Miyoshi, Japan
Miyoshi, Japan

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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.


Sekino Y.,Miyoshi Central Hospital | Mochizuki H.,Miyoshi Central Hospital | Kuniyasu H.,Nara Medical University
Journal of Medical Case Reports | Year: 2013

Introduction. Adenocarcinomas represent less than 2 percent of all urothelial neoplasms. Hepatoid adenocarcinoma is rare in the urinary bladder. Pathological diagnosis is based on a combination of histological features resembling hepatocellular carcinoma and positive immunostaining for α-fetoprotein. Case presentation. We report a case of hepatoid adenocarcinoma of the urinary bladder. A 49-year-old Japanese woman underwent a total mastectomy, and post-operatively abdominal computed tomography revealed a tumor of the urinary bladder. Trans-urethral resection of the bladder tumor was performed, and pathological examination revealed a hepatoid adenocarcinoma of the urinary bladder. Our patient has had no evidence of recurrence 20 months after surgery to remove the tumor. Conclusions: Hepatoid adenocarcinoma seems to be an aggressive malignant neoplasm that is rare in the urinary bladder. This case report is only the ninth case of hepatoid adenocarcinoma in the urinary bladder to appear in the literature. It is important to be aware of atypical cancer localizations in order to reach a correct diagnosis. © 2013 Sekino et al.; licensee BioMed Central Ltd.


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.


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.


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.


PubMed | Red Cross, Hiroshimakinen Hospital, Higashihiroshima Medical Center, Hiroshima City Asa Citizens Hospital and 9 more.
Type: Journal Article | Journal: Journal of gastroenterology | Year: 2016

The risk for lymph node metastasis and the prognostic significance of pedunculated-type T1 colorectal carcinomas (CRCs) require further study. We aimed to assess the validity of the 2014 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines based on long-term outcomes of pedunculated-type T1 CRCs.In this multicenter retrospective cohort study, we examined 176 patients who underwent resection endoscopically or surgically at 14 institutions between January 1990 and December 2010. Patients meeting the JSCCR curative criteria were defined as endoscopically curable (e-curable) and those who did not were non-e-curable. We evaluated the prognosis of 116 patients (58 e-curable, 58 non-e-curable) who were observed for>5years after treatment.Overall incidence of lymph node metastasis was 5% (4/81; 95% confidence interval 1.4-12%: three cases of submucosal invasion depth1000m [stalk invasion] and lymphatic invasion, one case of head invasion and budding grade 2/3). There was no local or metastatic recurrence in the e-curable patients, but six of them died of another cause (observation period, 80months). There was no local recurrence in the non-e-curable patients; however, distant metastasis was observed in one patient. Death due to the primary disease was not observed in non-e-curable patients, but six of them died of another cause (observation period, 72months).Our data support the validity of the JSCCR curative criteria for pedunculated-type T1 CRCs. Endoscopic resection cannot be considered curative for pedunculated-type T1 CRC with head invasion alone.


PubMed | Hiroshima University, Miyoshi Central Hospital and University of Tokyo
Type: | Journal: Academic radiology | Year: 2016

This study aimed to evaluate the effects of iterative reconstruction (IR) algorithms on computer-assisted detection (CAD) software for lung nodules in ultra-low-dose computed tomography (ULD-CT) for lung cancer screening.We selected 85 subjects who underwent both a low-dose CT (LD-CT) scan and an additional ULD-CT scan in our lung cancer screening program for high-risk populations. The LD-CT scans were reconstructed with filtered back projection (FBP; LD-FBP). The ULD-CT scans were reconstructed with FBP (ULD-FBP), adaptive iterative dose reduction 3D (AIDR 3D; ULD-AIDR 3D), and forward projected model-based IR solution (FIRST; ULD-FIRST). CAD software for lung nodules was applied to each image dataset, and the performance of the CAD software was compared among the different IR algorithms.The mean volume CT dose indexes were 3.02mGy (LD-CT) and 0.30mGy (ULD-CT). For overall nodules, the sensitivities of CAD software at 3.0 false positives per case were 78.7% (LD-FBP), 9.3% (ULD-FBP), 69.4% (ULD-AIDR 3D), and 77.8% (ULD-FIRST). Statistical analysis showed that the sensitivities of ULD-AIDR 3D and ULD-FIRST were significantly higher than that of ULD-FBP (P<.001).The performance of CAD software in ULD-CT was improved by using IR algorithms. In particular, the performance of CAD in ULD-FIRST was almost equivalent to that in LD-FBP.


