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使用间-四(羟苯基)二氢卟吩的光动力疗法。一种动物模型。

Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model.

作者信息

Lofgren L A, Ronn A M, Abramson A L, Shikowitz M J, Nouri M, Lee C J, Batti J, Steinberg B M

机构信息

Department of Otolaryngology and Communicative Disorders, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY.

出版信息

Arch Otolaryngol Head Neck Surg. 1994 Dec;120(12):1355-62. doi: 10.1001/archotol.1994.01880360051010.

DOI:10.1001/archotol.1994.01880360051010
PMID:7980901
Abstract

OBJECTIVE

To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems.

DESIGN

Nonrandomized control trial.

SETTING

Division of ear, nose, and throat research at a tertiary care teaching hospital.

MATERIALS

Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines.

INTERVENTION

Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light.

OUTCOME MEASURES

Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response.

RESULTS

The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2.

CONCLUSIONS

m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.

摘要

目的

以感染棉尾兔乳头瘤病毒的兔和犬喉为模型系统,评估强效光敏剂间-四(羟苯基)二氢卟酚(m-THPC)。

设计

非随机对照试验。

地点

一家三级护理教学医院的耳鼻喉研究科室。

材料

使用兔子进行相对潴留率研究和组织耐受性测试。用犬进行光激活后喉部正常组织肿胀的研究。

干预

给动物注射0.3mg/kg的m-THPC。在不同时间间隔,将组织暴露于652nm的光线下。

观察指标

观察指标包括四个要素:(1)血浆浓度随时间的衰减;(2)正常组织与肿瘤中药物浓度最大比值出现的时间间隔和持续时间;(3)在最佳时间间隔下正常组织(皮肤和喉黏膜)的最大允许光照量;(4)疗效——部分缓解和完全缓解的肿瘤数量。

结果

注射药物后4至8天出现最大的乳头瘤与皮肤比值(10:1)。6天时兔皮肤损伤阈值为40至60J/cm²。犬喉水肿和红斑阈值为50至70J。在光剂量为25至75J/cm²时,面积小于100mm²的乳头瘤治愈率达到75%。

结论

m-THPC在治疗乳头瘤病毒诱导的肿瘤方面显示出疗效。我们提出了一个方案,用于快速优化以最小的正常组织损伤破坏肿瘤所需的因素,从而能够确定任何光敏剂的最佳治疗方案。

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