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https://www.readbyqxmd.com/read/29340082/reciprocal-sensitivity-of-diffuse-large-b-cell-lymphoma-cells-to-bcl-2-inhibitors-bird-2-versus-venetoclax
#1
Tamara Vervloessem, Haidar Akl, Thomas Tousseyn, Humbert De Smedt, Jan B Parys, Geert Bultynck
Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some cancers with elevated Bcl-2 display poor responses towards BH3 mimetics, suggesting an additional function for anti-apoptotic Bcl-2 in these cancers. Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5-trisphosphate receptor (IP3R)...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#2
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29321062/notch-signaling-triggered-via-the-ligand-dll4-impedes-m2-macrophage-differentiation-and-promotes-their-apoptosis
#3
Sylvain Pagie, Nathalie Gérard, Béatrice Charreau
BACKGROUND: Notch signaling controls many cellular processes, including cell fate determination, cell differentiation, proliferation and apoptosis. In mammals, four Notch receptors (Notch 1-4) can interact with five distinct ligands [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported that Notch activation is modulated in endothelial cells and monocytes during inflammation and showed that inflammation upregulates DLL4 on endothelial cells. DLL4 promotes differentiation of blood monocytes into proinflammatory M1 macrophages...
January 10, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29319219/osthole-induces-human-nasopharyngeal-cancer-cells-apoptosis-through-fas-fas-ligand-and-mitochondrial-pathway
#4
Pei-Ying Liu, Dun-Cheng Chang, Yu-Sheng Lo, Yi-Ting Hsi, Chia-Chieh Lin, Yi-Ching Chuang, Shu-Hui Lin, Ming-Ju Hsieh, Mu-Kuan Chen
Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase...
January 10, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29318382/mir-29-silencing-modulates-the-expression-of-target-genes-related-to-proliferation-apoptosis-and-methylation-in-burkitt-lymphoma-cells
#5
Luciano Mazzoccoli, Marcela Cristina Robaina, Alexandre Gustavo Apa, Martin Bonamino, Luciana Wernersbach Pinto, Eduardo Queiroga, Carlos E Bacchi, Claudete Esteves Klumb
PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression...
January 9, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29316653/synergistic-association-of-valproate-and-resveratrol-reduces-brain-injury-in-ischemic-stroke
#6
Lara Faggi, Giuseppe Pignataro, Edoardo Parrella, Vanessa Porrini, Antonio Vinciguerra, Pasquale Cepparulo, Ornella Cuomo, Annamaria Lanzillotta, Mariana Mota, Marina Benarese, Paolo Tonin, Lucio Annunziato, PierFranco Spano, Marina Pizzi
Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275), respectively, an activator of the AMP-activated kinase (AMPK)-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs), synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29314368/spectroscopic-studies-on-photoinduced-reactions-of-the-anticancer-prodrug-trans-trans-trans-pt-n3-2-oh-2-py-2
#7
Peter J Sadler, Robbin Vernooij, Tanmaya Joshi, Michael Horbury, Bim Graham, Ekaterina Izgorodina, Vasilios Stavros, Leone Spiccia, Bayden Wood
The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py = pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption and UV-Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and multi-curve resolution alternating least squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans [Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water...
January 3, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29312548/mimicking-the-bim-bh3-domain-overcomes-resistance-to-egfr-tyrosine-kinase-inhibitors-in-egfr-mutant-non-small-cell-lung-cancer
#8
Jinjing Xia, Hao Bai, Bo Yan, Rong Li, Minhua Shao, Liwen Xiong, Baohui Han
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied to treat EGFR-mutant non-small cell lung cancer (NSCLC). BIM is a BH3 domain-containing protein encoded by BCL2L11. Some EGFR-mutant NSCLC patients showing BIM deletion polymorphism are resistant to EGFR TKIs. We retrospectively investigated BIM deletion polymorphism in NSCLC patients, its correlation with EGFR TKI (erlotinib) resistance, and the mechanism underlying the drug resistance. Among 245 EGFR-mutant NSCLC patients examined, BIM deletion polymorphism was detected in 43 (12...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304442/structural-analysis-of-the-o-polysaccharide-from-the-lipopolysaccharide-of-pseudomonas-putida-bim-b-1100
#9
Evelina L Zdorovenko, Alexander S Shashkov, Alexandra A Kadykova, Elena P Kiseleva, Victoria V Savich, Galina I Novik, Yuriy A Knirel
Two specific polysaccharides, together with an →4)-α-d-Glcp-(1→ glucan (bacterial glycogen), were obtained from a lipopolysaccharide preparation isolated from the bacterium Pseudomonas putida BIM B-1100 by phenol/water extraction. The following structures of the polysaccharides were established by composition analysis, Smith degradation, ESI-MS, and 1D and 2D NMR spectroscopy.
