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Platinum resistance

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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
#1
Anosheh Afghahi, Kirsten M Timms, Shaveta Vinayak, Kristin C Jensen, Allison W Kurian, Robert W Carlson, Pei-Jen Chang, Elizabeth A Schackmann, Anne-Renee Hartman, James M Ford, Melinda L Telli
BACKGROUND: 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 BRCA1/2-mutant breast cancer patients with poor response to neoadjuvant platinum-based therapy. METHODS: 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/28079002/neurotoxicity-associated-with-platinum-based-anti-cancer-agents-what-are-the-implications-of-copper-transporters
#2
Vanesa Stojanovska, Rachel McQuade, Emma Rybalka, Kulmira Nurgali
Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of interstrand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance...
January 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28074905/mir-488-inhibits-proliferation-and-cisplatin-sensibility-in-non-small-cell-lung-cancer-nsclc-cells-by-activating-the-eif3a-mediated-ner-signaling-pathway
#3
Chao Fang, Yi-Xin Chen, Na-Yiyuan Wu, Ji-Ye Yin, Xiang-Ping Li, Hsuan-Shun Huang, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Our previous studied indicated that eukaryotic translation initiation factor 3a (eIF3a) increases the sensitive of platinum-based chemotherapy in lung cancer. MiRNAs play an important role in lung carcinogenesis and drug response. In this study, we aimed to identify potential endogenous miRNAs that inhibit eIF3a expression and determine their influence of this inhibition on cisplatin resistance. Using bioinformatics analysis prediction and confirmation with dual-luciferase reporter assays, we found that miRNA-488 inhibited eIF3a expression by directly binding to the 3'UTR of eIF3a...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067457/oxide-nanotrap-anchored-platinum-nanoparticles-with-high-activity-and-sintering-resistance-by-area-selective-atomic-layer-deposition
#4
Xiao Liu, Qianqian Zhu, Yun Lang, Kun Cao, Shengqi Chu, Bin Shan, Rong Chen
An area-selective atomic layer deposition (AS-ALD) method is described to construct oxide nanotraps to anchor Pt nanoparticles (NPs) on Al2 O3 supports. The as-synthesized catalysts have exhibited outstanding room-temperature CO oxidation activity, with a significantly lowered apparent activation energy (ca. 22.17 kJ mol(-1) ) that is half that of pure Pt catalyst with the same loading. Furthermore, the structure shows excellent sintering resistance with the high catalytic activity retention up to 600 °C calcination...
January 9, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28062477/imgn853-is-active-in-patients-with-fr%C3%AE-positive-ovarian-cancer
#5
(no author information available yet)
A FRα-targeting antibody-drug conjugate induces responses in patients with platinum-resistant tumors.
January 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28060758/exosomes-as-mediators-of-platinum-resistance-in-ovarian-cancer
#6
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...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052592/innocent-but-deadly-non-toxic-organoiridium-catalysts-promote-selective-cancer-cell-death
#7
Lu Yang, Sohini Bose, Anh H Ngo, Loi Hung Do
We demonstrate that non-toxic organoiridum complexes can selectively chemosensitize cancer cells toward platinum anti-proliferative agents. Treatment of human cancer cells (breast, colon, eye/retina, head/neck, lung, ovary, and blood) with the iridium chemosensitizers led to the lowering of the Pt drug carboplatin's 50% growth inhibition concentration (IC50) by up to about 30-50%. Interestingly, non-cancer cells were mostly resistant to the chemosensitizing effects of the iridium complexes. Cell culture studies indicate that cancer cells that were administered with Ir show significantly higher reactive oxygen species concentrations as well as NAD+/NADH ratios (oxidized vs...
January 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28047715/we-de-201-08-multi-source-rotating-shield-brachytherapy-apparatus-for-prostate-cancer
#8
H Dadkhah, X Wu, Y Kim, R Flynn
PURPOSE: To introduce a novel multi-source rotating shield brachytherapy (RSBT) apparatus for the precise simultaneous angular and linear positioning of all partially-shielded 153Gd radiation sources in interstitial needles for treating prostate cancer. The mechanism is designed to lower the detrimental dose to healthy tissues, the urethra in particular, relative to conventional high-dose-rate brachytherapy (HDR-BT) techniques. METHODS: Following needle implantation, the delivery system is docked to the patient template...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046131/biological-recovery-of-platinum-complexes-from-diluted-aqueous-streams-by-axenic-cultures
#9
Synthia Maes, Ruben Props, Jeffrey P Fitts, Rebecca De Smet, Frank Vanhaecke, Nico Boon, Tom Hennebel
The widespread use of platinum in high-tech and catalytic applications has led to the production of diverse Pt loaded wastewaters. Effective recovery strategies are needed for the treatment of low concentrated waste streams to prevent pollution and to stimulate recovery of this precious resource. The biological recovery of five common environmental Pt-complexes was studied under acidic conditions; the chloro-complexes PtCl42- and PtCl62-, the amine-complex Pt(NH3)4Cl2 and the pharmaceutical complexes cisplatin and carboplatin...
