記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas. CASE PRESENTATION: A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer "T3", left tongue cancer "T2" and lower left lip cancer "T1", N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period. CONCLUSIONS: This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma.

DOI： 10.1186/s13014-023-02282-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There are a few reports that focus on radiotherapy (RT) and cetuximab (CET) therapy exclusively for oral cancer. This retrospective study aimed to investigate the efficacy and safety of RT and CET therapy for locally advanced (LA) or recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC). Seventy-nine patients from 13 hospitals who underwent RT and CET therapy for LA or R/M OSCC between January 2013 and May 2015 were enrolled in the study. Response, overall survival (OS), disease-specific survival (DSS), and adverse events were investigated. The completion rate was 62/79 (78.5%). The response rates in patients with LA and R/M OSCC were 69% and 37.8%, respectively. When only completed cases were examined, the response rates were 72.2% and 62.9%, respectively. The 1- and 2-year OS were 51.5% and 27.8%, respectively (median, 14 months), for patients with LA OSCC, and 41.5% and 11.9% (median, 10 months) for patients with R/M OSCC. The 1- and 2-year DSS were 61.8% and 33.4%, respectively (median, 17 months), for patients with LA OSCC, and 76.6% and 20.4% (median, 12 months) for patients with R/M OSCC. The most common adverse event was oral mucositis (60.8%), followed by dermatitis, acneiform rash, and paronychia. The completion rate was 85.7% in LA patients and 70.3% in R/M patients. The most common reason for noncompletion was an inadequate radiation dose due to worsening general conditions in R/M patients. Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin.

DOI： 10.3390/ijerph20054545

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本睡眠歯科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: SIRT6 is one of seven human sirtuin genes and is known to act as an onco-suppressor gene in colorectal and ovarian cancers, although it is up-regulated in other cancers. Thus, SIRT6 is considered performing both tumor-suppressing and promoting roles. However, the association of SIRT6 with oral squamous cell carcinoma (OSCC) and its role in OSCC pathogenesis is currently unclear. This study aimed to investigate the expression of SIRT6 in patients with OSCC and its potential as a biomarker for early detection and prognosis prediction. MATERIALS AND METHODS: Immunohistochemistry, quantitative real-time RT-PCR, and microarray analyses were performed to determine SIRT6 expression and its association with clinicopathological features in OSCC using clinical specimens. RESULTS: SIRT6 mRNA and protein expression levels were higher in OSCC tissues than in noncancerous tissues (p<0.05). SIRT6 expression was predominant in patients aged ≥65 years and significantly correlated with shorter overall survival. In the microarray analysis, some SIRT6-associated genes, such as ANXA2, were up-regulated in OSCC. CONCLUSION: SIRT6 plays a role in tumor homeostasis, leading to a poor prognosis in OSCC. SIRT6 may represent a novel target not only for treatment, but also as a prognostic marker in OSCC.

DOI： 10.21873/anticanres.15872

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：日本病態生理学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fusobacterium nucleatum is associated with the progression of colorectal cancer. Thus, the possibility of preventing colorectal cancer or its progression by targeting F. nucleatum has been explored. As F. nucleatum is associated with periodontitis, we analysed whether treating periodontitis could influence F. nucleatum abundance in the colon. Patients with colorectal tumours who underwent colonoscopy were recruited. Patients diagnosed with periodontitis by a dentist were treated for approximately 3 months. Endoscopic resection of colorectal tumours was performed after periodontitis treatment, and resected tumours were pathologically classified as high-(HGD) or low-grade dysplasia (LGD). Saliva and stool samples were collected before and after the treatment. Of the 58 patients with colorectal tumours, 31 were included in the study, 16 showed improvement in periodontitis, and 11 showed no improvement. Stool F. nucleatum levels before treatment were significantly lower in the LGD group than in the HGD group. A significant decrease in faecal F. nucleatum levels was observed in patients who underwent successful treatment but not in those whose treatment failed. Salivary F. nucleatum levels were not altered in patients despite periodontal treatment. Thus, successful periodontitis treatment reduces stool F. nucleatum levels and may aid research on periodontitis and suppression of colorectal cancer development.

DOI： 10.1038/s41598-021-03083-4

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化管学会  

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記述言語：英語  

Steroid has recently been reported as a treatment for new coronavirus disease (COVID-19). The incidence of oropharyngeal candidiasis due to the inhaled steroid ciclesonide is lower than that due to other inhaled steroids. We report the first case of oral candidiasis with COVID-19 pneumonia using ciclesonide. A 75-year-old man was hospitalized for COVID-19 pneumonia. After admission, an oral combination of lopinavir/ritonavir was administered, and ciclesonide was inhaled for 7 days. On the 14th day of hospitalization, white plaque was found in his oral mucosa. Candida albicans was identified by oral bacterial tests, and amphotericin B was initiated. On the 35th hospital day, negative result for C. albicans was confirmed. Intraoral monitoring and intervention by dental care workers are considered important for the prevention of infectious complications induced by corticosteroids.

DOI： 10.1177/2050313X211048279

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Treatment failure in oral cancer is mainly caused by uncontrolled cervical lymph node (LN) metastasis. We previously reported that CD11b+ cells are recruited into tumor hypoxic areas following radiation, leading to re-vascularization and relapse. Since lymphatic vessel formation has similarities with vascular formation, we examined whether surgery induces hypoxia and stimulates lymphangiogenesis. MATERIALS AND METHODS: The recruitment of CD11b+ cells and the formation of lymphatic vessels were examined using orthotopic tongue cancer mouse models with glossectomy. RESULTS: Surgery on OSC-19 tumor induced LN metastases and hypoxia, followed by CD11b+ cell influx. These phenomena were not observed in the no tumor or SAT tumor models. Stimulation of lymphangiogenesis was observed in the CD11b+ cell influx area, as the tumor grew. The localization of CD11b+ cells was changed from the lymph nodules to the medullary sinuses. CONCLUSION: Surgery-induced hypoxia in oral tumors leads to CD11b+ cell infiltration, lymphangiogenesis, and LN metastasis.

DOI： 10.21873/anticanres.14706

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). METHODS: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). RESULTS: The median follow-up time was 24 (range: 1-124) months. The median prescribed dose was 60 (6-70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0-87.6; SCRT: 50.4, 95% CI: 27.6-73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7-85.2; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2-86.4; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. CONCLUSIONS: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

DOI： 10.1186/s12885-020-07638-y

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

65歳女。左側頸部の有痛性腫瘤を主訴に受診した。同部に不動性で弾性硬の腫瘤を触知し、圧痛が著明であった。血液検査で軽度の炎症所見を認めた。造影CTで左側顎下部に腫大したリンパ節を認めたが、触診での圧痛部位とは異なっていた。左側総頸動脈分岐部に血管壁肥厚を認めた。また、圧痛と一致する部位で、総頸動脈分岐部を取り巻く範囲に軟組織陰影を認めた。超音波検査で疼痛部は左側総頸動脈分岐部に一致しており、周囲に軟組織陰影が確認された。同部の血管壁内膜に石灰化プラークの貯留を認め、内膜中膜複合体は2.3mmと動脈硬化の所見であった。動脈炎や動脈解離などとの鑑別のため脳神経外科と神経内科、膠原病内科に併診したところ、これらの疾患は否定的であり、carotidyniaと診断した。外来通院下に経過観察を行い、約2週間で症状は自然軽快した。

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01073&link_issn=&doc_id=20200410360003&doc_link_id=10.5794%2Fjjoms.66.136&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.66.136&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ultraviolet treatment of titanium implants makes their surfaces hydrophilic and enhances osseointegration. However, the mechanism is not fully understood. This study hypothesizes that the recruitment of fibrinogen, a critical molecule for blood clot formation and wound healing, is influenced by the degrees of hydrophilicity/hydrophobicity of the implant surfaces. Computational fluid dynamics (CFD) implant models were created for fluid flow simulation. The hydrophilicity level was expressed by the contact angle between the implant surface and blood plasma, ranging from 5° (superhydrophilic), 30° (hydrophilic) to 50° and 70° (hydrophobic), and 100° (hydrorepellent). The mass of fibrinogen flowing into the implant interfacial zone (fibrinogen infiltration) increased in a time dependent manner, with a steeper slope for surfaces with greater hydrophilicity. The mass of blood plasma absorbed into the interfacial zone (blood plasma infiltration) was also promoted by the hydrophilic surfaces but it was rapid and non-time-dependent. There was no linear correlation between the fibrinogen infiltration rate and the blood plasma infiltration rate. These results suggest that hydrophilic implant surfaces promote both fibrinogen and blood plasma infiltration to their interface. However, the infiltration of the two components were not proportional, implying a selectively enhanced recruitment of fibrinogen by hydrophilic implant surfaces.

DOI： 10.3390/ijms21020660

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy. METHODS: A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m2 docetaxel and 150 mg/m2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks. RESULTS: The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P < .05). No grade 5 toxicities were observed. CONCLUSIONS: Intra-arterial infusion chemotherapy concurrent with radiotherapy was effective for advanced maxillary gingival SCC.

DOI： 10.1002/hed.25607

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report a case of squamous cell carcinoma of the buccal mucosa with N3 cervical lymph node metastasis in a 63-year-old man. The patient was treated with combination therapy comprising radiotherapy (2 Gy/day, total of 70 Gy), superselective intra-arterial chemotherapy via a superficial temporal artery (docetaxel, total of 70 mg/m2 and cisplatin, total of 175 mg/m2), cetuximab (initial dose of 400 mg/m2 with subsequent weekly doses of 250 mg/m2 intravenously), and four sessions of hyperthermia for cervical lymph node metastases. The patient responded well to the therapy, with a complete response of the primary tumor. Radical neck dissection was performed with reconstructive surgery, including resection of the overlying skin. A pathologic complete response was achieved for the N3 and all other cervical lymph node metastases. The patient showed no evidence of recurrence in the 3 years following treatment. Based on the findings in the present case, the use of retrograde superselective intra-arterial chemoradiotherapy combined with hyperthermia and cetuximab seems to be a promising modality for patients with N3 cervical lymph node metastasis of oral cancer.

