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Chemotherapy resistance ovarian carcinoma

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https://www.readbyqxmd.com/read/27918136/development-of-cell-permeable-non-helical-constrained-peptides-to-target-a-key-protein-protein-interaction-in-ovarian-cancer
#1
Mareike M Wiedmann, Yaw Sing Tan, Yuteng Wu, Shintaro Aibara, Wenshu Xu, Hannah F Sore, Chandra S Verma, Laura Itzhaki, Murray Stewart, James D Brenton, David R Spring
There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines. To inhibit the protein function, cell-permeable, non-helical constrained proteomimetics to target the HNF1β-importin α protein-protein interaction were designed, guided by X-ray crystallographic data and molecular dynamics simulations...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27917296/stat1-associated-intratumoural-th1-immunity-predicts-chemotherapy-resistance-in-high-grade-serous-ovarian-cancer
#2
Katrina K Au, Cécile Le Page, Runhan Ren, Liliane Meunier, Isabelle Clément, Kathrin Tyrishkin, Nichole Peterson, Jennifer Kendall-Dupont, Timothy Childs, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Jeremy A Squire, Anne-Marie Mes-Masson, Madhuri Koti
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8(+) T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8(+) T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#3
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27825116/ginsenoside-rb1-targets-chemotherapy-resistant-ovarian-cancer-stem-cells-via-simultaneous-inhibition-of-wnt-%C3%AE-catenin-signaling-and-epithelial-to-mesenchymal-transition
#4
Shan Deng, Chris Kong Chu Wong, Hung-Cheng Lai, Alice Sze Tsai Wong
Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767100/ccne1-copy-number-gain-and-overexpression-identify-ovarian-clear-cell-carcinoma-with-a-poor-prognosis
#5
Ayse Ayhan, Elisabetta Kuhn, Ren-Chin Wu, Hiroshi Ogawa, Asli Bahadirli-Talbott, Tsui-Lien Mao, Haruhiko Sugimura, Ie-Ming Shih, Tian-Li Wang
Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced-stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin E1 expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival...
October 21, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27711690/near-infrared-light-mediated-photoactivation-of-cytotoxic-re-i-complexes-by-using-lanthanide-doped-upconversion-nanoparticles
#6
Ming Hu, Jixian Zhao, Xiangzhao Ai, Maja Budanovic, Jing Mu, Richard D Webster, Qian Cao, Zongwan Mao, Bengang Xing
Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation...
September 13, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27671528/novel-abcg2-antagonists-reverse-topotecan-mediated-chemotherapeutic-resistance-in-ovarian-carcinoma-xenografts
#7
Jerec W Ricci, Debbie M Lovato, Virginia Severns, Larry A Sklar, Richard S Larson
Chemotherapeutic resistance remains a challenge in the treatment of ovarian carcinoma, especially in recurrent disease. Despite the fact that most patients with newly diagnosed tumors attain complete remission following cytoreductive surgery and chemotherapy, ovarian carcinoma has a recurrence rate that exceeds 75%. The ATP-binding cassette family G member 2 (ABCG2) efflux protein has been described as one mechanism that confers multiple-drug resistance to solid tumors and contributes to topotecan resistance in ovarian carcinoma...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27663731/improved-i-p-drug-delivery-with-bioadhesive-nanoparticles
#8
Yang Deng, Fan Yang, Emiliano Cocco, Eric Song, Junwei Zhang, Jiajia Cui, Muneeb Mohideen, Stefania Bellone, Alessandro D Santin, W Mark Saltzman
The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27641463/-high-dose-chemotherapy-as-a-strategy-to-overcome-drug-resistance-in-solid-tumors
#9
Frédéric Selle, Joseph Gligorov, Daniele G Soares, Jean-Pierre Lotz
The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated...
September 15, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27614696/in-vivo-anti-tumor-activity-of-the-parp-inhibitor-niraparib-in-homologous-recombination-deficient-and-proficient-ovarian-carcinoma
#10
Mariam M AlHilli, Marc A Becker, S John Weroha, Karen S Flatten, Rachel M Hurley, Maria I Harrell, Ann L Oberg, Matt J Maurer, Kieran M Hawthorne, Xiaonan Hou, Sean C Harrington, Sarah McKinstry, X Wei Meng, Keith M Wilcoxen, Kimberly R Kalli, Elizabeth M Swisher, Scott H Kaufmann, Paul Haluska
OBJECTIVE: Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo...
September 7, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27610161/ftir-biospectroscopy-investigation-on-cisplatin-cytotoxicity-in-three-pairs-of-sensitive-and-resistant-cell-line
#11
Ensieh Farhadi, Farzad Kobarfard, Farshad H Shirazi
Fourier Transformed Infrared Spectroscopy (FTIR) has extensively been used for biological applications. Cisplatin is one the most useful antineoplastic chemotherapy drugs for a variety of different human cancers. One of the clinical problems in its application, which would consequently affect the therapeutic outcome of its application, is the occurrence of resistance to this agent. In this project three different pairs of sensitive and resistant cell lines of human ovarian A2780 and its resistant pair of A2780-CP, human ovarian OV2008 and its resistant pair of C13, and finally human lung carcinoma of HTB56 and its resistant pair of HTB56-CP were grown in the laboratory under the standard procedure...
