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https://www.readbyqxmd.com/read/29031039/the-anti-apoptotic-mechanism-of-metformin-against-apoptosis-induced-by-ionizing-radiation-in-human-peripheral-blood-mononuclear-cells
#1
S Kolivand, E Motevaseli, M Cheki, A Mahmoudzadeh, A Shirazi, V Fait
BACKGROUND: In a previous article, we showed that metformin (MET) can reduce ionizing radiation (IR) induced apoptosis in human peripheral blood mononuclear cells. However, the anti-apoptotic mechanism of MET against IR remains unclear. The present study attempts to investigate the mechanism of action of MET in limiting X-ray induced apoptosis in human peripheral blood mononuclear cells. MATERIAL AND METHODS: Mononuclear cells were treated with MET for 2 hours and irradiated with 6 MV X-rays...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29027214/development-of-an-alternative-zebrafish-model-for-drug-induced-intestinal-toxicity
#2
Bokyeong Ryu, C-Yoon Kim, Hanseul Oh, Ukjin Kim, Jin Kim, Cho-Rok Jung, Byoung-Hee Lee, Seungki Lee, Seo-Na Chang, Ji Min Lee, Hyung-Min Chung, Jae-Hak Park
An evaluation of intestinal toxicity is important because the mucosal lining of the gastrointestinal tract is the first barrier for oral xenobiotics. Until now, a rat model has been recommended as the standard intestinal toxicity model and the Caco-2 cell line, originated from a human colon adenocarcinoma, has been used as an alternative to this model, but there are limitations regarding cost-effectiveness and the need for mimicry of the human system. In this study, we investigated whether zebrafish could be a valid alternative to rats and Caco-2 cells as an intestinal toxicity model...
October 13, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29025092/heat-stress-induces-autophagy-in-pig-ovaries-during-follicular-development
#3
Benjamin J Hale, Candice L Hager, Jacob T Seibert, Joshua T Selsby, Lance H Baumgard, Aileen F Keating, Jason W Ross
Hyperthermia or heat stress (HS) occurs when heat dissipation mechanisms are overwhelmed by external and internal heat production. Hyperthermia negatively affects reproduction and potentially compromises oocyte integrity and reduces developmental competence of ensuing embryos. Autophagy is the process by which cells recycle energy through the reutilization of cellular components and is activated by a variety of stressors. Study objectives were to characterize autophagy-related proteins in the ovary following cyclical HS during the follicular phase...
August 28, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29024661/paclitaxel-reduces-axonal-bclw-to-initiate-ip3r1-dependent-axon-degeneration
#4
Sarah E Pease-Raissi, Maria F Pazyra-Murphy, Yihang Li, Franziska Wachter, Yusuke Fukuda, Sara J Fenstermacher, Lauren A Barclay, Gregory H Bird, Loren D Walensky, Rosalind A Segal
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of many cancer treatments. The hallmark of CIPN is degeneration of long axons required for transmission of sensory information; axonal degeneration causes impaired tactile sensation and persistent pain. Currently the molecular mechanisms of CIPN are not understood, and there are no available treatments. Here we show that the chemotherapeutic agent paclitaxel triggers CIPN by altering IP3 receptor phosphorylation and intracellular calcium flux, and activating calcium-dependent calpain proteases...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/29022246/alpha-lipoic-acid-mitigates-toxic-induced-demyelination-in-the-corpus-callosum-by-lessening-of-oxidative-stress-and-stimulation-of-polydendrocytes-proliferation
#5
Nima Sanadgol, Fereshteh Golab, Hassan Askari, Fatemeh Moradi, Marziyeh Ajdary, Mehdi Mehdizadeh
Multiple Sclerosis (MS), is a disease that degenerates myelin in central nervous system (CNS). Reactive oxygen species (ROSs) are toxic metabolites, and accumulating data indicate that ROSs-mediated apoptosis of oligodendrocytes (OLGs) plays a major role in the pathogenesis of MS under oxidative stress conditions. In this study, we investigated the role of endogenous antioxidant alpha-lipoic acid (ALA) as ROSs scavenger in the OLGs loss and myelin degeneration during cuprizone (cup)-induced demyelination in the experimental model of MS...
