浅野 尚文 (アサノ ナオフミ)

Asano, Naofumi

写真a

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医学部 整形外科学教室 (信濃町)

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  • 博士(医学), 慶應義塾, 課程, 2017年03月

    Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma

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  • 整形外科専門医, 2011年03月

 

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  • 整形外科学

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  • 骨軟部腫瘍、肉腫

 

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  • Malignant Peripheral Nerve Sheath Tumor of the Femur: A Rare Diagnosis Supported by Complete Immunohistochemical Loss of H3K27me3

    Sugawara, M., Kobayashi, E., Asano, N., Yoshida, A. and Kawai, A.

    Int J Surg Pathol 25 ( 7 ) 629 - 634 2017年10月

    ISSN  1066-8969

     概要を見る

    The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging because of the wide morphological spectrum and suboptimal performance of conventional immunohistochemical markers. MPNST arising primarily in the bone is exceptional, and its definitive diagnosis, particularly out of the neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a highly specific biomarker of MPNSTs. In this article, we report a case of sporadic MPNST of the proximal femur that showed complete loss of H3K27me3. The patient was treated with limb-sparing surgery and postoperative radiotherapy. He developed multiple lung and bone metastases 4 months after surgery. Our case confirms the utility of H3K27me3 immunohistochemistry to yield a definitive diagnosis of sporadic MPNST in a rare primary site.

  • Preoperative evaluation of renal cell carcinoma patients with bone metastases on risks for blood loss, performance status and lethal event

    Yoshiyama, A., Morii, T., Susa, M., Morioka, H., Kobayashi, E., Asano, N., Mori, T., Anazawa, U., Watanabe, I., Takeuchi, K., Kushima, Y., Aoyagi, T. and Ichimura, S.

    J Orthop Sci 22 ( 5 ) 924 - 930 2017年09月

    ISSN  0949-2658

     概要を見る

    BACKGROUND: Surgical treatment for renal cell carcinoma metastases can be an effective modality for improving survival and patients' quality of life. However, it is often difficult to decide on the optimal surgical approach due to the lesion's high vascularity and uncertainty regarding postoperative performance status and survival. PATIENTS AND METHODS: Blood loss, postoperative performance status, overall survival, postoperative complication and related risk factors for surgical treatment were analysed in 61 renal cell carcinoma patients with bone metastases. RESULTS: Pelvic location and impending/pathological fracture in the metastatic lesion were both significant risk factors for increased blood loss. An unresectable primary lesion and poor preoperative performance status were independent risk factors for poor postoperative performance status. A shorter duration from the discovery of primary lesion to bone metastasis, the number of metastases, and unresectable primary lesion were independent risk factors for shorter survival. Postoperative complications were identified in 15 cases (24.6%). CONCLUSION: The preoperative prediction of intraoperative blood loss, performance status and survival in renal cell carcinoma patients with bone metastases may be possible based on the risk factors identified in this study.

  • Impact of geriatric factors on surgical and prognostic outcomes in elderly patients with soft-tissue sarcoma

    Tsuda, Y., Ogura, K., Kobayashi, E., Hiruma, T., Iwata, S., Asano, N., Kawai, A., Chuman, H., Ishii, T., Morioka, H., Kobayashi, H. and Kawano, H.

