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      • The Impact of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer

        ( Manabu Kawai ),( Seiko Hirono ),( Ken-ichi Okada ),( Motoki Miyazawa ),( Yuji Kitahata ),( Ryohei Kobayashi ),( Masaki Ueno ),( Shinya Hayami ),( Hiroki Yamaue ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Backgrounds: According to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines, pancreatic ductal adenocarcinoma (PDAC) can be classified as resectable, borderline resectable, or unresectable. Although borderline resectable PDAC (BRPC) may technically be resectable, it has particularly high risks of margin-positive resection and postoperative recurrence. Therefore, preoperative treatment is recommended for BRPC patients in both the NCCN Guidelines and an expert consensus statement. However, the establishment of the most appropriate neoadjuvant therapy is needed by further studies. The aim of these studies is to evaluate the impact of neoadjuvant chemotherapy for BRPC and confirm the safety and efficacy of two regimens of neoadjuvant therapy for BRPC. Our Clinical Trials: First, we evaluated the impact of neoadjuvant chemotherapy for BRPC. 143 BRPC-A patients undergoing pancreatectomy were reviewed from among 330 pancreatic cancer patients, including 111 potentially resectable pancreatic cancer patients and 76 BRPC with portal vein involvement patients. We compared the clinicopathological factors of 40 BRPC-A patients treated with neoadjuvant treatment followed by surgery and those of 103 BRPC-A patients treated with upfront surgery. The R0 rate and progression-free survival of BRPC-A patients who received neoadjuvant therapy and subsequent surgical resection were significantly better compared to those who received upfront surgery (R0: P = 0.041; progression-free survival: P = 0.033), but overall survival was not significantly different. Neoadjuvant treatment followed by surgery might provide clinical benefits for BRPC-A patients; however, the establishment of the most appropriate neoadjuvant treatment is needed by further studies. To evaluate appropriate neoadjuvant treatment, two prospective pilot trials were conducted as follows; modified FOLFIRINOX (without bolus 5-FU and LV, also decreased the dose of irinotecan; FIRINOX) and nab-paclitaxel plus gemcitabine therapy. Modified FOLFIRINOX was given to the first five patients in the 4-cycle group of the regimen and next five patients in the 8-cycle group. The primary end point was the toxicity of the therapy and one of the secondary end points were the optimal duration. The overall rate of grade 3 and 4 events was 80 %: 3 patients (60%) in the four-cycle group and five patients (100%) in the eight-cycle group had grade 3 or 4 adverse events. There was no incidence of serious adverse effect such as febrile neutropenia, sepsis, liver abscess or uncontrollable diarrhea. There was no clinically relevant morbidity presented in patients who underwent surgery. R0 rates by intention to treat were 60.0% in the four-cycle group and 40 % in the eight-cycle group (P = 0.999). The histopathologic treatment effect based on the Evans grade revealed grade I (n = 1), IIa (n = 3) in the four-cycle group and grade I (n = 2), IIa (n = 1) in the eight-cycle group. Nab-paclitaxel plus gemcitabine therapy: the primary endpoint was the toxicity, and secondary endpoints were the resection rate, the R0 resection rate. The overall rate of any grade and grade 3-4 events were 100% and 90%. The majority of these adverse events represented expected neutropenia. The resection and R0 resection rates were 80% and 70%, respectively. Conclusion: FIRINOX therapy was feasible and safe for strictly selected patients with BRPC. On the other hand, nab-paclitaxel plus gemcitabine therapy was safe and feasible without strict selection of patients with BRPC. A multicenter phase II study is in progress to investigate the efficacy of neoadjuvant nab-paclitaxel plus gemcitabine therapy on overall survival (UMIN000024154).

      • KCI등재

        Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation

        Manabu Tsukamoto,Toshiharu Mori,Eiichiro Nakamura,Yasuaki Okada,Hokuto Fukuda,Yoshiaki Yamanaka,Ken Sabanai,Ke-Yong Wang,Takeshi Hanagiri,Satoshi Kuboi,Kazuhiro Yatera,Akinori Sakai 대한골다공증학회 2020 Osteoporosis and Sarcopenia Vol.6 No.4

        Objectives: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers. Methods: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1 and serum levels of bone metabolism biomarkers. Results: All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors. Conclusions: The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.

