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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/28651126/tnf-%C3%AE-exerts-cytotoxic-effects-on-multidrug-resistant-breast-cancer-mcf-7-mx-cells-via-a-non-apoptotic-death-pathway
#1
Morteza Ghandadi, Javad Behravan, Khalil Abnous, Melika Ehtesham Gharaee, Fatemeh Mosaffa
Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed. Although, treatment of MCF-7 cells with TNF-α activated NF-kB and caused RIP1 ubiquitination, TNF-α exposure led to JNK and RIP1 phosphorylation in MCF-7/MX cells...
June 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28650490/hypoxia-induced-tumor-cell-resistance-is-overcome-by-synergistic-gapdh-sirna-and-chemotherapy-co-delivered-by-long-circulating-and-cationic-interior-liposomes
#2
Jibin Guan, Jin Sun, Feilong Sun, Bo Lou, Dong Zhang, Vida Mashayekhi, Negar Sadeghi, Gert Storm, Enrico Mastrobattista, Zhonggui He
Chemotherapeutic drug resistance of tumor cells under hypoxic conditions is caused by the inhibition of apoptosis by autophagy and drug efflux via adenosine triphosphate (ATP)-dependent transporter activation, among other factors. Here, we demonstrate that disrupting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression can reduce the autophagy and ATP levels in tumor cells. To test whether GAPDH knockdown is sufficient to overcome drug resistance, a nanocarrier (asymmetry-membrane liposome) was designed to encapsulate GAPDH-siRNA with a low dose of paclitaxel (PTX)...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28649853/cationic-liposome-co-encapsulation-of-smac-mimetic-and-zvad-using-a-novel-lipid-bilayer-fusion-loaded-with-mlkl-pdna-for-tumor-inhibition-in-vivo
#3
Dan Sun, Linshu Zhao, Junzhong Lin, Yun Zhao, Yu Zheng
The increase in multidrug resistance among colon cancer cells presents a challenge for the development of effective therapies. Small-molecule analogs of second mitochondria-derived activator of caspase (SMAC) mimetic in association with mixed lineage kinase domain-like protein (MLKL)-pDNA and z-VAD-fmk have shown ideal antitumor effects in colon cancer cells in vitro via induction of RIP3-dependent necroptosis. To achieve synergistic antitumor effects in vivo, liposomes loaded with SMAC mimetic, MLKL-pDNA and z-VAD-fmk have been developed using novel lipid fusion methods to co-localize the molecules of interest within the tumor cells...
June 26, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28646911/autophagy-and-multidrug-resistance-in-cancer
#4
REVIEW
Ying-Jie Li, Yu-He Lei, Nan Yao, Chen-Ran Wang, Nan Hu, Wen-Cai Ye, Dong-Mei Zhang, Zhe-Sheng Chen
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal...
June 24, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28645831/synthesis-and-biological-evaluation-of-jl-a7-derivatives-as-potent-abcb1-inhibitors
#5
Miaobo Pan, Jian Cui, Lei Jiao, Hesham Ghaleb, Chen Liao, Jiaqi Zhou, Mutta Kairuki, Haiyan Lin, Wenlong Huang, Hai Qian
Cancer chemotherapy failure is often due to the overexpression of ATP-binding cassette (ABC) transporters (particularly ABCB1), resulting in a variety of structurally and pharmacologically unrelated drugs efflux. The multidrug resistance (MDR) phenomenon could be reversed by ABCB1 inhibitors. Now, JL-A7 as the lead compound based on a triazol-N-ethyl-tetrahydroisoquinoline scaffold, 18 compounds were designed and synthesized. Substitution in para positions yielded high activities toward ABCB1. Moreover, compound 5 could effectively block the drug efflux function of ABCB1 and increase the accumulation of anti-cancer drugs to achieve effective treatment concentration in MDR cells...
