Heat shock protein (Hsp) in tumor cells has been proposed to enhance their resistance to chemotherapeutic agents. In the present study, we investigated the influence of Hsp expression on the irinotecan resistance of human colorectal cancer cells. Among eight Hsp genes tested in this study, we confirmed that the expression of Hsp27 correlated with irinotecan resistance in colorectal cancer cells. Specific inhibition of Hsp27 expression using an antisense oliogodeoxynucleotide increased the irinotecan sensitivity. On the contrary, an overexpression of Hsp27 decreased the irinotecan sensitivity in colorectal cancer cells. Elevated expression of Hsp27 decreased caspase-3 activity in colorectal cancer cells. The expression level of Hsp27 determined by immunohistochemical analysis correlated with the clinical response to irinotecan in colorectal cancer patients. Hsp27 expression levels of irinotecan-non-responder (mean staining score, 6.28; proportion of high staining score, 64.2%) were significantly higher compared to those of irinotecan-responder (mean staining score, 3.16; proportion of high staining score, 33.3%) (P for ttest = 0.045). These findings suggest that Hsp27 is involved in the irinotecan resistance of colorectal cancer cells possibly by reducing caspase-3 activity.
Background/Aim: Claudin18.2 (CLDN18.2) is a tight junction protein that has been identified as a promising target in gastric cancer. This study aimed to evaluate the clinical relevance of CLDN18.2 expression in gastric cancer. Patients and Methods: This study included 367 patients diagnosed with gastric cancer, who underwent curative surgical resection. Immunohistochemical staining for CLDN18.2 was carried out, and expression was scored semi-quantitatively, based on staining intensity and the percentage of staining. Results: CLDN18.2 expression was observed in 273 patients (74.4%), and 108 (29.4%) were classified as CLDN18.2-positive by predefined criteria. CLDN18.2 expression was not correlated with age, sex, tumor location, or stage. Expression rates were higher in diffusetype and HER2-positive tumors. In multivariate survival analysis, CLDN18.2 expression was not associated with survival outcomes. Conclusion: Higher expression of CLDN18.2 was observed in diffuse-type and HER2-positive gastric cancers. Meanwhile, CLDN18.2 expression was not associated with survival in patients with gastric cancer.
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