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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/28214549/atp-dependent-activity-and-mitochondrial-localization-of-drug-efflux-pumps-in-doxorubicin-resistant-breast-cancer-cells
#1
Julie Dartier, Elsa Lemaitre, Igor Chourpa, Caroline Goupille, Stéphane Servais, Stéphan Chevalier, Karine Mahéo, Jean-François Dumas
BACKGROUND: We hypothesized that, among the mechanisms of drug-resistance acquired by doxorubicin (DOX)-resistant breast cancer cells to maintain cell survival, ATP-dependent drug efflux pumps could be expressed in their mitochondrial membranes and this might limit the accumulation of DOX in this subcellular compartment in relation to mitochondrial ATP production. Methods/results Mitochondrial DOX accumulation: the presence and the activity of mitochondrial efflux pumps and their relationship with mitochondrial ATP synthesis were analyzed in DOX-resistant (MCF-7dox(R)) and -sensitive (MCF-7(S)) breast cancer cells...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212576/galectin-1-knockdown-improves-drug-sensitivity-of-breast-cancer-by-reducing-p-glycoprotein-expression-through-inhibiting-the-raf-1-ap-1-signaling-pathway
#2
Fang Wang, Pengwei Lv, Yuanting Gu, Lin Li, Xin Ge, Guangcheng Guo
Galectin-1 (Gal-1), a member of the galectin family of carbohydrate binding proteins, plays a pivotal role in various cellular processes of tumorigenesis. The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines. MTT assay and flow cytometry revealed that Gal-1 knockdown improved sensitivity to paclitaxel (PTX) and adriamycin (ADR) in MCF-7/PTX and MCF-7/ADR cells via inhibition of cell viability and promotion of cell apoptosis, while MDR1 overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210973/renal-drug-transporters-and-drug-interactions
#3
REVIEW
Anton Ivanyuk, Françoise Livio, Jérôme Biollaz, Thierry Buclin
Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side...
February 16, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28207079/the-growing-threat-of-antimicrobial-resistance
#4
Jose M Munita, Samuel Shelburne, David E Greenberg, Cesar A Arias
The emergence and widespread dissemination of multidrug-resistant organisms is considered one of the three most important public health threats for humankind in the 21st century and jeopardizes the practice of modern medicine. Failure to tackle this problem in a comprehensive fashion could result in a dire post-antibiotic era, impairing the future development of treatments against important diseases, such as cancer, and transplant medicine, among others. Here, we provide a global perspective of the problem and describe some of the most important antibiotic-resistant organisms affecting the health of our patients...
February 1, 2017: Texas Medicine
https://www.readbyqxmd.com/read/28206986/in-situ-generated-d-peptidic-nanofibrils-as-multifaceted-apoptotic-inducers-to-target-cancer-cells
#5
Xuewen Du, Jie Zhou, Huainin Wang, Junfeng Shi, Yi Kuang, Wu Zeng, Zhimou Yang, Bing Xu
Nanofibrils of small molecules, as a new class of biofunctional entities, exhibit emergent properties for controlling cell fates, but the relevant mechanism remains to be elucidated and the in vivo effect has yet to be examined. Here, we show that D-peptide nanofibrils, generated by enzyme-instructed self-assembly (EISA), pleiotropically activate extrinsic death signaling for selectively killing cancer cells. Catalyzed by alkaline phosphatases and formed in situ on cancer cells, D-peptide nanofibrils present autocrine proapoptotic ligands to their cognate receptors in a juxtacrine manner, as well as directly cluster the death receptors...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28205160/non-fermentative-gram-negative-rods-bacteremia-in-children-with-cancer-a-14-year-single-center-experience
#6
D Averbuch, C Avaky, M Harit, P Stepensky, I Fried, T Ben-Ami, V Temper, Y Peled, H Troen, R Masarwa, W Abu Ahmad, M Weintraub, S Revel-Vilk, D Engelhard
PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp...
