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Carboplatin resistant ovarian cancer

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https://www.readbyqxmd.com/read/28804784/birinapant-sensitizes-platinum-resistant-carcinomas-with-high-levels-of-ciap-to-carboplatin-therapy
#1
V La, R Fujikawa, D M Janzen, M Nunez, L Bainvoll, L Hwang, K Faull, G Lawson, S Memarzadeh
Platinum drugs are the frontline therapy in many carcinomas, including high-grade serous ovarian cancers. Clinically, high-grade serous carcinomas have an apparent complete response to carboplatin, but tumors invariably recur and response to platinum drugs diminishes over time. Standard of care prohibits re-administration of platinum drugs to these patients who are labeled as having platinum-resistant disease. In this stage patients are treated with non-platinum agents and outcomes are often poor. In vivo and in vitro data presented here demonstrate that this clinical dogma should be challenged...
2017: NPJ Precis Oncol
https://www.readbyqxmd.com/read/28790113/neurotensin-receptor-1-antagonist-sr48692-improves-response-to-carboplatin-by-enhancing-apoptosis-and-inhibiting-drug-efflux-in-ovarian-cancer
#2
Jin Liu, Mikael Agopiantz, Joel Poupon, Zherui Wu, Pierre-Alexandre Just, Bruno Borghese, Evelyne Ségal-Bendirdjian, Guillaume Gauchotte, Anne Gompel, Patricia Forgez
PURPOSE: The high affinity receptor 1 (NTSR1) and its agonist, neurotensin (NTS), is correlated with tumor cell aggressiveness in most solid tumors. As chemo-resistance and tumor aggressiveness are often related; we decided to study the role of the NTSR1 complex within platinum-based chemotherapy responses. In an ovarian model, we studied carboplatin because it is the main standard of care for ovarian cancer (OC). EXPERIMENTAL DESIGN: Experimental tumors and in vitro studied were performed using SKOV3 and A2780 cells treated with carboplatin, with or without a very specific NTSR1 antagonist, SR48692...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28737129/association-between-polymorphisms-in-ctr1-ctr2-atp7a-and-atp7b-and-platinum-resistance-in-epithelial-ovarian-cancer
#3
Tailin Li, Jingbo Peng, Feiyue Zeng, Keqiang Zhang, Jinyang Liu, Xi Li, Qianying Ouyang, Guo Wang, Liansheng Wang, Zhaoqian Liu, Yingzi Liu
The copper transporters CTR1, CTR2, ATP7A, and ATP7B regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in CTR1, CTR2, ATP7A, and ATP7B on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28733701/copper-ii-complexes-of-bidentate-ligands-exhibit-potent-anti-cancer-activity-regardless-of-platinum-sensitivity-status
#4
Mohamed Wehbe, Cody Lo, Ada W Y Leung, Wieslawa H Dragowska, Gemma M Ryan, Marcel B Bally
Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC50 ~ 1 μM platinum) and insensitive (IC50 > 5 μM platinum) cell lines...
July 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#5
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28713952/exploration-of-the-sequential-gene-changes-in-epithelial-ovarian-cancer-induced-by-carboplatin-via-microarray-analysis
#6
Shuqing Wei, Jianwu Liu, Yuxia Shi, Xi Zhang, Yongming Yang, Qingzhen Song
The purpose of the current study was to explore the carboplatin‑induced sequential changes in gene expression and screen out key genes, which were associated with effects of carboplatin on epithelial ovarian cancer (EOC). The microarray dataset GSE13525 was downloaded from the Gene Expression Omnibus database, including 6 EOC cell samples separately treated with carboplatin at 24, 30 and 36 h (case group), and 6 samples treated with phosphate‑buffered saline at the same time points (control group). A total of 3 sets of differentially expressed genes (DEGs) were respectively identified in case samples at 24, 30 and 36 h compared with the control group via the Limma package, and separately recorded as DEG‑24, DEG‑30 and DEG‑36...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28700338/moc31pe-immunotoxin-targeting-peritoneal-metastasis-from-epithelial-ovarian-cancer
#7
Yvonne Andersson, Synne Ihler Haavardtun, Ben Davidson, Anne Dørum, Karianne G Fleten, Øystein Fodstad, Kjersti Flatmark
