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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/29036899/targeting-strategies-for-the-combination-treatment-of-cancer-using-drug-delivery-systems
#1
REVIEW
Janel Kydd, Rahul Jadia, Praveena Velpurisiva, Aniket Gad, Shailee Paliwal, Prakash Rai
Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment-due to the hostile tumor microenvironment-that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration...
October 14, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29035832/new-insights-into-vinca-alkaloids-resistance-mechanism-and-circumvention-in-lung-cancer
#2
REVIEW
Ying Zhang, Shao-Hui Yang, Xiu-Li Guo
Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29030194/doughnut-shaped-bovine-serum-albumin-nanoparticles-loaded-with-doxorubicin-for-overcoming-multidrug-resistance-in-cancer-cells
#3
Zahra Kayani, Omidreza Firuzi, Abdol-Khalegh Bordbar
Traditional spherical albumin nanoparticles remain the dominant shape of nano-carriers described in the literature at present, due to their simple desolvation method of synthesis. However, non-spherical shapes also show great promise as cancer drug delivery vectors. In this study, we report a novel synthetic strategy based on dimethyl sulfoxide (DMSO) addition during desolvation step, to produce doughnut-shaped bovine serum albumin nanoparticles (DBSA-NPs), while maintaining narrow size distributions and homogeneity...
October 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29024700/high-ybx1-expression-indicates-poor-prognosis-and-promotes-cell-migration-and-invasion-in-nasopharyngeal-carcinoma
#4
Lei-Lei Zhou, Jie Ni, Wan-Ting Feng, Rong Yao, Shun Yue, Ya-Ning Zhu, Hai-Yan Tang, Ling-Yun Lv, Ji-Feng Feng, Wei-Guo Zhu
Y-box binding protein-1 (YBX1) is a multifunctional protein and often acts as an indicator of poor prognosis in cancers. Increasing evidence has shown that the levels of YBX1 protein were closely associated with multidrug resistance, relapse, metastasis and poor prognosis in cancers. However, its role in nasopharyngeal carcinoma (NPC) metastasis remains unknown. In our study, we discovered that the expression of YBX1 was increased in nasopharyngeal carcinoma tissues. YBX1 protein levels positively correlated with T stage and metastasis of NPC patients...
October 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29022498/atp-binding-cassette-exporters-structure-and-mechanism-with-a-focus-on-p-glycoprotein-and-mrp1
#5
Maite Rocío Arana, Guillermo Altenberg
The majority of proteins that belong to the ATP-binding cassette (ABC) superfamily are transporters that mediate the efflux of substrates from cells. These exporters include multidrug resistance proteins of the ABCB and ABCC subfamilies, such as P-glycoprotein (Pgp) and MRP1, respectively. These proteins are not only involved in the resistance of cancer to cytotoxic agents, but also in the protection from endo and xenobiotics, and the determination of drug pharmacokinetics, as well as in the pathophysiology of a variety of disorders...
October 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29018094/substrate-induced-conformational-changes-in-the-nucleotide-binding-domains-of-lipid-bilayer-associated-p-glycoprotein-during-atp-hydrolysis
#6
Maria E Zoghbi, Leo Mok, Douglas J Swartz, Anukriti Singh, Gregory A Fendley, Ina L Urbatsch, Guillermo A Altenberg
P-glycoprotein (Pgp) is an efflux pump important in multidrug resistance of cancer cells and in determining drug pharmacokinetics. Pgp is a prototype ATP-binding cassette (ABC) transporter with two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP. Conformational changes at the NBDs (the Pgp engines) lead to changes across Pgp transmembrane domains that result in substrate translocation. According to current alternating access models (substrate binding pocket accessible only to one side of the membrane at a time) binding of ATP promotes NBD dimerization, resulting in external accessibility of the drug-binding site (outward-facing, closed NBD conformation), and ATP-hydrolysis leads to dissociation of the NBDs with the subsequent return of the accessibility of the binding site to the cytoplasmic side (inward-facing, open NBD conformation)...
October 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29016119/9-deazapurines-as-broad-spectrum-inhibitors-of-the-abc-transport-proteins-p-glycoprotein-p-gp-abcb1-multidrug-resistance-associated-protein-1-mrp1-abcc1-and-breast-cancer-resistance-protein-bcrp-abcg2
#7
Katja Stefan, Sven Marcel Schmitt, Michael Wiese
P-glycoprotein (P-gp, ABCB1), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) and Breast Cancer Resistance Protein (BCRP, ABCG2) are the three major ABC transport proteins conferring resistance to many structurally diverse anticancer agents leading to the phenomenon called multidrug resistance (MDR). Much effort was put on the development of clinically useful compounds to reverse MDR. Broad-spectrum inhibitors of ABC transport proteins can be of great use in cancers that simultaneously co-express two or three transporters...