February 15, 2017: Infection
https://www.readbyqxmd.com/read/28199887/killing-colon-cancer-cells-through-pcd-pathways-by-a-novel-hyaluronic-acid-modified-shell-core-nanoparticle-loaded-with-rip3-in-combination-with-chloroquine
#7
Xueyan Hou, Chengli Yang, Lijing Zhang, Tingting Hu, Dan Sun, Hua Cao, Fan Yang, Gang Guo, Changyang Gong, Xiaoning Zhang, Aiping Tong, Rui Li, Yu Zheng
Due to extensive apoptosis defects and multidrug resistance, there is great interest regarding non-apoptotic programmed cell death (PCD) pathways, such as lysosomal-mediated programmed cell death (LM-PCD), necroptosis and autophagy. Because there is an intricate effector network among these PCD pathways, it is expected that they may act synergistically in cancer therapy. In this study, chloroquine (CQ) was found to significantly upregulate receptor-interacting protein kinase 3 (RIP3) expression, and RIP3 were involved in CQ-related autophagy...
January 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28198567/sirolimus-for-vincristine-resistant-kasabach-merritt-phenomenon-report-of-eight-patients
#8
Huaijie Wang, Yitao Duan, Ya Gao, Xinkui Guo
BACKGROUND: The use of sirolimus for patients with multidrug-resistant Kasabach-Merritt phenomenon (KMP) has been reported in recent years. We present the experience of a single center in treating vincristine-resistant KMP using sirolimus alone. METHODS: Children with vincristine-resistant KMP who were treated with oral sirolimus alone were eligible for inclusion in the study. We evaluated responses according to graded response criteria and acute toxicities according to the National Cancer Institute Common Toxicity Criteria...
February 15, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28195491/prodrug-like-pegylated-protein-toxin-trichosanthin-for-reversal-of-chemoresistance
#9
Yingzhi Chen, Meng Zhang, Hongyue Jin, Yisi Tang, Aihua Wu, Qin Xu, Yongzhuo Huang
Multidrug resistance (MDR) is a main obstacle in cancer chemotherapy. The MDR mechanisms involve P-glycoprotein (P-gp) overexpression, abnormality of apoptosis-related protein, and altered expression of drug-targeting proteins. Therapeutic proteins are emerging as candidates for overcoming cancer MDR because of not only their large molecular size that potentially circumvents the P-gp-mediated drug efflux but also their distinctive bioactivity distinguished from small-molecular drugs. Herein we report trichosanthin, a plant protein toxin, possesses synergistic effect with paclitaxel (PTX) in the PTX-resistance A549/T nonsmall cell lung cancer (NSCLC) cells, by reversing PTX-caused caspase 9 phosphorylation and inducing caspase 3-dependent apoptosis...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28191840/se-ru-decorated-porous-metal-organic-framework-nanoparticles-for-the-delivery-of-pooled-sirnas-to-reversing-multidrug-resistance-in-taxol-resistant-breast-cancer-cells
#10
Qingchang Chen, Meng Xu, Wenjing Zheng, Taoyuan Xu, Hong Deng, Jie Liu
We report here a novel and personalized strategy of selenium/ruthenium nanoparticles modified metal organic frameworks MIL-101(Fe) for delivering pooled small interfering RNAs (siRNAs) to enhance therapy efficacy by silencing multi-drug resistance (MDR) genes and interfere with microtubule (MT) dynamics in MCF-7/T (Taxol-resistance) cell. The existence of coordinatively unsaturated metal sites (CUSs) in MIL-101(Fe) can strongly interactions with the electron-rich functional groups of cysteine, which can be regarded as the linkage between selenium/ruthenium nanoparticles and MIL-101(Fe)...