DOI： 10.1007/s11282-018-0319-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21873/anticanres.12985

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and objectives: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in the present study. In the DIACRT group, 25 patients had late T2, and 20 patients had T3. A total of nine patients had late T2 and two had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months, respectively. The five-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for the DIACRT group, and 60.6% and 63.6% for the WIACRT group, respectively. The LC rate and OS of the DIACRT group were significantly higher than those of the WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods in both groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

DOI： 10.3390/medicina54040052

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy. MATERIALS AND METHODS: Between June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50-70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50-70 mg/m2; cisplatin, total 125-175 mg/m2) for 5-7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox's proportional hazards model was used for both univariate and multivariate analyses. RESULTS: The median follow-up for all patients was 38.5 months (range, 3-129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification. CONCLUSION: Retrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.

DOI： 10.1016/j.oraloncology.2018.02.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

Purpose: The purpose of this study was to assess the efficacy and safety of cetuximab plus platinum-based chemotherapy for patients specifically diagnosed with recurrent or metastatic oral squamous cell carcinoma (OSCC). Methods: We conducted a multicenter retrospective observational study of patients who underwent first-line cetuximab plus platinum-based chemotherapy between December 2012 and June 2015. 65 patients received weekly cetuximab (week 1, 400 mg/m2
subsequent weeks, 250 mg/m2) plus a maximum of six 3-weekly cycles of cisplatin (80 or 100 mg/m2, day 1) or carboplatin (at an area under the curve of 5 mg/mL/min as a 1-h intravenous infusion on day 1) and 5-fluorouracil (800 or 1000 mg/m2/day, days 1–4). Patients with stable disease who received cetuximab plus platinum-based chemotherapy continued to receive cetuximab until disease progression or unacceptable toxicities, whichever occurred first. Results: The median follow-up was 10.5 (range 1.2–34.2) months. The best overall response and the disease control rates were 46.2 and 67.7%, respectively. The median overall survival and progression-free survival rates were 12.1 and 7.8 months, respectively. The most common grades 3–4 adverse events were skin rash (9.2%) followed by leukopenia (6.2%). None of the adverse events were fatal. Conclusion: The results of our multicenter retrospective study, which was the largest of its kind to date, suggest that first-line cetuximab plus platinum-based chemotherapy is suitable and well-tolerated for the systemic therapy of recurrent or metastatic OSCC.

DOI： 10.1007/s00280-018-3531-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Society of Hard Tissue Regenerative Biology  

This study aimed to evaluate the mechanical stress on resected mandibular bone against occlusal force using dental implant without any bone grafting by finite element analysis to reduce the risk of the bone fracture. A model of marginal resection of the symphysis of the mandible, in which the bone height of the region was 5, 10 or 15 mm, was prepared. Two, four, or six implant-supported fixed prostheses (superstructure) or overdenture were set up in the model and loaded with 500N of occlusal force. The von Mises stress on the resected region was the highest when two implants were bilaterally placed at positions closest to the resected region. The von Mises stress value on the resected region could be high enough to induce the bone fracture. The mechanical stress was reduced up to &lt
50 % by adding implant at posterior position and connecting all implants. The presence of superstructure on 4 or 6 implants significantly decreased the von Mises stress when the residual bone height was 10 or 15 mm. Use of 6 implants showed no significant advantage at the stress reduction compared to use of 4 implants. When the residual bone height was 5 mm, reinforcement of the residual bone or bone graft should be considered to avoid the bone fracture. Although the present results were obtained under restrictive conditions, the number of implant, implant position, and prostheses style could reduce the von Mises stress and the risk of bone fracture on the resected region.

DOI： 10.2485/jhtb.27.11

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Impact Journals LLC  

N,N'-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/ quantitation of drug distribution.

DOI： 10.18632/oncotarget.24570

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s13014-017-0847-3

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective. To evaluate the therapeutic results and control of occult neck metastasis in patients with T2-4N0 oral tongue squamous cell carcinoma treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy.
Study Design. Forty-two patients with T2-4N0 tongue cancer (17 with late T2; 13 with T3; and 12 with T4a disease, M0) were treated with intra-arterial chemoradiotherapy. Treatment consisted of retrograde superselective intra-arterial chemotherapy (docetaxel 50-70 mg/m(2), cisplatin 125-175 mg/m(2)) and daily concurrent radiotherapy (50-70 Gy) for 5-7 weeks.
Results. The median follow-up for all patients was 46.5 months (range, 8-105 months). Primary-site complete response was achieved in 42 of 42 cases (100%). Three-year overall survival, progression-free survival, and local control rates were 85.0%, 77.8%, and 91.7%, respectively. Delayed neck metastasis was detected in 5 of 42 cases (11.9%). Grade 3 or 4 toxic changes included oral mucositis in 92.9%, neutropenia in 21.4%, and thrombocytopenia in 4.8%. Grade 3 toxicities included anemia in 16.7%, radiation dermatitis in 9.5%, nausea in 4.8%, and fever in 2.4%.
Conclusions. Retrograde superselective intra-arterial chemotherapy for T2-4N0 tongue cancer provided good overall survival and local control rates and was effective for occult neck metastasis.

DOI： 10.1016/j.oooo.2017.02.004

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INDIAN ACAD SCIENCES  

Ayurveda is a holistic medical system of traditional medicine, and Triphala is one of the most popular formulations in Ayurveda. Triphala is composed of three kinds of herb, Terminalia chebula, Terminalia bellirica, and Emblica officinalis. Since Triphala is shown to exhibit a protective activity against ionizing radiation in mice, we investigated its activity in HeLa cells. We found that Triphala showed the protective effects against X-radiation and bleomycin, both of which generate DNA strand breaks, in HeLa cells. Further, Triphala efficiently eliminated reactive oxygen species (ROS) in HeLa cells. Thus, the antioxidant activity of Triphala would likely play a role in its protective actions against X-radiation and bleomycin because both agents damage DNA through the generation of ROS. These observations suggested that the radioprotective activity of Triphala can be, at least partly, studied with the cells cultured in vitro. The simple bioassay system with human cultured cells would facilitate the understanding of the molecular basis for the beneficial effects of Triphala.

DOI： 10.1007/s12038-016-9639-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare low-grade malignant neoplasm with a predilection for children and young adults, and typically arises in the lung, abdominopelvic region, and retroperitoneum. IMTs in the maxillofacial region are extreme rare. Approximately 50% of IMT harbor rearrangements of the anaplastic lymphoma kinase (ALK) gene at 2p23 with various fusion partners. CASE PRESENTATION: We herein report a case of intraosseous IMT of the mandible with a novel ATIC-ALK fusion. Tooth 43 did not erupt after the loss of tooth 83 in an 11-year-old girl with no previous history of trauma. Panoramic tomography showed a unilocular radiolucent lesion in the right anterior mandible resorbing the root of tooth 42 and the medial side of the root of tooth 44. Computed tomography revealed a well- circumscribed 3-cm osteolytic lesion of the right anterior mandible eroding the buccal cortical plate. The entire lesion was curetted out. A histopathological examination revealed the proliferation of plump spindle cells with a storiform architecture and lymphocytes scattered around spindle cells. The spindle cells showed diffuse cytoplasmic staining for ALK by immunohistochemistry. A fluorescence in situ hybridization analysis revealed the translocation of a part of the ALK gene locus at chromosome 2p23. A rapid amplification of cDNA ends analysis confirmed the rearrangement of ALK and identified ATIC as a partner of this ALK fusion mutant. CONCLUSION: To the best of our knowledge, this is the first case of intraosseous IMT of the mandible with a novel ATIC-ALK fusion. We also herein reviewed similar tumors reported in the literature.

DOI： 10.1186/s13000-016-0586-z

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Despite the fact that radiation is one of the standard therapies in the treatment of patients with oral cancer, tumours can recur even in the early stages of the disease, negatively impacting prognosis and quality of life. We previously found that CD11b(+) bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b(+) myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumour and increased infiltration of CD11b(+) myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2M phi s) and are associated with the promotion of vascularization. M2M phi s promoted tumour progression in recurrence after irradiation compared to non-irradiated tumours. In addition, we found that CD11b(+) myeloid cells, as well as CD206(+) M2M phi s, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in irradiated OSCC patients.

DOI： 10.1038/srep27548

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

We previously investigated the utility of mu-oxo N,N'-bis(salicylidene) ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anticancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.

DOI： 10.1038/srep24629

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective. To investigate whether 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) uptake of primary tumor in oral squamous cell carcinoma (OSCC) could predict prognosis.
Study Design. Sixty-nine patients with OSCC who underwent retrograde superselective intra-arterial chemoradiotherapy were recruited and underwent dual-time-point FDG positron emission tomography twice, before treatment and 4 weeks after treatment. FDG uptake was defined as the standardized uptake value (SUVmax). The retention index (RI) and the percent change in SUV (% change SUV), derived from the dual-time-point scan, were calculated.
Results. On univariate analysis, patients with high pre-SUV, RI, and percent change SUV values had significantly worse overall survival and disease-free survival compared with patients with low values. On multivariate analysis, high pre-RI (&gt;= 20.6%) and high percent change SUV (&gt;= 60.0%) (delayed-image) were associated with significantly worse overall survival. High pre-SUV (&gt;= 9.6) (delayed-image) and high pre-RI (&gt;= 20.6%) were associated with significantly shorter disease-free survival.
Conclusions. Dual-time-point FDG positron emission tomography in OSCC provided prognostic information and predicted patient outcome.

