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https://www.readbyqxmd.com/read/29453135/dual-inhibitors-of-the-pro-survival-proteins-bcl-2-and-mcl-1-derived-from-natural-compound-meiogynin-a
#1
Alma Abou Samra, Aude Robert, Crystal Gov, Loëtitia Favre, Laure Eloy, Eric Jacquet, Jérôme Bignon, Joëlle Wiels, Sandy Desrat, Fanny Roussi
Thirty analogues of natural meiogynin A, a pan-Bcl-2 inhibitor, were prepared in order to elaborate cytotoxic compounds on specific cancer cells overexpressing one or more proteins of the Bcl-2 family. The interaction of all the new analogues with Bcl-xL, Mcl-1 and Bcl-2 proteins was first evaluated by fluorescence polarization assay (FPA) and showed that modulation of the lateral chain has a dramatic impact as subtle changes significantly modify the activity on the target proteins. The acetoxymethyl prodrugs of the two most active compounds were then elaborated to determine their cytotoxicity on B cell lines...
February 5, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29446977/establishment-growth-proliferation-and-gene-expression-of-buffalo-bubalus-bubalis-transgenic-fetal-fibroblasts-containing-human-insulin-gene-and-production-of-embryos-by-handmade-cloning-using-these-cells
#2
Parul Mehta, Ramakant Kaushik, Karn Pratap Singh, Ankur Sharma, Manoj Kumar Singh, Manmohan Singh Chauhan, Prabhat Palta, Suresh Kumar Singla, Radhey Sham Manik
The aim of the present study was to compare transgenic cells, containing human insulin gene kept under the control of mammary gland-specific buffalo beta-lactoglobulin promoter, and their counterparts, that is, nontransgenic cells, for examining their potential for the production of embryos following somatic cell nuclear transfer (SCNT). The gene construct was delivered into buffalo fetal fibroblasts (BFF) by nucleofection following which, the transfected cells were selected by culture in the presence of G418 for 3 weeks...
February 15, 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29440272/antagonistic-effects-of-nitric-oxide-in-a-glioblastoma-photodynamic-therapy-model-mitigation-by-bet-bromodomain-inhibitor-jq1
#3
Jonathan M Fahey, Jennifer S Stancill, Brian C Smith, Albert W Girotti
Endogenous nitric oxide (NO) generated by inducible NO synthase (iNOS) promotes glioblastoma cell proliferation and invasion, and also plays a key role in glioblastoma resistance to chemotherapy and radiotherapy. Non-ionizing photodynamic therapy (PDT) has anti-tumor advantages over conventional glioblastoma therapies. Our previous studies revealed that glioblastoma U87 cells upregulate iNOS after a photodynamic challenge and that resulting NO not only increased resistance to apoptosis, but rendered surviving cells more proliferative and invasive...
February 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29438890/flavonoids-from-chinese-bayberry-leaves-induced-apoptosis-and-g1-cell-cycle-arrest-via-erk-pathway-in-ovarian-cancer-cells
#4
Yu Zhang, Shiguo Chen, Chaoyang Wei, Gary O Rankin, Xingqian Ye, Yi Charlie Chen
Ovarian cancer is one of the leading causes of death related to the female reproductive system in western countries. Adverse side effects and resistance to platinum based chemotherapy have become the major obstacles for ovarian cancer treatment. Natural products have gained great attention in cancer treatment in recent years. Chinese bayberry leaves flavonoids (BLF) containing rich content of myricitrin (myricetin 3-O-rhamnoside) and a part of quercetrin (quercetin 3-rhamnoside) inhibited the growth of an ovarian cancer cell line A2780/CP70...
January 31, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29434770/microrna-519a-inhibits-the-proliferation-and-promotes-the-apoptosis-of-ovarian-cancer-cells-through-targeting-signal-transducer-and-activator-of-transcription-3
#5
Fei Tian, Ligang Jia, Zhaoping Chu, Hua Han, Yuan Zhang, Jianhui Cai
Ovarian cancer is a highly prevalent cancer among women. Recent studies have indicated that microRNAs (miRs) may serve important roles in the pathogenesis of ovarian cancer. miR-519a was observed to be downregulated in tissue samples of patients with ovarian cancer; however, its role in ovarian cancer requires further investigation. The aim of the present study was to examine the role of miR-519a in the pathogenesis of ovarian cancer and determine its direct target. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the expression of miR-519a in 20 patients ovarian cancer and 20 normal ovarian tissue samples...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29428944/clusterin-reduces-cold-ischemia-reperfusion-injury-in-heart-transplantation-through-regulation-of-nf-kb-signaling-and-bax-bcl-xl-expression
#6
Guodong Liu, Hongmei Zhang, Fengyun Hao, Jing Hao, Lixiao Pan, Qing Zhao, Jinshan Wo
BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury...
