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poor ovarian response

Honghong Zhou, Yongshuo Liu, Rui Zhu, Fang Ding, Xiufeng Cao, Dongxin Lin, Zhihua Liu
Snail is a key regulator of epithelial-mesenchymal transition (EMT) and plays an important role in tumor progression and metastasis. Snail is rapidly degraded in the cells and its protein level is critically controlled. Although several E3 ligases regulating Snail degradation have been defined, the deubiquitinases (DUBs) responsible for Snail deubiquitination are less studied. We identified ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) as a DUB that stabilizes Snail through preventing its ubiquitination and proteasomal degradation...
March 21, 2018: Oncogene
Raluca Eftimie, Esraa Hassanein
BACKGROUND: Early cancer diagnosis is one of the most important challenges of cancer research, since in many cancers it can lead to cure for patients with early stage diseases. For epithelial ovarian cancer (which is the leading cause of death among gynaecologic malignancies) the classical detection approach is based on measurements of CA-125 biomarker. However, the poor sensitivity and specificity of this biomarker impacts the detection of early-stage cancers. METHODS: Here we use a computational approach to investigate the effect of combining multiple biomarkers for ovarian cancer (e...
March 20, 2018: Journal of Translational Medicine
Hope Cottrill, Stephanie Cason, Scott Caroen, Bryan Oronsky, Elvis Donaldson
This case report describes the clinical course of a heavily pretreated patient enrolled on the Phase II QUADRUPLE THREAT clinical trial (NCT02489903) with recurrent metastatic epithelial ovarian cancer that was previously treated with a platinum doublet and that benefited from another reintroduction of a platinum doublet after a brief priming period with RRx-001. Platinum-taxane combination is the initial treatment of choice in ovarian cancer and the "go-to regimen" for patients with recurrent, platinum-sensitive disease...
January 2018: Journal of Investigative Medicine High Impact Case Reports
Priyanka Singh, Laura M Jenkins, Ben Horst, Victoria Alers, Shrikant Pradhan, Prabhjot Kaur, Tapasya Srivastava, Nadine Hempel, Balázs Győrffy, Eugenia V Broude, Nam Y Lee, Karthikeyan Mythreye
Inhibin is a heterodimeric TGF-β family ligand that is expressed in many cancers and is a selective biomarker for ovarian cancers, however its tumor-specific functions remain unknown. Here we demonstrate that the α subunit of Inhibin (INHA), which is critical for the functionality of dimeric Inhibin A/B, correlates with microvessel density (MVD) in human ovarian tissues and xenografts and is predictive of poor clinical outcomes in multiple cancers. We demonstrate that Inhibin regulated angiogenesis is necessary for metastasis...
March 13, 2018: Cancer Research
Brian Z Ring, Rajmohan Murali, Robert A Soslow, David D L Bowtell, Sian Fereday, Anna DeFazio, Nadia Traficante, Catherine J Kennedy, Alison Brand, Raghwa Sharma, Paul Harnett, Goli Samimi
BACKGROUND: Chemo-resistance is a major challenge in ovarian cancer treatment, resulting in poor survival rates. Identifying markers of treatment response is imperative for improving outcome while minimizing unnecessary side effects. We have previously demonstrated that expression of transducin-like enhancer of split 3 (TLE3) is associated with favorable progression-free survival in taxane-treated ovarian cancer patients with non-serous histology. The purpose of this study was to perform an independent evaluation of the association of TLE3 expression with response to taxane-based chemotherapy in non-serous ovarian cancer, to validate its role as a potential therapeutic response marker for taxane-based chemotherapy...
March 12, 2018: Cancer Epidemiology, Biomarkers & Prevention
Johanna M Gostner, Eva Obermayr, Ioana E Braicu, Nicole Concin, Sven Mahner, Adriaan Vanderstichele, Jalid Sehouli, Ignace Vergote, Dietmar Fuchs, Robert Zeillinger
OBJECTIVE: Circulating tumor cells (CTCs) may represent a chronic stimulus for the immune system. In the present study we investigated the potential association of CTCs, the immune activation marker neopterin, and the ratio of kynurenine to tryptophan (Kyn/Trp) as a measure for tryptophan breakdown. METHODS: Neopterin, tryptophan and kynurenine levels were measured in plasma samples from patients with benign gynecological diseases (n=65) and with primary advanced epithelial ovarian cancer (EOC) at diagnosis (n=216) and six months after adjuvant platinum-based chemotherapy (n=45) by an enzyme-linked immunosorbent assay and high performance liquid chromatography...
