Gelatinases refer to a group of enzymes known as matrix metalloproteinases. Matrix metalloproteinases are produced by both normal and malignant cells. 72 kDa and 92 kDa gelatinases degrade type N collagen. These enzymes have been implicated in tumor invasion and metastasis; however, the mechanism regulating the production of tumor gelatinases is unknown. Previous studies suggested that some cytokines may regulate the synthesis of gelatinases. In this study, we investigated the effect of tumor necrosis factor-α(TNF-α) on the production of 72 kDa and 92 kDa gelatinases in two oral cancer cell lines (KB and TCM cells). Stimulation of cell lines with TNF-α(10 and 5 U/ml) enhanced production of 72 kDa and 92 kDa gelatinase in both cell lines. The results suggested that TNF-α plays a role in the regulation of gelatinase production by tumor cells.

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Angiogenesis, the induction of new capillaries and venules, is associated with tuomr growth and may promote the metastasis of tumor cells. Tumor angiogenesis in rabbits with VX 2 carcinoma of the tongue was investigated to determine relations with tumor size, metastasis, and proliferative activity. After implantation in the rabbit tongue, VX 2 carcinoma grew slowly until day 12 and then started to grow rapidly and metastasize. To estimate the proliferative activity of the tumor, the ratios of proliferating cell nuclear antigen (PCNA) were computer-generated with a CAS 200 image analysis system. The PCNA positive area was small (50.54%) on day 7 and increased significantly (73.19%) on day 12, Microvessels were immunohistologically stained with anti-CD31 antibody and counted. Microvessel density was low (29.35) on day 7 and increased significangly (70.1) on day 12. Concomitant increases in PCNA positive area and microvessel density suggest that tumor angiogenesis is related to the prolferative activity of VX 2 carcinoma of the tongue. Angiographic and vascular cast studies also suggested the presence of newly-formed microvessels in the tongue tumor. Furthermore, PCNA-positive cells in tumor nests were frequently observed near highly vascularized areas. These data suggest that tumor angiogenesis plays an important role in the progression of VX 2 carcinoma of the tongue.

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The author established three new cell lines of squamous cell carcinoma (KM-1, KM-2, and KM-3) from three oral cancer patients, to study the effects of cisplatin (CDDP) on oral cancer. This paper describes the characteristics of these cell lines and the cell kinetic effects of CDDP on the cell lines.
The cell lines, which had a doubling time of about 24 hours, showed a monolayer growth pattern resembling pavement stones. To prove that these cell lines were derived from epithelial tumors, four types of immunohistochemical stains were used to histologically examine tumors heterotransplanted in nude mice (BALB/c, nu/nu). Epidermal growth factor, cytokeratin, and epithelial membrane antigen were positive, and vimentin was negative. The histological characteristics of the transplanted tumors derived from KM-1 and KM-3 were similar to those of the original oral tumor; howevers, characteristics of KM-2 differed slightly. The cell lines were thus confirmed to be squamous cell carcinoma cell lines. The DNA ploidy pattern of each cell line, measured by flow cytometry (FCM), was DNA aneuploidy; the DNA index was about 1.35. Fluorescence in situ hybridization (FISH) with centromere-specific DNA probes was used to study numerical aberrations of chromosomes 1, 4, 11, and 17. Chromosome 1 of KM-2 and KM-3 and chromosome 17 of KM-3 increased aneuploidy (more than 3 signals), while chromosome 17 of KM-2 increased monosomy.
The effects of CDDP, applied at three concentrations (100μM, 10μM, and 1 μM) on the cell kinetics of the three cell lines were analyzed by dual parameter DNA/BrdU flow cytometric analysis. With low concentrations of CDDP (10 μM and 1 μM), the cell cycle proceeded slowly for 48 hours, but with high concentrations (100μM) it stopped within 24 hours. This suppression of the cell cycle was caused by a decline in the rate of DNA synthesis and a delay in transition of the cell cycle from the G1 phase to S phase of from the G 2/M phase to G1 phase. Although the rate of DNA synthesis by KM-1 and KM-3 decreased during the first 24 hours after CDDP treatment, DNA synthesis by KM-2 maintained a relatively high rate for 24 hours and then rapidly decreased by 48 hours. These findings suggested that abnormalities of the G1 check point caused by inactivation of p53 gene, which is a tumor suppressor gene, may have resulted in different sensitivity to CDDP, because KM-2 was associated with substantial monosomy of chromosome 17, including the p53 gene.
Death of KM-1 cells treated with CDDP was examined with Papanicolaou staining and FCM, which included the phosphate-citrate buffer (PC buffer) method and TdT-mediated dUTP-digoxigenin nich end labeling (TUNEL) method. While cells treated with 100μ MCDDP showed sub-G₁ peak and many DNA strand breaks with FCM, Papanicolaou staining showed very few apoptotic cells. The results suggested that CDDP mainly induces necrotic cell death.

