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Masato Fujii

Publications and source records attributed to Masato Fujii.

25 records · Page 2Linked to original sources

Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice.

Marimastat, a matrix metalloproteinese inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. Even with novel approaches such as molecular targeting of cancer chemotherapy, peritoneal dissemination of gastric cancer has little sensitivity to anticancer drugs, and it is impossible to inhibit its growth completely. Intraperitoneal injection of TMK-1 into nude mice at 5 x 10( 5) cells / body resulted in carcinomatous peritonitis that mimicked clinical cases. Continuous administration of marimastat (18 mg / kg / day) from 24 h after the tumor inoculation successfully inhibited the growth of peritoneal dissemination nodules. Combined administration of marimastat (18 mg / kg / day) and mitomycin C (MMC, 2 mg / kg) showed synergistic inhibition of growth of peritoneal dissemination, being superior to MMC alone (2 mg / kg). Although marimastat alone could not increase survival time with statistical significance, combined administration of marimastat and MMC had a survival benefit with statistical significance. The combination of marimastat and MMC increased the preventive effect on peritoneal dissemination. Marimastat seems to be a candidate for the prevention of peritoneal spread of gastric carcinoma.

Animals↗

[Statistical analysis of maxillary sinus squamous cell carcinoma].

Cases of squamous cell carcinoma of the maxillary sinus initially treated at Keio University Hospital between January 1981 and December 1998 studied retrospectively involved 60 untreated cases--46 men and 14 women aged 36 to 86 years (mean: 59.8 years). Of these, 7 had T2, 41 T3 and 12 T4 tumors based on 1997 AJCC TNM classification. Seven (11.7%) had nodal involvement but none had distant metastasis at diagnosis. Of the 60, 53 (88.3%) were stage III or IV. Prognostic factors and survival were statistically analyzed for 59 cases, excluding the 60th who died of another cause. Follow-up was 4 to 227 months, with a median of 59 months and a mean of 38 months. Of the 59, 48 (81.4%) underwent neoadjuvant chemotherapy (NAC). Survival was estimated using the Kaplan-Meier method as univariate analysis. Cause-specific 5-year survival was 56.8% for all stages, 68.2% for T2, 60.0% for T3, and 41.7% for T4. T stage classification was thus a significant independent prognostic factor in multivariate analysis using Cox's proportional hazards model (p = 0.0240). It also identified T stage classification (p = 0.0486) and NAC (p = 0.0419) as significant independent factors affecting survival with organ preservation. We also statistically analyzed 48 cases treated with NAC, which showed complete response (CR) for 11, partial response (PR) for 25, no change (NC) for 11, and progressive disease (PD) for 1. Responders (CR + PR) showed significantly better survival and organ preservation than nonresponders (NC + PD). The NAC response enables us to predict prognosis. T4 cases without NAC response should be treated intensively.

Adult↗

[Comparative clinical studies for head and neck cancer in Japan].

Very few large multi-institutional comparative clinical studies for head and neck cancer are reported in Japan. Many studies for organ-preservation with better QOL have been reported around the world, and comparative clinical studies are also necessary in Japan to evaluate organ-preservation treatment. I reviewed comparative clinical studies for head and neck cancer in Japan. Inuyama et al. reported a multi-institutional randomized clinical trial (RCT) that compared the efficacy of CBDCA + PEP and CDDP + PEP. Comparative clinical studies for combination chemotherapy, CDDP + PEP + MTX (PPM) vs. CDDP + PEP + 5-FU (PPF), and PPM vs. CDDP + PEP (PP) are reported. Effects and toxicity are different with each regimen, but the differences are not statistically significant. An RCT of neoadjuvant chemotherapy (NAC) for nasopharyngeal cancer with a small sample size was reported. Three-year survival was significantly better for the NAC group. An RCT of concurrent chemo-radiotherapy with CDDP vs. CBDCA was also reported. CBDCA with radiation was significantly better in terms of 2- and 5-year survival. This result is interesting but the low-dose CDDP with radiation 4 times per week is not standard. A large nationwide RCT with 560 cases investigating adjuvant chemotherapy with UFT was conducted in 1987. The differences in 3-year survival and 3-year disease-free survival with or without UFT adjuvant were not statistically significant, but the incidence of distant metastasis was significantly lower in the UFT adjuvant group. Comparative clinical studies of 5-HT3 antagonists for chemotherapy including CDDP are reported. We conducted a crossover comparative clinical study on the combination of azasetron and dexamethasone. The combination with dexamethasone significantly prevented acute emesis induced by CDDP. Comparative clinical studies of head and neck cancer have not provided good evidence, with the exception of an RCT of adjuvant chemotherapy with UFT, in the past. Well-designed comparative clinical studies with the cooperation of head and neck surgeons, radio-oncologists, and medical oncologists should be considered in order to acquire high-level evidence.

