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gemcitabine resistance

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https://www.readbyqxmd.com/read/27919951/rho-associated-protein-kinase-rock-inhibitors-inhibit-survivin-expression-and-sensitize-pancreatic-cancer-stem-cells-to-gemcitabine
#1
Hiroyuki Takeda, Masashi Okada, Shuhei Suzuki, Kenta Kuramoto, Hirotsugu Sakaki, Hikaru Watarai, Tomomi Sanomachi, Shizuka Seino, Takashi Yoshioka, Chifumi Kitanaka
BACKGROUND: Targeting pathways regulating survivin expression, which has been implicated in multidrug resistance of cancer cells, is a promising strategy to overcome cancer chemoresistance. To date, the role of rho-associated protein kinases (ROCKs) in survivin expression remains largely unknown. MATERIALS AND METHODS: The effects of ROCK inhibitors Y-27632 and fasudil on survivin expression and cell viability were determined by immunoblot analysis and dye exclusion, respectively, in PANC-1 CSLC, a cancer stem cell line derived from a serum-cultured, gemcitabine-sensitive pancreatic cancer cell line, PANC-1...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27909718/enzalutamide-inhibits-proliferation-of-gemcitabine-resistant-bladder-cancer-cells-with-increased-androgen-receptor-expression
#2
Koji Kameyama, Kengo Horie, Kosuke Mizutani, Taku Kato, Yasunori Fujita, Kyojiro Kawakami, Toshio Kojima, Tatsuhiko Miyazaki, Takashi Deguchi, Masafumi Ito
Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling...
November 24, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27906635/a-specific-inhibitor-of-lactate-dehydrogenase-overcame-the-resistance-toward-gemcitabine-in-hypoxic-mesothelioma-cells-and-modulated-the-expression-of-the-human-equilibrative-transporter-1
#3
Elisa Giovannetti, Leticia G Leon, Valentina E Gómez, Paolo A Zucali, Filippo Minutolo, Godefridus J Peters
Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27903751/microdose-induced-drug-dna-adducts-as-biomarkers-of-chemotherapy-resistance-in-humans-and-mice
#4
Maike Zimmermann, Si-Si Wang, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Ted Ognibene, Hongyuan Yang, Susan Airhart, Kenneth W Turteltaub, George D Cimino, Clifford G Tepper, Alexandra Drakaki, Karim Chamie, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27897011/a-spatiotemporal-model-to-simulate-chemotherapy-regimens-for-heterogeneous-bladder-cancer-metastases-to-the-lung
#5
Kimberly R Kanigel Winner, James C Costello
Tumors are composed of heterogeneous populations of cells. Somatic genetic aberrations are one form of heterogeneity that allows clonal cells to adapt to chemotherapeutic stress, thus providing a path for resistance to arise. In silico modeling of tumors provides a platform for rapid, quantitative experiments to inexpensively study how compositional heterogeneity contributes to drug resistance. Accordingly, we have built a spatiotemporal model of a lung metastasis originating from a primary bladder tumor, incorporating in vivo drug concentrations of first-line chemotherapy, resistance data from bladder cancer cell lines, vascular density of lung metastases, and gains in resistance in cells that survive chemotherapy...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27893715/tgf%C3%AE-promotes-mesenchymal-phenotype-of-pancreatic-cancer-cells-in-part-through-epigenetic-activation-of-vav1
#6
P-H Huang, P-J Lu, L-Y Ding, P-C Chu, W-Y Hsu, C-S Chen, C-C Tsao, B-H Chen, C-T Lee, Y-S Shan, C-S Chen
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893326/randomized-prospective-biomarker-trial-of-ercc1-for-comparing-platinum-and-nonplatinum-therapy-in-advanced-non-small-cell-lung-cancer-ercc1-trial-et
#7
Siow Ming Lee, Mary Falzon, Fiona Blackhall, James Spicer, Marianne Nicolson, Abhro Chaudhuri, Gary Middleton, Samreen Ahmed, Jonathan Hicks, Barbara Crosse, Mark Napier, Julian M Singer, David Ferry, Conrad Lewanski, Martin Forster, Sally-Ann Rolls, Arrigo Capitanio, Robin Rudd, Natasha Iles, Yenting Ngai, Michael Gandy, Rachel Lillywhite, Allan Hackshaw
Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor...
