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Platinum resistance

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https://www.readbyqxmd.com/read/28521614/overcoming-platinum-resistance-in-ovarian-cancer-treatment-from-clinical-practice-to-emerging-chemical-therapies
#1
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/28514339/-increased-oral-fluid-remineraling-function-by-endogenous-and-exogenous-saturation-methods-of-its-mineral-complexes
#2
O G Avraamova, Yu A Ippolitov, Ya A Plotnikova, P V Seredin, D V Goloshapov, E O Aloshina
RELEVANCE: One of the most common problems in modern caries prevention is the development of techniques to increase tooth resistance to the effects of cariogenic factors. Therefore, research is needed to study the chemical composition of tissues like teeth and body fluids surrounding the tooth to prevent demineralization process. The purpose of determining the effectiveness of work- and correlation relationship between endo saturation exogenous methods oral liquid mineral complexes. MATERIAL AND METHODS: In 95 patients analyzed the chemical composition and structure of the oral fluid by IR spectroscopy...
2017: Stomatologii︠a︡
https://www.readbyqxmd.com/read/28513634/mitochondria-targeted-platinum-ii-complexes-dual-inhibitory-activities-on-tumor-cell-proliferation-and-migration-invasion-via-intracellular-trafficking-of-%C3%AE-catenin
#3
Jingling Li, Xiaoli He, Yeling Zou, Dandan Chen, Liecheng Yang, Jiaming Rao, Huabing Chen, Michael C W Chan, Lin Li, Zhengqing Guo, Leshuai W Zhang, Chunying Chen
Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis...
May 17, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28512410/rrx-001-priming-of-pd-1-inhibition-in-the-treatment-of-small-cell-carcinoma-of-the-vagina-a-rare-gynecological-tumor
#4
Christina Brzezniak, Bryan Oronsky, Jane Trepel, Thomas A Summers, Pedro Cabrales, Min-Jung Lee, Regina Day, Saheli Jha, Scott Caroen, Karen Zeman, Lindsey Ferry, Cindy Harmer, Neil Oronsky, Michelle Lybeck, Harry E Lybeck, James F Brown, Tony R Reid, Corey A Carter
Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28511063/competitive-reactions-among-glutathione-cisplatin-and-copper-phenanthroline-complexes
#5
Enzo Cadoni, Elisa Valletta, Graziano Caddeo, Francesco Isaia, Maria Grazia Cabiddu, Sarah Vascellari, Tiziana Pivetta
A large number of cancers are treated with cisplatin (CDDP). However, its use is limited by drug resistance, which is often related to intracellular levels of thiol-containing molecules such as glutathione (GSH). The role of GSH in cisplatin-resistant cancer cells is still unclear. GSH may form adducts with CDDP which results in the deactivation of the drug, and, actually, a high intracellular level of GSH was observed in some cisplatin-resistant cancers. To overcome drug resistance, CDDP is often administered in combination with one or more drugs to exploit a possible synergistic effect...
May 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28510571/second-line-pazopanib-in-patients-with-relapsed-and-refractory-small-cell-lung-cancer-a-multicentre-phase-ii-study-of-the-hellenic-oncology-research-group
#6
F Koinis, S Agelaki, V Karavassilis, N Kentepozidis, E Samantas, S Peroukidis, P Katsaounis, E Hartabilas, I I Varthalitis, I Messaritakis, G Fountzilas, V Georgoulias, A Kotsakis
BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28498842/prognostic-significance-and-predictors-of-the-system-inflammation-score-in-ovarian-clear-cell-carcinoma
#7
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
#8
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/28498503/p62-sqstm1-as-an-oncotarget-mediates-cisplatin-resistance-through-activating-rip1-nf-%C3%AE%C2%BAb-pathway-in-human-ovarian-cancer-cells
#9
Xiao-Yu Yan, Yu Zhang, Juan-Juan Zhang, Li-Chao Zhang, Ya-Nan Liu, Yao Wu, Ya-Nan Xue, Sheng-Yao Lu, Jing Su, Lian-Kun Sun
Platinum-based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to DNA. p62 (also known as SQSTM1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug-resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498256/paragon-anzgog-0903-phase-2-study-of-anastrozole-in-women-with-estrogen-or-progesterone-receptor-positive-platinum-resistant-or-refractory-recurrent-ovarian-cancer
#10
Anthony Bonaventura, Rachel L OʼConnell, Cristina Mapagu, Philip J Beale, Orla M McNally, Linda R Mileshkin, Peter T Grant, Alison M Hadley, Jeffery C H Goh, Katrin M Sjoquist, Julie Martyn, Anna DeFazio, James Scurry, Michael L Friedlander
BACKGROUND: There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptor-positive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer. METHODS: Postmenopausal women who had estrogen and/or progesterone receptor-positive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28498253/targeting-foxm1-improves-cytotoxicity-of-paclitaxel-and-cisplatinum-in-platinum-resistant-ovarian-cancer
#11
Gina L Westhoff, Yi Chen, Nelson N H Teng
OBJECTIVE: Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. METHODS: Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28496304/evaluation-of-the-antitumor-activity-of-nov202-a-novel-microtubule-targeting-and-vascular-disrupting-agent
#12
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/28492290/atezolizumab-a-novel-pd-l1-inhibitor-in-cancer-therapy-with-a-focus-in-bladder-and-non-small-cell-lung-cancers
#13
A Krishnamurthy, A Jimeno
In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell-mediated immune response against cancer cells. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby enhancing T-cell activity against tumor cells...
