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Tight junction and gap junction are major cell junctions that play important roles in cellular communication and structural integrity. Alterations of these junctions are known to be involved in cancer pathogenesis. Claudins and connexins are major tight and gap junction proteins, but genetic alterations of these genes have not been reported in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). Claudin genes CLDN5 and CKDN6, and connexin genes GJB6 and GJB7 have mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with MSI. We analyzed 79 GCs and 145 CRCs, and found CLDN5 frameshift mutations in 3 (3%) CRCs and 1 (2.9%) GC, CLDN6 frameshift mutations in 6 (6%) CRCs, GJB6 frameshift mutations in 5 (5%) CRCs and GJB7 frameshift mutation in one CRC (1%) with high MSI (MSI-H). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutations in 16 CRCs and found that CLDN6 and GJB6 frameshift mutations showed regional ITH in 2 (12.5%) and 2 (12.5%) cases, respectively. Our results show that CLDN5, CLDN6, GJB6 and GJB7 genes harbor not only frameshift mutations but also mutational ITH, which together may be features of GC and CRC with MSI-H. Based on the roles of cellular junctions in cancers, frameshift mutations of tight junction and gap junction genes might contribute to tumorigenesis by altering their functions in GC and CRC.

The purpose of this study was to compare and analyze the effects of Crossfit training method on physical fitness in 30’s men. Subjects were divided into 2 groups: AMRAP(as many repetition as possible)group(n=50), TA(time attack)group(n=50). Measurement variables were physical fitness muscular strength, muscular endurance, flexibility, cardiovascular endurance, power. The two - way ANOVA was conducted to analyze the differences and interactions between group and time. In the case of interaction effect, Duncon test was conducted to Post hoc. All significance levels were verified at .05. The results were as follows; There were no significant statistically difference in the change of muscular strength, flexibility and power. but AMRAP group and TA group showed some differences in the amount of muscular strength according to the measurement time. and there were no significant effect of interaction between group and measurement time for muscular endurance, flexibility, cardiovascular endurance and power. Consequently, it showed that 8 weeks Crossfit training method made a similar effect on body composition and physical fitness in 30’s men.

Nucleotide-binding and leucine-rich repeat protein (NLRP) genes are involved in inflammasome formation that plays a role in inflammation/host defense and cell death. Both cell death and inflammation are crucial for cancer development, but the roles of NLRPs in cancer are partially known. In this study, we analyzed mononucleotide repeats in coding sequences of NLRP1, NLRP2, NLRP4 and NLRP9, and found 1, 1, 1 and 8 frameshift mutation (s) in gastric (GC) and colonic cancers (CRC), respectively. Five of the 32 high microsatellite instability (MSI-H) GCs (15.5%) and 6 of 113 MSI-H CRCs (5.5%) exhibited the frameshift mutations. There was no NLRP frameshift mutations in microsatellite stable (MSS) GCs and CRCs. We also discovered that 2 of 16 CRCs (12.5%) harbored intratumoral heterogeneity (ITH) of the NLRP9 frameshift mutations in one or more areas. In both GC and CRC with MSI-H, NLRP9 expression in NLRP9-mutated cases was significantly lower than that in NLRP9-non-mutated cases. Our data indicate that NLRP9 is altered at multiple levels (frameshift mutation, mutational ITH and loss of expression), which together could contribute to pathogenesis of MSI-H GC and CRC.

TRAF2 and TRAF3 genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of TRAF2 and TRAF3 in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed TRAF2 and TRAF3 frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68 microsatellite-stable (MSS) CCs). We identified TRAF2 and TRAF3 frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs, we analyzed the mutations in multi-regions for 39 CCs (16 MSI-H and 23 MSS CCs), and discovered that 12.5% (2/16) and 6.3% (1/16) of MSI-H CCs exhibited regional difference in TRAF2 and TRAF3 mutations, respectively. In the multi-region samples of 23 MSS CCs, neither TRAF2 nor TRAF3 frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that TRAF2 and TRAF3 frameshift mutations and their regional difference as well as altered expressions are present in MSI-H CCs, which could contribute to MSI-H cancer development.