October 12, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29022237/dysfunction-of-membrane-trafficking-leads-to-ischemia-reperfusion-injury-after-transient-cerebral-ischemia
#6
REVIEW
Dong Yuan, Chunli Liu, Bingren Hu
Neurons require an extraordinarily high level of membrane trafficking activities because of enriched axonal terminals and dendritic branches. For that reason, defects in the membrane trafficking pathway are a hallmark of most, and may be all, neurodegenerative disorders. A major cellular membrane trafficking pathway is the Golgi apparatus (Golgi hereafter)-late endosome-lysosome axis for supplying lysosomal enzymes. This pathway is regulated by N-ethylmaleimide-sensitive factor (NSF) ATPase. This review article is to discuss a novel hypothesis that brain ischemia inactivates NSF ATPase, resulting in a cascade of events of disruption of the Golgi-endosome-lysosome pathway, release of cathepsin B (CTSB), and induction of mitochondrial outer membrane permeabilization (MOMP) during the postischemic phase...
October 11, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29021515/clinicopathological-analysis-of-320-cases-of-diffuse-large-b-cell-lymphoma-using-the-hans-classifier
#7
Akifumi Ichiki, Joaquim Carreras, Masashi Miyaoka, Yara Yukie Kikuti, Tadashi Jibiki, Kei Tazume, Shigeki Watanabe, Tamotsu Sasao, Yoshiaki Obayashi, Makoto Onizuka, Ken Ohmachi, Fumiaki Yoshiba, Yukari Shirasugi, Yoshiaki Ogawa, Hiroshi Kawada, Naoya Nakamura, Kiyoshi Ando
The estimation of clinical prognosis for diffuse large B-cell lymphoma (DLBCL) with a quick, cost-efficient method is necessary because of the clinical heterogeneity of this disease, which leads to death, relapsed or refractory disease in approximately 40% of patients. We analyzed 320 cases diagnosed from 2007 to 2013 treated with R-CHOP therapy at Tokai University Hospital and associated institutions. DLBCL was classified according to the cell-of-origin using the Hans algorithm [germinal center B-cell-like (GCB) vs non-GCB subtypes], and into 6 subgroups derived from combinations of CD10, BCL6 and MUM1 markers...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#8
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in MM cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase I study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/29017053/apoptosis-up-the-ante
#9
Palaniraja Thandapani, Iannis Aifantis
The clinical success of the BH3-mimetic venetoclax has generated increasing interest to target BCL2 family proteins in oncology. In this issue of Cancer Cell, Reyna and colleagues demonstrate the potential of a pharmacological activator of the pro-apoptotic protein BAX to suppress acute myeloid leukemia both alone and together with venetoclax.
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28992336/molecular-and-cytogenetic-effects-of-thai-royal-jelly-modulation-through-c-myc-h-tert-nrf2-ho-1-bcl2-bax-and-cyclins-in-human-lymphocytes-in-vitro
#10
Wantha Jenkhetkan, Sumon Thitiorul, Chalerm Jansom, Treetip Ratanavalachai
Royal jelly (RJ) is widely used as a food supplement for anti-aging and beauty. However, its use has been linked to asthma and hemorrhagic colitis. Since its mechanisms of toxicity have not been fully identified, we conducted an investigation to elucidate its molecular and cytogenetic effects. Using human lymphocytes in vitro, treatments with RJ (0.0005-5 mg/ml) for 3 h did not induce sister chromatid exchanges until 5 mg/ml was used. Treatments for 24 h showed a dose-dependent reduction in BCL2/BAX, c-MYC/BAX and HO-1/BAX ratios...
September 15, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28990517/anesthetic-agents-and-neuronal-autophagy-what-we-know-and-what-we-don-t
#11
Lili Xu, Jianjun Shen, Patrick M McQuillan, Zhiyong Hu
Numerous experimental data have demonstrated that neonatal animal exposure to commonly used anesthetic agents may cause neuronal death resulting in cognitive impairment. The underlying mechanism(s) remain elusive. Depending on the circumstances, autophagy may produce an effect that can be either protective or deleterious. Recent evidence demonstrates that this process can reduce the development of ethanol induced neurotoxicity and, as we know, ethanol has γ-Aminobutyric acid (GABA) agonist and N-methyl-D-aspartate (NMDA) antagonist characteristics similar to commonly used volatile anesthetic agents...
