Nuclear localization of beta-catenin and plakoglobin in primary and metastatic human colonic carcinomas, colonic adenomas, and normal colon.

Beta-catenin is a cytoskeleton-associated signaling molecule shown to be elevated in various carcinomas but mostly in colon cancer owing to its impaired degradation. In contrast, its close homologue plakoglobin was shown to suppress the tumorigenicity of certain tumor cells. In the present study, we have used a semiquantitative immunohistochemical approach to evaluate the extent of nuclear localization of beta-catenin in human colonic adenocarcinomas and adenomas and compared it to the distribution of plakoglobin in the same tissues. We show that beta-catenin accumulates in the nuclei of the epithelium of primary and metastatic colonic adenocarcinoma as well as in colonic adenomas. In contrast, nuclear plakoglobin levels in these tissues were low, even compared to those found in epithelial cells of normal colon. These results support the view that the increase in beta-catenin levels in colon cancer cells occurs early in the tumorigenic process, leading to its nuclear localization, not only in invasive adenocarcinoma, but also in colonic adenoma with mild dysplasia.

Diagnostic value of AgNOR staining in thyroid cytology.

OBJECTIVE: To determine the value of the argyrophil nucleolar organizer region (AgNOR) technique on scrape cytology of thyroid lesions. STUDY DESIGN: AgNOR counts were evaluated in smears of 70 thyroid lesions that were sent for frozen section and included 15 cases of follicular adenoma, 10 cases of follicular carcinoma, 13 cases of papillary carcinoma, 23 cases of nodular goiter and 9 cases of Hashimoto's thyroiditis. Forty-one slides out of 70 were freshly prepared, and 29 slides had been previously stained with hematoxylin and eosin and then destained with alcohol. The number of AgNOR dots was recorded for 50 cells, and the mean number was calculated. RESULTS: The mean AgNOR counts were statistically significantly higher in malignant lesions in comparison to benign lesions. CONCLUSION: AgNOR staining could be of use in cytologic material from thyroid lesions.

Clotrimazole treatment of oral candidiasis in patients with neoplastic disease.

A double-blind controlled study was performed to evaluate the effectiveness of clotrimazole in the treatment of oral candidiasis in patients with neoplastic disease. Six of seven patients who received clotrimazole had resolution of symptoms and signs of oral candidiasis. In five of six patients who received placebo, clinical progression of signs and symptoms occurred, esophagitis developed, and amphotericin B therapy had to be given. No toxicity was observed that could be attributed to clotrimazole. The results were statistically significant (p = 0.025 by Fisher's exact test). Clotrimazole is effective therapy for oral candidiasis in patients with neoplastic disease, and may prevent the development of esophagitis.

Systemic chemotherapy for a primary germ cell tumor of the brain: a pharmacokinetic study.

Systemic administration of most chemotherapeutic agents has been assumed to be ineffective in the treatment of primary and metastatic brain tumors because these agents fail to cross the intact blood-brain barrier. However, agents which fail to penetrate the intact blood-brain barrier may penetrate it under conditions which include the presence of tumor in the central nervous system (CNS) and prior CNS irradiation. This paper reports the results of pharmacokinetic studies of bleomycin, cisplatin, and vinblastine in the CNS of a patient with a primary germ cell tumor of the brain who had received prior radiotherapy. Significant concentrations of bleomycin and cisplatin, but not of vinblastine, were reached in the cerebrospinal fluid (CSF) of the patient following iv administration. The area under the bleomycin CSF concentration times time curve was 25% of the area under the bleomycin plasma concentration times time curve. The areas under two cisplatin CSF curves were 50% and 155% of the areas under the corresponding free cisplatin plasma curves. Moreover, an objective response of the tumor to the chemotherapy was documented. This study provides evidence that, under certain circumstances, significant concentrations of cisplatin and bleomycin may be obtained in human CSF following systemic administration and that it may be possible to treat primary or metastatic CNS tumors with agents effective against systemic tumor of the same histologic type.