December 25, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/29298654/determination-of-the-apoptotic-effect-and-molecular-docking-of-benzamide-derivative-xt5-in-k562-cells
#10
Tulin Ozkan, Yalda Hekmatshoar, Tugba Ertan-Bolelli, Andry Nur Hidayat, Meral Beksac, Esin Aki-Yalcin, Ismail Yalcin, Asuman Sunguroglu
BACKGROUND: The tyrosine kinase inhibitor imatinib used as a first line treatment in chronic myeloid leukemia (CML) patients, may lead to resistance and failure to therapy. Novel combinations of imatinib with other drugs is a strategy to improve treatment efficiency. OBJECTIVE: In this study, the antileukemic and apoptotic effects of a benzamide derivative XT5 and benzoxazole derivative XT2B and their combination with imatinib were investigated in imatinib-sensitive (K562S) and imatinib-resistant (K562R) CML cells...
December 29, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#11
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29296778/asxl1-and-bim-germ-line-variants-predict-response-and-identify-cml-patients-with-the-greatest-risk-of-imatinib-failure
#12
Justine E Marum, David T Yeung, Leanne Purins, John Reynolds, Wendy T Parker, Doris Stangl, Paul P S Wang, David J Price, Jonathan Tuke, Andreas W Schreiber, Hamish S Scott, Timothy P Hughes, Susan Branford
Scoring systems used at diagnosis of chronic myeloid leukemia (CML), such as Sokal risk, provide important response prediction for patients treated with imatinib. However, the sensitivity and specificity of scoring systems could be enhanced for improved identification of patients with the highest risk. We aimed to identify genomic predictive biomarkers of imatinib response at diagnosis to aid selection of first-line therapy. Targeted amplicon sequencing was performed to determine the germ line variant profile in 517 and 79 patients treated with first-line imatinib and nilotinib, respectively...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291353/fluorescently-labelled-morphine-derivatives-for-bioimaging-studies
#13
Raymond Lam, Arisbel B Gondin, Meritxell Canals, Barrie Kellam, Stephen J Briddon, Bim Graham, Peter J Scammells
Opioids, like morphine, are the mainstay analgesics for the treatment and control of pain. Despite this, they often exhibit severe side effects that limit dose; patients often become tolerant and dependent on these drugs, which remains a major health concern. The analgesic actions of opioids are primarily mediated via the μ-opioid receptor, a member of the G protein-coupled receptor superfamily. Thus far, development of small molecule fluorescent ligands for this receptor has resulted in antagonists, somewhat limiting the use of these probes...
January 1, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29291023/combined-venetoclax-and-alvocidib-in-acute-myeloid-leukemia
#14
James Bogenberger, Clifford Whatcott, Nanna Hansen, Devora Delman, Chang-Xin Shi, Wontak Kim, Hillary Haws, Katherine Soh, Ye Sol Lee, Peter Peterson, Adam Siddiqui-Jain, Steven Weitman, Keith Stewart, David Bearss, Ruben Mesa, Steven Warner, Raoul Tibes
More effective treatment options for elderly acute myeloid leukemia (AML) patients are needed as only 25-50% of patients respond to standard-of-care therapies, response duration is typically short, and disease progression is inevitable even with some novel therapies and ongoing clinical trials. Anti-apoptotic BCL-2 family inhibitors, such as venetoclax, are promising therapies for AML. Nonetheless, resistance is emerging. We demonstrate that venetoclax combined with cyclin-dependent kinase (CDK) inhibitor alvocidib is potently synergistic in venetoclax-sensitive and -resistant AML models in vitro, ex vivo and in vivo...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282361/influence-of-bcl2l11-polymorphism-on-osteonecrosis-during-treatment-of-childhood-acute-lymphoblastic-leukemia
#15
Maria Plesa, Vincent Gagné, Sanja Glisovic, Melissa Younan, Bahram Sharif-Askari, Caroline Laverdière, Nathalie Alos, Jean-Marie Leclerc, Stephen E Sallan, Donna Neuberg, Jeffery L Kutok, Lewis B Silverman, Daniel Sinnett, Maja Krajinovic
Osteonecrosis (ON) is corticosteroid-related complication, reported in children with acute lymphoblastic leukemia (ALL). We have previously found that polymorphisms in BCL2L11 gene coding for pro-apoptotic Bim protein influence reduction of overall survival (OS) in a corticosteroid (CS) dose-dependent manner in childhood ALL patients. The same set of SNPs was here investigated for an association with CS-related ON assessed retrospectively in 304 children with ALL from Quebec (QcALL cohort) who received Dana-Farber Cancer Institute (DFCI) ALL treatment protocols...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29278499/bim-binding-remotely-regulates-bax-activation-insights-from-the-free-energy-landscapes
#16
Souvik Sinha, Atanu Maity, Shubhra Ghosh Dastidar
Activation of the pro-apoptotic BAX protein, a BCl-2 family member, is known to trigger the apoptosis by forming pores in the mitochondrial outer membrane (MOM). While in the cytosol, release of its transmembrane C-terminal helix (called α9 helix) from a well-characterized binding pocket (BC groove) and subsequent permeabilization of MOM is understood to be the initiating events of the activation. In concern of what initiates the BAX activation, so far one plausible suggestion has been that the transient attachment of BH3-only peptide on a distal site from BC groove triggers the activation process...
