Ichikawa H.,National Cancer Center Research Institute |
Ichikawa H.,Niigata University |
Kanda T.,Niigata University |
Kanda T.,Tsubame Rosai Hospital |
And 5 more authors.
Journal of Proteome Research | Year: 2013
To reveal the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed a proteomic study of tumor and matched nontumor tissues obtained from surgically resected specimens of 22 patients with or without LNM. Using laser microdissection, we recovered specific populations of tumor and nontumor cells. We used two-dimensional difference gel electrophoresis with a large format electrophoresis apparatus to obtain protein expression profiles consisting of 3228 protein spots, and we classified them according to their expression pattern. We found that macrophage-capping protein (CapG) was up-regulated in the tumor tissues of patients with LNM, whereas it showed an equivalent expression level between nontumor and tumor tissues of patients without LNM. It was reported that CapG associated with invasion and metastasis in various malignancies. However, CapG was not investigated in gastric cancer until our study. Western blotting of the laser microdissected tissue samples confirmed up-regulation of CapG in the tumor tissues of patients with LNM. Functional assays demonstrated that CapG promoted tumor cell invasion, but not cell proliferation. The association between CapG expression and LNM is a novel finding in gastric cancer. Further investigation for a prognostic utility of CapG may lead to a risk stratification therapy for gastric cancer. © 2013 American Chemical Society.
Fushida S.,Kanazawa University |
Nashimoto A.,Niigata Cancer Center Hospital |
Fukushima N.,Yamagata Prefectural Central Hospital |
Kawachi Y.,Nagaoka Chuo General Hospital |
And 3 more authors.
Japanese Journal of Clinical Oncology | Year: 2012
The standard treatment for T4 locally advanced gastric cancer is gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy with S-1 for 12 months; however, prognostic outcome in Stage IIIb has been insufficient. It is expected that survival is improved by preoperative treatment with a triplet regimen of docetaxel, cisplatin and S-1 (divided DCS therapy). A multicenter Phase II study has been conducted to evaluate the safety and efficacy of two courses of preoperative chemotherapy followed by gastrectomy. Fifty-five patients are required for this study. The primary endpoint of the study is pathological response rate of primary lesions. Secondary endpoints are overall survival, disease-free survival, R0 resection rate and adverse events. © The Author 2011. Published by Oxford University Press. All rights reserved.
Yamaguchi R.,Hamamatsu University School of Medicine |
Kato F.,Hamamatsu University School of Medicine |
Hasegawa T.,Keio University |
Katsumata N.,National Health Research Institute |
And 4 more authors.
Endocrine Journal | Year: 2013
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by primary hypocortisolism and normal mineralocorticoid production. Recently, NNT encoding the nicotinamide nucleotide transhydrogenase has been identified as a causative gene for FGD. Thus, we examined NNT in six Japanese FGD patients with no recognizable mutation in the previously known four responsible genes for FGD (MC2R, MRAP, STAR, and MCM4), and identified a novel homozygous substitution (c.644T>C; p.Phe215Ser) in a single 17.5-year-old boy. His parents were heterozygous for this mutation. This substitution was absent from 120 Japanese control subjects and was not registered in public databases including JSNP Database. The phenylalanine residue at the 215th codon was evolutionally conserved, and the p.Phe215Ser was assessed to be a pathologic mutation by in silico protein function analyses. The results, in conjunction with the previous data, imply that NNT mutations account for 5-10% of FGD patients, and that underlying factor(s) still remains to be clarified in a substantial fraction of FGD patients. © The Japan Endocrine Society.
Yoshihara K.,Niigata University |
Tajima A.,Tokai University |
Adachi S.,Niigata University |
Quan J.,Niigata University |
And 5 more authors.
Genes Chromosomes and Cancer | Year: 2011
We investigated characteristics of germline copy number variations (CNV) in BRCA1-associated ovarian cancer patients by comparing them to CNVs present in sporadic ovarian cancer patients. Germline CNVs in 51 BRCA1-associated, 33 sporadic ovarian cancer patients, and 47 healthy women were analyzed by both signal intensity and genotyping data using the Affymetrix Genome-Wide Human SNP Array 6.0. The total number of CNVs per genome was greater in the sporadic group (median 26, range 12-34) than in the BRCA1 group (median 21, range 11-35; post hoc P < 0.05) or normal group (median 20, range 7-32; post hoc P < 0.05). While the number of amplifications per genome was higher in the sporadic group (median 13, range 7-26) than in the BRCA1 group (median 8, range 3-23; post hoc P < 0.001), the number of deletions per genome was higher in the BRCA1 group (median 12, range 6-24) than in the sporadic group (median 9, range 3-17; post hoc P < 0.01). In addition, 31 previously unknown CNV regions were present specifically in the BRCA1 group. When we performed pathway analysis on the 241 overlapping genes mapped to these novel CNV regions, the 'purine metabolism' and '14-3-3-mediated signaling' pathways were over-represented (Fisher's exact test, P < 0.01). Our study shows that there are qualitative differences in genomic CNV profiles between BRCA1-associated and sporadic ovarian cancer patients. Further studies are necessary to clarify the significance of the genomic CNV profile unique to BRCA1-associated ovarian cancer patients. © 2010 Wiley-Liss, Inc.
