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In amyotrophic lateral sclerosis (ALS) patients, dysphagia eventually occurs independent of time of onset. We studied dysphagia conditions in the early stage of ALS, principally at the oral phase. Videofluoroscopic and manometric studies were conducted on 11 patients (5 males and 6 females, age range = 47-82 years) who were diagnosed at our Neurology Clinic as having ALS. All patients were able to ingest orally. Swallowing scores on the ALS severity scale were from 10 to 5. In the oral phase of swallowing, abnormal movements of the anterior and/or posterior tongue were recognized in 8 cases. Dysphagia severity tended to be particularly influenced by dysfunction of the posterior tongue. Manometric studies were almost normal in all cases except one. These results suggested that the early stage of dysphagia in ALS was mainly caused by oral dysfunction, and the oral phase disorders began in some cases with a decreased function of bolus transport at the anterior part of the tongue, and in other cases with a deteriorated function of holding the bolus at the posterior part of the tongue. In conclusion, the tongue function of holding the bolus in the oral cavity mainly affects the severity of the early stage of dysphagia in ALS.

We report two head and neck cancer patients who responded to TS-1. Case 1, a 52-year-old man was admitted to our department a diagnosis of supraglottic laryngeal cancer (T3N2cM0) on January 25, 2000. Concurrent chemoradiotherapy consisting of 2 courses of chemotherapy and radiation therapy at 70.2 Gy was administered. After the treatment, a biopsy showed a remaining cancer in the primary lesion. Since the patient refused to undergo surgery, the patient was followed up at the outpatient clinic using UFT at 400 mg/day. Because pulmonary metastasis was detected by chest CT, administration of TS-1 was started. TS-1 was administered at the conventional dose of 120 mg/day for 4 weeks followed by a 2-week rest. According to a CT conducted after 2 courses, the mass in the lung field disappeared and the clinical outcome was judged to be a CR. The TS-1 administration is still continuing, and the patient's condition also remains a CR. Case 2 was a patient with highly-differentiated adenocarcinoma in the ethmoid sinus (T3N2bM0). The patient was inoperable and was given radiation therapy of 64.8 Gy. Because of no change of the tumor after radiotherapy, TS-1 was administered at 60 mg x 2/day for 4 weeks followed by a 2-week rest. After TS-1 was administered for 3 courses, a CT showed a remarkable regression of the tumor resulting in a PR for the primary and the neck lesion. Upper gastrointestinal endoscopy during the 4th course detected a gastric ulcer of the A1 stage, and the patient was immediately admitted to the hospital. The ulcer was an adverse reaction of grade 3, which was improved by conservative therapy. TS-1 was restarted with a dose of 100 mg/day on April 11. No particular adverse reaction has been observed since then. The patient has received 13 courses of TS-1 and is still receiving TS-1. No clear tumor has been observed, and the clinical outcome is considered to be a CR. TS-1 is considered to be an excellent oral anticancer drug in terms of its anti-tumor effect and the patient's QOL.

Matrix metalloproteinases (MMPs) have been implicated in tumor invasion, metastasis, and angiogenesis. We have recently shown that MMI-166, a new orally active MMP inhibitor specific for MMP-2 and -9, suppressed experimental metastasis of Lewis lung cancer, C-H1 human colon cancer, and pancreatic cancer without affecting tumor growth in vitro. In the present study, we determined whether oral administration of MMI-166 reduces tumor growth not only in such tumors but also in squamous cell carcinoma of head and neck (SCCHN). MMI-166 inhibited both activity of MMP-2 and -9 without affecting steady state levels of their mRNAs in SCCHN. Interestingly, protein levels of MMP-2 and -9 from the cultures were drastically diminished by culturing with MMI-166. This was also observed in xenografts of MMI-166-administered mice. In addition, daily oral administration of MMI-166 (100mg/kg) inhibited local tumor growth accompanied by the reduction of blood vessel density and Ki-67-positivity and increase in terminal deoxynucleotidyl transferase-mediated cUDP nick-end labeling (TUNEL)-positivity. These results suggested that orally administered MMI-166 reduced in vivo tumor growth of SCCHN through inhibition of angiogenesis and induction of apoptosis accompanied by the reduction of MMP productions and activities. Therefore, MMI-166 seems to be useful for tumor dormancy therapy of SCCHN.

Laminin-5 (LN-5), an important basement membrane (BM) protein consisting of laminin alpha3, beta3 and gamma 2 chains, has been suggested to be involved in tumor cell invasion and tissue repair. In this study, the distribution of the LN-5 subunits in atypical adenomatous hyperplasia (AAH) and different types of adenocarcinomas of the lung was examined by immunohistochemical analysis. In AAH and non-sclerosing, well-differentiated adenocarcinomas, the LN gamma 2 chain was frequently detected along with the continuous BMs. These BMs were also positive for both LN alpha3 and beta3 chains, suggesting that LN-5 had been deposited. In contrast, the cytoplasmic staining for the LN gamma 2 chain was frequently observed in tumor cells of sclerosing, well-differentiated adenocarcinomas, as well as of moderately and poorly differentiated adenocarcinomas, without any evidence of co-expression of the LN alpha3 and beta3 chains. This staining pattern of the LN gamma 2 chain was prominent in carcinoma cells invading into interstitial stroma and was associated with the formation of a central scar in the tumor tissues. These results suggest that the LN gamma 2 chain monomer could be an important indicator of progression of lung adenocarcinoma.

We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.

Twelve patients with mucosal melanoma in the head and neck were treated at Yokohama city University from 1975 to 1994. The sex distribution was 5 male and 7 female, and the age ranged from 40 to 79 years-old. The highest number of patients were in their sixties. In 10 cases tumors arose in the nasal cavity, in one case in the maxillary sinus and in other case in the oral cavity. The treatment modality for this tumor consisted of various combination therapies including surgery, radiotherapy, chemotherapy and immunotherapy. Combination chemotherapy consisting of dimethyltriazeno imidazole carboxamide (DTIC, Dacarbazine), amino methyl pyrimidinyl methyl chlorethyl nitrorosourea hydrochloride (ACNU) and vincristine (VCR). Cisplatin (CDDP) was recently used for cases where other chemotherapy was not effective. Surgical treatment in the initial therapy was performed in 8 patients. In three of these 8 cases, the surgical margin was positive. One of them was dead after 9 months, another dead with complication after 1 year and the other survived free of any tumor. Immunotherapy using OK-432, interleukin-2, LAK therapy and low dose CPM was effective for some patients. The 5-year survival rate was 44%. Patients with surgical treatments in the initial therapy had longer survival than those without surgical treatments.