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intrinsic apoptosis pathway

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https://www.readbyqxmd.com/read/29156680/vemurafenib-resistance-via-de-novo-rbm-genes-mutations-and-chromosome-5-aberrations-is-overcome-by-combined-therapy-with-palbociclib-in-thyroid-carcinoma-with-braf-v600e
#1
Zeus A Antonello, Nancy Hsu, Manoj Bhasin, Giovanni Roti, Mukta Joshi, Paul Van Hummelen, Emily Ye, Agnes S Lo, S Ananth Karumanchi, Christine R Bryke, Carmelo Nucera
Purpose: Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-))...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152118/sensitization-of-neuroblastoma-for-vincristine-induced-apoptosis-by-smac-mimetic-lcl161-is-attended-by-g2-cell-cycle-arrest-but-is-independent-of-nf%C3%AE%C2%BAb-rip1-and-tnf-%C3%AE
#2
Doerte Langemann, Magdalena Trochimiuk, Birgit Appl, Patrick Hundsdoerfer, Konrad Reinshagen, Georg Eschenburg
We demonstrated sensitization for chemotherapy by Smac mimetic (SM) LCL161, a potent antagonist of inhibitor of apoptosis proteins (IAP), in neuroblastoma (NB). Vinca alkaloids, particularly vincristine (VCR), displayed the strongest impact on inhibition of proliferation and apoptosis induction in combination with LCL161. The underlying signaling pathways remain elusive, though. LCL161 induces a quick degradation of cellular IAP 1 (cIAP-1). Combination of LCL161 with VCR had only marginal effects on X-linked IAP (XIAP) protein expression...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152082/panbinostat-decreases-cflip-and-enhances-killing-of-cancer-cells-by-immunotoxin-lmb-100-by-stimulating-the-extrinsic-apoptotic-pathway
#3
Xiu-Fen Liu, Qi Zhou, Raffit Hassan, Ira Pastan
LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29145490/rnai-screen-reveals-a-role-of-sphk2-in-dengue-virus-mediated-apoptosis-in-hepatic-cell-lines
#4
Atthapan Morchang, Regina Ching Hua Lee, Pa-Thai Yenchitsomanus, Gopinathan Pillai Sreekanth, Sansanee Noisakran, Justin Jang Hann Chu, Thawornchai Limjindaporn
Hepatic dysfunction is a feature of dengue virus (DENV) infection. Hepatic biopsy specimens obtained from fatal cases of DENV infection show apoptosis, which relates to the pathogenesis of DENV infection. However, how DENV induced liver injury is not fully understood. In this study, we aim to identify the factors that influence cell death by employing an apoptosis-related siRNA library screening. Our results show the effect of 558 gene silencing on caspase 3-mediated apoptosis in DENV-infected Huh7 cells. The majority of genes that contributed to apoptosis were the apoptosis-related kinase enzymes...
2017: PloS One
https://www.readbyqxmd.com/read/29145487/defining-external-factors-that-determine-neuronal-survival-apoptosis-and-necrosis-during-excitotoxic-injury-using-a-high-content-screening-imaging-platform
#5
Ujval Anilkumar, Petronela Weisova, Jasmin Schmid, Tytus Bernas, Heinrich J Huber, Heiko Düssmann, Niamh M C Connolly, Jochen H M Prehn
Cell death induced by excessive glutamate receptor overactivation, excitotoxicity, has been implicated in several acute and chronic neurological disorders. While numerous studies have demonstrated the contribution of biochemically and genetically activated cell death pathways in excitotoxic injury, the factors mediating passive, excitotoxic necrosis are less thoroughly investigated. To address this question, we developed a high content screening (HCS) based assay to collect high volumes of quantitative cellular imaging data and elucidated the effects of intrinsic and external factors on excitotoxic necrosis and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#6
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29137255/potential-genotoxic-and-cytotoxicity-of-emamectin-benzoate-in-human-normal-liver-cells
#7
Zhijie Zhang, Xinyu Zhao, Xiaosong Qin
Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133058/design-and-synthesis-of-thienopyrimidine-urea-derivatives-with-potential-cytotoxic-and-pro-apoptotic-activity-against-breast-cancer-cell-line-mcf-7
#8
Eman F Abdelhaleem, Mohammed K Abdelhameid, Asmaa E Kassab, Manal M Kandeel
A series of novel tetrahydrobenzothieno[2,3-d]pyrimidine urea derivatives was synthesized according to fragment-based design strategy. They were evaluated for their anticancer activity against MCF-7 cell line. Three compounds 9c, 9d and 11b showed 1.5-1.03 folds more potent anticancer activity than doxorubicin. In this study, a promising multi-sited enzyme small molecule inhibitor 9c, which showed the most potent anti-proliferative activity, was identified. The anti-proliferative activity of this compound appears to correlate well with its ability to inhibit topoisomerase II (IC50 = 9...