DOI： 10.1016/j.oooo.2015.10.018

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記述言語：日本語   出版者・発行元：(一社)日本病理学会  

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background/Aim: The subset of T-cells positive for expression of cluster of differentiation (CD) 57 has been associated with various cancer phenotypes. However, the presence of CD57(+) T-cells in patients with oral squamous cell carcinoma (OSCC) has yet to be confirmed. In the present study, we examined the diagnostic significance of the presence of CD57(+) T-cells in peripheral blood (PB) from patients with OSCC. Materials and Methods: The subset of CD57(+) T-cells in PB was analyzed in 43 patients with OSCC by fluorescence-activated cell sorting (PACS) analysis. Results: The proportion of CD57(+) T-cells, including both CD8(+) and CD4(+) subsets, significantly increased with clinical stage, especially in parallel with tumor size. Conclusion: Our results suggest that an increase in the population of CD57(+) T-cells is a potent prognostic marker and may also influence the systemic immunity of patients with OSCC.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-014-0309-8

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Purpose: To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy.
Materials and methods: One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60 mg/m(2), cisplatin, total 150 mg/m(2)) and daily concurrent radiotherapy (total of 60 Gy) for 6 weeks.
Results: The median follow-up for all patients was 46.2 months (range, 10-76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients.
Conclusion: Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.radonc.2014.03.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Background: In experimental models of glioblastoma multiforme (GBM), irradiation (IR) induces local expression of the chemokine CXCL12/SDF-1, which promotes tumour recurrence. The role of CXCR7, the high-affinity receptor for CXCL12, in the tumour's response to IR has not been addressed.
Methods: We tested CXCR7 inhibitors for their effects on tumour growth and/or animal survival post IR in three rodent GBM models. We used immunohistochemistry to determine where CXCR7 protein is expressed in the tumours and in human GBM samples. We used neurosphere formation assays with human GBM xenografts to determine whether CXCR7 is required for cancer stem cell (CSC) activity in vitro.
Results: CXCR7 was detected on tumour cells and/or tumour-associated vasculature in the rodent models and in human GBM. In human GBM, CXCR7 expression increased with glioma grade and was spatially associated with CXCL12 and CXCL11/I-TAC. In the rodent GBM models, pharmacological inhibition of CXCR7 post IR caused tumour regression, blocked tumour recurrence, and/or substantially prolonged survival. CXCR7 expression levels on human GBM xenograft cells correlated with neurosphere-forming activity, and a CXCR7 inhibitor blocked sphere formation by sorted CSCs.
Conclusions: These results indicate that CXCR7 inhibitors could block GBM tumour recurrence after IR, perhaps by interfering with CSCs.

DOI： 10.1038/bjc.2013.830

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：URBAN & VOGEL  

Purpose. The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma.
Methods and materials. In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors.
Results. Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment.
Conclusion. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma.

DOI： 10.1007/s00066-013-0468-1

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer.
Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m(2); CDDP, total 100-150 mg/m(2)) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks.
Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971; 1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively.
Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3 metastatic lymph nodes experienced a high rate of distant metastases. (C) 2012 Elsevier Inc.

DOI： 10.1016/j.ijrobp.2012.02.057

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Sirtuin proteins regulate diverse cellular pathways that influence genomic stability, metabolism and ageing(1,2). SIRT7 is a mammalian sirtuin whose biochemical activity, molecular targets and physiological functions have been unclear. Here we show that SIRT7 is an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase that stabilizes the transformed state of cancer cells. Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. The spectrum of SIRT7 target genes is defined in part by its interaction with the cancer-associated E26 transformed specific (ETS) transcription factor ELK4, and comprises numerous genes with links to tumour suppression. Notably, selective hypoacetylation of H3K18Ac has been linked to oncogenic transformation, and in patients is associated with aggressive tumour phenotypes and poor prognosis(3-6). We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells, including anchorage-independent growth and escape from contact inhibition. Moreover, SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by the viral oncoprotein E1A. Finally, SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice. Together, our work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs and tumour formation in vivo.

DOI： 10.1038/nature11043

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CELL PRESS  

The histone lysine methyltransferase NSD2 (MMSET/WHSC1) is implicated in diverse diseases and commonly overexpressed in multiple myeloma due to a recurrent t(4;14) chromosomal translocation. However, the precise catalytic activity of NSD2 is obscure, preventing progress in understanding how this enzyme influences chromatin biology and myeloma pathogenesis. Here, we show that dimethylation of histone H3 at lysine 36 (H3K36me2) is the principal chromatin-regulatory activity of NSD2. Catalysis of H3K36me2 by NSD2 is sufficient for gene activation. In t(4;14)-positive myeloma cells, the normal genome-wide and gene-specific distribution of H3K36me2 is obliterated, creating a chromatin landscape that selects for a transcription profile favorable for myelomagenesis. Catalytically active NSD2 confers xenograft tumor formation upon t(4;14)negative cells and promotes oncogenic transformation of primary cells in an H3K36me2-dependent manner. Together, our findings establish H3K36me2 as the primary product generated by NSD2 and demonstrate that genomic disorganization of this canonical chromatin mark by NSD2 initiates oncogenic programming.

DOI： 10.1016/j.molcel.2011.08.042

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background: 5-Fluorouracil (5-FU) is widely used in the treatment of head and neck squamous cell carcinoma (HNSCC). However, development of drug resistance is one of the major causes of HNSCC treatment failure. The goal of this study was to investigate the mechanism of 5-FU resistance and to develop a novel combination therapy with another agent which sensitizes cells to 5-FU. Materials and Methods: A 5-FU-resistant cell line, UM-SCC-23F/R, was developed from UM-SCC-23 cells. We determined sensitivities to 5-FU, etodolac and a combination treatment and also analyzed the expressions of cyclooxygenase-2 (COX-2) and thymidylate synthase (TS). Results: Selective COX-2 inhibitor, etodolac, sensitized UM-SCC-23F/R cells to 5-FU. Expression of COX-2 decreased after etodolac treatment in both cell lines. While overexpression of TS was observed in UM-SCC-23F/R cells, etodolac inhibited TS expression, suggesting that the sensitizing effect induced by etodolac depends on TS suppression. Conclusion: We demonstrate for the first time an important inhibitory effect of etodolac on TS expression leading to sensitization to 5-FU in 5-FU-resistant cells. Our data suggest that TS inhibition can be accomplished by this routinely used nonsteroidal anti-inflammatory drug, and this may have a role as novel effective cancer treatment for 5-FU-resistant cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC CLINICAL INVESTIGATION INC  

Despite the high doses of radiation delivered in the treatment of patients with glioblastoma multiforme (GBM), the tumors invariably recur within the irradiation field, resulting in a low cure rate. Understanding the mechanism of such recurrence is therefore important. Here we have shown in an intracranial GBM xenograft model,that irradiation induces recruitment of bone marrow-derived cells (BMDCs) into the tumors, restoring the radiation-damaged vasculature by vasculogenesis and thereby allowing the growth of surviving tumor cells. BMDC influx was initiated by induction of HIF-1 in the irradiated tumors, and blocking this influx prevented tumor recurrence. Previous studies have indicated that BMDCs are recruited to tumors in part through the interaction between the HIF-1-dependent stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4. Pharmacologic inhibition of HIF-1 or of the SDF-1/CXCR4 interaction prevented the influx of BMDCs, primarily CD11b(+) myelomonocytes, and the postirradiation development of functional tumor vasculature, resulting in abrogation of tumor regrowth. Similar results were found using neutralizing antibodies against CXCR4. Our data therefore suggest a novel approach for the treatment of GBM: in addition to radiotherapy, the vasculogenesis pathway needs to be blocked, and this can be accomplished using the clinically approved drug AMD3100, a small molecule inhibitor of SDF-1/CXCR4 interactions.

DOI： 10.1172/JCI40283

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：6  

Interleukin-13 receptor-targeted cytotoxin (IL13-PE38) is highly cytotoxic to certain types of human cancers expressing abundant levels of IL-13Ralpha2 chain. Although IL13-PE38 is being tested in a Phase III clinical trial in brain tumors, the activity of IL13-PE38 alone or when combined with taxane, a chemotherapeutic drug for oral squamous cell carcinoma (OSCC), has not been investigated. Here, we show that approximately 40% of OSCCs (n = 50) in a tissue array are strongly positive for IL-13Ralpha2, whereas normal oral mucosa (n = 10) expresses very low or undetectable levels evaluated by immunohistochemistry. IL13-PE38 was highly cytotoxic to OSCC cell lines, but not cytotoxic to normal oral fibroblasts. IL13-PE38 mediated a synergistic antitumor effect with paclitaxel in OSC-19 in vitro and in vivo in the orthotopic OSCC tongue tumor model. Real-time tumor growth was monitored by optical imaging using a Xenogen-IVIS imaging system. Treated animals showed significant (p < 0.05) improvement in survival, which correlated with in vivo imaging of tumor response without evidence of visible toxicity. Gene transfer of IL-13Ralpha2 in oral cancer cells increased sensitivity of OSCC cell line to IL13-PE38 in vitro. Retrovirus-mediated gene-transfer of IL-13Ralpha2 in HSC-3 into tongue tumors in vivo dramatically enhanced the antitumor activity of IL13-PE38, providing complete elimination of established tumors and prolonging survival of these animals. These results indicate that IL13-PE38 in combination with paclitaxel acting via different mechanisms may be a potential treatment option for IL-13Ralpha2 expressing OSCC or for the treatment of non-IL-13Ralpha2 expressing OSCC combined with gene transfer of IL-13Ralpha2.

DOI： 10.1002/ijc.24067

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Human head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy. Identification of unique or overexpressed cell-associated or cell surface antigens is critical for diagnosis and development of cancer vaccines and targeted therapies for HNSCC. We have used high throughput microarray technology to search for candidate targets in HNSCC.
Methods: Gene expression profiling in 17 HNSCC tumors and 3 normal tonsil tissues was performed by microarray. QRT-PCR analysis was performed to validate the microarray results. The five candidate genes were further characterized by immunohistochemical technique in surgical samples and tissue arrays.
Results: A total of 192 up-regulated genes at statistical significance of p &lt; 0.01 and log2 ratio &gt;= 1 were identified in HNSCC tumors compared to normal tissues. These genes belong to immune response, cell growth, cell cycle regulation, oncogenes, metabolism and others. Five potential novel target genes (FABP5, CD24, CD44, CD74, and HSP27) were identified, which were highly expressed in HNSCC tumor samples and tissue arrays. CD24, CD44, and CD74 proteins were expressed on the cell surface, and FABP5 and HSP27 proteins were predominantly expressed in the cytoplasm of HNSCC.
Conclusion: Five genes and their products may serve as a diagnostic biomarker or therapeutic target for HNSCC. While additional work is needed to elucidate the biological significance of these proteins, CD24 and CD74 expressed only in small proportion of cells indicating tumor heterogeneity and subtypes of tumor initiating cells (CD24+/CD44+) present in HNSCC.

