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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/28820055/an-update-on-circumventing-multidrug-resistance-in-cancer-by-targeting-p-glycoprotein
#1
Xiaoqian Yang, Xiaoduan Li, Zhenfeng Duan, Xipeng Wang
BACKGROUND: The ultimate emergence of multidrug resistance remains a severe limitation of chemotherapy treatment for patients with cancer. The best-characterized cause of drug resistance involves the overexpression of P-glycoprotein (Pgp), which decreases the intracellular accumulation of chemotherapeutic agents in drug-resistant cancer cells. Thus, Pgp has become an attractive potential target for treating chemotherapy-resistant cancer, butthe outcomes of using chemotherapy in combination with Pgp inhibitors in clinical trials to date have been disappointing...
June 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28819699/cudc-907-a-dual-hdac-and-pi3k-inhibitor-reverses-platinum-drug-resistance
#2
Kenneth K W To, Li-Wu Fu
Platinum (Pt)-based anticancer drugs are the mainstay of treatment for solid cancers. However, resistance to Pt drugs develops rapidly, which can be caused by overexpression of multidrug resistance transporters and activation of DNA repair. CUDC-907 is a potent molecular targeted anticancer agent, rationally designed to simultaneously inhibit histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K). We investigated the potentiation effect of CUDC-907 on Pt drugs in resistant cancer cells. ABCC2 stably-transfected HEK293 cells and two pairs of parental and Pt-resistant cancer cell lines were used to test for the circumvention of resistance by CUDC-907...
August 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28819388/role-of-y-box-protein-1-in-cancer-as-potential-biomarker-and-novel-therapeutic-target
#3
REVIEW
Pramod Kumar Maurya, Alok Mishra, Birendra Singh Yadav, Swati Singh, Prashant Kumar, Amit Chaudhary, Shweta Srivastava, Suriya Narayan Murugesan, Ashutosh Mani
The Y-box binding protein (YB-1) is known to be a multifunctional transcription and translation factor during expression of several proteins. It is a vital oncoprotein that regulates cancer cell progression and proliferation. YB-1 is over-expressed in various human cancers such as breast cancer, colon cancer, lung cancer, gastric cancer, oesophageal cancer and glioblastoma. Nuclear expression of YB-1 is found to be associated with multidrug resistance and cancer cell progression. YB-1 is reported to regulate many cellular signalling pathways in different types of cancer proliferation...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818459/a-novel-delocalized-lipophilic-cation-chlorambucil-conjugate-inhibits-p-glycoprotein-in-hepg2-adm-cells
#4
Teng Liu, Yongbo Peng, Xiong Li, Lian Liu, Fang Liu, Leye He
Multidrug resistance (MDR) limits the application of a large number of cancer-fighting agents in clinical therapy. One reason is that P-glycoprotein (Pgp) efflux pumps are usually overexpressed and lead to drug efflux in the cancer cells, which limits the viability of many chemotherapeutics. Current available inhibitors which block the Pgp pump efflux are usually not widely used in clinical practice, because they change other drug pharmacokinetic profiles or increase side effects. Here, through covalent linkage of cancer-targeting delocalized lipophilic cation FF and DNA-damaging drug nitrogen mustard chlorambucil (CLB), we rationally designed and synthesized a tumor-targeting anticancer agent FFCLB...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28816939/correlations-of-icam-1-gene-polymorphisms-with-susceptibility-and-multidrug-resistance-in-colorectal-cancer-in-a-chinese-population
#5
Lu-Bing Liu, Tong Liu, Fu-Ze Xin
