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Carboplatin resistant ovarian cancer

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https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/28240014/general-characteristics-and-cytotoxic-effects-of-nano-poly-butyl-cyanoacrylate-containing-carboplatin-on-ovarian-cancer-cells
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28131812/the-translational-blocking-of-%C3%AE-5-and-%C3%AE-6-integrin-subunits-affects-migration-and-invasion-and-increases-sensitivity-to-carboplatin-of-skov-3-ovarian-cancer-cell-line
#12
Julio César Villegas-Pineda, Alfredo Toledo-Leyva, Juan Carlos Osorio-Trujillo, Verónica Ivonne Hernández-Ramírez, Patricia Talamás-Rohana
Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays...
February 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28104527/b7-h3-targeted-212-pb-radioimmunotherapy-of-ovarian-cancer-in-preclinical-models
#13
Benjamin B Kasten, Rebecca C Arend, Ashwini A Katre, Harrison Kim, Jinda Fan, Soldano Ferrone, Kurt R Zinn, Donald J Buchsbaum
INTRODUCTION: Novel therapies that effectively kill both differentiated cancer cells and cancer initiating cells (CICs), which are implicated in causing chemotherapy-resistance and disease recurrence, are needed to reduce the morbidity and mortality of ovarian cancer. These studies used monoclonal antibody (mAb) 376.96, which recognizes a B7-H3 epitope expressed on ovarian cancer cells and CICs, as a carrier molecule for targeted α-particle radioimmunotherapy (RIT) in preclinical models of human ovarian cancer...
April 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28087643/tumor-brca1-reversion-mutation-arising-during-neoadjuvant-platinum-based-chemotherapy-in-triple-negative-breast-cancer-is-associated-with-therapy-resistance
#14
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
Purpose: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed patients with BRCA1/2-mutant breast cancer with poor response to neoadjuvant platinum-based therapy.Experimental Design: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin, and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n = 80)...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28060758/exosomes-as-mediators-of-platinum-resistance-in-ovarian-cancer
#15
Jennifer Crow, Safinur Atay, Samagya Banskota, Brittany Artale, Sarah Schmitt, Andrew K Godwin
Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031411/a-systematic-analysis-of-negative-growth-control-implicates-the-dream-complex-in-cancer-cell-dormancy
#16
James MacDonald, Yudith Ramos-Valdes, Pirunthan Perampalam, Larissa Litovchick, Gabriel E DiMattia, Frederick A Dick
Epithelial ovarian cancer (EOC) generates multicellular aggregates called spheroids that detach from the primary tumor and disseminate through ascites. Spheroids possess a number of characteristics of tumor dormancy including withdrawal from the cell cycle and resistance to chemotherapeutics. This report systematically analyzes the effects of RNAi depletion of 21 genes that are known to contribute to negative regulation of the cell cycle in 10 ovarian cancer cell lines. Interestingly, spheroid cell viability was compromised by loss of some cyclin-dependent kinase inhibitors such as p57(Kip2), as well as Dyrk1A, Lin52, and E2F5 in most cell lines tested...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28031236/proteomics-analysis-of-ovarian-cancer-cell-lines-and-tissues-reveals-drug-resistance-associated-proteins
#17
Isa N Cruz, Helen M Coley, Holger B Kramer, Thumuluru Kavitah Madhuri, Nur A M Safuwan, Ana Rita Angelino, Min Yang
BACKGROUND: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. MATERIALS AND METHODS: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting...
January 2, 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28013349/pharmacology-and-toxicology-of-the-novel-investigational-agent-cantrixil-trx-e-002-1
#18
REVIEW
Muhammad Wasif Saif, Andrew Heaton, Kimberley Lilischkis, James Garner, David M Brown
PURPOSE: Recurrent, chemo-resistant ovarian cancer is thought to be due to a subgroup of slow-growing, drug-resistant cancer cells with stem-like properties and a high capacity for tumour repair. Cantrixil targets this sub-population of cells and is being developed as an intraperitoneal therapy to be used as first-line therapy in combination with carboplatin for epithelial ovarian cancer. The studies presented here justify further development. METHODS: A GLP dog CV study using a 4 × 4 Latin Square Crossover study was conducted using telemetric ECG recordings from dogs post IP administration to assess for cardiac abnormalities...
February 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27998224/phase-ii-study-of-wee1-inhibitor-azd1775-plus-carboplatin-in-patients-with-tp53-mutated-ovarian-cancer-refractory-or-resistant-to-first-line-therapy-within-3-months
#19
Suzanne Leijen, Robin M J M van Geel, Gabe S Sonke, Daphne de Jong, Efraim H Rosenberg, Serena Marchetti, Dick Pluim, Erik van Werkhoven, Shelonitda Rose, Mark A Lee, Tomoko Freshwater, Jos H Beijnen, Jan H M Schellens
Purpose AZD1775 is a first-in-class, potent, and selective inhibitor of WEE1 with proof of chemopotentiation in p53-deficient tumors in preclinical models. In a phase I study, the maximum tolerated dose of AZD1775 in combination with carboplatin demonstrated target engagement. We conducted a proof-of-principle phase II study in patients with p53 tumor suppressor gene ( TP53)-mutated ovarian cancer refractory or resistant (< 3 months) to first-line platinum-based therapy to determine overall response rate, progression-free and overall survival, pharmacokinetics, and modulation of phosphorylated cyclin-dependent kinase (CDK1) in skin biopsies...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27980217/the-association-between-copper-transporters-and-the-prognosis-of-cancer-patients-undergoing-chemotherapy-a-meta-analysis-of-literatures-and-datasets
#20
REVIEW
Si Sun, Jing Cai, Qiang Yang, Simei Zhao, Zehua Wang
Copper transporter 1 (CTR1), copper transporter 2 (CTR2), copper-transporting p-type adenosine triphosphatase 1 and 2 (ATP7A and ATP7B) are key mediators of cellular cisplatin, carboplatin and oxaliplatin accumulation. In this meta-analysis, we aimed to evaluate the relation of CTR1, CTR2, ATP7A and ATP7B to overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and treatment response (TR) of cancer patients who received chemotherapy based on published literatures, the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets...
February 28, 2017: Oncotarget
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