D protein response activation observed in fibroblast cells from neuronopathic GD patients might be a typical mediator of apoptosis in neurodegenerative lysosomal storage issues. This suggests that mutated hGBAs may trigger apoptosis by means of ER stress in Drosophila eyes.results showed that Ambroxol can reduce ER stress and ameliorate neurodevelopmental defects in Drosophila with the RecNciI mutation. The complex allele RecNciI also contains L444P point mutation. The data suggests that Ambroxol acts as a pharmacological chaperone for the RecNciI GlcCerase variant in Drosophila eye. As ER pressure contributes to neurodegeneration across a selection of neurodegenerative disorders [24], Ambroxol may have an essential use in ameliorating neurodegeneration in GD patients.AcknowledgmentsWe thank Professor Shoji Tsuji at the University of Tokyo for the gift on the hGBA cDNAs. Stocks of GMR-GAL4 flies were obtained from the National Institute of Genetics Fly Stock Center (Shizuoka, Japan). Stocks of hs-GAL4, CG31414[Mi], CG31148[Mi], NMDA Receptor Antagonist web elav-GAL4, UAS-SNCA-WT, UAS-SNCA-A53T and UAS-SNCA-A30P flies were obtained from the Bloomington Stock Center (Bloomington, IN, USA).Author ContributionsConceived and created the experiments: TS M. Shimoda NI. Performed the experiments: TS TK. Analyzed the information: TS. Contributed reagents/ materials/analysis tools: M. Shimoda HDR ST NI. Wrote the paper: TS M. Shimoda. Guided the experiments: KI SH HA KK TY NG M. Setou ST. Offered substantial input into the writing of your manuscript: ST NI.Ambroxol ameliorates neurodevelopmental defects and decreases ER anxiety induced by mutant hGBA expression in Drosophila eyeAmbroxol is generally known as a pharmacological chaperone for mutant TLR7 Antagonist Synonyms glucocerebrosidase such as the L444P point mutation [30]. Our
VOLUMENUMBERJUNEJOURNAL OF CLINICAL ONCOLOGYONCOLOGY GRAND ROUNDSStrategies for Relapsed Peripheral T-Cell Lymphoma: The Tail That Wags the CurveMatthew A. Lunning, Alison J. Moskowitz, and Steven Horwitz, Memorial Sloan-Kettering Cancer Center, New York, NY See accompanying write-up on page 1970 The Oncology Grand Rounds series is designed to place original reports published within the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a evaluation of your relevant literature, plus a summary with the authors’ recommended management approaches. The purpose of this series should be to assist readers far better fully grasp tips on how to apply the outcomes of important studies, which includes these published in Journal of Clinical Oncology, to individuals noticed in their own clinical practice.A 69-year-old woman was referred for additional evaluation and management of relapsed angioimmunoblastic T-cell lymphoma.Atdiagnosis,shereceivedsixcyclesofdose-adjustedEPOCH(etoposide,prednisone,vincristine,cyclophosphamide, and doxorubicin) and accomplished a full response (CR). Her very first surveillance computed tomography scan 3 months later demonstrated enlarging cervical lymphadenopathy. A lymph node excision confirmed relapsed angioimmunoblasticT-celllymphomawithatypicallymphocytesexpressingCD3,CD4,CD10,PD-1,andEBER,withlossof CD5(Fig1).AclonalT-cellreceptorbetaandgammarearrangementbypolymerasechainreactionwasidenticaltothat inherinitialdiagnosticbiopsy.Atourinitialconsultation,optionsforstandardaswellasinvestigationaltherapieswere discussed, and HLA typing was initiated. The patient was enrolled onto an investigational phase II study; even so, she developed progressive disease following two cycles.