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Platinum resistance

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https://www.readbyqxmd.com/read/28738967/-recent-advances-in-association-of-estrogen-and-non-small-cell-lung-cancer
#1
Xiaosheng Ding, Chuanhao Tang, Zhijie Wang, Jun Liang
Lung cancer, of which approximately 85% are non-small cell lung cancer (NSCLC), is one of the most prevalent cancers and the most leading cause of cancer mortality. Despite recent improvements in its treatment, the prognosis remains dismal. Previous studies have clearly proved that estrogen and estrogen receptors (ER) are involve in the pathogenesis and development of lung cancer. More and more evidences showed antiestrogen therapy may reverse the drug-resistance of platinum based chemotherapy in NSCLC patients and can enhance curative effect of epidermal growth factor receptor tyrosine kinase inhibitor...
July 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28737129/association-between-polymorphisms-in-ctr1-ctr2-atp7a-and-atp7b-and-platinum-resistance-in-epithelial-ovarian-cancer
#2
Tailin Li, Jingbo Peng, Feiyue Zeng, Keqiang Zhang, Jinyang Liu, Xi Li, Qianying Ouyang, Guo Wang, Liansheng Wang, Zhaoqian Liu, Yingzi Liu
The copper transporters CTR1, CTR2, ATP7A, and ATP7B regulate intracellular concentration of platinum by mediating its uptake and efflux in cells. We sought to explore the effect of genetic polymorphisms in CTR1, CTR2, ATP7A, and ATP7B on platinum resistance in patients suffering from epithelial ovarian cancer (EOC). A total of 152 Chinese EOC patients were enrolled in this study, all of whom underwent adjuvant chemotherapy using platinum and taxane after maximal debulking surgery. In total, 11 single-nucleotide polymorphisms (SNPs) in CTR1, CTR2, ATP7A, and ATP7B were genotyped in these patients...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28736741/elevated-tumor-mutational-burden-and-prolonged-clinical-response-to-anti-pd-l1-antibody-in-platinum-resistant-recurrent-ovarian-cancer
#3
Christopher B Morse, Julia A Elvin, Laurie M Gay, John B Liao
•We report an ovarian cancer patient with a prolonged response to immunotherapy.•Comprehensive genomic profiling may detect patients who benefit from immunotherapy.•Mutational burden thresholds for ovarian cancer may be lower than other cancers.
August 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28733701/copper-ii-complexes-of-bidentate-ligands-exhibit-potent-anti-cancer-activity-regardless-of-platinum-sensitivity-status
#4
Mohamed Wehbe, Cody Lo, Ada W Y Leung, Wieslawa H Dragowska, Gemma M Ryan, Marcel B Bally
Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC50 ~ 1 μM platinum) and insensitive (IC50 > 5 μM platinum) cell lines...
July 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28732901/multiple-polysaccharide-drug-complex-loaded-liposomes-a-unique-strategy-in-drug-loading-and-cancer-targeting
#5
Hima Bindu Ruttala, Thiruganesh Ramasamy, Biki Gupta, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs...
October 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28732061/melatonin-pre-treatment-mitigates-shsy-5y-cells-against-oxaliplatin-induced-mitochondrial-stress-and-apoptotic-cell-death
#6
Mohammad Waseem, Upasana Sahu, Mohd Salman, Arnab Choudhury, Sudeshna Kar, Heena Tabassum, Suhel Parvez
Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage...
2017: PloS One
https://www.readbyqxmd.com/read/28730758/platinum-derivatives-a-multidisciplinary-approach
#7
Sinziana Gheorghe-Cetean, Calin Cainap, Luminita Oprean, Adriana Hangan, Piroska Virag, Eva Fischer-Fodor, Alexandra Gherman, Simona Cainap, Anne-Marie Constantin, Istvan Laszlo, Catalin Vlad, Radu Oprean
Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28729428/fluorine-18-labeled-carboplatin-derivative-for-pet-imaging-of-platinum-drug-distribution
#8
Narottam Lamichhane, Gajanan K Dewkar, Sundaresan Gobalakrishnan, Li Wang, Purnima Jose, Muhammad Otabashi, Jean-Luc Morelle, Nicholas Farrell, Jamal Zweit
Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, and emphasizes the need to directly measure intra-tumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance, by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we are contributing to this endeavor by reporting on the development of a fluorine-18 labeled carboplatin derivative ((18)F-FCP) that can be used to potentially image drug uptake and retention, including intra-tumoral distribution, by positron emission tomography (PET)...
