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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28425245/xenobiotic-drug-metabolizing-enzyme-and-tp53-polymorphisms-and-clinical-outcome-in-advanced-nonsmall-cell-lung-cancer-patients
#1
Volkan Karacaoğlan, Ahmet Oğuz Ada, Serdar Bilgen, Guzide Tuğba Çetinkaya, Emre Soydaş, Celalettin Semih Kunak, Sibel Meryem Alpar, Meral Gülhan, Mümtaz Işcan
BACKGROUND/AIM: The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. MATERIALS AND METHODS: Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP)...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28420874/therapeutic-targeting-using-tumor-specific-peptides-inhibits-long-non-coding-rna-hotair-activity-in-ovarian-and-breast-cancer
#2
Ali R Özeş, Yinu Wang, Xingyue Zong, Fang Fang, Jay Pilrose, Kenneth P Nephew
Long non-coding RNAs (lncRNAs) play key roles in human diseases, including cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA) provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but targeting lncRNAs in vivo has proven to be difficult. In the current study, we describe a peptide nucleic acids (PNA)-based approach to block the ability of HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and resensitize resistant ovarian tumors to platinum...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28415744/emt-like-circulating-tumor-cells-in-ovarian-cancer-patients-are-enriched-by-platinum-based-chemotherapy
#3
Issam Chebouti, Sabine Kasimir-Bauer, Paul Buderath, Pauline Wimberger, Siegfried Hauch, Rainer Kimmig, Jan Dominik Kuhlmann
BACKGROUND: Assuming that tumor cell dissemination requires a shift to a mesenchymal phenotype, we analyzed the incidence of epithelial-to-mesenchymal-transition (EMT)-like circulating tumor cells (CTCs) in ovarian cancer patients and inquired, how their molecular phenotypes respond to platinum-based chemotherapy and influence outcome. RESULTS: Before surgery, overall detection rate for epithelial CTCs was 18%. EMT-like CTCs were more frequently observed (30%) and were mutually exclusive to epithelial CTCs in the majority of patients (82%)...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388557/ercc1-expressing-circulating-tumor-cells-as-a-potential-diagnostic-tool-for-monitoring-response-to-platinum-based-chemotherapy-and-for-predicting-post-therapeutic-outcome-of-ovarian-cancer
#4
Issam Chebouti, Jan Dominik Kuhlmann, Paul Buderath, Stephan Weber, Pauline Wimberger, Yvonne Bokeloh, Siegfried Hauch, Rainer Kimmig, Sabine Kasimir-Bauer
BACKGROUND: We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis of ovarian cancer. The goal of our current research was to determine how the auxiliary assessment of ERCC1-transcripts influences overall CTC-detection rate. We extended this investigation from an initially predictive setting to paired pre- and post-therapeutic blood analysis in order to see, whether ERCC1+CTCs dynamics mirror response to chemotherapy...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/28386196/oridonin-effectively-reverses-the-drug-resistance-of-cisplatin-involving-induction-of-cell-apoptosis-and-inhibition-of-mmp-expression-in-human-acute-myeloid-leukemia-cells
#5
Yuan Zhang, Lihua Wang, Youmei Zi, Lingxiu Zhang, Yan Guo, Yan Huang
Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML) cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells...
March 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28376831/let-7e-sensitizes-epithelial-ovarian-cancer-to-cisplatin-through-repressing-dna-double-strand-break-repair
#6
Man Xiao, Jing Cai, Liqiong Cai, Jinghui Jia, Lisha Xie, Ying Zhu, Bangxing Huang, Dongdong Jin, Zehua Wang
BACKGROUND: Resistance to platinum-based chemotherapy remains a great challenge for ovarian cancer treatment. The human let-7 family contains 13 members located on nine different chromosomes, and most members have been implicated in the modulation of drug sensitivity in cancers. Our previous study showed that deregulation of let-7e in epithelial ovarian cancer (EOC) promoted the development of resistance to cisplatin. In the present study, we aimed to investigate the underlying mechanism and further evaluate the clinical value of let-7e in predicting chemo-response and prognosis in EOC...
