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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/28532539/-detection-of-serum-peptides-in-patients-with-lung-squamous-cell-carcinoma-by-maldi-tof-ms-and-analysis-of-their-correlation-with-chemotherapy-efficacy
#1
Guanhua Zhao, Bin Xu, Xiaoyan Li, Chuanhao Tang, Haifeng Qin, Hong Wang, Shaoxing Yang, Weixia Wang, Hongjun Gao, Kun He, Xiaoqing Liu
BACKGROUND: Treatment options for patients with squamous cell carcinoma of the lung (SCC) are limited in chemotherapy. However, not all patients could benefit form standard platinum regimen. Considering the dismal prognosis of patients with advanced SCC, a greater focus on selecting sensitive chemotherapy regimens remains of upmost importance to improve outcomes in this disease. In this study, we used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to detect pre-chemotherapy serum peptides in advanced lung squamous cell carcinoma patients accepting paclitaxel combined with platinum chemotherapy and to analyze the correlation between serum peptides and chemotherapy efficacy...
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28529554/novel-drugs-in-pediatric-gliomas
#2
Dongli Zhang, Xiaoming Liu, Conghai Fan, Jiao Chen
Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therapeutic drugs is clearly evolving and has been observed to be promising future therapeutic avenue against gliomas...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521614/overcoming-platinum-resistance-in-ovarian-cancer-treatment-from-clinical-practice-to-emerging-chemical-therapies
#3
Federica Tomao, Claudia Marchetti, Alessia Romito, Anna Di Pinto, Violante Di Donato, Innocenza Palaia, Marco Monti, Ludovico Muzii, Pierluigi Benedetti Panici
The objective of this review is to summarize results from clinical trials that tested cytotoxic drugs and target strategies for the treatment of platinum resistant (PR) recurrent ovarian cancer (ROC) with particular attention to Phase III and ongoing trials. Areas covered: Since platinum free interval (PFI) represents the most important predictive factor for response to platinum re-treatment in ROC, non-platinum regimens are conventionally considered the most appropriate approaches. Impressive progress has been made in recent decades, resulting in the identification of most effective cytotoxic agents and in the development of new target strategies...
May 18, 2017: Expert Opinion on Pharmacotherapy
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/28498554/differential-resistance-to-platinum-based-drugs-and-5-fluorouracil-in-p22phox-overexpressing-oral-squamous-cell-carcinoma-implications-of-alternative-treatment-strategies
#5
Chih-Chang Hung, Chen-Yu Chien, Pei-Yu Chu, Yu-Jen Wu, Chang-Shen Lin, Chih-Jen Huang, Leong-Perng Chan, Yen-Yun Wang, Shyng-Shiou F Yuan, Tzyh-Chyuan Hour, Jeff Yi-Fu Chen
BACKGROUND: We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown. METHODS: The p22phox expression in tissues and apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft mouse model...
May 12, 2017: Head & Neck
https://www.readbyqxmd.com/read/28496304/evaluation-of-the-antitumor-activity-of-nov202-a-novel-microtubule-targeting-and-vascular-disrupting-agent
#6
Linda Rickardson, Emma Kutvonen, Satu Orasniemi, Marita Högberg, Marko J Kallio, Stefan Rehnmark
PURPOSE: Overall, ~65% of patients diagnosed with advanced ovarian cancer (OC) will relapse after primary surgery and adjuvant first-line platinum- and taxane-based chemotherapy. Significant improvements in the treatment of OC are expected from the development of novel compounds having combined cytotoxic and antiangiogenic properties that make them effective on refractory tumors. METHODS: Permeability of NOV202 was determined with Caco-2 monolayer assay. The compound's pharmacokinetic profile and plasma:brain distribution were assessed in male C57Bl/6 mice...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28487093/expression-of-cdca3-is-a-prognostic-biomarker-and-potential-therapeutic-target-in-non-small-cell-lung-cancer
#7
Mark N Adams, Joshua T Burgess, Yaowu He, Kathy Gately, Cameron Snell, Shu-Dong Zhang, John D Hooper, Derek J Richard, Kenneth J O'Byrne
INTRODUCTION: Non-small cell lung cancer (NSCLC) is the leading cause for cancer-related deaths worldwide. New therapeutic targets are needed as resistance to current treatment, such as platinum-based chemotherapy, are inevitable. The purpose of this study was to determine the functional relevance and therapeutic potential of cell division cycle associated protein-3 (CDCA3) in NSCLC. MATERIALS AND METHODS: The expression of CDCA3 in squamous and non-squamous NSCLC was investigated using bioinformatics, western blot analysis of matched tumour and normal tissue and immunohistochemistry of a tissue microarray...
