1 (NAG-1) in MyD88-positive type I EOC stem-like cells, compared with that in MyD88-negative type II EOC cells...
September 30, 2016: Oncotarget
X C Sun, A C Zhang, L L Tong, K Wang, X Wang, Z Q Sun, H Y Zhang
We investigated the relationship between miR-146a and miR-196a2 genetic polymorphisms and development of ovarian cancer in a Chinese population. A total of 134 patients and 227 control subjects were involved in our study between January 2012 and October 2014 from China-Japan Union Hospital of Jilin University. Genotyping of miR-146a and miR-196a2 was accomplished by polymerase chain reaction coupled with restriction fragment length polymorphism analysis. Unconditional multiple-logistic regression analysis indicated that the GG genotype of miR-146a was associated with an increased risk of ovarian cancer when compared to the CC genotype, and the adjusted OR (95%CI) was 3...
August 29, 2016: Genetics and Molecular Research: GMR
Ahmad Mahdian-Shakib, Ruhollah Dorostkar, Mahdi Tat, Mohammad Sadegh Hashemzadeh, Navid Saidi
Ovarian cancer (OC) is the most lethal of malignant gynecological cancers, and has a very poor prognosis, frequently, attributable to late diagnosis and responsiveness to chemotherapy. In spite of the technological and medical approaches over the past four decades, involving the progression of several biological markers (mRNA and proteins biomarkers), the mortality rate of OC remains a challenge due to its late diagnosis, which is expressly ascribed to low specificities and sensitivities. Consequently, there is a crucial need for novel diagnostic and prognostic markers that can advance and initiate more individualized treatment, finally increasing survival of the patients...
September 29, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Peter G Rose, James J Java, Mark A Morgan, Angeles Alvarez-Secord, Joshua P Kesterson, Frederick B Stehman, David P Warshal, William T Creasman, Parviz Hanjani, Robert T Morris, Larry J Copeland
PURPOSE: GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule >1cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS). METHODS: Among the 550 patients enrolled on GOG-152, two-hundred-sixteen patients were randomly assigned following 3cycles of cisplatin and paclitaxel to receive SCS...
September 27, 2016: Gynecologic Oncology
Dante Cicchetti, Susan Hetzel, Fred A Rogosch, Elizabeth D Handley, Sheree L Toth
A genome-wide methylation study was conducted among a sample of 114 infants (M age = 13.2 months, SD = 1.08) of low-income urban women with (n = 73) and without (n = 41) major depressive disorder. The Illumina HumanMethylation450 BeadChip array with a GenomeStudio Methylation Module and Illumina Custom model were used to conduct differential methylation analyses. Using the 5.0 × 10-7 p value, 2,119 loci were found to be significantly different between infants of depressed and nondepressed mothers. Infants of depressed mothers had greater methylation at low methylation sites (0%-29%) compared to infants of nondepressed mothers...
September 30, 2016: Development and Psychopathology
Catalin Vlad, Paul Kubelac, Andrea Onisim, Bogdan Fetica, Annamaria Fulop, Alexandru Irimie, Patriciu Achimas-Cadariu
PURPOSE: The tumor microenvironment in ovarian cancer (OC) seems to play an important role, and besides tumor cells, biomarkers can derive from endothelial cells. We investigated CDCP1 and ADAM12 expression in relation with other clinical and pathological characteristics in OC patients. METHODS: We retrospectively evaluated patient files between 2006-2011. A histochemical score was developed to evaluate tumor staining, the microvessel density (MVD), and stromal expression patterns for both ADAM12 and CDCP1...
July 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Elizabeth H Stover, Panagiotis A Konstantinopoulos, Ursula A Matulonis, Elizabeth M Swisher
Drugs targeting DNA damage repair (DDR) pathways are exciting new agents in cancer therapy. Many of these drugs exhibit synthetic lethality with defects in DNA repair in cancer cells. For example, ovarian cancers with impaired homologous recombination DNA repair show increased sensitivity to poly- (ADP-ribose) polymerase (PARP) inhibitors. Understanding the activity of different DNA repair pathways in individual tumors, and the correlations between DNA repair function and drug response, will be critical to patient selection for DNA repair targeted agents...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yu Ma, Yan Lu, Bingjian Lu
Reliable biomarkers for the detection of early ovarian carcinoma are currently unavailable. MicroRNA and long non-coding RNA may be important in cancer initiation and progression by regulating gene expression through post-transcriptional mechanisms. MicroRNAs, such as miR-26a and miR-132, have been investigated as novel biomarkers for diagnosis, prognosis, monitoring of therapeutic response, and therapeutic targets in ovarian carcinomas. Some long non-coding RNAs, such as H19 and UCA1, may be involved in the pathogenesis of ovarian carcinomas...
October 20, 2016: Cancer Investigation
Curtis A Clark, Harshita Gupta, Gangadhara R Sareddy, Srilakshmi Pandeswara, Shunhua Lao, Bin Yuan, Justin M Drerup, Alvaro Padron, Jose R Conejo-Garcia, Kruthi Murthy, Yang Liu, Mary Jo Turk, Kathrin Thedieck, Vincent Hurez, Rong Li, Ratna K Vadlamudi, Tyler J Curiel
PD-L1 antibodies produce efficacious clinical responses in diverse human cancers, but the basis for their effects remains unclear, leaving a gap in understanding of how to rationally leverage the therapeutic activity. PD-L1 is widely expressed in tumor cells but its contributions to tumor pathogenicity are incompletely understood. In this study, we evaluated the hypothesis that PD-L1 exerts tumor cell-intrinsic signals that are critical for pathogenesis. Using RNAi methodology, we attenuated PD-L1 in the murine ovarian cell line ID8agg and the melanoma cell line B16 (termed PD-L1lo cells), which express basal PD-L1...
September 26, 2016: Cancer Research
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