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Chemotherapy resistance ovarian carcinoma

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https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#1
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28619062/platinum-containing-compound-platinum-pyrithione-suppresses-ovarian-tumor-proliferation-through-proteasome-inhibition
#2
Hongbiao Huang, Ni Liu, Yuning Liao, Ningning Liu, Jianyu Cai, Xiaohong Xia, Zhiqiang Guo, Yanling Li, Qirong Wen, Qi Yin, Yan Liu, Qingxia Wu, Dhivya Rajakumar, Xiujie Sheng, Jinbao Liu
BACKGROUND: Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent. METHOD: MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis...
June 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28588062/secondary-somatic-mutations-restoring-rad51c-and-rad51d-associated-with-acquired-resistance-to-the-parp-inhibitor-rucaparib-in-high-grade-ovarian-carcinoma
#3
Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V Tinker, Nelson N H Teng, Maria I Harrell, Michael J Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M Kass, Meghan R Sullivan, Gregory J Brunette, Kara A Bernstein, Robert L Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M O'Malley, Amit M Oza, James X Sun, Liliane Robillard, Lara Maloney, David D L Bowtell, Heidi Giordano, Matthew J Wakefield, Scott H Kaufmann, Andrew D Simmons, Thomas C Harding, Mitch Raponi, Iain A McNeish, Elizabeth M Swisher, Kevin Lin, Clare L Scott
High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC...
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28498842/prognostic-significance-and-predictors-of-the-system-inflammation-score-in-ovarian-clear-cell-carcinoma
#4
Hongwei Zhang, Jiaqi Lu, Yingying Lu, Jiayi Zhou, Zehua Wang, Haiou Liu, Congjian Xu
Chronic inflammation is a well-known epidemiologic factor of ovarian clear cell carcinomas (OCCC), but has an uncertain role in prognosis. We developed a systemic inflammation score (SIS) based on preoperative serum albumin and neutrophil-to-lymphocyte ratio (NLR) for predicting progression-free survival (PFS) and overall survival (OS) in OCCC patients. A retrospective review was performed in 155 patients with OCCC undergoing primary debulking and chemotherapy at a single institute between 1995 and 2010. Cox regression models were fitted to analyze the effect of prognostic factors on PFS and OS...
2017: PloS One
https://www.readbyqxmd.com/read/28481779/claudin-4-expression-is-associated-with-survival-in-ovarian-cancer-but-not-with-chemotherapy-response
#5
Laura Martín de la Fuente, Susanne Malander, Linda Hartman, Jenny-Maria Jönsson, Anna Ebbesson, Mef Nilbert, Anna Måsbäck, Ingrid Hedenfalk
The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression models were used to assess the effect of claudin-4 overexpression on progression-free survival and overall survival (OS)...
May 5, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28477068/the-role-of-mir-130a-in-cancer
#6
REVIEW
He-da Zhang, Lin-Hong Jiang, Da-Wei Sun, Jian Li, Zhen-Ling Ji
MicroRNAs (miRs) are short and highly conserved non-coding RNAs molecules consisting of 18-25 nucleotides that regulate gene expression at post-transcriptional level by direct binding to complementary binding sites within the 3'untranslated region (3'UTR) of target mRNAs. New evidences have demonstrated that miRNAs play an important role in diverse physiological processes, including regulating cell growth, apoptosis, metastasis, drug resistance, and invasion. In chromosomes 11 and 22 of the miR-130 family, paralogous miRNA sequences, miR-130a and miR-130b are situated, respectively...
May 5, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28454274/role-of-endoplasmic-reticulum-stress-on-cisplatin-resistance-in-ovarian-carcinoma
#7
Jing Tian, Rong Liu, Quanxin Qu
Endoplasmic reticulum (ER) is an essential site of cellular homeostasis regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from apoptosis. The present study examined the effects and mechanism of ERS on cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with Saquinavir were subjected to western blot and reverse transcription-quantitative polymerase chain reaction analysis to determine protein and messenger RNA (mRNA) expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454268/tcrp1-expression-is-associated-with-platinum-sensitivity-in-human-lung-and-ovarian-cancer-cells
#8
Xiaorong Liu, Meiling Feng, Guopei Zheng, Yixue Gu, Chengkun Wang, Zhimin He
Platinum-based drugs, including cisplatin (DDP) and oxaliplatin (L-OHP), are among the most potent chemotherapy drugs, and are widely utilized for the treatment of human lung and ovarian cancer. However, certain patients do not respond to platinum-based agents, and even those who initially benefit from the treatment will eventually exhibit resistance to these drugs. Although certain factors have been investigated for their potential to predict platinum resistance, more effective predictors for the improved management of patients with lung and ovarian cancer are required...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28450177/ovarian-cancer-stem-cells-more-questions-than-answers
#9
REVIEW
Petronella Beatrix Ottevanger
Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission...