February 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28187461/lysosomal-accumulation-of-anticancer-drugs-triggers-lysosomal-exocytosis
#11
Benny Zhitomirsky, Yehuda G Assaraf
We have recently shown that hydrophobic weak base anticancer drugs are highly sequestered in acidic lysosomes, inducing TFEB-mediated lysosomal biogenesis and markedly increased lysosome numbers per cell. This enhanced lysosomal sequestration of chemotherapeutics, away from their intracellular targets, provoked cancer multidrug resistance. However, little is known regarding the fate of lysosome-sequestered drugs. While we suggested that sequestered drugs might be expelled from cancer cells via lysosomal exocytosis, no actual drug-induced lysosomal exocytosis was demonstrated...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185939/ph-redox-and-photothermal-tri-responsive-dna-polyethylenimine-conjugated-gold-nanorod-as-nanocarrier-for-specific-intracellular-co-release-of-doxorubicin-and-chemosensitizer-pyronaridine-to-combat-multidrug-resistant-cancer
#12
Yun Wang, Zhipeng Zhang, Shaohui Xu, Feihu Wang, Yuanyuan Shen, Shengtang Huang, Shengrong Guo
Pharmacotherapy of multidrug resistant (MDR) cancer remains a challenging task in clinic. Herein, a pH-responsive DNA and disulfide-linked polyethylenimine functionalized gold nanorod was developed for specific co-delivery of chemotherapeutic agent doxorubicin (DOX) and chemosensitizer pyronaridine (PND) to effectively overcome MDR cancer cells. DOX and PND were firstly carried by a multifunctional nanocomplex for reversing MDR cancer. The nanocomplex can responsively and rapidly release its drugs payload under acidic pH environment (pH, ~ 5), intracellular GSH concentration content (5mM) and/or 808nm NIR laser irradiation...
February 6, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28185449/positively-charged-combinatory-drug-delivery-systems-against-multi-drug-resistant-breast-cancer-beyond-the-drug-combination
#13
Xu Yan, Qingsong Yu, Linyi Guo, Wenxuan Guo, Shuli Guan, Hao Tang, Shanshan Lin, Zhihua Gan
The formation and development of cancer is usually accompanied by angiogenesis and is related to multiple pathways. The inhibition of one pathway by monotherapy might result in the occurrence of drug resistance, tumor relapse, or metastasis. Thus, a combinatory therapeutic system that targets several independent pathways simultaneously is preferred for the treatment. To this end, we prepared combinatory drug delivery systems consisting of cytotoxic drug SN38, pro-apoptotic KLAK peptide, and survivin siRNA with high drug loading capacity and reductive responsiveness for the treatment of multi-drug-resistant (MDR) cancer...
February 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28184922/reversal-of-p-gp-mediated-multidrug-resistance-in-colon-cancer-by-cinobufagin
#14
Zeting Yuan, Xiaojing Shi, Yanyan Qiu, Tingting Jia, Xia Yuan, Yu Zou, Cheng Liu, Hui Yu, Yuxia Yuan, Xue He, Ke Xu, Peihao Yin
Cinobufagin (CBF) is isolated from the skin and posterior auricular glands of the Asiatic toad (Bufo gargarizans). This study investigated the reversal effect of CBF on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in colon cancer. The effect of CBF on the cytotoxicity of anticancer drugs in P-gp overexpressing LoVo/ADR, HCT116/L, Cao-2/ADR cells and their parental cells was determined using CCK-8 assay. Apoptosis of anti-cancer drugs and accumulation of doxorubicin (DOX) and Rhodamine 123 (Rho123) in P-gp overexpressing cells were evaluated by flow cytometry...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28181548/thiazole-valine-peptidomimetic-ttt-28-antagonizes-multidrug-resistance-in-vitro-and-in-vivo-by-selectively-inhibiting-the-efflux-activity-of-abcb1
#15
Yi-Jun Wang, Bhargav A Patel, Nagaraju Anreddy, Yun-Kai Zhang, Guan-Nan Zhang, Saeed Alqahtani, Satyakam Singh, Suneet Shukla, Amal Kaddoumi, Suresh V Ambudkar, Tanaji T Talele, Zhe-Sheng Chen
Multidrug resistance (MDR) attenuates the chemotherapy efficacy and increases the probability of cancer recurrence. The accelerated drug efflux mediated by ATP-binding cassette (ABC) transporters is one of the major MDR mechanisms. This study investigated if TTT-28, a newly synthesized thiazole-valine peptidomimetic, could reverse ABCB1-mediated MDR in vitro and in vivo. TTT-28 reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1 overexpressing cells by selectively blocking the efflux function of ABCB1, but not interfering with the expression level and localization of ABCB1...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181464/physicochemical-characterization-of-chitosan-hyaluronan-coated-solid-lipid-nanoparticles-for-the-targeted-delivery-of-paclitaxel-a-proof-of-concept-study-in-breast-cancer-cells
#16
Javier Campos, Manuel Varas-Godoy, Ziyad Samir Haidar
AIM: To investigate the potential of modified solid lipid nanoparticles (SLN) for the delivery of paclitaxel (PAX). MATERIALS & METHODS: SLN loaded with PAX were prepared via modified high-pressure hot homogenization. Formulation parameters were optimized to obtain a high-quality delivery system. SLN cores were coated, layer-by-layer, with a chitosan and hyaluronan (HA) shell. Selectivity toward HA receptors was tested in a breast cancer cell line, MCF-7. RESULTS: Stable and reproducible nano-sized and negatively charged nanoparticles resulted...
