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https://www.readbyqxmd.com/read/28436164/synthesis-and-sar-study-of-novel-anticancer-protoflavone-derivatives-investigation-of-cytotoxicity-and-interaction-with-the-abcb1-and-abcg2-multidrug-efflux-transporters
#1
Balázs Dankó, Szilárd Tóth, Ana Martins, Vágvölgyi Máté, Norbert Kúsz, Joseph Molnár, Fang-Rong Chang, Yang-Chang Wu, Gergely Szakács, Attila Hunyadi
There is a constant need for new therapies against multidrug resistant (MDR) cancer. Natural compounds represent a promising class of novel anticancer agents. Recently, we have shown that protoflavones display activity in multidrug resistant cancer cell lines overexpressing the drug efflux pump P-glycoprotein. In the present study, 52 protoflavones, including 22 new derivatives were synthesized and tested against a panel of sensitive parental cells and their MDR derivatives obtained by transfection with the human ABCB1 or ABCG2 genes, or by adaptation to chemotherapeutics...
April 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28432589/expression-and-function-of-abcg2-and-xiap-in-glioblastomas
#2
Ivette F Emery, Archana Gopalan, Stephanie Wood, Kin-Hoe Chow, Chiara Battelli, Joshy George, Hagen Blaszyk, Jeffrey Florman, Kyuson Yun
Despite multimodal treatment that includes surgery, radiation and chemotherapy, virtually all glioblastomas (GBM) recur, indicating that these interventions are insufficient to eradicate all malignant cells. To identify potential new therapeutic targets in GBMs, we examined the expression and function of proteins that are associated with therapy resistance and cancer cell survival. We measured the expression of eight such proteins in 50 GBM samples by immunohistochemistry and analyzed patient survival. We report that GBM patients with high expression of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than those with low expression...
April 21, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28430649/abcg2-and-ncf4-polymorphisms-are-associated-with-clinical-outcomes-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#3
Duo Liu, Nan Wu, Haiming Sun, Mei Dong, Tianzhu Guo, Peng Chi, Guofu Li, Donglin Sun, Yan Jin
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427160/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#4
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417924/novel-nano-therapeutic-approach-actively-targets-human-ovarian-cancer-stem-cells-after-xenograft-into-nude-mice
#5
Amoura Abou-ElNaga, Ghada Mutawa, Ibrahim M El-Sherbiny, Hassan Abd-ElGhaffar, Ahmed A Allam, Jamaan Ajarem, Shaker A Mousa
The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian tumors resides in a tiny population of cancer cells known as ovarian cancer stem cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX) against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an emulsion solvent evaporation method, supported by incorporation of folic acid (FA) as the ligand...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416605/photodynamic-therapy-using-photosensitizer-encapsulated-polymeric-nanoparticle-to-overcome-atp-binding-cassette-transporter-subfamily-g2-function-in-pancreatic-cancer
#6
Yoon Jin Roh, Ju Hee Kim, In-Wook Kim, Kun Na, Jae Myung Park, Myung-Gyu Choi
Chlorin-based photosensitizers are commonly used in photodynamic therapy (PDT).  These drugs are effluxed by cell-membrane transporters, such as the ATP-binding cassette subfamily G member 2 (ABCG2). PDT efficacy is limited in tumor cells expressing high levels of these proteins. Pancreatic cancer cell lines AsPC-1 and MIA PaCa-2, which have high and low ABCG2 expression, respectively, were used and ABCG2-overexpressing MIA PaCa-2 cells were generated. We compared PDT efficacy between Chlorin e6 (Ce6) and cationic photosensitizer-encapsulated polymeric nanoparticle (PS-pNP) which is comprised with Ce6, polyethylene glycol and polyethylenimine...
April 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28414325/hedgehog-signaling-pathway-affects-the-sensitivity-of-hepatoma-cells-to-drug-therapy-through-the-abcc1-transporter
#7
Jia Ding, Xiao-Tian Zhou, Hao-Yu Zou, Jian Wu
The poor response to drug therapy often seen in hepatocellular carcinoma requires insight into the molecular interplay responsible for intrinsic or acquired drug resistance. We previously demonstrated that the CD133(-)/EpCAM(-) subpopulation of the Huh-7 hepatoma cell line features aberrant activation of the hedgehog signaling (Hh) pathway and chemoresistance. The prevailing hypothesis of the present study is that hedgehog signaling may govern expression of ATP-binding cassette (ABC) transporters, which are responsible for drug resistance in the CD133(-)/EpCAM(-) subpopulation...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28411177/expression-of-mrp1-and-abcg2-is-associated-with-adverse-clinical-outcomes-of-the-papillary-thyroid-carcinoma-with-a-solid-component
#8
Ryuji Ohashi, Kiyoko Kawahara, Shigeki Namimatsu, Ritsuko Okamura, Takehito Igarashi, Iwao Sugitani, Zenya Naito
Solid variant of papillary thyroid carcinoma is characterized by a solid component (SC) retaining classical cytological features of papillary thyroid carcinoma (PTC). Despite some controversies, PTC cases with SC (PTCSC) have poor prognosis compared to well-differentiated PTC. We investigated if cancer stem cells (CSC) may have a role in pathogenesis of PTCSC. PTCSC tumors (n=27) was histologically represented by mixture of papillary component (PC) and varying degree of SC involving 10-85% of the tumor. Immunohistochemical expression of CSC markers ABCG2 and MRP1, and HBME1 and CK19 was compared between SC and PC within each tumor in association with clinicopathological parameters...