May 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28486985/the-salvage-therapy-in-lung-adenocarcinoma-initially-harbored-susceptible-egfr-mutation-and-acquired-resistance-occurred-to-the-first-line-gefitinib-and-second-line-cytotoxic-chemotherapy
#8
Chih-Jen Yang, Jen-Yu Hung, Ming-Ju Tsai, Kuan-Li Wu, Ta-Chih Liu, Shah-Hwa Chou, Jui-Ying Lee, Jui-Sheng Hsu, Ming-Shyan Huang, Inn-Wen Chong
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib can provide better efficacy and prolonged progression free survival (PFS) than cytotoxic chemotherapy for metastatic lung non-squamous cell carcinoma harboring susceptible EGFR mutations when used as first-line therapy. Cytotoxic chemotherapy is regarded as being the standard therapy to overcome acquired resistance to an initial EGFR TKI. However, there is currently no consensus on how best to treat patients who develop resistance to both an initial EGFR TKI and chemotherapy...
May 10, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28486623/platinum-induced-mitochondrial-dna-mutations-confer-lower-sensitivity-to-paclitaxel-by-impairing-tubulin-cytoskeletal-organization
#9
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/28482906/foxm1-expression-is-significantly-associated-with-chemotherapy-resistance-and-adverse-prognosis-in-non-serous-epithelial-ovarian-cancer-patients
#10
Renata A Tassi, Paola Todeschini, Eric R Siegel, Stefano Calza, Paolo Cappella, Laura Ardighieri, Moris Cadei, Mattia Bugatti, Chiara Romani, Elisabetta Bandiera, Laura Zanotti, Laura Tassone, Donatella Guarino, Concetta Santonocito, Ettore D Capoluongo, Luca Beltrame, Eugenio Erba, Sergio Marchini, Maurizio D'Incalci, Carla Donzelli, Alessandro D Santin, Sergio Pecorelli, Enrico Sartori, Eliana Bignotti, Franco Odicino, Antonella Ravaggi
BACKGROUND: Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro. METHODS: Gene signatures were generated by microarray for 14 clear-cell and 26 endometrioid EOCs, and 15 normal endometrium snap-frozen biopsies...
May 8, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28481967/bevacizumab-with-or-after-chemotherapy-for-platinum-resistant-recurrent-ovarian-cancer-exploratory-analyses-of-the-aurelia-trial
#11
A Bamias, E Gibbs, C Khoon Lee, L Davies, M Dimopoulos, F Zagouri, A-S Veillard, J Kosse, A Santaballa, M R Mirza, G Tabaro, I Vergote, H Bloemendal, M Lykka, A Floquet, V Gebski, E Pujade-Lauraine
Background: In the open-label randomised phase III AURELIA trial, adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) significantly improved progression-free survival and response rate versus chemotherapy alone, but not overall survival (OS). We explored the effect of bevacizumab use after disease progression (PD) in patients randomised to chemotherapy alone. Patients and methods: In AURELIA, 361 women with PROC were randomised to chemotherapy alone or with bevacizumab...
May 8, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28481779/claudin-4-expression-is-associated-with-survival-in-ovarian-cancer-but-not-with-chemotherapy-response
#12
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/28473707/dna-methylation-and-transcriptome-changes-associated-with-cisplatin-resistance-in-ovarian-cancer
#13
Riikka J Lund, Kaisa Huhtinen, Jussi Salmi, Juha Rantala, Elizabeth V Nguyen, Robert Moulder, David R Goodlett, Riitta Lahesmaa, Olli Carpén
High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resistance, the DNA methylation and transcriptomic changes, associated with the development of drug resistance in high-grade serous ovarian cancer, were examined from patient derived malignant ascites cells. In parallel with large-scale transcriptome changes, cisplatin resistance was associated with loss of hypermethylation at several CpG sites primarily localized in the intergenic regions of the genome...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467466/outcomes-and-prognoses-of-patients-with-ovarian-cancer-using-bevacizumab-6-year-experience-in-a-tertiary-care-hospital-of-northern-taiwan
#14
Wei-Chun Chen, Jiantai Timothy Qiu, Chyong-Huey Lai, Huei-Jean Huang, Cheng-Tao Lin, Min-Yu Chen, Hung-Hsueh Chou, Kuan-Gen Huang, Ting-Chang Chang
PURPOSE: Bevacizumab (BEV) has been used for ovarian cancer (OC) for years in Taiwan, but the associated data related to outcome is scant. This retrospective study reviewed patients with OC treated with BEV and analyzed their results. PATIENTS AND METHODS: All patients with OC treated with BEV from 2009 to 2015 in the Linkou branch of Chang Gung Memorial Hospital in Northern Taiwan were included. According to the means of administration, the patients were classified into 6 groups as follows: A-BEV plus chemotherapy (C/T) for initial platinum-resistant (PR) recurrent OC, B-BEV plus C/T for initial platinum-sensitive (PS) recurrent OC, C-BEV alone for recurrent OC, D-BEV plus 1st adjuvant C/T, E-BEV plus neoadjuvant C/T, and F-intraperitoneal (IP) BEV...
