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https://www.readbyqxmd.com/read/29138856/differentially-expressed-proteins-in-the-human-esophageal-cancer-cell-line-eca%C3%A2-109-in-the-presence-and-absence-of-gemcitabine
#1
Zenghuang Ma, Xiaojie Xue
The present study aimed to screen and study the roles of differentially expressed proteins in the human esophageal cancer cell line Eca‑109, in the presence and absence of gemcitabine (GEM). The 3‑(4,5)‑dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method was used to assay the vitality of the Eca‑109 cells following treatment with GEM (1‑16 µg/ml). The cell apoptosis was measured by using fluorescence activated cell sorting. The proteins in the treated Eca‑109 cells were extracted, validated, and assayed via two‑dimensional gel electrophoresis combined with matrix‑assisted laser desorption/ionization time of flight mass spectrometry (MALDI‑TOF‑MS)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29137334/the-coffee-diterpene-kahweol-enhances-sensitivity-to-sorafenib-in-human-renal-carcinoma-caki-cells-through-down-regulation-of-mcl-1-and-c-flip-expression
#2
Kyoung-Jin Min, Hee Jung Um, Jee In Kim, Taeg Kyu Kwon
Sorafenib is approved for the treatment of hepatocellular carcinoma (HCC) and advanced renal cell carcinoma (RCC). However, low tumor response and side effects have been widely reported. Therefore, to improve the efficacy of sorafenib, we investigated whether combined treatment with sorafenib and kahweol, the coffee-specific diterpene, has a synergistic effect on apoptotic cell death. Combined treatment with sorafenib and kahweol markedly induced caspase-mediated apoptosis in renal carcinoma Caki cells. Combined treatment with sorafenib and kahweol induced down-regulation of Mcl-1 and c-FLIP expression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137317/mcl-1-stabilization-confers-resistance-to-taxol-in-human-gastric-cancer
#3
Wu Shuang, Lili Hou, Yan Zhu, Qun Li, Wanglai Hu
Taxol has been extensively used as an antineoplastic drug to treat human gastric cancer. However, the acquired drug resistance invariably develops and greatly limits the therapeutic efficacy of Taxol. Identification of the underlying resistance mechanisms may inform the development of new therapies of gastric cancers to Taxol treatment. Here we report that upregulation of Mcl-1 (Myeloid cell leukemia-1) confers acquired resistance to Taxol in human gastric cancer. Mcl-1 is shown to be stabilized in Taxol -resistant gastric cancer cells because of the hyper-activation of the PI3K/Akt signaling pathway...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#4
Xiaoqian Ma, Cejun Yang, Juan Zhang, Jia Wang, Wei Li, Chang Xu, Pengfei Rong, Bin Ye, Minghua Wu, Jianhui Jiang, Shounan Yi, Wei Wang
BACKGROUND: Neonatal pig islet-like cell clusters (NICC) are an attractive source of insulin-producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC after their transplantation due to apoptosis resulted from islet isolation and instant blood-mediated inflammatory reaction remains to be overcome. METHODS: EGM2 medium depleted with hydrocortisone and supplemented with 50 mmol/L isobutylmethylxanthine, 10 mmol/L nicotinamide, and 10 mmol/L glucose was used to culture NICC at day 1, the day after isolation and changed every other day...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29128627/inhibition-of-jak1-by-microrna-708-promotes-sh-sy5y-neuronal-cell-survival-after-oxygen-and-glucose-deprivation-and-reoxygenation
#5
Chao Huang, Haitao Zhou, Xiangyang Ren, Junfang Teng
