• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.27 no.5
• /
• pp.373-384
• /
• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Korean Journal of Food Science and Technology
• /
• v.42 no.2
• /
• pp.204-209
• /
• 2010

This study was conducted to investigate the anti-diabetic activity of Kocat-D1, which is widely used in traditional medicine to treat diabetes in Shandong, China. Sprague Dawley rats (8 weeks of age) were separated into 4 groups: a normal control, streptozotocin (STZ)-induced diabetic rat group (DM control), Kocat-D1-1 (diabetic rat treated with 0.25 g/kg/day hot water extract), and Kocat-D1-2 (diabetic rat treated with 1 g/kg/day hot water extract). After eight weeks of treatment, the fasting blood glucose levels of the Kocat-D1-1 ($334.3{\pm}32.9\;mg/dL$) and Kocat-D1-2 group ($259.5{\pm}35.0\;mg/dL$) were significantly lower when compared to the DM control group ($451{\pm}42.6\;mg/dL$). Furthermore, the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), albumin and high-density lipoprotein (HDL) cholesterol in the serum of the Kocat-D1-2 group were significantly normalized when compared to the DM control group. However, significant differences were not observed between the Kocat-D1-1 group and the DM control group. Histochemical staining of the liver of the Kocat-D1-2 group revealed no fat accumulation. The insulin level was significantly upregulated in the Kocat-D1-2 group ($0.13{\pm}0.02\;ng/mL$) when compared to the DM control group ($0.05{\pm}0.04\;ng/mL$). The relative volume of $\beta$-cells in the pancreas of the Kocat-D1-2 group ($49.4{\pm}4.2%$) also increased significantly when compared to the DM control group ($12.9{\pm}7.9%$). These results suggest that Kocat-D1 exerts an anti-hyperglycemic effect through the enhancement of insulin secretion.

• Nuclear Medicine and Molecular Imaging
• /
• v.42 no.4
• /
• pp.307-313
• /
• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.