April 4, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28369553/ceritinib-in-patients-with-advanced-crizotinib-treated-anaplastic-lymphoma-kinase-rearranged-nsclc-japanese-subset
#7
Toyoaki Hida, Miyako Satouchi, Kazuhiko Nakagawa, Takashi Seto, Shingo Matsumoto, Katsuyuki Kiura, Hiroshi Nokihara, Haruyasu Murakami, Kota Tokushige, Ben Hatano, Makoto Nishio
Introduction: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer is sensitive to tyrosine kinase inhibitors; however, resistance can develop. Data are presented from the phase II trial (ASCEND-2) evaluating efficacy and safety in a subset of Japanese patients with ALK-rearranged non-small cell lung cancer previously treated with platinum-based chemotherapy, who experienced disease progression on crizotinib. Methods: Patients with advanced ALK-rearranged non-small cell lung cancer, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/day...
March 28, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28356150/pregnane-x-receptor-is-associated-with-unfavorable-survival-and-induces-chemotherapeutic-resistance-by-transcriptional-activating-multidrug-resistance-related-protein-3-in-colorectal-cancer
#8
Yan Dong, Zhe Wang, Gan-Feng Xie, Chong Li, Wen-Wei Zuo, Gang Meng, Cheng-Ping Xu, Jian-Jun Li
BACKGROUND: Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but the regulatory mechanism is poorly understood. METHODS: Oxaliplatin (L-OHP) content in tumor cells was analyzed by mass cytometry. The roles of PXR on cancer cell proliferation, apoptosis and tumor growth with L-OHP-treated were investigated by MTS, colony formation, flow cytometry and xenograft tumor assays...
March 29, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28350100/overexpression-of-mir-203-increases-the-sensitivity-of-nsclc-a549-h460-cell-lines-to-cisplatin-by-targeting-dickkopf-1
#9
Ruirui Cheng, Chunya Lu, Guojun Zhang, Guowei Zhang, Guoqiang Zhao
The number of new lung cancer cases diagnosed yearly is high, and the mortality rate has not substantially declined. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and adenocarcinoma accounts for the largest proportion of NSCLC. Currently, platinum-based combined chemotherapy, particularly cisplatin (DDP) is still the main form of treatment for advanced NSCLC. However, cisplatin resistance often occurs in patients who receive chemotherapy. Previous studies offer various explanations for how miRNAs affect cisplatin resistance, but the underlying mechanism remains largely unknown...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28345838/ercc1-expression-in-metastatic-triple-negative-breast-cancer-patients-treated-with-platinum-based-chemotherapy
#10
Mohamed Ali EL Baiomy, Wagdi F El Kashef
Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345024/ovad1-a-novel-potent-and-selective-chimeric-oncolytic-virus-developed-for-ovarian-cancer-by-3d-directed-evolution
#11
Irene Kuhn, Maxine Bauzon, Nicola Green, Len Seymour, Kerry Fisher, Terry Hermiston
Effective therapeutics for ovarian cancer continue to be urgently needed, particularly for chemotherapy-resistant cases. Here we present both a 3D-Matrigel culture-based expansion of our directed evolution method for generation of oncolytic virotherapies and two promising ovarian-cancer targeted oncolytic viruses, OvAd1 and OvAd2. OvAd1 was developed using Matrigel cell cultures, whereas OvAd2 was developed in parallel using traditional monolayer tissue culture methods. Both viruses are potent against a panel of platinum-resistant ovarian cancer cell lines and are attenuated on normal cells in vitro, resulting in therapeutic windows of ∼200-fold...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28341869/the-profile-of-serum-micrornas-predicts-prognosis-for-resected-gastric-cancer-patients-receiving-platinum-based-chemotherapy
#12
Jianning Song, Jie Yin, Zhigang Bai, Jun Zhang, Hua Meng, Jun Cai, Wei Deng, Xuemei Ma, Zhongtao Zhang
BACKGROUND AND AIM: Adjuvant chemotherapy is an important component in the treatment of gastric cancer (GC) patients; however, some patients do not respond to the drugs. We aimed to develop a practical profile based on serum microRNAs (miRNAs) that can be used to predict patients likely to respond to treatment. METHODS: Microarrays were used to screen cisplatin-resistant SGC7901/DDP GC cells and the parental SGC7901 cell lines for miRNAs related to chemotherapy sensitivity...