February 5, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29426985/cypripedin-a-phenanthrenequinone-from-dendrobium-densiflorum-sensitizes-non-small-cell-lung-cancer-h460-cells-to-cisplatin-mediated-apoptosis
#7
Onsurang Wattanathamsan, Surassawadee Treesuwan, Boonchu Sritularuk, Varisa Pongrakhananon
The life-threatening potential of lung cancer has increased over the years due to its acquisition of chemotherapeutic resistance, especially to cisplatin, a first-line therapy. In response to this development, researchers have turned their attention to several compounds derived from natural origins, including cypripedin (CYP), a phenanthrenequinone substance extracted from Dendrobium densiflorum. The aim of the present study was to investigate the ability of CYP to induce apoptosis and enhance cisplatin-mediated death of human lung cancer NCI-H460 cells using cell viability and apoptosis assays...
February 9, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29425832/small-activating-rna-induced-expression-of-vhl-gene-in-renal-cell-carcinoma
#8
Moo Rim Kang, Ki Hwan Park, Chang Woo Lee, Myeong Youl Lee, Sang-Bae Han, Long-Cheng Li, Jong Soon Kang
Recent studies have reported that chemically synthesized double-stranded RNAs (dsRNAs), also known as small activating RNA (saRNAs), can specifically induce gene expression by targeting promoter sequences by a mechanism termed RNA activation (RNAa). In the present study, we designed 4 candidate saRNAs targeting the Von Hippel-Lindau (VHL) gene promoter. Among these saRNAs, dsVHL-821 significantly inhibited cell growth by up-regulating VHL at both the mRNA and protein levels in renal cell carcinoma 769-P cells...
February 6, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29425759/expression-of-proteins-upregulated-in-hepatocellular-carcinoma-in-patients-with-alcoholic-hepatitis-ah-compared-to-non-alcoholic-steatohepatitis-nash-an-immunohistochemical-analysis-of-candidate-proteins
#9
Jiajie George Lu, Luan Nguyen, Sara Samadzadeh, Maryam Masouminia, Alejandro Mendoza, Owen Sweeney, Brittany Tillman, Nikoo Afifyan, Timothy Morgan, Barbara A French, Samuel W French
Both non-alcoholic steatohepatitis (NASH) and alcoholic hepatitis (AH) can lead to cirrhosis and hepatocellular carcinoma. However, the rate of progression to cirrhosis and tumorigenesis in AH is greater than that in NASH. We asked whether there are differences between the two conditions in the expression levels of proteins involved in the pathogenesis of hepatocellular carcinoma. The proteins tested were presented at the 2017 American Association for the Study of Liver Diseases (AASLD) Liver Meeting as overexpressed in hepatocellular carcinoma: KLF4, SCL19A1, FANCG, HRH-1, DNMT1, DNMT3B, TNFR2, DUSP4, EGFR, Integrin α6, HDACII, PDE3A, BCL-XL, and MTCO2...
