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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/28528299/selective-targeting-and-therapy-of-metastatic-and-multidrug-resistant-tumors-using-a-long-circulating-podophyllotoxin-nanoparticle
#1
Aniruddha Roy, Yucheng Zhao, Yang Yang, Andras Szeitz, Tara Klassen, Shyh-Dar Li
Treatment options for metastatic and multidrug resistant (MDR) tumors are limited, and most of the chemotherapeutic drugs exhibit low efficacy against MDR cancers. An anti-tubulin agent podophyllotoxin (PPT) displays high potency against MDR tumor cells. However, due to its poor solubility and non-specificity, PPT cannot be used systemically. We have developed a self-assembling nanoparticle dosage form for PPT (named Celludo) by covalently conjugating PPT and polyethylene glycol (PEG) to acetylated carboxymethyl cellulose (CMC-Ac) via ester linkages...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#2
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28527651/clinical-efficacy-of-cycling-empirical-antibiotic-therapy-for-febrile-neutropenia-in-pediatric-cancer-patients
#3
Hideto Teranishi, Yuhki Koga, Hisanori Nishio, Wakako Kato, Hiroaki Ono, Shunsuke Kanno, Kentaro Nakashima, Hidetoshi Takada
BACKGROUND: Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. METHODS: Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#4
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28524273/synthesis-and-biological-evaluation-of-novel-peptides-based-on-antimicrobial-peptides-as-potential-agents-with-anti-tumor-and-multidrug-resistance-reversing-activities
#5
Bo Zhang, Wei Shi, Jieming Li, Chen Liao, Limei Yang, Wenlong Huang, Hai Qian
Tumor chemotherapy, which plays an important role in the clinical treatment of metastatic cancer, is limited by low selectivity and drug resistance in clinical application. In our study, we selected antimicrobial peptide BP100 as a lead peptide, designed and synthesized a series of novel antineoplastic peptides through solid-phase synthesis. Amongst them, B4 and B8 showed excellent anti-cancer activity. As revealed by further investigations, these peptides could disrupt the cell membrane, trigger the cytochrome C release into cytoplasm and ultimately lead to apoptosis...
May 19, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28523942/combinatorial-therapeutic-approaches-with-rnai-and-anticancer-drugs-using-nanodrug-delivery-systems
#6
Anish Babu, Anupama Munshi, Rajagopal Ramesh
RNA interference (RNAi) is emerging as a powerful approach in cancer treatment. siRNA is an important RNAi tool that can be designed to specifically silence the expression of genes involved in drug resistance and chemotherapeutic inactivity. Combining siRNA and other therapeutic agents can overcome the multidrug resistance (MDR) phenomenon by simultaneously silencing genes and enhancing chemotherapeutic activity. Moreover, the therapeutic efficiency of anticancer drugs can be significantly improved by additive or synergistic effects induced by siRNA and combined therapies...
May 19, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28522191/enhanced-tumor-therapy-via-drug-co-delivery-and-in-situ-vascular-promoting-strategy
#7
Mingxing Yin, Songwei Tan, Yuling Bao, Zhiping Zhang
Conventional tumor starving therapy by reducing its vessel density may be effective at early treatment but potentially contributes to tumor hypoxia, drug resistance and metastasis. A new strategy through enhancing tumor angiogenesis in combination with effective chemotherapeutic drugs, has shown successful tumor growth and spread inhibition. To achieve in situ release of angiogenic and antitumor drugs in tumor, we designed a precise ratiometric polymeric hybrid micelle system for co-delivering nitric oxide and paclitaxel...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28521675/chemotherapy-with-si-rna-and-anti-cancer-drugs
#8
Kamaljeet Kaur, Goutam Rath, Saket Chandra, Ranjit Singh, Amit K Goyal
To treat cancer, chemotherapy is a key therapeutic approach which is associated with several limitations. This chemotherapeutical agents exhibit multi drug resistance coupled with undesirable side effects. This multidrug resistance is exhibited by tumor cell due to actuation of drug out flow mechanism, programmed cell death and protection mechanisms etc. One of the therapeutic approaches to cure cancer is RNA interference (RNAi). Small interfering RNA (si-RNA) is considered as a major therapeutic tool used to control expression of a particular gene...
May 18, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28508185/titan-phase-iii-study-of-doxorubicin-cyclophosphamide-followed-by-ixabepilone-or-paclitaxel-in-early-stage-triple-negative-breast-cancer
#9
Denise A Yardley, Edward R Arrowsmith, Brooke R Daniel, Janice Eakle, Adam Brufsky, David R Drosick, Fred Kudrik, Linda D Bosserman, Mark R Keaton, Sharon A Goble, Jeffrey A Bubis, Victor M Priego, Kelly Pendergrass, Yvonne Manalo, Martin Bury, Donald S Gravenor, Gladys I Rodriguez, Roger C Inhorn, Robyn R Young, William N Harwin, Caryn Silver, John D Hainsworth, Howard A Burris
PURPOSE: Ixabepilone is a microtubule stabilizer with activity in taxane-refractory metastatic breast cancer and low susceptibility to taxane-resistance mechanisms including multidrug-resistant phenotypes and high β-III tubulin expression. Since these resistance mechanisms are common in triple-negative breast cancer (TNBC), ixabepilone may have particular advantages in this patient population. This study evaluated the substitution of ixabepilone for paclitaxel following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early-stage TNBC...
