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cisplatin resistance

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https://www.readbyqxmd.com/read/28733701/copper-ii-complexes-of-bidentate-ligands-exhibit-potent-anti-cancer-activity-regardless-of-platinum-sensitivity-status
#1
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/28731184/bufalin-reverses-acquired-drug-resistance-by-inhibiting-stemness-in-colorectal-cancer-cells
#2
Jian Sun, Ke Xu, Yanyan Qiu, Hong Gao, Jianhua Xu, Qingfeng Tang, Peihao Yin
Drug resistance is an obstacle to chemotherapy in tumor patients. Recent studies have shown that the high stemness of cancer cells may be induced by chemotherapeutic drugs, which is correlated with drug resistance. In the present study, we investigated the effects of bufalin on the stemness of colorectal cancer. We found that cisplatin could induce high stemness through the tumorsphere formation assay in vitro and in vivo in the colorectal cancer cell lines HCT116 and LoVo. In addition, cisplatin-treated tumorsphere cells showed drug‑resistant properties...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#3
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28729771/microarray-gene-expression-analysis-of-chemosensitivity-for-docetaxel-cisplatin-and-5-fluorouracil-tpf-combined-chemotherapeutic-regimen-in-hypopharyngeal-squamous-cell-carcinoma
#4
Meng Lian, Haizhou Wang, Jugao Fang, Jie Zhai, Ru Wang, Xixi Shen, Yifan Yang, Zhihong Ma, Honggang Liu
OBJECTIVE: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. METHODS: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR)...
June 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28729428/fluorine-18-labeled-carboplatin-derivative-for-pet-imaging-of-platinum-drug-distribution
#5
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
#6
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/28726784/binding-of-doxorubicin-to-sorcin-impairs-cell-death-and-increases-drug-resistance-in-cancer-cells
#7
Ilaria Genovese, Annarita Fiorillo, Andrea Ilari, Silvia Masciarelli, Francesco Fazi, Gianni Colotti
Sorcin is a calcium binding protein that plays an important role in multidrug resistance (MDR) in tumors, since its expression confers resistance to doxorubicin and to other chemotherapeutic drugs. In this study, we show that Sorcin is able to bind doxorubicin, vincristine, paclitaxel and cisplatin directly and with high affinity. The high affinity binding of doxorubicin to sorcin has been demonstrated with different techniques, that is, surface plasmon resonance, fluorescence titration and X-ray diffraction...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28723865/microrna-106b-5p-regulates-cisplatin-chemosensitivity-by-targeting-polycystic-kidney-disease-2-in-non-small-cell-lung-cancer
#8
Shaorong Yu, Xiaobing Qin, Tingting Chen, Leilei Zhou, Xiaoyue Xu, Jifeng Feng
Systemic therapy with cytotoxic agents remains one of the main treatment methods for non-small-cell lung cancer (NSCLC). Cisplatin is a commonly used chemotherapeutic agent, that, when combined with other drugs, is an effective treatment for NSCLC. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. Unfortunately, the potential mechanism underlying such resistance remains unclear. In this study, we explored the mechanism of microRNA-106b-5p (miR-106b-5p), which is involved in the resistance to cisplatin in the A549 cell line of NSCLC...
July 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28721581/autophagy-regulated-by-lncrna-hotair-contributes-to-the-cisplatin-induced-resistance-in-endometrial-cancer-cells
#9
Meng-Yao Sun, Jian-Yong Zhu, Chun-Yan Zhang, Miao Zhang, Ya-Nan Song, Khalid Rahman, Li-Jun Zhang, Hong Zhang
OBJECTIVES: To identify whether lncRNAs (long non-coding RNA) participate in the regulation of cisplatin-resistant induced autophagy in endometrial cancer cells. RESULTS: Autophagy activity was significantly boosted in cisplatin-resistant Ishikawa cells, a human endometrial cancer cell line, compared with that in parental Ishikawa cells. After analyzing the overall long noncoding RNA (lncRNA) profiling, a meaningful lncRNA, HOTAIR, was identified. It was down-regulated simultaneously in cisplatin-resistant Ishikawa cells and parental Ishikawa cells treated with cisplatin...
