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Miyoshi, Japan

Shimomoto T.,Nara Medical University | Ohmori H.,Nara Medical University | Luo Y.,Nara Medical University | Chihara Y.,Nara Medical University | And 5 more authors.
Clinical and Experimental Metastasis | Year: 2012

We examined the effects of hyperglycemic conditions on liver metastasis of colorectal cancer (CRC). Angiotensin (A)-II increased growth, invasion, and anti-apoptotic survival in HT29 and CT26 cells. In contrast, angiotensinogen (ATG) increased these features in HT29 cells but not in CT26 cells. HT29 cells expressed A-II type 1 receptor, chymase, and rennin, whereas CT26 cells did not express renin. Renin expression and ATG-induced cell growth, invasion, and survival induced and increased as glucose concentration increased in HT29 cells and also CT26 cells. An inhibitor of renin or chymase abrogated A-II production in HT29 cells. Reduction of hepatic ATG production by cholesterol-conjugated antisense S-oligodeoxynucleotide suppressed liver metastasis of HT29 cells. An examination of 121 CRC patients showed that diabetes in CRC cases was associated with higher blood HbA1c, higher renin and A-II concentrations in the primary tumors, and higher incidence of liver metastasis than in nondiabetic cases. These results suggest that diabetes-associated angiotensin activation enhances liver metastasis of CRC and may therefore provide a possible target for antimetastatic therapy in CRC. © 2012 Springer Science+Business Media B.V.

Kuniyasu H.,Nara Medical University | Luo Y.,Nara Medical University | Fujii K.,Nara Medical University | Sasahira T.,Nara Medical University | And 5 more authors.
Gut | Year: 2010

Objective: To examine the role of CD10, a characteristic marker of liver metastasis of colorectal cancers (CRCs). Design: The effect of CD10 and Met-enkephalin (MENK) in CD10-positive and -negative human CRC cells was investigated under in vitro and in vivo conditions. Human CRC samples were examined. Main outcome measure: CD10-positive and CD10-knockdown HT29 cells and CD10-negative and CD10-transfected Colo320 cells in nude mice were treated with MENK and/or the CD10 inhibitor (thiorphan). Intracellular signalling of MENK and d-opioid receptor (DOR) was examined by immunoblotting. Results: MENK inhibited the growth, invasion and survival of CRC cells following thiorphan-induced CD10 inactivation. Thiorphan suppressed liver metastasis of CD10-positive CRC cells. Inoculation of mice with CRC cells induced MENK expression in the liver. Inhibition of hepatic MENK expression by cholesterol-conjugated antisense S-oligodeoxynucleotide increased liver metastasis of CRC cells even when the cells did not express CD10. DOR activation by MENK decreased the phosphorylation of epidermal growth factor receptor and extracellular signal-regulated kinase and increased p38-dependent apoptosis. Nitric oxide was found to induce DOR expression in CRC cells. Co-treatment with thiorphan and a nitric oxide donor had a marked antitumour effect on liver metastasis of HT29 cells. Of 68 CRC patients, 19 (28%) showed CD10 expression, which was dependent on the extent of liver metastasis. MENK concentration in metastasis-positive human liver was higher than that in the normal liver. Conclusion: CD10 expression in CRC cells abrogates the anti-tumour effect of hepatic MENK by degrading it, which enhances liver metastasis of CD10-positive CRC cells.

Harada Y.,Hiroshima University | Nakasa T.,Hiroshima University | Mahmoud E.E.,Hiroshima University | Kamei G.,Miyoshi Central Hospital | And 3 more authors.
Journal of Orthopaedic Research | Year: 2015

The present study investigated intra-articular injection of bone-marrow-derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight-bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra-articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra-articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Tsumura K.,Miyoshi Central Hospital
Otolaryngology - Head and Neck Surgery (Japan) | Year: 2012

We reported a case of previously healthy 35-year-old man with Moraxella osloensis bacteremia. Computed tomographic imaging of the chest revealed bilateral pleural effusion and multiple areas of consolidation with cavitation. He was successfully treated with intravenous administration Meropenem (MEPM) for 13 days, and was continued 4 weeks of oral antibiotics. The clinical findings of lung lesion and postanginal sepsis led to diagnosis of Lemierre's syndrome. The predominant pathogen was an aerobic gram-negative cocco-bacillus, M. osloensis. The bacillus was isolated from blood culture, and was identified definitively by sequencing analysis of the 16S ribosomal RNA gene.

Moriwaka Y.,Nara Medical University | Luo Y.,Nara Medical University | Ohmori H.,Nara Medical University | Fujii K.,Nara Medical University | And 3 more authors.
Pathobiology | Year: 2010

Background: Cancer-secreted high mobility group 1 (HMGB1) induces apoptosis of macrophages and suppresses the host anti-cancer immune system. Objective: We here examined the effect of HMGB1 on macrophages in the lymph nodes of colorectal cancer (CRC) patients. Methods: Regional lymph nodes of 50 Dukes C CRCs were compared with 50 Dukes B CRCs. Results: Dukes C tumors exhibited higher HMGB1 labeling indices and higher HMGB1 concentrations in primary tumors than Dukes B CRCs. Macrophages in the regional lymph nodes were decreased in non-metastasized nodes as well as metastasized nodes in Dukes C cases, whereas macrophage numbers in Dukes B nodes were higher than in Dukes C nodes. Nodal HMGB1 concentration was higher in Dukes C nodes than in Dukes B nodes, being inversely correlated with macrophage numbers. Nodal HMGB1 concentration was correlated with HMGB1 concentration and lymph vessel density in the primary tumors. Conclusion: These data suggest that HMGB1 secreted from primary tumors spread to the regional lymph nodes decreases the number of macrophages to attenuate the anti-metastatic defense of the lymph nodes in patients with CRCs. © 2010 S. Karger AG, Basel.

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