T Mori

Gifu University, Gihu, Gifu, Japan

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Publications (496)1044.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA (miR)-203 is downregulated and acts as an anti-oncomir in melanoma cells. Here, using human and canine melanoma cells, we elucidated the effects of miR-203 on cyclic adenosine monophosphate response element binding protein (CREB)/microphthalmia-associated transcription factor (MITF)/RAB27a pathway, which is known to be important for the development and progression of human melanoma. In this study, we showed that miR-203 directly targeted CREB1 and regulated its downstream targets, MITF and RAB27a. miR-203 significantly suppressed the growth of human and canine melanoma cells and inhibited melanosome transport through the suppression of the signalling pathway. In conclusion, miR-203 was shown to be a common tumour-suppressive miRNA in human and canine melanoma and thus to play a crucial role in the biological mechanisms of melanoma development.
    Veterinary and Comparative Oncology 09/2014; · 1.56 Impact Factor
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    ABSTRACT: Malignant melanoma (MM) is one of the most aggressive cancers in dogs and in humans. However, the molecular mechanisms of its development and progression remain unclear. Presently, we examined the expression profile of microRNAs (miRs) in canine oral MM tissues and paired normal oral mucosa tissues by using the microRNA-microarray assay and quantitative RT-PCR. Importantly, a decreased expression of miR-203 was significantly associated with a shorter survival time. Also, miR-203 and -205 were markedly down-regulated in canine and human MM cell lines tested. Furthermore, the ectopic expression of miR-205 had a significant inhibitory effect on the cell growth of canine and human melanoma cells tested by targeting erbb3. Our data suggest that miR-203 is a new prognostic factor in canine oral MMs and that miR-205 functions as a tumour suppressor by targeting erbb3 in both canine and human MM cells.
    Veterinary and Comparative Oncology 06/2013; 11(2):113-23. · 1.56 Impact Factor
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    ABSTRACT: We examined whether mutation of the platelet-derived growth factor receptor protein tyrosine kinase (PDGFR)-α and PDGFR-β genes contributes to their overexpression in canine vascular tumours. Genomic sequences of trans- or juxtamembrane regions of PDGFR-α and PDGFR-β were analysed with immunohistochemical staining and polymerase chain reaction-direct sequencing using DNA from paraffin-embedded neoplastic tissues of 27 hemangiosarcomas (HSAs) and 20 hemangiomas (HAs). Immunohistochemically, 75% of the HA cases were positive for PDGFR-α and almost most of the HA cases were negative for PDGFR-β. Of the HSA cases, 55.6% were negative for PDGFR-α and 63% were strongly positive for PDGFR-β. Among the HA cases, 1 missense mutation was detected in PDGFR-α exon 18 and 1 in PDGFR-β exon 17. Two HSA cases had missense mutations in exon 14 and 1 in exon 17 of PDGFR-β. Thus, genomic mutation of trans- or juxtamembrane regions of PDGFRs was not the main mechanism driving the activation of receptors in HSA and HA.
    Veterinary and Comparative Oncology 04/2013; · 1.56 Impact Factor
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    ABSTRACT: An 11-year-old male Bearded Collie was brought to the Gifu University Animal Medical Centre with a skin mass on the lateral right thigh. Physical examination revealed a 30 × 65-mm oval mass with an alopecic and ulcerated surface. Histopathology of the surgically excised sample confirmed malignant trichoepithelioma. Five months after the surgery, the dog experienced lumbar pain resulting from metastasis to the lumbar vertebrae. Radiation therapy (RT) was performed and it alleviated the lumbar pain. Nine months after the surgery, multiple skin metastases were identified. RT was performed at each occurrence, which reduced the size of each tumour and resulted in a partial response; however, systemic metastasis occurred and the dog died 17 months after the initial surgery. Canine malignant trichoepithelioma is a rare tumour, so an effective treatment has not been determined. Data from our case study indicate that RT has potential for pain control of primary and metastatic malignant trichoepithelioma.