Maruyama H.,Niigata University |
Takata T.,Nagaoka Chuo General Hospital |
Tsubata Y.,Niigata Prefectural Central Hospital |
Tazawa R.,Niigata University |
And 5 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2013
Background and objectives Previous reports of Fabrydisease screening indialysispatients indicate thata-galactosidase A activity alone cannot specifically and reliably identify appropriate candidates for genetic testing; a marker for secondary screening is required. Elevated plasma globotriaosylsphingosine is reported to be a hallmark of classic Fabry disease. The purpose of this studywas to examine the usefulness of globotriaosylsphingosine as a secondary screening target for Fabry disease. Design, setting, participants, & measurements This study screened 1453 patients, comprising 50% of the male dialysis patients in Niigata Prefecture between July 1, 2010 and July 31, 2011. Screening for Fabry disease was performed by measuring the plasma α-galactosidase A enzyme activity and the globotriaosylsphingosine concentration, by high-performance liquid chromatography. Genetic testing and genetic counseling were provided. Results A low level of plasma α-galactosidase A activity (<4.0 nmol/h per milliliter) was observed in 47 patients (3.2%). Of these, 3 (0.2%) had detectable globotriaosylsphingosine levels. These patients all had α-galactosidase A gene mutations: one was p.Y173X and two were the nonpathogenic p.E66Q. The patient with p.Y173X started enzyme replacement therapy. Subsequent screening of his family identified the samemutation in his elder sister and her children. Genetic testing for 33 of the other 44 patients detected 7 patients with p.E66Q. Thus, the plasma lyso-Gb3 screen identified Fabry disease with high sensitivity (100%) and specificity (94.3%). Conclusions Plasma globotriaosylsphingosine is a promising secondary screening target that was effective for selecting candidates for genetic counseling and testing and for uncovering unrecognized Fabry disease cases.
Tanaka H.,Nagaoka Chuo General Hospital
Therapeutic Research | Year: 2011
Objective : To compare the efficacy of betahistine mesilate for the treatment of attacks of vertigo, especially Meniere's disease, between 18 mg/day, a dose which is common, and 36 mg/day, a dose shown to be useful in a double-blind placebo-controlled study in Japan. Method: In this retrospective study, the clinical response was evaluated in 30 and 34 patients who received betahistine mesilate at a dose of 18 mg/day and 36 mg/day, respectively, for three months. Patients had been prescribed with Travelmin Combination Tablets to be taken as needed during attacks of vertigo. Outcome measures included the number of Travelmin tablets taken to attacks of vertigo, the number of hospitalizations for attacks of vertigo, and the number of outpatient intravenous infusions required at visit with attacks of vertigo. Result : The age and gender of the study population were similar between the dose groups. The total number of Travelmin tablets taken for attacks of vertigo during the three-month treatment with betahistine mesilate was significantly lower in the 36 mg/day group (6.03±7.23 tablets in average) compared to the 18 mg/day group (13.7±14.44 tablets in average) (p<0.05). The number of hospitalizations and outpatient intravenous infusions were also lower in the 36 mg/day group, but not significantly. Conclusion : Betahistine mesilate at 36 mg/day (12 mg t. i. d), a dose used in the double-blind comparative study, was considered to be more appropriate in improving symptoms of vertigo and equilibrium function.
Okamura T.,Nagaoka Chuo General Hospital
Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2013
We report a case of hyperammonemic encephalopathy related to 5-FU in an aged patient with recurrent colon cancer treated with FOLFIRI therapy. An 80-year-old man underwent right hemicolectomy for cecal cancer. After 10 months, surgical resection was performed for its local recurrence. He was then treated with FOLFIRI therapy, and during the fifth course, he presented with a sudden onset of congestive disturbances. Through radiographic examination and laboratory data, only hyperammonemia was found; he was therefore diagnosed with hyperammonemic encephalopathy. By starting branchedamino acid solutions for its treatment, his consciousness and serum ammonia were promptly improved. Hyperammonemic encephalopathy related 5-FU is caused by increasing ammonia production and its metabolic inhibition, and is worsened by renal dysfunction, dehydration, constipation, infections, or body weight loss. On account of the potential decrease of metabolic function of liver and kidney, an aged person tends to have hyperammonnemia more than a youth. Clinicians should be aware of the adverse events associated with hyperammonemia when then administer a large amount of 5-FU to elderly patients.
Sorimachi T.,Niigata University |
Nishino K.,Niigata University |
Morita K.,Niigata University |
Takeuchi S.,Nagaoka Chuo General Hospital |
And 2 more authors.