MicroRNAs mediates gene expression in various diseases. Studies have shown that aberrant expression of miRNAs affected cerebral protection. In this study, we have investigated the effects of microRNA-708 (miR-708) on cell survival of oxygen and glucose-deprived reoxygenation (OGD/R) human neuroblastoma cells (SH-SY5Y) and explored whether miR-708 inhibited neuronal death by targeting JAK1. In vitro model of ischemia was used to investigate the neuroprotective functions of miR-708. MiR-708 mimics/siJAK1 transfected SH-SY5Y cells were treated with OGD...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29122991/maternal-embryonic-leucine-zipper-kinase-is-a-novel-target-for-proliferation-associated-high-risk-myeloma
#6
Arnold Bolomsky, Roy Heusschen, Karin Schlangen, Kathrin Stangelberger, Joséphine Muller, Wolfgang Schreiner, Niklas Zojer, Jo Caers, Heinz Ludwig
Treatment of high-risk patients is a major challenge in multiple myeloma. This is especially true for patients assigned to the gene-expression-profiling defined proliferation subgroup. Although recent efforts have identified some key players of proliferative myeloma, genetic interactions and players that can be targeted with clinically effective drugs have to be identified to overcome the poor prognosis of these patients. We therefore examined maternal embryonic leucine zipper kinase (MELK) for its implications in hyper-proliferative myeloma and analysed the activity of the MELK inhibitor OTSSP167 in vitro and in vivo...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29113504/enhancement-of-chemosensitivity-by-simultaneously-silencing-of-mcl-1-and-survivin-genes-using-small-interfering-rna-in-human-myelomonocytic-leukaemia
#7
Mahdi Jafarlou, Dariush Shanehbandi, Parvin Dehghan, Behzad Mansoori, F Othman, Behzad Baradaran
Acute myeloid leukaemia (AML) is a genetically heterogeneous, severe and rapidly progressing disease triggered by blocking granulocyte or monocyte differentiation and maturation. Overexpression of myeloid cell leukaemia-1 (Mcl-1) and Survivin is associated with drug resistance, tumour progression and inhibition of apoptotic mechanisms in leukaemia and several cancers. In the present study, we examined the combined effect of etoposide and dual siRNA-mediated silencing of Mcl-1 and Survivin on U-937 AML cells...
November 7, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29111786/active-hexose-correlated-compound-ahcc-inhibits-the-proliferation-of-ovarian-cancer-cells-by-suppressing-signal-transducer-and-activator-of-transcription-3-stat3-activation
#8
Jin Young Choi, Seul Lee, Sun-Mi Yun, Dong Hoon Suh, Kidong Kim, Jae Hong No, Eun-Hwan Jeong, Yong Beom Kim
The purpose of this study was to investigate the antiproliferative effect of active hexose correlated compound (AHCC), derived from basidiomycete mushroom culture, on ovarian cancer cell lines. An in vitro growth inhibition assay was performed using AHCC in ovarian cancer cell lines. Western blotting was performed to investigate the mechanism of the observed antiproliferative effect of AHCC. We identified that ovarian cancer cell viability was significantly reduced through treatment with AHCC compared to that in the control...
November 7, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29110251/inhibition-of-two-gastric-cancer-cell-lines-induced-by-fucoxanthin-involves-downregulation-of-mcl-1-and-stat3
#9
Rui-Xue Yu, Rui-Tao Yu, Zhong Liu
Fucoxanthin is a natural carotenoid that had never been previously demonstrated to have anti-tumor effect on human gastric adenocarcinoma SGC-7901 or BGC-823 cells. Here it was found to inhibit proliferation and induce apoptosis through JAK/STAT signal pathway in these cells; the mechanism by which this occurred was investigated. We find that fucoxanthin significantly increased the number of apoptotic cells by propidium iodide (PI) dye staining and flow cytometry. Fucoxanthin (50 or 75 μM) induced SGC-7901 cells cycle arrest at S phase, while BGC-823 cells arrest at G2/M phase...
