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https://www.readbyqxmd.com/read/29156803/tet1-inhibits-cell-proliferation-by-inducing-rassf5-expression
#1
Bo-Tai Li, Chao Yu, Ying Xu, Sheng-Bing Liu, Heng-Yu Fan, Wei-Wei Pan
Tet methylcytosine dioxygenases (TETs) catalyze the oxidative reactions of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). However, TET1 roles in ovarian cancer cell growth are unknown. Here, we show that ectopic expression of TET1 increased 5hmC levels, and inhibited proliferation and colony formation in ovarian cancer cell lines. Furthermore, in vitro and in vivo functional studies demonstrated that TET1 overexpression is necessary for the suppression of ovarian cancer growth, whereas depletion of TET1 expression had the opposite effect...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156771/novel-post-transcriptional-and-post-translational-regulation-of-pro-apoptotic-protein-bok-and-anti-apoptotic-protein-mcl-1-determine-the-fate-of-breast-cancer-cells-to-survive-or-die
#2
Benjamin Onyeagucha, Panneerdoss Subbarayalu, Nourhan Abdelfattah, Subapriya Rajamanickam, Santosh Timilsina, Rosa Guzman, Carla Zeballos, Vijay Eedunuri, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, Ratna K Vadlamudi, Manjeet K Rao
Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156754/functional-characterization-of-a-novel-transcript-of-ercc1-in-chemotherapy-resistance-of-ovarian-cancer
#3
Jia Liu, Lin Zhang, Ping Mao, Guoqiang Jiang, Likun Liu, Jing Wang, Wei Yang, Lawrence Owusu, Weiling Li
Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156715/connective-tissue-growth-factor-mediates-tgf-%C3%AE-1-induced-low-grade-serous-ovarian-tumor-cell-apoptosis
#4
Jung-Chien Cheng, Hsun-Ming Chang, Peter C K Leung
Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156714/investigation-of-factors-affecting-the-efficacy-of-3c23k-a-human-monoclonal-antibody-targeting-misiir
#5
Sarah E Gill, Qing Zhang, Gary L Keeney, William A Cliby, S John Weroha
MISIIR is a potential target for ovarian cancer (OC) therapy due to its tissue-specific pattern of expression. 3C23K is a novel therapeutic monoclonal anti-MISIIR antibody designed to recruit effector cells and promote cell death through ADCC (antibody dependent cell-mediated cytotoxicity). Our objective was to determine the tolerability and efficacy of 3C23K in OC patient-derived xenografts (PDX) and to identify factors affecting efficacy. Quantitative RT-PCR, immunohistochemistry (IHC), and flow cytometry were used to categorize MISIIR expression in established PDX models derived from primary OC patients...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156674/novel-combinations-of-pi3k-mtor-inhibitors-with-dacomitinib-or-chemotherapy-in-pten-deficient-patient-derived-tumor-xenografts
#6
Irene Brana, Nhu-An Pham, Lucia Kim, Shingo Sakashita, Ming Li, Christine Ng, Yuhui Wang, Peter Loparco, Rafael Sierra, Lisa Wang, Blaise A Clarke, Benjamin G Neel, Lillian L Siu, Ming-Sound Tsao
PTEN inactivation occurs commonly in human cancers and putatively activates the PI3K/AKT/ mTOR pathway. Activation of this pathway has been involved in resistance to chemotherapy or anti-EGFR/HER2 therapies. We evaluated the combination of PI3K-mTOR inhibitors with chemotherapy or the pan-HER inhibitor dacomitinib in PTEN-deficient patient-derived tumor xenografts (PDX). Three PDXs were selected for their lack of PTEN expression by immunohistochemistry: a triple-negative breast cancer (TNBC), a KRAS G12R low-grade serous ovarian cancer (LGSOC), and KRAS G12C and TP53 R181P lung adenocarcinoma (LADC)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156673/induction-of-dise-in-ovarian-cancer-cells-in-vivo
#7
Andrea E Murmann, Kaylin M McMahon, Ashley Haluck-Kangas, Nandini Ravindran, Monal Patel, Calvin Y Law, Sonia Brockway, Jian-Jun Wei, C Shad Thaxton, Marcus E Peter
The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3'UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and cancer stem cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156351/benzamide-porphyrins-with-directly-conjugated-and-distal-pyridyl-or-pyridinium-groups-substituted-to-the-porphyrin-macrocycles-study-of-the-photosensitising-abilities-as-inducers-of-apoptosis-in-cancer-cells-under-photodynamic-conditions
#8
Devashish Sengupta, Zeaul Hoque Mazumdar, Avinaba Mukherjee, Debdulal Sharma, Amit Kumar Halder, Samita Basu, Tarun Jha
Amphiphilic porphyrin photosensitisers (PSs) having combinations of directly substituted pyridyl group(s) at the meso-position of a porphyrin macrocycle, and/or indirectly linked pyridyl groups as benzamide derivatives are reported. The compounds 5,10,15,20-tetrakis-(4-pyridylbenzamide)porphyrin (A.2), 5,10,15,20-tetra[N-(pyridine-4-yl)benzamidium] porphyrin (A.3), 5-mono-(4-pyridyl)-10,15,20-tris-(4-pyridylbenzamide)porphyrin (B.2) and 5-mono-(4-methylpyridinium)-10,15,20-tris-(4-pyridiniumbenzamide)porphyrin (B...