June 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28641010/alpha-mangostin-reverses-multidrug-resistance-by-attenuating-the-function-of-the-multidrug-resistance-linked-abcg2-transporter
#6
Chung-Pu Wu, Sung-Han Hsiao, Megumi Murakami, Yu-Jen Lu, Yan-Qing Li, Yang-Hui Huang, Tai-Ho Hung, Suresh V Ambudkar, Yu-Shan Wu
The ATP-binding cassette (ABC) drug transporter ABCG2 can actively efflux a wide variety of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular accumulation of these drugs. Therefore, the overexpression of ABCG2 often contributes to the development of multidrug resistance (MDR) in cancer cells, which is one of the major obstacles to successful cancer chemotherapy. Moreover, ABCG2 is highly expressed in various tissues including the intestine and blood-brain barrier (BBB), limiting the absorption and bioavailability of many therapeutic agents...
June 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28640209/quinolin-6-yloxyacetamides-are-microtubule-destabilizing-agents-that-bind-to-the-colchicine-site-of-tubulin
#7
Ashwani Sharma, Gonzalo Sáez-Calvo, Natacha Olieric, Francisco de Asís Balaguer, Isabel Barasoain, Clemens Lamberth, J Fernando Díaz, Michel O Steinmetz
Quinolin-6-yloxyacetamides (QAs) are a chemical class of tubulin polymerization inhibitors that were initially identified as fungicides. Here, we report that QAs are potent anti-proliferative agents against human cancer cells including ones that are drug-resistant. QAs act by disrupting the microtubule cytoskeleton and by causing severe mitotic defects. We further demonstrate that QAs inhibit tubulin polymerization in vitro. The high resolution crystal structure of the tubulin-QA complex revealed that QAs bind to the colchicine site on tubulin, which is targeted by microtubule-destabilizing agents such as colchicine and nocodazole...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28639112/kuguacin-j-isolated-from-bitter-melon-leaves-modulates-paclitaxel-sensitivity-in-drug-resistant-human-ovarian-cancer-cells
#8
Pornsiri Pitchakarn, Sonthaya Umsumarng, Sariya Mapoung, Pisamai Ting, Piya Temviriyanukul, Wanisa Punfa, Wilart Pompimon, Pornngarm Limtrakul
We previously reported the multidrug resistance-reversing ability of kuguacin J (KJ) in cervical cancer cells via the inhibition of P-glycoprotein (P-gp) function. This study investigated whether KJ could promote cisplatin- and paclitaxel (PTX)-induced cancer cell death in drug-resistance human ovarian cancer cells (SKOV3). Cytotoxicity testing showed that SKOV3 was more resistant to cisplatin and PTX compared to drug-sensitive human ovarian cancer cells (A2780). The cytotoxicity of PTX was significantly increased in SKOV3 cells when co-treated with KJ...
June 21, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28637003/structural-recognition-of-tubulysin-b-derivatives-by-multidrug-resistance-efflux-transporters-in-human-cancer-cells
#9
Michal Stark, Yehuda G Assaraf
Multidrug resistance (MDR) is a major hindrance to curative chemotherapy of various human malignancies. Hence, novel chemotherapeutics must be evaluated for their recognition by MDR efflux transporters. Herein we explored the cytotoxic activity of synthetic tubulysin B (Tub-B, EC1009) derivatives (Tub-B-hydrazide/EC0347 and Tub-B bis-ether/EC1820), and their recognition by the MDR efflux transporters P-glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633130/synthesis-screening-and-pro-apoptotic-activity-of-novel-acyl-spermidine-derivatives-on-human-cancer-cell-lines
#10
Syed Shoeb Razvi, Hani Choudhry, Said Salama Moselhy, Taha Abduallah Kumosani, Mohammed Nihal Hasan, Mazin A Zamzami, Khalid Omer Abualnaja, Abdulrahman Labeed Al-Malki, Mahmoud Alhosin, Tadao Asami
The polyamines putrescine, spermidine, and spermine are polycationic, alkyl polyamines which play a significant role in eukaryotic cell proliferation. The polyamine metabolism and function are dysregulated in tumor cells making them an attractive therapeutic target by employing polyamine analogs. These analogs have a high degree of similarity with the structure of polyamines but not with their function. Multidrug resistance is a major factor in the failure of many chemotherapeutic drugs which necessitates further research and exploration of better novel alternatives...