October 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28988613/amelioration-of-panadol-induced-nephrotoxicity-via-down-regulation-of-bax-bcl2-ratio-with-some-antioxidants
#12
Nouf Al-Rasheed, Laila M Faddah, Iman H Hasan, Hanaa M Ali, Nawal Al-Rasheed, Nagla F El Oraby, Mahmoud H Mohamed
BACKGROUND: Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, Thymoquinone (THQ), Curcumin (CUR) and α-Lipoic acid (LA) either alone or in combination against APAP nephrotoxicity, focused on modulation of Bax/Bcl2 pathway. METHODS: APAP was administrated at a single dose then treated with the fore mentioned antioxidants...
May 6, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28987383/hsp90-inhibitor-nvp-auy922-enhances-the-anti-cancer-effect-of-bcl-2-inhibitor-abt-737-in-small-cell-lung-cancer-expressing-bcl-2
#13
Hannah Yang, Mi-Hee Lee, Intae Park, Hanwool Jeon, Junyoung Choi, Seyoung Seo, Sang-We Kim, Gou Young Koh, Kang-Seo Park, Dae Ho Lee
Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC...
October 4, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28987347/association-study-of-apoptosis-gene-polymorphisms-in-mitochondrial-diabetes-a-potential-role-in-the-pathogenicity-of-md
#14
Mouna Tabebi, Bodour Khabou, Hanen Boukadi, Mariam Ben Hamad, Bochra Ben Rhouma, Slim Tounsi, Abdellatif Maalej, Hassen Kamoun, Leila Keskes-Ammar, Mohamed Abid, Mouna Mnif, Faiza Fakhfakh
Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia and is maternally transmitted. Syndromic MD is a subgroup of MD including diabetic microangiopathy and macroangiopathy, in addition to extrapancreatic disorder. MD is caused by genetic mutations and deletions affecting mitochondrial DNA. This mitochondrial damage initiates apoptosis. In this study, we hypothesized that functional polymorphisms in genes involved in apoptotic pathway could be associated with the development of apoptosis in MD disease and increased its risk...
October 4, 2017: Gene
https://www.readbyqxmd.com/read/28986568/bik-reduces-hyperplastic-cells-by-increasing-bak-and-activating-dapk1-to-juxtapose-er-and-mitochondria
#15
Yohannes A Mebratu, Ivan Leyva-Baca, Marc G Wathelet, Neal Lacey, Hitendra S Chand, Augustine M K Choi, Yohannes Tesfaigzi
Bik reduces hyperplastic epithelial cells by releasing calcium from endoplasmic reticulum stores and causing apoptosis, but the detailed mechanisms are not known. Here we report that Bik dissociates the Bak/Bcl-2 complex to enrich for ER-associated Bak and interacts with the kinase domain of DAPk1 to form Bik-DAPk1-ERK1/2-Bak complex. Bik also disrupts the Bcl2-IP3R interaction to cause ER Ca(2+) release. The ER-associated Bak interacts with the kinase and calmodulin domains of DAPk1 to increase the contact sites of ER and mitochondria, and facilitate ER Ca(2+) uptake by mitochondria...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28985947/induction-of-the-chromosomal-translocation-t-14-18-by-targeting-the-bcl-2-locus-with-specific-binding-i-125-labeled-triplex-forming-oligonucleotides
#16
Volker Dahmen, Sabine Schmitz, Ralf Kriehuber
Triplex-Forming oligonucleotides (TFO) bind sequence-specific to the DNA double helix in-vitro and in-vivo and are a promising tool to manipulate genes or gene regulatory elements. TFO as a carrier molecule for short-range particle emitter such as Auger-Electron-Emitters (AEE) bear the potential to introduce radiation-induced site-specific complex DNA lesions, which are known to induce chromosomal translocations. We studied gene expression, translocation frequency and protein expression in SCL-II cells after transfection with the AEE Iodine-125 (I-125) labeled TFO-BCL2 targeting the human BCL2 gene...
