keyword
MENU ▼
Read by QxMD icon Read
search

BH3

keyword
https://www.readbyqxmd.com/read/28106939/maximizing-output-in-rna-programmed-peptidyl-transfer-reactions
#1
Margherita Di Pisa, Anett Hauser, Oliver Seitz
A chemical reaction that is triggered by specific RNA molecules may provide opportunities for the design of artificial feedback loops. We envision a peptidyl transfer reaction, in which mRNA encoding for antiapoptotic protein would instruct the synthesis of apoptosis-inducing peptides. In this study, we tackled the RNA-programmed synthesis of a 16mer peptide derived from the Bak-BH3 protein which inhibits the antiapoptotic protein Bcl-xL. The reaction involves the transfer of a thioester-linked donor peptide fragment from one PNA conjugate onto an acceptor peptide-PNA conjugate...
January 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28105175/analysis-of-transcription-profile-to-reveal-altered-signaling-pathways-following-the-overexpression-of-human-desumoylating-isopeptidase-2-in-pancreatic-cancer-cells
#2
Yu-Yin Fu, Yu-Huan Kang, Cong-Cong Shen, Rui-Xue Wang, Lin Yu, Xin-Yue Li, Dan-Dan Cui, Jin-Liang Yang, Yu-Qin Yao, Lan-Tu Gou
Human desumoylating isopeptidase 2 (DESI-2) is a member of the DESI family and contains a conserved PPPDE1 domain. Previous studies have demonstrated that DESI-2 overexpression may induce cell apoptosis. In the present study, differentially expressed genes were analyzed using a transcription microarray in DESI-2 overexpressing PANC-1 pancreatic cancer cells. A total of 45,033 genes were examined by microarray, which identified 1,766 upregulated and 1,643 downregulated genes. A series of altered signaling pathways were analyzed, in which certain essential signaling factors, including retinoid X receptor (RXR), BH3 interacting-domain death agonist, Ras homolog gene family member A (RhoA) and Rho-associated protein kinase, were further investigated at the protein level...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104700/inhibition-of-4ebp-phosphorylation-mediates-the-cytotoxic-effect-of-mtor-kinase-inhibitors-in-aggressive-b-cell-lymphomas
#3
Chengfeng Bi, Xuan Zhang, Ting Lu, Xiaoyan Zhang, Xianhuo Wang, Bin Meng, Huilai Zhang, Ping Wang, Julie M Vose, Wing C Chan, Timothy W McKeithan, Kai Fu
Mechanistic target of rapamycin complex 1 (mTORC1) is a central integrator of nutrient and growth factor inputs that controls cell growth in eukaryotes. The second generation of mTOR kinase inhibitors (TORKi), directly targeting the mTOR catalytic site, are more effective than rapamycin and its analogs in cancer treatment, particularly in inducing apoptosis. However, the mechanism underlying the cytotoxic effect of TORKi remains elusive. Herein, we demonstrated that TORKi-induced apoptosis is predominantly dependent on loss of mTORC1-mediated 4EBP activation...
January 19, 2017: Haematologica
https://www.readbyqxmd.com/read/28100580/venetoclax-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#4
Andrew W Roberts, Stephan Stilgenbauer, John F Seymour, David C S Huang
Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacological mimic of the proteins that initiate apoptosis (a so-called BH3-mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a Phase 1 study, including complete remissions in 20% of patients...
January 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28099007/pyridinium-boranephosphonate-modified-dna-oligonucleotides
#5
Subhadeep Roy, Sibasish Paul, Mithun Roy, Rajen Kundu, Luca Monfregola, Marvin H Caruthers
The synthesis of previously unknown derivatives of boranephosphonate that contain amine substitutions at boron and the incorporation of these derivatives into the backbone of DNA oligonucleotides is described. These derivatives result from iodine-mediated replacement of one BH3 hydride of a boranephosphonate linkage by pyridine, various substituted pyridines, other aromatic amines, and certain unsaturated amines. Oligonucleotides containing these backbone modifications show enhanced uptake, relative to unmodified DNA, in mammalian cells...
