National Hospital Organization Shimoshizu Hospital

Yotsukaidō, Japan

National Hospital Organization Shimoshizu Hospital

Yotsukaidō, Japan
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Tomizawa M.,National Hospital Organization Shimoshizu Hospital | Shinozaki F.,National Hospital Organization Shimoshizu Hospital | Sugiyama T.,National Hospital Organization Shimoshizu Hospital | Yamamoto S.,National Hospital Organization Shimoshizu Hospital | And 2 more authors.
World Journal of Gastroenterology | Year: 2010

AIM: To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed. METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol 3 kinase (PI3K), and PD98059, a specific inhibitor of mitogen-activated protein kinase, were added to the media. After 72 h, a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay was performed to analyze cell proliferation. A wound assay was performed to analyze cell motility with hematoxylin and eosin (HE) staining 48 h after addition of each inhibitor. RESULTS: All cell lines clearly expressed not only IGF-IR but also phosphorylated IGF-IR. PPP significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 36.9% ± 2.4% (mean ± SD), 30.9% ± 5.5%, 23.8% ± 3.9%, 37.1% ± 5.3%, 10.4% ± 4.5%, 52.5% ± 4.5% and 22.6% ± 0.4%, at 2 μmol/L, respectively (P < 0.05). LY294002 significantly suppressed proliferation of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 44.4% ± 7.6%, 32.9% ± 8.2%, 53.9% ± 8.0%, 52.8% ± 4.0%, 32.3% ± 4.2%, 51.8% ± 4.5%, and 30.6% ± 9.4%, at 50 μmol/L, respectively (P < 0.05). PD98059 did not significantly suppress cell proliferation. PPP at 2 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 cells to 3.0% ± 0.2%, 0%, 0%, 2.0% ± 0.1%, 5.0% ± 0.2%, 3.0% ± 0.1%, and 5.0% ± 0.2%, respectively (P < 0.05). LY294002 at 50 μmol/L suppressed motility of MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4 to 3.0% ± 0.2%, 0%, 3.0% ± 0.2%, 0%, 0%, 0% and 3% ± 0.1%, respectively (P < 0.05). PD980509 at 20 μmol/L did not suppress motility. Cells were observed by microscopy to analyze the morphological changes induced by the inhibitors. Cells in medium treated with 2 μmol/L PPP or 50 μmol/L LY294002 had pyknotic nuclei, whereas those in medium with 20 μmol/L PD98059 did not show apoptosis. CONCLUSION: IGF-IR and PI3K are good candidates for molecular therapy of pancreatic cancer. © 2010 Baishideng.


Tomizawa M.,National Hospital Organization Shimoshizu Hospital | Shinozaki F.,National Hospital Organization Shimoshizu Hospital | Sugiyama T.,National Hospital Organization Shimoshizu Hospital | Yamamoto S.,National Hospital Organization Shimoshizu Hospital | And 2 more authors.
Journal of Cellular Biochemistry | Year: 2013

Feeder-free culture of human induced pluripotent stem (hiPS) cells is necessary for their clinical application to avoid adverse effects of foreign proteins. hiPS cells were cultured with combinations of activin (A), CHIR99021 (C), basic fibroblast growth factor (F), and leukemia inhibitory factor (L) under feeder-free conditions. Culture was terminated after 12 passages or when the cell morphology changed from pluripotency. Pluripotency was analyzed by alkaline phosphatase (ALP) staining and immunostaining with antibodies to Oct3/4, Nanog, SSEA4, and TRA-1-60. SB431542 (SB), an activin inhibitor, was added to the culture, and the morphology of the cells was observed. hiPS cells cultured with A, AC, and ACL after 12 passages were positive for ALP staining. Oct3/4 was positive in hiPS cells cultured with A, AC, and ACL. hiPS cells were positive for Nanog when cultured with A and AC; however, Nanog signal was weaker in cells cultured with ACL. SSEA4 was positive in hiPS cells cultured with A and AC but almost negative in those cultured with ACL. hiPS cells were positive for TRA-1-60 when cultured with A, AC, and ACL. hiPS cells lose their undifferentiated morphology at six passages when cultured with A + SB, five passages with AC + SB, and nine passages with ACL. We conclude that feeder-free culture of hiPS cells requires A or AC to maintain pluripotency. J. Cell. Biochem. 114: 584-588, 2013. © 2012 Wiley Periodicals, Inc.


