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https://www.readbyqxmd.com/read/28526264/celecoxib-aggravates-cardiac-apoptosis-in-l-name-induced-pressure-overload-model-in-rats-immunohistochemical-determination-of-cardiac-caspase-3-mcl-1-bax-and-bcl-2
#1
Sarah M Mosaad, Sawsan A Zaitone, Abdelazim Ibrahim, Amani A El-Baz, Dina M Abo-Elmatty, Yasser M Moustafa
The mechanism of celecoxib cardiovascular adverse events was earlier investigated; yet in-depth investigations are needed to assess the involvement of its pro-apoptotic effect throughout this process. An in-vivo chronic rat model of pressure overload employing Nʷ-nitro-l-arginine methyl ester (L-NAME) was tested at different time intervals to ensure the occurrence of persistent myocardial apoptosis along with pressure overload. Seven groups of male Wistar rats were assigned as (i) distilled water; (ii-iv) L-NAME (60 mg/kg) for 6, 12 or 16 weeks; (v-vii) L-NAME [16 weeks] + celecoxib (25, 50 or 100 mg/kg), from week 13 to week 16...
May 16, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28522751/targeting-fbw7-as-a-strategy-to-overcome-resistance-to-targeted-therapy-in-non-small-cell-lung-cancer
#2
Mingxiang Ye, Yong Zhang, Xinxin Zhang, Jian-Bin Zhang, Pengyu Jing, Liang Cao, Nan Li, Xia Li, Libo Yao, Jian Zhang, Jian Zhang
Inhibition of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non-small cell lung cancer (NSCLC) patients with distinct clinicopathological features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/Erk-independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of anti-apoptotic protein MCL-1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#3
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28520795/birc6-mediates-imatinib-resistance-independently-of-mcl-1
#4
Denis O Okumu, Michael P East, Merlin Levine, Laura E Herring, Raymond Zhang, Thomas S K Gilbert, David W Litchfield, Yanping Zhang, Lee M Graves
Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL)...
2017: PloS One
https://www.readbyqxmd.com/read/28515282/talin-plays-a-critical-role-in-the-maintenance-of-the-regulatory-t-cell-pool
#5
Jane E Klann, Kelly A Remedios, Stephanie H Kim, Patrick J Metz, Justine Lopez, Lauren A Mack, Ye Zheng, Mark H Ginsberg, Brian G Petrich, John T Chang
Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1(fl/fl)Cd4(Cre) mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2Rα, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28511583/deciphering-the-crucial-residues-involved-in-heterodimerization-of-bak-peptide-and-anti-apoptotic-proteins-for-apoptosis
#6
Parthiban Marimuthu, Kalaimathy Singaravelu
B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of apoptosis, function via mitochondrial outer membrane permeabilization. The family members are involved in several stages of apoptosis regulation. The overexpression of the anti-apoptotic proteins leads to several cancer pathological conditions. This overexpression is modulated or inhibited by heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the hydrophobic groove present at the surface of anti-apoptotic proteins. Additionally, the heterodimerization displayed differences in binding affinity profile among the pro-apoptotic peptides binding to anti-apoptotic proteins...
May 16, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28503147/an-ethanolic-extract-of-ampelopsis-radix-exerts-anti-colorectal-cancer-effects-and-potently-inhibits-stat3-signaling-in-vitro
#7
Tao Su, Jing-Xuan Bai, Ying-Jie Chen, Xin-Ning Wang, Xiu-Qiong Fu, Ting Li, Hui Guo, Pei-Li Zhu, Yue Wang, Zhi-Ling Yu
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28502307/-knock-down-of-dab2-interacting-protein-dab2ip-promotes-proliferation-and-inhibits-apoptosis-of-bladder-cancer-cells
#8
Kai Zhang, Weiyi Wang, Kaijie Wu, Chen Ding, Jianning Zhu, Yiqing DU, Zhenfeng Guan, Xinyang Wang, Jinhai Fan
Objective To study the expression of DAB2 interacting protein (DAB2IP) in human bladder cancer tissues and analyze its relationship with pathological grade and clinical stage, and observe its role in drug resistance of bladder cancer cells. Methods The expression of DAB2IP in primary and recurrent bladder cancers was detected by immunohistochemical staining. RNA interference (RNAi) technique was used to down-regulate the expression of DAB2IP in 5637 and 253J bladder cancer cells. MTT assay and clone formation assay were performed to test the sensitivity of cancer cells to pirarubicin...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28499784/gsk-3-as-a-novel-prognostic-indicator-in-leukemia
#9
REVIEW
Peter P Ruvolo
While leukemias represent a diverse set of diseases with malignant cells derived from myeloid or lymphoid origin, a common feature is the dysregulation of signal transduction pathways that influence leukemogeneisis, promote drug resistance, and favor leukemia stem cells. Mutations in PI3K, PTEN, RAS, or other upstream regulators can activate the AKT kinase which has central roles in supporting cell proliferation and survival. A major target of AKT is Glycogen Synthase Kinase 3 (GSK3). GSK3 has two isoforms (alpha and beta) that were studied as regulators of metabolism but emerged as central players in cancer in the early 1990s...
