P-4: Characterization of Lymphoma-Initiating Cells

P-4：淋巴瘤起始细胞的表征

• 批准号: 7507433
• 负责人: Craig T. Jordan
• 金额: $ 16.57万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7507433
• 关键词: Adult; Automobile Driving; B-Lymphocytes; Biological Assay; Biological Preservation; Breast; Cell Cycle; Cell Lineage; Cells; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials Design; Colon; Cytotoxic Chemotherapy; Data; Development; Disease; Flow Cytometry; Future; Genus Cola; Goals; Hematopoietic stem cells; Heterogeneity; Hodgkin Disease; Human; Human Cell Line; In Vitro; Investigation; Lymphoma; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of brain; Measures; Methods; Minor; Multiple Myeloma; Mutation; Non-Hodgkin' s Lymphoma; Outcome; Pathogenesis; Pharmaceutical Preparations; Play; Population; Prevalence; Property; Prostate; Range; Refractory Disease; Relapse; Resistance; Role; Source; Specimen; Standards of Weights and Measures; Stem cells; Structure; Surface Antigens; Techniques; Therapeutic; Tissues; Transplantation; Treatment Protocols; Tumor Biology; Xenograft procedure; base; cancer cell; cancer stem cell; concept; design; drug sensitivity; in vivo; leukemia; neoplastic cell; novel; prospective; reconstitution; self-renewal; theories; therapeutic target; tumor

Project 4: Most cancers comprise a heterogenous population of cells with marked differences in their proliferative potential and the ability to reconstitute the tumor after transplantation. There is now compelling evidence that tumors from disparate malignancies harbor a minor population of tumor cells, termed 'cancer stem cells', that possess the unique stem cell property of self-renewal. We hypothesize that clinical non-Hodgkin's Ivmphoma arises from such biologically distinct tumor-initiating cells - a lymphoma stem cell (LySC). The goal of this project is to identify, characterize, and target the tumor-initiating cells found within the context of primary human non-Hodgkin's lymphoma (NHL). In malignancies of differentiated adult tissue such as breast, colon, prostate, and brain cancer, cell populations with the critical stem cell-like properties of selfrenewal and differentiative capacity have been identified. Thus mutation/transformation of a B-lymphocyte could result in the acquisition of functionally defined stem cell properties. Preliminary data derived from NHL specimens present several lines of evidence in support of our hypothesis. In concordance with a central component of stem cell based diseases, we find clear phenotypic and functional heterogeneity in primary and cultured lymphoma specimens. These data strongly support a role for LySC in the pathogenesis of NHL. Further, because cancer stem cells are generally less sensitive to conventional cytotoxic therapy, we propose that the LySC population may represent a central reservoir for cells giving rise to clinical relapse and refractory disease. Therefore, the identification and subsequent targeting of LySC is a critical step toward optimizing therapeutic outcomes in NHL.

项目4： 大多数癌症都包含异性群细胞种群，其增殖有明显差异 潜力和移植后重建肿瘤的能力。现在有令人信服的证据表明 来自不同恶性肿瘤的肿瘤具有较小的肿瘤细胞，称为“癌症干细胞”，这是 具有自我更新的独特干细胞特性。我们假设临床非霍奇金的 IVMPHOMA由这种生物学上不同的肿瘤炎性细胞 - 淋巴瘤干细胞（LYSC）产生。这 该项目的目标是识别，表征和针对在 原发性人非霍奇金淋巴瘤（NHL）。在分化成年组织的恶性肿瘤中 乳腺癌，结肠，前列腺和脑癌，具有临界干细胞样特性的细胞种群 并已经确定了区分能力。因此B淋巴细胞的突变/转化 可能导致获得功能定义的干细胞性质。源自NHL的初步数据 标本提供了几条证据，以支持我们的假设。与中央一致 干细胞疾病的成分，我们发现原发性疾病明确的表型和功能异质性 和培养的淋巴瘤标本。这些数据强烈支持LYSC在 NHL。此外，由于癌症干细胞通常对常规细胞毒性疗法敏感，所以我们 提出LYSC种群可能代表细胞引起临床复发的细胞中心储藏 和难治性疾病。因此，LYSC的识别和后续靶向是关键步骤 致力于优化NHL的治疗结果。