April 24, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28440503/cd24-expression-is-a-marker-for-predicting-clinical-outcome-and-regulates-the-epithelial-mesenchymal-transition-in-ovarian-cancer-via-both-the-akt-and-erk-pathways
#10
Kiyoko Nakamura, Yoshito Terai, Akiko Tanabe, Yoshihiro J Ono, Masami Hayashi, Kazuya Maeda, Satoe Fujiwara, Keisuke Ashihara, Michihiko Nakamura, Yoshimichi Tanaka, Tomohito Tanaka, Satoshi Tsunetoh, Hiroshi Sasaki, Masahide Ohmichi
The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma...
June 2017: Oncology Reports
https://www.readbyqxmd.com/read/28436990/tcrp1-promotes-nih-3t3-cell-transformation-by-over-activating-pdk1-and-akt1
#11
C Wang, H Liu, Q Qiu, Z Zhang, Y Gu, Z He
Tongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our precious studies demonstrated that TCRP1 was involving in chemotherapy and radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian cancer cells. In this study, we showed that TCRP1 overexpression promotes cell transformation and tumorigenesis through hyperphosphorylation of the oncogenic kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1-mediated cell transformation...
April 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28436947/dedifferentiation-into-blastomere-like-cancer-stem-cells-via-formation-of-polyploid-giant-cancer-cells
#12
N Niu, I Mercado-Uribe, J Liu
Our recent perplexing findings that polyploid giant cancer cells (PGCCs) acquired embryonic-like stemness and were capable of tumor initiation raised two important unanswered questions: how do PGCCs acquire such stemness, and to which stage of normal development do PGCCs correspond. Intriguingly, formation of giant cells due to failed mitosis/cytokinesis is common in the blastomere stage of the preimplantation embryo. However, the relationship between PGCCs and giant blastomeres has never been studied. Here, we tracked the fate of single PGCCs following paclitaxel-induced mitotic failure...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28397106/efficacy-of-neratinib-in-the-treatment-of-her2-neu-amplified-epithelial-ovarian-carcinoma-in-vitro-and-in-vivo
#13
Gulden Menderes, Elena Bonazzoli, Stefania Bellone, Jonathan D Black, Salvatore Lopez, Francesca Pettinella, Alice Masserdotti, Luca Zammataro, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
Epithelial ovarian carcinoma is the most lethal of gynecologic malignancies. There is a need to optimize the currently available treatment strategies and to urgently develop novel therapeutic agents against chemotherapy-resistant disease. The objective of our study was to evaluate neratinib's preclinical efficacy in treating HER2-amplified ovarian cancer. Neratinib's efficacy in treating HER2-amplified ovarian cancer was studied in vitro utilizing six primary tumor cell lines with differential HER2/neu expression...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28359078/safety-and-utility-of-image-guided-research-biopsies-in-relapsed-high-grade-serous-ovarian-carcinoma-experience-of-the-britroc-consortium
#14
T Goranova, D Ennis, A M Piskorz, G Macintyre, L A Lewsley, J Stobo, C Wilson, D Kay, R M Glasspool, M Lockley, E Brockbank, A Montes, A Walther, S Sundar, R Edmondson, G D Hall, A Clamp, C Gourley, M Hall, C Fotopoulou, H Gabra, S Freeman, L Moore, M Jimenez-Linan, J Paul, J D Brenton, I A McNeish
BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA...
