Effects of sex hormones on rat tongue carcinoma induced by 4-nitroquinoline 1-oxide (4NQO).

We investigated the regulatory effects of sex hormones on tongue carcinoma initiated by orally administration 4-nitroquinoline 1-oxide (4NQO) to rats. Animals of either sex were classified into three groups. The male rats in each group received an estrogen administration (Me), orchiectomy (Mor), or both treatments (Me/or) while the female rats also received testosterone administration (Ft), ovariectomy (Fov), or both treatments (Ft/ov). The differences in the carcinogenic progress among these groups were examined by macroscopic and microscopic observation of tongue tissues. The incidence of cancer in the tongue tissue was 100% in the group reinforced with testosterone (testosterone+group) (Ft, Ft/ov, Me) but only 56.0% in the group not reinforced with testosterone (testosterone-group) (Fov, Mor). These findings suggest that sex hormones play a role in the onset of 4NQO-induced tongue carcinoma.

Patterns of mandibular invasion by gingival squamous cell carcinoma.

PURPOSE: This study examined patterns of invasion of lower gingiva cancer into the mandible. Our goal was to clarify the most common routes for gingival squamous cell carcinoma to enter and spread within the mandible. PATIENTS AND METHODS: The subjects were 176 patients with lower gingival squamous cell carcinoma who underwent mandibulectomy; all tumors were examined histopathologically. The method of mandibulectomy was decided on the basis of conventional plain radiographic and computed tomographic findings. RESULTS: The tumor extended to the periosteum in 33%, to the cortical bone in 23%, and to the bone marrow in 9% of the patients who underwent mandibular resection. The remaining 35% of our patients had no evidence of mandibular invasion. CONCLUSION: The area of bone resorption on preoperative clinical and radiographic examinations often disagreed with the extent of mandibular invasion on histopathologic examination.

Effect of YM529 on a model of mandibular invasion by oral squamous cell carcinoma in mice.

PURPOSE: This study examined the mechanisms of osteoclast-mediated bone invasion in a model of oral squamous cell carcinoma (OSCC). C3H/HeN mice were inoculated with SCC VII cells into the masseter region to establish an animal model of mandibular invasion by OSCC. EXPERIMENTAL DESIGN: The mice were divided into three groups: a control group, given daily s.c. injections of saline; group 1, given 2 microg per mouse per day of the bisphosphonate YM529; and group 2, given 10 microg per mouse per day of YM529. After 3 weeks of treatment, the lesions were studied by micro-computed tomography. After tartrate-resistant acid phosphatase (TRAP) staining, the osteoclasts were easily identified, and the percentages of the area occupied by osteoclasts were calculated by computer for each sample. The tumors were analyzed by RT-PCR to determine the mRNA expression of interleukin-6 (IL-6), parathyroid hormone-related protein (PTHrP), tumor necrosis factor-alpha (TNF-alpha), receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin. RESULTS: SCC VII cells rapidly multiplied in the masseter muscle of the mice. Bone invasion was evident only in the control group on micro-computed tomography. On TRAP-stained slices, the percentages of osteoclasts in groups 1 and 2 were significantly lower than that in the control group. The mRNA expressions of IL-6, PTHrP, THF-alpha, and RANK decreased as the concentration of YM529 increased. CONCLUSIONS: We conclude that various cancer-derived cytokines play important roles in the invasion of bone by OSCC. YM529, a third-generation bisphosphonate, can suppress osteoclast-mediated bone invasion by OSCC. The mechanism of this effect might involve inhibition of cytokines such as IL-6, PTHrP, TNF-alpha, and RANK by YM529.

Material analysis of AO plate fracture cases.

PURPOSE: The clinical observation of fracture cases and material evaluation of fractured titanium plates were performed to investigate the causes of fracture. PATIENTS AND METHODS: Fracture of titanium plates occurred in 4 patients of the 110 mandibular reconstructions. We clinically and experimentally evaluated plate fracture cases among cases in which primary reconstruction using titanium plates was performed after the mandibular resection. RESULTS: Titanium plate fracture was frequently observed in L-type defect cases in which angle-type plates were used, and fracture mainly occurred in the anterior region of the mandibular angle. Material analysis suggested that the occurrence of fracture can be prevented by eliminating constricted parts on the internal side of the plates. CONCLUSIONS: The causes of fracture were thought to be the use of plates under the conditions of comparatively frequent repeated application of stress or fatigue fracture caused by stress concentration, depending on the form of the plate.

[A case of primary lung cancer in a young female with tongue cancer].

