Koji Miyanishi

Sapporo Medical University, Sapporo, Hokkaidō, Japan

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Publications (94)365.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Branched‑chain amino acids (BCAAs) and trace element deficiencies are associated with poor prognosis in hepatitis C virus (HCV)‑infected patients. The aim of this study was to investigate the effects of BCAA and zinc‑enriched supplementation on prognostic factors in HCV‑infected patients. Fifty‑three HCV‑infected patients were enrolled in this multicenter randomized controlled trial. The patients were assigned to either the placebo (n=27) or supplement group (n=26; 6,400 mg/day BCAAs and 10 mg/day zinc) and were followed up for 60 days. Primary outcomes were prognostic factors for chronic liver disease, including the serum BCAA‑to‑tyrosine ratio (BTR), zinc levels and α‑fetoprotein (AFP) levels. There were no significant differences in any of the prognostic factors between the placebo and supplement groups at baseline. In the supplement group, the BTR and zinc levels were significantly increased compared with the placebo group (BTR: 5.14±1.59 vs. 4.23±1.14, P=0.0290; zinc: 76±11 vs. 68±11 µg/dl, P=0.0497). No significant differences were observed in AFP levels between the groups in the whole analysis. However, a stratification analysis showed a significant reduction in ΔAFP levels in the supplement group, with elevated AFP levels compared with the other groups (‑2.72±3.45 ng/ml, P=0.0079). It was demonstrated that BCAA and zinc‑enriched supplementation increased the BTR and zinc levels in the HCV‑infected patients. Furthermore, the supplementation reduced the serum AFP levels in patients who had elevated serum AFP levels at baseline. Thus, BCAA and zinc‑enriched supplementation may prolong the survival of HCV‑infected patients by improving amino acid imbalance and zinc deficiency, and by partly downregulating AFP.
    Molecular Medicine Reports 11/2014; · 1.17 Impact Factor
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    ABSTRACT: To investigate the effectiveness of phenol for the relief of cancer pain by endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN).
    World journal of gastroenterology : WJG. 08/2014; 20(30):10512-7.
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    ABSTRACT: Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-yearold woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response. Dose reduction and delay occurred owing to hematological toxicity and febrile neutropenia. As second-line chemotherapy, the patient was administered a single daily dose of 800 mg of pazopanib. Because of an episode of hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanibwas reduced to a daily dose of 600 mg, which had to be further reduced to a daily dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial response for a total of 4.3 months when treated with pazopanib. Therefore, this drug may be a new treatment option for patients showing metastatic STS after previous chemotherapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 08/2014; 41(8):1041-4.
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    ABSTRACT: Background and study aims: The clinical utility of computed virtual chromoendoscopy with flexible spectral imaging color enhancement (FICE) in capsule endoscopy (CE) remains controversial. To clarify the clinical utility of FICE-enhanced CE in evaluating small bowel lesions, we quantitatively assessed white light (WL), FICE, and blue mode (BM) images and examined the sensitivity of these 3 imaging modes of small-bowel lesions from patients who underwent CE. Methods: The CIELAB color difference (ΔE) and visual analogue scales (VAS) were measured in 261CE images (3 different lesion categories) using WL and FICE set 1, 2, and 3, and BM images, respectively. Three endoscopists reviewed CE videos with WL, 3 FICE mode settings, and BM, and compared the sensitivity and detectability for small intestinal diseases from 50 patients who underwent CE. Results: In the assessment of visibility in the 152 vascular lesion images, the ΔE and VAS of FICE set 1, 2, and BM images were significantly higher than that of WL images. In 88 erosion/ulceration images, the ΔE and VAS of FICE set 1 and 2 images were significantly higher than that of WL images. In 21 tumor images, there were no significant differences in ΔE among these modalities.When analyzed on a per-patient basis, FICE settings 1 and 2 had the highest sensitivity (100%) and specificity (97.3–100%) for vascular lesions. As for erosive/ ulcerative lesions, FICE setting 2 had the highest sensitivity (100%) and specificity (97.2 %). For tumors or polyps, WL had the highest sensitivity (90.9 %) and specificity (87.1 %). In per-lesion analysis, FICE settings 1 and 2 showed significantly superior detection ability overWL for vascular lesions. In the detection of erosive/ulcerative lesions, FICE setting 2 was significantly superior to WL. In tumor images, there was no significant improvement with any of the settings relative to WL images. Conclusions: FICE is most useful for improving CE image quality and detection in cases of angioectasia and erosion/ulceration of the small intestine.