    Australian Veterinary Journal 06/2012; 90(6):210-3. · 0.92 Impact Factor
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    ABSTRACT: Hemangiosarcoma (HSA) is a malignant neoplasia of vascular endothelial cells (ECs). Our previous report on the expression of vascular endothelial growth factor, basic fibroblast growth factor, and their receptors in canine HSA suggested an autocrine/ paracrine mechanism of tumor growth. However, the influence of other angiogenic growth factors in canine HSA was not elucidated; therefore, the expression of platelet-derived growth factor (PDGF) and its receptors was investigated by immunohistochemical analysis. Forty-six canine HSAs and 21 canine cutaneous hemangiomas (HAs) were analyzed. For immunohistochemistry, anti-PDGF-BB, anti-PDGFR-α, and anti-PDGFR-β antibodies were utilized as primary antibodies. Immunoreactivities were scored as strongly positive (>25% positive neoplastic cells), weakly positive (1-25% positive neoplastic cells), and negative if not staining at all. In cutaneous HA, 33.3% and 57.1% of cases were strongly and weakly positive, respectively, and 43.5% and 13.0% of HSAs were strongly and weakly positive for PDGF-BB, respectively. Moreover, 38.1% and 28.6% of cutaneous HAs cases were strongly and weakly positive, respectively, and 23.9% and 4.3% of HSAs cases were strongly and weakly positive, respectively, for PDGFR-α. Thirty-five HSAs cases (76.1%) were strongly positive, and the remaining 11 (23.9%) were weakly positive for PDGFR-β. In contrast, 18 (72.0%) cutaneous HAs were negative, and only 3 cases (12.0%) were weakly positive, for PDGFR-β. The proportion of strongly positive cases of HSAs was significantly higher than that of cutaneous HA for PDGFR-β (P<0.01), while PDGFR-α was highly expressed in cutaneous HA and may be related to pathogenesis of cutaneous HA. Therefore, PDGFR-β may be associated with the malignant nature of canine HSA.
    Histology and histopathology 05/2012; 27(5):601-7. · 2.28 Impact Factor
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    ABSTRACT: Fascin-1 expression was examined in 9 cutaneous melanocytomas and 47 oral melanomas. The cases were scored on the basis of extent and intensity of staining, and combined scores were calculated. Fascin-1 expression was observed in 5/9 (56%) melanocytomas and 46/47 (98%) melanomas. The combined score for fascin-1 was significantly greater in stage III/IV melanomas than in stage I/II melanomas (P < 0.05). In addition, strong fascin-1 staining was associated with a significantly shortened survival time (P < 0.05). The results of this study suggest that fascin-1 overexpression correlates with the malignancy of canine melanoma and has the potential to be a new immunohistochemical marker to predict the clinical course of canine melanoma. In addition, targeted therapy for fascin-1 may represent a new strategy for the treatment of canine melanoma.
    Veterinary and Comparative Oncology 11/2011; · 1.56 Impact Factor
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    ABSTRACT: KIT, a transmembrane receptor tyrosine kinase, is one of the specific targets for anti-cancer therapy. In humans, its expression and mutations have been identified in malignant melanomas and therapies using molecular-targeted agents have been promising in these tumours. As human malignant melanoma, canine malignant melanoma is a fatal disease with metastases and the poor response has been observed with all standard protocols. In our study, KIT expression and exon 11 mutations in dogs with histologically confirmed malignant oral melanomas were evaluated. Although 20 of 39 cases were positive for KIT protein, there was no significant difference between KIT expression and overall survival. Moreover, polymerase chain reaction amplification and sequencing of KIT exon 11 in 17 samples did not detect any mutations and proved disappointing. For several reasons, however, KIT expression and mutations of various exons including exon 11 should be investigated in more cases.
    Veterinary and Comparative Oncology 09/2011; 9(3):219-24. · 1.56 Impact Factor
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    ABSTRACT: We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2010; 24(2):383-96. · 10.16 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 27(52).
