16 research outputs found
Enhanced Autophagy and Reduced Expression of Cathepsin D Are Related to Autophagic Cell Death in Epstein-Barr Virus-Associated Nasal Natural Killer/T-Cell Lymphomas: An Immunohistochemical Analysis of Beclin-1, LC3, Mitochondria (AE-1), and Cathepsin D in Nasopharyngeal Lymphomas
This study investigated autophagy in 37 cases of nasopharyngeal lymphomas including 23 nasal natural killer (NK)/T-cell lymphomas (NKTCL), 3 cytotoxic T-cell lymphomas (cytotoxic-TML) and 9 B-cell lymphomas (BML) by means of antigen-retrieval immunohistochemistry of beclin-1, LC3, mitochondria (AE-1) and cathepsin D. Peculiar necrosis was noted in EBV+ lymphomas comprising 21 NKTCL, 2 cytotoxic-TML and 1 BML. Lymphomas without peculiar necrosis showed high expression of beclin-1, macrogranular cytoplasmal stain of LC3 with sporadic nuclear stain, a hallmark of autophagic cell death (ACD), some aggregated mitochondria and high expression of cathepsin D, suggesting a state of growth with enhanced autophagy with sporadic ACD. EBV+ NKTCL with the peculiar necrosis, showed significantly low level of macrogranular staining of LC3, aggregated mitochondria and low expression of cathepsin D in the cellular areas when degenerative lymphoma cells showed decreased beclin-1, significantly advanced LC3-labeled autophagy, residual aggregated mitochondria and significantly reduced expression of cathepsin D, suggesting advanced autophagy with regional ACD. Consequently it was suggested that enhanced autophagy and reduced expression of lysosomal enzymes induced regional ACD under EBV infection in NKTCL
Concomitant administration of radiation with eribulin improves the survival of mice harboring intracerebral glioblastoma
Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a nonâtaxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in Mâphase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiationâinduced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patientâderived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas
Beth Levine in memoriam
Beth Levine was born on 7 April 1960 in Newark, New Jersey. She went to college at Brown University where she received an A.B. Magna Cum Laude, and she attended medical school at Cornell University Medical College, receiving her MD in 1986. She completed her internship and residency in Internal Medicine at Mount Sinai Hospital in New York, and her fellowship in Infectious Diseases at The Johns Hopkins Hospital. Most recently, Beth was a Professor of Internal Medicine and Microbiology, Director of the Center for Autophagy Research, and holder of the Charles Sprague Distinguished Chair in Biomedical Science at the University of Texas Southwestern Medical Center in Dallas. Beth died on 15 June 2020 from cancer. Beth is survived by her husband, Milton Packer, and their two children, Rachel (26 years old) and Ben (25 years old).