    Gastrointestinal Endoscopy 05/2014; · 5.21 Impact Factor
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    ABSTRACT: Therapy-related leukemia (TRL) has been reported to occur after treatment with alkylating agents and/or topoisomerase II inhibitors. Oxaliplatin (OXP) is used as a key drug for the treatment of colorectal cancer (CRC). Cisplatin and carboplatin have been linked with TRL, but the involvement of OXP is questionable. A 74-year-old male was diagnosed with peritoneal metastasis from CRC in July 2011. The patient received nine cycles of 5-fluorouracil (5-FU), leucovorin (LV), and OXP (mFOLFOX-6 regimen) and three cycles of 5-FU and LV only, resulting in a clinical complete response. However, recurrence of CRC was detected by CT within 3 months after the last course of chemotherapy. In April 2013, laboratory tests showed pancytopenia and 15% blast cells. A bone marrow examination revealed multilineage dysplasia and 20.4% myeloblasts. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. The patient was diagnosed with TRL and treated with a combination of azacitidine (AZA) and cetuximab (Cmab) for both cancers. AZA might be useful in TRL when a patient needs to be treated simultaneously for more than one primary cancer because of its low toxicity. Moreover, Cmab is an effective therapeutic tool in TRL patients with metastatic CRC with the wild-type K-ras gene.
    Case Reports in Oncology 05/2014; 7(2):316-22.
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    ABSTRACT: Radiation therapy (RTx) has been employed as a curative therapy for prostatic adenocarcinoma. RTx-induced sarcomas (RISs) are rare, late adverse events, representing less than 0.2% of all irradiated patients. RISs are more aggressive tumors than prostatic adenocarcinomas. Herein, we present a case with RTx-induced prostatic leiomyosarcoma after permanent brachytherapy for prostatic adenocarcinoma. A 69-year-old male presented with dysuria and gross hematuria. Six years previously, he had been diagnosed with localized prostate cancer and was treated by permanent brachytherapy. Urethroscopy showed stenosis by a tumor at the prostate. Transurethral prostatectomy was performed for a diagnosis. Based on pathological findings, the diagnosis was leiomyosarcoma of the prostate. He was treated with three cycles of neoadjuvant chemotherapy (CTx) that consisted of doxorubicin and ifosfamide (AI), followed by a prostatocystectomy with intrapelvic lymphadenectomy. The tumor extended from the prostate and infiltrated the bladder wall and serosa with lymphatic and venous invasion. The surgical margin was negative, and no residual prostatic adenocarcinoma was observed. The proportion of necrotic tumor cells by neoadjuvant CTx was around 50%. Subsequently, adjuvant CTx was offered, but the patient chose a follow-up without CTx. Local recurrence and lung metastasis were detected by computed tomography 3 months after the surgery. He was treated again with AI. However, CTx was not effective and he died 6 months after the operation. In conclusion, an effective treatment strategy for prostatic sarcoma should be developed in the near future, although the clinical feature of prostatic sarcoma remains unclear due to its rare incidence.
    Case Reports in Oncology 05/2014; 7(2):565-70.
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    ABSTRACT: Narrowband ultraviolet B phototherapy (NB-UVB) is a therapeutic alternative for haematopoietic stem cell transplantation-related skin graft-versus-host disease (GVHD). The beneficial effects of this intervention may be induced by direct irradiation of inflammatory cells in the skin; however, the putative involvement of indirect effects on systemic immunity has not been elucidated. To address this issue, 11 acute skin GVHD patients refractory to standard corticosteroid treatment and with no gut/liver involvement were treated with NB-UVB irradiation. The median number of treatments was 10 times, with a mean cumulative exposure of 6.36 J/cm(2). No other immunosuppressive therapy was initiated during irradiation. Eight patients achieved an objective complete response, two had a partial response, and one showed no change. None of the patients experienced progressive skin GVHD or newly diagnosed gut/liver GVHD. NB-UVB was well tolerated, with no patients discontinuing irradiation due to toxicity. We additionally demonstrated by flow cytometry that NB-UVB irradiation induces the increment of the proportion of regulatory T cell (Tregs) in patients' peripheral blood. These results suggest that NB-UVB may exert beneficial effects on steroid-refractory skin GVHD through the expansion of Tregs.
    International journal of hematology 02/2014; · 1.17 Impact Factor
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    ABSTRACT: Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt's lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt's lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death.
