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Biomedical subjects

Masato Fujii

Publications and source records attributed to Masato Fujii.

At least 19 recordsLinked to original sources
PubMed2006

Value of CT thallium-201 SPECT fusion imaging over SPECT alone for detection and localization of nasopharyngeal and maxillary cancers.

OBJECTIVE: The purpose of this study was to investigate the incremental clinical utility of CT and high-resolution SPECT fusion imaging. MATERIALS AND METHODS: Eighteen patients with nasopharyngeal cancer or cancers around the maxilla were scanned with high-resolution SPECT at the time of initial diagnosis (18 studies) and during follow-up after chemoradiotherapy (23 studies). SPECT results were compared with histologic findings or the findings of other imaging techniques. In addition, automatic image registration without fiducial markers was performed from CT and SPECT data, and the effect of fusion imaging on the localization of abnormalities was evaluated. RESULTS: All of the original 18 untreated lesions showed high uptake. Recurrent tumors had a tendency to show high uptake (seven of nine patients), whereas little or no uptake generally represented no recurrence (12 of 14 patients) (chi-square test with Yates correction: chi2 = 6.80, p < 0.01). In two patients, physiologic uptake in the unilateral prevertebral muscle was revealed on image fusion. In four of the nine recurrent nasopharyngeal cancers (44%), SPECT alone could not determine abnormalities in uptake sites, whereas CT/SPECT fusion imaging clearly localized the sites and was helpful for treatment strategy. CONCLUSION: High-resolution thallium-201 (201Tl) SPECT has a very high detection rate in patients with nasopharyngeal cancer and cancers around the maxilla. However, the anatomic identification or localization of the uptake sites is sometimes difficult without CT/SPECT fusion imaging. This technique without external markers is practically feasible to generate clinically valid fusion images.

Adult↗
PubMed2006

[Surgical management of parapharyngeal space tumors].

Despite its rarity, information on the diagnosis of parapharyngeal space tumors such as through imaging and aspiration biopsy cytology, is slowly accumulating. Little detailed examination has been conducted, however, on surgical approach, complications, and sequelae. We report the results of a retrospective review of 27 patients with primary parapharyngeal space tumors-25 with benign disease and 2 with malignant lesions-treated surgically. Surgical approach, postoperative complications, sequelae, and operative indications of parapharyngeal space tumors were examined in 28 operations on the 27 patients. Tumors found in the prestyloid region in CT or MRI are treated as salivary gland or malignant tumors. Those found in the poststyloid region are treated as shwannoma or paraganglioma. The transcervical approach is often used in patients with shwannoma, while a variety of approaches are selected for patients with salivary gland tumors. Complications occur in 50% of patients, however, bias based on pathological diagnosis has not been examined to the degree needed. Sequelae in our series occurred in 46.4% of our patients. Sequela in the patients with shwannoma, however, is 81.8%, compared to 9.1% in patients with salivary gland tumors. Prestyloid parapharyngeal space tumors seem to be "automatically" indicated for surgery, because the surgical risk is lower than the risk of inaction. In poststyloid parapharyngeal space tumors, however, it appears necessary to judge indication for surgery more carefully while considering the social background, age, and occupation of prospective surgical candidates.

Adult↗
PubMed2006

[Combination therapy with S-1 and CDDP for head and neck cancer].

The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future.

Adult↗
PubMed2005

Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea.

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.

Acute Disease↗
PubMed2005

[Aberrant promoter hypermethylation of tazarotine-induced gene 1 (TIG1) in head and neck cancer].

We tested the methylation status of tazarotine induced gene 1 (TI(G1) in head and neck cancer cell lines and primary tumors by the methylation-specific polymerase chain reaction (MSP). MSP showed that the TIG1 promoter was methylated in all cell lines. We then used MSP to check the methylation status of TIG1 in primary head and neck cancer (n = 50). MSP showed TIG1 methylation in 31 (62%) head and neck cancers and no methylation in any normal samples. To confirm MSP results, we directly sequenced dense CpG regions. We found that promoter regions contained methylated cytosines. We thus observed a cancer-specific pattern of TIG1 methylation in primary head and neck cancer. Our results support the notion that promoter methylation is an important mechanism of TIG1 gene inactivation and occurs frequently in head and neck cancer. TIG1 methylation represents a new molecular marker for targeting diagnostic and therapeutic approaches in these cancers.