February 6, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29423058/muc1-induces-m2-type-macrophage-influx-during-postpartum-mammary-gland-involution-and-triggers-breast-cancer
#10
Yuan Li, Zhi Pang, Xinran Dong, Xiaodong Liao, Huayun Deng, Chunhua Liao, Yahui Liao, Guoqiang Chen, Lei Huang
The microenvironment of postpartum mammary gland involution (PMI) has been linked to the increased risk of breast cancer and poor outcome of patients. Nevertheless the mechanism underlying regulates the microenvironment remains largely unknown. MUC1, which is abnormally overexpressed in most breast cancer, is physiologically expressed in PMI. Using MUC1 cytoplasm domain (MUC1-CD) transgenic mice, we reveal that the overexpression of MUC1-CD in mammary epithelial cells increases M2 type macrophage infiltration in PMI...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423005/transcription-factor-phf19-positively-regulates-germinal-center-reactions-that-underlies-its-role-in-rheumatoid-arthritis
#11
Fanyou Ning, Chong Wang, Suling Niu, Haiyan Xu, Kai Xia, Nan Wang
The Polycomb Repressive Complex 2 (PRC2) component PHD Finger Protein 19 (phf19) gene has been identified to be associated with rheumatoid arthritis (RA) risk. Here we show that Phf19 is highly expressed in murine germinal centers (GCs) and RA patients. To investigate the function of Phf19 in lymphocytes, we generated RAG1-deficient mice reconstituted with Phf19 or control-vector transduced bone marrow (BM) cells. Lymphogenesis in primary lymphoid tissues of Phf19-RM is normal, however, Phf19-RM form enlarged GCs and generate more antibody-secreting cells (ASCs)...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29417954/idh1-r132h-predicts-sensitivity-to-bcl-xl-inhibition-mediated-programmed-cell-death
#12
COMMENT
Georg Karpel-Massler, Chiaki Tsuge Ishida, Markus D Siegelin
No abstract text is available yet for this article.
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412690/platelet-procoagulant-phenotype-is-modulated-by-a-p38-mk2-axis-regulating-rtn4-nogo-proximal-to-the-endoplasmic-reticulum-utility-of-pathway-analysis
#13
Özgün Babur, Anh T P Ngo, Rachel A Rigg, Jiaqing Pang, Zhoe T Rub, Ariana E Buchanan, Annachiara Mitrugno, Larry L David, Owen J T McCarty, Emek Demir, Joseph E Aslan
Upon encountering physiological cues associated with damaged or inflamed endothelium, blood platelets set forth intracellular responses to ultimately support hemostatic plug formation and vascular repair. To gain insights into the molecular events underlying platelet function, we used a combination of interactome, pathway analysis and other systems biology tools to analyze associations amongst proteins functionally modified by reversible phosphorylation upon platelet activation. While an interaction analysis mapped out a relative organization of intracellular mediators in platelet signaling, pathway analysis revealed directional signaling relations around protein kinase C (PKC) isoforms and mitogen activated protein kinases (MAPKs) associated with platelet cytoskeletal dynamics, inflammatory responses and hemostatic function...
February 7, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29407584/the-combination-of-trail-and-mg-132-induces-apoptosis-in-both-trail-sensitive-and-trail-resistant-human-follicular-lymphoma-cells
#14
Jemal Adem, Mine Eray, Jonna Eeva, Ulla Nuutinen, Jukka Pelkonen
We have previously shown that the human follicular lymphoma cell line, HF28GFP, is sensitive to TRAIL-mediated apoptosis. Nevertheless, when the same cells overexpress anti-apoptotic Bcl-2 family protein, Bcl-xL (HF28Bcl-xL), they become resistant to TRAIL. Thus, these cell lines help us to investigate the action of novel apoptosis inducing candidate drugs. In the present study, we examined the effects of MG-132 (a proteasome inhibitor), LiCl (a glycogen synthase kinase-3 inhibitor) and/or TRAIL on pro-apoptotic Bcl-2 family proteins such as Bim and Bid...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29405977/bcl-2-antiapoptotic-family-proteins-and-chemoresistance-in-cancer
#15
Santanu Maji, Sanjay Panda, Sabindra K Samal, Omprakash Shriwas, Rachna Rath, Maurizio Pellecchia, Luni Emdad, Swadesh K Das, Paul B Fisher, Rupesh Dash
Cancer is a daunting global problem confronting the world's population. The most frequent therapeutic approaches include surgery, chemotherapy, radiotherapy, and more recently immunotherapy. In the case of chemotherapy, patients ultimately develop resistance to both single and multiple chemotherapeutic agents, which can culminate in metastatic disease which is a major cause of patient death from solid tumors. Chemoresistance, a primary cause of treatment failure, is attributed to multiple factors including decreased drug accumulation, reduced drug-target interactions, increased populations of cancer stem cells, enhanced autophagy activity, and reduced apoptosis in cancer cells...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29405820/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-parp1-inhibitor-niraparib-to-kill-ovarian-cancer-cells
#16
Laurence Booth, Jane L Roberts, Peter Samuel, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ovarian cancer cells. Neratinib and niraparib caused the ATM-dependent activation of AMPK which in turn was required to cause mTOR inactivation, ULK-1 activation and ATG13 phosphorylation. The drug combination initially increased autophagosome levels followed later by autolysosome levels...