April 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28404967/gli1-mediated-regulation-of-side-population-is-responsible-for-drug-resistance-in-gastric-cancer
#9
Beiqin Yu, Dongsheng Gu, Xiaoli Zhang, Jianfang Li, Bingya Liu, Jingwu Xie
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Chemotherapy is frequently used for gastric cancer treatment. Most patients with advanced gastric cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for cancer relapse following chemotherapy will help design new ways to treat gastric cancer. In this study, we revealed that the residual cancer cells following treatment with chemotherapeutic reagent cisplatin have elevated expression of hedgehog target genes GLI1, GLI2 and PTCH1, suggestive of hedgehog signaling activation...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402161/ein2-mediated-signaling-is-involved-in-pre-invasion-defense-in-nicotiana-benthamiana-against-potato-late-blight-pathogen-phytophthora-infestans
#10
Soriya Rin, Yuri Mizuno, Yusuke Shibata, Mayuka Fushimi, Shinpei Katou, Ikuo Sato, Sotaro Chiba, Kazuhito Kawakita, Daigo Takemoto
Nicotiana benthamiana ABCG1 and ABCG2 are ABC transporters which are probably involved in the export of capsidiol, the major phytoalexin of Nicotiana species. While capsidiol export by these transporters plays an essential role in post-invasion defense against Phytophthora infestans, they also export unidentified antimicrobial compound(s) involved in pre-invasion defense. In this study, promoter activity of NbABCG2 (Pabcg2a) was analyzed using a GFP marker. Expression of GFP under the control of Pabcg2a was significantly increased by co-expression with the INF1 elicitor from P...
April 12, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28397046/targeting-bcrp-abcg2-by-rna-interference-enhances-the-chemotherapy-sensitivity-of-human-colon-cancer-side-population-cells
#11
Jun Hu, Jian Li, Xin Yue, Jia-Cang Wang, Jun-Feng Wang, Jian-Zhong Liu, Da-Lu Kong
Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics. This study isolated side population (SP) cells from a colon cancer cell line (Colo-320) and examined their self-renewal and differentiation abilities. Compared to non-SP (NSP) cells, SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies. Additionally, more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28385543/rosuvastatin-pharmacokinetics-in-asian-and-white-subjects-wild-type-for-both-oatp1b1-and-bcrp-under-control-and-inhibited-conditions
#12
Hsin-Fang Wu, Nadya Hristeva, Jae Chang, Xiaorong Liang, Ruina Li, Lynda Frassetto, Leslie Z Benet
The FDA recommends rosuvastatin dosage reductions in Asian patients because pharmacokinetic studies have demonstrated an approximate two-fold increase in median exposure to rosuvastatin in Asian subjects when compared to Caucasian controls. Yet, no explanation for this ethnic difference has been confirmed. Here we show that rosuvastatin exposure in Asians and Whites does not differ significantly when all subjects are wildtype carriers for both Solute Carrier Organic anion transporter1B1 *1a and ATP Binding Cassette Subfamily G Member 2 c...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28383763/upregulated-mir-132-in-lgr5-gastric-cancer-stem-cell-like-cells-contributes-to-cisplatin-resistance-via-sirt1-creb-abcg2-signaling-pathway
#13
Lanfang Zhang, Xiaohe Guo, Dezhong Zhang, Yingying Fan, Lei Qin, Shuping Dong, Lanfang Zhang
Cisplatin resistance has long been a major problem that restricts its use. A novel paradigm in tumor biology suggests that gastric tumor chemo-resistance is driven by gastric cancer stem cell-like (GCSCs). Growing evidence has indicated that microRNAs (miRNAs) contributes to chemo-resistance in gastric cancer (GC). Here, Lgr5(+) cells derived from gastric cancer cell lines displayed stem cell-like features. Flow cytometry demonstrated the presence of a variable fraction of Lgr5 in 19 out of 20 GC specimens...
April 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28383515/abc-transport-proteins-in-cardiovascular-disease-a-brief-summary
#14
REVIEW
Toni Schumacher, Ralf A Benndorf
Adenosine triphosphate (ATP)-binding cassette (ABC) transporters may play an important role in the pathogenesis of atherosclerotic vascular diseases due to their involvement in cholesterol homeostasis, blood pressure regulation, endothelial function, vascular inflammation, as well as platelet production and aggregation. In this regard, ABC transporters, such as ABCA1, ABCG5 and ABCG8, were initially found to be responsible for genetically-inherited syndromes like Tangier diseases and sitosterolemia. These findings led to the understanding of those transporter's function in cellular cholesterol efflux and thereby also linked them to atherosclerosis and cardiovascular diseases (CVD)...
