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Articles by K Matsumoto
Total Records ( 10 ) for K Matsumoto
  K Matsumoto , J Huang , N Viswakarma , L Bai , Y Jia , Y. T Zhu , G Yang , J Borensztajn , M.S Rao , Y. J Zhu and J. K. Reddy

Nuclear receptor coactivator [peroxisome proliferator-activated receptor-binding protein (PBP)/mediator subunit 1 (MED1)] is a critical component of the mediator transcription complex. Disruption of this gene in the mouse results in embryonic lethality. Using the PBP/MED1 liver conditional null (PBP/MED1Liv) mice, we reported that PBP/MED1 is essential for liver regeneration and the peroxisome proliferator-activated receptor ligand Wy-14,643-induced receptor-mediated hepatocarcinogenesis. We now examined the role of PBP/MED1 in genotoxic chemical carcinogen diethylnitrosamine (DEN)-induced and phenobarbital-promoted hepatocarcinogenesis. The carcinogenic process was initiated by a single intraperitoneal injection of DEN at 14 days of age and initiated cells were promoted with phenobarbital (PB) (0.05%) in drinking water. PBP/MED1Liv mice, killed at 1, 4 and 12 weeks, revealed a striking proliferative response of few residual PBP/MED1-positive hepatocytes that escaped Cre-mediated deletion of PBP/MED1 gene. No proliferative expansion of PBP/MED1 null hepatocytes was noted in the PBP/MED1Liv mouse livers. Multiple hepatocellular carcinomas (HCCs) developed in the DEN-initiated PBP/MED1fl/fl and PBP/MED1Liv mice, 1 year after the PB promotion. Of interest is that all HCC developing in PBP/MED1Liv mice were PBP/MED1 positive. None of the tumors was PBP/MED1 negative implying that hepatocytes deficient in PBP/MED1 are not susceptible to neoplastic conversion. HCC that developed in PBP/MED1Liv mouse livers were transplantable in athymic nude mice and these maintained PBP/MED1fl/fl genotype. PBP/MED1fl/fl HCC cell line derived from these tumors expressed PBP/MED1 and deletion of PBP/MED1fl/fl allele by adeno-Cre injection into tumors caused necrosis of tumor cells. These results indicate that PBP/MED1 is essential for the development of HCC in the mouse.

  A Tsubota , K Matsumoto , K Mogushi , K Nariai , Y Namiki , S Hoshina , H Hano , H Tanaka , H Saito and N. Tada

To identify key genes involved in the complex multistep process of hepatotumorigenesis, we reduced multivariate clinicopathological variables by using the Long–Evans Cinnamon rat, a model with naturally occurring and oxidative stress-induced hepatotumorigenesis. Gene expression patterns were analyzed serially by profiling liver tissues from rats of a naive status (4 weeks old), through to those with chronic hepatitis (26 and 39 weeks old) to tumor development (67 weeks old). Of 31 099 probe sets used for microarray analysis, 87 were identified as being upregulated in a stepwise manner during disease progression and tumor development. Quantitative real-time reverse transcription–polymerase chain reaction and statistical analyses verified that IQGAP1 and vimentin mRNA expression levels increased significantly throughout hepatotumorigenesis. A hierarchical clustering algorithm showed both genes clustered together and in the same cluster group. Immunohistochemical and western blot analyses showed similar increases in protein levels of IAGAP1 and vimentin. Finally, pathway analyses using text-mining technology with more comprehensive and recent gene–gene interaction data identified IQGAP1 and vimentin as important nodes in underlying gene regulatory networks. These findings enhance our understanding of the multistep hepatotumorigenesis and identification of target molecules for novel treatments.

  T Okada , H Ihara , R Ito , M Nakano , K Matsumoto , Y Yamaguchi , N Taniguchi and Y. Ikeda

The baculovirus–insect cell expression system is in widespread use for expressing post-translationally modified proteins. As a result, it is potentially applicable for the production of glycoproteins for therapeutic and diagnostic purposes. For practical use, however, remodeling of the biosynthetic pathway of host-cell N-glycosylation is required because insect cells produce paucimannosidic glycoforms, which are different from the typical mammalian glycoform, due to trimming of the non-reducing terminal β1,2-GlcNAc residue of the core structure by a specific β-N-acetylglucosaminidase. In order to establish a cell line which could be used as a host for the baculovirus-based production of glycoproteins with mammalian-type N-glycosylation, we prepared and characterized Spodoptera frugiperda Sf21 cells that had been transfected with the rat cDNA for β1,4-N-acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of a bisecting GlcNAc. As evidenced by structural analyses of N-glycans prepared from whole cells and the expressed recombinant glycoproteins, the introduction of GnT-III led to the production of bisected hybrid-type N-glycans in which the β1,2-GlcNAc residue at the 1,3-mannosyl branch is completely retained and which has the potential to be present in mammalian cells. These results and other related findings suggest that bisected oligosaccharides are highly resistant to β-N-acetylglucosaminidase activity of the S. frugiperda fused lobes gene product, or other related enzymes, which was confirmed in Sf21 cells. Our present study demonstrates that GnT-III transfection has the potential to be an effective approach in humanizing the N-glycosylation of lepidopteran insect cells, thereby providing a possible preliminary step for the generation of complex-type glycoforms if the presence of a bisecting GlcNAc can be tolerated.