May 8, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28493974/serum-%C3%AE-1-antitrypsin-aat-antagonizes-intrinsic-apoptosis-induction-in-neutrophils-from-patients-with-systemic-inflammatory-response-syndrome
#10
Theresia Sarabhai, Christoph Peter, Anne-Kathrin Bär, Joachim Windolf, Borna Relja, Sebastian Wesselborg, Thorsten Wahlers, Adnana Paunel-Görgülü
Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28493826/targeting-the-apoptotic-mcl-1-puma-interface-with-a-dual-acting-compound
#11
Jiyuan Liu, Zhen Tian, Nan Zhou, Xueying Liu, Chenyi Liao, Beilei Lei, Jianing Li, Shengyong Zhang, Hui Chen
Despite intensive efforts in the search for small molecules with anti-cancer activity, it remains challenging to achieve both high effectiveness and safety, since many agents lack the selectivity to only act on cancer cells. The interface of two apoptotic proteins, myeloid cell leukemia-1 (Mcl-1) and p53 upregulated modulator of apoptosis (PUMA), has been recently affirmed as a target for treating cancers, as the disruption of Mcl-1-PUMA binding can reduce cancer cell survival and protect normal cells from apoptosis...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28492347/the-soy-derived-peptide-vglycin-inhibits-the-growth-of-colon-cancer-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#12
Chang Gao, Rui Sun, Ya-Rong Xie, An-Li Jiang, Mei Lin, Min Li, Zheng-Wang Chen, Ping Zhang, Honglin Jin, Jue-Ping Feng
Vglycin, a novel natural polypeptide isolated from pea seeds, possesses antidiabetic properties. Our previous studies have shown that Vglycin can induce the differentiation of human colon adenocarcinoma cells. We aimed to determine the anticancer activity of Vglycin against colon cancer cells and to elucidate related apoptosis-inducing mechanisms. Treatment with purified Vglycin significantly reduced growth, viability, and colony formation of CT-26, SW480, and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating the expression of proliferating cell nuclear antigen...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28491825/hcmv-activation-of-erk-mapk-drives-a-multi-factorial-response-promoting-the-survival-of-infected-myeloid-progenitors
#13
Verity Kew, Mark Wills, Matthew Reeves
Viral binding and entry provides the first trigger of a cell death response and thus how human cytomegalovirus (HCMV) evades this - particularly during latent infection where a very limited pattern of gene expression is observed - is less well understood. It has been demonstrated that the activation of cellular signalling pathways upon virus binding promotes the survival of latently infected cells by the activation of cell encoded anti-apoptotic responses. In CD34+ cells, a major site of HCMV latency, ERK signalling is important for survival and we now show that the activation of this pathway impacts on multiple aspects of cell death pathways...
2017: Journal of Molecular Biochemistry
https://www.readbyqxmd.com/read/28491238/inhibition-of-mir-302-suppresses-hypoxia-reoxygenation-induced-h9c2-cardiomyocyte-death-by-regulating-mcl-1-expression
#14
Yao-Ching Fang, Chi-Hsiao Yeh
MicroRNAs play important roles in cell proliferation, differentiation, and apoptosis, and their expression influences cardiomyocyte apoptosis resulting from ischemia-induced myocardial infarction. Here, we determined the role of miR expression in cardiomyocyte apoptosis during hypoxia and reoxygenation. The rat cardiomyocyte cell line H9c2 was incubated for 3 h in normal or hypoxia medium, followed by reoxygenation for 24 h and transfection with a miR-302 mimic or antagomir. The effect of miR-302 on myeloid leukemia cell-differentiation protein-1 (Mcl-1) expression was determined by western blot, real-time polymerase chain reaction, and luciferase reporter assays, with cell viability assays...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28490664/inhibiting-the-oncogenic-translation-program-is-an-effective-therapeutic-strategy-in-multiple-myeloma
#15
Salomon Manier, Daisy Huynh, Yu J Shen, Jia Zhou, Timur Yusufzai, Karma Z Salem, Richard Y Ebright, Jiantao Shi, Jihye Park, Siobhan V Glavey, William G Devine, Chia-Jen Liu, Xavier Leleu, Bruno Quesnel, Catherine Roche-Lestienne, John K Snyder, Lauren E Brown, Nathanael Gray, James Bradner, Luke Whitesell, John A Porco, Irene M Ghobrial
Multiple myeloma (MM) is a frequently incurable hematological cancer in which overactivity of MYC plays a central role, notably through up-regulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small-molecule library for anti-MM activity. The most potent hits identified were rocaglate scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, the most promising rocaglate...
