Radiation-induced molecular targets

辐射诱导的分子靶标

• 批准号: 10926052
• 负责人: Norman Coleman
• 金额: $ 196.88万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926052
• 关键词: Abscopal effect; Aftercare; Biological; Biological Markers; Cell Survival; Cells; Clinic; Clinical; Combined Modality Therapy; Complex; Data; Dose; Drug Design; Drug usage; Endothelial Cells; Epigenetic Process; Fractionation; Genes; Growth; Health; Heat-Shock Proteins 90; Human; Immune; Immune response; Immunotherapy; In Vitro; Intensity-Modulated Radiotherapy; Laboratories; Magnetic Resonance Imaging; MicroRNAs; Miniature Swine; Molecular; Molecular Target; Normal tissue morphology; Ontology; Pathway interactions; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Predisposition; Proteomics; Radiation; Radiation Dose Unit; Radiation Injuries; Radiation Oncology; Radiation therapy; Readiness; Services; Systems Analysis; Techniques; Technology; Testing; Update; Work; biodosimetry; biological adaptation to stress; biomarker identification; cancer care; cell killing; chemoradiation; drug-sensitive; fractionated radiation; image guided radiation therapy; immunoregulation; in vivo; inhibitor; interest; mass casualty; metabolic abnormality assessment; metabolomics; molecular targeted therapies; programs; response; survival prediction; targeted agent; tissue injury; tumor

The long-standing focus of our laboratory program involves the radiation and microenvironmental stress response. We are now focusing on "radiation inducible targets" that is, exploring the use of multi-fractionated (MF) radiation as well as higher single doses (SD) to induce a cellular phenotype that makes the cell susceptible for molecular targeted therapy and immunotherapy. In essence, radiation would set up the tumor for enhanced drug killing and enhanced immune response. This project has now demonstrated that different dose sizes of radiation- MF and SD - (10 Gy x1, 2 Gy x5, 1 Gy x10 and down to 0.5 Gy x 10) produce different phenotypes. We have demonstrated that the cells post-radiation are more drug sensitive to a drug post-radiation than before at 1 week and up to 3 months later, indicating stable adaptation. This is applicable to drugs available for clinical use. We are now working with experts in complex systems analysis to identify pathways to target and working on timing of radiation and drug(s). With the major interest in immune modulation, our work has significant bearing on the dose and fractionation of radiation that can be exploited for immune enhancement for tumor control, including direct and abscopal effects. We are working with Jim Mitchell of RBB and Murali Cherukuri of RBB who has hyperpolarized MRI techniques to study metabolic adaptation. Closely related to this work are efforts being done on identifying biomarkers and machanisms of radiation injury. This relates to work I do in the Administration for Strategic Preparedness and Response in Health and Human Services (HHS). We are working on the potential of bringing these mitigators into cancer care.

我们实验室计划的长期重点涉及辐射和微环境应激反应。我们现在专注于“辐射诱导靶点”，即探索使用多分割（MF）辐射以及更高的单剂量（SD）诱导细胞表型，使细胞对分子靶向治疗和免疫治疗敏感。从本质上讲，辐射将建立肿瘤，以增强药物杀伤和增强免疫反应。该项目现已证明，不同剂量的辐射- MF和SD -（10戈伊x1、2戈伊x5、1戈伊x10和低至0.5戈伊x10）产生不同的表型。我们已经证明，放射后的细胞在放射后1周和长达3个月后比放射前对药物更敏感，表明稳定的适应。这适用于可供临床使用的药物。我们现在正在与复杂系统分析专家合作，以确定靶向途径，并研究辐射和药物的时机。随着对免疫调节的主要兴趣，我们的工作对辐射的剂量和分级具有重要意义，这些辐射可以用于肿瘤控制的免疫增强，包括直接和远位效应。我们正在与RBB的Jim Mitchell和Murali Cherukuri合作，他们拥有超极化MRI技术来研究代谢适应。与这项工作密切相关的是正在努力确定辐射损伤的生物标志物和机制。这涉及到我在卫生与公众服务战略准备和反应管理局（HHS）的工作。我们正在研究将这些缓解剂引入癌症护理的可能性。

项目成果

The pervasive crisis of diminishing radiation therapy access for vulnerable populations in the United States, part 2: American Indian patients.

• DOI: 10.1016/j.adro.2017.08.010
• 发表时间: 2018-01
• 期刊: Advances in radiation oncology
• 影响因子: 2.3
• 作者: McClelland S 3rd;Leberknight J;Guadagnolo BA;Coleman CN;Petereit DG
• 通讯作者: Petereit DG

Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation.

• DOI: 10.1667/rr14186.1
• 发表时间: 2015-09
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Prasanna PG;Narayanan D;Hallett K;Bernhard EJ;Ahmed MM;Evans G;Vikram B;Weingarten M;Coleman CN
• 通讯作者: Coleman CN

Gene Expression Profiles from Heart, Lung and Liver Samples of Total-Body-Irradiated Minipigs: Implications for Predicting Radiation-Induced Tissue Toxicity.

• DOI: 10.1667/rade-20-00123.1
• 发表时间: 2020-10-02
• 期刊: Radiation research
• 影响因子: 3.4
• 作者: Chopra S;Moroni M;Martello S;Bylicky M;May J;Hritzo B;MacMillan L;Coleman CN;Aryankalayil MJ
• 通讯作者: Aryankalayil MJ

Editorial: "global challenges in radiation oncology".

• DOI: 10.3389/fonc.2015.00103
• 发表时间: 2015
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Petereit DG;Coleman CN
• 通讯作者: Coleman CN

Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model.

• DOI: 10.1186/s12967-021-02998-w
• 发表时间: 2021-08-07
• 期刊: Journal of translational medicine
• 影响因子: 7.4
• 作者: Aryankalayil MJ;Martello S;Bylicky MA;Chopra S;May JM;Shankardass A;MacMillan L;Sun L;Sanjak J;Vanpouille-Box C;Eke I;Coleman CN
• 通讯作者: Coleman CN