Biomarkers, Tumor↗
PubMed2005

[Clinical study of bronchiolitis obliterans organizing pneumonia (BOOP) primed by radiation for breast cancer].

Bronchiolitis obliterans organizing pneumonia (BOOP) primed by radiation therapy for the breast cancer (BOOP-RT/BC) has been recognized recently. In this study, we reported 9 such cases and discussed steroid therapy. Mean radiation dose and interval from completion of radiation therapy to the appearance of BOOP-RT/BC were 47.3 Gy and 5.6 months respectively. BOOP-RT/BC recurrence was observed by 5 episodes in 3 of 9 cases (recurrence rate was 33%). Steroid therapy showed a remarkable improvement in both primary and recurrent disease, and no residual symptom or BOOP shadow was detectable at the end of the observation except for shadows due to radiation fibrosis. All but one patient were prescribed prednisolone, with a mean initial dose of 32.5 mg/day and a mean treatment duration of 46.7 weeks. One patient improved without treatment. No case suffered from respiratory failure which needed mechanical ventilation or was motile. Considering these findings and the fact that almost all patients are middle aged or senior women who are susceptible to osteoporosis, we conclude that steroid therapy for BOOP-RT/BC should be carefully considered.

Adult↗
PubMed2005

[Combination therapy with TS-1].

The combination with cisplatin (CDDP) and 5-FU is considered the chemotherapy of choice for squamous cell carcinoma of the head and neck (HNSCC). TS-1, a modulation of tegafur developed in Japan, is an orally administered active agent for HNSCC. Some clinical phase I/II studies on the combination of CDDP and TS-1 have been reported. The combination showed a good response rate, 67.6% for both advanced and recurrent HNSCC, in our clinical phase II study. Regimens of TS-1 combined with carboplatin or nedaplatin are also reported.TS-1 containing regimens appear to be effective for HNSCC, and multi-institutional phase II studies with large sample size are needed in future. The combination TS-1 and radiotherapy, its dose and schedule,are being studied in phase I trials for advanced HNSCC. Patient compliance is better than with 5-FU injection because TS-1 is orally administered. The adverse effect, especially in terms of bone marrow toxicity, is equal or better than with 5-FU injection. The TS-1 combination with radiotherapy is a useful regimen for outpatients. The efficacy and adverse effects should be studied in carefully designed phase I/II trials. TS-1 will be one of the key drugs for HNSCC in future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Aphonia and dysphagia after gastrectomy.

A 67-year-old male was referred to our otolaryngological clinic because of aphonia and dysphagia. His voice was breathy and he could not even swallow saliva following a total gastrectomy for gastric carcinoma performed 2 weeks previously. Laryngeal fiberscopy revealed major glottal incompetence when he tried to phonate. However, both vocal folds abducted over the full range during inhalation. The patient could not swallow saliva because of a huge glottal chink, even during phonation. Based on these findings, he was diagnosed as having bilateral incomplete cricoarytenoid dislocation after intubation. The patient underwent speech therapy; within 1 min his vocal fold movement recovered dramatically and he was able to phonate and swallow. There have been few case reports of bilateral cricoarytenoid dislocation, and no effective rehabilitation has been reported. We believe that our method of vocal rehabilitation serves as a useful reference for physicians and surgeons worldwide.

Aged↗
PubMed2004

A novel animal model of acute cochlear mitochondrial dysfunction.

Acute mitochondrial dysfunction in the cochlea is likely to result in hearing loss as a consequence of local energy shortage, similar to ischemia- or noise-induced hearing loss. To establish an animal model of acute cochlear mitochondrial dysfunction, we applied a mitochondrial toxin, 3-nitropropionic acid (3-NP) in the rat cochlea. Rats treated with 500mM 3-NP exhibited permanent threshold shifts in acoustic brainstem response while the same volume of 300mM 3-NP caused temporary threshold shifts. Histological examination in the permanent threshold shift model revealed severe degeneration of fibrocytes within spiral ligament and spiral limbus, indicating these cells are vulnerable to acute mitochondrial dysfunction. This model represents a novel tool for investigating the pathophysiology of acute cochlear mitochondrial dysfunction.

