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Ishiguro M.,Tokyo Medical and Dental University | Kotake K.,Tochigi Cancer Center | Nishimura G.,Red Cross | Tomita N.,Hyogo College of Medicine | And 13 more authors.
BMC Cancer | Year: 2013

Background: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. Methods/design: The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients' clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. Discussion: A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the "personalized therapy" in adjuvant chemotherapy for colon cancer. Trial registration: ClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013. © 2013 Ishiguro et al.; licensee BioMed Central Ltd. Source


Harada Y.,Kochi Medical School Kohasu | Ishida W.,Kochi Medical School Kohasu | Fukuda K.,Kochi Medical School Kohasu | Sumi T.,Kochi Medical School Kohasu | And 3 more authors.
Medical Molecular Morphology | Year: 2013

Bone marrow (BM)-derived stem cells have the potential to differentiate into multiple lineages of tissue resident cells. BM-derived cells have been detected in the mouse cornea, but most of these cells were found to be CD45 + or CD11b+ immunocompetent cells. Although some BM-derived cells in the cornea were negative for these cell surface markers, it has remained unclear whether cells of BM origin can differentiate into corneal resident cells. To address this issue, we subjected wild-type mice that had been exposed to a lethal dose of radiation to intravenous injection with BM cells from green fluorescent protein (GFP) transgenic mice. Two months after cell transplantation, fluorescence microscopy revealed the presence of numerous GFP+ cells throughout the cornea, with intense GFP fluorescence being apparent around the limbal region. Immunohistofluorescence analysis of corneal cross-sections revealed that most of the BM-derived GFP+ cells expressed CD45 or CD11b, although a few GFP+ cells were negative for these markers. Immunostaining of individual cells isolated from the corneal stroma, however, showed that a small proportion (~1 %) of GFP+ BM-derived cells expressed the keratocyte-specific proteoglycan keratocan. Our results suggest that BM-derived cells introduced intravenously are able to differentiate into resident cells of the corneal stroma. © 2013 The Japanese Society for Clinical Molecular Morphology. Source


Taniguchi Y.,Metabolism and Nephrology | Takata T.,Kochi Medical School Kohasu | Sano S.,Kochi Medical School Kohasu | Ohnishi T.,Kochi Medical School Kohasu | And 3 more authors.
Annals of Nuclear Medicine | Year: 2013

Enthesitis, defined as the inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis, and joint capsules, is a hallmark of spondyloarthritis (SpA). New imaging techniques including magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography with computed tomography using 18F-fluorodeoxyglucose capable of detecting morphological and metabolic abnormalities and monitoring disease activity have improved the assessment and management of enthesitis of SpA. © 2012 The Japanese Society of Nuclear Medicine. Source


Yatabe T.,Kochi Medical School Kohasu | Tamura T.,Kochi Medical School Kohasu | Yamashita K.,Kochi Medical School Kohasu | Yokoyama M.,Kochi Medical School Kohasu
Journal of Clinical Anesthesia | Year: 2016

Study objective Some outpatient procedures are performed under sedation with dexmedetomidine, although the effect of dexmedetomidine on cognitive function remains unclear. This study investigated the effect of dexmedetomidine on cognitive function in healthy volunteers. Design Observation study in volunteers. Setting University-affiliated teaching hospital. Patients Six healthy volunteers. Interventions After infusion of a 6-μg/kg per hour loading dose of dexmedetomidine for 10 minutes, a maintenance infusion of 0.4 μg/kg per hour was administered for 4 hours. Measurements Cognitive function was evaluated before infusion (baseline) and at 2, 4, 6, and 8 hours after infusion. Cognitive function, response speed, accuracy, and consistency were measured by CogHealth. Depth of sedation was evaluated at 1-hour intervals by evaluating the Bispectral Index. Data are presented as the change from baseline. Main results The Bispectral Index value was significantly lower from 10 minutes to 6 hours after infusion versus the pre-infusion value. Response speed was also significantly lower at 2 hours and 4 hours after infusion (92 ± 8%, P<.0001; 93 ± 6%, P<.0001), as was consistency (96 ± 7%, P=.0009; 96 ± 5%, P=.0003). Response accuracy was unaltered by the infusion. Conclusions Dexmedetomidine slightly reduced response speed and consistency, but did not affect response accuracy. Cognitive function was restored to pre-administration values 2 hours after the infusion of dexmedetomidine was discontinued. © 2016 Elsevier Inc. All rights reserved. Source


Yoshioka R.,Kochi Medical School Kohasu | Ono M.,Kochi Medical School Kohasu | Oe K.,Kochi Medical School Kohasu | Ochi T.,Kochi Medical School Kohasu | And 5 more authors.
International Medical Journal | Year: 2014

Objective: It has been considered that sex hormones, especially estrogen, have important roles in regulation of serum uric acid (UA). However, the regulation of serum UA in menopause or by inhibition of estrogen has not been well elucidated. We investigated tamoxifen, an estrogen receptor inhibitor, in terms of its functional roles in regulation of serum UA and its contribution to renal function in pre-menopause and post-menopause patients with breast cancer. Methods: We examined 234 patients with breast cancer who were treated with tamoxifen for at least 5 years. Serum UA and creatinine (Crn) in pre-menopause patients and post-menopause patients were investigated and compared before and 5 years after treatment with tamoxifen. Results: Basal serum UA were significantly higher in post-menopause than in pre-menopause patients (4.65 ± 1.25 mg/dL vs 4.29 ± 0.98 mg/dL, p < 0.05). Serum UA were increased only in pre-menopause patients by treatment with tamoxifen (from 4.29 ± 0.98 to 4.65 ± 1.05 mg/dL, p < 0.01); however, no change in serum UA was found in post-menopause patients. Basal Crn were well correlated to basal UA in all patients (r = 0.3396, p < 0.0001). However, inhibition of estrogen did not influence renal dysfunction in either group of patients. Inhibition of estrogen by tamoxifen leads to elevation of serum UA only in pre-menopause patients. Conclusions: Estrogen has more effective roles in lowering serum UA than in affecting renal functions, and treatment with tamoxifen might not influence renal function. © 2014 Japan Health Sciences University & Japan International Cultural Exchange Foundation. Source

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