May 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28325254/egfr-inhibition-in-nsclc-new-findings%C3%A2-and-opened-questions
#13
REVIEW
Francesco Passiglia, Angela Listì, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Viviana Bazan, Antonio Russo
The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients' outcomes...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325092/effectiveness-of-low-dose-oral-etoposide-treatment-in-patients-with-recurrent-and-platinum-resistant-epithelial-ovarian-cancer
#14
Yakup Bozkaya, Mutlu Doğan, Gökmen Umut Erdem, Gökhan Tulunay, Hikmet Uncu, Zafer Arık, Umut Demirci, Ozan Yazıcı, Nurullah Zengin
The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment...
March 21, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#15
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28291545/adding-bevacizumab-to-single-agent-chemotherapy-for-the-treatment-of-platinum-resistant-recurrent-ovarian-cancer-a-cost-effectiveness-analysis-of-the-aurelia-trial
#16
Weiya Z Wysham, Elisabeth M Schaffer, Theresa Coles, Dario R Roque, Stephanie B Wheeler, Kenneth H Kim
OBJECTIVE: AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. METHODS: A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial...
March 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28288821/reversal-of-cisplatin-resistance-in-human-gastric-cancer-cells-by-a-wogonin-conjugated-pt-iv-prodrug-via-attenuating-casein-kinase-2-mediated-nuclear-factor-%C3%AE%C2%BAb-pathways
#17
Feihong Chen, Xiaodong Qin, Gang Xu, Shaohua Gou, Xiufeng Jin
Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity. While, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28285694/sbrt-for-oligoprogressive-oncogene-addicted-nsclc
#18
REVIEW
L Basler, S G C Kroeze, M Guckenberger
Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. Despite initial activity of the TKIs, ultimately all patients present with disease progression after about a year on TKI therapy due to resistance development...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28274569/predictive-value-of-circulating-tumor-cells-ctcs-captured-by-microfluidic-device-in-patients-with-epithelial-ovarian-cancer
#19
Maria Lee, Eun Jae Kim, Youngnam Cho, Sunshin Kim, Hyun Hoon Chung, Noh Hyun Park, Yong-Sang Song
OBJECTIVE: To test an electrically conductive chip, incorporating a nanoroughened microfluidic platform for the capture of circulating tumor cells (CTCs), and assess its clinical merit in instances of epithelial ovarian cancer (EOC). METHODS: A total of 54 patients with EOC recruited between August 2014 and May 2015 were enrolled in this prospective study. CTCs in peripheral blood were detected in advance of primary tumor resection and before initiating adjuvant chemotherapy for recurrent disease...
March 6, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28273485/clinical-factors-of-response-in-patients-with-advanced-ovarian-cancer-participating-in-early-phase-clinical-trials
#20
Angela George, Rebecca Kristeleit, Saeed Rafii, Caroline O Michie, Rebecca Bowen, Vasiliki Michalarea, Tom van Hagen, Mabel Wong, Grigorios Rallis, L Rhoda Molife, Juanita Lopez, Udai Banerji, Susana N Banerjee, Martin E Gore, Johann S de Bono, Stan B Kaye, Timothy A Yap
Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010...
March 5, 2017: European Journal of Cancer
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