May 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28349821/lamp3-expression-correlated-with-poor-clinical-outcome-in-human-ovarian-cancer
#15
Di Wang, Xuemin Cao, Yuquan Zhang, Yuanlin Liu, Chan Yao, Wenliang Ge, Yunzhao Xu
Lysosome-associated membrane protein 3 belongs to the lysosome-associated membrane glycoprotein family, which is associated with lymph node, metastasis, poor overall survival, and resistance to chemotherapy and radiotherapy. Epithelial ovarian cancer is one of the most deadly global female gynecologic malignant tumors. Its clinical outcome is poor and most epithelial ovarian cancer patients tend to relapse because of drug resistance. However, lysosome-associated membrane protein 3 expression in epithelial ovarian cancer and its relationship between clinicopathologic factors remain poorly understood...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28320418/ovarian-cancer-stem-cells-still-an-elusive-entity
#16
REVIEW
Michela Lupia, Ugo Cavallaro
The cancer stem cell (CSC) model proposes that tumor development and progression are fueled and sustained by undifferentiated cancer cells, endowed with self-renewal and tumor-initiating capacity. Ovarian carcinoma, based on its biological features and clinical evolution, appears as a prototypical example of CSC-driven disease. Indeed, ovarian cancer stem cells (OCSC) would account not only for the primary tumor growth, the peritoneal spread and the relapse, but also for the development of chemoresistance, thus having profound implication for the treatment of this deadly disease...
March 20, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28265509/new-in-vitro-system-to-predict-chemotherapeutic-efficacy-of-drug-combinations-in-fresh-tumor-samples
#17
Frank Christian Kischkel, Julia Eich, Carina I Meyer, Paula Weidemüller, Jens Krapfl, Rauaa Yassin-Kelepir, Laura Job, Marius Fraefel, Ioana Braicu, Annette Kopp-Schneider, Jalid Sehouli, Rudy Leon De Wilde
BACKGROUND: To find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR)-Test(®). Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods...
2017: PeerJ
https://www.readbyqxmd.com/read/28259988/targeting-glutamine-metabolism-and-the-focal-adhesion-kinase-additively-inhibits-the-mammalian-target-of-the-rapamycin-pathway-in-spheroid-cancer-stem-like-properties-of-ovarian-clear-cell-carcinoma-in%C3%A2-vitro
#18
Masakazu Sato, Kei Kawana, Katsuyuki Adachi, Asaha Fujimoto, Mitsuyo Yoshida, Hiroe Nakamura, Haruka Nishida, Tomoko Inoue, Ayumi Taguchi, Juri Ogishima, Satoko Eguchi, Aki Yamashita, Kensuke Tomio, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Yutaka Osuga, Tomoyuki Fujii
Ovarian cancer is one of the leading causes of death in the world, which is linked to its resistance to chemotherapy. Strategies to overcome chemoresistance have been keenly investigated. Culturing cancer cells in suspension, which results in formation of spheroids, is a more accurate reflection of clinical cancer behavior in vitro than conventional adherent cultures. By performing RNA-seq analysis, we found that the focal adhesion pathway was essential in spheroids. The phosphorylation of focal adhesion kinase (FAK) was increased in spheroids compared to adherent cells, and inhibition of FAK in spheroids resulted in inhibition of the downstream mammalian target of the rapamycin (mTOR) pathway in ovarian clear cell carcinomas...
February 23, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28251557/establishment-and-characterization-of-a-platinum-and-paclitaxel-resistant-high-grade-serous-ovarian-carcinoma-cell-line
#19
Pang-Ning Teng, Nicholas W Bateman, Guisong Wang, Tracy Litzi, Brian E Blanton, Brian L Hood, Kelly A Conrads, Wei Ao, Kate E Oliver, Kathleen M Darcy, William P McGuire, Keren Paz, David Sidransky, Chad A Hamilton, G Larry Maxwell, Thomas P Conrads
High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy...
March 1, 2017: Human Cell
https://www.readbyqxmd.com/read/28197007/use-of-clozapine-alongside-chemotherapy-in-a-treatment-resistant-bipolar-disorder-patient-with-ovarian-carcinoma-a-case-report-and-brief-review
#20
Ashish Pakhre, Aarya Krishnan, Raman Deep Pattanayak, Sudhir K Khandelwal
Regular monitoring of blood counts ensures the safety of clozapine use; however, certain clinical situations may pose a dilemma for management such as use of clozapine in the presence of myelosuppressive chemotherapy. Further, there is very limited literature to guide such decisions. We report a case of a clozapine-stabilized, treatment-resistant bipolar disorder patient with ovarian carcinoma requiring chemotherapy. The clinical challenges are discussed in light of a brief review of the available reports.
October 2016: Indian Journal of Psychiatry
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