July 18, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28720068/inhibitory-effect-of-par-4-combined-with-cisplatin-on-human-wilms-tumor-cells
#10
Jun Wang, Yunjie Li, Fangfang Ma, Huifeng Zhou, Rong Ding, Binbin Lu, Li Zou, Junxia Li, Rugang Lu
Wilms' tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms' tumor. Wilms' tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28719341/label-free-quantitative-proteomics-analysis-on-the-cisplatin-resistance-in-ovarian-cancer-cells
#11
F Wang, Y Zhu, S Fang, S Li, S Liu
Quantitative proteomics has been made great progress in recent years. Label free quantitative proteomics analysis based on the mass spectrometry is widely used. Using this technique, we determined the differentially expressed proteins in the cisplatin-sensitive ovarian cancer cells COC1 and cisplatin-resistant cells COC1/DDP before and after the application of cisplatin. Using the GO analysis, we classified those proteins into different subgroups bases on their cellular component, biological process, and molecular function...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718636/long-chain-alkyl-esters-of-hydroxycinnamic-acids-as-promising-anticancer-agents-selective-induction-of-apoptosis-in-cancer-cells
#12
José C J M D S Menezes, Najmeh Edraki, Shrivallabh Kamat, Mahsima Khoshneviszadeh, Zahra Kayani, Hossein Hadavand Mirzaei, Ramin Miri, Nasrollah Erfani, Maryam Nejati, José A S Cavaleiro, Tiago B Silva, Luciano Saso, Fernanda M Borges, Omidreza Firuzi
Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally-occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16 and C18 alkyl esters of p-coumaric, ferulic, sinapic and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC50 values of 0...
July 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28716524/the-e3-ligase-hectd3-promotes-esophageal-squamous-cell-carcinoma-escc-growth-and-cell-survival-through-targeting-and-inhibiting-caspase-9-activation
#13
Yi Li, Xiaowei Wu, Lin Li, Yongshuo Liu, Chengshan Xu, Dan Su, Zhihua Liu
Apoptosis resistance is an acquired hallmark of cancer cells and many factors can contribute to the tumor cell apoptosis resistance. In this study, we demonstrated that HECTD3, overexpressed in human esophageal squamous cell carcinoma (ESCC), confers cells resistance to cisplatin-induced apoptosis and promotes cancer cell survival. HECTD3 can bind and ubiquitinate caspase-9, which leads to inhibiting caspase-9 oligomerization and association with Apaf-1, and results in suppressing caspase-9 activation and inhibiting apoptosis...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28714963/fhit-loss-confers-cisplatin-resistance-in-lung-cancer-via-the-akt-nf-%C3%AE%C2%BAb-slug-mediated-puma-reduction
#14
D-W Wu, M-C Lee, N-Y Hsu, T-C Wu, J-Y Wu, Y-C Wang, Y-W Cheng, C-Y Chen, H Lee
This corrects the article DOI: 10.1038/onc.2014.184.