March 9, 2018: Gynecologic Oncology
Tannaz Zamaniara, Robabeh Taheripanah, Sayyed Mohammad Hossein Ghaderian, Elnaz Zamaniara, Sara Sadat Afjeh Aghabozorgi
BACKGROUND: One of the major problems in IVF is the poor response of the ovary to gonadotropins. ESRI and FSHR are two effective genes on controlled ovarian hyperstimulation (COH). OBJECTIVES: Evaluating the correlation of alleles and genotypes of polymorphism (-29G/A) located in the FSH receptor gene and polymorphism (XbaI G/A) located in Estrogen receptor genes with the ovary's response would help to anticipate the results of ovulation in IVF cycles. METHODS: In the present study, two hundred (200) blood samples were taken from infertile women aged 20 to 39 who were under IVF therapy...
January 19, 2018: Human Antibodies
Thor Haahr, Sandro C Esteves, Peter Humaidan
Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage...
March 9, 2018: Reproductive Biology and Endocrinology: RB&E
Akira Iwase, Satoko Osuka, Maki Goto, Tomohiko Murase, Tomoko Nakamura, Sachiko Takikawa, Fumitaka Kikkawa
It has been more than 15 years since the measurement of serum anti-Müllerian hormone (AMH) first allowed the quantitative assessment of ovarian reserve. Meanwhile, the clinical implication of serum AMH has been expanding. The measurement of serum AMH has been applied in various clinical fields, including assisted reproduction, menopause, reproductive disorders and assessment of ovarian damage/toxicity. Well-known findings about the usefulness of serum AMH revealed by numerous studies executed in the early era include decline with aging, a good correlation with oocyte yield in assisted reproduction, upregulation in polycystic ovarian syndrome and a decrease on ovarian surgery and toxic treatment...
March 8, 2018: Journal of Obstetrics and Gynaecology Research
Rosa Mistica C Ignacio, Yuan-Lin Dong, Syeda M Kabir, Hyeongjwa Choi, Eun-Sook Lee, Andrew J Wilson, Alicia Beeghly-Fadiel, Margaret M Whalen, Deok-Soo Son
Ovarian cancer (OC) has the highest rate of mortality among gynecological malignancy. Chemokine receptor CXCR2 in OC is associated with poor outcomes. However, the mechanisms by which CXCR2 regulates OC proliferation remain poorly understood. We generated CXCR2-positive cells from parental p53 wild-type (WT), mutant and null OC cells, and assessed the roles of CXCR2 on proliferation of OC cells in p53-dependent and independent manner. CXCR2 promoted cell growth rate: p53WT > mutant = null cells. Nutlin-3, a p53 stabilizer, inhibited cell proliferation in p53WT cells, but had little effect in p53-mutant or null cells, indicating p53-dependence of CXCR2-mediated proliferation...
February 9, 2018: Oncotarget
Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Sofia Genta, Massimo Aglietta, Anna Sapino, Giorgio Valabrega
BACKGROUND: Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. OBJECTIVES: To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis...
March 5, 2018: Recent Patents on Anti-cancer Drug Discovery
Belinda van Zyl, Denise Tang, Nikola A Bowden
Ovarian cancer has poor survival rate due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum resistant with subsequent relapses. Extensive research on individual biomarkers of platinum-resistance has revealed many potential targets for the development new treatments...
February 27, 2018: Endocrine-related Cancer
E Scott Sills, Natalie S Rickers, Xiang Li, Gianpiero D Palermo
Platelets modulate clinically relevant yet incompletely understood tissue regeneration processes, and platelet rich plasma (PRP) has been previously used with some success in various non-reproductive medical contexts. Here, we extended PRP application to ovarian tissue with a view to document impact on ovarian reserve among women attending for infertility treatment. PRP was freshly isolated from patients (n= 4) with diminished ovarian reserve as determined by at least one prior IVF cycle canceled for poor follicular recruitment response or estimated by serum AMH and/or FSH, no menses for ≥1 year...