May 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28506645/multiple-roles-of-glyoxalase-1-mediated-suppression-of-methylglyoxal-glycation-in-cancer-biology-involvement-in-tumour-suppression-tumour-growth-multidrug-resistance-and-target-for-chemotherapy
#10
REVIEW
Naila Rabbani, Mingzhan Xue, Martin O Weickert, Paul J Thornalley
Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all human cells. It catalyses the glutathione-dependent removal of the endogenous reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side product of anaerobic glycolysis. It modifies protein and DNA to form mainly hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal accumulation of MG, dicarbonyl stress, increases adduct levels which may induce apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a tumour suppressor protein and small molecule inducers of Glo1 expression may find use in cancer prevention...
May 12, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28503421/differential-expression-of-breast-cancer-resistance-protein-lung-resistance-protein-and-multidrug-resistance-protein-1-in-retinas-of-streptozotocin-induced-diabetic-mice
#11
Meng-Shuang Li, Meng Xin, Chuan-Long Guo, Gui-Ming Lin, Jun Li, Xiang-Gen Wu
AIM: To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein (BCRP), lung resistance protein (LRP), and multidrug resistance protein 1 (MDR1) at the inner blood-retinal barrier (BRB) during the development of early diabetic retinopathy (DR) and/or aging in mice. METHODS: Relative mRNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28499449/perk-induces-resistance-to-cell-death-elicited-by-endoplasmic-reticulum-stress-and-chemotherapy
#12
Iris C Salaroglio, Elisa Panada, Enrico Moiso, Ilaria Buondonno, Paolo Provero, Menachem Rubinstein, Joanna Kopecka, Chiara Riganti
BACKGROUND: Nutrient deprivation, hypoxia, radiotherapy and chemotherapy induce endoplasmic reticulum (ER) stress, which activates the so-called unfolded protein response (UPR). Extensive and acute ER stress directs the UPR towards activation of death-triggering pathways. Cancer cells are selected to resist mild and prolonged ER stress by activating pro-survival UPR. We recently found that drug-resistant tumor cells are simultaneously resistant to ER stress-triggered cell death. It is not known if cancer cells adapted to ER stressing conditions acquire a chemoresistant phenotype...
May 12, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28498438/dexamethasone-reduces-side-population-fraction-through-downregulation-of-abcg2-transporter-in-mcf-7-breast-cancer-cells
#13
Jong Bin Kim, Sung Eun Hwang, Sang-Pil Yoon
Side population (SP) cells represent a rare population among breast cancer cells. SP cells have been reported to act as cancer stem‑like cells, and to participate in the development of multidrug resistance via modulating the expression of ATP-binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid drug that has been used as an adjuvant treatment to enhance the efficacy of chemotherapeutic agents; however, its effects in breast cancer have yet to be thoroughly investigated. In the present study, the effects of dexamethasone were investigated using the human MCF‑7 breast cancer cell line, and SPs were examined in detail...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28496304/evaluation-of-the-antitumor-activity-of-nov202-a-novel-microtubule-targeting-and-vascular-disrupting-agent
#14
Linda Rickardson, Emma Kutvonen, Satu Orasniemi, Marita Högberg, Marko J Kallio, Stefan Rehnmark
PURPOSE: Overall, ~65% of patients diagnosed with advanced ovarian cancer (OC) will relapse after primary surgery and adjuvant first-line platinum- and taxane-based chemotherapy. Significant improvements in the treatment of OC are expected from the development of novel compounds having combined cytotoxic and antiangiogenic properties that make them effective on refractory tumors. METHODS: Permeability of NOV202 was determined with Caco-2 monolayer assay. The compound's pharmacokinetic profile and plasma:brain distribution were assessed in male C57Bl/6 mice...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28493713/cetuximab-prevents-methotrexate-induced-cytotoxicity-in-vitro-through-epidermal-growth-factor-dependent-regulation-of-renal-drug-transporters
#15
Pedro Caetano-Pinto, Amer Jamalpoor, Janneke Ham, Anastasia Goumenou, Monique Mommersteeg, Dirk Pijnenburg, Rob Ruijtenbeek, Natalia Sánchez-Romero, Bertrand van Zelst, Sandra Heil, Jitske Jansen, Martijn J Wilmer, Carla M L van Herpen, Rosalinde Masereeuw
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells over-expressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4) and P-glycoprotein (P-gp) in methotrexate handling upon EGF and/or cetuximab treatment...
