The effects of hormonotherapy administered concurrent radiotherapy and trastuzumab on cardiac toxicity in rats.

OBJECTIVE: This experimental study aims to investigate whether radiotherapy (RT) plus trastuzumab (T) followed by subsequent hormonotherapy increase the cumulative toxic effect on cardiac functions in rats. METHODS: A total of 70 Wistar-Albino female rats with a mean weight 213 ± 27 g were randomly divided into equal seven groups. The first group (C) underwent no procedure. The second group (RT) underwent the whole thoracic radiation including heart. The third group (T) was administered T through tail vein alone. The fourth group (RT+T+Tx) was administered T initially and the whole thoracic radiation at two hours, followed by tamoxifen at one week. The fifth group (RT+T+Le) was administered T and then underwent thoracic radiation, followed by letrozole. The sixth group (T+RT+An) was administered T and then underwent thoracic radiation, followed by anastrazole. The seventh group (T+RT+Ex) was administered T and then underwent thoracic radiation, followed by exemestane at one week. Hormonotherapy was administered to the rats in the Group 5, 6 and 7, as indicated in the Group 4. Radiation therapy was administered following T treatment at two hours as a single 12 Gy fraction. After the rats were sedated under anesthesia and sacrificed at 24 weeks, cardiac tissues were removed. Serial sections obtained following paraffin blockage were stained and the ratio of myocardial fibrosis was assessed. According to statistical analyses by the one-way ANOVA test and Tukey HSD test, a significant difference between test components. RESULTS: At the end of the study, no loss and adverse effects were seen in any group. There was a statistically significant difference among atrium, ventricle and aorta (p<0.001). The mean value of fibrosis scores increased in the rats which underwent RT. In the assessment of atrium, a significant difference was found between RT group and RT+T+An group and also T group and RT+T+Fe group (p<0.001). In the assessment of ventricule, a statistically significant difference was observed among RT, RT+T+An and RT+T+Ex. In the assessment of aorta, the scores of RT group was significantly higher than RT+T+An and RT+T+Ex. A statistically significant difference was observed among these groups (p<0.001). CONCLUSION: Our study results suggested that there was no significant additional cardiotoxicity of adjuvant hormonotherapy following concomitant RT and T treatment, compared to RT in terms of cardiac fibrosis.

Is increased colon subepithelial collagen layer thickness in diabetic patients related to collagenous colitis? An immunohistochemical study.

In this study, we evaluated immunohistochemically whether increased thickness of the colon subepithelial collagen layer in diabetic patients relates to collagenous colitis. A total of 100 patients (25 in each group) were included in this study. There were diabetic patients with chronic diarrhea in the first group, diabetic patients without chronic diarrhea in the second group, non-diabetic patients with chronic diarrhea in the third group, and control patients in the fourth group. The endoscopic biopsy specimens were obtained from the rectum, sigmoid colon, and descending colon. The thickness of the subepithelial collagen layer was measured using the ocular micrometer method. The immunohistochemical staining was performed with type 1 collagen and fibronectin antibody. The thickness of the colon subepithelial collagen layer in diabetic patients with or without diarrhea was significantly greater than that in control patients. This thickened subepithelial collagen layer in diabetic patients was stained with fibronectin antibody, but not with type 1 collagen antibody in the immunohistochemical study. These immunohistochemical staining characteristics were not similar to those in collagenous colitis, but were similar to those in normal subjects. Increased colon subepithelial collagen layer thickness in diabetic patients does not relate to collagenous colitis.

The role of c-erbB-2 expression on the survival of patients with small-cell lung cancer.

The aim of this study was to determine the incidence and role of c-erbB-2 overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 1998 and 2004. c-erbB-2 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. Sixty-seven patients with SCLC were identified (6 females, 61 males; median age- 56.5 yr, range-34-75) all of whom had adequate tissue specimens available for c-erB-2 testing. Of the 67 specimens, 12 (17.9%) showed c-erbB-2 overexpression. Seventy-five of the cases were positive for c-erbB-2, had extensive disease. The median overall survival of patients with SCLC whose tumors were positive and negative for c-erbB-2 were 8 +/- 0.9 months (95%CI 6.3-9.7) and 11 +/- 1.5 months (95%CI 8.0-14.0), respectively. c-erbB-2 overexpression detected using immunohistochemistry is observed in 17.9% of patients with SCLC and has statistically significant prognostic value. Our findings suggest that c-erbB-2 may be a potential target for site-specific immunotherapy in SCLC. Considering one technique examined, further molecular investigation is needed to confirm these preliminary findings.