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Interleukin-2 (IL-2) with anti-CD 3 antibody can induce large numbers of lymphokine activated killer (CD3LAK) cells. However, CD3LAK cells are less cytotoxicity than LAK cells treated with IL-2 alone. Therefore, enhancement by lectins of the cytotoxicity of activated lymphocytes is regarded as lectin-dependent cellular cytotoxicity (LDCC). We studied the enhancement of cytotoxicity by PHA or PWM against PBMC (peripheral blood mononuclear cell)-CD3LAK cells derived from peripheral blood mononuclear cells from a normal donor as well as PBMC-CD3LAK and TIL (tumor infiltrated lymphocyte)-CD3LAK cells obtained from two patients with tongue cancer (stage II). The treatment with PHA or PWM was given to two groups: one (additional group) was treated with PHA or PWM in the effector phase. Another (pretreatment group) was treated with the lectins, described above, and then excess lectin was washed from the surface of the CD3LAK cells. Cytotoxicity in the above two groups was estimated with a ⁵¹Cr release assay for four hours. We found that the NK activity of the PBMC-CD3LAK cells derived from a normal donor was significantly enhanced by PHA or PWM, with the exception of NK activity in the pretreatment group. LAK activity of the above cells was enhanced significantly only by PWM in the additional group. In contrast, LAK activity of PBMC-CD3LAK cells derived from case 2 was significantly enhanced by PWM in both groups. The NK activity of TIL-CD3LAK cells derived from case 1 was enhanced by PHA or PWM, and the LAK activity of these cells was also enhanced significantly by PWM in both groups. The LAK activity of TIL-CD3LAK cells derived from case 2 was enhanced by PWM in both groups. As for cytotoxicity against the autologous tumor, PBMC-CD3LAK cells derived from case 2 were also slightly enhanced by PHA or PWM in both groups, but TIL-CD3LAK cells were enhanced significantly more than the PBMC-CD3LAK cells in all studies. These results suggest differences between PBMC-CD3LAK and TIL-CD3LAK cells in repertoire and in the sugar chain expressed on the tumor cell surface. In addition, PHA or PWM induced high levels of TNF-α in both PBMC-CD3LAK and TIL-CD3LAK cells, but this cytokine did not contribute to enhanced cytotoxicity

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Seventeen patients with squamous cell carcinoma of the buccal mucosa were studied.
The subjects included 11 men and 6 women. 44 to 80 years of age (mean, 67.6 years). There were 3 stage I patients (17.6%), 5 stage II patients (29.4%), 2 stage II patients (11.8%), and 7 stage IV patients (41.2%).
Initial treatment consisted mainly of surgery in 8 cases (47.1%), radiotherapy in 5 cases (29.4%), and a combination of surgery and radiotherapy in 4 cases (23.5%).
Regional lymph node metastases were observed in 4 cases (23.5%) on initial examination and in 1 case later. Radical neck dissections were performed in all cases. The disease was uncontrollable in 2 cases.
Local recurrence occurred in 5 cases (29.4%). The rate of recurrence in T 3 +T 4 cases was significantly higher than that in T 1 +T 2 cases (t-test: p<0.05).
The five-year cumulative survival rate calculated by the Kaplan-Meier method, was 52.3% for the entire group of 17 patients. Outcome was not good in patients with advanced lesions (T3, T4) and tumors showing diffuse invasion. Local recurrence occurred