    Blood Cancer Journal 01/2014; 4:e180. · 1.40 Impact Factor
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    ABSTRACT: Solitary fibrous tumor of the central nervous system is uncommon, with only around 200 reported cases. Further, extracranial metastasis is extremely rare, and only 5 cases of hematogenous metastases have been reported so far. To the best of our knowledge, there have been no reports of solitary fibrous tumor of the central nervous system metastasizing to the pancreas. A 62-year-old woman was referred for evaluation of a pancreatic mass, which was strongly suspected to be a neuroendocrine tumor. However, the histological findings and immunohistochemical profile indicated the presence of a solitary fibrous tumor. Because the medical history revealed previous transcranial resection for intracranial meningioma 16 years ago, we conducted a pathological review of the brain specimen obtained by the first operation and found that it had the same histology and immunohistochemical profile as the current endoscopic ultrasound-guided fine-needle aspiration specimen. Consequently, the final diagnosis, on the basis of the brain specimen, was changed from meningioma to solitary fibrous tumor of the central nervous system, and the pancreatic mass was diagnosed as metastasis from solitary fibrous tumor of the central nervous system. The patient underwent middle pancreatectomy; the pancreatic specimen also had the same histology and immunohistochemical profile as the brain specimen. Histological findings and immunohistochemical profile obtained by EUS-FNA are invaluable for the correct diagnosis to avoid excessive surgical procedures.
    JOP: Journal of the pancreas 01/2014; 15(1):58-62.
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    ABSTRACT: Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient.
    Internal Medicine 01/2014; 53(16):1759-62. · 0.97 Impact Factor
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    ABSTRACT: Background:Transforming growth factor-β (TGF-β) is a major inducer of epithelial-mesenchymal transition (EMT) in different cell types. TGF-β-mediated EMT is thought to contribute to tumour cell spread and metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-β is unclear.Methods:Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-β downstream molecules were analysed by western blot. Fucosylation of TGF-β receptor (TβR) was examined by lectin blot analysis.Results:Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TβR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT.Conclusion:Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-β-mediated EMT.British Journal of Cancer Advance Online Publication, 19 November 2013 doi:10.1038/bjc.2013.699 www.bjcancer.com.
    British Journal of Cancer 11/2013; · 5.08 Impact Factor
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    ABSTRACT: A 62-year-old man with transfusion-dependent severe aplastic anemia received immunosuppressive therapy (IST) with rabbit antithymocyte globulin and cyclosporine A in April 2010. However, his transfusion dependency did not improve. As more than 100 red blood cell (RBC) transfusions had been performed, he was administered iron chelation therapy (ICT) with deferasirox (DFX) to improve iron overload starting in July 2011. Consequently, both RBC and platelet transfusion dependency gradually improved concomitant with a decrease in serum ferritin. The bone marrow (BM) biopsy findings before administration of DFX showed severe iron accumulation and strong positive immunostaining for 8-OHdG, a marker of oxidative stress due to free iron. One year after ICT, the number of BM hematopoietic cells was increased and both iron deposition and oxidative stress were decreased. These findings suggest that DFX may contribute to hematological improvement in patients with IST-refractory aplastic anemia.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 11/2013; 54(11):2047-52.
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    ABSTRACT: The evidence that rituximab is effective therapy for refractory warm or cold autoimmune hemolytic anemia (AIHA) has been accumulating; however, the efficacy of rituximab for mixed-type AIHA is not evident. Herein, we report a case of mixed-type AIHA refractory to corticosteroids and splenectomy, but successfully treated with rituximab (375 mg/m(2)/day, once weekly, four times). She achieved a complete response, which has been maintained for 16 months, to date, despite steroid tapering. Our case suggests that rituximab therapy should be considered for refractory AIHA even of mixed-type.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 11/2013; 54(11):2053-5.
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    ABSTRACT: PURPOSE: The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer. METHODS: Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry. RESULTS: A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4 %, and disease control ratio was 100 %. Grade 4 neutropenia developed in 53.5 % of patients and febrile neutropenia in 16.3 %. Non-hematological grade 3/4 adverse events were anorexia (23.3 %), nausea (14.0 %), and diarrhea (23.3 %), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7 %, and a pathological response was found in 65.9 % of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5 %. CONCLUSIONS: Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.
