基本情報
- 所属
- 自治医科大学 附属病院耳鼻咽喉科 教授東京大学医科学研究所附属病院脳腫瘍外科 非常勤講師
- 学位
- 医学博士(自治医科大学)
- J-GLOBAL ID
- 200901012308530180
- researchmap会員ID
- 5000100064
【専門領域】頭頸部癌、頭頸部外科学
【基礎研究】癌細胞の生物学的活性(浸潤能、転移能、幹細胞)、嗅上皮組織の再生
【臨床研究】機能形態温存治療(上顎洞癌集学治療、外科手術)、抗癌薬同時併用化学放射線治療、分子標的薬同時併用放射線治療、導入化学療法、高齢者の癌治療
【主な所属学会】ASCO、AAO-HNS、癌学会、癌治療学会、日本耳鼻咽喉科学会、頭頸部癌学会、頭頸部外科学会、日本鼻学会
【その他】東京大学医科学研究所附属病院脳腫瘍外科と共同研究「進行性嗅神経芽細胞腫患者に対する増殖型遺伝子組換え単純ヘルペスウイルスG47Δを用いたウイルス療法の臨床研究、JCOG「JCOG1008局所進行頭頸部扁平上皮癌術後再発High-Risk患者に対するHigh dose CDDPを同時併用する術後補助化学放射線療法とweekly CDDOPを同時併用する術後補助化学放射線療法ランダム化第II/III相試験
【基礎研究】癌細胞の生物学的活性(浸潤能、転移能、幹細胞)、嗅上皮組織の再生
【臨床研究】機能形態温存治療(上顎洞癌集学治療、外科手術)、抗癌薬同時併用化学放射線治療、分子標的薬同時併用放射線治療、導入化学療法、高齢者の癌治療
【主な所属学会】ASCO、AAO-HNS、癌学会、癌治療学会、日本耳鼻咽喉科学会、頭頸部癌学会、頭頸部外科学会、日本鼻学会
【その他】東京大学医科学研究所附属病院脳腫瘍外科と共同研究「進行性嗅神経芽細胞腫患者に対する増殖型遺伝子組換え単純ヘルペスウイルスG47Δを用いたウイルス療法の臨床研究、JCOG「JCOG1008局所進行頭頸部扁平上皮癌術後再発High-Risk患者に対するHigh dose CDDPを同時併用する術後補助化学放射線療法とweekly CDDOPを同時併用する術後補助化学放射線療法ランダム化第II/III相試験
研究キーワード
1研究分野
1経歴
1論文
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Cancer medicine 13(13) e7431 2024年7月BACKGROUND: Cancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis. METHODS: First, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed. RESULTS: Among the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival. CONCLUSIONS: The stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors.
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Oral oncology 154 106868-106868 2024年5月30日OBJECTIVES: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008. MATERIALS AND METHODS: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m2 (weekly arm) or 3-weekly cisplatin at 100 mg/m2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration. RESULTS: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %. CONCLUSIONS: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen.
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Science progress 107(3) 368504241274022-368504241274022 2024年Maxillary angiosarcoma, an aggressive tumor derived from vascular endothelial cells, is very rare. Recently, antivascular endothelial growth factor (VEGF) therapies have attracted considerable attention. We describe the clinical course of a patient with maxillary angiosarcoma and discuss the expression of VEGF signaling molecules assessed via immunohistological analysis. An 81-year-old man presented with an aggressive tumor in the left maxillary sinus. Biopsy revealed atypical nuclear cell proliferation, and the tumor was suspected to be a sarcoma. The maxillary malignancy was treated using a multidisciplinary approach with a combination of surgery, radiotherapy, and regional chemotherapy. Examination of the specimen obtained in the first surgery revealed maxillary angiosarcoma, found to be positive for CD31, while negative for CD34, D2-40, and factor Ⅷ. Although no pathological residual tumor was observed after the planned wide surgery, cervical lymph node and distant metastases occurred. The patient died 24 months after the first surgery. Staining revealed VEGF receptor (VEGFR) 1, VEGFR2, phosphorylated Ak strain transforming, mitogen-activated protein kinase, and signal transducer and activator of transcription 3 positivity. Although our findings do not indicate that anti-VEGF therapy is beneficial for treating maxillary angiosarcomas, we found that VEGFR signaling pathways were activated in maxillary angiosarcomas similar to angiosarcomas originating at other sites. Herein, we report a case of maxillary angiosarcoma, focused on VEGFR and signaling pathway activation. To our knowledge, this is the first report to describe VEGFR system immunostaining findings in maxillary angiosarcoma.