      • KCI등재

        Neonatal Isolation Increases the Susceptibility to Learned Helplessness through the Aberrant Neuronal Activity in the Ventral Pallidum of Rats

        Hironori Kobayashi,Manabu Fuchikami,Kenichi Oga,Tatsuhiro Miyagi,Sho Fujita,Satoshi Fujita,Satoshi Okada,Yasumasa Okamoto,Shigeru Morinobu 대한정신약물학회 2024 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.22 No.2

        Objective: Environmental deprivation, a type of childhood maltreatment, has been reported to constrain the cognitive developmental processes such as associative learning and implicit learning, which may lead to functional and morphological changes in the ventral pallidum (VP) and pessimism, a well-known cognitive feature of major depression. We examined whether neonatal isolation (NI) could influence the incidence of learned helplessness (LH) in a rat model mimicking the pessimism, and the number of vesicular glutamate transporter 2 (VGLUT2)-expressing VP cells and Penk-expressing VP cells. Methods: The number of escape failures from foot-shocks in the LH test was measured to examine stress-induced depression-like behavior in rats. The number of VGLUT2-expressing VP cells and Penk-expressing VP cells was measured by immunohistochemistry. Results: In NI rats compared with Sham rats, the incidence of LH in adulthood was increased and VGLUT2-expressing VP cells but not Penk-expressing VP cells in adulthood were decreased. VGLUT2-expressing VP cells were decreased only in the LH group of NI rats and significantly correlated with the escape latency in the LH test. Conclusion: These findings suggest that the aberrant VP neuronal activity due to environmental deprivation early in life leads to pessimistic associative and implicit learning. Modulating VP neuronal activity could be a novel therapeutic and preventive strategy for the patients with this specific pathophysiology.

      • Evaluation of N-myristoylation Prediction Tool using Machine Learning

        Sayaka Kado,Ryo Okada,Manabu Sugii,Hiroshi Matsuno,Satoru Miyano 대한전자공학회 2008 ITC-CSCC :International Technical Conference on Ci Vol.2008 No.7

        Protein sequences constitute molecular complex in an organism. However it is difficult to find a sequence rule such as cascade reaction signals, post translational modification signals and so on. These sequence signals perform an essential role in regulating cellular structure and function. In previous study, we could find sequence rules of Nmyristoylated proteins easily with computational approach. Subsequently, we have developed a CGI tool to predict Nmyristoylated proteins with their sequence rules. In this study, we performed accuracy evaluation of our developed CGI tool. As a result, we show that developed CGI tool predict Nmyristoylated proteins effectively with characteristics of Nmyristoylated protein sequences.

      • KCI등재

        Ultrasonically Assisted Grinding for Mirror Surface Finishing of Dies with Electroplated Diamond Tools

        Hiromi Isobe,Keisuke Hara,Akira Kyusojin,Manabu Okada,Hideo Yoshihara 한국정밀공학회 2007 International Journal of Precision Engineering and Vol.8 No.2

        This paper describes ultrasonically assisted grinding used to obtain a glossy surface quickly and precisely. High-quality surfaces are required for plastic injection molding dies used in the production of plastic parts such as dials for cellular phones. Traditionally, in order to finish the dies, manual polishing by a skilled worker has been required after the machining processes, such as electro discharge machining (EDM), which leaves an affected layer, and milling, which leaves tooling marks. However, manual polishing causes detrimental geometrical deviations of the die and consumes several days to finish a die surface. Therefore, a machining process for finishing dies without manual polishing to improve the surface roughness and form accuracy would be extremely valuable. In this study, a 3D positioning machine equipped with an ultrasonic spindle was used to conduct grinding experiments. An electroplated diamond tool was used for these experiments. Generally, diamond tools cannot grind steel because of excessive wear as a result of carbon atoms diffusing into bulk steel and chips. However, ultrasonically assisted grinding can achieve a fine surface (roughness Rz of 0.4 ㎛) on die steel without severe tool wear. The final aim of this study is to realize mirror surface grinding for injection molding dies without manual polishing. To do this, it is necessary to fabricate an electroplated diamond tool with high form accuracy and low run-out. This paper describes a tool-making method for high precision grinding and the grinding performance of a self-electroplated tool. The ground surface textures, tool performance and tool life were investigated. A ground surface roughness Rz of 0.14 ㎛ was achieved. Our results show that the spindle speed, feed rate and cross feed affected the surface texture. One tool could finish 5000㎟ of die steel surface without any deterioration of the ground surface roughness.