DOI： 10.1186/1758-3284-1-27

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC IMMUNOLOGISTS  

Nonalcoholic steatohepatitis (NASH), the most common cause of chronic liver fibrosis, progresses to cirrhosis in up to 20% of patients. We report that hepatic stellate cells (HSC) in sinusoidal lesions of liver of patients with NASH express high levels of high-affinity IL-13R (IL-13R alpha 2), which is colocalized with smooth muscle actin, whereas fatty liver and normal liver specimens do not express IL-13R alpha 2. HSCs engineered to overexpress IL-13R alpha 2 respond to IL-13 and induce TGFBI promoter activity and TGF-beta 1 production. We also developed NASH in rats by feeding a choline-deficient L-amino acid diet. These rats developed liver fibrosis as assessed by H&E staining, Masson's trichrome and Sirius red staining, and hydroxyproline assays. Treatment of these rats with IL-13R-directed cytotoxin caused a substantial decline in fibrosis and liver enzymes without organ toxicity. These studies demonstrate that functional IL-13R alpha 2 are overexpressed in activated HSCs involved in NASH and that IL-13 cytotoxin ameliorates pathological features of NASH in rat liver, indicating a novel role of this cytotoxin in potential therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

We have previously shown that spores of the nonpathogenic clostridial strain C. sporogenes genetically engineered to express the E. coli-derived cytosine deaminase gene are effective in converting systemically injected nontoxic 5-fluorocytosine into the toxic anticancer drug 5-fluorouracil, thereby producing tumor-specific antitumor activity. To improve the expression of E. coli-derived genes with this system, we first replaced the original fdP promoter in the vector with one of two powerful endogenous clostridial promoters: that of the thiolase gene (thlP) and that for the clostridial transcription factor abrB310 (abrBP). These substitutions improved protein expression levels of the prodrug-activating genes by 2- to 3-fold in comparison with fdP-driven expression. However, despite these strong promoters, we found much higher expression of the nitroreductase (NTR) protein in the E. coli host compared with the clostridial host, which we hypothesized could be the result of different codon use between the two organisms. To test this, we constructed new expression vectors with an artificially synthesized NTR gene using optimized clostridial codons (sNTR). Results from both enzymatic assays and Western blots of cell extracts from clostridial transformants harboring plasmid constructs of thlP-sNTR and abrBP-sNTR showed that the expression and activity of the NTR gene product was increased by similar to 20-fold compared with the original construct. In vivo studies with i.v. administered sNTR-expressing C. sporogenes spores in SiHa tumor-bearing mice showed significantly improved antitumor efficacy when combined with either 5-aziridinyl-2,4-dinitrobenzamide (CB1954) or the novel dinitrobenzamide mustard prodrug, PR-104.

DOI： 10.1158/0008-5472.CAN-08-1698

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Anaplasma phagocytophilum (Ap), the etiologic agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. We define and compare the spectra of host gene expression in response to Ap infection of human neutrophils and of HL-60 cells using long (70-mer)-oligonucleotide array technology. In addition to apoptosis-related genes, genes involved in signaling pathways, transcriptional regulation, immune response, host defense, cell adhesion, and cytoskeleton were modulated in neutrophils infected with Ap. Ap infection affected the same pathways in HL-60 cells but transcriptional changes occurred more slowly and in a reduced spectrum of genes. Gene expression changes detected by microarray were confirmed for randomly selected genes by QRT-PCR and Western blot studies. These studies demonstrate for the first time that the ERK pathway is activated in Ap-infected neutrophils and also define multiple pathways that are activated during intracellular Ap infection, which together serve to prolong the cell survival that is needed to allow bacterial replication and survival in neutrophils, which otherwise would rapidly apoptose. Published by Elsevier Inc.

DOI： 10.1016/j.ygeno.2008.05.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

We have shown previously that high-affinity receptors for interleukin-13 (IL-11R alpha 2) are overexpressed on a variety of solid cancer cells, diseased fibroblasts, and other cells, and a chimeric fusion protein composed of human IL-13 and mutated Pseudomonas exotoxin (IL-13-PE38) is highly and specifically cytotoxic to these cells in vitro and in vivo. To improve the specificity for the target, we isolated specific antibodies against IL-13R alpha 2 from human single-chain Fv (scFv) antibody phage library and developed immunotoxin by selecting two high-affinity clones of scFv and fused to PE. The fusion chimeric gene was expressed in Escherichia coli, and highly purified IL-13R-specific immunotoxin, termed anti-IL-13R alpha 2(scFv)-PE38, was tested for its cytotoxicity. This molecule was highly cytotoxic to U251 glioma and PM-RCC renal cell carcinoma cell lines in vitro. The cytotoxic activity was neutralized by purified extracellular domain of IL-13R alpha 2 but not by IL-13, indicating that cytotoxic activity is specific. Anti-IL-13R alpha 2(scFv)-PE38 showed significant antitumor activity in immuno-deficient mice with s.c. glioma tumors. Both i.p. and i.t. routes of administration showed antitumor activity in a dose-dependent manner. The maximum tolerated dose of anti-IL-13R alpha 2(scFv)-PE38 was 200 mu g/kg i.p. twice daily for 5 days. These results indicate that anti-IL13R alpha 2(scFv)-PE38 is a highly selective therapeutic agent for cancer therapy and should be further tested in animal models of human cancer.

DOI： 10.1158/1535-7163.MCT-07-2131

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomycescerevisiae(1,2). In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing- like phenotype(3). However, the molecular mechanisms of SIRT6 function are unclear. SIRT6 is a chromatin- associated protein(3), but no enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown. Here we show that the human SIRT6 protein is an NAD(+)-dependent, histone H3 lysine 9 ( H3K9) deacetylase that modulates telomeric chromatin. SIRT6 associates specifically with telomeres, and SIRT6 depletion leads to telomere dysfunction with end- to- end chromosomal fusions and premature cellular senescence. Moreover, SIRT6- depleted cells exhibit abnormal telomere structures that resemble defects observed in Werner syndrome, a premature ageing disorder(4,5). At telomeric chromatin, SIRT6 deacetylates H3K9 and is required for the stable association of WRN, the factor that is mutated in Werner syndrome(4,5). We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function. Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome.

DOI： 10.1038/nature06736

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Targeting cell surface receptors with cytotoxins or immunotoxins provides a unique opportunity for tumor therapy. Here, we show the efficacy of the combination therapy of gemcitabine with an interleukin-4 (IL-4) cytotoxin composed of IL-4 and truncated Pseudomonas exotoxin in animal models of pancreatic ductal adenocarcinoma (PDA). We have observed that 42 of 70 (60%) tumor samples from patients with PDA express moderate- to high-density surface IL-4 receptor (11,411), whereas normal pancreatic samples express no or low-density IL-4R. IL-4 cytotoxin was specifically and highly cytotoxic [50% protein synthesis inhibition (IC50) ranging from &gt;0.1 to 13 ng/mL] to six of eight pancreatic cancer cell lines, whereas no cytotoxicity (IC50 &gt;1,000 ng/mL) was observed in normal human pancreatic duct epithelium cells, fibroblasts, and human umbilical vein endothelial cells (HUVEC). We also showed that IL-4 cytotoxin in combination with gemcitabine exhibited synergistic antitumor activity in vitro. To confirm synergistic antitumor activity in vivo and monitor precise real-time disease progression, we used a novel metastatic and orthotopic mouse model using green fluorescent protein-transfected cancer cells and whole-body imaging system. The combination of both agents caused complete eradication of tumors in 40% of nude mice with small established PDA tumors. In addition, combined treatment significantly prolonged the survival of nude mice bearing day 14 advanced distant metastatic PDA tumors. Similar results were observed in mice xenografted with PDA obtained from a patient undergoing surgical resection. These results indicate that IL-4 cytotoxin combined with gemcitabine may provide effective therapy for the treatment of patients with PDA.

DOI： 10.1158/0008-5472.CAN-06-4558

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FEDERATION AMER SOC EXP BIOL  

A high-affinity receptor for interleukin (IL)-13 (interleukin-13R alpha 2) is over-expressed in disease-related fibroblasts and neoplastic cells and is involved in cancer, allergic, and inflammatory diseases. The extracellular domain of IL-13R alpha 2 (ECD alpha 2) could be cleaved, which serves as a decoy receptor. We have expressed and purified ECD alpha 2 in both Escherichia coli ( E. coli) and mammalian systems as a soluble fragment and studied its biological activities. Although both products of ECD alpha 2 showed IL-13 inhibitory activities, mammalian cell-derived ECD alpha 2 appeared to be superior compared with purified protein from E. coli. When expressed in E. coli, ECD alpha 2 appeared to be a monomer of 42 but a 60 kDa protein when purified from mammalian cells due to heavy glycosylation. The purified glycosylated ECD alpha 2 efficiently inhibited IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines, IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines. The improved potency of mammalian cell-derived ECD alpha 2 was shown over ECD alpha 2/Fc fusion protein. The N-linked glycosylation of ECD alpha 2 was found to be essential for optimal IL-13 inhibitory activity as deglycosylation by PNGase F showed lower activity. ECD alpha 2 did not inhibit IL-4-induced STAT6 phosphorylation, indicating that inhibitory effects of ECD alpha 2 are receptor specific. These results indicate that glycosylated ECD alpha 2 can serve as a potent inhibitor of IL-13 in a variety of conditions in which IL-13 is a key mediator, e. g., pulmonary, allergic, fibrotic, and neoplastic diseases.