Antineoplastic Agents↗

[Bronchioloalveolar carcinoma complicated by a lesion resembling bronchiolitis obliterans organizing pneumonia in the opposite lung].

A 50-year-old woman with abnormal shadows in her chest radiograph was admitted for a more detailed examination in April 2000. A chest CT scan showed infiltrates surrounded by ground-glass opacities in the right upper lobe, and ground-glass opacities with partial infiltrative changes in the left lower lobe. A diagnosis of adenocarcinoma like bronchioloalveolar carcinoma (BAC) was made for the lesion in the right upper lobe by means of a transbronchial biopsy. However, the specimen from the left lower lobe showed nonspecific changes, and bronchiolitis obliterans organizing pneumonia (BOOP) or a metastatic lesion from the BAC was suspected. We prescribed steroids for the short term. Since the lesion in the left lobe disappeared, we performed a right upper lobectomy. In cases of primary lung carcinoma, BOOP in the opposite lung is rare and it was difficult to decide on the operability. We concluded that steroid therapy is useful for distinguishing between inflammatory and tumorous lesions in cases in which a detailed examination is difficult.

Adenocarcinoma, Bronchiolo-Alveolar↗

[A case of sarcoidosis manifesting as annular opacities after multiple nodular shadows].

A 40-year old man was admitted to our hospital because nodular shadows in the right upper lung field had shown deterioration on chest radiographs during a regular check-up (Sep. 28, 2000). Transbronchial lung biopsy specimens showed findings compatible with sarcoidosis. During follow-up, the nodular shadows became bigger, spread in both lung fields and turned into multiple annular opacities. In December, lung biopsy specimens obtained by VATS showed central areas of ground-glass attenuation corresponding to areas of alveolar septal inflammation, in contrast to the denser periphery, where polypoid organized granulation tissue in peripheral air spaces predominated. After 2 months, the opacities disappeared without treatment. In our case, the annular opacities on CT corresponded histologically to BOOP. It is interesting to note the relationship between sarcoidosis and BOOP.

Adult↗

The inhibitory effect of matrix metalloproteinase inhibitor ONO-4817 on lymph node metastasis in tongue carcinoma.

BACKGROUND: ONO-4817 is a novel matrix metalloproteinase (MMP) inhibitor which has a broad inhibitory spectrum for MMPs. We investigated the inhibitory effect of ONO-4817 on cervical lymph node metastasis of tongue carcinoma. MATERIALS AND METHODS: HSC-3-M3, a cell line derived from human tongue carcinoma with high metastatic potential for lymph node, was used. The direct cytotoxicity of ONO-4817 was assessed by MTT assay and the gelatinolytic activity by gelatin zymography and film in situ zymography (FIZ). The inhibitory effect on lymph node metastasis was examined by orthotopic implantation model with nude mice. RESULTS: ONO-4817 had no direct cyototoxicity on HSC-3-M3 cells. Gelatin zymography and FIZ demonstrated a suppression of MMP-9 activation and a marked inhibition of gelatinolysis. Additionally, a suppression of cervical lymph node metastasis was shown by therapeutic experiment. CONCLUSION: The MMP inhibitor, ONO-4817, is a candidate for adjunctive therapy of cervical lymph node metastasis in tongue carcinoma.

Animals↗

CCND1 amplification predicts sensitivity to chemotherapy and chemoradiotherapy in head and neck squamous cell carcinoma.

BACKGROUND: Cyclin D1 has been reported to be associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: FISH was performed on 58 patients. Thirty-two received neoadjuvant chemotherapy (NAC) as primary treatment and 21 with hypopharyngeal squamous cell carcinoma (HPC) received chemoradiotherapy. RESULTS: CCND1 amplification was identified in 31 (53%) patients and the incidence was higher in HPC (p = 0.0068). Four (31%) out of 13 patients with CCND1 amplification responded to NAC whereas the response rate in the non-amplified group was 79% (p = 0.011). CCND1 amplification with a homogeneously staining region (HSR) was accompanied by cyclin D1 protein overexpression (p < 0.0001). HPC showed HSR more frequently (p = 0.033) and the survival rate of the subgroup with HSR was lower than that without (p < 0.05). CONCLUSION: Detection of CCND1 amplification using FISH may be a useful marker of sensitivity to NAC and chemoradiotherapy for HNSCC.

Aged↗