    Cancer Chemotherapy and Pharmacology 01/2013; · 2.80 Impact Factor
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    ABSTRACT: BACKGROUND: The rate of onset of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) has been reported recently to be comparable to that of patients with chronic hepatitis C. However, the precise mechanism contributing to carcinogenesis in the former remains unclear. Although increased oxidative stress is presumed to play a role in carcinogenesis in patients with NASH, this relationship remains to be directly proven. In this study, we investigated the involvement of oxidative DNA damage in hepatocarcinogenesis in patients with NASH. METHODS: Patients with nonalcoholic fatty liver disease who were treated at our university hospital were eligible for enrolment in the study(n = 49). The study cohort included 30 patients with NASH without HCC (NASH without HCC), six HCC patients with NASH (NASH-HCC), and 13 patients with simple steatosis. Quantitative immunohistochemistry with a KS-400 image analyzing system was used for 8-hydroxy-2'-deoxyguanosine (8-OHdG) detection. RESULTS: The 8-OHdG content in the liver tissue of NASH-HCC patients was significantly different from that in the other patients. The median immunostaining intensity was 8.605 in the NASH-HCC cases, which was significantly higher than that in the cases of NASH without HCC (4.845; P = 0.003). Multivariate analysis using hepatic 8-OHdG content as a factor in addition to age and fasting blood sugar revealed a significant difference in clinicopathological factors between NASH-HCC and NASH without HCC cases. Old age (P = 0.015) and high relative immunostaining intensity for intrahepatic 8-OHdG (P = 0.037) were identified as independent factors. CONCLUSIONS: 8-OHdG content in liver tissue may serve a marker of oxidative stress and could be a particularly useful predictor of hepatocarcinogenesis.
    Journal of Gastroenterology 01/2013; · 3.79 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established diagnostic method for patients with suspected pancreatic ductal carcinoma (PDC). Rapid on-site evaluation (ROSE) has been reported to improve the accuracy. However, an on-site cytopathologist is not routinely available in many institutions. One of the solutions may be ROSE by endosonographer. The aim was to examine whether diagnostic accuracy increases through ROSE by endosonographer using our cytological criteria. METHODS: Patients who underwent EUS-FNA of solid pancreatic masses from January 2006 until August 2009 (n=53, Period 1) and September 2009 to April 2011 (n=85, Period 2) were retrospectively identified. Before initiating ROSE at the start of period 2, two endosonographers underwent training for cytological interpretation, which was focused on four cytological features of PDC: anisonucleosis, nuclear membrane irregularity, overlapping, and enlargement. During EUS-FNA in period 2, endosonographers classified the Diff-Quik smears under three atypical grades and evaluated the adequacy. All diagnoses were made by one pathologist without knowledge of clinical information. RESULTS: The rate of "inconclusive" diagnoses, interpreted as "suspicious", "atypical" and "inadequate for diagnosis" was reduced from 26.4% in period 1 to 8.2% in period 2 (P=0.004). Moreover, diagnostic accuracy was increased from 69.2% in period 1 to 91.8% in period 2 (P<0.001). CONCLUSIONS: This cytological grading system used in ROSE by endosonographers is invaluable for diagnosis of pancreatic solid masses.
    Journal of Gastroenterology and Hepatology 01/2013; · 3.33 Impact Factor
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    ABSTRACT: BACKGROUND: This retrospective study was carried out to compare computed tomographic (CT) gastrography and conventional optical gastroscopy (GS) in order to evaluate the effectiveness of chemotherapy in primary gastric lesions. METHODS: Patients with unresectable advanced and unresected early gastric cancer who had primary lesions and had received chemotherapy were enrolled. For primary lesions, CT gastrography and endoscopic assessment were done after chemotherapy, based on the Japanese Classification of Gastric Carcinoma (JCGC) criteria, 13th edition, and the Response Evaluation Criteria in Solid Tumors (RECIST). For metastatic solid lesions including lymph nodes, CT assessment was done based on the RECIST criteria. RESULTS: Data from 23 patients were analyzed. With median follow-up of 9.4 months (range 2-23 months), 58 examinations were assessed by GS and CT gastrography. Setting optical endoscopic results as the gold standard, the accuracy of CT gastrography for primary gastric lesions was 77.6 % (45 of 58) (weighted κ = 0.72; P < 0.01) according to the JCGC 13th edition criteria and 90.0 % (52 of 58) (weighted κ = 0.75; P < 0.01) according to the RECIST. When all results were divided into two groups [the non-progressive disease (non-PD) group and PD group], accuracy was 93.1 % (52 of 58) (κ = 0.81; P < 0.01), sensitivity was 100 %, and specificity was 75.0 % (12 of 16). In addition, the predictability of PD was 100 % (12 of 12). The four cases of failure in specification were the following: a case of gastric remnant cancer, a case with insufficient distension of the stomach, a healed case with stenosis and scarring, and a case in which the wrong position had been selected for the examination. The average period until PD was 9.9 months (range 5-18 months), and the concordance period between GS and CT gastrography was 7.2 months in both non-PD and PD cases. CONCLUSIONS: There was good concordance between the evaluations of GS and CT gastrography. CT gastrography exhibited favorable results in accuracy as well as 100 % PD predictability, which implied the possibility of using CT gastrography as a substitute for endoscopic assessments at post-chemotherapy assessments.