      • SCIEKCI등재

        Ultrasonically Assisted Grinding for Mirror Surface Finishing of Dies with Electroplated Diamond Tools

        Isobe, Hiromi,Hara, Keisuke,Kyusojin, Akira,Okada, Manabu,Yoshihara, Hideo Korean Society for Precision Engineering 2007 International Journal of Precision Engineering and Vol.8 No.2

        This paper describes ultrasonically assisted grinding used to obtain a glossy surface quickly and precisely. High-quality surfaces are required for plastic injection molding dies used in the production of plastic parts such as dials for cellular phones. Traditionally, in order to finish the dies, manual polishing by a skilled worker has been required after the machining processes, such as electro discharge machining (EDM), which leaves an affected layer, and milling, which leaves tooling marks. However, manual polishing causes detrimental geometrical deviations of the die and consumes several days to finish a die surface. Therefore, a machining process for finishing dies without manual polishing to improve the surface roughness and form accuracy would be extremely valuable. In this study, a 3D positioning machine equipped with an ultrasonic spindle was used to conduct grinding experiments. An electroplated diamond tool was used for these experiments. Generally, diamond tools cannot grind steel because of excessive wear as a result of carbon atoms diffusing into bulk steel and chips. However, ultrasonically assisted grinding can achieve a fine surface (roughness Rz of $0.4{\mu}m$) on die steel without severe tool wear. The final aim of this study is to realize mirror surface grinding for injection molding dies without manual polishing. To do this, it is necessary to fabricate an electroplated diamond tool with high form accuracy and low run-out. This paper describes a tool-making method for high precision grinding and the grinding performance of a self-electroplated tool. The ground surface textures, tool performance and tool life were investigated A ground surface roughness Rz of 0.14 um was achieved Our results show that the spindle speed, feed rate and cross feed affected the surface texture. One tool could finish $5000mm^2$ of die steel surface without any deterioration of the ground surface roughness.

      • Diethyldithiocarbamate Suppresses an NF-κB Dependent Metastatic Pathway in Cholangiocarcinoma Cells

        Srikoon, Pattaravadee,Kariya, Ryusho,Kudo, Eriko,Goto, Hiroki,Vaeteewoottacharn, Kulthida,Taura, Manabu,Wongkham, Sopit,Okada, Seiji Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

        Cholangiocarcinoma (CCA) is a tumor of biliary ducts, which has a high mortality rate and dismal prognosis. Constitutively activation of the transcription factor nuclear factor kappa-B (NF-${\kappa}B$) has been previously demonstrated in CCA. It is therefore a potential target for CCA treatment. Effects of diethyldithiocarbamate (DDTC) on NF-${\kappa}B$-dependent apoptosis induction in cancer have been reported; however, anti-metastasis has never been addressed. Therefore, here the focus was on DDTC effects on CCA migration and adhesiond. Anti-proliferation, anti-migration and anti-adhesion activities were determined in CCA cell lines, along with p65 protein levels and function. NF-${\kappa}B$ target gene expression was determined by quantitative RT-PCR. DDTC inhibited CCA cell proliferation. Suppression of migration and adhesion were observed prior to anti-CCA proliferation. These effects were related to decreased p65, reduction in NF-${\kappa}B$ DNA binding, and impaired activity. Moreover, suppression of ICAM-1 expression supported NF-${\kappa}B$-dependent anti-metastatic effects of DDTC. Taken together, DDTC suppression of CCA migration and adhesion through inhibition of NF-${\kappa}B$ signaling pathway is suggested from the current study. This might be a promising treatment choice against CCA metastasis.

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