DOI： 10.1096/fj.06-5995fje

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS INC  

BACKGROUND. Epithelial ovarian cancer demonstrates high mortality due to diagnosis at an advanced stage. In the search for a biomarker for early diagnosis and a target for therapy, the issue of whether interleukin-13 receptor (IL-13R), shown to be expressed on a variety of human cancers, is expressed in ovarian tumor samples was explored. In addition, whether this receptor serves as a biomarker and can be targeted by IL-13 cytotoxin was examined.
METHODS. IL-13R expression in 15 normal and 68 ovarian tumor tissue samples was determined by immunohistochemistry. Correlation between clinicopathologic features and IL-13R expression was analyzed. The efficacy of IL-13R-directed cytotoxin was determined in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer.
RESULTS. Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express IL-13R alpha 2, a high-affinity IL-13R subunit chain, whereas normal ovary samples expressed none or very low levels. The majority of clear cell ovarian carcinomas with the worst prognosis showed strong staining for IL-13R alpha 2. IL-13 cytotoxin was highly cytotoxic to the IGROV-1 ovarian cancer cell line in vitro, and it mediated significant antitumor activity against a xenografted tumor model. The antitumor effects were confirmed by treating orthotopically implanted or peritoneal metastatic ovarian tumors, which showed significant extension of survival in immunodeficient mice. IL-13 cytotoxin also prevented cachexia in treated mice. The soluble form of IL-13R alpha 2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group.
CONCLUSIONS. IL-13R alpha 2 is a promising target for ovarian cancer therapy, and the soluble form of IL-13R may be a possible surrogate marker for disease monitoring.

DOI： 10.1002/cncr.22134

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Purpose: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13R alpha 2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response.
Experimental Design: To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13R alpha 2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only.
Results and Conclusions: When animals with IL-13R alpha 2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13R alpha 2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8(+) and CD4(+) T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8(+) T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response.

DOI： 10.1158/1078-0432.CCR-06-0192

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記述言語：英語   出版者・発行元：ADENINE PRESS  

The treatment of patients with malignant brain tumors, in particular glioblastoma multiforme (GBM) is very challenging because of their diffuse infiltrative nature and the cytological heterogeneity. The median survival of patients with newly diagnosed GBM is only 12-15 months, and only 8-12% of them survive for two years. Novel approaches for brain tumor therapy are needed. Recently, targeted therapies have emerged as promising modality for cancer targeting. We have discovered that high affinity plasma membrane receptor for interleukin-13 (IL-13), an immune regulatory cytokine, is over-expressed in 60-80% of malignant brain tumors. To target these IL-13R, we generated a chimeric fusion protein, composed of human IL-13 and mutated Pseudomonas exotoxin (PE), termed IL-13 cytotoxin (1L-13-PE), and tested its cytotoxicity to IL-13R-expressing GBM cells. IL-13 cytotoxin was highly potent and selective in killing IL-13R-expressing GBM cells. In contrast, normal cells including brain, immune, and endothelial cells were generally not affected by this cytotoxin due to no or low expression of IL-13R. In vivo pre-clinical studies for safety and toxicity were also performed in mice, rats, and monkeys, and IL-13 cytotoxin was found to be well tolerated by both systemic and intracerebral administrations. IL-13 cytotoxin was found to mediate remarkable efficacy in animal models of human brain tumors. Encouraged by these pre-clinical studies, four Phase 1/2 clinical trials in adult patients with recurrent malignant glioma have been completed. These clinical trials involved convection-enhanced delivery (CED) of IL-13 cytotoxin either intratumoral or intraparenchymal after resection of tumor. CED is a novel loco-regional drug delivery method for intracranial tumors that relies on a continuous pressure gradient to distribute drug into interstitial space. This route of IL-13 cytotoxin administration appears to be very well tolerated and have a good risk-benefit profile. Most recently, a randomized controlled Phase 3 clinical trial (PRECISE) with intraparenchymal IL-13 cytotoxin administration was completed and subjects are being monitored for safety and survival.

DOI： 10.1177/153303460600500307

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Regulation of cell surface molecules by matrix metalloproteinases (MMPs), as well as MMPs-catalyzed degradation of extracellular matrix, is important for tumor invasion and metastasis. Our previous study (Kioi, M., Yamamoto, K., Higashi, S., Koshikawa, N., Fujita, K., and Miyazaki, K. (2003) Oncogene 22, 8662-8670) demonstrated that active matrilysin specifically binds to the surface of colon cancer cells and induces notable cell aggregation due to processing of the cell membrane protein(s). Furthermore, these aggregated cells showed a dramatically enhanced metastatic potential. To elucidate the mechanism of matrilysin-induced cell aggregation, we attempted to identify the matrilysin-binding substance on the cell surface. Here, we demonstrate that cholesterol sulfate on the cell surface is a major matrilysin-binding substance. We found that active matrilysin bound to the cell membrane and cholesterol sulfate incorporated into liposomes with similar affinities. Treatment of colon cancer cells with beta-cyclodextrin significantly reduced not only matrilysin binding to the cell surface but also matrilysin-dependent proteolysis and cell aggregation. Interestingly, replenishment of cholesterol sulfate, but not cholesterol, neutralized the effects of beta-cyclodextrin. Taken together, it is likely that binding of matrilysin to cholesterol sulfate facilitates the matrilysin-catalyzed modulation of cell surface proteins, thus inducing the cancer cell aggregation.

DOI： 10.1074/jbc.M510377200

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Because the most characteristic property of ovarian cancer is i.p. spread, the majority of patients are diagnosed at an advanced stage, leading to limited availability of options for curative therapies. With an intent to identify targeted therapeutic approaches, we have observed that similar to 60% of 21 ovarian cancer tissue samples express a high density of interleukin-4 receptor (IL-4R), whereas normal ovarian tissues tested (n = 7) expressed no or low levels of IL-4R. To target IL-4R, we have developed IL-4 cytotoxin, in which circular-permuted IL-4 is fused to a mutated form of Pseudomonas exotoxin. This cytotoxin is specifically and highly cytotoxic to PA-1, IGROV-1, and SK-OV3 ovarian carcinoma cell lines in vitro. In addition, it shows remarkable antitumor activities against established s.c. ovarian tumors in immunodeficient animals. i.p. administration of IL-4 cytotoxin in mice with orthotopically implanted ovarian tumors caused regression of established tumors and prevented these animals from tumor metastasis. Continuous i.p. infusion of IL-4 cytotoxin prolonged survival of tumor-bearing mice even with bulky disease. These results indicate that IL-4R-targeted cytotoxin may be a useful agent for the management of patients with ovarian cancer, and further studies need to be done to evaluate its safety, tolerability, and efficacy.

DOI： 10.1158/0008-5472.CAN-05-1043

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

The interleukin-13 receptor alpha 2 (IL-13R alpha 2) chain is a primary IL-13 binding and internalization component of the IL-13R system. Previous studies have shown that human brain tumors, including glioblastoma multiforme (GBM), overexpress IL-13R alpha 2 chain, while normal brain cells do not express this protein or express very low levels of it. To target IL-13R on brain tumor cells, the authors have developed an IL-13R-directed cytotoxin termed IL13-PE38QQR to induce specific cancer cell killing. To investigate the role of IL-13R alpha 2 chain in GBM, cells were treated with antisense oligonucleotide or siRNA to IL-13R alpha 2 chain, and cellular IL-13 binding and sensitivity to IL-13 cytotoxin were assessed. IL-13R alpha 2 gene interference in GBM cells showed decreased ligand binding, and consequently IL-13 cytotoxin exhibited less cytotoxicity to these cells. The authors next evaluated the antitumor activity of IL-13 cytotoxin in native IL-13R-expressing tumors and after gene transfer of IL-13R alpha 2 by injecting plasmid in U87MG tumors subcutaneously implanted in nude mice. These mice were then treated with IL-13 cytotoxin. Mean tumor size in mice receiving intraperitoneal or intratumoral IL-13 cytotoxin was significantly smaller in control tumors; however, tumor sizes were much smaller in IL-13R alpha 2-transfected tumors. Furthermore, convection-enhanced delivery of IL-13Ra2 cDNA in intracranially established U87MG glioma followed by IL-13 cytotoxin administration by the same route mediated tumor regression and prolonged survival of animals by 164% compared with control. These results indicate that IL-13R alpha 2 chain in GBM cells is essential for IL-13 cytotoxin-induced cytotoxicity and that IL-13R alpha 2 chain plays a critical biologic role in IL-13 cytotoxin-mediated therapy for GBM.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC HEMATOLOGY  

Hodgkin lymphoma represents unique clinicopathologic features because Hodgkin and Reed-Sternberg (H-RS) cells produce a variety of cytokines, express a variety of cytokine receptors, and are surrounded by numerous nonmalignant immunoreactive cells. We found that receptors for interleukin-4 (IL-4R) are highly expressed in H-RS cells. To target interleukin-4 receptor (IL-4R), we used a recombinant protein fusing circularly permuted human IL-4 and Pseudomonas exotoxin termed IL4(38-37)-PE38KDEL, or IL-4 cytotoxin. The cytotoxic effect of IL-4 cytotoxin on H-RS cell lines was determined to be moderate to high in vitro. We developed an infiltrating model of Hodgkin disease (HD) by injecting an adherent population of HDMyZ cells subcutaneously into the flanks of beige/nude/X-linked immunodeficient mice. The animal model exhibited spontaneous metastasis of H-RS cells to lymph nodes and dissemination to vital organs, including the lungs. Intraperitoneal or intratumoral treatment of these mice with IL-4 cytotoxin resulted in regression of the primary tumor mass and a decrease in the incidence of lymph node metastasis. Mice injected with HD-MyZ cells demonstrated 203% prolonged survival (mean survival, 63 days) compared with control (mean survival, 31 days) when they received systemic IL-4 cytotoxin treatment. Because numerous H-RS cell lines express receptors for IL-4, IL-4 cytotoxin may be a unique agent for the treatment of Hodgkin lymphoma.