May 10, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28485156/the-effects-of-lentivirus-mediated-shrna-interference-targeting-mcl-1-on-growth-of-nk-t-cell-lymphoma
#16
X Zhang, C Shi, G Yue, H Guo, X Fu, X Li, L Li, X Wang, Z Li, Y Chang, M Zhang, Q Chen
Myeloid leukemia-1 (Mcl-1) gene has been reported as an important factor in various types of cancer, but little research was processed on natural killer (NK)/T-cell lymphoma, a kind of a highly aggressive disease with a poor prognosis. Here we investigated the expression of Mcl-1 in seven lymphoma cell lines and its potential role as a molecular drug target for NK/T-cell lymphoma therapy by using lentivirus-mediated shRNA interference targeting Mcl-1 (lenti-shMcl-1). In our study, the expression of Mcl-1 in different lymphoma cell lines were evaluated firstly, after that lenti-shMcl-1 was constructed and transduced into NK/T-cell lymphoma cell line SNK-6 which had a high level expression of Mcl-1...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28477025/eribulin-alone-or-in-combination-with-the-plk1-inhibitor-bi-6727-triggers-intrinsic-apoptosis-in-ewing-sarcoma-cell-lines
#17
Lilly Magdalena Weiß, Manuela Hugle, Simone Fulda
In this study, we investigated the molecular mechanisms of eribulin-induced cell death and its therapeutic potential in combination with the PLK1 inhibitor BI 6727 in Ewing sarcoma (ES). Here, we show that eribulin triggers cell death in a dose-dependent manner in a panel of ES cell lines. In addition, eribulin at subtoxic, low nanomolar concentrations acts in concert with BI 6727 to induce cell death and to suppress long-term clonogenic survival. Mechanistic studies reveal that eribulin monotherapy at cytotoxic concentrations and co-treatment with eribulin at subtoxic concentrations together with BI 6727 arrest cells in the M phase of the cell cycle prior to the onset of cell death...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28472749/neutral-pegylated-liposomal-formulation-for-efficient-folate-mediated-delivery-of-mcl1-sirna-to-activated-macrophages
#18
Eugénia Nogueira, Jaime Freitas, Ana Loureiro, Patrícia Nogueira, Andreia C Gomes, Ana Preto, Alexandre M Carmo, Alexandra Moreira, Artur Cavaco-Paulo
Cationic liposomes are efficient vectors for systemic delivery of therapeutic small interfering RNA (siRNA), taking advantage of RNA interference (RNAi), a naturally occurring gene-silencing mechanism in mammalian cells. However, toxicity at high concentrations, short circulating half-lives and lack of specificity restrict their successful application in a wider scale. The purpose of this study was to evaluate the efficiency of neutral liposomes containing polyethylene glycol (PEG) to encapsulate siRNA in their aqueous core...
April 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28469783/wp1130-increases-cisplatin-sensitivity-through-inhibition-of-usp9x-in-estrogen-receptor-negative-breast-cancer-cells
#19
Peifen Fu, Feiya Du, Yu Liu, Minya Yao, Shufeng Zhang, Xiaoxiao Zheng, Shusen Zheng
Approximately 30% of all breast cancers are caused by a lack of estrogen receptor (ER), which renders the cancer resistant to endocrine-based therapy. Many studies suggest that ubiquitin-specific peptidase 9, X-linked (usp9x) regulates multiple cellular behaviors, such as tumor growth, invasion, and resistance to chemotherapeutic agents. This study aimed to evaluate the anti-tumor effects of WP1130, a partially selective inhibitor of deubiquitinating enzymes, in breast cancer cells. We found that WP1130 enhanced cisplatin cytotoxicity in ER-negative tumor cells (MDA-MB-231 and MDA-MB-468), but had little effect in ER-positive Bcap-37 cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28467689/vernodalol-enhances-trail-induced-apoptosis-in-diffuse-large-b-cell-lymphoma-cells
#20
Wenjun Wu, Yang Yang, Gang Deng, Liang Ma, Guoqing Wei, Gaofeng Zheng, Xiaoyan Han, Donghua He, Yi Zhao, Jinsong He, Zhen Cai, Rui Yu
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent anti-tumour agent that triggers apoptosis in cells from multiple types of carcinoma but not in normal cells. However, diverse mechanisms are associated with insensitivity to TRAIL in various cancers. TRAIL efficacy may be enhanced by combining TRAIL with a sensitizer. In this study, vernodalol, a sesquiterpene lactone, sensitized diffuse large B-cell lymphoma (DLBCL) cells to TRAIL-induced apoptosis. Vernodalol increased the expression of death receptor (DR) 5, and silencing of DR5 with a small interfering RNA (siRNA) reduced the effect of vernodalol on TRAIL-mediated apoptosis...
May 3, 2017: Molecular Carcinogenesis
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