April 2017: Drugs of Today
https://www.readbyqxmd.com/read/28490629/pharmacological-targeting-of-rad6-enzyme-mediated-translesion-synthesis-overcomes-resistance-to-platinum-based-drugs
#14
Matthew A Sanders, Brittany Haynes, Pratima Nangia-Makker, Lisa A Polin, Malathy P Shekhar
Platinum drug-induced crosslink repair requires the concerted activities of translesion synthesis (TLS), Fanconi anemia (FA) and homologous recombination repair pathways. The E2 ubiquitin-conjugating enzyme Rad6 is essential for TLS. Here, we show that Rad6 plays a universal role in platinum-based drug tolerance. Using a novel Rad6-selective small molecule inhibitor (SMI#9) targeting the Rad6 catalytic site, we demonstrate that SMI#9 potentiates the sensitivities of cancer cells with innate or acquired cisplatin or oxaliplatin resistance...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28490518/chk1-inhibition-in-small-cell-lung-cancer-produces-single-agent-activity-in-biomarker-defined-disease-subsets-and-combination-activity-with-cisplatin-or-olaparib
#15
Triparna Sen, Pan Tong, C Allison Stewart, Sandra Cristea, Aly Valliani, David S Shames, Abena Redwood, Youhong Fan, Lerong Li, Bonnie S Glisson, John Minna, Julien Sage, Don L Gibbons, Helen Piwnica-Worms, John Heymach, Jing Wang, Lauren Averett Byers
Effective targeted therapies for small cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacological blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models...
May 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28487823/3d-nanoprinting-via-laser-assisted-electron-beam-induced-deposition-growth-kinetics-enhanced-purity-and-electrical-resistivity
#16
Brett B Lewis, Robert Winkler, Xiahan Sang, Pushpa R Pudasaini, Michael G Stanford, Harald Plank, Raymond R Unocic, Jason D Fowlkes, Philip D Rack
We investigate the growth, purity, grain structure/morphology, and electrical resistivity of 3D platinum nanowires synthesized via electron beam induced deposition with and without an in situ pulsed laser assist process which photothermally couples to the growing Pt-C deposits. Notably, we demonstrate: 1) higher platinum concentration and a coalescence of the otherwise Pt-C nanogranular material, 2) a slight enhancement in the deposit resolution and 3) a 100-fold improvement in the conductivity of suspended nanowires grown with the in situ photothermal assist process, while retaining a high degree of shape fidelity...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/28487093/expression-of-cdca3-is-a-prognostic-biomarker-and-potential-therapeutic-target-in-non-small-cell-lung-cancer
#17
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
#18
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
#19
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/28484093/enhanced-antitumor-efficacy-of-cisplatin-for-treating-ovarian-cancer-in-vitro-and-in-vivo-via-transferrin-binding
#20
Huifang Peng, Hongwei Jin, Huiqin Zhuo, Heqing Huang
Cisplatin is a widely used anticancer drug, while non-targeted delivery, development of drug resistance, and serious side effects significantly limit its clinical use. In order to improve the tumor-targeting properties of cisplatin, transferrin (Tf) was employed as a carrier to transfer cisplatin into cancer cells via transferrin receptor 1 (TfR1) mediated endocytosis. The binding ability of cisplatin and Tf could be improved by pretreating Tf with 10% ethanol, and the binding number of cisplatin for each Tf molecule could reach to 40 without structural or functional impairment of Tf...
April 21, 2017: Oncotarget
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