2016: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/27590741/ovarian-cancer-chemoresistance-relies-on-the-the-stem-cell-reprogramming-factor-pbx1
#12
Jin-Gyoung Jung, Ie-Ming Shih, Joon Tae Park, Emily Gerry, Tae Hoen Kim, Ayse Ayhan, Karen Handschuh, Ben Davidson, Amanda Nickles Fader, Licia Selleri, Tian-Li Wang
The evolution of chemoresistance is a fundamental characteristic of cancer that ultimately defeats its clinical management. However, it may be possible improve patient outcomes significantly by defeating nodal resistance mechanisms which cancers rely upon during the evolution to an untreatable state. Here we report an essential role for upregulation of the stem cell reprogramming factor PBX1 in mediating chemoresistance in recurrent ovarian carcinomas. In clinical specimens, high levels of PBX1 expression correlated with shorter survival in post-chemotherapy ovarian cancer patients...
September 2, 2016: Cancer Research
https://www.readbyqxmd.com/read/27581327/low-grade-serous-ovarian-cancer-a-review
#13
REVIEW
Anis Kaldawy, Yakir Segev, Ofer Lavie, Ron Auslender, Victoria Sopik, Steven A Narod
Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy...
November 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27558151/ovarian-cancer
#14
Ursula A Matulonis, Anil K Sood, Lesley Fallowfield, Brooke E Howitt, Jalid Sehouli, Beth Y Karlan
Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested...
August 25, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27470344/inhibition-of-autophagy-sensitizes-mdr-phenotype-ovarian-cancer-skvcr-cells-to-chemotherapy
#15
Bing Liang, Xiaodong Liu, Yang Liu, Dejuan Kong, Xiaomei Liu, Rui Zhong, Shumei Ma
UNLABELLED: AUTOPHAGY: is an intracellular lysosomal degradation pathway where its primary function is to allow cells to survive under stressful conditions. Autophagy is, however, a double-edge sword that can either promote cell survival or cell death. CHEMORESISTANCE: is a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown. OBJECTIVE: The aim of the present study was to explore the role of autophagy in vincristine (VCR) resistant ovarian cancer cells...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27469379/targeting-the-mitogen-activated-protein-kinase-pathway-in-low-grade-serous-carcinoma-of-the-ovary
#16
Jennifer McLachlan, Martin Gore, Susana Banerjee
Until recently, there has been little change in the management of epithelial ovarian cancer with the majority of women receiving identical systemic therapy, regardless of histological subtype. The heterogeneity of epithelial ovarian cancer is now well established, with distinct subtypes characterized by specific molecular alterations and patterns of clinical behavior. Low-grade serous carcinoma is a rare subtype associated with an indolent biological behavior and inherent resistance to chemotherapy. The mitogen-activated protein kinase pathway plays a prominent role in the pathogenesis of low-grade serous carcinoma, and provides an attractive target for novel therapeutic agents...
August 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27468472/-employing-dna-damage-response-inhibitors-to-enhance-chemosensitivity-of-ovarian-carcinoma-cells
#17
Si-yuan Cai, Zi-zhi Tang, Ming Zeng, Xiao-jun Wang, Jiang-yan Lou, Cong Liu, Jie Chen
OBJECTIVE: To assess the sensitisation effects of DDR inhibitors combined with conventional chemotherapeutics agents (cisplatin et al) in a drug-resistant ovarian cancer cell line(OVCAR-8). METHODS: Inhibitors of DDR regulators with cisplatin were applied to challenge OVCAR-8, and evaluated the DNA damage response (DDR) and cytotoxic effects of different combination of chemicals. Inhibition of proliferation to OVCAR-8 of different drugs was evaluated by MTT assay...
May 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/27461360/cyclin-e-as-a-potential-therapeutic-target-in-high-grade-serous-ovarian-cancer
#18
J Kanska, M Zakhour, B Taylor-Harding, B Y Karlan, W R Wiedemeyer
Cyclin E1 (CCNE1) gene amplification occurs in approximately 20% of ovarian high grade serous carcinoma (HGSC) and is associated with chemotherapy resistance and, in some studies, overall poor prognosis. The role of cyclin E1 in inducing S phase entry relies upon its interactions with cyclin dependent kinases (CDK), specifically CDK2. Therapies to target cyclin E1-related functions have centered on CDK inhibitors and proteasome inhibitors. While many studies have helped elucidate the functions and regulatory mechanisms of cyclin E1, further research utilizing cyclin E1 as a therapeutic target in ovarian cancer is warranted...
October 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27383536/microrna-125b-suppresses-ovarian-cancer-progression-via-suppression-of-the-epithelial-mesenchymal-transition-pathway-by-targeting-the-set-protein
#19
Xiaoyan Ying, Kuang Wei, Zhe Lin, Yugui Cui, Jie Ding, Yun Chen, Boqun Xu
BACKGROUND/AIMS: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer. METHODS: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR-125b was measured using real-time polymerase chain reaction (RT-PCR)...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27341024/annexin-a4-fucosylation-enhances-its-interaction-with-the-nf-kb-p50-and-promotes-tumor-progression-of-ovarian-clear-cell-carcinoma
#20
Huimin Wang, Lu Deng, Mingbo Cai, Huiyu Zhuang, Liancheng Zhu, Yingying Hao, Jian Gao, Juanjuan Liu, Xiao Li, Bei Lin
OBJECTIVE: To study the structural relationship between annexin A4 and the Lewis y antigen and compare their expression and significance in ovarian clear cell carcinoma, and to explore how annexin A4 fucose glycosylation effects the interaction between annexin A4 and NF-kB p50, and how it promotes tumour progression of ovarian clear cell carcinoma. METHODS: Structural relationships between annexin A4 and Lewis y antigen were detected using immunoprecipitation. Annexin A4 and Lewis y antigen expression in various subtypes of ovarian cancer tissues was detected by immunohistochemistry, and the relation between their expression was examined...
June 22, 2016: Oncotarget
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