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中文摘要
翻译
血卟啉衍生物和其他光敏剂的使用 与光激活相结合目前正在进行研究, 一种用于治疗腹膜腔内和腹膜后肿瘤的抗肿瘤方法 胸内肿瘤。这种方式的一个主要优势是显而易见的 增敏染料与肿瘤的选择性保留。一只小鼠的腹水 卵巢癌和人卵巢肿瘤已经被用来研究 腹膜腔内药物分布的特点。 最初,小鼠模型被用来研究胸腔耐受 腔结构对正在探索的光疗技术的影响。这个 小鼠模型的局限性要求扩展 犬毒性评价模型的建立及应用 光疗法。不同波长的光,不同的激光传输 系统,不同的感光剂,不同的能量剂量,不同的 给药方式,不同的监测装置 学习。我们已经证明,光疗可以有效地用于 治疗小鼠腹水瘤。我们还表明,在这两只小鼠身上 而犬模型,腹膜浆膜表面对AT有耐受性 至少0.5J/cm2,这项工作可以推广到人体。在……里面 小鼠的系统,我们已经证明了胸腔,就像 腹膜腔,对红光治疗非常敏感 (630 Nm)。必须控制剂量率,以最大限度地减少热量积累 (从前向投影光纤输出的小于150 mW的光纤是 通常可以容忍)。我们已经将毒性研究扩展到狗身上 胸腔并显示出食道、顶骨等结构 而内脏胸膜、心脏可耐受35J/cm2红光。我们现在有了 使用DHE/630 nm激光治疗不能切除的患者完成I期试验 胸内间皮瘤和腹膜内卵巢/肉瘤/结肠 癌症。目前,32.5J/cm已用于临床治疗 胸内间皮瘤。我们已经开始了卵巢的第三阶段研究 并提交了腹膜后肉瘤的治疗方案。我们 正在探索使用光免疫疗法作为一种额外的手段 药物递送。人肺移植无瘤小鼠模型的建立 癌症被用来研究光免疫疗法。血卟啉是 共价结合到特定的针对 异种移植。结果表明,肿瘤是可以根除的,而且 皮肤光毒性被消除。我们正在探索使用 化学发光作为光传递到空腔空间的一种手段。一个 正在使用一种新型的水溶性试剂。
英文摘要
The use of hematoporphyrin derivative and other photosensitizing agents in combination with light activation is currently being investigated as an anti-tumor modality for the treatment of intraperitoneal and intrathoracic tumors. A major advantage of this modality is the apparent selective retention of the sensitizing dye with tumors. A murine ascites ovarian carcinoma and a human ovarian tumor have been used to study the characteristics of drug distribution in the peritoneal cavity. Initially, murine models were used to study the tolerance of the thoracic cavity structures to the phototherapy techniques being explored. The limitations of the murine model has required the extensions of the investigation to the canine model for evaluation of the toxicity of Phototherapy. Different wavelengths of light, different laser delivery systems, different sensitizers, different doses of energy, different modes of drug administration, and different monitoring devices were studied. We have shown that Phototherapy can be used to effectively treat a murine ascites tumor. We have also shown that in both the murine and the canine model, the peritoneal serosal surface is tolerant of at least 0.5 J/cm2 and that this work can be extended to human subjects. In the murine system, we have shown that the thoracic cavity, like the peritoneal cavity, is exquisitely sensitive to treatment with red light (630 nm). The dose rate must be controlled to minimize heat buildup (less than 150 mW fiber output from a forward projecting optical fiber is usually tolerated). We have extended a toxicity study to the canine thoracic cavity and shown that structures such as the esophagus, parietal and visceral pleura, heart can tolerate 35 J/cm2 red light. We have now finished the Phase I trial using DHE/630 nm light to treat unresectable intrathoracic mesothelioma and intraperitoneal ovarian/sarcoma/colon carcinoma. Currently, 32.5 J/cm has been used the clinical treatment of intrathoracic mesothelioma. We have begun a Phase III study for ovarian carcinoma and have submitted a protocol for retroperitoneal sarcoma. We are exploring the use of photoimmunotherapy as an additional means of drug delivery. An athymic murine model transplanted with human lung cancer was used to study photoimmunotherapy. Hematoporphyrin was covalently bound to the specific monoclonal antibody directed against the xenograft. The results show that tumor can be eradicated and that dermatophototoxicity is eliminated. We are exploring the use of chemiluminescence as a means of light delivery to the cavitary spaces. A new class of water soluble agents are being used.
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INTRACELLULAR MODULATION OF SPECIFIC INTRACELLULAR PROTEINS
RELATIONSHIP OF CELLULAR REDOX STATE AND THERMOTOLERANCE
  • 批准号:
    3939515
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    A RUSSO
  • 依托单位:
INTRACELLULAR MODULATION OF SPECIFIC INTRACELLULAR PROTEINS
  • 批准号:
    3752415
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    A RUSSO
  • 依托单位:
DEVELOPMENT OF SUPEROXIDE DISMUTASE MIMICS
  • 批准号:
    3774576
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    --
  • 负责人:
    A RUSSO
  • 依托单位:
海外基金