Nucleotide-binding and leucine-rich repeat protein (NLRP) genes are involved in inflammasome formation that plays a role in inflammation/host defense and cell death. Both cell death and inflammation are crucial for cancer development, but the roles of NLRPs in cancer are partially known. In this study, we analyzed mononucleotide repeats in coding sequences of NLRP1, NLRP2, NLRP4 and NLRP9, and found 1, 1, 1 and 8 frameshift mutation (s) in gastric (GC) and colonic cancers (CRC), respectively. Five of the 32 high microsatellite instability (MSI-H) GCs (15.5%) and 6 of 113 MSI-H CRCs (5.5%) exhibited the frameshift mutations. There was no NLRP frameshift mutations in microsatellite stable (MSS) GCs and CRCs. We also discovered that 2 of 16 CRCs (12.5%) harbored intratumoral heterogeneity (ITH) of the NLRP9 frameshift mutations in one or more areas. In both GC and CRC with MSI-H, NLRP9 expression in NLRP9-mutated cases was significantly lower than that in NLRP9-non-mutated cases. Our data indicate that NLRP9 is altered at multiple levels (frameshift mutation, mutational ITH and loss of expression), which together could contribute to pathogenesis of MSI-H GC and CRC.

PURPOSE The purpose of this study was to compare and analyze the effects of Taekwondo training including 8-week inspiratory muscle training on physical fitness, CRP, pulmonary function and isokinetic muscle function of middle-aged male smokers. METHODS 21 middle-aged male smokers were divided into 3 groups: inspiratory muscle training+Taekwondo training group (n=7), Taekwondo training group (n=7) and control group (n=7). Measurement variables were physical fitness (Body composition, muscular strength, muscular endurance, flexibility, cardiorespiratory function, balance), CRP, pulmonary function (FVC, FEV1, FEV1/FVC), and isokinetic muscle function (peak torque %BW, average power %BW). The repeated measure ANOVA was conducted to analyze the differences and interactions between groups and periods. In the case of any difference, t-test was conducted to perform post hoc test between pre and post treatment and the contrast was conducted to perform post hoc test between groups. One-way analysis of variance (ANOVA) was used between groups, and repeated measures t-test was used between groups. All significance levels were verified at .05. RESULTS As a result, the combined exercise group also showed statistically significant changes in the physical fitness (Body composition, muscular strength, muscular endurance, flexibility, cardiorespiratory function), pulmonary function (FEV1, FEV1/FVC), and isokinetic muscle function (peak torque %BW). CONCLUSIONS Consequently, it shows that 8 weeks Taekwondo training including inspiratory muscle training made a positive effect on fat content, muscular strength, muscular endurance, cardio respiratory fitness, R-extension in peak torque %BW in middle-aged male smokers.

Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3) is candidate tumor suppressor gene (TSG) in various cancers. EPB41L3 downregulation has been identified in many solid cancers including gastric (GC) and colorectal cancers (CRCs), but somatic inactivating mutation along with protein expression in cancers are largely unexplored. The aim of our study was to find whether EPB41L3 gene was mutated and expressionally altered in GC and CRC. EPB41L3 gene has a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 124 CRCs, and found that only one CRC with MSI-H (1.3%) harbored the frameshift mutation within the repeat. In immunohistochemistry, loss of EPB41L3 expression was identified in 49% of GCs and 42% of CRCs. Our data may indicate EPB41L3 that loss of expression but not frameshift mutation may play a role in GC and CRC development by inhibiting TSG functions of EPB41L3.

Many genes act as both tumor suppressor gene (TSG) and proto-oncogene depending on cellular context and cancer type. Nemo-like kinase (NLK) encoding a serine/threonine kinase, Yin Yang 1 (YY1) encoding a zinc-finger transcription factor and PA2G4 encoding an ErbB3 binding protein have both of these two opposing functions. In the present study, we analyzed NLK, YY1 and PA2G4 frameshift mutations in sporadic GC and CRC with high microsatellite instability (MSI-H). Also, regional intratumoral heterogeneity (ITH) of frameshift mutations of these genes was analyzed in CRCs. We found frameshift mutations of NLK, YY1 and PA2G4 in CRC and GC with MSI-H (17/132: 12.9%), but not in those with MSS (0/90). Two (12.5%), one (6.3%) and one (6.3%) CRC (s) of the 16 CRCs exhibited ITH of NLK, YY1 and PA2G4 mutations among the 4–7 regions, suggesting that ITH of the frameshift mutations might be frequent in the CRCs. These results suggest that frameshift mutations of NLK, YY1 and PA2G4 along with the ITH might contribute to MSI-H cancer pathogenesis.