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Frontiers in medicine 11 1247625-1247625 2024年INTRODUCTION: The Hippo pathway consists of mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC). METHODS: The analyses included oral epithelial dysplasia (OED, n = 7), carcinoma in situ (CIS, n = 14), and oral squamous cell carcinoma (OSCC, n = 109). RESULTS: Cytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5/7 cases), CIS (9/14 cases), and poorly differentiated OSCC (8/8 cases) but was low/lost in a proportion of differentiated OSCC (60/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35/71 cases), compared to moderately and poorly differentiated OSCC (11/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (p < 0.0001). CONCLUSION: Among the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.
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Cureus 15(12) e49939. doi:10.7759/cureus.49939 2023年12月 査読有り
MISC
254-
栃木県医学会々誌 33(33) 178-181 2003年10月10日頭頸部癌に重複した食道表在癌治療経験を報告した.対象は,1992年〜2003年5月までに治療した8例(全例男性,平均59歳)であった.頭頸部癌は下咽頭癌4例,喉頭癌2例,甲状腺癌,舌癌各1例で,甲状腺乳頭癌を除き全てが扁平上皮癌であった.治療は放射線照射を主体とした集学的治療を施行した.表在癌発見の契機は頭頸部癌治療前のスクリーニング時が5例,頭頸部癌治療後の定期検査による内視鏡検査が2例,表在癌治療後の下咽頭癌発見が1例であった.占拠部位はMtが4例,Ltが2例,UtとCeが各1例で,深達度はsmが2例,m3が2例,m2以下が4例であった.治療は内視鏡的粘膜切除術が4例,根治術が2例,放射線治療が2例であった.転帰は2例に下咽頭癌死を認めたが,表在癌による死亡はなかった.なお,頭頸部癌(喉頭癌)に重複した進行食道癌7例では,頭頸部癌治療後3年以上経過してからの発見(6例)で,原病死5例と極めて予後不良であった
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GENE THERAPY 10(1) 51-58 2003年1月The application of adeno-associated virus (AAV) vectors to cancers is limited by their low transduction efficiency. Previously, we reported that gamma-ray enhanced the second-strand synthesis, leading to the improvement of the transgene expression, and cytocidal effect of the herpes simplex virus type-1 thymidine kinase (HSVtk) and ganciclovir (GCV) system. In this study, we extended this in vitro findings to in vivo. First, the laryngeal cancer cell line (HEp-2) and HeLa were treated with AAVtk/GCV, the number of surviving cells was reduced as the concentration of GCV increased. Furthermore, the 4 Gy irradiation enhanced the killing effects of AAVtk/GCV by four-fold on HeLa cells and 15-fold on HEp-2 cells. Following the in vitro experiments, we evaluated the transgene expression and the antitumor activity of the AA V vectors in combination with gamma-ray in nude mice inoculated with HEp-2 subcutaneously. The LacZ expression was observed in the xenografted tumors and significantly increased by gamma-ray. The AAVtk/GCV system suppressed the tumors growth, and gamma-ray augmented the antitumor activity by five-fold. These findings suggest that the combination of AAVtk/GCV system with radiotherapy is significantly effective in the treatment of cancers and may lead to reduction of the potential toxicity of both AAVtk/GCV and gamma-ray.
講演・口頭発表等
11共同研究・競争的資金等の研究課題
17-
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