November 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29156299/outcomes-from-ovarian-cancer-screening-in-the-plco-trial-histologic-heterogeneity-impacts-detection-overdiagnosis-and-survival
#9
Sarah M Temkin, Eric A Miller, Goli Samimi, Christine D Berg, Paul Pinsky, Lori Minasian
AIM: A mortality benefit from screening for ovarian cancer has never been demonstrated. The aim of this study was to evaluate the screening outcomes for different histologic subtypes of ovarian cancers. METHODS: Women in the screening arm of the Prostate, Lung, Colorectal and Ovarian Screening Trial underwent CA-125 and transvaginal ultrasound annually for 3-5 years. We compared screening test characteristics (including overdiagnosis) and outcomes by tumour type (type II versus other) and study arm (screening versus usual care)...
November 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29155418/esrp1-is-overexpressed-in-ovarian-cancer-and-promotes-switching-from-mesenchymal-to-epithelial-phenotype-in-ovarian-cancer-cells
#10
H M Jeong, J Han, S H Lee, H-J Park, H J Lee, J-S Choi, Y M Lee, Y-L Choi, Y K Shin, M J Kwon
This corrects the article DOI: 10.1038/oncsis.2017.87.
November 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29155058/foxo-1-contributes-to-the-efficacy-of-the-combination-of-the-xpo1-inhibitor-selinexor-and-cisplatin-in-ovarian-carcinoma-preclinical-models
#11
Cristina Corno, Simone Stucchi, Michelandrea De Cesare, Nives Carenini, Serena Stamatakos, Emilio Ciusani, Lucia Minoli, Eugenio Scanziani, Christian Argueta, Yosef Landesman, Nadia Zaffaroni, Laura Gatti, Paola Perego
The XPO1/CRM1 inhibitor selinexor (KPT-330), is currently being evaluated in multiple clinical trials as an anticancer agent. XPO1 participates in the nuclear export of FoxO-1, which we previously found to be decreased in platinum-resistant ovarian carcinoma. The aim of this study was to determine whether enriching FoxO-1 nuclear localization using selinexor would increase ovarian cancer cell sensitivity to cisplatin. Selinexor, as a single agent, displayed a striking antiproliferative effect in different ovarian carcinoma cell lines...
November 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29153542/adherence-to-treatment-recommendations-and-outcomes-for-women-with-ovarian-cancer-at-first-recurrence
#12
Miriam Champer, Yongmei Huang, June Y Hou, Ana I Tergas, William M Burke, Grace Clarke Hillyer, Cande V Ananth, Alfred I Neugut, Dawn L Hershman, Jason D Wright
OBJECTIVE: Treatment selection for recurrent ovarian cancer is typically based on the duration of time between the completion of adjuvant, platinum-based therapy and the time of recurrence, the platinum free interval (PFI). We examined the use of, and outcomes associated with platinum-based chemotherapy based on the PFI in women with recurrent ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women aged >65years with epithelial ovarian cancer who underwent surgery and platinum-based chemotherapy and who developed a recurrence >3months after the completion of adjuvant therapy...