2017: PloS One
https://www.readbyqxmd.com/read/28042086/curcumin-a-potentially-powerful-tool-to-reverse-cisplatin-induced-toxicity
#10
REVIEW
Ramin Rezaee, Amir Abbas Momtazi, Alireza Monemi, Amirhossein Sahebkar
Curcumin is a naturally occurring polyphenol isolated from Curcuma longa that has gained considerable interest over the last decades due to its beneficial effects for human health. Moreover, the usage of cisplatin, a platinum-based chemotherapeutic, is associated with several adverse effects affecting the quality of life of the patients. Also, cisplatin therapy is jeopardized by a great challenge of resistance which reduces the efficacy of this drug. In order to conquer these dark sides of cisplatin therapy, curcumin has been widely used to fight against cisplatin-resistant cancer cells and decrease its unwanted side effects (e...
December 29, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28032148/the-relationship-between-platinum-drug-resistance-and-epithelial-mesenchymal-transition
#11
REVIEW
Anamaria Brozovic
One of the most commonly used chemotherapeutics, platinum drugs are used to treat a wide range of cancer types. Although many cancers initially respond well to those drugs, drug resistance occurs frequently and different molecular mechanisms have been associated with it. However, predictive biomarkers of cellular response in specific tumour types still do not exist. Epithelial-mesenchymal transition (EMT) is a malignant cancer phenotype characterized by aggressive invasion and metastasis, and resistance to apoptosis...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28031535/resistance-to-glucose-starvation-as-metabolic-trait-of-platinum-resistant-human-epithelial-ovarian-cancer-cells
#12
Anna Pastò, Anna Pagotto, Giorgia Pilotto, Angela De Paoli, Gian Luca De Salvo, Alessandra Baldoni, Maria Ornella Nicoletto, Francesca Ricci, Giovanna Damia, Chiara Bellio, Stefano Indraccolo, Alberto Amadori
Deregulated glucose metabolism is observed in cancer but whether this metabolic trait influences response to or is modulated by cytotoxic drugs is unknown. We show here that tumor cells from epithelial ovarian cancer (EOC) patients can be categorized, according to their in vitro viability under glucose starvation, into glucose deprivation-sensitive (glucose-addicted, GA) and glucose deprivation-resistant (glucose non-addicted, GNA). When EOC cells were cultured in the absence of glucose, all samples from platinum (PLT)-sensitive patients felt into the GA group; they disclosed higher expression of glucose metabolism enzymes, higher proliferation rates and in vitro sensitivity to PLT...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031529/the-prognostic-value-of-ki67-in-ovarian-high-grade-serous-carcinoma-an-11-year-cohort-study-of-chinese-patients
#13
Ming Chen, Shuzhong Yao, Qinghua Cao, Meng Xia, Junxiu Liu, Mian He
OBJECTIVE: This study sought to assess the prognostic role of Ki67 in primary ovarian high-grade serous carcinoma (HGSC) and to determine whether Ki67 expression can predict responsiveness to platinum and paclitaxel chemotherapy. RESULTS: A total of 318 women were included in the analysis and the median follow-up time was 48 months (range, 3-150 months). Ki67 proliferation indices ranged from 3% to 95% with a median of 40%. Using 40% as the cut-off value for the Ki67 index, we classified 141 patients as having low Ki67 expression and 177 patients as having high Ki67 expression...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031409/functional-activation-of-mutant-p53-by-platinum-analogs-in-cisplatin-resistant-cells-is-dependent-on-phosphorylation
#14
Xiaolei Xie, Guangan He, Zahid H Siddik
: Dysfunctionality of the p53 tumor suppressor is a major cause of therapeutic drug resistance in cancer. Recently we reported that mutant, but otherwise functional, p53V172F was inactivated in cisplatin-resistant 2780CP/Cl-16 and 2780CP/Cl-24 human ovarian tumor cells by increased recruitment of the inhibitor MDM4. The current study demonstrates that, unlike cisplatin, platinum analogs oxaliplatin and DACH-diacetato-dichloro-Pt(IV) (DAP), strongly stabilize and activate p53V172F in resistant cells, as indicated by prolonged p53 half-life and transactivation of targets p21 (CDKN1A) and MDM2...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28029313/safety-and-activity-of-mirvetuximab-soravtansine-imgn853-a-folate-receptor-alpha-targeting-antibody-drug-conjugate-in-platinum-resistant-ovarian-fallopian-tube-or-primary-peritoneal-cancer-a-phase-i-expansion-study
#15
Kathleen N Moore, Lainie P Martin, David M O'Malley, Ursula A Matulonis, Jason A Konner, Raymond P Perez, Todd M Bauer, Rodrigo Ruiz-Soto, Michael J Birrer
Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6...
