Isaku Yoshioka

University of Toyama, Тояма, Toyama, Japan

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Publications (12)16.16 Total impact

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    ABSTRACT: Background/Purpose: Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. Methods: AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. Results: Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC50 of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). Conclusions: Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC. © 2013 S. Karger AG, Basel.
    European Surgical Research 11/2013; 51(3-4):108-117. · 0.75 Impact Factor
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    ABSTRACT: Abstract Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of (18)F-FDG PET are not specific for malignancy because (18)F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for (18)F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on (18)F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on (18)F-FDG PET.
    International surgery 10/2013; 98(4):372-378. · 0.31 Impact Factor
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    ABSTRACT: The clinical outcome of gastrointestinal stromal tumor (GIST) has been improved by the introduction of molecular-targeting drugs. However, resistance to these drugs appears during the course of treatment. The aim of this study was to establish and characterize a human xenograft model of GIST. GIST tissue from a patient with esophageal GIST was implanted under the skin of a NOD-SCID mouse. The tumor became successfully engrafted and we investigated the effects of imatinib and sunitinib on this model. KIT mutation was investigated by complementary DNA analysis, and c-KIT (CD117) expression was evaluated by immunohistological staining. cDNA analysis of the tumor revealed a KIT mutation in exon 11. c-KIT expression was observed in each passaged tumor. Both imatinib and sunitinib significantly reduced the size of the xenograft tumor. We established a novel xenograft model of human GIST in mice. This xenograft model may be useful for studying GIST.
    Anticancer research 01/2013; 33(1):175-81. · 1.71 Impact Factor
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    ABSTRACT: Aim: To understand the role of iPS inductive genes in esophageal cancer, we examined the expression of Sex determining region Y-box 2 (SOX2), Octamer-binding transcription factor 3/4 (OCT3/4), Krueppel-like factor 4 (KLF4), c-Myelocytomatosis viral oncogene (c-MYC) and Tir Na Nog (NANOG) using an esophageal squamous cell carcinoma tissue micrroarray. The immunohistochemical expression levels of the five genes were compared to the clinicopathological data of the 81 patients with esophageal cancer. There was no relationship between the expression of the five genes and TNM factors of the patients. High expression of NANOG was an independent favorable prognostic factor (p=0.041). Among the patients who received postoperative cisplatin-based chemotherapy, patients with NANOG-positive tumor had significantly better prognosis than those whose tumors were NANOG negative (p=0.024). On the other hand, those with c-MYC-positive expression tended to have a worse prognosis and were resistant to cisplatin-based chemotherapy. NANOG expression was found to be an independent prognostic factor for patient with esophageal cancer. Patients with NANOG-positive expression tumor may be good candidates for cisplatin-based treatment.
    Anticancer research 12/2012; 32(12):5507-14. · 1.71 Impact Factor
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    ABSTRACT: Prognosis for patients with gallbladder carcinoma (GBC) is poor and the standard treatment for GBC has not yet been established. We established the human GBC cell line TYGBK-1, from a patient with papillary, tubular adenocarcinoma. The doubling time was 48 hours. This cell line has a missense mutation of p53 and no mutation of the K-RAS gene. This cell line was transplantable to nude mice. We characterized the sensitivity of TYGBK-1 to gemcitabine. We also examined the association of two gemcitabine-related genes (deoxycytidine kinase, dCK, and Hu antigen R, HuR). Among four GBC cell lines (TYGBK-1, NOZ, G-415, TGBC2TKB), TYGBK-1 and NOZ exhibited sensitivity to gemcitabine. Furthermore, these cells expressed both dCK and HuR mRNA, rather than gemcitabine-resistant cells. The newly established GBC cell line TYGBK-1, may represent an effective tool for development of chemotherapeutic treatment for GBC.
    Anticancer research 08/2012; 32(8):3211-8. · 1.71 Impact Factor
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    ABSTRACT: Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.
    Oncology Reports 06/2012; 27(6):1741-7. · 2.30 Impact Factor
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    ABSTRACT: Recently, prone position esophagectomy for esophageal cancer is thought to be an easier and safer procedure. Here, we introduced prone position for enucleation of the fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) positive esophageal leiomyoma. The patient was a 47-year-old man with a 4 cm mid-thoracic esophageal submucosal tumor. The tumor was enucleated safely without injury of the esophageal mucosa under the gravity effect of the prone position with use of a sponge spacer and Sengstaken-Blakemore balloon. Postoperative examination revealed that the tumor was a leiomyoma that was positive for smooth muscle actin and negative for CD117. Postoperative course was uneventful and the patient was discharged on day 7 after the operation. The prone position with use of a sponge spacer and Sengstaken-Blakemore balloon was a safer and easier procedure for the enucleation of the esophageal submucosal tumor.
    General Thoracic and Cardiovascular Surgery 05/2012; 60(8):542-5.
