Improving Chemotherapy with a Novel Oxygen-Delivery Protein

用新型输氧蛋白改善化疗

• 批准号: 8396231
• 负责人: Ana Krtolica
• 金额: $ 30万
• 依托单位: OMNIOX, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8396231
• 关键词: Address; Affect; Affinity; Antineoplastic Agents; Biological Assay; Biological Models; Blood; Blood Transfusion; Blood capillaries; Blood flow; Breathing; Bromodeoxyuridine; Buffers; Cell Culture Techniques; Cell Cycle Arrest; Cell Fraction; Cell Hypoxia; Cell Proliferation; Cells; Characteristics; Colonic Neoplasms; Colorectal; Colorectal Neoplasms; Culture Media; Data; Diffusion; Dose; Drug resistance; Effectiveness; Ensure; Exhibits; Fluorouracil; Goals; HCT116 Cells; Hour; Human; Hyperbaric Oxygen; Hypoxia; In Vitro; Lead; Malignant Neoplasms; Measures; Metabolism; Modeling; Mus; Neoplasm Metastasis; Nitric Oxide; Outcome; Oxygen; Patients; Phase; Phenotype; Pimonidazole; Population; Proliferating; Proteins; Regimen; Resected; Resistance; Safety; Series; Solid Neoplasm; Staging; Staining method; Stains; Technology; Testing; Therapeutic; Thick; Time; Treatment outcome; Tumor Tissue; Variant; Xenograft Model; base; cancer cell; cancer therapy; cancer type; capillary; cell killing; chemotherapeutic agent; chemotherapy; clinically relevant; improved; in vivo; in vivo Model; innovation; killings; neoplastic cell; novel; novel strategies; research study; response; tumor; tumor growth; tumor xenograft; tumorigenic

Omniox has identified a breakthrough tunable oxygen (O2) delivery technology that perfuses deep into tumors and eliminates hypoxia. Hypoxia, a prominent feature in solid tumors, affects multiple characteristics of tumor cells that lead to higher drug resistance. This proposal describes a series of experiments that will select an optimal candidate that delivers sufficient oxygen to overcome these obstacles, sensitizing neoplastic cells to chemotherapy and greatly improving tumor control. Hypoxic tumor microenvironments harbor cell populations that are pro-tumorigenic, pro-angiogenic and pro-metastatic. While the degree to which these populations overlap remains to be elucidated and may vary between different stages and types of tumors, it is clear that hypoxic tumor cells exhibit high resistance to common chemotherapeutic agents and are thus, likely responsible for tumor reoccurrence and, potentially, metastasis. Consequently, tumor hypoxia has been shown to correlate with poorer patient outcomes in multiple cancer types. Oxygenating hypoxic regions of tumors has the potential to, sensitizing tumors to antineoplastic therapies. Previous efforts to eliminate tumor hypoxia via hyperbaric oxygen, blood transfusions, or inhaled oxygen have not been successful. Even when blood oxygenation is extremely high, hypoxic microenvironments persist due to aberrant tumor blood flow and long diffusion distances that create oxygen gradients from tumor capillaries to hypoxic niches. A different approach is needed to overcome tumor hypoxia, reduce tumor resistance to chemotherapeutic agents and significantly improve treatment outcomes. In this proposal, Omniox is developing a novel set of oxygen carrying proteins to address the tumorigenic issues associated with tumor hypoxia.

Omniox已经确定了一种突破性的可调氧气（O2）输送技术， 并消除缺氧。缺氧是实体瘤的一个突出特征， 肿瘤细胞特性 导致更高的耐药性。该提案描述了一系列实验， 提供足够氧气以克服这些障碍的最佳候选者， 使肿瘤细胞对化疗敏感，并大大改善肿瘤控制。 低分化肿瘤微环境庇护细胞群 促肿瘤发生、促血管生成和促转移。虽然这些人口 重叠仍有待阐明，并且可能在不同阶段和不同类型的肿瘤之间变化，很明显， 低氧肿瘤细胞对普通化疗剂表现出高抗性，因此可能 负责肿瘤复发和潜在的转移。因此，肿瘤缺氧已被证明是 与多种癌症患者预后较差相关。 使肿瘤的缺氧区域氧化有可能使肿瘤对 心理治疗。以前通过高压氧，输血， 或吸入氧气都没有成功。即使血氧含量极高， 由于异常的肿瘤血流和长的扩散距离， 从肿瘤毛细血管到缺氧小生境的梯度。需要一种不同的方法来克服肿瘤缺氧， 降低肿瘤对化疗剂的耐药性并显著改善治疗结果。 在这项提案中，Omniox正在开发一种新的携氧蛋白，以解决肿瘤发生的问题。 与肿瘤缺氧有关的问题。