December 26, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29277445/biased-g-protein-coupled-receptor-agonism-mediates-neu1-sialidase-and-matrix-metalloproteinase-9-crosstalk-to-induce-transactivation-of-insulin-receptor-signaling
#17
Fiona Haxho, Sabah Haq, Myron R Szewczuk
G protein-coupled receptors (GPCR) can participate in a number of signaling pathways, and this property led to the concept of biased GPCR agonism. Agonists, antagonists and allosteric modulators can bind to GPCRs in different ways, creating unique conformations that differentially modulate signaling through one or more G proteins. A unique neuromedin B (NMBR) GPCR-signaling platform controlling mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP9) crosstalk has been reported in the activation of the insulin receptor (IR) through the modification of the IR glycosylation...
December 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29275934/enhanced-intracellular-peptide-delivery-by-multivalent-cell-penetrating-peptide-with-bioreducible-linkage
#18
Hyungjin Kim, Mizuki Kitamatsu, Takashi Ohtsuki
Multivalent cell-penetrating peptides (CPPs) have been reported to show enhancement in cellular uptake and endosomolytic activity. However, its application was limited to trans-delivery of cargo which is lower in cellular uptake efficiency of cargo than cis-delivery. Here, we tried the cis-delivery of cargo with multivalent CPP by preparing bioreducible dimeric CPP-cargo with apoptotic activity using TatBim peptide, a fusion of Tat CPP and Bim peptide derived from Bim apoptosis-inducing protein. Dimeric TatBim was almost twice as highly internalized by cells and significantly induced apoptosis compared to monomeric TatBim...
December 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29274957/phenotypic-fermentation-characterization-and-resistance-mechanism-analysis-of-bacteriophage-resistant-mutants-of-lactobacillus-delbrueckii-ssp-bulgaricus-isolated-from-traditional-chinese-dairy-products
#19
Kaibo Deng, Wei Fang, Baodong Zheng, Song Miao, Guicheng Huo
Bacteriophage infection is a large factor in dairy industrial production failure on the basis of pure inoculation fermentation, and developing good commercial starter cultures from wild dairy products and improving the environmental vigor of starter cultures by enhancing their phage resistance are still the most effective solutions. Here we used a spontaneous isolation method to obtain bacteriophage-resistant mutants of Lactobacillus delbrueckii ssp. bulgaricus strains that are used in traditional Chinese fermented dairy products...
December 20, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29274585/knockdown-of-the-long-non-coding-rna-hottip-inhibits-colorectal-cancer-cell-proliferation-and-migration-and-induces-apoptosis-by-targeting-sgk1
#20
Tianyou Liu, Tao Yu, Haiying Hu, Keping He
More and more long non-coding RNA (lncRNA) might be serve as molecular biomarkers for tumor cell progression. HOTTIP has been recently revealed as oncogenic regulator in several cancers. However, it remains unclear about whether and how HOTTIP regulates Colorectal cancer (CRC). In the present study, we assayed the expression of HOTTIP in CRC tissues and cell lines, and detected CRC cells (HCT-116 and SW620) proliferation, migration, and apoptosis when HOTTIP was knocked down. Furthermore, we discovered the underlying mechanism...
December 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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