DOI： 10.1182/blood-2004-08-3216

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS  

Object. Interleukin-13 receptor (IL-13R)-targeted cytotoxin (IL-13-PE38) displays a potent antitumor activity against a variety of human tumors including glioblastoma multiforme (GBM) and, thus, this agent is being tested in the clinical trial for the treatment of recurrent GBM. In this study, the authors determined the safety and distribution kinetics of IL-13 cytotoxin when infused intracranially by a bolus injection and by convection-enhanced delivery (CED) in an athymic nude mouse model of GBM.
Methods. For the safety studies, athymic nude mice were given intracranial infusions of IL-13 cytotoxin into normal parenchyma by either a bolus injection or a 7-day-long CED. Toxicity was assessed by performing a histological examination of the mouse brains. For the drug distribution studies, nude mice with intracranially implanted U251 GBM tumors were given an intratumor bolus or a CED infusion of IL-13 cytotoxin. Brain tumor samples obtained between 0.25 and 72 hours after the infusion were assessed for drug distribution kinetics by performing immunohistochemical and Western blot analyses.
Based on the histological changes in the tumor and brain, the maximum tolerated dose of intracranial IL-13 cytotoxin infusion in nude mice was determined to be 4 mug when delivered by a bolus injection and 10 mug when CED was used. Drug distribution reached the maximum level I hour after the bolus injection and the volume of distribution was determined to be 19.3 +/- 5.8 mm(3). Interleukin-13 cytotoxin was barely detectable 6 hours after the injection. Interestingly, when delivered by bolus injections IL-13 cytotoxin exhibited superior distribution in larger rather than smaller tumors. Convection-enhanced delivery was superior for drug distribution in the U251 tumors because when CED was used the drug remained in the tumors 6 hours after the infusion.
Conclusions. These studies provide confirmation of a previous hypothesis that CED of IL-13 cytotoxin is superior to bolus injections not only for the safety of the normal brain but also for maintaining drug levels for a prolonged period in infused brain tumors. These findings are highly relevant and important for the optimal clinical development of IL-13 cytotoxin or any other targeted antitumor agent for GBM therapy, in which multiple routes of delivery of an agent are being contemplated.

DOI： 10.3171/jns.2004.101.6.1004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

We have shown previously that a chimeric fusion protein composed of human interleukin-13 (IL-13) and Pseudomonas exotoxin (PE), termed IL-13 cytotoxin (IL13-PE38), is specifically cytotoxic to various cancer cell lines and primary cell cultures derived from a variety of solid cancers. In addition, we have shown that IL-13 mutant IL-13E13K, in which glutamic acid (E) residue at position 13 of IL-13 molecule was substituted by a lysine (K), is a powerful antagonist of IL-13 and binds to IL-13 receptor with a higher affinity compared with wild-type IL-13. In this study, we have generated an IL-13 cytotoxin IL13E13K-PE38, in which IL-13 antagonist is fused to PE to determine whether this molecule has improved cytotoxicity to tumor cells compared with wild type (wt)IL13-PE38. Highly purified IL13E13K-PE38 was tested in various tumor cell lines including seven glioblastoma multiforme cell lines to compare its binding to the cells, in vitro cytotoxicity, in vivo antitumor activity, and safety in mouse model with wtIL13-PE38. IL13E13K-PE38 bound to U251MG and IL-13Ralpha2 chain-transfected tumor cell lines with 3 to 10 times higher affinity compared with wtIL13-PE38.. However, IL13E13K-PE38 did not show higher cytotoxicity compared with wtIL13PE38 in glioblastoma multiforme or any other cell lines tested. The antitumor activity of IL13E13K-PE38, when administered intraperitoneally to nude mice bearing U251 tumors, was also similar to wtIL13-PE38. Some improvement in antitumor activity was observed when lower doses of IL13E13K-PE38 were injected intratumorally in subcutaneous tumors. These results indicate that in general, IL13E13K-PE38 mediates similar cytotoxicity and antitumor activity to wtIL13-PE38 despite its improved binding affinity to IL-13 receptors.

DOI： 10.1158/1078-0432.CCR-04-0700

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

As interleukin (IL)-13 and IL-4 play a major role in various diseases including asthma, allergy, and malignancies, it is desirable to generate a molecule that blocks the effects of both cytokines. We previously generated a human IL-13 mutant (IL-13E13K), which is a powerful antagonist of IL-13, blocking the biological activities of IL-13. We now show that IL-13E13K also competitively inhibits signaling and biological activities of IL-4 through type 11 and partially through type III IL-4 receptor (R) system. IL-13E13K completely blocked the IL-4-induced phosphorylation of STAT6 and IL-4-dependent protein synthesis in cells expressing type 11 and partially type Ill IL-4R but not type I IL-4R. Consistent with the inhibition of biological activities, IL-13E13K inhibited IL-4 binding to type 11 IL-4R-expressing cells but not to type I IL-4R-expressing cells. The inhibition efficiency of IL-4 binding by IL-13E13K was relatively lower compared to wtIL-13 even though IL-13E13K bound to IL-13Ralpha1 positive cells with a similar affinity to IL-4Ralpha. These results indicate that Glu 13 in IL- 13 associates with IL-4Ralpha, and mutation to lysine decreases its binding ability to IL-4Ralpha chain. IL-13E13K binds to IL-13Ralpha1, which is shared by both IL-13R and IL-4R systems. Consequently, IL-13E13K inhibits IL-4 binding to these cells and prevents heterodimer formation between IL-13Ralpha1 and IL-4Ra chains. This interference by IL-13E13K blocks the biological activities of not only IL-13 but also partially of IL-4. Thus, IL-13E13K may be a useful agent for the treatment of diseases such as asthma, allergic rhinitis, and cancer, which are dependent on signaling through both IL-4 and IL-13 receptors. Published by Elsevier Inc.

DOI： 10.1016/j.cellimm.2004.06.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Matrilysin (MMP-7) is thought to contribute to invasive growth and metastasis of colon carcinoma and many other human cancers. The present study demonstrates that treatment of human colon carcinoma cells with active matrilysin induces cell aggregation in vitro and promotes liver metastasis in nude mice. When two kinds of colon carcinoma cell lines were incubated with active matrilysin, this enzyme efficiently bound to the cell surface and induced loose cell aggregation, which led to E-cadherin-mediated tight cell aggregation. Synthetic MMP inhibitors inhibited both the membrane binding of matrilysin and matrilysin-induced cell aggregation, while TIMP-2 inhibited only the cell aggregation. Two other active MMPs, stromelysin and gelatinase A, neither bound to cell membrane nor induced cell aggregation. Tumor cells in loose cell aggregates could reaggregate even after they were freed from matrilysin and dispersed. When injected into the spleen of nude mice, the tumor cells in the stable aggregates produced much larger metastatic nodules in the livers than control cells and those in the loose aggregates. These results suggest that matrilysin may enhance metastatic potential of tumor cells by processing a cell surface protein(s) and thereby inducing loose and then tight aggregation of tumor cells.

DOI： 10.1038/sj.onc.1207181

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記述言語：日本語   出版者・発行元：(一社)歯科基礎医学会  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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© 2019 Wiley Periodicals, Inc. Background: The aim of this study was to evaluate the prognostic factors and treatment outcomes of advanced maxillary gingival squamous cell carcinoma (SCC) treated with intra-arterial infusion chemotherapy concurrent with radiotherapy. Methods: A total of 46 patients were reviewed retrospectively in this study. The treatment schedule comprised intra-arterial chemotherapy (total, 60 mg/m2 docetaxel and 150 mg/m2 cisplatin) and three-dimensional computed tomography based, daily conventional radiotherapy (total, 60 Gy/30 fr) for 6 weeks. Results: The median follow-up period was 40 months (range, 3-110 months). The 3-year overall survival and locoregional control rates for all patients were 64.3% and 84.3%, respectively. The OS rate of the patients with N0-1 was significantly higher than that of the patients with N ≥ 2 (P &lt;.05). No grade 5 toxicities were observed. Conclusions: Intra-arterial infusion chemotherapy concurrent with radiotherapy was effective for advanced maxillary gingival SCC.

DOI： 10.1002/hed.25607

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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© 2019 Novin Medical Radiation Institute. All rights reserved. Background: The aim of this retrospective study was to evaluate the therapeutic outcomes and organ preservation in patients with squamous cell carcinoma of the buccal mucosa treated with radiotherapy and retrograde superselective intra-arterial chemotherapy. Materials and Methods: Between April 2006 and March 2016, 28 patients (3 with stage II; 8 with stage III; and 17 with stage IV) with squamous cell carcinoma of the buccal mucosa were treated with definitive intra-arterial chemoradiotherapy. The median follow-up for all patients was 39months (range, 4-123months). Catheterization of the tumor feeding arteries from the superficial temporal and/or occipital arteries was performed. Treatment consisted of radiotherapy (total 50-70 Gy) and daily concurrent superselective intra-arterial chemotherapy (docetaxel, 50-70 mg/m2, cisplatin, total 125-175 mg/ m2) for 5-7 weeks. Results: After intra-arterial chemoradiotherapy, primary site complete response was achieved in 25 (89.3%) of 28 cases. Three-year local control and overall survival rates were 82.1% and 85.4%, respectively. Grade 3 or 4 toxicities included mucositis in 96.4%, and dermatitis in 28.6% of patients. Grade 3 toxicities included dysphagia in 35.7%, neutropenia in 28.6%, anemia in 10.7%, and fever in 7.1% of patients. Conclusion: Retrograde superselective intra-arterial chemoradiotherapy for squamous cell carcinoma of the buccal mucosa provided good local control and overall survival.