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    ABSTRACT: BACKGROUND: Adequate blood supply for the reconstructed organ is important for safe esophagogastric anastomosis during esophagectomy. Recently, indocyanine green (ICG) has been used for visualization of the blood supply when anastomosis is performed in vascular surgery. To visualize the blood supply for reconstruction, we employed ICG fluorescence during esophagectomy. METHODS: From August 2008, 40 patients received cervical or thoracic esophagectomy. They consisted of 33 patients having esophagectomy for thoracic esophageal cancer, 3 being treated for cervical esophageal cancer, and 4 with double cancer of the thoracic and cervical regions. Before and after pulling up the reconstructed organ, 2.5 mg of ICG was injected as a bolus. Then ICG fluorescence was detected by a camera and recorded. RESULTS: ICG fluorescence was easily detected in all patients at 1 min after injection. The vascular network was well visualized in the gastric wall, colonic grafts, and free jejunal grafts. In five patients, we also performed anastomosis between the short gastric vein and the external cervical vein or superficial cervical vein. The intraoperative and postoperative course of all patients was uneventful apart from three anastomotic leakages. CONCLUSIONS: ICG fluorescence can be employed to evaluate the blood supply to reconstructed organs and can be useful in selecting the patients who do not need additional vessel anastomosis. However, anastomotic leakage was not reduced, so the microcirculation detected by ICG fluorescence did not necessarily provide appropriate blood supply for a viable anastomosis.
    Esophagus 12/2011; 8(4):259-266. · 0.83 Impact Factor
  • The American surgeon 07/2010; 76(7):789-90. · 0.92 Impact Factor
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    ABSTRACT: Recently, we have reported that surgical stress promoted the metastasis of murine colon carcinoma cells to the lung by inducing the expression of proteases such as matrix metalloprotease-9 (MMP-9) in lung tissue. Urinary trypsin inhibitor (UTI) is a serine protease inhibitor frequently used to treat pancreatitis and to improve the microcirculatory environment. The purpose of this study was to investigate the anti-metastatic properties of UTI in an animal model of surgical stress-induced cancer metastasis. The intraperitoneal administration of UTI after the intravenous injection of colon 26-L5 carcinoma (colon 26-L5) cells into mice subjected to surgical stress suppressed the enhancement of lung metastasis (p<0.05). Furthermore, we investigated the effect of UTI on tumor growth, adhesion to fibronectin, migration, invasion and enzymatic degradation in colon 26-L5. UTI reduced the invasive ability and the degradation by MMP-9 of gelatin substrate in colon 26-L5 cells. UTI may improve therapeutic efficacy in cancer patients after major surgery.
    Anticancer research 01/2005; 25(2A):815-20. · 1.71 Impact Factor
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    ABSTRACT: Although it is well-known that excessive surgical stress augments the growth of residual cancer and metastasis, whether surgical stress is increased according to the degree of surgical manipulation and can consequently lead to the enhancement of cancer metastasis has not been thoroughly examined. Moreover, the molecules associated with response for stress-enhanced metastasis have not been well-analyzed. The aim of this study was to examine whether cancer metastasis is enhanced with an increase of surgical stress with an experimental lung metastasis model and to analyze the related molecules responsible for stress-enhanced metastasis. Colon 26-L5 carcinoma cells (1.5 x 10(4)/mouse) were injected intravenously into 6-week-old female BALB/c mice (Japan SLC, Hamamatsu, Japan). Two hours later, the mice were divided into 5 groups: untreated controls (the C group); mice given anesthesia only (the A group); mice given anesthesia and laparotomy (the AL group); mice given anesthesia, laparotomy, and appendectomy (the ALAp group); and mice given anesthesia, laparotomy, appendectomy, and left hepatic lobectomy (the ALApH group). The anesthesia procedures were the same in all groups (intraperitoneal administration of 0.8 mg/mouse sodium pentobarbital). In the AL, ALAp, and ALApH groups, a 3-cm long laparotomy was performed, and the time of the whole operation was just 5 minutes. All mice were killed 14 days after the procedures, and the number of lung metastases on the lung surface was counted manually. At the same time, BALB/c mice without tumor burden were given the same 5 kinds of surgical stress, and the messenger RNA expression of various metastasis-related molecules in the lung was measured with reverse transcriptase-polymerase chain reaction at 6, 24, and 48 hours after surgical stress. We also examined the effect of ONO-4817 (an inhibitor of matrix metalloproteinases ([MPs]) on lung metastasis in the mice with the 5 kinds of surgical stress. The numbers of lung metastases on the lung surface and the messenger RNA expression of MMP-9, membrane type IBMMP, and urokinase-type plasminogen activator at 24 hours after surgery were enhanced in proportion to the degree of surgical stress. Moreover, ONO-4817 significantly inhibited lung metastasis. These results strongly suggest that increased surgical stress augments cancer metastasis via surgical stress-induced expression of proteinases in the target organ of metastasis.
    Surgery 06/2003; 133(5):547-55. · 3.37 Impact Factor
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    ABSTRACT: Primary malignant melanoma of the esophagus (PMME) is a rare disease. Here, we describe a case of PMME that was identified at a very early stage. A 65-year-old man underwent upper gastrointestinal endoscopy and was found to have a pigmented small nodule in the lower esophagus. A biopsy was taken and diagnosed as malignant melanoma, so the patient then received radical esophagectomy. Histopathological examination showed atypical cell infiltrate in the lamina propria mucosae without lymph-node metastasis. The patient was followed up without adjuvant chemotherapy. Multiple liver and lung metastases were found at 19 months after surgery, and the patient received DAV-feron (DTIC/ACNU/VCR/IFN-β) therapy. However, the tumors progressed and the patient died of the disease at 27 months after surgery. More detailed surveys after surgery with diagnostic imaging and tumor markers are recommended. Adjuvant chemotherapy is worth considering, even in patients with early-stage PMME.
    Esophagus · 0.83 Impact Factor