Kobayashi T.,Gunma University |
Saji T.,Toho University |
Takeuchi K.,Saitama University |
Nakamura T.,Gunma University |
And 17 more authors.
The Lancet | Year: 2012
Background Evidence indicates that corticosteroid therapy might be beneficial for the primary treatment of severe Kawasaki disease. We assessed whether addition of prednisolone to intravenous immunoglobulin with aspirin would reduce the incidence of coronary artery abnormalities in patients with severe Kawasaki disease. Methods We did a multicentre, prospective, randomised, open-label, blinded-endpoints trial at 74 hospitals in Japan between Sept 29, 2008, and Dec 2, 2010. Patients with severe Kawasaki disease were randomly assigned by a minimisation method to receive either intravenous immunoglobulin (2 g/kg for 24 h and aspirin 30 mg/kg per day) or intravenous immunoglobulin plus prednisolone (the same intravenous immunoglobulin regimen as the intravenous immunoglobulin group plus prednisolone 2 mg/kg per day given over 15 days after concentrations of C-reactive protein normalised). Patients and treating physicians were unmasked to group allocation. The primary endpoint was incidence of coronary artery abnormalities during the study period. Analysis was by intention to treat. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000000940. Findings We randomly assigned 125 patients to the intravenous immunoglobulin plus prednisolone group and 123 to the intravenous immunoglobulin group. Incidence of coronary artery abnormalities was significantly lower in the intravenous immunoglobulin plus prednisolone group than in the intravenous immunoglobulin group during the study period (four patients [3%] vs 28 patients [23%]; risk difference 0 20, 95% CI 0 12-0 28, p<0 0001). Serious adverse events were similar between both groups: two patients had high total cholesterol and one neutropenia in the intravenous immunoglobulin plus prednisolone group, and one had high total cholesterol and another non-occlusive thrombus in the intravenous immunoglobulin group. Interpretation Addition of prednisolone to the standard regimen of intravenous immunoglobulin improves coronary artery outcomes in patients with severe Kawasaki disease in Japan. Further study of intensified primary treatment for this disease in a mixed ethnic population is warranted. Funding Japanese Ministry of Health, Labour and Welfare.
Shi X.,Fukuoka University |
Shi X.,Chinese PLA General Hospital |
Yasumoto S.,Fukuoka University |
Kurahashi H.,Fukuoka University |
And 5 more authors.
Brain and Development | Year: 2012
Mutations in SCN2A, the gene encoding α2 subunit of the neuronal sodium channel, are associated with a variety of epilepsies: benign familial neonatal-infantile seizures (BFNIS); genetic epilepsy with febrile seizures plus (GEFS+); Dravet syndrome (DS); and some intractable childhood epilepsies. More than 10 new mutations have been identified in BFNIS, all of them are missense. To date, only one nonsense mutation has been found in a patient with intractable childhood epilepsy and severe mental decline. Recently, microduplication of chromosome 2q24.3 (containing eight genes including SCN2A, SCN3A, and the 3' end of SCN1A) was reported in a family with dominantly inherited neonatal seizures and intellectual disability. Functional studies of SCN2A mutations show that they can cause divergent biophysical defects in Na V1.2 and impair cell surface expressions. There is no consistent relationship between genotype and phenotype. © 2011 The Japanese Society of Child Neurology.