January 18, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28094768/bcl-w-has-a-fundamental-role-in-b-cell-survival-and-lymphomagenesis
#6
Clare M Adams, Annette S Kim, Ramkrishna Mitra, John K Choi, Jerald Z Gong, Christine M Eischen
Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28079890/structural-insight-into-an-evolutionarily-ancient-programmed-cell-death-regulator-the-crystal-structure-of-marine-sponge-bhp2-bound-to-lb-bak-2
#7
Sofia Caria, Mark G Hinds, Marc Kvansakul
Sponges of the porifera family harbor some of the evolutionary most ancient orthologs of the B-cell lymphoma-2 (Bcl-2) family, a protein family critical to regulation of apoptosis. The genome of the sponge Geodia cydonium contains the putative pro-survival Bcl-2 homolog BHP2, which protects sponge tissue as well as mammalian Hek-293 and NIH-3T3 cells against diverse apoptotic stimuli. The Lake Baikal demosponge Lubomirskia baicalensis has been shown to encode both putative pro-survival Bcl-2 (LB-Bcl-2) and pro-apoptotic Bcl-2 members (LB-Bak-2), which have been implied in axis formation (branches) in L...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079889/deletion-of-the-bh3-only-protein-noxa-alters-electrographic-seizures-but-does-not-protect-against-hippocampal-damage-after-status-epilepticus-in-mice
#8
Naoki Ichikawa, Mariana Alves, Shona Pfeiffer, Elena Langa, Yasmina E Hernández-Santana, Hidenori Suzuki, Jochen Hm Prehn, Tobias Engel, David C Henshall
Several members of the Bcl-2 gene family are dysregulated in human temporal lobe epilepsy and animal studies show that genetic deletion of some of these proteins influence electrographic seizure responses to chemoconvulsants and associated brain damage. The BH3-only proteins form a subgroup comprising direct activators of Bax-Bak that are potently proapoptotic and a number of weaker proapoptotic BH3-only proteins that act as sensitizers by neutralization of antiapoptotic Bcl-2 family members. Noxa was originally characterized as a weaker proapoptotic, 'sensitizer' BH3-only protein, although recent evidence suggests it too may be potently proapoptotic...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079887/drp-1-is-required-for-bh3-mimetic-mediated-mitochondrial-fragmentation-and-apoptosis
#9
Mateus Milani, Dominic P Byrne, Georgia Greaves, Michael Butterworth, Gerald M Cohen, Patrick A Eyers, Shankar Varadarajan
The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28075124/ptni-nio-clusters-coated-by-hollow-sillica-novel-design-for-highly-efficient-hydrogen-production-from-ammonia-borane
#10
Yuzhen Ge, Wanyue Ye, Zameer Hussain Shah, Xijie Lin, Rongwen Lu, Shufen Zhang
Ammonia-borane (NH3·BH3; AB) has been considered as an excellent chemical material for hydrogen storage. However, developing highly efficient catalysts for continuous hydrogen generation from AB is still a challenge for future fuel cell applications. The combination of Pt with Ni is an effective strategy to achieve active bimetallic nanocatalyst, and the particle size has proved to play a crucial role in determining its final activity. However, the synthesis of PtNi bimetallic catalyst in the size of highly dispersed clusters has always been a challenge...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#11
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28069133/bh3-only-proteins-in-health-and-disease
#12
J A Glab, G W Mbogo, H Puthalakath
BH3-only proteins are proapoptotic members of the broader Bcl-2 family, which promote cell death by directly or indirectly activating Bax and Bak. The expression of BH3-only proteins is regulated both transcriptionally and posttranscriptionally in a cell type-specific and a tissue-specific manner. Research over the last 20 years has provided significant insights into their roles in tissue homeostasis and various pathologies, which in turn has led to the development of novel therapeutics for numerous diseases...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28067996/virtual-screening-sar-and-discovery-of-5-indole-3-yl-2-2-nitrophenyl-amino-1-3-4-oxadiazole-as-a-novel-bcl-2-inhibitor
#13
Noha I Ziedan, Rania Hamdy, Alessandra Cavaliere, Malamati Kourti, Filippo Prencipe, Andrea Brancale, Arwyn T Jones, Andrew D Westwell
A new series of oxadiazoles were designed to act as inhibitors of the anti-apoptotic Bcl-2 protein. Virtual screening led to the discovery of new hits that interact with Bcl-2 at the BH3 binding pocket. Further study of the structure-activity relationship of the most active compound of the first series, compound 1, led to the discovery of a novel oxadiazole analogue, compound 16j, that was a more potent small molecule inhibitor of Bcl-2. 16j had good in vitro inhibitory activity with sub-micromolar IC50 values in a metastatic human breast cancer cell line (MDA-MB-231) and a human cervical cancer cell line (HeLa)...