Dr. Levine was as an international leader in the field of autophagy research. Her laboratory identified the mammalian autophagy gene BECN1/beclin 1; identified conserved mechanisms underlying the regulation of autophagy (e.g. BCL2-BECN1 complex formation, insulin-like signaling, EGFR, ERBB2/HER2 and AKT1-mediated BECN1 phosphosphorylation); and provided the first evidence that autophagy genes are important in antiviral host defense, tumor suppression, lifespan extension, apoptotic corpse clearance, metazoan development, Na,K-ATPase-regulated cell death, and the beneficial metabolic effects of exercise. She developed a potent autophagy-inducing cell permeable peptide, Tat-beclin 1, which has potential therapeutic applications in a range of diseases. She was a founding Associate Editor of the journal Autophagy and an editorial board member of Cell and Cell Host & Microbe. She has received numerous awards/honors in recognition of her scientific achievement, including: The American Cancer Society Junior Faculty Research Award (1994); election into the American Society of Clinical Investigation (2000); the Ellison Medical Foundation Senior Scholars Award in Global Infectious Diseases (2004); elected member, American Association of Physicians (2005); appointment as a Howard Hughes Medical Institute Investigator (2008); Edith and Peter OâDonnell Award in Medicine (2008); elected fellow, American Association for the Advancement of Science (2012); election into the National Academy of Sciences (2013); election into the Academy of Medicine, Engineering and Science of Texas (2013); the ASCI Stanley J. Korsmeyer Award (2014); Phyllis T. Bodel Women in Medicine Award, Yale University School of Medicine (2018); recipient, Barcroft Medal, Queenâs University Belfast (2018).Fil: An, Zhenyi. No especifĂca;Fil: Ballabi, Andrea. No especifĂca;Fil: Bennett, Lynda. No especifĂca;Fil: Boya, Patricia. No especifĂca;Fil: Cecconi, Francesco. No especifĂca;Fil: Chiang, Wei Chung. No especifĂca;Fil: Codogno, Patrice. No especifĂca;Fil: Colombo, Maria Isabel. No especifĂca;Fil: Cuervo, Ana Maria. No especifĂca;Fil: Debnath, Jayanta. No especifĂca;Fil: Deretic, Vojo. No especifĂca;Fil: Dikic, Ivan. No especifĂca;Fil: Dionne, Keith. No especifĂca;Fil: Dong, Xiaonan. No especifĂca;Fil: Elazar, Zvulun. No especifĂca;Fil: Galluzzi, Lorenzo. No especifĂca;Fil: Gentile, Frank. No especifĂca;Fil: Griffin, Diane E.. No especifĂca;Fil: Hansen, Malene. No especifĂca;Fil: Hardwick, J. Marie. No especifĂca;Fil: He, Congcong. No especifĂca;Fil: Huang, Shu Yi. No especifĂca;Fil: Hurley, James. No especifĂca;Fil: Jackson, William T.. No especifĂca;Fil: Jozefiak, Cindy. No especifĂca;Fil: Kitsis, Richard N.. No especifĂca;Fil: Klionsky, Daniel J.. No especifĂca;Fil: Kroemer, Guido. No especifĂca;Fil: Meijer, Alfred J.. No especifĂca;Fil: MelĂ©ndez, Alicia. No especifĂca;Fil: Melino, Gerry. No especifĂca;Fil: Mizushima, Noboru. No especifĂca;Fil: Murphy, Leon O.. No especifĂca;Fil: Nixon, Ralph. No especifĂca;Fil: Orvedahl, Anthony. No especifĂca;Fil: Pattingre, Sophie. No especifĂca;Fil: Piacentini, Mauro. No especifĂca;Fil: Reggiori, Fulvio. No especifĂca;Fil: Ross, Theodora. No especifĂca;Fil: Rubinsztein, David C.. No especifĂca;Fil: Ryan, Kevin. No especifĂca;Fil: Sadoshima, Junichi. No especifĂca;Fil: Schreiber, Stuart L.. No especifĂca;Fil: Scott, Frederick. No especifĂca;Fil: Sebti, Salwa. No especifĂca;Fil: Shiloh, Michael. No especifĂca;Fil: Shoji, Sanae. No especifĂca;Fil: Simonsen, Anne. No especifĂca;Fil: Smith, Haley. No especifĂca;Fil: Sumpter, Kathryn M.. No especifĂca;Fil: Thompson, Craig