November 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27888811/the-role-of-p53-in-cancer-drug-resistance-and-targeted-chemotherapy
#8
REVIEW
Karin Hientz, André Mohr, Dipita Bhakta-Guha, Thomas Efferth
Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab)...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#9
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885740/asp5878-a-selective-fgfr-inhibitor-to-treat-fgfr3-dependent-urothelial-cancer-with-or-without-chemoresistance
#10
Aya Kikuchi, Tomoyuki Suzuki, Taisuke Nakazawa, Masateru Iizuka, Ayako Nakayama, Tohru Ozawa, Minoru Kameda, Nobuaki Shindoh, Tadashi Terasaka, Masaaki Hirano, Sadao Kuromitsu
FGF/FGFR gene aberrations such as amplification, mutation and fusion are associated with many types of human cancers including urothelial cancer. FGFR kinase inhibitors are expected to be a targeted therapy for urothelial cancer harboring FGFR3 gene alternations. ASP5878, a selective inhibitor of FGFR1, 2, 3 and 4 under clinical investigation, selectively inhibited cell proliferation of urothelial cancer cell lines harboring FGFR3 point mutation or fusion (UM-UC-14, RT-112, RT4 and SW 780) among 23 urothelial cancer cell lines...
November 25, 2016: Cancer Science
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#11
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27878232/involvement-of-bleomycin-hydrolase-and-poly-adp-ribose-polymerase-1-in-ubc9-mediated-resistance-to-chemotherapy-agents
#12
Yang Chen, Huixian Zhang, Qiyang He
Ubiquitin-conjugating protein 9 (Ubc9), the sole enzyme for sumoylation, plays critical roles in many physiological functions, such as DNA damage repair and genome integrity. Its overexpression led to poor prognosis and drug resistance in tumor chemotherapy. However, the underlying mechanism by which Ubc9 promotes tumor progress and influences the susceptibility to antitumor agents remains elusive. In this study, we used nine antitumor agents with distinct actions to explore Ubc9-mediated resistance in human breast carcinoma MCF-7 cells...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27858107/gemcitabine-dexamethasone-and-cisplatin-gdp-as-salvage-chemotherapy-for-patients-with-relapsed-or-refractory-peripheral-t-cell-lymphoma-not-otherwise-specified
#13
Fei Qi, Mei Dong, Xiaohui He, Yexiong Li, Weihu Wang, Peng Liu, Jianliang Yang, Lin Gui, Changgong Zhang, Sheng Yang, Shengyu Zhou, Yuankai Shi
Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014...
November 17, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27845899/bisdemethoxycurcumin-exerts-pro-apoptotic-effects-in-human-pancreatic-adenocarcinoma-cells-through-mitochondrial-dysfunction-and-a-grp78-dependent-pathway
#14
Haopeng Yang, Shengjun Fan, Yu An, Xin Wang, Yan Pan, Yilixiati Xiaokaiti, Jianhui Duan, Xin Li, Lu Tie, Min Ye, Xuejun Li
Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833395/establishment-of-various-biliary-tract-carcinoma-cell-lines-and-xenograft-models-for-appropriate-preclinical-studies
#15
Hidenori Ojima, Seri Yamagishi, Kazuaki Shimada, Tatsuhiro Shibata
We recently reported several driver genes of biliary tract carcinoma (BTC) that are known to play important roles in oncogenesis and disease progression. Although the need for developing novel therapeutic strategies is increasing, there are very few BTC cell lines and xenograft models currently available for conducting preclinical studies. Using a total of 88 surgical BTC specimens and 536 immunodeficient mice, 28 xenograft models and 13 new BTC cell lines, including subtypes, were established. Some of our cell lines were found to be resistant to gemcitabine, which is currently the first choice of treatment, thereby allowing highly practical preclinical studies to be conducted...