January 9, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28055968/bh3-mimetics-suppress-cxcl12-expression-in-human-malignant-peripheral-nerve-sheath-tumor-cells
#14
Christopher D Graham, Niroop Kaza, Hawley C Pruitt, Lauren M Gibson, Barbara J Klocke, Lalita A Shevde, Steven L Carroll, Kevin A Roth
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Schwann cell-derived neoplasms of the peripheral nervous system that have recently been shown to possess an autocrine CXCL12/CXCR4 signaling loop that promotes tumor cell proliferation and survival. Importantly, the CXCL12/CXCR4 signaling axis is driven by availability of the CXCL12 ligand rather than CXCR4 receptor levels alone. Therefore, pharmacological reduction of CXCL12 expression could be a potential chemotherapeutic target for patients with MPNSTs or other pathologies wherein the CXCL12/CXCR4 signaling axis is active...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28053104/structural-insight-into-african-swine-fever-virus-a179l-mediated-inhibition-of-apoptosis
#15
Suresh Banjara, Sofia Caria, Linda K Dixon, Mark G Hinds, Marc Kvansakul
: Programmed cell death is a tightly controlled process critical for the removal of damaged or infected cells. Pro- and anti-apoptotic proteins of the Bcl-2 family are pivotal mediators of this process. African Swine Fever virus (ASFV) is a large DNA virus, the only member of the Asfarviridae family, and harbors A179L, a putative Bcl-2 like protein. A179L has been shown to bind to several pro-apoptotic Bcl-2 proteins, however the hierarchy of binding and the structural basis for apoptosis inhibition are currently not understood...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28045528/insights-into-the-thermal-eliminations-and-photoeliminations-of-b-n-heterocycles-a-theoretical-study
#16
Wen-Jie Wu, Quan-Song Li, Ze-Sheng Li
Understanding the photochemistry of organoboron compounds is essential to expand optoelectronic applications. In this work, the complete active space self-consistent field (CASSCF) and its second-order perturbation (CASPT2) methods combining with density functional theory (DFT) have been employed to investigate the elimination mechanisms of compound 6,7-dihydro-5(4)-benzo[d]pyrido[2,1-f][1,2]azaborininr (B4) on the ground state (S0) and the first excited state (S1). B4 is one of the 1,2-B,N-heterocycles that undergo competitive thermal elimination and photoelimination depending on the substitution groups on the B atom and the chelate backbone, thus providing a high-selectivity synthesis strategy for luminescent compounds...
January 18, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28028022/multiple-myeloma-cells-capacity-to-decompose-h2o2-determines-lenalidomide-sensitivity
#17
Sinto Sebastian, Yuan X Zhu, Esteban Braggio, Chang-Xin Shi, Sonali C Panchabhai, Scott A Van Wier, Greg J Ahmann, Marta Chesi, P Leif Bergsagel, A Keith Stewart, Rafael Fonseca
Lenalidomide is an immunomodulatory drug (IMiDs) with clinical efficacy in multiple myeloma (MM) and other late B-cell neoplasms. Although cereblon (CRBN) is an essential requirement for IMiD action, the complete molecular and biochemical mechanisms responsible for lenalidomide-mediated sensitivity or resistance remain unknown. Here, we report that IMiDs work primarily via inhibition of peroxidase-mediated intracellular H2O2 decomposition in MM cells. MM cells with lower H2O2-decomposition capacity were more vulnerable to lenalidomide-induced H2O2 accumulation and associated cytotoxicity...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/28026162/hbfl-1-hnoxa-interaction-studies-provide-new-insights-on-the-role-of-bfl-1-in-cancer-cell-resistance-and-for-the-design-of-novel-anticancer-agents
#18
Elisa Barile, Guya D Marconi, Surya K De, Carlo Baggio, Luca Gambini, Ahmed F Salem, Manoj K Kashyap, Januario E Castro, Thomas J Kipps, Maurizio Pellecchia
Upregulation of antiapoptotic Bcl-2 proteins in certain tumors confers cancer cell resistance to chemotherapy or radiations. Members of the antiapoptotic Bcl-2 proteins, including Bcl-2, Mcl-1, Bcl-xL, Bcl-w, and Bfl-1, inhibit apoptosis by selectively binding to conserved α-helical regions, named BH3 domains, of pro-apoptotic proteins such as Bim, tBid, Bad, or NOXA. Five antiapoptotic proteins have been identified that interact with various selectivity with BH3 containing pro-apoptotic counterparts. Cancer cells present various and variable levels of these proteins, making the design of effective apoptosis based therapeutics challenging...
December 27, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/28017967/duvelisib-treatment-is-associated-with-altered-expression-of-apoptotic-regulators-that-helps-in-sensitization-of-chronic-lymphocytic-leukemia-cells-to-venetoclax-abt-199
#19
V M Patel, K Balakrishnan, M Douglas, T Tibbitts, E Y Xu, J L Kutok, M Ayers, A Sarkar, R Guerrieri, W G Wierda, S O'Brien, N Jain, H M Stern, V Gandhi
Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma (iNHL). In CLL, duvelisib monotherapy is associated with high iwCLL and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene-expression studies (RNA seq, Nanostring, Affymetrix array, and real time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28017613/developmental-regulation-of-mitochondrial-apoptosis-by-c-myc-governs-age-and-tissue-specific-sensitivity-to-cancer-therapeutics
#20
Kristopher A Sarosiek, Cameron Fraser, Nathiya Muthalagu, Patrick D Bhola, Weiting Chang, Samuel K McBrayer, Adam Cantlon, Sudeshna Fisch, Gail Golomb-Mello, Jeremy A Ryan, Jing Deng, Brian Jian, Chris Corbett, Marti Goldenberg, Joseph R Madsen, Ronglih Liao, Dominic Walsh, John Sedivy, Daniel J Murphy, Daniel Ruben Carrasco, Shenandoah Robinson, Javid Moslehi, Anthony Letai
It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 profiling, we find that mitochondria of many adult somatic tissues, including brain, heart, and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage...
January 9, 2017: Cancer Cell
keyword
keyword
50686
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"