May 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28490877/low-density-lipoprotein-coupled-micelles-with-reduction-and-ph-dual-sensitivity-for-intelligent-co-delivery-of-paclitaxel-and-sirna-to-breast-tumor
#16
Wen-Jing Zhu, Shu-di Yang, Chen-Xi Qu, Qiao-Ling Zhu, Wei-Liang Chen, Fang Li, Zhi-Qiang Yuan, Yang Liu, Ben-Gang You, Xue-Nong Zhang
Multidrug resistance (MDR) is a major obstacle for the clinical therapy of malignant human cancers. The discovery of RNA interference provides efficient gene silencing within tumor cells for reversing MDR. In this study, a new "binary polymer" low-density lipoprotein-N-succinyl chitosan-cystamine-urocanic acid (LDL-NSC-SS-UA) with dual pH/redox sensitivity and targeting effect was synthesized for the co-delivery of breast cancer resistance protein small interfering RNA (siRNA) and paclitaxel (PTX). In vivo, the co-delivering micelles can accumulate in tumor tissue via the enhanced permeability and retention effect and the specific recognition and combination of LDL and LDL receptor, which is overexpressed on the surface of tumor cell membranes...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28490700/-role-of-tgf-%C3%AE-1-in-multi-drug-resistance-in-small-cell-lung-cancer-and-its-clinical-significance
#17
Huanxin Liu, Wei Wang, Guoxiang Zhang, Linlang Guo
To investigate the role of transforming growth factor β1 (TGF-β1) in multi-drug resistance in small cell lung cancer and its clinical significance.
 Methods: The mRNA and protein expressions of TGF-β1 in H69 and H69AR cells were detected by real-time PCR and Western blot, respectively. After silence of TGF-β1, the sensitivity of H69AR to drugs was detected by CCK8 assay. The expressions of TGF-β1 in lung cancer and paracarcinoma tissues were examined by QRT-PCR and immunohistochemistry. The relationship of TGF-β1 expression with clinical pathological features and prognosis of patients was studied...
April 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28489292/dual-stimuli-responsive-nanoparticles-for-controlled-release-of-anticancer-and-anti-inflammatory-drugs-combination
#18
Liandong Feng, Yuqi Wang, Zhiliang Luo, Zheng Huang, Yan Zhang, Kai Guo, Deju Ye
Dual stimuli-responsive nanoparticles capable of fine-tuning drug release to augment therapeutic efficacy have become as promising tools for anticancer drugs delivery. However, rational design of these 'smart' nanoparticles for selective delivery and controlling release of multidrug combination in cancer cells to achieve synergistic effects remain challenging. Here we report a pH/redox dual responsive nanoparticle FA-DOX-Ind-NP based on a novel tumor targeting and biodegradable poly(β-amino ester) polymer, and demonstrate its high ability to enter into cancer cells and release a combination of anticancer drug doxorubicin and nonsteroidal anti-inflammatory drug indomethacin to achieve synergistic chemo-anti-inflammatory effects and overcome multidrug resistance...
May 10, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28488578/triterpenoids-from-aglaia-abbreviata-exert-cytotoxicity-and-multidrug-resistant-reversal-effect-in-mcf-7-adm-cells-via-reactive-oxygen-species-induction-and-p-glycoprotein-inhibition
#19
Juan Cen, Beibei Zheng, Rubing Bai, Li Zhang, Feng Zhang, Xia Zhang
Triterpenoids from the Aglaia have been shown cytotoxicity on a broad spectrum of human tumor cells. In the present study, we extracted triterpenoids AA-5 (1) and AA-6 (2) from stems of Aglaia abbreviata, and studied their cytotoxicity in multidrug resistant (MDR) MCF-7/ADM cells. After 48 h treatment, AA-5 (1) and AA-6 (2) significantly increased mitochondrial-mediated apoptosis by enhancing reactive oxygen species (ROS) with depressed mitochondrial membrane potential and caspase-9 activities. The drug efflux transporter P-glycoprotein (P-gp) and the intracellular antioxidant systems, involving Glutathione S-Transferase π, Glutathione and heme oxygenase-1, were also inhibited via the ROS-depressed Akt/NF-E2-related factor 2 pathway...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487651/mechanism-underlying-the-reversal-of-drug-resistance-in-p-glycoprotein-expressing-leukemia-cells-by-pinoresinol-and-the-study-of-a-derivative
#20
María L González, D Mariano A Vera, Jerónimo Laiolo, Mariana B Joray, Mariana Maccioni, Sara M Palacios, Gabriela Molina, Priscila A Lanza, Samanta Gancedo, Vivian Rumjanek, María C Carpinella
P-glycoprotein (P-gp) is a membrane protein associated with multidrug resistance (MDR) due to its key role in mediating the traffic of chemotherapeutic drugs outside cancer cells, leading to a cellular response that hinders efforts toward successful therapy. With the aim of finding agents that circumvent the MDR phenotype mediated by P-gp, 15 compounds isolated from native and naturalized plants of Argentina were screened. Among these, the non-cytotoxic lignan (±) pinoresinol successfully restored sensitivity to doxorubicin from 7 μM in the P-gp overexpressed human myelogenous leukemia cells, Lucena 1...
2017: Frontiers in Pharmacology
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