October 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28992456/prediction-of-new-chromene-based-inhibitors-of-tubulin-using-structure-based-virtual-screening-and-molecular-dynamics-simulation-methods
#8
Hassan Aryapour, Maryam Dehdab, Farzin Sohraby, Afshar Bargahi
Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds. In order to validate our hit compounds, molecular dynamics simulations and related analysis were carried out and the results suggest that our hit compounds (PubChem CIDs: 16814409, 17594471, 57367244 and 69899719) can prove to be potential inhibitors of tubulin...
September 27, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28991260/protein-and-chemotherapy-profiling-of-extracellular-vesicles-harvested-from-therapeutic-induced-senescent-triple-negative-breast-cancer-cells
#9
E L Kavanagh, S Lindsay, M Halasz, L C Gubbins, K Weiner-Gorzel, M H Z Guang, A McGoldrick, E Collins, M Henry, A Blanco-Fernández, P O' Gorman, P Fitzpatrick, M J Higgins, P Dowling, A McCann
Triple negative breast cancer (TNBC) is an aggressive subtype with relatively poor clinical outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemoresistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy...
October 9, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28987820/transfer-of-multidrug-resistance-among-acute-myeloid-leukemia-cells-via-extracellular-vesicles-and-their-microrna-cargo
#10
Céline Bouvy, Adeline Wannez, Julie Laloy, Christian Chatelain, Jean-Michel Dogné
The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested. The aim of this research was to investigate the role of EVs in chemo-resistance in acute myeloid leukemia. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was studied along with its multi-resistant strain, HL60/AR that overexpresses the multidrug resistance protein 1 (MRP-1)...
September 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28987325/anti-tumor-compound-ry10-4-suppresses-multidrug-resistance-in-mcf-7-adr-cells-by-inhibiting-pi3k-akt-nf-%C3%AE%C2%BAb-signaling
#11
Xiaofan Yang, Yufeng Ding, Miao Xiao, Xin Liu, Jinlan Ruan, Pingping Xue
RY10-4, an anti-tumor agent, exerts cytotoxicity to various human cancer cell lines. However, few studies reported the effect of combined application of RY10-4 and chemotherapeutic drugs against cancer cells with multidrug resistance (MDR). In this study, P-glycoprotein (P-gp), which is reported to mediate MDR to anti-cancer drugs, was proved to be overexpressed in the adriamycin (ADR)-resistant human breast cancer cells, namely MCF-7/ADR cells. Furthermore, RY10-4 application resulted in a downregulation of P-gp in MCF-7/ADR cells, thus leading to higher chemosensitivity to ADR...
October 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28979163/a-p53-regulated-apoptotic-gene-signature-predicts-treatment-response-and-outcome-in-pediatric-acute-lymphoblastic-leukemia
#12
Russell O Bainer, Matthew R Trendowski, Cheng Cheng, Deqing Pei, Wenjian Yang, Steven W Paugh, Kathleen H Goss, Andrew D Skol, Paul Pavlidis, Ching-Hon Pui, T Conrad Gilliam, William E Evans, Kenan Onel
Gene signatures have been associated with outcome in pediatric acute lymphoblastic leukemia (ALL) and other malignancies. However, determining the molecular drivers of these expression changes remains challenging. In ALL blasts, the p53 tumor suppressor is the primary regulator of the apoptotic response to genotoxic chemotherapy, which is predictive of outcome. Consequently, we hypothesized that the normal p53-regulated apoptotic response to DNA damage would be altered in ALL and that this alteration would influence drug response and treatment outcome...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28978268/balaglitazone-reverses-p-glycoprotein-mediated-multidrug-resistance-via-upregulation-of-pten-in-a-ppar%C3%AE-dependent-manner-in-leukemia-cells
#13
Bahman Yousefi, Ako Azimi, Maryam Majidinia, Vahid Shafiei-Irannejad, Reza Badalzadeh, Behzad Baradaran, Nosratollah Zarghami, Nasser Samadi
Multidrug resistance in tumor cells is still a big challenge in cancer treatment. Therefore, identification ofsafe and effective multidrug resistance-reversing compounds with minimal side effects is an important approach in cancer treatment. Here, we investigated the role and potential mechanisms of peroxisome proliferator-activated receptor γ in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. The effect of doxorubicin on cell viability following treatment with balaglitazone, a peroxisome proliferator-activated receptor γ agonist, was evaluated using trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28977811/-interdisciplinary-treatment-of-patients-with-pulmonary-tuberculosis
#14
Joachim Pfannschmidt, Nicolas Schönfeld
Today surgical procedures for pulmonary tuberculosis are highly selective but owing to the increasing incidence of multidrug resistant tuberculosis has been becoming more and more relevant. Besides the treatment of tuberculosis foci in multidrug resistance tuberculosis to eliminate the source of relapse, complications as sequelae of tuberculosis are among the most frequent indications for surgery. In patients with cavernous lesions, destroyed lobe or lung, bronchiectasis, pleural empyema or hemoptysis thoracic surgical procedures may be warranted...