  T Onda , H Yoshikawa , T Yasugi , K Matsumoto and Y. Taketani

The optimal goal of interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) remains undefined. The aim of this study was to determine the optimal goal of IDS following NAC on the basis of long-term survival by the disease status at the end of interval look surgery (ILS) or IDS during the treatment in the setting of upfront primary debulking surgery (PDS).


From January 1986 through December 2000, we performed treatment in the setting of upfront PDS in 128 patients with Stage III/IV epithelial ovarian cancer. Sixty-six patients with residual disease (RD) at PDS underwent interval surgery (IS) such as ILS or IDS; 4 patients after two cycles of chemotherapy and 62 after three or more cycles. We investigated how disease status at the end of IS was associated with overall survival (OS).


The 5-year OS rates for no, minimal and gross RD were not available (n = 0), 67% (n = 3) and 0% (n = 1) after two cycles, and 47% (n = 42), 0% (n = 18) and 0% (n = 2) after three or more cycles, respectively. No visible tumors at the end of IS after three or more cycles of chemotherapy were necessary for 5-year survival.


If the optimal goal of IDS is defined as the surgery that is expected to result in long-term survival in the NAC setting treatment, our data on the assessment of peritoneal findings during the upfront PDS setting treatment suggest that only complete resection with no RD could be the optimal goal of IDS in the NAC setting treatment.

  S Shirotake , E Kikuchi , K Matsumoto , S Yazawa , T Kosaka , A Miyajima , K Nakagawa and M. Oya

The role of pelvic lymphadenectomy in patients with lymph node-negative bladder cancer at radical cystectomy (RC) has not yet been examined in detail. We retrospectively reviewed patients who underwent RC with pelvic lymphadenectomy for bladder cancer from January 1987 to March 2008.


We identified consecutive data on 169 patients who underwent RC for bladder cancer. The mean follow-up was 64 months (range: 1–253 months). Node-positive status (pN(+)) was seen in 16 patients and 91 were diagnosed as node-negative (pN(–)). The lymph node status of the remaining 62 patients was unclear (pN(x)). We analysed the association between lymph node status and cancer-specific survival (CSS), and examined the role of the number of retrieved lymph nodes, particularly in pN(–).


The median number of retrieved nodes was 12.9 and 10.2 for stage pN(+) and stage pN(–), respectively. In 91 patients with pN(–), multivariate analysis revealed that pathological T3-4 (P = 0.0276) and less than nine retrieved lymph nodes (P = 0.0108) were independent risk factors for CSS. In a subgroup of 83 patients with pT3-4, Kaplan–Meier curves showed that the 5-year CSS rate in pN(–) patients with less than nine retrieved lymph nodes was 38.8%, which was extremely similar to the 40.8% in pN(+) and 45.1% in pN(x).


Our results demonstrate that at least nine lymph nodes should be removed to improve the survival of pN(–) patients at RC and lymphadenectomy, and would provide information not only on prognosis but also on the therapeutic impact on pT3-4 invasive bladder cancer.

  K Matsumoto , K Nakagawa , A Hashiguchi , H Kono , E Kikuchi , H Nagata , A Miyajima and M. Oya

The diagnosis of prostate cancer is based on the results of ultrasonography-guided needle biopsy of the prostate, but cancer foci are often not visible in conventional transrectal ultrasonography. Sonazoid is a new microbubble contrast agent. The purpose of our study was to compare areas of contrast material enhancement in the prostate at ultrasonography with whole-mount radical prostatectomy specimens to determine if the use of Sonazoid improves the detection rate of prostate cancer.


Fifty patients with biopsy-proven cancer of the prostate who were scheduled to undergo radical prostatectomy were recruited for this study. The day before the operation, each patient was evaluated with ultrasonography at baseline and again during intravenous infusion of Sonazoid. A map of ultrasonography findings was created prospectively at the time of imaging. Following radical prostatectomy, independent mapping of the pathologic results was performed and the maps were compared.


Ultrasonography evaluation at baseline demonstrated that at least one focus of cancer was identified in 20 of the 50 subjects (40.0%). Meanwhile at least one cancer focus was enhanced in 31 of the 50 patients (62.0%) when Sonazoid was used. The combination of baseline grayscale imaging and contrast-enhanced imaging allowed identification of at least one focus of cancer in 40 patients (80.0%). Contrast-enhanced ultrasonography can improve sensitivity, especially for the detection of large cancer, peripheral zone cancer and highly malignant cancer.


Our study has demonstrated significantly improved detection of prostate cancer with the combination of baseline grayscale imaging and contrast-enhanced imaging compared with conventional ultrasonography techniques only, and this technique may be applicable to targeted biopsy.