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The author analyzed magnetic resonance imaging (MRI) findings of the temporomandibular joint (TMJ) in asymptomatic subjects to design standardized diagnostic criteria for anterior disc displacement.
Both TMJs were examined on sagittal images in 129 subjects who had no joint noise, joint pain, muscular pain, or limited opening. Two hundred twelve joints in 106 subjects, including 89 men and 17 women 19 to 71 years of age, were examined with respect to morphologic characteristics of the disc, the antero-posterior length of the disc, reduction or non-reduction of the disc, and the relative position of the disc to the condyle.
Discs with reduction were observed in more than 95% of the examined joints, and discs without reduction were more often noted in women than in men. More than 85% of the examined discs were biconcave, and disc deformation was more common in women than in men.
Analysis of the distribution of the posterior band position relative to the top of the condyle, a landmark for identifying anteriorly displaced discs, indicated that the disc was properly located if its posterior margin was within 4 mm from the top of the condyle, and that the posterior margin was positioned anteriorly to the apex of the condyle in 40% of the joints. On the other hand, the central thin zone of the disc, the relation of which to the condyle is another landmark for disc displacement, was antero-inferior to the anterior prominence of the condyle in approximately 12% of the examined joints.
The results suggest that the prevalence of anterior disc displacement differs according to the criteria used for diagnosis. Therefore, more comprehensive criteria are required for the diagnosis of anterior disc displacement.

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Effects of aging on the regeneration of bone were evaluated by comparing male New Zealand White Rabbits of different ages with respect to the healing process of bony cavities in the mandible. Rabbits were divided into two groups according to age: a 14-weekold group, representing young or growing rabbits, and a 30-week-old group, representing adult or aging rabbits. A bony cavity of 12×10×4mm was prepared in the mandible of both groups; the periosteum was preserved carefully. Bone formation and cellular proliferation were examined morphologically, histomorphometically, and immunohistochemically using anti-BrdU monoclonal antibody. The results were as follows:
1) New bone formation and bone remodeling in the bony cavities of adult rabbit mandibles started later and the rate of bone formation was lower than that of the young rabbits.
2) The number of BrdU-positive cells in the bony cavities of the adult group was significantly less than that of the young group. The results suggested that aging was associated with decreased osteoblast acitivity.
3) Although adult rabbits showed significantly less new bone formation than young rabbits during the healing of bony cavities, the bony cavities in both groups were filled with new bone, and the mandibular outline was repaired by new cortical bone resulting from remodeling of newly formed bone 28 days after surgery.
4) During the healing process, the periosteum seems to play an important role in the formation of the mandibular outline, irrespective of age.

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Allogeneic blood transfusion involves risks such as viral infections and graft versus host disease. Autologous blood transfusion (ABT) can eliminate these side effects. However, ABT can cause other problems when anemia persists after blood collection. We gave ABT with recombinant human erythropoietin (EPO) to 19 patients undergoing orthognathic surgery and assessed the effectiveness of EPO. Autologous blood collection (400ml) was done on the 14th and 7 th days before operation (total, 800ml). Twelve patients received each 6, 000 IU of EPO every 2 days from the 14 th preoperative day for 6 times, a total dose of 36, 000 IU (group EPO). Seven patients did not receive EPO during autologous blood collection (control). Oral ferrous sulfate was given to both groups. In group EPO, just before operation the mean values (mean±1 SD) for RBC, Hb and Ht were 91.2±4.8%, 91.0±5.2%, and 93.5±4.5% of the baseline (14 days before operation) values, respectively. These values were significantly different between group EPO and control (RBC 85.6±5.7%, Hb 85.0±5.0%, Ht 87.5±5.9%). There were no significant differences between Hb and RBC values just before the 2nd collection and those just before operation in group EPO. No complications were observed during autologous blood collection with the use of EPO. Thus, ABT with EPO was useful in oral and maxillofacial surgery.

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Ninety cases of tongue cancer (1975-1995) were clinicostatistically investigated according to occurrence site, defind as the forward 1/3, central 1/3, and back 1/3 of the tongue.
1) Eighty-five percent of patients with cancers arising in the forward 1/3 and central 1/3 of the tongue sought medical consultation within one year after becoming aware of the lesion. However, in patients with cancer of the back 1/3, of the tongue one year or more was required before seeking medical consultation in about half of the cases.
2) Cases arising in the back 1/3 tended to increase with progression of stage from I to IV.
3) The 5-year survival rate of patients with tongue cancer occurring in the back 1/3 was significantly lower than those of patients with cancer of the foward 1/3 and central 1/3. Among patients with stage IV disease, 75% of those with tongue cancer of the back 14 died within one year after consultation, i.e., cases arising in the back % of the tongue had a very bad prognosis.