  • The Veterinary record 09/2009; 165(12):350-1. · 1.80 Impact Factor
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    ABSTRACT: Angiogenic homeobox genes regulate the behaviour of endothelial cells (ECs) during angiogenesis, so the aim of this study was to determine whether expression of these genes may be a determinant of malignancy in canine haemangiosarcoma (HSA). Homeobox proteins were evaluated immunohistochemically in tissue samples from canine HSAs (n=78), haemangiomas (HAs; n=30) and samples of granulation tissue (n=8). Active ECs in granulation tissue were positively labelled by antisera specific for HoxA9, HoxB3, HoxD3, HoxB7, Pbx1 and Meis1. Quiescent ECs in granulation tissue did not express HoxD3 and Pbx1. There were significantly more neoplastic cells positively labelled for HoxA9, HoxB3, HoxD3 and Pbx1 in HSA compared with HA. Almost all tumours were positive for HoxB7 and Meis1. HoxB3, HoxD3, Pbx1 and Meis1 proteins were detected in 80-90% of the HSAs, but in <20% of the HAs. Overall, homeobox protein expression in HSA appears to have a phenotype similar to that of active ECs in angiogenesis. The expression of homeobox genes associated with angiogenesis might be associated with the malignant growth of HSA.
    Journal of comparative pathology 06/2009; 141(2-3):199-203. · 1.73 Impact Factor
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    ABSTRACT: We performed immunohistochemical investigation of the basement membrane (BM) components, namely, type IV collagen and laminin, in 83 canine hemangiosarcomas (HSAs), 22 hemangiomas, and some granulation tissues (GTs). Additionally, we analyzed the expression and activities of matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1-MMP (MT1-MMP) using the same samples by immunohistochemistry and gelatin zymography to investigate whether MMPs were associated with the BM degradation. In immunohistochemistry for the BM components, many HSAs showed discontinuous linear/negative immunoreactivity in the BM (type IV collagen: 49.4%/14.5%, laminin: 60.3%/10.8%, respectively). In contrast, almost all hemangiomas showed continuous staining in the BM (type IV collagen: 90.9%, laminin: 95.5%, respectively). Interestingly, positive cytoplasmic immunoreactivity for type IV collagen and laminin was observed in 97.6% and 91.6% HSA, respectively. Although MMP-9 immunoreactivity wasn't detected in neoplastic and active angiogenic endothelial cells (ECs), MMP-2 was detected in all ECs of GTs and in neoplastic cells of both vascular tumors. A strong immunoreactivity for MT1-MMP was observed in active angiogenic ECs in GTs and in neoplastic ECs in HSAs. However, almost all hemangiomas showed weak/negative immunoreactivity. In gelatin zymography, significantly strong activity of active MMP-2 was observed in HSAs, similar to that in active angiogenesis in GTs; however, weak/no activity of active MMP-2 was detected in hemangiomas. In canine HSA, neoplastic cells had active MMP-2, possibly activated by MT1-MMP, and discontinuous status of BM might be associated with activity of active MMP-2.
    Histology and histopathology 05/2009; 24(4):437-46. · 2.28 Impact Factor
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    ABSTRACT: To investigate whether anti-apoptotic factors play a role in the malignant growth of canine haemangiosarcomas (HSAs), 83 HSAs and 22 haemangiomas were examined immunohistochemically for bcl-2 and survivin expression. Additionally, bcl-2 and survivin mRNA expression was quantified by semiquantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunolabelling for bcl-2 was observed in 50 of the 83 HSA samples (60.2%) but in none of the haemangiomas. The average survivin positive index was 24.7% in the HSAs and 0.6% in the haemangiomas. In contrast to the high average value for survivin mRNA expression, which was approximately six times that for the haemangiomas, no significant difference was observed between HSAs and haemangiomas for the average bcl-2 mRNA expression level. The discrepancy between bcl-2 mRNA and bcl-2 protein expression requires further investigation, but the results suggest that malignant proliferation in canine HSAs is associated with bcl-2 and survivin expression.
    Journal of Comparative Pathology 08/2008; 139(1):1-7. · 1.38 Impact Factor
  • Medical Mycology - MED MYCOL. 01/2008; 36(2):107-112.
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    ABSTRACT: During a search for causative genes in patients with concurrent multiple primary colon tumours, we found a novel case with a germline mutation of the p53 gene, from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that this patient had, one large advanced carcinoma exhibited a somatic p53 mutation and a somatic APC mutation, in addition to the germline p53 mutation. Two early carcinomas and three adenomas had somatic APC mutations but no somatic p53 mutation or loss of the p53 allele. K-ras-2 mutations were detected in an advanced carcinoma and an early carcinoma. The present results suggest that a patient with a certain type of germline p53 mutation is predisposed to concurrent multiple colon tumours. It is also suggested that in such a patient, a somatic APC mutation is involved in tumour formation and that an additional somatic p53 mutation contributes to tumour progression.
