Anti-proliferative and apoptotic effect of cannabinoids on human pancreatic ductal adenocarcinoma xenograft in BALB/c nude mice model.

Human pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal tumor of the exocrine pancreas. Cannabinoids extracted from the hemp plant Cannabis sativa have been suggested as a potential therapeutic agent in several human tumors. However, the anti-tumor effect of cannabinoids on human PDAC is not entirely clarified. In this study, the anti-proliferative and apoptotic effect of cannabinoid solution (THC:CBD at 1:6) at a dose of 1, 5, and 10 mg/kg body weight compared to the negative control (sesame oil) and positive control (5-fluorouracil) was investigated in human PDAC xenograft nude mice model. The findings showed that cannabinoids significantly decreased the mitotic cells and mitotic/apoptotic ratio, meanwhile dramatically increased the apoptotic cells. Parallelly, cannabinoids significantly downregulated Ki-67 and PCNA expression levels. Interestingly, cannabinoids upregulated BAX, BAX/BCL-2 ratio, and Caspase-3, meanwhile, downregulated BCL-2 expression level and could not change Caspase-8 expression level. These findings suggest that cannabinoid solution (THC:CBD at 1:6) could inhibit proliferation and induce apoptosis in human PDAC xenograft models. Cannabinoids, including THC:CBD, should be further studied for use as the potent PDCA therapeutic agent in humans.

Antitumor Effects of Cannabinoids in Human Pancreatic Ductal Adenocarcinoma Cell Line (Capan-2)-Derived Xenograft Mouse Model.

Background: Pancreatic cancer is considered a rare type of cancer, but the mortality rate is high. Cannabinoids extracted from the cannabis plant have been interested as an alternative treatment in cancer patients. Only a few studies are available on the antitumor effects of cannabinoids in pancreatic cancer. Therefore, this study aims to evaluate the antitumor effects of cannabinoids in pancreatic cancer xenografted mouse model. Materials and Methods: Twenty-five nude mice were subcutaneously transplanted with a human pancreatic ductal adenocarcinoma cell line (Capan-2). All mice were randomly assigned into 5 groups including negative control (gavage with sesame oil), positive control (5 mg/kg 5-fluorouracil intraperitoneal administration), and cannabinoids groups that daily received THC:CBD, 1:6 at 1, 5, or 10 mg/kg body weight for 30 days, respectively. Xenograft tumors and internal organs were collected for histopathological examination and immunohistochemistry. Results: The average tumor volume was increased in all groups with no significant difference. The average apoptotic cells and caspase-3 positive cells were significantly increased in cannabinoid groups compared with the negative control group. The expression score of proliferating cell nuclear antigen in positive control and cannabinoids groups was decreased compared with the negative control group. Conclusions: Cannabinoids have an antitumor effect on the Capan-2-derived xenograft mouse model though induce apoptosis and inhibit proliferation of tumor cells in a dose-dependent manner.

Screening for diabetic retinopathy in rural area using single-field, digital fundus images.

OBJECTIVE: To evaluate the practicability of using single-field, 2.3 million-pixel, digital fundus images for screening of diabetic retinopathy in rural areas. MATERIAL AND METHOD: All diabetic patients who regularly attended the diabetic clinic at Kabcheang Community Hospital, located at 15 kilometers from the Thailand-Cambodia border, were appointed to the hospital for a 3-day diabetic retinopathy screening programme. The fundi of all patients were captured in single-field, 45 degrees, 2.3 million-pixel images using nonmydriatic digital fundus camera and then sent to a reading center in Bangkok. The fundi were also examined through dilated pupils by a retinal specialist at this hospital. The grading of diabetic retinopathy from two methods was compared for an exact agreement. RESULTS: The average duration of single digital fundus image capture was 2 minutes. The average file size of each image was 750 kilobytes. The average duration of single image transmission to a reading center in Bangkok via satellite was 3 minutes; via a conventional telephone line was 8 minutes. Of all 150 patients, 130 were assessed for an agreement between dilated fundus examination and digital fundus images in diagnosis of diabetic retinopathy. The exact agreement was 0.87, the weighted kappa statistics was 0.74. The sensitivity of digital fundus images in detecting diabetic retinopathy was 80%, the specificity was 96%. For diabetic macular edema the exact agreement was 0.97, the weighted kappa was 0.43, the sensitivity was 43%, and the specificity was 100%. CONCLUSION: The image capture of the nonmydriatic digital fundus camera is suitable for screening of diabetic retinopathy and single-field digital fundus images are potentially acceptable tools for the screening. The real-time image transmission via telephone lines to remote reading center, however, may not be practical for routine diabetic retinopathy screening in rural areas.