2017: PloS One
https://www.readbyqxmd.com/read/28466786/methoxyphenyl-chalcone-sensitizes-aggressive-epithelial-cancer-to-cisplatin-through-apoptosis-induction-and-cancer-stem-cell-eradication
#15
Yu-Kai Su, Wen-Chien Huang, Wei-Hwa Lee, Oluwaseun Adebayo Bamodu, Muhammad Ary Zucha, Indwiani Astuti, Heri Suwito, Chi-Tai Yeh, Chien-Min Lin
Current standard chemotherapy for late stage ovarian cancer is found unsuccessful due to relapse after completing the regimens. After completing platinum-based chemotherapy, 70% of patients develop relapse and resistance. Recent evidence proves ovarian cancer stem cells as the source of resistance. Therefore, treatment strategy to target both cancer stem cells and normal stem cells is essential. In this study, we developed a novel chalcone derivative as novel drug candidate for ovarian cancer treatment. We found that methoxyphenyl chalcone was effective to eliminate ovarian cancer cells when given either as monotherapy or in combination with cisplatin...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28463955/capilliposide-c-sensitizes-esophageal-squamous-carcinoma-cells-to-oxaliplatin-by-inducing-apoptosis-through-the-pi3k-akt-mtor-pathway
#16
Zhipeng Shen, Lixia Xu, Juan Li, Ni Zhang
BACKGROUND Although platinum-based chemotherapy is the most effective strategy for esophageal cancer, toxicity and drug resistance limit the dose administration and the application of chemotherapy. Capilliposide C (CPS-C) is isolated from the Chinese herb Lysimachia capillipes Hemsl and is approved to be effective against carcinomas. However, the activity of CPS-C against esophageal cancer remains unclear. The present study was conducted to assess the chemosensitizing effects of CPS-C for enhancing the therapeutic efficacy of oxaliplatin in esophageal squamous carcinoma cells and explore the underlying mechanism...
May 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28463570/anaplastic-lymphoma-kinase-inhibitors-in-phase-i-and-phase-ii-clinical-trials-for-non-small-cell-lung-cancer
#17
Niki Karachaliou, Mariacarmela Santarpia, Maria Gonzalez Cao, Cristina Teixido, Aaron E Sosa, Jordi Berenguer, Alejandra Rodriguez Capote, Giuseppe Altavilla, Rafael Rosell
Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development...
May 2, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28455291/hyper-phosphorylation-of-sequestosome-1-distinguishes-resistance-to-cisplatin-in-patient-derived-high-grade-serous-ovarian-cancer-cells
#18
Elizabeth V Nguyen, Kaisa Huhtinen, Young Ah Goo, Katja Kaipio, Noora Andersson, Ville Rantanen, Johanna Hynninen, Riitta Lahesmaa, Olli Carpen, David R Goodlett
Platinum-resistance is a major limitation to effective chemotherapy regimens in high-grade serous ovarian cancer (HGSOC). To better understand the mechanisms involved we characterized the proteome and phosphoproteome in cisplatin sensitive and resistant HGSOC primary cells using a mass spectrometry-based proteomic strategy. PCA analysis identified a distinctive phosphoproteomic signature between cisplatin sensitive and resistant cell lines. The most phosphorylated protein in cisplatin resistant cells was sequestosome-1 (p62/SQSTM1)...
April 28, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28454268/tcrp1-expression-is-associated-with-platinum-sensitivity-in-human-lung-and-ovarian-cancer-cells
#19
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/28454085/baseline-clinical-predictors-of-antitumor-response-to-the-parp-inhibitor-olaparib-in-germline-brca1-2-mutated-patients-with-advanced-ovarian-cancer
#20
Saeed Rafii, Charlie Gourley, Rajiv Kumar, Elena Geuna, Joo Ern Ang, Tzyvia Rye, Lee-May Chen, Ronnie Shapira-Frommer, Michael Friedlander, Ursula Matulonis, Jacques De Greve, Amit M Oza, Susana Banerjee, L Rhoda Molife, Martin E Gore, Stan B Kaye, Timothy A Yap
BACKGROUND: The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib...
April 10, 2017: Oncotarget
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