BACKGROUND: Colorectal cancer (CRC) is a malignant gastrointestinal tumor with a high mortality rate, including both colon and rectal cancer. In order to provide clinical guidance for the treatment of CRC, this study is conducted to investigate the correlations of intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms with susceptibility and multidrug resistance (MDR) of colorectal cancer (CRC). METHODS: A total of 195 patients with CRC were selected as the observation group and 188 healthy people enrolled as the control group...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28814831/schiff-base-derived-from-thiosemicarbazone-and-anthracene-showed-high-potential-in-overcoming-multidrug-resistance-in-vitro-with-low-drug-resistance-index
#6
Jie Bai, Rui-Hui Wang, Yan Qiao, Aidong Wang, Chen-Jie Fang
Multidrug resistance (MDR) is a huge obstacle in cancer chemotherapeutics. Overcoming MDR is a great challenge for anticancer drug discovery. Here, DNA binding and cytotoxicity of Schiff base L1 and L2 were explored to assess their efficiency in fighting cancer and overcoming the MDR. L1 and L2 could treat extremely chemoresistant MCF-7/ADR cell as drug-sensitive cell, with drug resistance index (DRI) <2.13, showing high potential in overcoming the MDR. The apoptotic ratio induced by L1 and L2 was low for both MCF-7 and MCF-7/ADR cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28813596/molecular-imaging-of-p-glycoprotein-in-chemoresistant-tumors-using-a-dual-modality-pet-fluorescence-probe
#7
Mengzhe Wang, Chengqiong Mao, Hui Wang, Xueying Ling, Zhanhong Wu, Zi-Bo Li, Xin Ming
Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28811220/euphorbia-lunulata-extract-acts-on-multidrug-resistant-gastric-cancer-cells-to-inhibit-cell-proliferation-migration-and-invasion-arrest-cell-cycle-progression-and-induce-apoptosis
#8
Zhaoying Fu, Xiaodong Han, Juan Du, Xiaoxiao Han, Weipeng Liu, Shumei Shao, Xiaobin Liu
ETHNOPHARMACOLOGICAL RELEVANCE: The milky sap or the aboveground part of the plant Euphorbia lunulata has long been used by Chinese people to treat noncancerous growths and cancerous ailments but the specific mode of action and the action mechanism remain to be elucidated. AIM OF THE STUDY: To investigate the effects of Euphorbia lunulata extract on cell proliferation, migration, invasion, cell cycle progression, and apoptosis of multidrug resistant human gastric cancer cells; To study the mechanism of apoptosis induction by Euphorbia lunulata extract in multidrug resistant human gastric cancer cells...
August 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28810651/kanglaite-inhibits-the-expression-of-drug-resistance-genes-through-suppressing-pvt1-in-cisplatin-resistant-gastric-cancer-cells
#9
Xian-Wen Zhang, Liang Liu, Xi-Zhi Zhang, Ping Bo
Kanglaite (KLT) was shown to alleviate the development of multidrug resistance (MDR) clinically. The purpose of this study is to examine the mechanism of KLT for chemotherapy resistance in gastric cancer cells involving the regulation of MDR-related proteins. The cisplatin-resistant BGC823/DPP and SGC7901/DDP cells were treated with 1, 2.5 and 5 µl/ml of KLT for 24, 36 and 48 h. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to detect the cell viability and cell apoptosis, respectively...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28796494/dioxomorpholines-and-derivatives-from-a-marine-facultative-aspergillus-species
#10
Manuel A Aparicio-Cuevas, Isabel Rivero-Cruz, Mariano Sánchez-Castellanos, Daniel Menéndez, Huzefa A Raja, Pedro Joseph-Nathan, María Del Carmen González, Mario Figueroa
Two new dioxomorpholines, 1 and 2, three new derivatives, 3-5, and the known compound PF1233 B (6) were isolated from a marine-facultative Aspergillus sp. MEXU 27854. Their structures were established by 1D and 2D NMR and HRESIMS data analysis. The absolute configuration of 1 and 2 was elucidated by comparison of experimental and DFT-calculated vibrational circular dichroism spectra. Compounds 3, 5, and 6 were noncytotoxic to a panel of human cancer cell lines with different functional status for the tumor-suppressor protein p53, but were inhibitors of P-glycoprotein-reversing multidrug resistance in a doxorubicin-resistant cell line...
