The effects of cPrG x HCl and epirubicin on the suppression of cell growth were examined on human breast cancer cell line (MDA-MB-231). Either cPrG x HCl or epirubicin alone showed a tumor growth inhibition in a time- and dose-dependent manner, however, the combinatory use of cPrG x HCl together with epirubicin resulted in prominent synergistic effects on the breast cancer cells. In the in vitro studies, the combinatory use of these two drugs accelerated apoptotic cell death as revealed by morphological changes as well as by the appearance of subG1 population by flow cytometry. In addition, confocal microscopy revealed that the accumulation of epirubicin in nucleus increased apparently when cPrG x HCl were present. In the in vivo assay, nude mice bearing xenografted tumor cells received 4 weeks of intraperitoneal administration of cPrG-HCl and epirubicin. After 12 days, the combinatory treatment significantly suppressed the tumor growth compared to the controls. The TUNEL staining revealed that tumor cells in cPrG x HCl plus epirubicin-treated mice exhibited a higher apoptotic rate. In addition, 31P-NMR studies on the xenografted tumor revealed that cPrG x HCl lowered tumor pHi (below pH 6.9). while it did not affected muscle pHi. No pathological changes were observed in any intrinsic organs and the serum alanine aminotransferase levels remained within normal limits among the groups. These results suggest that the combinatory use of cPrG x HCl and epirubicin may be useful for breast cancer therapy.
We performed a sequential endoscopic examination of esophageal carcinogenesis induced by N-nitrosomethylbenzylamine (NMBA) in F344 rats. The endoscopic findings were consistent with the histological changes observed in the specimens obtained by a biopsy and/or an autopsy. Sevenweek-old male F344 rats received a weekly subcutaneous injection of 0.5 mg/kg NMBA for 15 weeks. The first endoscopic change that was detected was redness of the musosa due to the dilatation of the submucosal blood vessels. Subsequently, the mucosal redness became obscure, and we observed a focal loss of the visible blood vessel network due to hyperkeratosis, followed by the appearance of plaque-like elevated lesions due to acanthosis. Then, smooth and irregular polyps appeared as a result of the development of papilloma without or with dysplastic potential, respectively. Finally, rough elevation appeared as a result of carcinoma in situ and invasive squamous cell carcinoma. The present endoscopic findings correlated closely with the histological changes, indicating that sequential fiberscopic examination may be useful for monitoring esophageal carcinogenesis.
Because many viruses can survive extremely cold temperatures for extended periods of time, transmission of viral diseases from person to person using improper cryosurgical techniques might conceivably occur. To investigate the survivability of herpes simplex virus during cryotherapy, virus was first inoculated onto cotton-tipped applicators from either tissue cultures or from active lesions on patients, and then frozen for variable times in liquid nitrogen (-196 degrees C). After thawing, the applicators were cultured for the virus. The virus survived 12 hours of freezing (the maximum time of freezing in the study), which suggests that herpes simplex could be transmitted between cryosurgical patients if care is not taken to use separate cotton-tipped applicators and liquid nitrogen containers for each case.
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