  K Matsumoto , A Oki , T Satoh , S Okada , T Minaguchi , M Onuki , H Ochi , S Nakao , M Sakurai , A Abe , H Hamada and H. Yoshikawa

Polymorphisms in cytokine genes can influence immune responses to human papillomavirus infection, possibly modifying risks of cervical cancer. Using an amplification refractory mutation system-polymerase chain reaction method, we analyzed a single nucleotide polymorphism (A/G) at position –1082 in interleukin-10 promoter region in 440 Japanese women: 173 women with normal cytology, 163 women with cervical intraepithelial neoplasia and 104 women with invasive cervical cancer. The carrier frequency of interleukin-10 –1082 G alleles associated with higher interleukin-10 production increased with disease severity: 9.8% for normal cytology; 19.6% for cervical intraepithelial neoplasia; 29.8% for invasive cervical cancer (P for trend <0.001). Among cytologically normal women, human papillomavirus infections were more common in those who were positive for an interleukin-10 –1082 G allele (P = 0.04). In conclusion, our data suggest that interleukin-10 –1082 gene polymorphism may serve as a marker of genetic susceptibility to cervical cancer among Japanese women.

  K Matsumoto , H Honda , T Shibata , D Sanada , Y Wada , E Ashikaga , A Kuroki , K Kitazawa and T. Akizawa

An elderly woman presented with haematuria and proteinuria accompanied by elevated serum myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A renal biopsy revealed mild mesangial proliferation with fibrocellular crescent formation and a membranous glomerular lesion. Immunofluorescence microscopy using FITC-labelled rabbit anti-human MPO antibodies revealed granular MPO deposition along the glomerular capillary walls (GCW) with a staining profile similar to that of glomerular IgG deposition. The one-year follow-up renal biopsy revealed minimal IgG and undetectable MPO deposition. Both MPO and MPO-ANCA might have been responsible for the IgG immune depositions along the GCW in this patient.

  K Yamauchi , K Wakahara , M Fukuta , K Matsumoto , H Sumi , K Shimizu and K. Miyamoto

Background: Little epidemiological research on characteristics of upper extremity injuries resulting from snowboarding has been conducted, particularly in relation to snowboarding stance, falling direction, and the side of the body where the injury occurs.

Hypothesis: Snowboarding stance and the direction of the fall may influence the frequency of the side or the location of the upper extremity injury.

Study Design: Descriptive epidemiology study.

Methods: This study analyzed the information obtained from 1918 patients with fractures or dislocations of the upper extremity (excluding the fingers and scapula) sustained during snowboarding/sliding between 2000 and 2008. Diagnosis, injured part and side, stance (regular or goofy), and falling directions were prospectively analyzed. Associations among these parameters were also analyzed.

Results: As characterized by skill level, patients were beginners (57.9%), intermediates (38.0%), and experts (4.0%). Eighty-eight percent had not received instruction from licensed instructors. Diagnoses included wrist fractures (53.7%), upper arm fractures (16.8%), shoulder dislocations (11.5%), and elbow dislocations (9.8%). In sum, 1742 (90.8%) patients were in regular stance when they fell, whereas 176 (9.2%) were in goofy stance. There was a significant difference in the prevalence of the injured side between the 2 stances. When the injured sides were classified according to the sliding direction, wrist fractures (61.7%) occurred on the side opposite the sliding direction, whereas shoulder dislocations (65.6%), upper arm fractures (82.9%), and elbow dislocations (79.8%) occurred on the same side as the sliding direction. When the injured sides were classified according to the falling direction, wrist fractures (68.1%) and elbow dislocations (63.5%) occurred because of backward falls, and shoulder dislocations (68.9%) and upper arm fractures (60.7%) occurred because of forward falls.

Conclusion: Two snowboarding stances as well as 2 falling directions had a significant influence on the frequency of the injured side in the upper extremity.

  T Ebihara , M Azuma , H Oshiumi , J Kasamatsu , K Iwabuchi , K Matsumoto , H Saito , T Taniguchi , M Matsumoto and T. Seya

In myeloid dendritic cells (mDCs), TLR3 is expressed in the endosomal membrane and interacts with the adaptor toll/interleukin 1 receptor homology domain–containing adaptor molecule 1 (TICAM-1; TRIF). TICAM-1 signals culminate in interferon (IFN) regulatory factor (IRF) 3 activation. Co-culture of mDC pretreated with the TLR3 ligand polyI:C and natural killer (NK) cells resulted in NK cell activation. This activation was triggered by cell-to-cell contact but not cytokines. Using expression profiling and gain/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1–inducing membrane protein that participates in mDC-mediated NK activation. Of the nine candidates screened, one contained a tetraspanin-like sequence and satisfied the screening criteria. The protein, referred to as IRF-3–dependent NK-activating molecule (INAM), functioned in both the mDC and NK cell to facilitate NK activation. In the mDC, TICAM-1, IFN promoter stimulator 1, and IRF-3, but not IRF-7, were required for mDC-mediated NK activation. INAM was minimally expressed on NK cells, was up-regulated in response to polyI:C, and contributed to mDC–NK reciprocal activation via its cytoplasmic tail, which was crucial for the activation signal in NK cells. Adoptive transfer of INAM-expressing mDCs into mice implanted with NK-sensitive tumors caused NK-mediated tumor regression. We identify a new pathway for mDC–NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.

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