Yamanaka H.,National Hospital Organization Shimoshizu Hospital
Journal of orthopaedic surgery (Hong Kong) | Year: 2012

To review clinical results of total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients with large bone defects of the tibial condyle. Records of 33 knees in 27 women and 3 men aged 44 to 80 (mean, 63.6) years who underwent primary TKA for RA with large tibial bone defects were reviewed. 16 knees had peripheral defects extending to the bone cortex, whereas 17 knees had central defects that did not extend to the bone cortex. The femorotibial angle (FTA) was <170o in 15 knees, 170o to 180o in 3 knees, and >180o in 15 knees. The mean duration of RA was 13.5 (range, 3-35) years. In 14 knees with severe bone defects, bone grafts (harvested from articular surfaces of knee bones and fixed without screws or Kirschner wires) and/ or metal wedges (for peripheral defects) were used to fill the defects. Clinical outcome was assessed pre- and post-operatively using Knee Society scores. The mean follow-up duration was 6.3 (range, 2.3-13.2) years. The mean depth of tibial bone defects was 11.2 (range, 1-25) mm, whereas the mean width ratio of the bone defects was 36.5% (range, 16.4-76.9%). Mean extension and flexion (range of motion) improved from -12.5o and 113.4o to -5.1o and 115.6o, respectively. The mean Knee Society knee score improved from 35 (range, 21-59) to 85 (range, 49-95), whereas the mean Knee Society function score improved from 30 (range, 25-53) to 80 (range, 44-97) [p<0.001, Wilcoxon signed rank test]. The cruciate retention prosthesis was used in 6 knees; the posterior stabilised prosthesis was used in 27 knees; and the constrained condylar knee prosthesis was used in 3 knees. No patient had any infection or implant loosening. TKA achieved favourable outcome for RA patients with large tibial bone defects. The type of prosthesis used and the use of bone grafts and/ or metal wedges were based on the depth and width ratio of the bone defects.


Tomizawa M.,National Hospital Organization Shimoshizu Hospital | Shinozaki F.,National Hospital Organization Shimoshizu Hospital | Sugiyama T.,National Hospital Organization Shimoshizu Hospital | Yamamoto S.,National Hospital Organization Shimoshizu Hospital | And 2 more authors.
Journal of Cellular Biochemistry | Year: 2012

Insulin-like growth factor (IGF)-I is up-regulated in pancreatic cancer tissues. Pancreatic cancer cell lines were analyzed in serum-free media as a model of the fibrous tissues that these cells often invade. Pancreatic cancer surgical specimens were immunostained with anti-IGF-I receptor (IGF-IR)β antibody. The growth of pancreatic cancer cells in serum-free media was also analyzed. Cell lysates were analyzed for protein by western blot analysis. Cells cultured in the presence of picropodophyllin (PPP), LY294002, or PD98059, were subjected to cell proliferation and scratch assays. In addition, BrdU uptake and apoptosis were analyzed in these cells. IGF-IRβ was detected in pancreatic cancer cells invading fibrous tissues. NOR-P1 grew most rapidly in serum-free media. The concentrations of IGF-I and IGF-II in the media were higher in NOR-P1 than the other cell lines. Cell proliferation in NOR-P1 cells was enhanced by IGF-I or IGF-II treatment more than in MIA-Paca2 or PK-1 cells. PPP, LY294002, and PD98059 suppressed proliferation and motility of NOR-P1 cells and inhibited BrdU uptake, while PPP induced apoptosis. IGF-IRβ may be a potential therapeutic target to inhibit invasion of pancreatic cancer. © 2012 Wiley Periodicals, Inc.


Yamanaka H.,National Hospital Organization Shimoshizu Hospital | Goto K.-I.,National Hospital Organization Shimoshizu Hospital | Suzuki M.,National Hospital Organization Shimoshizu Hospital
Journal of Orthopaedic Surgery and Research | Year: 2012

Background: Total knee arthroplasty (TKA) is a common form of treatment to relieve pain and improve function in cases of rheumatoid arthritis (RA). Good clinical outcomes have been reported with a variety of TKA prostheses. The cementless Hi-Tech Knee II cruciate-retaining (CR)-type prosthesis, which has 6 fins at the anterior of the femoral component, posterior cruciate ligament (PCL) retention, flat-on-flat surface component geometry, all-polyethylene patella, strong initial fixation by the center screw of the tibial base plate, 10 layers of titanium alloy fiber mesh, and direct compression molded ultra high molecular weight polyethylene (UHMWPE), is appropriate for TKA in the Japanese knee.The present study was performed to evaluate the clinical results of primary TKA in RA using the cementless Hi-Tech Knee II CR-type prosthesis.Materials and methods: We performed 32 consecutive primary TKAs using cementless Hi-Tech Knee II CR-type prosthesis in 31 RA patients. The average follow-up period was 8 years 3 months. Clinical evaluations were performed according to the American Knee Society (KS) system, knee score, function score, radiographic evaluation, and complications.Results: The mean postoperative maximum flexion angle was 115.6°, and the KS knee score and function score improved to 88 and 70 after surgery, respectively. Complications, such as infection, occurred in 1 patient and revision surgery was performed. There were no cases of loosening in this cohort, and prosthesis survival rate was 96.9% at 12 years postoperatively.Conclusion: These results suggest that TKA using the cementless Hi-Tech Knee II CR-type prosthesis is a very effective form of treatment in RA patients at 5 to 12 years postoperatively. Further long-term follow-up studies are required to determine the ultimate utility of this type of prosthesis. © 2012 Yamanaka et al; licensee BioMed Central Ltd.


