TMET-30. ENHANCED RADIOSENSITIZATION OF GLIOMAS BY METABOLIC TARGETING OF SALVAGE PATHWAY OF NAD SYNTHESIS THROUGH NAMPT INHIBITION
نویسندگان
چکیده
Abstract BACKGROUND Pathway-specific targeted agents have failed to improve outcome in patients with high grade gliomas. Tumor recurrence is driven by glioma heterogeneity and emergence of therapy-resistant subpopulations. We previously reported that metabolic targeting NAMPT, the rate limiting enzyme NAD salvage synthesis pathway, circumvents induces cytotoxicity mitochondrial membrane depolarization generation reactive oxygen species. Based on these data, we examined potential for NAMPT inhibition synergize ionizing radiation enhance vitro vivo. METHODS Using a panel genetically heterogeneous patient-derived stem-like cells (GSC), effects using KPT9274, potent inhibitor, combination cell proliferation clonogenicity Cell Titre Glo assay, colony formation assays secondary sphere formation. Changes DNA damage-related proteins were visualized immunofluorescence assay confocal microscopy. Effects gene expression protein levels assessed western blot, reverse phase array (RPPA) RNA Seq. RESULTS reduced rate, self-renewal clonogenic capacity vitro. Combining KPT-9274 caused synergistic GSC. RPPA RNASeq results showed downregulation several repair which was further confirmed staining indicating crucial role resistance therapies. Results ongoing vivo studies assess PK/PD, drug toxicity survival benefits this therapy orthotopic GSC intracranial mouse model will be reported. CONCLUSIONS Our suggest through sensitizes radiotherapy. Ongoing delineating mechanistic basis their impact as rationale clinical assessment
منابع مشابه
control of the optical properties of nanoparticles by laser fields
در این پایان نامه، درهمتنیدگی بین یک سیستم نقطه کوانتومی دوگانه(مولکول نقطه کوانتومی) و میدان مورد مطالعه قرار گرفته است. از آنتروپی ون نیومن به عنوان ابزاری برای بررسی درهمتنیدگی بین اتم و میدان استفاده شده و تاثیر پارامترهای مختلف، نظیر تونل زنی(که توسط تغییر ولتاژ ایجاد می شود)، شدت میدان و نسبت دو گسیل خودبخودی بر رفتار درجه درهمتنیدگی سیستم بررسی شده اشت.با تغییر هر یک از این پارامترها، در...
15 صفحه اولTGF-β1 enhanced myocardial differentiation through inhibition of the Wnt/β-catenin pathway with rat BMSCs
Objective(s): To investigate and test the hypotheses that TGF-β1 enhanced myocardial differentiation through Wnt/β-catenin pathway with rat bone marrow mesenchymal stem cells (BMSCs).Materials and Methods: Lentiviral vectors carrying the TGF-β1 gene were transduced into rat BMSCs firstly. Then several kinds of experimental methods were u...
متن کاملNAMPT-Mediated Salvage Synthesis of NAD+ Controls Morphofunctional Changes of Macrophages
Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H) (i.e. NAD+ and NADH) and NADP(H) (i.e. NADP+ and NADPH) play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between ac...
متن کاملcomparison of catalytic activity of heteropoly compounds in the synthesis of bis(indolyl)alkanes.
heteropoly acids (hpa) and their salts have advantages as catalysts which make them both economically and environmentally attractive, strong br?nsted acidity, exhibiting fast reversible multi-electron redox transformations under rather mild conditions, very high solubility in polar solvents, fairly high thermal stability in the solid states, and efficient oxidizing ability, so that they are imp...
15 صفحه اولstudy of cohesive devices in the textbook of english for the students of apsychology by rastegarpour
this study investigates the cohesive devices used in the textbook of english for the students of psychology. the research questions and hypotheses in the present study are based on what frequency and distribution of grammatical and lexical cohesive devices are. then, to answer the questions all grammatical and lexical cohesive devices in reading comprehension passages from 6 units of 21units th...
ذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.1035