Cellular Mechanisms

细胞机制

• 批准号: 10576840
• 负责人: James B. McCarthy
• 金额: $ 4.85万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10576840
• 关键词: Affect; Animal Model; Antibodies; Architecture; Area; Biological; Biological Markers; Biophysics; Budgets; Cancer Center; Cancer Center Support Grant; Categories; Cell Adhesion; Cell Communication; Cell Line; Cell membrane; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Communication; Complex; Cytoskeletal Modeling; Development; Diagnosis; Direct Costs; Drug Design; Drug usage; Epigenetic Process; Event; Extracellular Matrix; Faculty; Fibrosis; Funding; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Goals; Grant; Growth; Growth Factor; Hormones; Imaging technology; Immunology; In Vitro; Institution; Intervention; Invaded; Journals; Laboratories; Lead; Maintenance; Malignant - descriptor; Malignant Neoplasms; Metabolism; Midwestern United States; Modality; Molecular; Monitor; National Cancer Institute; Neoplasm Metastasis; Oncogenic; Oncology; Paper; Pharmaceutical Chemistry; Phenotype; Pilot Projects; Protein Kinase; Publishing; Recombinants; Recurrence; Refractory Disease; Research; Resistance; Resource Sharing; Schools; Science; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Source; Stimulus; Stromal Change; Structure; Therapeutic; Toxin; Transcriptional Regulation; Translational Research; Tumor Cell Biology; Tumor Promotion; Work; autocrine; biomarker discovery; biomechanical test; cancer cell; cancer stem cell; cell growth; cell motility; cell stroma; cell type; college; cytokine; epigenome; genome-wide; improved; in vivo; innovation; meetings; member; migration; multidisciplinary; neoplastic cell; new therapeutic target; novel; novel therapeutics; paracrine; patient derived xenograft model; physical science; posttranscriptional; programs; protein complex; recruit; sensor; small molecule; steroid hormone; steroid hormone receptor; therapy resistant; tool; transcriptome; translational potential; treatment response; tumor; tumor behavior; tumor diagnosis; tumor growth; tumor metabolism; tumor microenvironment; tumor progression; tumorigenic; validation studies; working group

Cellular Mechanisms Program Summary Cellular Mechanisms (CM) is a new research program in the Masonic Cancer Center (MCC) formed when the Cell Signaling and Tumor Microenvironment Programs merged into one highly integrated program to strengthen the science of cellular mechanisms of cancer and expand opportunities for translation of research discoveries into new therapeutic modalities. The Program’s goal is to identify biological mechanisms that drive cancer development, tumor progression, and metastasis, including therapy-resistant recurrence, and then develop novel targeted therapies. The 3 integrated Aims are 1) to identify oncogenic signaling pathways within and between diverse cells in tumors that can be targeted to limit tumor growth, invasion, and metastasis; 2) to define epigenetic events in tumor transcriptomes that enhance malignancy or resistance to therapy; 3) to determine how tumors cause protumorigenic changes in the associated stroma and how “cancerized” stroma and tumor-reactive host cells impact tumor progression, invasion, migration, and metastasis. The Program is co-led by Drs. Carol Lange and James McCarthy and has 45 members, representing 19 departments and 8 schools or colleges. For the last budget year, CM members were supported by $4.8 million in direct costs from the National Cancer Institute; cancer-focused, sponsored funding from all sources totaled over $10.7 million (direct costs). Since 2013, CM members have published 1027 papers, 8% of which resulted from intraprogrammatic collaborations, 22% from interprogrammatic collaborations, and 82% from external collaborations; 89 were published in journals with an impact score of 10 or higher. Since 2013, 221 clinical trials across all clinical research categories have opened under this programmatic area and have accrued 1132 subjects. The MCC has provided substantial value to the program, including recruitment of 5 new faculty and funding of $1.08M in pilot projects that have led to over $5.5 million in externally funded grants. CM members use all 10 MCC Shared Resources. In addition, the MCC was instrumental in supporting the 2nd annual Regional Midwest Tumor Microenvironment Meeting in May of 2015, which hosted 132 attendees from 7 academic institutions. Members of this well-integrated interdisciplinary Program bring complimentary expertise to identifying how tumor and host cell interactions impact tumor progression, elucidating the complexities of metastatic and hormone-refractory disease, and determining how deregulation of signaling inputs to transcriptional control might be exploited to improve therapy. The study of targetable factors related to stroma remodeling and fibrosis is also a research strength. Novel therapies are being developed using antibodies, recombinant toxins, small molecules, and medicinal chemistry/fragment-based drug design to target signaling pathways and alter tumor metabolism. Program members have substantial interactions with the Immunology and Genetic Mechanisms Programs. The CM Program fulfills key components of the Cellular and Molecular Therapeutics and Biomarker Discovery (SPG1 and SPG4) MCC Strategic Scientific Priorities.

细胞机制计划摘要 细胞机制 (CM) 是共济会癌症中心 (MCC) 成立时的一个新研究项目 细胞信号转导和肿瘤微环境项目合并为一个高度集成的项目， 加强癌症细胞机制的科学并扩大研究转化的机会 该计划的目标是确定驱动新治疗方式的生物机制。 癌症发展、肿瘤进展和转移，包括治疗耐药性复发，然后 开发新的靶向治疗方法，这 3 个综合目标是 1) 识别其中的致癌信号通路。 以及可以靶向限制肿瘤生长、侵袭和转移的不同细胞之间；2) 定义肿瘤转录组中增强恶性肿瘤或治疗耐药性的表观遗传事件 3) 确定肿瘤如何引起相关基质的促肿瘤变化以及基质如何“癌化” 肿瘤反应性宿主细胞影响肿瘤的进展、侵袭、迁移和转移。 由 Carol Lange 博士和 James McCarthy 博士共同领导，有 45 名成员，代表 19 个部门和 8 个 在上一个预算年度，CM 成员获得了 480 万美元的直接费用支持。 国家癌症研究所；来自各种来源的以癌症为重点的赞助资金总计超过 1070 万美元 （直接成本）自2013年以来，CM成员发表了1027篇论文，其中8%来自于 计划内合作，22% 来自计划间合作，82% 来自外部 自 2013 年以来，已有 221 篇论文发表在影响力评分为 10 或更高的期刊上。 所有临床研究类别的试验均已在该规划领域下开展，并已累计 1132 项 MCC 为该计划提供了巨大的价值，包括招聘 5 名新教师和 为试点项目提供了 108 万美元的资金，这些项目已为 CM 成员提供了超过 550 万美元的外部资助。 使用全部 10 个 MCC 共享资源 此外，MCC 在支持第二届年度会议方面发挥了重要作用。 2015 年 5 月举行的中西部地区肿瘤微环境会议，来自 7 个国家和地区的 132 名与会者参加了会议 这个综合性跨学科项目的成员带来了免费的专业知识。 肿瘤和宿主细胞相互作用如何影响肿瘤进展，阐明了复杂性 转移性和激素难治性疾病，并确定信号输入的放松管制如何 转录控制可用于改善治疗。 重塑和纤维化也是利用抗体开发新疗法的研究优势。 重组毒素、小分子和药物化学/基于片段的药物设计以靶向信号传导 途径并改变肿瘤代谢。计划成员与免疫学有实质性的相互作用。 CM 计划实现了细胞和分子的关键组成部分。 治疗和生物标志物发现（SPG1 和 SPG4）MCC 战略科学重点。