Peritoneal metastasis (PM) is an important feature of epithelial ovarian cancer (EOC) and is a frequent site of drug resistant disease recurrence, identifying PM-EOC an important clinical challenge. The MOC31PE immunotoxin targets and kills tumor cells expressing the epithelial cell adhesion molecule (EpCAM), which is highly expressed in EOC, and MOC31PE is being investigated for use in treatment of PM-EOC.The efficacy of MOC31PE treatment alone and in combination with cytotoxic drugs was investigated in two human EpCAM expressing EOC cell lines, B76 and MDHA-2774, in vitro and in corresponding mouse models mimicking PM-EOC...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28685075/combination-of-irinotecan-and-platinum-for-platinum-resistant-or-refractory-recurrent-ovarian-cancers-a-preliminary-case-series
#8
Takashi Shibutani, Masashi Takano, Morikazu Miyamoto, Tomoyuki Yoshikawa, Tadashi Aoyama, Hiroaki Soyama, Junko Hirata, Ayako Suzuki, Hidenori Sasa, Kenichi Furuya
Non-platinum single agents are usually used for patients with platinum-resistant recurrent ovarian cancers (ROC). However, the efficacy of these drugs is limited. The aim of the present study was to evaluate the efficacy and adverse events (AE) of combination therapy with irinotecan and platinum (CPT-Pt) for ROC. A total of 28 platinum-resistant or refractory patients with ROC treated with CPT-Pt at the National Defense Medical College Hospital institution between 2002 and 2012 were identified. All patients received taxane and carboplatin (TC) as a first-line treatment and relapsed within 6 months after completion of TC, or progressed during TC therapy...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28664915/kinase-driven-metabolic-signalling-as-a-predictor-of-response-to-carboplatin-paclitaxel-adjuvant-treatment-in-advanced-ovarian-cancers
#9
Maria Isabella Sereni, Elisa Baldelli, Guido Gambara, Antonella Ravaggi, K Alex Hodge, David S Alberts, Jose M Guillen-Rodriguez, Ting Dong, Maurizio Memo, Franco Odicino, Roberto Angioli, Lance A Liotta, Sergio L Pecorelli, Emanuel F Petricoin, Mariaelena Pierobon
BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#10
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28608931/the-association-between-germline-brca2-variants-and-sensitivity-to-platinum-based-chemotherapy-among-men-with-metastatic-prostate-cancer
#11
Mark M Pomerantz, Sandor Spisák, Li Jia, Angel M Cronin, Istvan Csabai, Elisa Ledet, A Oliver Sartor, Irene Rainville, Edward P O'Connor, Zachary T Herbert, Zoltan Szállási, William K Oh, Philip W Kantoff, Judy E Garber, Deborah Schrag, Adam S Kibel, Matthew L Freedman
BACKGROUND: Breast cancer 2 (BRCA2)-associated breast and ovarian cancers are sensitive to platinum-based chemotherapy. It is unknown whether BRCA2-associated prostate cancer responds favorably to such treatment. METHODS: A retrospective analysis of a single-institution cohort of men with castration-resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate-specific antigen response to carboplatin-based chemotherapy...
June 13, 2017: Cancer
https://www.readbyqxmd.com/read/28486623/platinum-induced-mitochondrial-dna-mutations-confer-lower-sensitivity-to-paclitaxel-by-impairing-tubulin-cytoskeletal-organization
#12
Giulia Girolimetti, Flora Guerra, Luisa Iommarini, Ivana Kurelac, Daniele Vergara, Michele Maffia, Michele Vidone, Laura Benedetta Amato, Giulia Leone, Sabrina Dusi, Valeria Tiranti, Anna Myriam Perrone, Cecilia Bucci, Anna Maria Porcelli, Giuseppe Gasparre
Development of chemoresistance is a cogent clinical issue in oncology, whereby combination of anticancer drugs is usually preferred also to enhance efficacy. Paclitaxel (PTX), combined with carboplatin, represents the standard first-line chemotherapy for different types of cancers. We here depict a double-edge role of mitochondrial DNA (mtDNA) mutations induced in cancer cells after treatment with platinum. MtDNA mutations were positively selected by PTX, and they determined a decrease in the mitochondrial respiratory function, as well as in proliferative and tumorigenic potential, in terms of migratory and invasive capacity...
May 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28459431/mirna-34c-5p-inhibits-amphiregulin-induced-ovarian-cancer-stemness-and-drug-resistance-via-downregulation-of-the-areg-egfr-erk-pathway
#13
S-L Tung, W-C Huang, F-C Hsu, Z-P Yang, T-H Jang, J-W Chang, C-M Chuang, C-R Lai, L-H Wang
Epithelial ovarian cancer is the most lethal gynecological cancer mainly due to late diagnosis, easy spreading and rapid development of chemoresistance. Cancer stem cells are considered to be one of the main mechanisms for chemoresistance, as well as metastasis and recurrent disease. To explore the stemness characteristics of ovarian cancer stem cells, we successfully enriched ovarian cancer stem-like cells from an established ovarian cancer cell line (SKOV-I6) and a fresh ovarian tumor-derived cell line (OVS1)...