    Jpn J Clin Oncol 47 ( 5 ) 422 - 429 2017年05月

    ISSN  0368-2811

     概要を見る

    Objective: Patients aged >/=65 years requiring surgery for soft-tissue sarcoma are a concern in an aging society. We aimed to reveal the association of clinical/geriatric factors with survival period or postoperative events in such patients who underwent surgery. Methods: We enrolled patients aged >/=65 years who underwent surgery for localized soft-tissue sarcoma at five institutions. We retrospectively collected clinical/geriatric factors and laboratory data, and analyzed their association with outcomes using univariate and multivariate analyses. Results: Among the 202 patients included, mean age at presentation was 73 years. Surgical margin was R0 in 139 patients (69%). The Eastern Cooperative Oncology Group performance status was >/=2 in 15 (7%). Thirty patients (15%) showed thinness (body mass index <18.49 kg/cm2). High-sensitivity-modified Glasgow prognostic score >/=1 was seen in 52 patients (26%). Multivariate analysis showed that R1 surgical margin was significantly correlated with poor sarcoma-specific survival (hazard ratio for R1 vs. R0, 3.17; P = 0.001) and event-free survival (hazard ratio for R1 vs. R0, 2.56; P < 0.001). Higher Eastern Cooperative Oncology Group performance status was significantly associated with poor sarcoma-specific survival (hazard ratio for >/=2 vs. 0 or 1, 2.15; P = 0.038), and higher sensitivity-modified Glasgow prognostic score was significantly associated with poor event-free survival (hazard ratio for >/=1 vs. 0, 1.74; P = 0.046). Severe thinness (body mass index <16.00) was a risk factor for postoperative events (odds ratio for body mass index <16.00 vs. >/=16.00, 8.15, P = 0.010). Conclusions: Negative surgical margin was associated with better survival. Coexisting conditions had an impact on outcomes in elderly soft-tissue sarcoma patients.

  • Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma

    Asano, N., Yoshida, A., Mitani, S., Kobayashi, E., Shiotani, B., Komiyama, M., Fujimoto, H., Chuman, H., Morioka, H., Matsumoto, M., Nakamura, M., Kubo, T., Kato, M., Kohno, T., Kawai, A., Kondo, T. and Ichikawa, H.

    Oncotarget 8 ( 8 ) 12941 - 12952 2017年02月

    ISSN  1949-2553

     概要を見る

    Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes. Potential driver mutations were found in only six (11%) samples; however, gene amplification events (other than MDM2 and CDK4 amplification) were identified in 30 (54%) samples. Receptor tyrosine kinase (RTK) genes in particular were amplified in 18 (32%) samples. In addition, growth of a WDLPS cell line with IGF1R amplification was suppressed by simultaneous inhibition of CDK4 and IGF1R, using palbociclib and NVP-AEW541, respectively. Combination therapy with CDK4 and RTK inhibitors may be an effective therapeutic option for WDLPS/DDLPS patients with RTK gene amplification.

  • Immunohistochemistry for trimethylated H3K27 in the diagnosis of malignant peripheral nerve sheath tumours

    Asano, N., Yoshida, A., Ichikawa, H., Mori, T., Nakamura, M., Kawai, A. and Hiraoka, N.

    Histopathology 70 ( 3 ) 385 - 393 2017年02月

    ISSN  0309-0167

     概要を見る

    AIMS: The diagnosis of a malignant peripheral nerve sheath tumour (MPNST) can be challenging, as the morphological criteria and existing immunohistochemical markers are not entirely specific. The recent discovery of frequent inactivation of polycomb repressive complex 2 in MPNSTs suggests that immunohistochemical detection of histone 3 trimethylated on lysine 27 (H3K27me3) could be of diagnostic help. This study aimed to clarify the utility of this marker. METHODS AND RESULTS: We performed immunostaining studies, with monoclonal (C36B11) and polyclonal antibodies in parallel. With the monoclonal antibody, 56% of 54 conventional MPNSTs showed complete loss of staining, whereas 17% showed mosaic loss and 28% showed intact staining. Three MPNSTs showed a novel geographical pattern of complete loss. All three epithelioid MPNSTs retained intact staining. Among 232 non-MPNSTs, only two (0.9%) showed complete loss of staining. Mosaic loss was observed in 38% of non-MPNSTs, whereas the remaining 61% retained intact staining. For conventional MPNSTs, complete loss of H3K27me3 was significantly associated with a higher TNM stage (P = 0.013), a deeper location (P = 0.004), and the presence of heterologous differentiation (P = 0.003). Polyclonal antibodies did not recognize 34% of cases that showed complete loss with the use of monoclonal antibodies. CONCLUSIONS: We confirmed that complete loss of H3K27me3 immunohistochemical staining is moderately sensitive and highly specific for MPNSTs. In contrast to prior studies, we found that mosaic loss of H3K27me3 staining is non-specific, and caution that such a pattern should not be considered to be diagnostic. We recommend the use of a monoclonal antibody to obtain better performance.

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  • 脱分化型脂肪肉腫に対するエピゲノム解析

    2018年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 浅野 尚文, 若手研究, 補助金,  代表

 

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  • 整形外科学講義

    2019年度