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We clinically analyzed 135 patients with newly diagnosed squamous cell carcinoma of the lip, oral cavity, and maxillary sinus region who presented at our department between 1985 and 1994. The result are summarized below.
(1) The 5-year cumulative survival rate was 68.2% overall, 75.6% in 117 patients who underwent operation, and 20.8% in 18 patients who underwent no operation.
(2) The number of cases and 5-year cumulative survival rate according to stage classification, were as follows: Stage I, 26 cases, 87.4%; Stage II, 45 cases, 78.1%; Stage M, 29 cases, 61.1%; Stage IV, 31 cases, 45.3%. In the operation group, the survival of stage IV patients improved substantially (61.3%).
(3) In the operation group, the outcome was excellent for patients in whom the lesion was located in the soft palate, central part of the jaw bone, the buccal mucosa, and the lower gingiva. On the other hand, the 5-year cumulative survival rate was under 70% for patients with lesions in the oral floor, the tongue, the lower lip, and the upper gingiva.
(4) In the operation group, there was a significant difference between the pN (+) group (35.2%) and pN (-) group (84.4%) with respect to the 5-year cumulative survival rate.
(5) The 5-year cumulative survival rate in the blood transfusion group (73.3%) was slightly inferior to that in the no-blood transfusion group (76.1%), but the difference was not significant.
(6) In the operation group (117 patients), 27 patients died of their tumors. Local recurrence occurred in 21 patients (17.9%). The tumor control rate was 73.5%.

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Mucoepidermoid carcinoma is relatively rare in childhood.
We report a case of mucoepidermoid carcinoma (low grade malignancy) in the buccal mucosa of a 13-year-old girl. She was treated by oral surgery alone, to avoid negative effects on growth and development. The tumor was located in the left buccal mucosa at the front of the Raphe pterygomandibularis. It was a round, solid mass with an elastic hard consistency and the size of a walnut. The tumor was resected with part of the masseter muscle, the temporal muscle, the external and internal pterygoid muscles, and the periosteum of the tuber maxillae. There has been no evidence of local recurrence or metastasis as of 35 months after operation, but the patient has difficulty in mouth openning.

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We report a rare case of mucoepidermoid carcinoma arising from a minor salivary gland in the lower lip. Mucoepidermoid carcinoma is a salivary gland neoplasm that is characterized by varying combinations of mucous, epidermoid, and intermediate cells. As for the minor salivary glands, the palate is the most common site for the development of this tumor. A 60-year-old woman presented at our clinic on February 8, 1994 because of a mass in the lower lip. There was a well-circumscribed swelling, measuring 18mm in diameter, in the lower lip. It was elastic soft and movable on palpation. Histopathological diagnosis of a mucoepidermoid carcinoma was made on examination of a biopsy specimen. With the patient under general anesthesia, the tumor was excised with a 5-mm safety margin on March 3, 1994. Histopathological examination of the surgical specimen showed a well-differentiated mucoepidermoid carcinoma. After surgery, the patient had a fairly good prognosis with no evidence of local recurrence or distant metastasis.

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We report a case of peripheral odontogenic fibroma arising in the mandible.
A 26-year-old Japanese woman visited our hospital because of gingival swelling in the right premolar region of the mandible.
The diagnosis was epulis, and the lesion was extracted. The pathological diagnosis was peripheral odontogenic fibroma. This may be the llth case reported in Japan.

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A case of mandibular deformity with central odontogenic fibroma is reported. A 21-year-old woman presented with facial asymmetry. On clinical examination, the center of the mandible was found to have shifted about 10 mm to the left. On radiographic examination, a radiolucent area with the impacted 6 was seen from 5 to the ramus in the mandible. Initially, we started preoperative orthodontic treament. Then, we resected the tumor and reconstructed the mandible with an autogenous iliac bone graft. After another 6 months, we performed sagittal splitting ramus osteotomy (SSRO). Six months after SSRO, an ITI Bonefit^® system was implanted into the right molar region to restore the occlusion. The histopathological diagnosis of this tumor was central odontogenic fibroma.