December 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28027876/ercc2-xpd-lys751gln-alter-dna-repair-efficiency-of-platinum-induced-dna-damage-through-p53-pathway
#16
Guopei Zhang, Yangyang Guan, Yuejiao Zhao, Tahar van der Straaten, Sha Xiao, Ping Xue, Guolian Zhu, Qiufang Liu, Yuan Cai, Cuihong Jin, Jinghua Yang, Shengwen Wu, Xiaobo Lu
Platinum-based treatment causes Pt-DNA adducts which lead to cell death. The platinum-induced DNA damage is recognized and repaired by the nucleotide excision repair (NER) system of which ERCC2/XPD is a critical enzyme. Single nucleotide polymorphisms in ERCC2/XPD have been found to be associated with platinum resistance. The aim of the present study was to investigate whether ERCC2/XPD Lys751Gln (rs13181) polymorphism is causally related to DNA repair capacity of platinum-induced DNA damage. First, cDNA clones expressing different genotypes of the polymorphism was transfected to an ERCC2/XPD defective CHO cell line (UV5)...
December 24, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28027849/chemotherapy-for-epithelial-ovarian-fallopian-tube-and-primary-peritoneal-cancer
#17
REVIEW
Kate Webber, Michael Friedlander
Chemotherapy plays a key role in the management of women with epithelial ovarian, fallopian tube and primary peritoneal cancer (EOC). Platinum- and taxane-based regimens are the standard of care for adjuvant treatment in early-stage EOC and first-line therapy for advanced stage disease. Efforts to define the optimal scheduling, timing and route of administration are ongoing. The majority of women with EOC will develop recurrent disease, and treatment options for these women are depend on the time that has elapsed from first-line therapy...
November 23, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/28026870/vulvar-and-vaginal-melanoma-a-unique-subclass-of-mucosal-melanoma-based-on-a-comprehensive-molecular-analysis-of-51-cases-compared-with-2253-cases-of-nongynecologic-melanoma
#18
June Y Hou, Caitlin Baptiste, Radhika Bangalore Hombalegowda, Ana I Tergas, Rebecca Feldman, Nathaniel L Jones, Sudeshna Chatterjee-Paer, Ama Bus-Kwolfski, Jason D Wright, William M Burke
BACKGROUND: Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers. METHODS: In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes...
December 27, 2016: Cancer
https://www.readbyqxmd.com/read/28025103/polymer-coated-nanoparticles-carrier-platforms-for-hydrophobic-water-and-air-sensitive-metallo-organic-compounds
#19
Daniel Valdeperez, Tianqiang Wang, Jens P Eußner, Bastian Weinert, Jianyuan Hao, Wolfgang J Parak, Stefanie Dehnen, Beatriz Pelaz
Many of the relevant compounds for anticancer therapy are metal-based compounds (metallodrugs), being platinum-based drugs such as cisplatin, carboplatin (Paraplatin(®)), and oxaliplatin (Eloxatin(®)) the most widely used. Despite this, their application is limited by issues such as cell-acquired platinum resistance and manifold side effects following systemic delivery. Thus, the development of new metal-based compounds is highly needed. The catalytic properties of a variety of metal-based compounds are nowadays very well known, which opens new opportunities to take advantage of them inside living cells or organisms...
December 23, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28024697/reversal-of-platinum-drug-resistance-by-the-histone-deacetylase-inhibitor-belinostat
#20
Kenneth Kin-Wah To, Wing-Sum Tong, Li-Wu Fu
OBJECTIVES: To investigate and elucidate the mechanism for the potentiation of cisplatin anticancer activity by belinostat in platinum (Pt)-resistant lung cancer cells. MATERIALS AND METHODS: Combination of cisplatin and belinostat was investigated in two pairs of parental and cisplatin-resistant non-small cell lung cancer (NSCLC) cell lines. The Pt-resistant cell models exhibited overexpression of the efflux transporter ABCC2 and enhanced DNA repair capacity. Cellular accumulation of cisplatin and extent of DNA platination were measured by inductively coupled plasma optical emission spectrometer...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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