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28713273/inhibition-of-6-phosphogluconate-dehydrogenase-reverses-cisplatin-resistance-in-ovarian-and-lung-cancer
#15
Wujian Zheng, Qi Feng, Jiao Liu, Yanke Guo, Lvfen Gao, Ruiman Li, Meng Xu, Guizhen Yan, Zhinan Yin, Shuai Zhang, Shuangping Liu, Changliang Shan
Cisplatin (DDP) is currently one of the most commonly used chemotherapeutic drugs for treating ovarian and lung cancer. However, resistance to cisplatin is common and it often leads to therapy failure. In addition, the precise mechanism of cisplatin resistance is still in its infancy. In this study, we demonstrated that the oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase (6PGD) promotes cisplatin resistance. We showed that cisplatin-resistant cancer cells (C13(∗) and A549DDP), had higher levels of 6PGD compared to their cisplatin-sensitive counterparts (OV2008 and A549)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28713155/hypoxia-induces-universal-but-differential-drug-resistance-and-impairs-anticancer-mechanisms-of-5-fluorouracil-in-hepatoma-cells
#16
Jing-Qiu Li, Xian Wu, Lu Gan, Xiang-Liang Yang, Ze-Hong Miao
Hepatocellular carcinoma (HCC) is one of the most refractory cancers. The mechanisms by which hypoxia further aggravates therapeutic responses of advanced HCC to anticancer drugs remain to be clarified. Here, we report that hypoxia (1% O2) caused 2.55-489.7-fold resistance to 6 anticancer drugs (sorafenib, 5-fluorouracil [5-FU], gemcitabine, cisplatin, adriamycin and 6-thioguanine) in 3 HCC cell lines (BEL-7402, HepG2 and SMMC-7721). Among the 6 drugs, sorafenib, the sole one approved for HCC therapy, inhibited proliferation with little influence from hypoxia and displayed the smallest variation among the 3 HCC cell lines tested...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28711350/synthesis-and-biological-evaluation-of-pyrrole-based-chalcones-as-cyp1-enzyme-inhibitors-for-possible-prevention-of-cancer-and-overcoming-cisplatin-resistance
#17
Ibidapo S Williams, Prashant Joshi, Linda Gatchie, Mohit Sharma, Naresh K Satti, Ram A Vishwakarma, Bhabatosh Chaudhuri, Sandip B Bharate
Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC50 of ∼0.2μM in Sacchrosomes™ and CYP1B1-expressing live human cells. However, compound 3j which inhibited both CYP1A1 and CYP1B1 with an IC50 of ∼0.9µM, using the same systems, also potently antagonized B[a]P-mediated induction of AhR signaling in yeast (IC50, 1...
July 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28709644/horizontal-transfer-of-mir-106a-b-from-cisplatin-resistant-hepatocarcinoma-cells-can-alter-the-sensitivity-of-cervical-cancer-cells-to-cisplatin
#18
Grace R Raji, T V Sruthi, Lincy Edatt, K Haritha, S Sharath Shankar, V B Sameer Kumar
Recent studies indicate that horizontal transfer of genetic material can act as a communication tool between heterogenous populations of tumour cells, thus altering the chemosensitivity of tumour cells. The present study was designed to check whether the horizontal transfer of miRNAs released by cisplatin resistant (Cp-r) Hepatocarcinoma cells can alter the sensitivity of cervical cancer cells. For this exosomes secreted by cisplatin resistant and cisplatin sensitive HepG2 cells (EXres and EXsen) were isolated and characterised...
July 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28706134/heparin-antagonizes-cisplatin-resistance-of-a2780-ovarian-cancer-cells-by-affecting-the-wnt-signaling-pathway
#19
Daniel Bastian Pfankuchen, Fabian Baltes, Tahira Batool, Jin-Ping Li, Martin Schlesinger, Gerd Bendas
Low molecular weight heparin (LMWH), the guideline based drug for prophylaxis and treatment of cancer-associated thrombosis, was recently shown to sensitize cisplatin resistant A2780cis human ovarian cancer cells for cisplatin cytotoxicity upon 24 h pretreatment with 50 μg × mL-1 of the LMWH tinzaparin in vitro, equivalent to a therapeutic dosage. Thereby, LMWH induced sensitization by transcriptional reprogramming of A2780cis cells via not yet elucidated mechanisms that depend on cellular proteoglycans. Here we aim to illuminate the underlying molecular mechanisms of LMWH in sensitizing A2780cis cells for cisplatin...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28705091/molecular-approaches-to-potentiate-cisplatin-responsiveness-in-carcinoma-therapeutics
#20
Aayushi Jain, Devashree Jahagirdar, Pritish Nilendu, Nilesh Kumar Sharma
Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma...
July 14, 2017: Expert Review of Anticancer Therapy
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