    Gastric Cancer 11/2012; · 3.99 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Fibrosis associated with chronic pancreatitis is an irreversible lesion that can disrupt pancreatic exocrine and endocrine function. Currently, there are no approved treatments for this disease. We previously showed that siRNA against collagen-specific chaperone protein gp46, encapsulated in vitamin A-coupled liposomes (VA-lip-siRNAgp46), resolved fibrosis in a model of liver cirrhosis. This treatment was investigated for pancreatic fibrosis induced by dibutyltin dichloride (DBTC) and cerulein in rats. METHODS: Specific uptake of VA-lip-siRNAgp46, conjugated with 6'-carboxyfluorescein (FAM) by activated pancreatic stellate cells (aPSCs), was analysed by fluorescence activated cell sorting (FACS). Intracellular distribution of VA-lip-siRNAgp46-FAM was examined by fluorescent microscopy. Suppression of gp46 expression by VA-lip-siRNAgp46 was assessed by immunoblotting. Collagen synthesis in aPSCs was assayed by dye-binding. Specific delivery of VA-lip-siRNAgp46 to aPSCs in DBTC rats was verified following intravenous VA-lip-siRNA-FAM and (3)H-VA-lip-siRNAgp46. The effect of VA-lip-siRNA on pancreatic histology in DBTC- and cerulein-treated rats was determined by Azan-Mallory staining and hydroxyproline content. RESULTS: FACS analysis revealed specific uptake of VA-lip-siRNAgp46-FAM through the retinol binding protein receptor by aPSCs in vitro. Immunoblotting and collagen assay verified knockdown of gp46 and suppression of collagen secretion, respectively, by aPSCs after transduction of VA-lip-siRNAgp46. Specific delivery of VA-lip-siRNAgp46 to aPSCs in fibrotic areas in DBTC rats was confirmed by fluorescence and radioactivity 24 h after the final injection. 10 systemic VA-lip-siRNAgp46 treatments resolved pancreatic fibrosis, and suppressed tissue hydroxyproline levels in DBTC- and cerulein-treated rats. CONCLUSION: These data suggest the therapeutic potential of the present approach for reversing pancreatic fibrosis.
    Gut 11/2012; · 10.73 Impact Factor
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    ABSTRACT: Chronic disseminated intravascular coagulation (DIC) is a rare but life-threatening complication of dissecting aortic aneurysm. Although anticoagulant therapy may often proves effective for controlling DIC itself, patients would have to be hospitalized for a long period due to continuous infusion therapy. Subcutaneous injection of a highly concentrated preparation of heparin calcium may offer one alternative treatment for DIC; however, daily subcutaneous use of heparin for the treatment of DIC has impaired quality of life (QOL). The other alternative therapy is intravenous administration of recombinant human soluble thrombomodulin (rTM), which includes the active extracellular domain of thrombomodulin. Reportedly, rTM effectively resolves DIC by only 6 consecutive days of administration; however, how frequently rTM should be administered after the resolution of chronic DIC to have good control of it has been unclear. We report herein a case of chronic DIC complicated with dissecting aortic aneurysm, whose resolution of chronic DIC achieved by 6 consecutive days of rTM has been maintained by once a week administration of rTM on an outpatient basis.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 06/2012; 23(6):548-50. · 1.25 Impact Factor
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    ABSTRACT: Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias, and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. This study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000 ng/mL or they required more than 20 RBC transfusions (or 100 mL/kg of RBC). We prospectively analyzed 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.
    Free Radical Biology and Medicine 06/2012; 53(4):643-8. · 5.27 Impact Factor

Publication Stats

1k Citations
365.65 Total Impact Points

Institutions

  • 2000–2014
    • Sapporo Medical University
      • School of Medicine
      Sapporo, Hokkaidō, Japan
    • Sapporo Kosei General Hospital
      Sapporo, Hokkaidō, Japan
  • 2013
    • Steel Memorial Muroran Hospital
      Hokodate, Hokkaidō, Japan
  • 2012
    • Hokkaido Gastroenterology Hospital
      Edo, Tōkyō, Japan
  • 2000–2001
    • Nikko Memorial Hospital
      Hidachi, Ibaraki, Japan