Tomizawa M.,National Hospital Organization Shimoshizu Hospital | Shinozaki F.,National Hospital Organization Shimoshizu Hospital | Motoyoshi Y.,National Hospital Organization Shimoshizu Hospital | Sugiyama T.,National Hospital Organization Shimoshizu Hospital | And 3 more authors.
OncoTargets and Therapy | Year: 2013

Background: The Wnt pathway plays an important role in hepatocarcinogenesis. We analyzed the association of the Wnt pathway with the proliferation of hepatoma cells using Wnt3a and niclosamide, a drug used to treat tapeworm infection. Methods: We performed an MTS assay to determine whether Wnt3a stimulated proliferation of Huh-6 and Hep3B human hepatoma cell lines after 72 hours of incubation with Wnt3a in serum-free medium. The cells were subjected to hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) after 48 hours of incubation. RNA was isolated 48 hours after addition of Wnt3a or niclosamide, and cyclin D1 expression levels were analyzed by real-time quantitative polymerase chain reaction. The promoter activity of T-cell factor was analyzed by luciferase assay 48 hours after transfection of TOPflash. Western blot analysis was performed with antibodies against β-catenin, dishevelled 2, and cyclin D1. Results: Cell proliferation increased with Wnt3a. Niclosamide suppressed proliferation with or without Wnt3a. Hematoxylin and eosin and TUNEL staining suggested that apoptosis occurred in cells with niclosamide. Cyclin D1 was upregulated in the presence of Wnt3a and downregulated with addition of niclosamide. The promoter activity of T-cell factor increased with Wnt3a, whereas T-cell factor promoter activity decreased with niclosamide. Western blot analysis showed that Wnt3a upregulated β-catenin, dishevelled 2, and cyclin D1, while niclosamide downregulated them. Conclusion: Niclosamide is a potential candidate for the treatment of hepatoma. © 2013 Tomizawa et al.


Tomizawa M.,National Hospital Organization Shimoshizu Hospital | Shinozaki F.,National Hospital Organization Shimoshizu Hospital | Hasegawa R.,National Hospital Organization Shimoshizu Hospital | Togawa A.,National Hospital Organization Shimoshizu Hospital | And 6 more authors.
World Journal of Gastroenterology | Year: 2014

AIM: To investigate the early upper gastrointestinal endoscopy (endoscopy) significantly reduces mortality resulting from upper gastrointestinal (GI) bleeding. METHODS: Upper GI bleeding was defined as 1a, 1b, 2a, and 2b according to the Forrest classification. The hemoglobin (Hb), and C-reactive protein (CRP) were examined at around the day of endoscopy and 3 mo prior to endoscopy. The rate of change was calculated as follows: (the result of blood examination on the day of endoscopy-the results of blood examination 3 mo prior to endoscopy)/(results of blood examination 3 mo prior to endoscopy). Receiver operating characteristic curves were created to determine threshold values. RESULTS: Seventy-nine men and 77 women were enrolled. There were 17 patients with upper GI bleeding: 12 with a gastric ulcer, 3 with a duodenal ulcer, 1 with an acute gastric mucosal lesion, and 1 with gastric cancer. The area under the curve (AUC), threshold, sensitivity, and specificity of Hb around the day of endoscopy were 0.902, 11.7 g/dL, 94.1%, and 77.1%, respectively, while those of CRP were 0.722, 0.5 mg/dL, 70.5%, and 73%, respectively. The AUC, threshold, sensitivity, and specificity of the rate of change of Hb were 0.851,-21.3%, 76.4%, and 82.6%, respectively, while those of CRP were 0.901, 100%, 100%, and 82.5%, respectively. CONCLUSION: Predictors for upper GI bleeding were Hb < 11.7 g/dL, reduction rate in the Hb > 21.3% and an increase in the CRP > 100%, 3 mo before endoscopy. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.


