Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumor stem cells (BTSCs).

Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumor stem cells (BTSCs). Biochem Cell Biol. 2019 Oct 31;: Authors: Ross JA, Ahn BY, King J, Bressler KR, Senger DL, Thakor N Abstract Glioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity and the presence of a population of stem-like cells called brain tumor stem cells (BTSCs/BTICs). These cancer stem cells survive treatment and confer resistance to the current therapies-namely, radiation and the chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, and BTSCs resist this mechanism via a robust DNA damage response. Hence, recent studies aimed to sensitize BTSCs to TMZ using combination therapy, such as inhibition of DNA repair machinery. We have previously demonstrated in established GBM cell lines that eukaryotic initiation factor 5B (eIF5B) promotes the translation of pro-survival and anti-apoptotic proteins. Consequently, silencing eIF5B sensitizes these cells to TRAIL-induced apoptosis. However, established cell lines do not always recapitulate the features of human glioma. Therefore, we investigated this mechanism in patient-derived BTSCs. We show that silencing eIF5B leads to increased TMZ sensitivity in two BTSC lines, BT25 and BT48. Depletion of eIF5B decreases levels of anti-apoptotic proteins in BT48 and sensitizes these cells to TMZ-induced activation of caspa...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research

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Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Yong Zhao1, Peijuan Liu1, Zhiqian Xin1, Changhong Shi1, Yinlan Bai2, Xiuxuan Sun3, Ya Zhao1, Xiaoya Wang1,4, Li Liu1,5, Xuan Zhao1,4, Zhinan Chen3* and Hai Zhang1,6* 1Laboratory Animal Center, Air Force Medical University, Xi’an, China 2Department of Microbiology, Air Force Medical University, Xi’an, China 3Department of Cell Biology, National Translational Science Center for Molecular Medicine, Air Force Medical University, Xi’an, China 4College of Veterinary Medicine, Northwest A&F University, Yangling, China 5Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Nor...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Qiancheng Deng1, Yangyang Luo1,2, Christopher Chang3, Haijing Wu1, Yan Ding4* and Rong Xiao1* 1Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China 2Department of Dermatology, Hunan Children's Hospital, Changsha, China 3Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States 4Department of Dermatology, Hainan Provincial Dermatology Disease Hospital, Haikou, China Autoimmune diseases are usually complex and multifactorial, characterized by aberrant produc...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, we have shown the safety and efficacy of Vemurafenib in a pediatric patient with DS affected by PXA. Ethics Statement This study was carried out in accordance with the recommendations of the Internal Review Board of the Bambino Gesù Children's Hospital with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Internal Review Board of the Bambino Gesù Children's Hospital. Informed Consent The authors declare that written informed consent was obtained from the pat...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Cancers, Vol. 11, Pages 350: Arsenic Trioxide and (−)-Gossypol Synergistically Target Glioma Stem-Like Cells via Inhibition of Hedgehog and Notch Signaling Cancers doi: 10.3390/cancers11030350 Authors: Benedikt Linder Andrej Wehle Stephanie Hehlgans Florian Bonn Ivan Dikic Franz Rödel Volker Seifert Donat Kögel Glioblastoma is one of the deadliest malignancies and is virtually incurable. Accumulating evidence indicates that a small population of cells with a stem-like phenotype is the major culprit of tumor recurrence. Enhanced DNA repair capacity and expression of stemness marker gene...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Parker Kerrigan BC, Hossain A, Yamashita S, Lang FF Abstract Stem cells (SC) are the seeds of tissue repair and regeneration that have been extensively investigated as tumor-tropic vectors for gene delivery to solid cancers. SC have an inherent glioma tropism that supports their use as reliable vehicles to deliver therapeutic gene products to brain neoplasms. Several types of adult SC (ASC) have been used to carry antiglioma agents, and neural SC (NSC) and mesenchymal SC (MSC) are the most studied. The therapeutic cargoes that have been tested include secreted proteins, converting enzyme/prodrug suicide co...
Source: Progress in Neurological Surgery - Category: Neurosurgery Tags: Prog Neurol Surg Source Type: research
In conclusion, CAVD is highly prevalent. Long understood as a passive process, it is now known to be complex and one which involves pathophysiological mechanisms similar to those of atherosclerosis. Understanding these mechanisms could help to establish new therapeutic targets that might allow us to halt or at least slow down the progression of the disease. Early Steps in the Tissue Engineering of Intervertebral Discs https://www.fightaging.org/archives/2017/08/early-steps-in-the-tissue-engineering-of-intervertebral-discs/ In this paper, researchers report on progress towards the manufacture of interver...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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