Ina K.,Nagoya Memorial Hospital |
Kataoka T.,Nagoya Memorial Hospital
Anti-Cancer Agents in Medicinal Chemistry | Year: 2013
Natural compounds containing fungal β-glucans have been used to improve general health for thousands of years in China and Japan. Lentinan, the backbone of β-(1, 3)-glucan with β-(1, 6) branches, is one of the active ingredients purified from Shiitake mushrooms and has been approved as a biological response modifier for the treatment of gastric cancer in Japan. Despite recent advances in chemotherapeutic agents, unresectable or recurrent gastric cancer remains an incurable disease, with survival rates being far from satisfactory. Recent clinical studies have shown that chemo-immunotherapy using lentinan prolongs the survival of patients with advanced gastric cancer, as compared to chemotherapy alone. In addition, trastuzumab, an antibody against HER2/neu growth factor receptor, has been used for the treatment of gastric cancer in combination with cytotoxic chemotherapeutic agents. Lentinan may exert a synergistic action with anti-cancer monoclonal antibodies to activate complement systems through the mechanism of antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity. Because a better understanding of its biological activities should enable us to use lentinan more efficiently in the treatment of gastric cancer, immunological effects provided by β-glucans, a possible mode of action of lentinan, and its clinical application including future potential uses are discussed in the present review. © 2013 Bentham Science Publishers.
Nishida Y.,Nagoya University |
Kamada T.,Japan National Institute of Radiological Sciences |
Imai R.,Japan National Institute of Radiological Sciences |
Tsukushi S.,Nagoya University |
And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011
Purpose: To evaluate the efficacy, post-treatment function, toxicity, and complications of carbon ion radiotherapy (RT) for sacral chordoma compared with surgery. Methods and Materials: The records of 17 primary sacral chordoma patients treated since 1990 with surgery (n = 10) or carbon ion RT (n = 7) were retrospectively analyzed for disease-specific survival, local recurrence-free survival, complications, and functional outcome. The applied carbon ion dose ranged from 54.0 Gray equivalent (GyE) to 73.6 GyE (median 70.4). Results: The mean age at treatment was 55 years for the surgery group and 65 years for the carbon ion RT group. The median duration of follow-up was 76 months for the surgery group and 49 months for the carbon ion RT group. The local recurrence-free survival rate at 5 years was 62.5% for the surgery and 100% for the carbon ion RT group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively. Urinary-anorectal function worsened in 6 patients (60%) in the surgery group, but it was unchanged in all the patients who had undergone carbon ion RT. Postoperative wound complications requiring reoperation occurred in 3 patients (30%) after surgery and in 1 patient (14%) after carbon ion RT. The functional outcome evaluated using the Musculoskeletal Tumor Society scoring system revealed 55% in the surgery group and 75% in the carbon ion RT group. Of the six factors in this scoring system, the carbon ion RT group had significantly greater scores in emotional acceptance than did the surgery group. Conclusion: Carbon ion RT results in a high local control rate and preservation of urinary-anorectal function compared with surgery. © 2011 Elsevier Inc Printed in the USA. All rights reserved.
PubMed | Nara City Hospital, Nara Medical University, Keio University, Japan National Cardiovascular Center Research Institute and 5 more.
Type: | Journal: Japanese journal of clinical oncology | Year: 2017
Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients.This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/mBetween January 2011 and February 2014, a total of 76 chemotherapy-nave CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%).The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed.
Shen D.-K.,University of Bristol |
Saurya S.,University of Oxford |
Wagner C.,University of Bristol |
Wagner C.,University tsklinikum Erlangen |
And 4 more authors.
Infection and Immunity | Year: 2010
Type III secretion systems (T3SSs) are key determinants of virulence in many Gram-negative bacterial pathogens. Upon cell contact, they inject effector proteins directly into eukaryotic cells through a needle protruding from the bacterial surface. Host cell sensing occurs through a distal needle "tip complex," but how this occurs is not understood. The tip complex of quiescent needles is composed of IpaD, which is topped by IpaB. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which other virulence effector proteins may be translocated. IpaB is required for regulation of secretion and may be the host cell sensor. It binds needles via its extreme C-terminal coiled coil, thereby likely positioning a large domain containing its hydrophobic regions at the distal tips of needles. In this study, we used short deletion mutants within this domain to search for regions of IpaB involved in secretion regulation. This identified two regions, amino acids 227 to 236 and 297 to 306, the presence of which are required for maintenance of IpaB at the needle tip, secretion regulation, and normal pore formation but not invasion. We therefore propose that removal of either of these regions leads to an inability to block secretion prior to reception of the activation signal and/or a defect in host cell sensing. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: A randomised phase 2/3 non-inferiority study (FIRIS study)
Muro K.,Aichi Cancer Center Hospital |
Boku N.,Shizuoka Cancer Center |
Shimada Y.,National Cancer Center Hospital |
Tsuji A.,Kochi Health science Center |
And 16 more authors.