August 10, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28791369/cepharanthine-hydrochloride-reverses-p%C3%A2-glycoprotein-mediated-multidrug-resistance-in-human-ovarian-carcinoma-a2780-taxol-cells-by-inhibiting-the-pi3k-akt-signaling-pathway
#11
Chen-Zheng Huang, Ya-Feng Wang, Yan Zhang, You-Mei Peng, Yi-Xian Liu, Fang Ma, Jin-Hua Jiang, Qing-Duan Wang
Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. The major obstacle to treatment success is multidrug resistance (MDR) to chemotherapy drugs. Cepharanthine hydrochloride (CH), a natural alkaloid-derived compound, has shown MDR reversal potency in several tumor cell lines; however, the molecular mechanism is not entirely known. In the present study, we assessed whether CH sensitized malignant cells to chemotherapy drugs in ovarian cancer and explored the relevant mechanism. We found that CH reduced the IC50 value of paclitaxel and increased intracellular rhodamine-123 accumulation in human ovarian cancer A2780/Taxol cells in a concentration-dependent manner...
August 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28789891/design-synthesis-and-cytotoxic-activity-of-novel-7-substituted-camptothecin-derivatives-incorporating-piperazinyl-sulfonylamidine-moieties
#12
Cheng-Jie Yang, Zi-Long Song, Masuo Goto, Ying-Qian Liu, Kan-Yen Hsieh, Susan L Morris-Natschke, Yong-Long Zhao, Jun-Xiang Zhang, Kuo-Hsiung Lee
In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel 7-substituted CPT derivatives incorporating piperazinyl-sulfonylamidine moieties were designed, synthesized and evaluated for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB, and KB-VIN). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Remarkably, most of the compounds exhibited comparable cytotoxicity against the multidrug-resistant (MDR) KB-VIN and parental KB tumor cell lines, while irinotecan lost activity completely against KB-VIN...
July 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28782285/metformin-enhances-doxorubicin-sensitivity-via-inhibition-of-doxorubicin-efflux-in-p-gp-overexpressing-mcf-7-cells
#13
Vahid Shafiei-Irannejad, Nasser Samadi, Bahman Yousefi, Roya Salehi, Kobra Velaei, Nosratollah Zarghami
Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX) resistant breast cancer (MCF-7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P-gp mRNA/protein expression levels following treatment with metformin was determined using real time polymerase chain reaction (RT-PCR) and western blot analysis, respectively...
August 6, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28778071/suppression-of-pancreatic-adenocarcinoma-upregulated-factor-pauf-increases-the-sensitivity-of-pancreatic-cancer-to-gemcitabine-and-5fu-and-inhibits-the-formation-of-pancreatic-cancer-stem-like-cells
#14
Jae Hee Cho, Sun A Kim, Soo Been Park, Hee Man Kim, Si Young Song
Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44+CD24+ESA+ pancreatic CSCs...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28776259/increased-egfr-expression-induced-by-a-novel-oncogene-cug2-confers-resistance-to-doxorubicin-through-stat1-hdac4-signaling
#15
Sirichat Kaowinn, Seung Won Jun, Chang Seok Kim, Dong-Myeong Shin, Yoon-Hwae Hwang, Kyujung Kim, Bosung Shin, Chutima Kaewpiboon, Hyeon Hee Jeong, Sang Seok Koh, Oliver H Krämer, Randal N Johnston, Young-Hwa Chung
BACKGROUND: Previously, it has been found that the cancer upregulated gene 2 (CUG2) and the epidermal growth factor receptor (EGFR) both contribute to drug resistance of cancer cells. Here, we explored whether CUG2 may exert its anticancer drug resistance by increasing the expression of EGFR. METHODS: EGFR expression was assessed using Western blotting, immunofluorescence and capacitance assays in A549 lung cancer and immortalized bronchial BEAS-2B cells, respectively, stably transfected with a CUG2 expression vector (A549-CUG2; BEAS-CUG2) or an empty control vector (A549-Vec; BEAS-Vec)...