November 2017: Mutation Research
https://www.readbyqxmd.com/read/28985567/genetic-and-functional-drivers-of-diffuse-large-b%C3%A2-cell-lymphoma
#17
Anupama Reddy, Jenny Zhang, Nicholas S Davis, Andrea B Moffitt, Cassandra L Love, Alexander Waldrop, Sirpa Leppa, Annika Pasanen, Leo Meriranta, Marja-Liisa Karjalainen-Lindsberg, Peter Nørgaard, Mette Pedersen, Anne O Gang, Estrid Høgdall, Tayla B Heavican, Waseem Lone, Javeed Iqbal, Qiu Qin, Guojie Li, So Young Kim, Jane Healy, Kristy L Richards, Yuri Fedoriw, Leon Bernal-Mizrachi, Jean L Koff, Ashley D Staton, Christopher R Flowers, Ora Paltiel, Neta Goldschmidt, Maria Calaminici, Andrew Clear, John Gribben, Evelyn Nguyen, Magdalena B Czader, Sarah L Ondrejka, Angela Collie, Eric D Hsi, Eric Tse, Rex K H Au-Yeung, Yok-Lam Kwong, Gopesh Srivastava, William W L Choi, Andrew M Evens, Monika Pilichowska, Manju Sengar, Nishitha Reddy, Shaoying Li, Amy Chadburn, Leo I Gordon, Elaine S Jaffe, Shawn Levy, Rachel Rempel, Tiffany Tzeng, Lanie E Happ, Tushar Dave, Deepthi Rajagopalan, Jyotishka Datta, David B Dunson, Sandeep S Dave
Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28985492/primary-cardiac-diffuse-large-b-cell-lymphoma-with-concurrent-high-myc-and-bcl2-expression-in-an-immunocompetent-chinese-elderly-woman
#18
Ying Wan, Du He, Yunxia Ye, Wenyan Zhang, Sha Zhao, Yanhong Long, Min Chen, Can Küçük
Primary cardiac lymphoma is a rare type of extranodal lymphoma that involves only heart and/or pericardium. It is usually observed in immunodeficient people. However, immunocompetent patients may also suffer from this disease. Most primary cardiac lymphomas are of B-cell lineage, and they usually present as diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphoma with concurrently high MYC and BCL2 expression, which is named as double-expressor lymphoma (DEL), is a rare subtype of DLBCL. Here we report a rare case of a primary cardiac DEL in an immunocompetent 65-year old Chinese woman...
August 4, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28984869/bcl2-and-mir-15-16-from-gene-discovery-to-treatment
#19
REVIEW
Yuri Pekarsky, Veronica Balatti, Carlo M Croce
In 1984, we investigated the t(14;18) chromosomal translocations that frequently occur in patients with follicular lymphoma. We first identified a locus on chromosome 18 involved in these translocations with the chromosome 14 containing the immunoglobulin heavy chain locus. Within this region on chromosome 18, we then discovered a gene that we called BCL2, which was activated by the translocations. Since that time, many studies determined that BCL2 is one of the most important oncogenes involved in cancer by inhibiting apoptosis...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28984304/clinicopathological-and-genomic-analysis-of-double-hit-follicular-lymphoma-comparison-with-high-grade-b-cell-lymphoma-with-myc-and-bcl2-and-or-bcl6-rearrangements
#20
Masashi Miyaoka, Yara Y Kikuti, Joaquim Carreras, Haruka Ikoma, Shinichiro Hiraiwa, Akifumi Ichiki, Minoru Kojima, Kiyoshi Ando, Tomoyuki Yokose, Rika Sakai, Masahiro Hoshikawa, Naoto Tomita, Ikuo Miura, Katsuyoshi Takata, Tadashi Yoshino, Jun Takizawa, Silvia Bea, Elias Campo, Naoya Nakamura
Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles...
October 6, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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