February 9, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28181373/characterisation-of-photoaffinity-based-chemical-probes-using-fluorescence-imaging-and-native-state-mass-spectrometry
#17
Kanae Teruya, Gregory Rankin, Panagiotis Chrysanthopoulos, Kathryn Tonissen, Sally-Ann Poulsen
Chemical probes are small molecule reagents used by researchers for labeling and detection of biomolecules. We present the design, synthesis and characterisation of a panel of eleven structurally diverse photoaffinity labeling (PAL) probes as research tools for labeling the model enzyme carbonic anhydrase (CA) in challenging environments, including protein mixtures and cell lysates. We target ubiquitous CA II as well as the two cancer associated CAs (CA IX and CA XII), which are high priority as potential biomarkers of aggressive and/or multidrug resistant cancer...
February 8, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28177682/reversal-of-p-glycoprotein-medicated-multidrug-resistance-and-pharmacokinetics-study-in-rats-by-wyx-5
#18
Yuzhu Wang, Jian Cui, Yuxuan Dai, Yuxiang Wu, Wenlong Huang, Hai Qian, Liang Ge
Multidrug resistance (MDR) is one of the major obstacles confronted in cancer chemotherapy, which mainly due to the overexpression of P-glycoprotein (P-gp). Co-administration of anticancer drugs and P-gp inhibitors is a promising approach to overcome MDR. WYX-5, a novel P-gp inhibitor, shows a notable reversal effect with low cytotoxicity in vitro. In this paper, the reversal mechanism and safety of the MDR modulator WYX-5 were explored in vitro, and evaluated for its pharmacokinetics and effects on Adriamycin (ADM) metabolism <i>in vivo</i>...
December 22, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28177223/facial-layer-by-layer-engineering-of-upconversion-nanoparticles-for-gene-delivery-nir-initiated-fret-tracking-and-overcoming-drug-resistance-in-ovarian-cancer
#19
Min Lin, Yan Gao, Thomas J Diefenbach, Jacson K Shen, Francis J Hornicek, Yong Il Park, Feng Xu, Tian Jian Lu, Mansoor M Amiji, Zhenfeng Duan
Development of multidrug resistance (MDR) contributes to the majority of treatment failures in clinical chemotherapy. We report facial layer-by-layer engineered upconversion nanoparticles (UCNPs) for near infrared (NIR) initiated tracking and delivery of small interfering RNA (siRNA) to enhance chemotherapy efficacy by silencing the MDR1 gene and re-sensitizing resistant ovarian cancer cells to drug. Layer-by-layer engineered UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic interaction...
February 8, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28176940/targeted-multidrug-delivery-system-to-overcome-chemoresistance-in-breast-cancer
#20
Yuan Tang, Fariborz Soroush, Zhaohui Tong, Mohammad F Kiani, Bin Wang
Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy...
2017: International Journal of Nanomedicine
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