May 1, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28446239/dasatinib%C3%A2-%C3%A2-gefitinib-a-non-platinum-based-combination-with-enhanced-growth-inhibitory-anti-migratory-and-anti-invasive-potency-against-human-ovarian-cancer-cells
#14
Benoît Thibault, Bertrand Jean-Claude
BACKGROUND: Ovarian cancer is the leading cause of death for gynecological cancers and the 6th cause of women cancer death in developed countries. The late stage detection, the peritoneal dissemination and the acquisition of resistance against carboplatin are the main reasons to explain this poor prognosis and strengthen the need of alternative treatments to improve the management of ovarian cancer and/or to sensitize tumors to platinum salts. Epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (Met) and cellular Src kinase (c-Src) are crucial kinases implied in ovarian tumor growth, survival, invasion and resistance to carboplatin...
April 26, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28334047/clinical-validation-of-chemotherapy-predictors-developed-on-global-microrna-expression-in-the-nci60-cell-line-panel-tested-in-ovarian-cancer
#15
Kira Philipsen Prahm, Claus Høgdall, Mona Aarenstrup Karlsen, Ib Jarle Christensen, Guy Wayne Novotny, Steen Knudsen, Anker Hansen, Peter Buhl Jensen, Thomas Jensen, Mansoor Raza Mirza, Anne Weng Ekmann-Gade, Lotte Nedergaard, Estrid Høgdall
OBJECTIVE: Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival. METHODS: Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel...
2017: PloS One
https://www.readbyqxmd.com/read/28265509/new-in-vitro-system-to-predict-chemotherapeutic-efficacy-of-drug-combinations-in-fresh-tumor-samples
#16
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/28251557/establishment-and-characterization-of-a-platinum-and-paclitaxel-resistant-high-grade-serous-ovarian-carcinoma-cell-line
#17
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...
July 2017: Human Cell
https://www.readbyqxmd.com/read/28240014/general-characteristics-and-cytotoxic-effects-of-nano-poly-butyl-cyanoacrylate-containing-carboplatin-on-ovarian-cancer-cells
#18
Leila Kanaani, Meysam Ebrahimi Far, S Maryam Kazemi, Edris Choupani, Maral Mazloumi Tabrizi, Hasan Ebrahimi Shahmabadi, Azim Akbarzadeh Khiyavi
The initial response to treatment and subsequent development of resistance to carboplatin are very important challenges. Use of nano drug delivery is a new method to replace standard chemotherapy. In this research, both non-PEGylated and PEGylated nanoparticles (NPs) were prepared by mini-emulsion polymerization of poly (butyl cyanoacrylate) (PBCA) NPs. Characteristics such as size, polydispersity index (PDI), zeta potential, drug release, and stability were examined. In addition, infrared spectroscopy was used for description of the produced NPs...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28238155/safety-of-herbal-medicine-use-during-chemotherapy-in-patients-with-ovarian-cancer-a-bedside-to-bench-approach
#19
Eran Ben-Arye, Ofer Lavie, Noah Samuels, Hazem Khamaisie, Elad Schiff, Orit Gressel Raz, Jamal Mahajna
In this study, we explored herbal supplements used by patients during chemotherapy and test for herb-drug interactions and response of cancer cells to treatment. Patients with gynecological cancer referred to a complementary and integrative medicine (CIM) service were asked about their use of herbal medicine during chemotherapy. The leading five clinically relevant herbs selected for cytotoxicity analysis included the following: wheatgrass (Triticum aestivum), European mistletoe (Viscum album), ginger (Zingiber officinale), Ephedra (Ephedra campylopoda), and Oriental mistletoe (Viscum cruciatum)...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28214016/melk-expression-in-ovarian-cancer-correlates-with-poor-outcome-and-its-inhibition-by-otssp167-abrogates-proliferation-and-viability-of-ovarian-cancer-cells
#20
Reto S Kohler, Henriette Kettelhack, Alexandra M Knipprath-Mészaros, André Fedier, Andreas Schoetzau, Francis Jacob, Viola Heinzelmann-Schwarz
OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis)...
April 2017: Gynecologic Oncology
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