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A case of angiokeratoma occurring at the dorsal surface of the tongue is presented. The patient was a 6-year-old girl who had no other complication. The lesion was diagnosed clinically as a hemangioma. We examined biopsy specimens and performed cryosurgery. Histologically, cavernous dilatation of the papillary vessels and so-called “blood cyst” formation were observed. The pathological diagnosis was angiokeratoma. The postoperative murse was uneventful.

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A case of cavernous hemangioma with hypoplasia of the condylar process and asymmetry of the mandible is reported. A 35-year-old woman with a 20-year history of illness presented with limited mouth opening and left jaw joint pain. Panorama X-ray examination disclosed hypoplasia of the left condylar process and round calcified foci. Magnetic resonance imaging revealed a mass in the pterygoid plexus that extended around the mandibular neck. No feeding vessels or venous pooling of the tumor were found on angiography. The patient was placed under general anesthesia, and the tumor was resected by vertical mandibulectomy with an ultrasonic bone saw; a wide view of the pterygoid plexus was maintained. Asymmetry of the mandible was also improved by the operation. The pathological diagnosis was cavernous hemangioma with two phleboliths within the tumor mass. Facial appearance and oral function are normal with no evidence of recurrent disease as of 10 months postoperatively.

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Granular cell tumor, which characteristically has eosinophilic granules in the cytoplasm, is a relatively rare lesion in the oral and maxillofacial region. The authors encountered a case of a granular cell tumor arising in the floor of the mouth and investigated the immunohistochemical staining of the tumor. The patient was a 36-year-old man presenting with swelling of the floor of the mouth. Microscopic examination of a biopsy specimen revealed a granular cell tumor, and total resection of the tumor was performed. Histopathological examination disclosed a benign neurogenic tumor, adjacent to the minor salivary glands, which was composed of cells containing oval nuclei and abundant eosinophilic cytoplasm. On immunohistochemical examination of the tumor, the granules in the cytoplasm were positive for PAS staining and the tumor cells were strongly positive for S-100 protein staining. These findings revealed that the lesion was a granular cell tumor derived from Schwann cells.

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We report six cases of unilateral transverse facial cleft. Five patients were male and one was female. One case was diagnosed as solitary macrostomia, and other cases had accessory ears. Among latter cases, one also suffered from microtia and was diagnosed as the first and second branchial syndrome. Another case was diagnosed as Goldenhar syndrome because of the presence of epibulbar dermoid. The other cases were diagnosed as the first branchial syndrome.

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We report a rare case of bilateral hemorrhagic bone cysts of the mandible in a patient with idiopathic thrombocytopenic purpura (ITP).
A 12-year-old boy with ITP was examined to evaluate a swelling in the right side of the mandible. The initial panoramic radiograph showed multilocular radiolucent lesion resembling a hemophilic pseudotumor. Before operation, 10U of platelets were transfused. Under local anesthesia, fenestration was performed, and the involved tooth (right third molar) was extracted.
Microscopic examination of a biopsy spcimen revealed granulation tissue associated with fresh and old hemorrhage and hemosiderin deposition. A histopathologic diagnosis of hemorrhagic bone cyst was made.
After 5 years, the patient complained of swelling in the left side of the mandible. Ragiographic examination showed a multilocular radiolucent lesion that similar to the previous lesion. Before operation, 20U of platelets were transfused. While the patient was under general anesthesia, fenestration was performed, and I 5 6 7 8 were easily extracted. Primary hemostasis was completely achieved, and postoperative bleeding did not occur at either operation.
The results suggested that hemorrhagic bone cysts in ITP patients are similar ragiographically, microscopically to hemophilic pseudotumors.

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Storage pool disease is a rare congenital platelet-function disorder characterized by the absence of platelet dense granules and their contents, which causes prolongation of bleeding time. This report describes extraction of the bilateral third molars of the mandible and maxilla in a 22-year-old woman with storage pool disease. A conventional surgical technique was used. No evidence of collagen, ADP, or epinephrine-induced platelet aggregation was observed. Electron microscopy revealed the absence of dense granules. One hour after teeth extraction, the prolonged postoperative bleeding was controlled with the use of hemostatic preparations of gelatin and cellulose; a small gauze pack was placed over the socket and an anti-plasmin agent was injected.

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