September 2017: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/28976984/mycoplasma-associated-multidrug-resistance-of-hepatocarcinoma-cells-requires-the-interaction-of-p37-and-annexin-a2
#15
Danyang Liu, Yang Hu, Ying Guo, Zhu Zhu, Bingzheng Lu, Xuelan Wang, Yijun Huang
Mycoplasma infection has been reported to be associated with cancer migration, invasion, epithelial-mesenchymal transition as well as the resistance to nucleoside analogues chemotherapeutic drugs. In this study, we found that the sensitivity of hepatocarcinoma cells to Cisplatin, Gemcitabine and Mitoxantrone was increased by mycoplasma elimination. Similar to the effect of anti-mycoplasma agent, interrupting the interaction between Mycoplasma hyorhinis membrane protein P37 and Annexin A2 of host cells using the N-terminal of ANXA2 polypeptide enhanced the sensitivity of HCC97L cells to Gemcitabine and Mitoxantrone...
2017: PloS One
https://www.readbyqxmd.com/read/28970358/xenobiotic-nuclear-receptors-pxr-and-car-regulate-antiretroviral-drug-efflux-transporters-at-the-blood-testis-barrier
#16
Sana-Kay Whyte-Allman, Md Tozammel Hoque, Mohammad-Ali Jenabian, Jean-Pierre Routy, Reina Bendayan
Poor antiretroviral drug (ARV) penetration in the testes could, in part, be due to the presence of ATP-binding cassette membrane-associated drug efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs) expressed at the blood-testis barrier (BTB). The functional expression of these transporters is known to be regulated by ligand-activated nuclear receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR), in various tissues...
September 28, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28969069/lncrna-plasmacytoma-variant-translocation-1-is-an-oncogene-in-bladder-urothelial-carcinoma
#17
Zhongyuan Liu, Hui Zhang
Bladder cancer (BC) is the most lethal malignant cancer of the genitourinary system, and bladder urothelial carcinoma (BUC) is the most common type of BC. The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is overexpressed in several malignant tumors, including BC. Using a lncRNA array and quantitative real-time PCR, we detected greater expression of PVT1 in BUC tissues and cell lines resistant to doxorubicin (DOX) and cisplatin (DDP) than in DOX- and DDP-sensitive cells. PVT1 knockdown reduced proliferation and invasion by a DOX- and DDP-resistant T24/DR BUC cells, arrested cells in G1 phase, and increased apoptosis...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969035/pleiotrophin-promotes-chemoresistance-to-doxorubicin-in-osteosarcoma-by-upregulating-p-glycoprotein
#18
Dapeng Wu, Liguo Liu, Xuebing Yan, Chunyan Wang, Yaling Wang, Kun Han, Shuchen Lin, Zhihua Gan, Daliu Min
Chemoresistance is a major hindrance to successful treatment of osteosarcoma (OS). Pleiotrophin (PTN), a neurotrophic growth factor, has been linked to the malignant characteristics of various cancer types. We retrospectively examined the correlation between PTN expression and chemoresistance in OS in a cohort of 133 OS patients. Immunohistochemistry revealed that PTN expression correlated with the necrosis rate and local OS recurrence. In a prognostic analysis, high PTN expression was associated with poor overall and disease-free survival, and was an independent adverse prognostic factor for disease-free survival...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968471/modulation-of-the-mrna-binding-protein-hur-as-a-novel-reversal-mechanism-of-epirubicin-triggered-multidrug-resistance-in-colorectal-cancer-cells
#19
Guan-Liang Lin, Huei-Ju Ting, Ta-Chien Tseng, Vivian Juang, Yu-Li Lo
HuR (ELAVL1), a RNA-binding protein, plays a key role in posttranscriptional regulation of multidrug resistance (MDR)-related genes. Among various HuR-regulated oncogenic transcripts, the activation of galectin-3/β-catenin survival pathway is critical to induce transcription of cyclin D1, P-glycoprotein (P-gp) and/or multidrug resistance-associated proteins (MRPs). In this study, we aim to elucidate the HuR-regulating pathways related to epirubicin-mediated resistance in human colorectal carcinoma cells. The effects and mechanisms of epirubicin treatment on the expressions of upstream survival signals (e...
2017: PloS One
https://www.readbyqxmd.com/read/28964574/epigallocatechin-3-gallate-promotes-apoptosis-and-reversal-of-multidrug-resistance-in-esophageal-cancer-cells
#20
Liang Liu, Yingchao Ju, Jing Wang, Rongmiao Zhou
Evidence for demonstrating the role of the green tea component epigallocatechin-3-gallate (EGCG) in esophageal squamous cell carcinoma cells is limited. In this study, we investigated apoptosis induced by EGCG and the underlying molecular mechanisms in human esophageal squamous cell carcinoma cells. The growth-inhibitory effects of EGCG on esophageal cancer cell (Eca109 and Ec9706) were detected by MTT. Using flow cytometry, we determined the cellular apoptosis, bcl-2, bax and caspase-3 protein expression in Eca109 and Ec9706 cells following treatment with EGCG for 24h...
September 12, 2017: Pathology, Research and Practice
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