The Lancet Oncology | Year: 2010
Background: Fluorouracil and folinic acid with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) are widely used as first-line or second-line chemotherapy for metastatic colorectal cancer. However, infusional fluorouracil-based regimens, requiring continuous infusion and implantation of an intravenous port system, are inconvenient. We therefore planned an open-label randomised controlled trial to verify the non-inferiority of irinotecan plus oral S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate; IRIS) to FOLFIRI as second-line chemotherapy for metastatic colorectal cancer. Methods: Between Jan 30, 2006, and Jan 29, 2008, 426 patients with metastatic colorectal cancer needing second-line chemotherapy from 40 institutions in Japan were randomly assigned by a computer-based minimisation method to receive either FOLFIRI (n=213) or IRIS (n=213). In the FOLFIRI group, patients received folinic acid (200 mg/m2) and irinotecan (150 mg/m2) and then a bolus injection of fluorouracil (400 mg/m2) on day 1 and a continuous infusion of fluorouracil (2400 mg/m2) over 46 h, repeated every 2 weeks. In the IRIS group, patients received irinotecan (125 mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was progression-free survival, with a non-inferiority margin of 1·333. Statistical analysis was on the basis of initially randomised participants. This study is registered with ClinicalTrials.gov, number NCT00284258. Findings: All randomised patients were included in the primary analysis. After a median follow-up of 12·9 months (IQR 11·5-18·2), median progression-free survival was 5·1 months in the FOLFIRI group and 5·8 months in the IRIS group (hazard ratio 1·077, 95% CI 0·879-1·319, non-inferiority test p=0·039). The most common grade three or four adverse drug reactions were neutropenia (110 [52·1%] of 211 patients in the FOLFIRI group and 76 [36·2%] of 210 patients in the IRIS group; p=0·0012), leucopenia (33 [15·6%] in the FOLFIRI group and 38 [18·1%] in the IRIS group; p=0·5178), and diarrhoea (ten [4·7%] in the FOLFIRI group and 43 [20·5%] in the IRIS group; p<0·0001). One treatment-related death from hypotension due to shock was reported in the FOLFIRI group within 28 days after the end of treatment; no treatment-related deaths were reported in the IRIS group. Interpretation: Progression-free survival with IRIS is not inferior to that with FOLFIRI in patients receiving second-line chemotherapy for metastatic colorectal cancer. Treatment with IRIS could be an additional therapeutic option for second-line chemotherapy in metastatic colorectal cancer. Funding: Taiho Pharmaceutical Co Ltd and Daiichi Sankyo Co Ltd. © 2010 Elsevier Ltd.
Motoyama S.,Aichi University |
Motoyama S.,Mount Sinai School of Medicine |
Ito H.,Aichi University |
Sarai M.,Aichi University |
And 16 more authors.