PubMed | Hiroshima University, Miyoshi Central Hospital and Chugoku Rousai Hospital
Type: Journal Article | Journal: International journal of hematology | Year: 2016

The production of factor VIII (FVIII) inhibitory antibodies is a serious problem in patients with hemophilia A. Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors and has been shown to be successful in 70 % of patients with hemophilia A. However, a minority of hemophilia patients present life-long inhibitors. To eliminate such inhibitors, we designed an intravenous immunoglobulin (IVIG) strategy in combination with high dose recombinant FVIII for ITI in hemophilia A children with inhibitors. Four previously untreated patients produced inhibitors within 16 exposures to FVIII. The peak inhibitor titers in these patients ranged from 3 to 14 BU/mL. The patients received ITI combined with IVIG within 1.5 months after the inhibitors were detected. All patients showed a negative titer for inhibitors by 28 days, with no anamnestic responses. The recovery of FVIII in the plasma concentration was normalized within three months after initiation of ITI. An additional course of IVIG administration led to induction of complete tolerance by 20 months after initiation of ITI therapy in all patients. ITI treatment with high-dose FVIII combined with IVIG may be effective for the early elimination of inhibitors.


PubMed | International Drug Development Institute, Sakai City Hospital, Kanagawa Cancer Center, Osaka General Medical Center and 14 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

LBA4002 Background: Adjuvant chemotherapy with tegafur/uracil (UFT) used to be a tentative Japanese standard treatment and has been replaced by S-1 according to the result of the ACTS-GC trial, although there has been no direct comparison. Paclitaxel (PTX) has been widely used as one of the key drugs for unresectable GC. A randomized phase III trial with a two-by-two factorial design was planned to assess the survival benefit of sequential use of PTX and oral fluorinated pyrimidines (FPs) in comparison with FPs alone, and to compare UFT and S-1.Patients with serosa-invading GC who underwent R0/1 resection with extended (D2) lymph node dissection were randomized to receive either UFT 267mg/mBetween August 2004 and October 2007, 1,495 patients from 232 centers were randomized with the full analysis set of 1,433. Demographics were well balanced among arm A (n=359), B (n=364), C (n=355), and D (n=355); mean age was 64, 86% were PS 0, 68% of tumors were 8 cm or greater and 85% were clinically node positive. Grade 3-4 neutropenia or anorexia occurred in 11% or 6%, 13% or 7%, 13% or 2%, and 23% or 5% for arm A, B, C, and D, respectively. Other % grade 3-4 toxicities were less than 5%. Median follow-up was 1,875 days and 728 events occurred. Difference in DFS between C+D and A+B were not statistically significant (HR=0.92, 95%CI 0.80-1.07, p= 0.273). HR of A+C vs. B+D was 1.23 (95%CI 1.07-1.43) and hence the null hypothesis was not rejected.There was a trend for better DFS for sequential use of PTX followed by FPs. Comparison between the FPs demonstrated that UFT was inferior to S-1. Sequential PTX/S-1 is safe and effective for locally advanced GC in an adjuvant setting.C000000082.


Tsuburaya A.,Yokohama City University | Yoshida K.,Gifu University | Yoshino S.,Yamaguchi University | Takahashi M.,Yokohama Municipal Citizens Hospital | And 14 more authors.
The Lancet Oncology | Year: 2014

Background: The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1. Methods: We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m2 per day), S-1 only (80 mg/m2 per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m2) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082. Findings: We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively). Interpretation: Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan. Funding: Epidemiological and Clinical Research Information Network. © 2014 Elsevier Ltd.

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