February 28, 2018: Gynecological Endocrinology
Yoni Cohen, Samer Tannus, Nabigah Alzawawi, Weon-Young Son, Michael Dahan, William Buckett
Women of advanced age present a major challenge for fertility treatments. This study was designed to assess whether poor ovarian response (POR) according to the Bologna criteria is a significant predictor for live birth in women over 40. The outcomes of subsequent IVF cycles were also studied. The results of 1870 fresh IVF cycles in 1212 women were retrospectively analysed. The live birth per cycle was 3.3 times higher (11.61% versus 3.54%, P < 0.001) in good responders with more than three oocytes collected compared with women with less...
February 3, 2018: Reproductive Biomedicine Online
Yu-Fang Huang, Yi-Hui Wu, Wen-Fang Cheng, Shu-Ling Peng, Wan-Lin Shen, Cheng-Yang Chou
PURPOSE: Malignant ascites of epithelial ovarian cancer (EOC) help identify prognostic biomarkers or mechanisms of tumor progression. Vitamin D-binding protein (DBP) was revealed to be upregulated in EOC ascites in our previous proteomic study. Here, we examined the role of DBP in EOC. EXPERIMENTAL DESIGN: We analyzed ascites, serum, and tissue samples of patients with newly diagnosed EOC to determine the prognostic effects of DBP. We verified DBP function using orthotopic animal models and DBP regulation in ovarian cancer cell lines...
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Priyanka Grover, Sritama Nath, Monica D Nye, Ru Zhou, Mohammad Ahmad, Pinku Mukherjee
Pancreatic Ductal Adenocarcinoma (PDA) has a mortality rate that nearly matches its incidence rate. Transforming Growth Factor Beta (TGF-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. There is limited knowledge of how TGF-β function switches during tumorigenesis. Mucin 1 (MUC1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of PDA cases and is associated with poor prognosis. In PDA, MUC1 promotes tumor progression and metastasis via signaling through its cytoplasmic tail (MUC1-CT) and interacting with other oncogenic signaling molecules...
January 23, 2018: Oncotarget
Sevasti Manousakidi, Arnaud Guillaume, Caroline Pirou, Sylvina Bouleau, Bernard Mignotte, Flore Renaud, Nathalie Le Floch
Ovarian cancer remains associated with a high mortality rate and relapse is too frequently seen after chemotherapeutic treatment of granulosa cell tumors (GCTs) or epithelial ovarian cancers (EOCs). It is thus of major importance to progress in the knowledge of the molecular mechanisms underlying chemoresistance of ovarian tumors. Overexpression of Fibroblast Growth Factor 1 (FGF1) is observed in various cancers, correlates with poor survival and could be responsible for resistance to platinum-based chemotherapy of serous ovarian cancers...
February 21, 2018: Oncogenesis
Luis Felipe Sallum, Liliana Andrade, Larissa Bastos Eloy da Costa, Susana Ramalho, Amanda Canato Ferracini, Rodrigo de Andrade Natal, Angelo Borsarelli Carvalho Brito, Luis Otávio Sarian, Sophie Derchain
OBJECTIVE: The purpose of this study was to compare the immunohistochemical expression of BRCA1, Ki67, and β-catenin in women with low-grade (LGSOC) and high-grade serous ovarian carcinomas (HGSOC) and their relationship with clinicopathological features, response to platinum-based chemotherapy, and survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases, diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were included...
March 2018: International Journal of Gynecological Cancer
Saihua Ma, Ruihong Ma, Tian Xia, Masoud Afnan, Xueru Song, Fengqin Xu, Guimin Hao, Fangfang Zhu, Jingpei Han, Zhimei Zhao
BACKGROUND: Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients...
February 20, 2018: Trials
Nasrin Saharkhiz, Shahrzad Zademodares, Saghar Salehpour, Sedighe Hosseini, Leyla Nazari, Hatav Ghasemi Tehrani
Background: In this study, the effect of testosterone gel administration during ovulation induction on the fertility rate was examined in women with a poor ovarian response in in vitro fertilization (IVF) cycles. Materials and Methods: The current study is a single-blinded, randomized clinical trial. Patients who met inclusion (Bologna) criteria were placed in the antagonist cycle group. The patients were randomly divided into two groups each included 25 participants treated with a placebo (lubricant gel, the controls) and testosterone gel (intervention)...
2018: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
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