    Gut 03/2003; 52(2):304-6. · 10.73 Impact Factor
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    ABSTRACT: We analyzed the effectiveness of anti-cancer chemotherapy administered at home. Continuous hepatic arterial infusion (HAI) of 5-FU (250 mg/day) for unresectable liver metastases of colorectal cancer (129 cases) and systemic administration of 5-FU and CDDP (FP therapy) as a palliative treatment or for recurrent cases of colorectal cancer (145 cases) were evaluated. The response rate for HAI was 59.7%, and 50% survival according to the outcome of HAI was CR: 765 days PR: 607 days NC: 233 days and PD: 146 days. The residual life span of patients who showed CR or PR was significantly prolonged. The occurrence of complications from HAI was 15.1%. On the other hand, the response rate was 19.3%, and 50% survival was 292 days. The one-year survival rate was 38.7%. The mean duration of this chemotherapy and the mean stay at home were 188.2 days and 237.8 days, respectively. The mean rate of home stays was 68.6%. The group of performance status (PS) 0 or improving PS accounted for 74.5% of all cases. Those with a PS grade 3 or 4 accounted for only 1-4% of the patients. Finally, both chemotherapies could be continued at the outpatient clinic or at home.
    Gan to kagaku ryoho. Cancer & chemotherapy 01/2002; 28 Suppl 1:5-8.
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    ABSTRACT: The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) is generally poor and reports from large studies are scarce. We evaluated the efficacy of allogeneic bone marrow transplantation (allo-BMT) for children with this type of leukemia. The chemotherapy regimens consisted of an induction phase and very intensive consolidation followed by a reinduction phase and late intensification treatment. The selection of treatment modalities such as chemotherapy, allo-BMT, or autologous transplantation was made by each institute. The principal endpoint was the outcome of children with Ph(+) ALL according to the treatment options. Thirty-two patients (4.3%) were diagnosed as Ph(+) ALL out of the 741 cases of ALL consecutively enrolled in two protocols of the Tokyo Children's Cancer Study Group (TCCSG) from 1989 to 1994. Thirty patients (93.8%) were induced into complete remission (CR). Of these 30 patients, eight children electively received allo-BMT in the first CR. Six of these patients are in continuous remission at a median follow-up of 58 (range 48-105) months after the diagnosis. One patient died following recurrence and another patient died of graft vs. host disease. Three patients treated with autologous BMT or peripheral blood stem cell transplantation in the first CR experienced a subsequent relapse. In the remaining 19 patients, 13 patients were treated with very high-risk chemotherapy alone and all relapsed within 28 months. One patient was excluded from the analysis because he was treated with standard-risk chemotherapy until relapse. The other five patients were also excluded from the analysis because Philadelphia chromosome was not detected until they relapsed. None of the relapsed patients survived in spite of treatment including allo-BMT. In multivariate analysis, only allo-BMT remained as an independent factor for good prognosis. The only way to cure children with Ph(+) ALL was allo-BMT in this study and its outcome seemed promising.
    Medical and Pediatric Oncology 12/2001; 37(5):426-31.
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    ABSTRACT: Clinically, unresectable pelvic tumor is difficult to treat because the patients have poor prognosis and often suffer from severe pain and edema of the lower limbs due to the tumor invasion of the pelvic bone and the sciatic nerve. To improve QOL of such patients, we performed thermoradiotherapy (RTHT) or internal iliac arterial infusion of 5-FU (IIAI) for 7 patients who developed unresectable pelvic tumors which relapsed after surgery for 6 colorectal cancers and one leiomyosarcoma of the uterus. The mean tumor diameter was 10.2 cm and an evaluation by computed tomography revealed 2 of 6 tumors had a partial response (PR) and 3 no change (NC). Each of the 4 patients who had been ill in bed recovered to the point of being able to walk with a cane or wheel themselves in a wheelchair after the therapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2001; 28(11):1612-5.