DOI： 10.18869/acadpub.ijrr.17.2.283

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

正中の進行上顎歯肉癌で鼻部に至る場合の拡大手術は顔面皮膚欠損及び口腔機能の障害を伴い、quality of lifeの低下を引き起こす。今回われわれは上唇から鼻部に及ぶ局所進行正中上顎歯肉癌に対し4経路を用いた超選択的動注化学放射線治療を施行した。患者36歳、男性。上顎歯肉癌(T4aN1M0)。患者は手術拒否であったため、4経路を使用した逆行性超選択的動注化学放射線治療(照射total 70Gy、docetaxelをtotal 70mg/m2、cisplatinをtotal 175mg/m2)を施行した。加えて、頸部リンパ節転移に対するハイパーサーミアを週1回、計6回行なった。治療後、腫瘍原発の治療効果判定はCRを得たため原発切除を回避した。治療後58ヵ月経過し現在まで再発・転移なく経過している。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01499&link_issn=&doc_id=20190603300004&doc_link_id=http%3A%2F%2Fid.nii.ac.jp%2F1246%2F00001567%2F&url=http%3A%2F%2Fid.nii.ac.jp%2F1246%2F00001567%2F&type=%89%A1%95l%8Es%97%A7%91%E5%8Aw%81F%89%A1%95l%8Es%97%A7%91%E5%8Aw%8Aw%8Fp%8B%40%8A%D6%83%8A%83%7C%83W%83g%83%8A&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   出版者・発行元：Elsevier Ltd  

Objective: We previously reported that daily concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion for locally advanced oral cancer provided good local control and overall survival rates. This study was performed to evaluate the therapeutic results of daily concurrent intra-arterial chemoradiotherapy for patients with locally advanced squamous cell carcinoma of the mandibular gingiva. Methods: Sixteen patients with T3, 4 mandibular gingiva cancer who refused surgery underwent definitive intra-arterial chemoradiotherapy between August 2006 and July 2014. Treatment consisted of concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion (60 Gy, total dose
60 mg/m2 for docetaxel and 150 mg/m2 for cisplatin). Results: Complete response of the primary site was obtained in 14 patients (87.5%). Five-year local control and survival rates were 73.4%and 81.3%, respectively. Grade 3 or 4 toxicities including mucositis and neutropenia were seen in 13 patients (81.3%) and 6 patients (37.5%), respectively. Grade 3 osteoradionecrosis occurred as a late adverse event in 1 patient (6.3%). Conclusions: Retrograde daily concurrent intra-arterial chemoradiotherapy for locally advanced carcinoma of the mandibular gingiva provided good local control and overall survival rates. This method can become one of the therapeutic options for patients with locally advanced carcinoma of the mandibular gingiva.

DOI： 10.1016/j.ajoms.2018.05.002

Scopus

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01072&link_issn=&doc_id=20170802480007&doc_link_id=10.11277%2Fstomatology.66.65&url=https%3A%2F%2Fdoi.org%2F10.11277%2Fstomatology.66.65&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

DOI： 10.5794/jjoms.63.178

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

逆行性超選択的動注化学放射線療法を施行した口腔癌160例(男性100名、女性60名)を対象とし、易感染性状態を示す疾患を有する患者は24例であった。カテーテル先端の細菌培養検査では67例(41.9%)が陽性で、最も多く検出した菌種はStaphylococcus属であった。検出菌の多くが皮膚常在菌であった。3例にグラム陰性桿菌であるEnterobacter属の菌を検出し、そのうち2例はカテーテル関連血流感染症(CRBSI)発生例であった。血液培養検査は50例で行い、そのうち20例(12.5%)が陽性で、菌血症の状態を呈した。12例はカテーテル培養と血液培養検査の双方が陽性となり、そのうち7例(4.4%)で同一菌を同定したためCRBSIと診断した。160例における平均カテーテル留置日数は52.7日で、CRBSI発生率は1000×カテーテル留置口数あたり0.83であった。CRBSI発生に関与する因子について単変量解析を用いて比較検討し、年齢およびカテーテル留置日数で有意差を認めた。

DOI： 10.5794/jjoms.63.178

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01073&link_issn=&doc_id=20170501370001&doc_link_id=10.5794%2Fjjoms.63.178&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.63.178&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本口腔ケア学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

口腔内に初発症状を呈する節外性悪性リンパ腫(ML)は非常にまれである。われわれは2005年1月から2015年12月までの間に当科を受診した口腔悪性腫瘍患者1,081例のうち口腔内に初発症状を呈した節外性ML10例について臨床的特徴を検討した。男性は7例、女性は3例であり、年齢は8〜82歳(平均年齢:64.4歳)であった。8例が歯肉に生じており、その他の部位としては口底と頬粘膜に生じていた。病理診断ではびまん性大細胞型B細胞リンパ腫が7例を占めていた。Ann Arbor分類ではステージI、II、III、IVはそれぞれ、3、1、2、4例であった。さらに、本邦で報告された口腔内に初発症状を呈する節外性ML115例を検討した。口腔病変を診断する際には、MLが口腔内に発生しうることを念頭に置くべきである。(著者抄録)

DOI： 10.5981/jjhnc.42.339

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J04195&link_issn=&doc_id=20161115500012&doc_link_id=10.5981%2Fjjhnc.42.339&url=https%3A%2F%2Fdoi.org%2F10.5981%2Fjjhnc.42.339&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：(一社)日本口腔腫瘍学会  

口腔癌N0症例のうち20〜30%の頻度で後発頸部リンパ節転移が生じるが、経過観察するか予防的頸部郭清術を行うかといった頸部に対する治療方針に統一した見解は得られていない。様々な画像診断が行われるにも関わらず頸部リンパ節転移を正確に診断することは困難であるため、色素法、ラジオアイソトープ(RI)法、あるいはその両者を用いたセンチネルリンパ節生検(SLNB)が近年行われるようになってきた。しかし、RI法を用いたSLNBはどの施設でも行えるわけではない。そのため、RIを用いない方法として、口腔癌N0症例に対するインドシアニングリーン(ICG)蛍光法を用いたSLNBについて報告する。(著者抄録)

DOI： 10.5843/jsot.28.65

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02382&link_issn=&doc_id=20161004320003&doc_link_id=%2Fdy8ortum%2F2016%2F002803%2F004%2F0065-0070%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2016%2F002803%2F004%2F0065-0070%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

われわれは頸部リンパ節転移を有する進行口腔癌に対し逆行性超選択的動注化学放射線療法(以下動注CCRT)を施行し、転移リンパ節に対する治療効果につき検討したので報告する。対象は2007年2月から2010年11月までに進行口腔癌(T2-4bN1、2M0)に対し根治的動注CCRTを施行し、原発巣がCRのため原発は手術回避、頸部郭清術のみを行った20症例である。N分類はN1:5例、N2b:10例、N2c:5例であった。治療は浅側頭動脈、後頭動脈より逆行性に腫瘍の栄養動脈に動注カテーテルを留置し、動注CCRTを5-6週間(docetaxel:total 50-60mg/m2、cisplatin:total 125-150mg/m2、RT:total 50-60Gy)施行した。治療終了後5から8週に頸部郭清術を行い、摘出したリンパ節の病理組織学的検索を行ったところ、転移リンパ節がpCRであったのは20例中13例(65%)であった。その後経過観察中に頸部再発を認めたのは2例(10%)であった。20例中13例は生存、7例が死亡(6例が遠隔転移、1例が頸部の非制御)した。以上より動注CCRTは、口腔癌の頸部転移リンパ節にも有用であることが示唆された。(著者抄録)

DOI： 10.5843/jsot.28.27

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

われわれは頸部リンパ節転移を有する進行口腔癌に対し逆行性超選択的動注化学放射線療法(以下動注CCRT)を施行し、転移リンパ節に対する治療効果につき検討したので報告する。対象は2007年2月から2010年11月までに進行口腔癌(T2-4bN1、2M0)に対し根治的動注CCRTを施行し、原発巣がCRのため原発は手術回避、頸部郭清術のみを行った20症例である。N分類はN1:5例、N2b:10例、N2c:5例であった。治療は浅側頭動脈、後頭動脈より逆行性に腫瘍の栄養動脈に動注カテーテルを留置し、動注CCRTを5-6週間(docetaxel:total 50-60mg/m2、cisplatin:total 125-150mg/m2、RT:total 50-60Gy)施行した。治療終了後5から8週に頸部郭清術を行い、摘出したリンパ節の病理組織学的検索を行ったところ、転移リンパ節がpCRであったのは20例中13例(65%)であった。その後経過観察中に頸部再発を認めたのは2例(10%)であった。20例中13例は生存、7例が死亡(6例が遠隔転移、1例が頸部の非制御)した。以上より動注CCRTは、口腔癌の頸部転移リンパ節にも有用であることが示唆された。(著者抄録)

DOI： 10.5843/jsot.28.27

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J02382&link_issn=&doc_id=20160629420002&doc_link_id=%2Fdy8ortum%2F2016%2F002802%2F002%2F0027-0032%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2016%2F002802%2F002%2F0027-0032%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2016.34.15_suppl.6032

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCI LTD  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(公財)鈴木謙三記念医科学応用研究財団  

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記述言語：日本語   出版者・発行元：(公財)鈴木謙三記念医科学応用研究財団  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

サーチュインは、NAD+依存性の酵素で、老化、クロマチン制御、炎症、アポトーシス、転写など、さまざまな生命現象にかかわっている。サーチュインの活性化は、加齢に伴う代謝疾患、がん、心疾患、神経疾患、免疫疾患などの老化関連疾患の発症の抑制による健康寿命の延伸と寿命延長をもたらす。他方で、カロリー制限がさまざまな生物種において抗老化・寿命延長効果を示すことが古くから知られてきたが、その主要なメカニズムにサーチュインが関与していることが明らかにされている。サーチュインを活性化する薬剤がいくつか取得されており、すでに非臨床レベルでは、さまざまな老化関連疾患に対する薬効と寿命を延長する効果があることが示されている。(著者抄録)