June 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28632894/flavonoids-as-modulators-of-metabolic-enzymes-and-drug-transporters
#11
REVIEW
Anca Miron, Ana Clara Aprotosoaie, Adriana Trifan, Jianbo Xiao
Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs))...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28629893/a-new-nir-triggered-dox-and-icg-co-delivery-system-for-enhanced-multidrug-resistant-cancer-treatment-through-simultaneous-chemo-photothermal-photodynamic-therapy
#12
Yanna Yu, Zhipeng Zhang, Yun Wang, Hao Zhu, Fangzhou Li, Yuanyuan Shen, Shengrong Guo
It is a great challenge to combat multidrug resistant (MDR) cancer effectively. To address this issue, we developed a new near-infrared (NIR) triggered chemotherapeutic agent doxorubicin (DOX) and photosensitizer indocyanine green (ICG) co-release system by aid of NIR induced photothermal effect of gold nanocages (AuNCs) and temperature sensitive phase-change property of 1-tetradecanol at its melting point of 39°C, which could simultaneously exerted chemo/photothermal/photodynamic treatment on MDR human breast cancer MCF-7/ADR cells...
June 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28628227/microrna-mediated-drug-resistance-in-ovarian-cancer
#13
REVIEW
Aynaz Mihanfar, Amir Fattahi, Hamid Reza Nejabati
The development of intrinsic or acquired resistance to chemotherapeutic agents used in the treatment of various human cancers is a major obstacle for the successful abolishment of cancer. The accumulated efforts in the understanding the exact mechanisms of development of multidrug resistance (MDR) have led to the introduction of several unique and common mechanisms. Recent studies demonstrate the regulatory role of small noncoding RNA or miRNA in the several parts of cancer biology. Practically all aspects of cell physiology under normal and disease conditions are reported to be controlled by miRNAs...
June 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28627615/synthesis-of-folate%C3%A2-chitosan-nanoparticles-loaded-with-ligustrazine-to-target-folate-receptor-positive-cancer-cells
#14
Lichun Cheng, Hui Ma, Mingkun Shao, Qing Fan, Huiyi Lv, Jinyong Peng, Tangna Hao, Daiwei Li, Chenyang Zhao, Xingyue Zong
In addition to its vasodilatory effect, ligustrazine (LZ) improves the sensitivity of multidrug resistant cancer cells to chemotherapeutic agents. To enhance the specificity of LZ delivery to tumor cells/tissues, folate‑chitosan nanoparticles (FA‑CS‑NPs) were synthesized by combination of folate ester with the amine group on chitosan to serve as a delivery vehicle for LZ (FA‑CS‑LZ‑NPs). The structure of folate‑chitosan and characteristics of FA‑CS‑LZ‑NPs, including its size, encapsulation efficiency, loading capacity and release rates were analyzed...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624793/bufalin-reverses-abcb1-mediated-drug-resistance-in-colorectal-cancer
#15
Ze-Ting Yuan, Xiao-Jing Shi, Yu-Xia Yuan, Yan-Yan Qiu, Yu Zou, Cheng Liu, Hui Yu, Xue He, Ke Xu, Pei-Hao Yin
Multidrug resistance (MDR), mainly mediated by ABCB1 transporter, is a major cause for chemotherapy failure. Bufalin (BU), an active component of the traditional Chinese medicine chan'su, has been reported to have antitumor effects on various types of cancer cells. The purpose of this present study was to investigate the reversal effect of BU on ABCB1-mediated multidrug resistance in colorectal cancer. BU at safe concentration (5, 10, 20 nM) could reverse chemosensitivity of ABCB1-overexpression HCT8/ADR, LoVo/ADR and HCT8/ABCB1 nearly back to their parental cells level...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624193/mir-375-and-doxorubicin-co-delivered-by-liposomes-for-combination-therapy-of-hepatocellular-carcinoma