October 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27797249/impact-of-the-copper-transporter-protein-1-ctr1-polymorphism-on-adverse-events-among-advanced-nonsmall-cell-lung-cancer-patients-treated-with-a-carboplatin-gemcitabine-regimen
#16
Siriluk Kumpiro, Virote Sriuranpong, Nutthada Areepium
BACKGROUND: Platinum-based regimens are effective treatments for advanced non-small cell lung cancer (NSCLC), but the five-year survival rate is still less than 20%. One possible factor appears to be resistance involving polymorphisms in the CTR1 gene which plays an importance role in accumulation of platinum in the cytoplasm. PURPOSE: To establish both prevalence of CTR1 polymorphism and its impact on treatment related toxicity in Thai advanced NSCLC patients. MATERIALS AND METHODS: Thirty-two advanced NSCLC participants received carboplatin and gemcitabine during January to June 2016 at King Chulalongkorn Memorial Hospital (KCMH) were recruited for analysis of the CTR1 rs12686377 genotype...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27793935/antitumor-effects-of-eribulin-mesylate-in-gemcitabine-resistant-pancreatic-cancer-cell-lines
#17
Yuka Takezaki, Tsutomu Namikawa, Tsuyoshi Koyama, Eri Munekage, Masaya Munekage, Hiromichi Maeda, Hiroyuki Kitagawa, Kazuhiro Hanazaki
BACKGROUND/AIM: One reason of poor survival rate of patients with pancreatic cancer is the development of chemoresistance. The aim of the present study was to investigate the effects of eribulin mesylate in gemcitabine-refractory advanced pancreatic cancer cell lines. MATERIALS AND METHODS: Three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27792935/tissue-transglutaminase-activates-cancer-associated-fibroblasts-and-contributes-to-gemcitabine-resistance-in-pancreatic-cancer
#18
Jiyoon Lee, Bakhtiyor Yakubov, Cristina Ivan, David R Jones, Andrea Caperell-Grant, Melissa Fishel, Horacio Cardenas, Daniela Matei
Resistance to chemotherapy is a hallmark of pancreatic ductal adenocarcinoma (PDA) and has been partly attributed to the dense desmoplastic stroma, which forms a protective niche for cancer cells. Tissue transglutaminase (TG2), a Ca(2+)-dependent enzyme, is secreted by PDA cells and cross-links proteins in the tumor microenvironment (TME) through acyl-transfer between glutamine and lysine residues, promoting PDA growth. The objective of the current study was to determine whether secreted TG2 by PDA cells alters the response of pancreatic tumors to gemcitabine...
November 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27785603/linc-ror-confers-gemcitabine-resistance-to-pancreatic-cancer-cells-via-inducing-autophagy-and-modulating-the-mir-124-ptbp1-pkm2-axis
#19
Chenggang Li, Zhiming Zhao, Zhipeng Zhou, Rong Liu
PURPOSE: In this study, we investigated the regulation of linc-ROR on autophagy and gemcitabine resistance of pancreatic cancer cells and further studied the underlying involvement of the miR-124/PTBP1/PKM2 axis in this regulation. METHODS: Pancreatic cancer cell lines PANC-1 and MIAPaCa-2 cells were used as in vitro model. Autophagy was assessed by western blot of LC3 I/II and observation GFP-LC3 puncta. Cell viability was examined using CCK-8 assay. Cell apoptosis was examined by flow cytometric analysis of Annexin V/PI staining...
October 26, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27754848/nucleolin-targeting-impairs-the-progression-of-pancreatic-cancer-and-promotes-the-normalization-of-tumor-vasculature
#20
Maud-Emmanuelle Gilles, Federica Maione, Mélissande Cossutta, Gilles Carpentier, Laure Caruana, Sylvia Di Maria, Claire Houppe, Damien Destouches, Ksenya Shchors, Christopher Prochasson, Fabien Mongelard, Simona Lamba, Alberto Bardelli, Philippe Bouvet, Anne Couvelard, José Courty, Enrico Giraudo, Ilaria Cascone
Pancreatic cancer is a highly aggressive tumor, mostly resistant to the standard treatments. Nucleolin (NCL) is overexpressed in cancers and its inhibition impairs tumor growth. Herein we showed that NCL was overexpressed in human specimens of pancreatic ductal adenocarcinoma (PDAC) and that the overall survival significantly increased in patients with low levels of NCL. The NCL antagonist N6L strongly impaired the growth of primary tumors and liver metastasis in an orthotopic mouse model of PDAC (mPDAC). Similar anti-tumor effect of N6L has been observed in a highly angiogenic mouse model of pancreatic neuroendocrine tumor RIP-Tag2...
October 17, 2016: Cancer Research
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