October 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29131631/cytotoxicity-hemolytic-toxicity-and-mechanism-of-action-of-pulsatilla-saponin-d-and-its-synthetic-derivatives
#9
Zhong Chen, Huaqing Duan, Xiaohang Tong, Peiling Hsu, Li Han, Susan L Morris-Natschke, Shilin Yang, Wei Liu, Kuo-Hsiung Lee
The strong hemolytic toxicity of pulsatilla saponin D (1, HD50 6.3 μM) has hampered its clinical development as an injectable anticancer agent. To combat this challenge, 17 new derivatives of 1 with ring C, C-28, or C-3 modifications were synthesized and evaluated for cytotoxicity against several selected human tumor lines, as well as for hemolytic toxicity against rabbit erythrocytes. Structure-activity relationship (SAR) and structure-toxicity relationship (STR) correlations were also elucidated. Compared to the lead compound 1, the hemolytic activity of all 17 derivatives dropped dramatically...
November 13, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29130799/allergen-immunotherapy-modulates-sensitivity-of-treg-cells-to-apoptosis-in-a-rat-model-of-allergic-asthma
#10
Ankur Datta, Saibal Moitra, Prasanta K Das, Somnath Mondal, Sk Md Omar Faruk, Iman Hazra, Santanu K Tripathi, Swapna Chaudhuri
AIM: To study the apoptosis of Foxp3(+) Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. MATERIALS & METHODS: Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. RESULTS: Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy...
November 2017: Immunotherapy
https://www.readbyqxmd.com/read/29129777/trichloroethylene-metabolite-s-1-2-dichlorovinyl-l-cysteine-induces-lipid-peroxidation-associated-apoptosis-via-the-intrinsic-and-extrinsic-apoptosis-pathways-in-a-first-trimester-placental-cell-line
#11
Elana R Elkin, Sean M Harris, Rita Loch-Caruso
Trichloroethylene (TCE), a prevalent environmental contaminant, is a potent renal and hepatic toxicant through metabolites such as S-(1, 2-dichlorovinyl)-l-cysteine (DCVC). However, effects of TCE on other target organs such as the placenta have been minimally explored. Because elevated apoptosis and lipid peroxidation in placenta have been observed in pregnancy morbidities involving poor placentation, we evaluated the effects of DCVC exposure on apoptosis and lipid peroxidation in a human extravillous trophoblast cell line, HTR-8/SVneo...
November 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29125379/bcl-xl-bak-interaction-and-regulation-by-mirna-let-7b-in-the-intrinsic-apoptotic-pathway-of-stored-platelets
#12
Yuzhong Yan, Rufeng Xie, Qi Zhang, Xinfang Zhu, Jia Han, Rong Xia
Bcl-2 family proteins play key roles in the intrinsic apoptosis pathway in platelets, with both pro- and antiapoptotic protein expressions regulating survival during ex vivo storage. We detected a significant decrease in antiapoptotic Bcl-xL and increase in proapoptotic Bak expression on the third day of storage and as a result the ratio of Bak:Bcl-xL also decreased. Moreover, we identified an interaction between Bcl-xL and Bak. These shifts corresponded with activation of the apoptotic pathway, suggesting these proteins might play an important role in platelet survival...
November 10, 2017: Platelets
https://www.readbyqxmd.com/read/29123378/10h-3-6-diazaphenothiazine-induces-g2-m-phase-cell-cycle-arrest-and-caspase-dependent-apoptosis-and-inhibits-cell-invasion-of-a2780-ovarian-carcinoma-cells-through-the-regulation-of-nf-%C3%AE%C2%BAb-and-birc6-xiap-complexes
#13
Jianxin Zhang, Chen Ming, Wenzhi Zhang, Patrick Nwabueze Okechukwu, Beata Morak-Młodawska, Krystian Pluta, Małgorzata Jeleń, Abdah Md Akim, Kok-Pian Ang, Kah Kooi Ooi
The asymptomatic properties and high treatment resistance of ovarian cancer result in poor treatment outcomes and high mortality rates. Although the fundamental chemotherapy provides promising anticancer activities, it is associated with severe side effects. The derivative of phenothiazine, namely, 10H-3,6-diazaphenothiazine (PTZ), was synthesized and reported with ideal anticancer effects in a previous paper. In this study, detailed anticancer properties of PTZ was examined on A2780 ovarian cancer cells by investigating the cytotoxicity profiles, mechanism of apoptosis, and cell invasion...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29122993/the-microenvironmental-stromal-cells-abrogate-nf-%C3%AE%C2%BAb-inhibitor-induced-apoptosis-in-chronic-lymphocytic-leukemia
#14
Carl Philipp Simon-Gabriel, Katharina Foerster, Shifa Saleem, Dorothee Bleckmann, Marco Benkisser-Petersen, Nicolas Thornton, Kazuo Umezawa, Sarah Decker, Meike Burger, Hendrik Veelken, Rainer Claus, Christine Dierks, Justus Duyster, Katja Zirlik
NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the survival of chronic lymphocytic leukemia cells, we tested here whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor Dehydroxymethylepoxyquinomicin...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29119970/hispidulin-mediates-apoptosis-in-human-renal-cell-carcinoma-by-inducing-ceramide-accumulation
#15
Hui Gao, Ming-Quan Gao, Jian-Jun Peng, Mei Han, Kai-Li Liu, Yan-Tao Han
Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Hispidulin (10, 20 μmol/L) decreased the viability of ccRCC cells in dose- and time-dependent manners without affecting that of normal tubular epithelial cells...