Animals↗
PubMed2004

Constitutive and induced CD44 shedding by ADAM-like proteases and membrane-type 1 matrix metalloproteinase.

CD44 is a receptor for hyaluronan and mediates signaling that regulates complex cell behavior including cancer cell migration and invasion. Shedding of the extracellular portion of CD44 is the last step in the regulation of the molecule-releasing interaction between the ligand and cell. However, highly glycosylated forms of CD44 have hampered the identification of the exact cleavage sites for shedding and the responsible proteases. In this study, we found that expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) increased shedding of the 65-70 kDa CD44H (standard form) fragments and generated two additional smaller fragments. We purified the shed fragments and identified the cleaved sites by mass spectrometry. Specific antibodies that recognize the newly exposed COOH terminus by cleavage were prepared and used to analyze shedding at each site. Shedding of the 65-70 kDa fragments was inhibited by tissue inhibitor of metalloproteinase 3 (TIMP-3) but not by TIMP-1 and TIMP-2, suggesting involvement of a disintegrin and metalloproteinase (ADAM)-like proteases, although shedding is affected by MT1-MMP. Conversely, shedding of the two smaller fragments was inhibited by TIMP-2 and TIMP-3 but not TIMP-1, suggesting involvement of MT1-MMP itself. Shed fragments cleaved at these sites were also detected in human tumor tissues. Increased shedding at one of the MT1-MMP-sensitive sites was observed in the tumor compared with the surrounding normal tissue. However, no significant difference was observed with shedding by ADAM-like proteases. Thus, the cleavage sites for the shedding of CD44H were identified for the first time, and the results provide a basis for exploring the unknown biologic roles of shedding at different sites.

ADAM Proteins↗
PubMed2004

Phase I/II trial of weekly docetaxel and concomitant radiotherapy for squamous cell carcinoma of the head and neck.

BACKGROUND: A phase I/II trial of concurrent docetaxel and radiation for head and neck cancer was conducted to estimate the recommended dose schedule of docetaxel, and then to evaluate the therapeutic benefit. METHODS: Patients received radiation in 2.0-Gy single daily fractions to a total dose of 60 Gy. Docetaxel was administered weekly for 6 consecutive weeks. RESULTS: Docetaxel 15 mg/m(2) was considered the maximum tolerated dose (MTD). The recommended dose was decided as 10 mg/m(2). The phase II study was conducted using docetaxel at 10 mg/m(2). Thirty-nine patients were enrolled. The overall response rate was 96.9%. The prognosis of the complete response (CR) patients was significantly better than that of the partial response (PR) patients. Grade 3 or 4 adverse events consisted of lymphopenia, stomatitis, and anorexia. Thirty-two of the 35 eligible patients showed high compliance, of over 90%, and their toxicities were manageable. CONCLUSION: Even low-dose docetaxel shows a strong effect in combination with radiation, with a high survival rate in CR patients. The effect on survival will be assessed by further follow-up.A phase I/II trial of concurrent docetaxel and radiation for head and neck cancer was conducted to estimate the recommended dose schedule of docetaxel, and then to evaluate the therapeutic benefit.

Adult↗
PubMed2004

Intramuscular myxoma of scalene muscle: a case report.

Intramuscular myxoma is a benign mesenchymal tumor that commonly occurs in the larger skeletal muscles, and is rare in the head and neck. A case of intramuscular myxoma in the scalene muscle is described. This is the first report of this tumor arising in that muscle. It is difficult to diagnose pre-operatively from clinical features, CT scan and ultrasonography of the neck because of the lack of characteristic manifestation or radiographic features. Intramuscular myxoma has an infiltrative tendency, so there are several reports of recurrence because of incomplete excision or enucleation. In our case no recurrence was observed for 4 years, since the tumor was removed with the muscle adherent to it.

Adult↗
PubMed2004

[A case of subacute idiopathic interstitial pneumonia resistant to steroids, successfully treated with cyclophosphamide].