#16
Yin-Ping Fan, Jia-Zhi Liao, Ya-Qi Lu, De-An Tian, Feng Ye, Peng-Xuan Zhao, Guang-Ya Xiang, Wang-Xian Tang, Xing-Xing He
Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623290/tcrp1-transcriptionally-regulated-by-c-myc-confers-cancer-chemoresistance-in-tongue-and-lung-cancer
#17
Xiaoting Jia, Zhijie Zhang, Kai Luo, Guopei Zheng, Minying Lu, Ying Song, Hao Liu, Huisi Qiu, Zhimin He
Previously, we cloned a new gene termed 'tongue cancer resistance-associated protein 1' (TCRP1), which modulates tumorigenesis, enhances cisplatin (cDDP) resistance in cancers, and may be a potential target for reversing drug resistance. However, the mechanisms for regulating TCRP1 expression remain unclear. Herein, we combined bioinformatics analysis with luciferase reporter assay and ChIP assay to determine that c-Myc could directly bind to TCRP1 promoter to upregulate its expression. TCRP1 upregulation in multidrug resistant tongue cancer cells (Tca8113/PYM) and cisplatin-resistant A549 lung cancer cells (A549/DDP) was accompanied by c-Myc upregulation, compared to respective parental cells...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621774/mesoporous-polydopamine-nanoparticles-with-co-delivery-function-for-overcoming-multidrug-resistance-via-synergistic-chemo-photothermal-therapy
#18
Yuxin Xing, Jixi Zhang, Feng Chen, Junjie Liu, Kaiyong Cai
Theranostic agents for combined chemo-photothermal therapy have attracted intensive interest in the treatment of multi-drug resistance (MDR) in cancer therapy. However, the development of simple theranostic agents as dual hosts for both heat and a high payload of chemotherapeutic agents remains a big challenge. Herein, mesoporous polydopamine nanoparticles (MPDA) were successfully developed with properties of a high payload of DOX (up to 2000 μg mg(-1)) and the drug efflux inhibitor TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate), as well as strong near-infrared absorption...
June 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/28621229/the-role-of-nrf2-keap1-axis-in-colorectal-cancer-progression-and-chemoresistance
#19
Mohammad Reza Sadeghi, Farhad Jeddi, Narges Soozangar, Mohammad Hossein Somi, Nasser Samadi
Colorectal cancer is the third common cancer after lung and genital cancers worldwide with more than 1.2 million new cases diagnosed annually. Although extensive progress has been made in the treatment of colorectal cancer, finding novel targets for early diagnosis and effective treatment of these patients is an urgent need. Nuclear factor-erythroid 2-kelch-like ECH-associated protein 1 signaling pathway plays a key role in protecting cells from the damage of intracellular oxidative stress and extracellular oxidizing agents...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28619457/in-vitro-studies-of-phospholipid-modified-pamam-simdr1-complexes-for-the-reversal-of-multidrug-resistance-in-human-breast-cancer-cells
#20
Jing Liu, Jun Li, Nan Liu, Nana Guo, Chen Gao, Yanli Hao, Lei Chen, Xiaoning Zhang
The application of RNAi therapeutics is promising in combating several major human diseases including malignant tumors. However, this approach is limited due to its delivery barriers. In this study, we designed a new carrier system loaded with a functional siRNA targeting MDR1 gene to reverse multi-drug resistance (MDR) in human breast cancer MCF-7/ADR cells. Phospholipid-modified PAMAM-siMDR1 complexes were designed on the external decoration of polyamidoamine (PAMAM) with phospholipid (PL) and the electrostatical interaction between PAMAM and siMDR1 to form hybrid nanocomplexes (PL-dendriplexes)...
June 12, 2017: International Journal of Pharmaceutics
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