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    ABSTRACT: A 53-year-old female presented with abdominal pain, and computed tomography scan revealed a small, calcified lesion in the wall of the transverse colon. The symptoms later disappeared spontaneously, and she remained in good health. However, four years later, she developed lancinating abdominal pain and was admitted to our hospital. A large tumor with calcification was found in the left upper abdominal cavity. Curative resection of the tumor was performed, and the histology was compatible with extraskeletal osteosarcoma. We speculated that the tumor originated from the colonic wall, because a small calcification was observed in the wall of the transverse colon four years before surgery. To the best of our knowledge, this is the first report of primary colonic osteosarcoma.
    Diseases of the Colon & Rectum 10/2001; 44(9):1367-70. · 3.34 Impact Factor
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    ABSTRACT: One of the characteristics of tumors from patients with germline mutations of DNA mismatch repair genes is instability at microsatellite regions (MSI). We analysed alterations at repeated sequences of coding regions, as well as those of 5' upstream regions, in 29 MSI-High colorectal tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) and Turcot syndrome. We found that repeated sequences in 5' upstream regions were altered in these tumors, at considerable frequencies. The (A)10 repeat in the promoter region (position -178 to approximately -169) of the GAPDH gene was altered in 17% of the tumors. The (A)10(TA)9 in the 5' upstream region (position -318 to approximately -291) of the mitochondrial isoleucyl tRNA synthetase gene (IleRS-A), coded in nuclear DNA, was altered in 59% of the tumors, whereas (A)9 in the 5' upstream region (position -859 to approximately -851) of cytoplasmic isoleucyl tRNA synthetase gene (IleRS-B) was not altered. Alteration at repeated sequences in the coding regions were 72% at TGFbetaRII(A)10, 24% at IGFIIR(G)8, 45% at BAX(G)8, 55% at E2F4(CAG)13, 66% at caspase-5 (A)10, 31% at MBD4(A)10, 55% at hMSH3(A)8 and 34% at hMSH6(C)8. The number of altered genes increased with the advancement of carcinoma according to Dukes categories: mean numbers of altered genes within these 10 genes were 2.6 for Dukes A, 4.7 for Dukes B and 7.8 for Dukes C. The mean number for adenomas was 2.0. These results suggest that the MSI phenotype also causes alteration of 5' upstream regions which may affect apoptosis and some mitochondrial functions in HNPCC and Turcot tumors, and that accumulation of altered genes with repeated sequences is associated with the progression of HNPCC and Turcot colorectal tumors.
    Oncogene 09/2001; 20(37):5215-8. · 8.56 Impact Factor

Publication Stats

6k Citations
1,044.22 Total Impact Points

Institutions

  • 2008–2011
    • Gifu University
      • Department of Veterinary Medicine
      Gihu, Gifu, Japan
  • 1991–2003
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
    • Osaka National Hospital
      Ōsaka, Ōsaka, Japan
  • 1992–2001
    • Juntendo University
      • • Department of Internal Medicine
      • • Department of Medicine
      Edo, Tōkyō, Japan
  • 1991–1999
    • Keio University
      • • Department of Pediatrics
      • • School of Medicine
      Tokyo, Tokyo-to, Japan
  • 1998
    • St. Luke's International Hospital
      Edo, Tōkyō, Japan
  • 1986–1997
    • Osaka University
      • • Department of Surgery
      • • Department of Medical Genetics
      • • Division of Cellular and Molecular Biology
      • • Department of Oncogene Research
      • • School of Medicine
      Suita, Osaka-fu, Japan
  • 1995
    • Saitama Medical University
      • Department of Pediatrics
      Saitama, Saitama-ken, Japan
  • 1993–1995
    • The University of Tokyo
      • • Department of Precision Engineering
      • • Faculty and Graduate School of Agriculture and Life Sceince
      Tokyo, Tokyo-to, Japan
  • 1992–1995
    • National Institute of Radiological Sciences
      Tiba, Chiba, Japan
  • 1994
    • Kyoto University
      Kioto, Kyōto, Japan
  • 1992–1993
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
  • 1989–1992
    • Hoshi University
      • Faculty of Pharmaceutical Sciences
      Edo, Tōkyō, Japan
  • 1988
    • Osaka Prefecture Senshu Critical Care Medical Center
      Ōsaka, Ōsaka, Japan