November 6, 2017: Human Cell
https://www.readbyqxmd.com/read/29109414/involvement-of-autophagy-in-the-outcome-of-mitotic-catastrophe
#10
Irina V Sorokina, Tatiana V Denisenko, Gabriela Imreh, Pyotr A Tyurin-Kuzmin, Vitaliy O Kaminskyy, Vladimir Gogvadze, Boris Zhivotovsky
Evading cell death is a major driving force for tumor progression that is one of the main problems in current cancer research. Mitotic catastrophe (MC) represents attractive platform compromising tumor resistance to current therapeutic modalities. MC appeared as onco-suppressive mechanism and is defined as a stage driving the cell to an irreversible destiny, i.e. cell death via apoptosis or necrosis. Our study highlights that MC induction in colorectal carcinoma cell lines ultimately leads to the autophagy followed by apoptosis...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107111/entinostat-reverses-cisplatin-resistance-in-esophageal-squamous-cell-carcinoma-via-down-regulation-of-multidrug-resistance-gene-1
#11
Xiao-Ping Huang, Xuan Li, Min-Yi Situ, Li-Yun Huang, Jun-Ye Wang, Tian-Cheng He, Qi-Hang Yan, Xiu-Ying Xie, Yu-Jing Zhang, Yuan-Hong Gao, Yu-Hong Li, Tie-Hua Rong, Jian-Hua Fu, Qing-Qing Cai, Ming-Rong Wang
Cisplatin resistance frequently occurs in esophageal squamous cell carcinoma (ESCC). The underlying mechanism for cisplatin resistance in ESCC remains largely obscure. Here we report that entinostat reversed cisplatin resistance in ESCC both in vitro and in vivo by induction of apoptosis and inhibition of cell proliferation, accompanied by a decrease of multidrug resistance gene 1 (MDR1), P-Src, Mcl-1, Cyclin D1 and an increase of cleaved PARP. MDR1 expression was associated with worsen survival of ESCC patients with cisplatin-based chemotherapy...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29099483/the-bcl-2-arbiters-of-apoptosis-and-their-growing-role-as-cancer-targets
#12
REVIEW
Jerry M Adams, Suzanne Cory
Impaired apoptosis plays a central role in cancer development and limits the efficacy of conventional cytotoxic therapies. Deepening understanding of how opposing factions of the BCL-2 protein family switch on apoptosis and of their structures has driven development of a new class of cancer drugs that targets various pro-survival members by mimicking their natural inhibitors, the BH3-only proteins. These 'BH3 mimetic' drugs seem destined to become powerful new weapons in the arsenal against cancer. Successful clinical trials of venetoclax/ABT-199, a specific inhibitor of BCL-2, have led to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies...
November 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29096333/distinct-ephb4-mediated-mechanisms-of-apoptotic-and-resistance-to-dasatinib-in-human-chronic-myeloid-leukemia-and-k562-cell-lines
#13
Wei-Hong Zhao, Bin-Tao Huang, Jian-Yu Zhang, Qing-Chun Zeng
OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29093082/according-to-hcv-infection-stage-il-7-plus-4-1bb-triggering-alone-or-combined-with-pd-1-blockade-increases-traf1-low-hcv-specific-cd8-cell-reactivity
#14
Elia Moreno-Cubero, Dolores Subirá, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid, Antonio Madejón, Joaquín Miquel, Antonio Olveira, Alejandro González-Praetorius, Javier García-Samaniego, Juan-Ramón Larrubia
Hepatitis C virus (HCV)-specific CD8(+) T cells suffer a progressive exhaustion during persistent HCV infection (PI). This process could involve the positive immune checkpoint 4-1BB/4-1BBL, through the loss of its signal transducer TRAF1. To address this issue, peripheral HCV-specific CD8(+) T cells (Pentamer(+)/CD8(+)) from patients with PI and resolved infection after treatment (RI) were studied. Duration of HCV infection and liver fibrosis progression rate inversely correlated with the likelihood of detecting peripheral pentamer(+)/CD8(+) cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29090688/protein-sensing-and-discrimination-using-highly-functionalised-ruthenium-ii-tris-bipyridyl-protein-surface-mimetics-in-an-array-format
#15
Sarah H Hewitt, Andrew J Wilson
Ruthenium(ii) tris(bipyridyl) protein surface mimetics are used in an array format to sense and discriminate proteins including therapeutically relevant targets, hDM2 and MCL-1, using linear discriminant analysis (LDA).