August 3, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28766343/isothermal-point-mutation-detection-toward-a-first-pass-screening-strategy-for-multidrug-resistant-tuberculosis
#16
Benjamin Y C Ng, Eugene J H Wee, Kyra Woods, Will Anderson, Fiach Antaw, Hennes Z H Tsang, Nicholas P West, Matt Trau
Point mutations in DNA are useful biomarkers that can provide critical classification of disease for accurate diagnosis and to inform clinical decisions. Conventional approaches to detect point mutations are usually based on technologies such as real-time polymerase chain reaction (PCR) or DNA sequencing, which are typically slow and require expensive lab-based equipment. While rapid isothermal strategies such as recombinase polymerase amplification (RPA) have been proposed, they tend to suffer from poor specificity in discriminating point mutations...
August 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28763646/design-synthesis-and-biological-evaluation-of-4-anilinoquinoline-derivatives-as-novel-potent-tubulin-depolymerization-agents
#17
Yuanyuan Zhou, Wei Yan, Dong Cao, Mingfeng Shao, Dan Li, Fang Wang, Zhuang Yang, Yong Chen, Linhong He, Taijin Wang, Mingsheng Shen, Lijuan Chen
A series of novel 4-anilinoquinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, 14h exhibited the most potent cytotoxic activity with IC50 values ranging from 1.5 to 3.9 nM against all tested cancer cell lines, and showed promising efficacy in multidrug resistant cancer cells. Flow cytometry assay, immune-fluorescence staining, microtubule dynamics assays and competition assays with EBI identified that 14h was a novel tubulin depolymerization agent by binding to the colchicine site...
July 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28762997/investigating-the-biosynthesis-of-natural-products-from-marine-proteobacteria-a-survey-of-molecules-and-strategies
#18
REVIEW
Marshall L Timmermans, Yagya P Paudel, Avena C Ross
The phylum proteobacteria contains a wide array of Gram-negative marine bacteria. With recent advances in genomic sequencing, genome analysis, and analytical chemistry techniques, a whole host of information is being revealed about the primary and secondary metabolism of marine proteobacteria. This has led to the discovery of a growing number of medically relevant natural products, including novel leads for the treatment of multidrug-resistant Staphylococcus aureus (MRSA) and cancer. Of equal interest, marine proteobacteria produce natural products whose structure and biosynthetic mechanisms differ from those of their terrestrial and actinobacterial counterparts...
August 1, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28762597/visfatin-mediates-doxorubicin-resistance-in-human-non-small-cell-lung-cancer-via-akt-mediated-up-regulation-of-abcc1
#19
Zhili Cao, Naixin Liang, Huaxia Yang, Shanqing Li
OBJECTIVES: Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Increasing levels of visfatin are correlated with worse clinical prognosis of NSCLC. However, the effects of visfatin on drug resistant are still not well illustrated. MATERIALS AND METHODS: Effects of visfatin on drug resistant cells were checked by CCK-8 kit. Gene and protein variations were measured by real-time PCR and western blot analysis, respectively. RESULTS: Our present data confirmed that expression of visfatin was significantly increased in NSCLC cells and tissues...
August 1, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28760489/mdr-in-cancer-addressing-the-underlying-cellular-alterations-with-the-use-of-nanocarriers
#20
REVIEW
Manu S Singh, Salma N Tammam, Maryam A Shetab Boushehri, Alf Lamprecht
Multidrug resistance (MDR) is associated with a wide range of pathological changes at different cellular and intracellular levels. Nanoparticles (NPs) have been extensively exploited as the carriers of MDR reversing payloads to resistant tumor cells. However, when properly formulated in terms of chemical composition and physicochemical properties, NPs can serve as beyond delivery systems and help overcome MDR even without carrying a load of chemosensitizers or MDR reversing molecular cargos. Whether serving as drug carriers or beyond, a wise design of the nanoparticulate systems to overcome the cellular and intracellular alterations underlying the resistance is imperative...
July 29, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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