July 20, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28728896/platinum-iv-complexes-conjugated-with-phenstatin-analogue-as-inhibitors-of-microtubule-polymerization-and-reverser-of-multidrug-resistance
#9
Xiaochao Huang, Rizhen Huang, Shaohua Gou, Zhimei Wang, Zhixin Liao, Hengshan Wang
Pt(IV) complexes comprising a phenstatin analogue, as dual-targeting Pt(IV) prodrug, were designed and synthesized. They were found not only to carry the DNA binding platinum warhead into the tumor cells, but also to have a small molecular unit to inhibit tubulin polymerization. In vitro evaluation results revealed that Pt(IV) complexes showed better and more potent activity against the test human cancer cells including cisplatin resistant cell lines than their corresponding Pt(II) counterparts. In addition, the Pt(IV) derivative of cisplatin, complex 10, exhibited highly selective inhibition in human cancer cells and displayed no obvious toxicity to two human normal cell lines, respectively...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#10
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28714373/targeting-mir-21-decreases-expression-of-multi-drug-resistant-genes-and-promotes-chemosensitivity-of-renal-carcinoma
#11
Kelly Gaudelot, Jean-Baptiste Gibier, Nicolas Pottier, Brigitte Hémon, Isabelle Van Seuningen, François Glowacki, Xavier Leroy, Christelle Cauffiez, Viviane Gnemmi, Sébastien Aubert, Michaël Perrais
Renal cell carcinoma, the most common neoplasm of adult kidney, accounts for about 3% of adult malignancies and is usually highly resistant to conventional therapy. MicroRNAs are a class of small non-coding RNAs, which have been previously shown to promote malignant initiation and progression. In this study, we focused our attention on miR-21, a well described oncomiR commonly upregulated in cancer. Using a cohort of 99 primary renal cell carcinoma samples, we showed that miR-21 expression in cancer tissues was higher than in adjacent non-tumor tissues whereas no significant difference was observed with stages, grades, and metastatic outcome...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28712484/relevance-of-dna-damage-repair-in-the-management-of-prostate-cancer
#12
Patricia Banks, Wen Xu, Declan Murphy, Paul James, Shahneen Sandhu
Recent insights into the genomic aberrations that underlie and drive prostate cancer have redoubled efforts to molecularly stratify treatments based on predictive markers. Approximately 23% of patients with metastatic castration-resistant prostate cancer exhibit somatic or germline aberrations in genes implicated in DNA repair, such as BRCA2, BRCA1, ATM, CHEK2, and PALB2, as well as mismatch repair genes. At least 10% of men with advanced disease have germline mutations in DNA-repair genes (DRG). The enrichment of DRG defects in metastatic disease compared with localized, primary tumors suggests a possible role in carcinogenesis, disease progression, and potentially accounts for a more aggressive phenotype...
June 27, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28712280/radiation-for-persistent-or-recurrent-epithelial-ovarian-cancer-a-need-for-reassessment
#13
Noorie Choi, Ji Hyun Chang, Suzy Kim, Hak Jae Kim
PURPOSE: The role of radiotherapy (RT) was largely deserted after the introduction of platinum-based chemotherapy, but still survival rates are disappointingly low. This study focuses on assessing the clinical efficacy of RT in relation to chemotherapy resistance. MATERIALS AND METHODS: From October 2002 to January 2015, 44 patients were diagnosed with epithelial ovarian cancer (EOC) and treated with palliative RT for persistent or recurrent EOC. All patients received initial treatment with optimal debulking surgery and adjuvant platinum-based chemotherapy...