February 6, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29399562/antidiabetic-drug-metformin-protects-neuronal-cells-against-quinolinic-acid-induced-excitotoxicity-by-decreasing-intracellular-calcium
#17
Sujeong Jang, Sah-Hoon Park
The antidiabetic drug metformin has been found to have beneficial effects in various neurological disorders; however, the molecular mechanisms underlying these effects remain unclear. Here we report that metformin protects neuronal cells from quinolinic acid (QUIN)-induced excitotoxicity. For this, we pretreated N18D3 neuronal cells with metformin prior to QUIN for 24 h. We found that pretreating the cells with metformin significantly improved cell survival rate in a concentration-dependent manner and reduced apoptotic cell death, as revealed by a MTT assay and DAPI staining, respectively...
January 2018: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29399358/predictive-biomarkers-for-combined-chemotherapy-with-5-fluorouracil-and-cisplatin-in-oro-and-hypopharyngeal-cancers
#18
Yasuhisa Hasegawa, Mitsuo Goto, Nobuhiro Hanai, Taijiro Ozawa, Hitoshi Hirakawa
The present study aimed to identify significant correlations between gene expression and chemotherapy response to 5-fluorouracil (5-FU)/cisplatin in head and neck squamous cell carcinoma (HNSCC), and to identify patients who would benefit from induction chemotherapy for both organ preservation and survival. A total of 64 patients who underwent radical treatment for HNSCC were enrolled. All patients received induction chemotherapy with 5-FU/cisplatin and tumor responses were evaluated. Pretreatment biopsy specimens from all patients were assayed for mRNA expression of thymidylate synthase, dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, tymidine phosphorylase, glutathione S-transferase-pi, p53, RB Transcriptional Corepressor 1, B-cell lymphoma 2 (Bcl-2), Bcl-xL, E2F Transcription Factor 1, epidermal growth factor receptor, human epidermal growth factor receptor 2, phosphoinositide 3-kinase, phosphatase and tensin homolog, vascular endothelial growth factor (VEGF), cyclooxygenase-2, XPA, DNA Damage Recognition And Repair Factor, excision repair cross-complementing 1 (ERCC1), multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1, equilibrative nucleoside transporter 1 and β-tubulin by reverse transcription-quantitative polymerase chain reaction, and the association between the expression levels of these genes and patient response to chemotherapy was determined...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29394130/dznep-represses-bcl-2-expression-and-modulates-apoptosis-sensitivity-in-response-to-nutlin-3a
#19
Yalu Zhou, Ricardo E Perez, Lei Duan, Carl G Maki
MDM2 antagonists stabilize and activate wild-type p53, and histone methyltransferase (HMT) inhibitors reduce methylation on histone lysines and arginines. Both MDM2 antagonists and HMT inhibitors are being developed as cancer therapeutics. Wild-type p53 expressing HCT116 colon cancer cells were resistant to apoptosis in response to the MDM2 antagonist Nutlin-3a. However, co-treatment with the HMT inhibitor DZNep sensitized the cells to Nutlin-3a-induced apoptosis. This sensitization resulted from reduced activity of the Bcl-2 gene promoter and a reduction in Bcl-2 mRNA and protein...
February 2, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29391813/combination-of-betulinic-acid-with-diazen-1-ium-1-2-diolate-nitric-oxide-moiety-donating-a-novel-anticancer-candidate
#20
Laiyin Zhang, Shuangxing Hou, Bo Li, Jianjian Pan, Liping Jiang, Guiying Zhou, Hong Gu, Caixing Zhao, Huiping Lu, Fenfen Ma
Background: Betulinic acid (BA) is a complex lupane triterpenoid with unique antineoplastic activity. However, its antiproliferative activity is far from satisfaction. In order to improve its anticancer efficacy, betulinic acid was conjugated with a nitric oxide (NO)-releasing moiety to get a novel hybrid, BA-78. Methods: The antiproliferative activity of BA-78 against 6 cell lines and the ability of releasing nitric oxide were determined. The pro-apoptosis mechanism of BA-78 was investigated as well...
2018: OncoTargets and Therapy
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