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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Clinical and experimental evidence of Bcl-2 involvement in the response to photodynamic therapy.
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Clinical and experimental evidence of Bcl-2 involvement in the response to photodynamic therapy.

机译：Bcl-2参与光动力疗法反应的临床和实验证据。

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PURPOSE: The role of apoptosis related proteins in the response of human malignancies to photodynamic therapy (PDT) is under investigation. The aim of the study was to examine the role of p53 and of bcl-2 protein expression in the response to PDT. MATERIALS AND METHODS: Paraffin-embedded material from 37 patients with early esophageal cancer treated with PDT (argon dye laser after intravenous injection of hematoporphyrine derivative) was studied immunohistochemically for p53 protein nuclear accumulation and bcl-2 cytoplasmic expression. Patients with residual disease after two rounds of PDT received definitive radiotherapy. In a subsequent in vitro study, W138 human lung fibroblasts and W138-SV-40 virus transformed were assessed for their sensitivity to PDT. The constitutive bcl-2 overexpression of the transformed cells vs. normal cells (assessed with RT-PCR) was 16-fold. RESULTS: Positive bcl-2 and p53 expression was noted in 10 out of 36 (27%) and 14 out of 36 (39%) patients, respectively. Seven out of 11 tumors (63%) with bcl-2 expression responded completely to PDT vs. 6 out of 26 (23%) of cases with no bcl-2 expression (p = 0.02). No association of p53, T-stage and of histology grade with response to PDT or PDT/RT was noted. The sensitivity to PDT of transformed human fibroblasts compared to normal ones was 4 times more at a fluence of 4.3 J/cm2 (4% vs. 1% cell kill) as well as at a fluence of 5.4 J/cm2 (8% vs. 2% cell kill). CONCLUSION: Bcl-2 protein expression is associated with favorable response to PDT and can be used as a predictor of cancer response to PDT. This finding can be explained by experimental studies showing that PDT induces selective degradation of the bcl-2 protein, leading to apoptosis by decreasing the bcl-2/bax ratio. Studies on PDT combination with agents targeting bcl-2 (i.e. taxanes) are on going to eventually assess a super-additive effect.
机译：目的：凋亡相关蛋白在人类恶性肿瘤对光动力疗法（PDT）的反应中的作用正在研究中。该研究的目的是检查p53和bcl-2蛋白表达在对PDT应答中的作用。材料与方法：免疫组化研究了37例PDT（静脉注射造血卟啉衍生物后用氩染料激光）治疗的早期食道癌患者的石蜡包埋材料的p53蛋白核蓄积和bcl-2细胞质表达。经过两轮PDT治疗后有残留疾病的患者接受了明确的放疗。在随后的体外研究中，评估了转化的W138人肺成纤维细胞和W138-SV-40病毒对PDT的敏感性。转化细胞与正常细胞的组成型bcl-2过表达（通过RT-PCR评估）是16倍。结果：分别在36名患者中有10名（27％）和36名患者中有14名（39％）的bcl-2和p53表达阳性。具有bcl-2表达的11个肿瘤中有7个（63％）对PDT完全反应，而无bcl-2表达的26个病例中有6个（23％）（P = 0.02）。没有发现p53，T期和组织学等级与对PDT或PDT / RT的反应相关。在4.3 J / cm2的通量下（4％对1％的细胞杀伤）和5.4 J / cm2的通量下（8％对5％的通量），转化人成纤维细胞对PDT的敏感性是正常人的4倍。 2％的细胞杀死率）。结论：Bcl-2蛋白表达与对PDT的良好应答有关，可作为癌症对PDT应答的预测指标。这一发现可以通过实验研究来解释，该研究表明PDT诱导bcl-2蛋白的选择性降解，并通过降低bcl-2 / bax比值导致凋亡。关于PDT与靶向bcl-2（即紫杉烷）的药物的组合研究将最终评估超加性作用。

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