November 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29118905/intramyocardial-injection-of-thioredoxin-2-expressing-lentivirus-alleviates-myocardial-ischemia-reperfusion-injury-in-rats
#16
Yanyan Li, Yin Xiang, Song Zhang, Yan Wang, Jie Yang, Wei Liu, Fengtai Xue
The aim of this study is to explore the role of thioredoxin-2 (Trx2) in autophagy and apoptosis during myocardial ischemia-reperfusion (I/R) injury in vivo. In the study, adult male Sprague-Dawley rats were assigned to four groups at random and pretreated with normal saline (sham operation and I/R groups) and either a control lentivirus (Lv-GFP-N) or one expressing Trx2 (Lv-GFP-Trx2). Sevendays after pretreatment, rat MIRI models were produced via occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 6 h...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118899/alterations-in-tendon-microenvironment-in-response-to-mechanical-load-potential-molecular-targets-for-treatment-strategies
#17
REVIEW
Mohamed B Fouda, Finosh G Thankam, Matthew F Dilisio, Devendra K Agrawal
Rotator cuff (RC) tendons could beinflicted in many ways with an eventual outcome of pain, weakness and disability, which represent a large burden on health care cost. However, optimal healing, either conservatively or with surgical intervention, remains an issue that needs further investigation. Disorders of the RC tendons may result from external factors like trauma, or internal factors through physiologic and metabolic derangement. Most RC tendon disorders may be asymptomatic and may result from an over-activity of the inflicted shoulder and its tendons...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29115633/xiap-underlies-apoptosis-resistance-of-renal-cell-carcinoma-cells
#18
Wen Zheng Yang, Haijiang Zhou, Yong Yan
X‑linked inhibitor of apoptosis (XIAP), a key member of the inhibitors of apoptosis protein family, can inhibit apoptosis by directly binding to the initiator caspase‑9, ‑3 and ‑7, thereby promoting tumor cell survival during tumor progression. In the present study, XIAP basal expression levels were investigated and its contribution to the resistance to apoptosis was evaluated, in the RCC cell lines exposed to apoptosis‑inducing drugs. This was investigated by histological methods and western blot analysis...
October 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115629/oxymatrine-induces-a549-human-non%C3%A2-small-lung-cancer-cell-apoptosis-via-extrinsic-and-intrinsic-pathways
#19
Guang-Zhou Zhou, Yan-Yan Shi, Liu-Su Cui, A-Fang Li, Qing-Qing Wang, Min Liu
Oxymatrine is one of the primary natural compounds extracted from the Sophora flavescens, and has been reported to exhibit numerous pharmacological properties including cancer‑preventive and anti‑cancer effects, however the mechanisms as to how oxymatrine exhibits anti‑proliferative activity in non‑small cell lung carcinoma cells remains uncertain. The present study aimed to explore the mechanism of its anti‑cancer effect, and whether it is due to apoptosis induction and anti‑migration in the A549 lung cancer cell line...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111769/xpc-deficiency-alters-cigarette-smoke-dna-damage-cell-fate-and-accelerates-emphysema-development
#20
Catherine R Sears, Huaxin Zhou, Matthew J Justice, Amanda J Fisher, Jacob Saliba, Isaac Lamb, Jessica Wicker, Kelly S Schweitzer, Irina Petrache
Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein xeroderma pigmentosum group C (XPC) on CS-induced DNA damage repair and emphysema...
November 7, 2017: American Journal of Respiratory Cell and Molecular Biology
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