A 47-year-old woman was admitted to our hospital because of dry cough, fever, and subacute, progressive dyspnea. Chest radiography and computed tomography showed ground glass opacities in the lower lung fields. We suspected pneumonia caused by atypical pathogens and administered antibiotics, but they had no effect at all. Histopathologic findings from a transbronchial lung biopsy (TBLB) included intensive infiltration of mononuclear cells and edema on the alveolar wall with no evidence of fibrosis, fibroblasts, hyaline membrane, or granuloma. On the basis of these findings, we suspected interstitial pneumonia, but a surgical lung biopsy was not possible because the patient would not give her consent. After TBLB, corticosteroid was administered repetitively, but dyspnea was deteriorating as the ground glass opacities became more widespread, and tractional bronchiectasis appeared throughout the lung fields. Therefore, we decided to administer cyclophosphamide (CPA). This was very effective: all of her symptoms improved and the ground glass opacities and tractional bronchiectasis disappeared. Though we tapered and then discontinued corticosteroids a few months after CPA, there was no recurrence whatever. No signs suggesting the association of collagen vascular diseases were detected. The effectiveness of CPA in interstitial pneumonia associated with collagen vascular disease is occasionally reported, but the effect on idiopathic interstitial pneumonia, especially in acute and subacute progressive cases, is rarely reported. We think this is an interesting case to consider the availability of CPA in idiopathic interstitial pneumonia with subacute progression.

Anti-Inflammatory Agents↗
PubMed2003

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition.

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells.

Animals↗
PubMed2003

[Nausea and vomiting].

Nausea and vomiting are the most distressing side effects reported by patients undergoing CDDP-based cancer chemotherapy. Dopamine receptor antagonists and corticosteroids are used as anti-emetics for chemotherapy induced nausea and vomiting. Recently, a highly selective 5-HT3 receptor antagonist are proved to demonstrate antiemetic activity. 5-HT3 receptor antagonists are developed such as Granisetron, Ondansetron, Ramosetron, Azasetron. For acute emesis, complete control of vomiting was achieved in 80% of patients receiving 5-HT3 receptor antagonists. Though, it is reported to be only 20% effective for the complete control of delayed emesis. Psychiatric medications sometimes play a prominent role in the control of persisting emesis, particularly anticipatory or conditioned nausea. Nausea and vomiting are well controlled using various anti-emetics considering patient's condition and chemotherapy schedule.

Antineoplastic Agents↗
PubMed2002

Significance of epidermal growth factor receptor and tumor associated tissue eosinophilia in the prognosis of patients with nasopharyngeal carcinoma.

OBJECTIVE: The expression of epidermal growth factor receptor (EGFR) is one of the indicators, which can predict the malignant potential of squamous cell carcinoma of the head and neck (HNSCC). On the other hand, previous histological studies have proved tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for HNSCC. We studied the prognostic significance of co-expression of EGFR and TATE. METHODS: We examined the expression of EGFR and TATE in 53 patients with nasopharyngeal carcinoma (NPC). Biopsy specimens were subjected to immunohistochemical-staining for EGFR expression and Luna-staining for TATE. EGFR staining was considered negative when immuno-stained cells were less than 25% in a field. TATE was divided into four grades as grade 0 for 0-2 eosinophils in a high power field, grade 1 for 3-9, grade 2 for 10-29, and grade 3 for 30 or more. RESULTS: In terms of TATE expression, 27 patients were classified as grade 0, 12 as grade 1, six as grade 2, and eight as grade 3. Forty-four patients were EGFR positive and nine were negative. We found no statistical significance in the distribution of EGFR positivity and TATE grades. Among EGFR-positive patients, 5 year survival rates were significantly better in TATE-positive (grades 1, 2, 3) patients than in TATE-negative (grade 0) patients (P=0.0139). CONCLUSION: Eosinophils may be activated in the tumor tissue, in which the expression of EGFR is up-regulated. This suggests that the activated eosinophils in EGFR-positive tumors resulted in better prognoses. TATE infiltration and EGFR expression may be closely related to the malignant potential of NPC, and co-expression of TATE and EGFR may be an important prognostic factor.

Adolescent↗