American Journal of Neuroradiology | Year: 2011
BACKGROUND AND PURPOSE: If blood flow in the ICA is reduced by the use of a distal filter during CAS, flow stagnation proximal to the filter occurs and this increases the probability of floating debris. The floating debris that remains after filter retrieval may cause cerebral embolism. However, if blood flow is increased by aspiration of blood from the ICA through an aspiration catheter, debris could be removed while the filter is still in place. The purpose of this study was to investigate blood flow changes in the ICA induced by filter use and aspiration. MATERIAL AND METHODS: A filter-protection device (AngioGuard XP) was used during CAS in 13 consecutive patients with carotid stenosis. Blood flow velocity in the ICA was measured by carotid Doppler sonography during filter deployment, filter retrieval, and catheter aspiration. RESULTS: Blood flow velocity significantly decreased with filter placement and significantly increased with filter retrieval in patients with normal angiographic flow (P < .05). Aspiration of a 20-mL blood sample from the proximal ICA column significantly increased the blood flow velocity (P < .05). CONCLUSIONS: The blood flow changes in the ICA induced by the use of a distal filter may cause cerebral embolism in filter-protected CAS. A routine aspiration method can potentially reduce the amount of migrating debris during CAS, even in cases with angiographic normal flow.
Ishikawa K.,Niigata University |
Haneda J.,Nagaoka Chuo General Hospital |
Okamoto K.,Niigata University
Neuroradiology | Year: 2013
Introduction: With reported characteristic MR features, it is difficult to differentiate vestibular schwannomas (VSs) from cerebellopontine angle (CPA) meningiomas (CPAMs) in some cases. This study aimed to evaluate vestibular signal intensity changes in patients with VS and those with CPAM on three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA), and to test the effectiveness of the signal intensity change to differentiate these two common CPA tumors. Methods: We retrospectively reviewed 21 patients with unilateral VS, six patients with unilateral CPAM, and 25 control subjects. Setting regions of interest in the bilateral vestibules and cerebellar white matter on 3D-FIESTA, we compared the ratio of the signal intensity (SIR) of the vestibule to that of the cerebellar white matter (SIRv) among the VS, CPAM, and control subject groups. We also compared the ratio of SIRv on the affected side (a-SIRv) to that on the unaffected side (AURv) between the VS and CPAM. Results: The a-SIRv in the VS group was significantly lower than the overall SIRv in the control subjects (pre-contrast, P < 0.001; post-contrast, P < 0.001) and the a-SIRv in the CPAM group (pre-contrast, P = 0.001; post-contrast, P = 0.001). The AURv in the VS group was significantly lower than that in the CPAM groups (pre-contrast, P < 0.001; post-contrast, P < 0.001). Conclusion: Decreased vestibular signal intensity on the affected side on 3D-FIESTA was observed in patients with VS, but not in those with CPAM or in normal subjects. The signal intensity change has the potential to be used in differentiating VS from CPAM. © 2012 Springer-Verlag Berlin Heidelberg.
Nishimura A.,Nagaoka Chuo General Hospital |
Kawahara M.,Nagaoka Chuo General Hospital |
Suda K.,Nagaoka Chuo General Hospital |
Makino S.,Nagaoka Chuo General Hospital |
And 2 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2011
Background Conventional techniques for laparoscopicassisted colectomy (LAC) require abdominal minilaparotomy for extraction of the specimen. Abdominal wound complications often increase the invasiveness of LAC. To decrease the incidence of wound complications, natural orifice specimen extraction (NOSE) has been reported. However, only a few devices that allow smooth extraction and reduced intracorporeal contamination have been reported previously. We performed totally laparoscopic sigmoid colectomy using transanal specimen extraction (TASE) and the Alexis® wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA). We document this simple and safe technique and its short-term results. Methods We prospectively collected data on 18 patients who underwent totally laparoscopic sigmoid colectomy with TASE from April 2009 to July 2010. Lymph node dissection and transection of proximal and distal colon were performed in conventional manner. The transected rectal stump was opened transversely, and a long Babcock grasper was inserted transanally through the opened rectal stump. One of a pair of Alexis rings was held and pulled out of the anus. The other ring was placed in the opened rectal stump. The specimen was then extracted transanally through the Alexis. After the Alexis had been removed, the rectal opening was reclosed with a linear stapler. End-toend colorectal anastomosis was then performed using the double-stapling technique. Results Transanal extraction was achieved in 17 cases. We switched to conventional LAC in a case involving a bulky specimen. In 16 cases not including the combined cholecystectomy case, mean operation time was 241 min. One case was complicated by anastomotic leakage and wound infection, while another had enterocolitis. Median hospital stay was 6 days. All patients remained disease free. Mean Wexner score at 12 months after operation was 2.3. Conclusion Totally laparoscopic sigmoid colectomy using TASE and the Alexis appears to be feasible, safe, and oncologically acceptable for selected cases. © Springer Science+Business Media, LLC 2011.