November 1, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29074603/concurrent-inhibition-of-pim-and-flt3-kinases-enhances-apoptosis-of-flt3-itd-acute-myeloid-leukemia-cells-through-increased-mcl-1-proteasomal-degradation
#16
Shivani Kapoor, Karthika Natarajan, Patrick R Baldwin, Kshama A Doshi, Rena G Lapidus, Trevor J Mathias, Mario Scarpa, Rossana Trotta, Eduardo Davila, Manfred Kraus, Dennis Huszar, Adriana E Tron, Danilo Perrotti, Maria R Baer
PURPOSE: fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29069828/neutrophils-protect-lymphoma-cells-against-cytotoxic-and-targeted-therapies-through-cd11b-icam-1-binding
#17
Taghreed Hirz, Eva-Laure Matera, Kamel Chettab, Lars Petter Jordheim, Doriane Mathé, Anne Evesque, Justine Esmenjaud, Gilles Salles, Charles Dumontet
Innate immune cells constitute a substantial proportion of the cells within the tumor microenvironment. Besides the contribution of the microenvironment to tumor proliferation and survival, there is direct evidence that interactions between tumor cells and their microenvironment alter sensitivity to anti-cancer agents. Neutrophils, a key player in the innate immune system, have been less studied than many other immune cells regarding their impact on cancer cell response to anti-cancer agents. In our 2D and 3D coculture systems, human neutrophils and differentiated HL60 cells attenuated the sensitivity of various lymphoma cell lines to several anti-cancer agents, including targeted therapies...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29068469/bag3-dependent-expression-of-mcl-1-confers-resistance-of-mutant-kras-colon-cancer-cells-to-the-hsp90-inhibitor-auy922
#18
Chun Yan Wang, Su Tang Guo, Amanda Croft, Xu Guang Yan, Lei Jin, Xu Dong Zhang, Chen Chen Jiang
Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance remains an obstacle for the potential application of the inhibitor in the treatment of the disease. Here we report that Mcl-1 is important for survival of colon cancer cells in the presence of AUY922. Mcl-1 was upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922-induced apoptosis. This was due to its increased stability mediated by Bcl-2-associated athanogene domain 3 (BAG3), which was also increased in resistant colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic endoplasmic reticulum (ER) stress...
October 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29061914/therapeutics-targeting-bcl-2-in-hematological-malignancies
#19
REVIEW
Astrid Ruefli-Brasse, John C Reed
Members of the B-cell lymphoma 2 (BCL-2) gene family are attractive targets for cancer therapy as they play a key role in promoting cell survival, a long-since established hallmark of cancer. Clinical utility for selective inhibition of specific anti-apoptotic Bcl-2 family proteins has recently been realized with the Food and Drug Administration (FDA) approval of venetoclax (formerly ABT-199/GDC-0199) in relapsed chronic lymphocytic leukemia (CLL) with 17p deletion. Despite the impressive monotherapy activity in CLL, such responses have rarely been observed in other B-cell malignancies, and preclinical data suggest that combination therapies will be needed in other indications...
October 23, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29057925/induction-of-synthetic-lethality-in-idh1-mutated-gliomas-through-inhibition-of-bcl-xl
#20
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Yiru Zhang, Chang Shu, Takashi Tsujiuchi, Matei A Banu, Franklin Garcia, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Markus D Siegelin
Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H), which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2-HG). In six model systems, including patient-derived stem cell-like glioblastoma cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1-mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL inhibition-mediated apoptosis...
October 20, 2017: Nature Communications
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