April 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28381801/association-of-single-nucleotide-polymorphisms-in-stat3-abcb1-and-abcg2-with-stomatitis-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-sunitinib-a-retrospective-analysis-in-japanese-patients
#15
Aimi Watanabe, Kazuhiro Yamamoto, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Hideaki Miyake, Masato Fujisawa, Tsutomu Nakagawa, Ikuko Yano, Midori Hirai
Signal transducer and activator of transcription (STAT) 3 is a key factor in homeostasis of the oral mucosa by regulating the production of inflammatory cytokines. Sunitinib is a substrate of P-glycoprotein (multidrug resistance (MDR)-1/ABCB1) and breast-cancer resistance protein (BCRP/ABCG2). In this retrospective study, we evaluated the association between sunitinib-induced stomatitis and STAT3, ABCB1, and ABCG2 polymorphisms in patients with metastatic renal cell carcinoma (mRCC). Fifty-two Japanese patients with RCC treated with sunitinib were retrospectively genotyped to elucidate a potential association between STAT3, ABCB1, and ABCG2 polymorphisms and stomatitis development...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28380010/application-of-jc1-for-non-toxic-isolation-of-cells-with-mdr-transporter-activity-by-flow-cytometry
#16
J Mario Wolosin, Aldo Zamudio, Zheng Wang
The DNA intercalating dye Hoechst 33342 or its close analog DCV are actively removed from cells by the multidrug resistance transporter ABCG2, a protein overexpressed in metastatic cells and somatic stem cells. In bivariate blue-red flow cytometry fluorescent plots active Hoechst or DCV efflux combined with a concentration dependent bathochromic shifts of these nuclear dyes leads to the segregation of the transporter-rich cells into a distinct cell cohort tilted towards the shorter wavelength axis of the plot, the cohort is generically known as the side population (SP)...
2017: PloS One
https://www.readbyqxmd.com/read/28373423/new-and-old-genes-associated-with-topotecan-resistance-development-in-ovarian-cancer-cell-lines
#17
Andrzej Klejewski, Monika Świerczewska, Katarzyna Zaorska, Maciej Brązert, Michał Nowicki, Maciej Zabel, Radosław Januchowski
BACKGROUND: Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance. Topotecan is a drug used as second-line chemotherapy for this cancer type. We analyzed development of topotecan resistance in ovarian cancer cell lines. MATERIALS AND METHODS: A chemosensitivity assay, MTT test, was performed to assess drug resistance. Quantitative polymerase chain reaction (Q-PCR) assays were performed to determine ABCB1, ABCG2, ALDH1A1, IFIH1, SAMD4 and EPHA3 gene expression...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28370217/the-sensitivity-of-glioma-cells-to-pyropheophorbide-%C3%AE-methyl-ester-mediated-photodynamic-therapy-is-enhanced-by-inhibiting-abcg2
#18
Li Pan, Haidan Lin, Si Tian, Dingqun Bai, Yuhan Kong, Lehua Yu
BACKGROUND AND OBJECTIVE: To study the mechanisms of human glioblastoma cell resistance to methyl ester pyropheophorbide-a-mediated photodynamic therapy (MPPa-PDT) and the relationship between the cells and adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2). STUDY DESIGN/MATERIALS AND METHODS: The sensitivity of four human glioma cell lines (U87, A172, SHG-44, and U251) to MPPa-PDT was detected with a CCK-8 assay. Cell apoptosis, intracellular MPPa, and singlet oxygen were tested with flow cytometry...
March 29, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/28367588/effect-of-long-term-in-vitro-lithium-exposure-on-mrna-levels-of-claudin-3-cyp1a1-abcg2-and-gstm3-genes-in-the-hcmec-d3-human-brain-endothelial-cell-line
#19
Ramzi Shawahna, Kayathiri Ganeshamoorthy, Luo Huilong, Jean-Michel Scherrmann, Pierre-Olivier Couraud, Xavier Declèves
BACKGROUND AND OBJECTIVES: Lithium chloride (LiCl) has been shown to improve the tightness of brain endothelial cell monolayers in vitro by inhibition of the GSK-3β enzyme, activation of the Wnt/beta-catenin pathway and regulation of tight junction (TJ) protein expression. However, the effect of LiCl on the drug transporters and drug-metabolizing enzymes has not been addressed so far. The hCMEC/D3 cell line is a validated in vitro BBB model expressing transporters and drug-metabolizing enzymes (phase 1 and 2)...
April 3, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28363522/reversal-of-multidrug-resistance-by-marsdenia-tenacissima-and-its-main-active-ingredients-polyoxypregnanes
#20
Kenneth K W To, Xu Wu, Chun Yin, Stella Chai, Sheng Yao, Onat Kadioglu, Thomas Efferth, Yang Ye, Ge Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs...
May 5, 2017: Journal of Ethnopharmacology
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