PubMed | National Hospital Organization Shimoshizu Hospital
Type: Journal Article | Journal: Case reports in gastroenterology | Year: 2016

Biopsies are necessary for the management of duodenal tumors. However, the most suitable targets for biopsy are not known. An 82-year-old woman who regularly visited our hospital for rheumatoid arthritis underwent abdominal ultrasonography. This screening revealed a dilated pancreatic duct. Magnetic resonance cholangiopancreatography was performed, and dilatation of the pancreatic duct was confirmed. The patient underwent duodenoscopy to investigate the possibility of obstruction of the papilla of Vater. The examination revealed an elevated lesion around the papilla of Vater. Endoscopic ultrasonography and a 20-MHz mini-probe were used to investigate the depth of the invasion. The common bile and pancreatic ducts were intact. The mucosal and submucosal borders were indistinct; however, the border between the submucosa and muscularis propria was clear, suggesting that the muscularis propria was intact. Magnifying endoscopy was used to examine the surface of the elevated lesion, which revealed a depressed lesion. A biopsy specimen of the depressed lesion was taken, and the tumor was diagnosed as an adenocarcinoma. Another biopsy specimen from a non-depressed lesion was diagnosed as an adenoma. The patient was diagnosed with duodenal adenocarcinoma, and was recommended surgery. She declined surgery and was followed up for 34 months. Because it is possible for depressed lesions of duodenal tumors to be adenocarcinomas, biopsy specimens should be obtained from depressed lesions of duodenal tumors.


PubMed | National Hospital Organization Shimoshizu Hospital
Type: Journal Article | Journal: Oncology letters | Year: 2016

Metastasis negatively affects the prognosis of hepatocellular carcinoma (HCC). In the present study, niclosamide, which is known to suppress the proliferation of HCC cells, was investigated for possible suppressant effects on the migration of HCC cells. HLF and PLC/PRF/5 HCC cells were cultured in the presence of niclosamide. Cell proliferation was analyzed using the MTS assay. Cell migration was measured by performing a scratch assay. Expression levels of cyclin D1 and matrix metalloproteinase 9 (MMP9) were analyzed by performing revers transcription-quantitative polymerase chain reaction. Compared with the control treatment, treatment with 10 m niclosamide suppressed the proliferation of the HLF and PRL/PRF/5 cells to 49.93.7 and 17.911.5% (P<0.05), respectively. Furthermore, compared with the control treatment, treatment with 1.0 M niclosamide downregulated the expression of cyclin D1 to 52.44.4 and 23.95.4% (P<0.05) in the HLF and PRL/PRF/5 cells, respectively. In the scratch assay, treatment of the HLF cells with niclosamide (1.0 m) decreased the distance of the scratched line from the growing edge to 4.61.0 mm compared with the 9.21.4 mm observed with the control treatment (P<0.05). Similarly, treatment of the PRL/PRF/5 cells with niclosamide (1.0 m) also decreased the distance of the scratched line from the growing edge to 3.00.8 mm compared with the 5.50.9 mm observed with the control treatment (P<0.05). Further, MMP9 expression levels in the HLF cells treated with 1.0 m niclosamide decreased to 22.41.76% (P<0.05) compared with those in the untreated control HLF cells. Similarly, expression level of MMP9 in the PRL/PRF/5 cells treated with 1.0 m niclosamide deceased to 18.710.7% (P<0.05) compared with those in the untreated control PRL/PRF/5 cells. Overall, niclosamide downregulated the expression of MMP9 in and suppressed the migration of HCC cells.


PubMed | National Hospital Organization Shimoshizu Hospital
Type: Journal Article | Journal: Biomedical reports | Year: 2016

Lower gastrointestinal (GI) bleeding can be caused by colorectal polyps or cancer. The aim of the present study was to identify blood test variables and medications that can predict lower GI bleeding, which would allow for appropriate colonoscopy. The medical records of patients who underwent colonoscopy from September 2014 to September 2015 were retrospectively analyzed. The selected patients included 278 men (mean age, 67.011.5 years) and 249 women (mean age, 69.612.0 years). The diagnosis, medications, and blood test variables were compared between patients with and without bleeding. Logistic regression analysis was performed to determine the factors associated with lower GI bleeding. The presence of colorectal polyp and cancer was associated with lower GI bleeding (P=0.0044) with an odds ratio of 6.71 (P=0.0148). No lower GI bleeding was observed in patients taking non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or anticoagulants. The C-reactive protein (CRP) levels were significantly higher in patients with lower GI bleeding (P=0.0227). The Hb levels were lower in patients with lower GI bleeding, however this finding was not statistically significant (P>0.05). No blood test variable was associated with lower GI bleeding. Elevated CRP was associated with lower GI bleeding, while there was no association between the medications and lower GI bleeding.

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