November 15, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29153097/clinical-testing-with-a-panel-of-25-genes-associated-with-increased-cancer-risk-results-in-a-significant-increase-in-clinically-significant-findings-across-a-broad-range-of-cancer-histories
#13
Eric T Rosenthal, Ryan Bernhisel, Krystal Brown, John Kidd, Susan Manley
Genetic testing for inherited cancer risk is now widely used to target individuals for screening and prevention. However, there is limited evidence available to evaluate the clinical utility of various testing strategies, such as single-syndrome, single-cancer, or pan-cancer gene panels. Here we report on the outcomes of testing with a 25-gene pan-cancer panel in a consecutive series of 252,223 individuals between September 2013 and July 2016. The majority of individuals (92.8%) met testing criteria for Hereditary Breast and Ovarian Cancer (HBOC) and/or Lynch syndrome (LS)...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29152737/molecular-mechanisms-of-drug-resistance-in-ovarian-cancer
#14
REVIEW
Leyla Norouzi-Barough, Mohammad Reza Sarookhani, Mohammadreza Sharifi, Sahar Moghbelinejad, Saranaz Jangjoo, Rasoul Salehi
Ovarian cancer is the most lethal malignancy among the gynecological cancers, with a 5-year survival rate, mainly due to being diagnosed at advanced stages, recurrence and resistance to the current chemotherapeutic agents. Drug resistance is a complex phenomenon and the number of known involved genes and cross-talks between signaling pathways in this process is growing rapidly. Thus, discovering and understanding the underlying molecular mechanisms involved in chemo-resistance are crucial for management of treatment and identifying novel and effective drug targets as well as drug discovery to improve therapeutic outcomes...
November 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29152148/cox-2-expression-in-ovarian-cancer-an-updated-meta-analysis
#15
Haiming Sun, Xuelong Zhang, Donglin Sun, Xueyuan Jia, Lidan Xu, Yuandong Qiao, Yan Jin
The prognostic role of COX-2 expression in ovarian cancer patients has been studied for years, while results remain controversial. Thus we performed a meta-analysis to evaluate the prognostic impact of COX-2 expression on survival of ovarian cancer patients. The databases PubMed, Embase and CNKI were searched. Summary hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to analyze the correlations between COX-2 expression and overall survival (OS), and disease-free survival (DFS). A total of 1,867 patients from 18 studies were enrolled in the final analysis...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151961/galectin-1-promotes-tumor-progression-via-nf-%C3%AE%C2%BAb-signaling-pathway-in-epithelial-ovarian-cancer
#16
Le Chen, Ying Yao, Lijuan Sun, Jie Tang
Purpose: We previously reported that Galectin-1 (Gal-1) played a role in epithelial ovarian cancer (EOC) progression. In this study, we aimed to further investigate the association between Gal-1 expression and prognosis in EOC patients and tried to reveal some novel potential mechanisms of Gal-1 in EOC invasion and migration. Materials and Methods: Gal-1 and nucleus NF-κBp65 expression in 109 human epithelial ovarian cancer tissue specimens were evaluated by immunohistochemistry. The Cox model and survival curves were used to investigate the effect of Gal-1 on EOC prognosis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151946/gene-expression-profiling-reveals-novel-candidate-markers-of-ovarian-carcinoma-intraperitoneal-metastasis
#17
Katerina Elsnerova, Alena Bartakova, Josef Tihlarik, Jiri Bouda, Lukas Rob, Petr Skapa, Martin Hruda, Ivan Gut, Beatrice Mohelnikova-Duchonova, Pavel Soucek, Radka Vaclavikova
Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies. The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151939/clinical-impact-of-micrornas-associated-with-cancer-stem-cells-as-a-prognostic-factor-in-ovarian-carcinoma
#18
So Youn Cha, Yeon Ho Choi, Sohyun Hwang, Ju-Yeon Jeong, Hee Jung An
Background: Ovarian carcinoma is a highly lethal gynecological malignancy due to its frequent relapses and adoption of chemoresistance. To develop new biomarkers for disease progression in ovarian carcinoma, CSCs, which are considered to contribute to disease relapse and metastasis, were isolated from human ovarian carcinoma tissues, and differentially expressed microRNAs (miRNAs) in CSCs were identified and assessed the clinical implication of expression of these miRNAs. Methods: Primary cancer cells derived from human ovarian carcinomas were cultured and spheroid-forming cells (SFCs) were isolated...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150601/decoding-critical-long-non-coding-rna-in-ovarian-cancer-epithelial-to-mesenchymal-transition
#19
Ramkrishna Mitra, Xi Chen, Evan J Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M Eischen
Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150439/suppression-of-fip200-and-autophagy-by-tumor-derived-lactate-promotes-na%C3%A3-ve-t-cell-apoptosis-and-affects-tumor-immunity
#20
Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity...
November 17, 2017: Science Immunology
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