B.. No especifĂca;Fil: Thorburn, Andrew. No especifĂca;Fil: Thumm, Michael. No especifĂca;Fil: Tooze, Sharon. No especifĂca;Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de BioquĂmica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de BioquĂmica y Medicina Molecular; ArgentinaFil: Virgin, Herbert W.. No especifĂca;Fil: Wang, Fei. No especifĂca;Fil: White, Eileen. No especifĂca;Fil: Xavier, Ramnik J.. No especifĂca;Fil: Yoshimori, Tamotsu. No especifĂca;Fil: Yuan, Junying. No especifĂca;Fil: Yue, Zhenyu. No especifĂca;Fil: Zhong, Qing. No especifĂca
p21 Waf1 Cip1 Sdi1 㯠ă»ă€ăžăł Tă”ă€ă㊠ăăă±ăăă§ăŠ ăŠă€ă«ăč ㏠ăłăŒăăčă« Tax ă ăšăă ăă©ăłăčăă©ăŒă ăăżăŻ ăă·ă«ă·ăż ă”ă€ă㊠ă ăŸăŠă·ă§ăŻ ăȘ ăœăŻă·ăłă· ă«ă ăąăăăŒă·ăč ăȘ ăšăŻă»ă€ăčă«
äșŹéœć€§ćŠ0048æ°ć¶ă»èȘČçšć棫ć棫(ć»ćŠ)çČ珏10418ć·ć»ć珏2641ć·æ°ć¶||ć»||841(éć±ćłæžé€š)UT51-2003-N909äșŹéœć€§ćŠć€§ćŠéąć»ćŠç 究ç§ç
ççł»ć°æ»(äž»æ»)ææ æŸćČĄ é
é, ææ ć
ć±± ć, ææ äžé é éŠćż ćŠäœèŠć珏4æĄçŹŹ1é
è©ČćœDoctor of Medical ScienceKyoto UniversityDA
ăȘăčă«ăŒ ăŻă€ă«ă ă ăżăłă ă·ă„ăź ăăȘăąăł ă°ăŹă€ ă ă·ă§ăŠăŸăŠăŹ ăȘ ăă„ăŠă·ăł ă
Therapeutic drug monitoring in peritoneal dialysis: A case of nontuberculous mycobacterium catheterârelated infection treated with amikacin
The pharmacokinetics of amikacin makes it difficult to predict the appropriate dosing to avoid harmful side effects in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The implementation of therapeutic drug monitoring may be useful in controlling amikacin serum concentrations in patients receiving CAPD
TLR9 and beclin 1 crosstalk regulates muscle AMPK activation in exercise.
The activation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle coordinates systemic metabolic responses to exercise. Autophagy-a lysosomal degradation pathway that maintains cellular homeostasis-is upregulated during exercise, and a core autophagy protein, beclin 1, is required for AMPK activation in skeletal muscle. Here we describe a role for the innate immune-sensing molecule Toll-like receptor 9 (TLR9), and its interaction with beclin 1, in exercise-induced activation of AMPK in skeletal muscle. Mice that lack TLR9 are deficient in both exercise-induced activation of AMPK and plasma membrane localization of the GLUT4 glucose transporter in skeletal muscle, but are not deficient in autophagy. TLR9 binds beclin 1, and this interaction is increased by energy stress (glucose starvation and endurance exercise) and decreased by a BCL2 mutation that blocks the disruption of BCL2-beclin 1 binding. TLR9 regulates the assembly of the endolysosomal phosphatidylinositol 3-kinase complex (PI3KC3-C2)-which contains beclin 1 and UVRAG-in skeletal muscle during exercise, and knockout of beclin 1 or UVRAG inhibits the cellular AMPK activation induced by glucose starvation. Moreover, TLR9 functions in a muscle-autonomous fashion in ex vivo contraction-induced AMPK activation, glucose uptake and beclin 1-UVRAG complex assembly. These findings reveal a heretofore undescribed role for a Toll-like receptor in skeletal-muscle AMPK activation and glucose metabolism during exercise, as well as unexpected crosstalk between this innate immune sensor and autophagy proteins
Fatigue Is a Predictor for Cardiovascular Outcomes in Patients Undergoing Hemodialysis
Background and objectives: Despite potential significance of fatigue and its underlying components in the occurrence of cardiovascular diseases, epidemiologic data showing the link are virtually limited. This study was designed to examine whether fatigue symptoms or fatigue's underlying components are a predictor for cardiovascular diseases in high-risk subjects with ESRD