June 2017: Radiation Oncology Journal
https://www.readbyqxmd.com/read/28710915/potent-therapeutic-activity-against-peritoneal-dissemination-and-malignant-ascites-by-the-novel-anti-folate-receptor-alpha-antibody-khk2805
#14
Munetoshi Ando, Keiko Nagata, Kaito Nihira, Yui Suzuki, Yutaka Kanda, Maiko Adachi, Tsuguo Kubota, Naoya Kameyama, Mariko Nakano, Hiroshi Ando, Kazuya Yamano, Toshihiko Ishii, Ryuichiro Nakai, Kazuyasu Nakamura
Many ovarian cancer patients often show peritoneal metastasis with malignant ascites. However, unmet medical needs remain regarding controlling these symptoms after tumors become resistant to chemotherapies. We developed KHK2805, a novel anti-folate receptor α (FOLR1) humanized antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The primary aim of the present study was to evaluate whether the anti-tumor activity of KHK2805 was sufficient for therapeutic application against peritoneal dissemination and malignant ascites of platinum-resistant ovarian cancer in preclinical models...
July 11, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28710746/osimertinib-a-review-in-t790m-positive-advanced-non-small-cell-lung-cancer
#15
REVIEW
Yvette N Lamb, Lesley J Scott
Osimertinib (Tagrisso™) is an oral, CNS-active, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets EGFR TKI-sensitizing mutations and, crucially, the T790M mutation that often underlies acquired resistance to EGFR TKI therapy. Osimertinib has been approved in numerous countries for use in patients with T790M-positive advanced NSCLC. In the pivotal, international AURA3 trial in patients with T790M-positive advanced NSCLC who had disease progression after EGFR TKI therapy, osimertinib treatment significantly prolonged progression-free survival (PFS; primary endpoint) compared with platinum-pemetrexed therapy at the time of the primary analysis...
August 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28705409/clinical-benefit-and-risk-of-death-with-endocrine-therapy-in-ovarian-cancer-a-comprehensive-review-and-meta-analysis
#16
Laura Paleari, Sara Gandini, Nicoletta Provinciali, Matteo Puntoni, Nicoletta Colombo, Andrea DeCensi
BACKGROUND: Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown. METHODS: Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose...
July 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28696006/genetic-variation-in-the-dna-repair-pathway-as-a-potential-determinant-of-response-to-platinum-based-chemotherapy-in-breast-cancer
#17
REVIEW
Farimah Beheshti, Seyed Mahdi Hassanian, Majid Khazaei, Mahmoud Hosseini, Soodabeh ShahidSales, Malihe Hasanzadeh, Mina Maftouh, Gordon A Ferns, Amir Avan
Platinum-based chemotherapy is often used as a first-line treatment for patient with breast cancer. Platinum agents bind to DNA, forming adducts that contain intra and inter-strand crosslinks. It is possible that genetic variations of the DNA repair pathways may affect the activity, or efficacy of platinum, and hence resistance to platinum chemotherapy may be related to these genetic variants. We have summarized the known variants in the DNA repair pathway that have been reported to predict the response to platinum-based therapy in breast cancer...
July 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28692634/targeting-foxm1-improves-cytotoxicity-of-paclitaxel-and-cisplatinum-in-platinum-resistant-ovarian-cancer
#18
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...
July 7, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#19
Daolu Yuwen, Shanwei Mi, Yuzhu Ma, Wenjie Guo, Qiang Xu, Yan Shen, Yongqian Shu
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28685693/multi-targeted-anticancer-agents
#20
Wei Zheng, Yao Zhao, Qun Luo, Yang Zhang, Kui Wu, Fuyi Wang
There is great demand for the development of novel anticancer drugs, due to the increasing morbidity and high mortality of cancer. To date, chemotherapy still plays a central role in the clinical treatment of cancer, but this role is being reduced by targeted therapies. Since cancer is a complicated and multiple genes involved disease, drugs that act at multiple targets can enhance efficacy and lower drug resistance, and are thought to be the future of novel anticancer drug development. In this paper, we discuss the recent development of "single molecule, multi-target" anticancer agents that combine two or more pharmacophores in a single molecule, including organic multi-targeted anticancer agents and metal based complexes such as platinum, ruthenium, iridium and rhodium complexes...
July 7, 2017: Current Topics in Medicinal Chemistry
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