Journal of the American College of Cardiology | Year: 2015
Background Coronary computed tomography angiography (CTA)-verified positive remodeling and low attenuation plaques are considered morphological characteristics of high-risk plaque (HRP) and predict short-term risk of acute coronary syndrome (ACS). Objectives This study evaluated whether plaque characteristics by CTA predict mid-term likelihood of ACS. Methods The presence of HRP and significant stenosis (SS) of ≥70% were evaluated in 3,158 patients undergoing CTA. Serial CTA was performed in 449 patients, and plaque progression (PP) was evaluated. Outcomes (fatal and nonfatal ACS) were recorded during follow-up (mean 3.9 ± 2.4 years). Results ACS occurred in 88 (2.8%) patients: 48 (16.3%) of 294 HRP(+) and 40 (1.4%) of 2,864 HRP(-) patients. ACS was also significantly more frequent in SS(+) (36 of 659; 5.5%) than SS(-) patients (52 of 2,499; 2.1%). HRP(+)/SS(+) (19%) and HRP(+)/SS(-) (15%) had higher rates of ACS compared with no-plaque patients (0.6%). Although ACS incidence was relatively low in HRP(-) patients, the cumulative number of patients with ACS developing from HRP(-) lesions (n = 43) was similar to ACS patients with HRP(+) lesions (n = 45). In patients with serial CTA, PP also was an independent predictor of ACS, with HRP (27%; p < 0.0001) and without HRP (10%) compared with HRP(-)/PP(-) patients (0.3%). Conclusions CTA-verified HRP was an independent predictor of ACS. However, the cumulative number of ACS patients with HRP(-) was similar to patients with HRP(+). Additionally, plaque progression detected by serial CTA was an independent predictor of ACS. © 2015 American College of Cardiology Foundation.
Narita T.,Nagoya Memorial Hospital
[Rinshō ketsueki] The Japanese journal of clinical hematology | Year: 2013
A 45-year-old man with chronic myelogenous leukemia (CML) in the chronic phase was treated with imatinib mesylate (IM). Although partial cytogenetic response (CyR) was obtained in 3 months, the patient exhibited back pain after treatment with IM for 5 months. He was diagnosed with myeloblastic crisis of CML with 30% blasts in the bone marrow. An extramedullary tumor with a diameter of 5-cm was found adjacent to the pancreatic head. Mutation analysis of the bcr/abl chimeric gene was negative. After the treatment with dasatinib (140 mg/day) for 40 days, complete CyR was obtained by bone marrow examination and the extramedullary tumor shrunk resulting in partial response on computed tomography. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was performed from his HLA-DR one locus-mismatched sister. He has been in molecular remission for 24 months after allo-PBSCT and maintenance therapy with dasatinib has been administered. Dasatinib was tolerable without severe adverse events before and after allo-PBSCT in this case.
Tsukushi S.,Nagoya University |
Nishida Y.,Nagoya University |
Yamada Y.,Nagoya Memorial Hospital |
Yoshida M.,Aichi Cancer Center Research Institute |
Ishiguro N.,Nagoya University
Archives of Orthopaedic and Trauma Surgery | Year: 2010
Introduction We determined the diagnostic accuracy rate of 207 cases that underwent CT-guided needle biopsy for musculoskeletal lesions during the past 10 years, and describe the efficacy and indications of this method. Materials and methods We retrospectively analyzed a consecutive series of 207 cases that presented to our oncology group and underwent CT-guided needle biopsy during the 10-year period between April 1998 and March 2008. Diagnostic accuracy was assessed statistically by anatomical location and final diagnosis. The biopsy site was the spine/sacrum in 70 cases, pelvis in 53, extremities in 51, rib/scapula in 20, and retroperitoneum in 13. Bone lesions were detected in 176 cases and soft tissue lesions in 31. The final diagnosis was metastatic tumor in 63 cases, primary bone tumor in 63, primary soft tissue tumor in 23, infection in 18, and hematopoietic malignancy in 16 and non-tumorous lesions in 24. Results The diagnostic accuracy rate for all cases was 90%. No serious complications were seen. No statistically significant difference was found by anatomical site. According to the final diagnosis, benign tumors/malignant tumors (p\0.005), primary bone tumor (p\0.01), and infectious conditions (p\0.001) showed significantly low diagnostic accuracy rates. Discussion CT-guided needle biopsy is a safe method with high diagnostic accuracy for musculoskeletal lesions. However, in patients with a primary bone tumor, it should be indicated for the initial diagnosis. If a comprehensive assessment based on the imaging conflicts with the pathological findings, an open biopsy should be considered. © Springer-Verlag 2009.