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-4576

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

進行口腔癌に対する逆行性超選択的動注化学療法は、放射線療法との連日同時併用が可能となることから高い抗腫瘍効果が期待できる。今回われわれは、上顎歯肉扁平上皮癌(T3、4)の一次症例17例に対して根治的逆行性超選択的動注化学放射線療法を施行し、治療効果について検討した。治療は逆行性超選択的動注化学放射線療法(DOC:60mg/m2、CDDP:150mg/m2、60Gy)を6週間行った。治療終了4週間後に画像検索および原発部位の生検にて治療効果判定を行ったところ、CRが14例(82.4%)、PRが3例(17.6%)であった。CR症例14例については、経過観察中に1例に局所再発、1例に後発頸部リンパ節転移および肺転移を認めた。全17例中の4例が死亡し、Kaplan-Meier法による2年累積局所制御率は76.5%、2年累積生存率は81.4%であった。(著者抄録)

DOI： 10.5981/jjhnc.39.443

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記述言語：日本語   出版者・発行元：(株)羊土社  

サーチュインは長寿遺伝子とよばれ、いまや科学に直接携わる者だけではなく一般の人々にも広く知られる存在となり、サプリメントや食餌制限などでサーチュインを活性化させることで健康長寿をめざす試みがなされている。しかしその一方Nature誌などの一流誌にサーチュインの過去の研究を覆すnegative dataが掲載され、またそれに応酬する形で論文が出されるなど前例のない賑わいをみせている。本稿では、サーチュイン発見の歴史から最新の研究動向までを紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2013-5568

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記述言語：日本語   出版者・発行元：日本基礎老化学会  

サーチュインは長寿遺伝子とよばれ、いまや科学に直接たずさわる者だけではなく一般の人々にも広く知られる存在となった。サプリメントや薬、また食事制限などでサーチュインを活性化させることで健康長寿を目指す試みがなされている。そして世界中の研究者がこの領域にこぞって参入したことから、競争はますます激しくなり、新しい知見がつぎつぎと見出されている(図1)。しかしその一方でNatureなどの一流誌にサーチュインの過去の研究を覆すnegative dataが掲載され、またそれに応酬する形で論文が出されるなど前例のない事態がおきている。本稿では、サーチュイン発見の歴史と最新の研究の動向を紹介する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J01656&link_issn=&doc_id=20130214370001&doc_link_id=%2Fel3kisro%2F2013%2F003701%2F001%2F0001-0006%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fel3kisro%2F2013%2F003701%2F001%2F0001-0006%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本ハイパーサーミア学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

CiNii Books

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

腫瘍血管が癌進展と転移に大きな役割を果たしていることから血管新生阻害療法は新たな癌の治療法として高い注目を集めている。しかしながら従来の血管新生阻害薬は一過性の効果しか得られていないのが現状である。最近の研究で筆者らは局所に既存する腫瘍血管からの血管新生が放射線照射や抗癌剤などによって抑制された際に骨髄由来細胞の著しい腫瘍内への誘導が起こることを見出した。さらにこれらの骨髄由来細胞により脈管形成が引き起こされることが明らかとなった。骨髄細胞が誘導されるメカニズムには低酸素などの癌細胞周囲の微小環境の変化が重要であり、hypoxia-inducible factor-1(HIF-1)やstromal cell-derived factor-1(SDF-1)などの分子が深く関わっており、それらを阻害することで腫瘍の再発が抑制された。このことからがん治療後の微小環境変化により引きおこされる再発のメカニズムが明らかになり、新たな抗腫瘍血管療法の可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語  

DOI： 10.5981/jjhnc.37.386

Scopus

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記述言語：日本語   出版者・発行元：Japan Society for Head and Neck Cancer  

進行口腔癌に対する逆行性超選択的動注化学療法は放射線療法との連日同時併用が可能となることから高い抗腫瘍効果が得られる。今回われわれは進行口腔癌に対して根治的逆行性超選択的動注化学放射線療法を施行し，治療効果，累積生存率，局所制御率について検討したので報告する。2003年1月から2009年12月に受診した口腔・顎顔面悪性腫瘍688例中，根治的逆行性超選択的動注化学放射線療法を施行した175症例を対象とした。治療は逆行性超選択的動注化学放射線療法（docetaxel, total 60mg/m2, cisplatin, total 125-150mg/mm2, total 50-60Gy）を5～6週間行った。治療4週後に画像検索および原発の生検にて腫瘍残存の有無の確認を行ったところ，175例中160例（91.4%）がCR，腫瘍残存は15例（8.6%）に認めた。CRであった160例についてはその後の経過観察中に14例（8.0%）の再発を認めた。5年累積生存率および局所制御率はそれぞれ71.6%と82.2%であった。

DOI： 10.5981/jjhnc.37.386

Scopus

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記述言語：日本語   出版者・発行元：(株)羊土社  

サーチュイン(Sirtuin)のノックアウトマウスのなかでも、SIRT6のノックアウトマウスは最も顕著な老化様症状を示すが、その分子機構は長い間不明であった。しかし最近、SIRT6が特異的ヒストンの脱アセチル化酵素であることが発見され、テロメアと染色体の維持、DNA修復、代謝制御、そして転写制御と実にさまざまな生命現象にかかわっていることが次々に明らかにされている。本稿では、SIRT6の最近の知見に加え、老化や疾患とのかかわりについて紹介する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

進行口腔癌に対する逆行性超選択的動注化学療法は、放射線療法との連日同時併用が可能となることから高い抗腫瘍効果が得られる。われわれは進行口腔癌に対し超選択的動注化学放射線療法を施行し、術前治療としての効果および原発の手術回避について報告してきた。しかし、治療後に腫瘍が残存した症例、再発症例に対しては救済手術が必要となる。今回われわれは本療法を施行し、救済手術が必要であった症例につき術後合併症、予後につき報告する。2006年8月から2009年7月の3年間に横浜市立大学附属病院歯科口腔外科を受診した頭頸部領域の悪性腫瘍304例であり、当科において治療を行った症例は193例であった。そのうち根治療法として超選択的動注化学療法を施行した口腔癌症例102例(52.8%)につき検討を行った。治療は超選択的動注化学療法(docetaxel、total 60mg/m2、cisplatin、total 150mg/m2)、放射線連日同時併用療法(total 60Gy)を6週行うことを原則とした。102例については治療4週後に画像および原発の生検にて腫瘍残存の有無の確認を行ったところ、102例中pCRが90例(88.2%)、腫瘍残存は12例(11.8%)に認めた。原発がpCRであった90例において、経過観察中に4例(3.9%)の再発を認めた。原発に腫瘍残存を認めた12症例および治療後に再発を認めた4症例の16症例中、10症例に救済手術を施行した。救済手術を施行した10例中5例に術後の合併症を認めた。救済手術を行った10症例について4例は再発を認めた。10例中6症例は生存している。(著者抄録)

DOI： 10.5843/jsot.22.102

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

進行口腔癌に対する逆行性超選択的動注化学療法は、放射線療法との連日同時併用が可能となることから高い抗腫瘍効果が得られる。われわれは進行口腔癌に対し超選択的動注化学放射線療法を施行し、術前治療としての効果および原発の手術回避について報告してきた。しかし、治療後に腫瘍が残存した症例、再発症例に対しては救済手術が必要となる。今回われわれは本療法を施行し、救済手術が必要であった症例につき術後合併症、予後につき報告する。2006年8月から2009年7月の3年間に横浜市立大学附属病院歯科口腔外科を受診した頭頸部領域の悪性腫瘍304例であり、当科において治療を行った症例は193例であった。そのうち根治療法として超選択的動注化学療法を施行した口腔癌症例102例(52.8%)につき検討を行った。治療は超選択的動注化学療法(docetaxel、total 60mg/m2、cisplatin、total 150mg/m2)、放射線連日同時併用療法(total 60Gy)を6週行うことを原則とした。102例については治療4週後に画像および原発の生検にて腫瘍残存の有無の確認を行ったところ、102例中pCRが90例(88.2%)、腫瘍残存は12例(11.8%)に認めた。原発がpCRであった90例において、経過観察中に4例(3.9%)の再発を認めた。原発に腫瘍残存を認めた12症例および治療後に再発を認めた4症例の16症例中、10症例に救済手術を施行した。救済手術を施行した10例中5例に術後の合併症を認めた。救済手術を行った10症例について4例は再発を認めた。10例中6症例は生存している。(著者抄録)

DOI： 10.5843/jsot.22.102

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J02382&link_issn=&doc_id=20100916310004&doc_link_id=%2Fdy8ortum%2F2010%2F002203%2F005%2F0102-0106%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2010%2F002203%2F005%2F0102-0106%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(公社)日本生化学会  

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J-GLOBAL

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記述言語：英語  

CiNii Books

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：社団法人 日本口腔外科学会  

Pleomorphic adenoma of the submandibular gland is rare in children. Only 16 cases have been reported in the Japanese literature. In this paper, we report a pleomorphic adenoma arising in the submandibular gland of an 11-year-old girl. She complained of a mass of the left submandibular region. A hard, tender mass was palpable in this region. Computed tomography and magnetic resonance imaging showed swelling of the left submandibular gland. Under a clinical diagnosis of a benign tumor of the submandibular gland, the patient underwent total excision of the submandibular gland. The histopatholo...

DOI： 10.5794/jjoms.45.583

CiNii Books

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J-GLOBAL

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記述言語：日本語  

CiNii Books

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記述言語：日本語   出版者・発行元：社団法人 日本口腔外科学会  

Antiphospholipid antibody syndrome (APS) is characterized by thrombocytopenia, habitual abortion, and arteriovenous thrombosis.&lt;BR&gt;We report the case of a 32-year-old man with APS in whom an erupted maxillary third molar had to be extracted. The tooth was extracted while carefully monitoring hemostasis because of the presence of thrombocytopenia (2.4×10&lt;SUP&gt;4&lt;/SUP&gt;/μ&lt;I&gt;l&lt;/I&gt;). The wound healed without any local or systemic complications.&lt;BR&gt;When patients with APS are referred to oral and maxillofacial surgeons, it is important to be aware of APS, especially with regard to the perioperative ...

DOI： 10.5794/jjoms.44.229

CiNii Books

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