Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice over-expressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis. MATERIALS AND METHODS: At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing N-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed. RESULTS: Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia. CONCLUSION: These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.

Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. MATERIALS AND METHODS: Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed > or = 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase-polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients. RESULTS: CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393). CONCLUSION: DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.

Efficacy of an Injectable Thermosensitive Gel on Postoperative Adhesion in Rat Model

PURPOSE: For easy application to targeted area or in laparoscopic surgery, proper injectable antiadhesive agents are needed. The efficacy of two injectable antiadhesive agents- the thermosensitive poly (organophosphazene) hydrogel (Gel group) and a mixed solution of hyaluronate and carboxymethyl cellulose (Guardix-sol(R), Hanmi Medicare, Korea; Gd group) were compared with that of a positive control (one established membranous agent [Interceed(R), Johnson & Johnson, USA; IC group]) and negative control (phosphate buffered saline, control group). METHODS: Eight ischemic buttons were created on both sides of the peritoneum in twenty-four male Sprague Dawley rats. Each of the solutions, or membrane agent was applied before closing of the wound according to groups (six rats per group). Two rats in the IC group were excluded because of death or intraoperative bleeding. Animals were sacrificed at two or four weeks after surgery. The number of adhesion-forming ischemic buttons and the weight gain were analyzed. RESULTS: The overall number of adhered ischemic buttons were 23 in the control group (n=48), 22 in the Gd group (n=48), 14 in the Gel group (n=48) and 0 in the IC group (n=32). Overall number of adhered ischemic buttons of the Gd group was not significantly different from that of the control group (P=1.000). However that of the Gel group was smaller than that of the control group, although not statistically significant (P=0.093). CONCLUSION: The Gel group demonstrated some possibility of having an antiadhesive effect, and the Gd group failed to show antiadhesive effect, in contrast to IC group. A large-scale preclinical study is required to verify these findings.

Genetic Association of Mitochondrial DNA Polymorphisms with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Although many single nucleotide polymorphisms (SNPs) of mtDNA have been found to be associated with type 2 diabetes mellitus, the results of studies using different population samples and different methods are mixed. Therefore, we conducted a genetic association study of mtDNA SNPs and type 2 diabetes mellitus in a Korean sample and compared our results with those of studies conducted in other human populations. METHODS: A total of 298 blood samples from 147 type 2 diabetic patients and 151 normal controls were surveyed for SNPs via PCR directed sequencing. Sequencing analyses were performed using the SeqMan module of the DNASTAR program. The identified SNPs were compared to previously reported SNP lists on NCBI and V-mitoSNP. RESULTS: A total of 24 SNPs were identified in the MT-RNR2, MR-TL1 and MT-ND1 mtDNA genes in Korean type 2 diabetes mellitus patients and normal controls. The SNPs identified in the Korean sample were not closely associated with the type 2 diabetes mellitus phenotype, a significantly different result from those previously observed in European, Chinese and Japanese samples. Additionally, a haplotype and prevalence analysis could not detect any differences between the type 2 diabetes mellitus patients and normal controls. CONCLUSION: The 24 mtDNA SNPs were not associated with type 2 diabetes mellitus risk in our Korean sample. The results of the present study support the possibility that mtDNA SNPs have a differential effect on the risk of type 2 diabetes mellitus according to geographical origin.