Relationship Between the Alteration of Apoptosis Related Genes and Sensitivity for Radiotherapy and Chemotherapy in Human Cancer

对食道癌细胞系和结直肠癌细胞系中的p53、p21^&lt、WAF1/CIP1&gt；、Bcl2和Bax进行检测。P53和p21^&lt；WAF1/CIP1&gt；分别在约70%和40%的细胞株中表达。BCL-2在大多数食道癌细胞系和少数结直肠癌细胞系中表达。在所研究的大多数细胞系中都检测到Bax。为了寻找直肠癌放射敏感性的决定因素，我们选择了p53、p21和Bcl2作为放射敏感性的预测因素。应用免疫组织化学方法检测49例直肠癌患者放疗前(活检标本)和放疗后(切除标本)中P53、p21和Bcl2的表达及其与放射治疗病理疗效的关系。所有患者放疗总剂量均为+0Gy2.5Gy一次，每周5次。P53、p21/WAF1和Bcl2的表达分别为53.1%、30.6%和71.4%。P53和p21的表达呈显著负相关。36.7%的肿瘤有中度至明显的放射病理效应，其余肿瘤的病理效应不明显。在P53阳性肿瘤中，88.5%为放射抵抗，而在P53阴性肿瘤中，65.2%为放射敏感。在p21阳性的肿瘤中，80.0%对放射敏感，而在p21阴性的肿瘤中，82.4%的肿瘤具有放射抗性。联合检测p53(+)、p21(-)和P53(-)、p21(+)作为放射敏感性的预测指标，其敏感性(90.0%)、特异性(95.4%)和准确性(93.8%)均有所提高。Bcl2的表达与放射敏感性无关。免疫组织化学检测p53和p21蛋白表达可作为肺癌放射敏感性的独立预测指标。这两个因素的结合可以使放射敏感性肿瘤的选择更加敏感、特异和准确。

P53, p21^<WAF1/CIP1>, Bcl-2 and Bax were analyzed in esophageal and colorectal cancer cell lines. p53 and p21^<WAF1/CIP1> were expressed in about 70% and 40% of the cell lines respectively. Bcl-2 was expressed in the majority of the esophageal cancer cell lines and a few colorectal cancer cell lines. Bax was detected in most of the cell lines studied. To search for the determinant factors of radiosensitivity in rectal carcinoma, p53, p21 and Bcl-2 were selected for possible predictive factors for rediosensitivity. Expressions of p53, p21 and Bcl-2were studied in 49 rectal carcinomas by immunohistochemistry before (biopsy specimen) and after (resected specimen) radiatiion and their relations with pathologic effect of rediotherapy. The total dose of rediation was =0Gy in all patients, by 2.5Gy each time, 5 times a week. p53, p21/WAF1 and Bcl-2 expressions were 53.1%, 30.6% and 71.4%, respectively. There was a significant inverse correlation between the expression of p53 and p21. Moderate to marked pathologic effect of radiation was found in 36.7% of the tumors, while others showed little effect. Of the p53 positive tumors, 88.5% were radioresistant, while 65.2% of the p53 negative tumors were radiosensitive. Of the p21 positive tumors, 80,0% were radiosensitive, while 82.4% of the p21 negative tumors were radioresistant. The combinations of p53 (+) and p21 (-) , as a predictor of radioresistance, and p53 (-) and p21 (+), as a predictor of radiosensitivity, enhanced sensitivity (90.0%), specificity (95.4%) and accuracy (93.8%). The expression of Bcl-2 showed no correlation with radiosensitivity. Immunochemically detected p53 and p21 expression can be used as independent predictors for radiosensitivity of redctal carcinoma. The combination of these two factors can make the selection for radiosensitive tumor more sensitive, specific and accurate.