We describe a case of lung tumor in a 33-year-old woman with tongue cancer. She had noticed a painful sensation in her tongue in April 2000. The results of a physical examination showed a 22 x 11 mm ulcerated lesion on the right side of her tongue. A biopsy specimen showed a moderately differentiated squamous cell carcinoma. A preoperative chest radiograph showed no evidence of pulmonary metastasis. No neck lymphadenopathy was found. The tongue cancer was resected in September 2000, and the pathological stage was T2 N0 M0. A solitary pulmonary lesion appeared 8 months after the surgery. A Histological examination of a transbronchial lung biopsy specimen showed a moderately differentiated squamous cell carcinoma. It was difficult to distinguish histopathologically or immunohistochemically between a second primary tumor and a metastasis, but the pulmonary lesion was considered to be a second primary tumor on the basis of a single endobronchial lesion that appeared after the T2 tongue cancer with no regional recurrence or cervical lymphadenopathy. Treatment with chemotherapy and irradiation was not effective and the patient died 3 months after the diagnosis of lung cancer.

Allelic loss on chromosomes 2q, 3p and 21q: possibly a poor prognostic factor in oral squamous cell carcinoma.

Loss of heterozygosity (LOH) correlates with inactivate tumor suppressor gene. The aim of this study was to see if LOH on chromosomes 2q, 3p and 21q correlated with a poor prognostic factor in oral squamous cell carcinoma (SCC). We analyzed chromosomes 2q, 3p and 21q for LOH in 40 primary oral SCCs using 30 markers and constructed a deletion map for these chromosome arms. Significant LOH (>20%) occurred at alleles in chromosome bands 2q14-21 (21.7%), 2q32-35 (31.6%), 2q35 (21.1%), 2q36 (36.7%), 3p25 (32.4%), 3p21.3 (23.8%), 21q11.1 (52.4%), 21q21 (21.6%) and 21q22.1 (22.2%). A significant correlation was observed between the number of regions showing LOH at 2q and TNM clinical stage (P=0.0063), consistent with the progressive accumulation of genetic errors during the development oral SCC. The number at more than two LOH loci was significant with a poor prognosis at 2q (P=0.0208). These findings demonstrate that oral SCC exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis. This is the first study to demonstrate the prognostic significance of LOH at 2q, 3p and 21q for oral cancer and may help to identify patient who should receive more aggressive treatment.

Reconstruction of the inferior alveolar nerve by autologous graft: a retrospective study of 20 cases examining donor nerve length.

The purpose of this study was to confirm the length and kind of donor nerves used in nerve grafts for reconstruction of inferior alveolar nerve defects. The authors conducted a retrospective study of surgeries that were performed between 1977 and 1996. A total of 20 patients underwent nerve grafting procedures during this period. The greater auricular nerve was selected as the donor nerve in 16 cases, while the sural nerve was selected in 4. Mean lengths of donor nerves were 7.28 +/- 1.6 cm and 11.5 +/- 3.4 cm for the greater auricular and sural nerves, respectively. As indicated, the sural nerves were significantly longer (p < 0.01). Mean lengths of donor nerves grafted for partial resection and hemi-mandibulectomy were 7.23 +/- 1.6 cm and 10.8 +/- 3.4 cm, respectively. Statistical analysis indicated that grafts used in the hemi-mandibulectomy group were significantly longer (p < 0.05). In terms of types of donor nerve used in mandibulectomies, the greater auricular nerve was used in the majority of partial resections, and the sural nerve was employed for hemi-mandibulectomy.

Over-expression of DNA methyltransferases and CDKN2A gene methylation status in squamous cell carcinoma of the oral cavity.

The present study was designed to investigate the potential relationship between CDKN2A (p16) gene hypermethylation, which has reported to be frequently observed in oral squamous cell carcinomas (OSCCs), and expression of human DNA methyltransferases (DNMTs: DNMT1, DNMT3A and DNMT3B). Twenty-five pairs of primary OSCCs and matched normal oral mucosa tissues were examined. The p16 gene was hypermethylated (48%) in the tumors showing significant down-regulation of both mRNA and protein expressions. A demethylation assay on 8 OSCC-derived cell lines was also performed by means of treatment with the demethylating agent, 5-aza-2'-deoxycytidine. Four of 5 cell lines showing down-regulation of the p16 gene, revealed re-activation of gene expression after the treatment. In contrast, frequent over-expression of DNMT mRNA expression, also found in the expression of the proteins, was detected: DNMT1 at 72% and DNMT3A at 56%, and DNMT3B at 64%, respectively. However, we could not identify any statistical significance between p16-hypermethylation status in individual tumors and the expression of any of the three DNMTs. These data suggest that hypermethylation of the p16 gene and up-regulation of DNMTs are involved in oral carcinogenesis, but they may be through different mechanisms.

Histopathologic damage to vessels in head and neck microsurgery.

PURPOSE: This study assessed the incidence of pre-existing damage in recipient arteries excised before the vessels were used for microvascular anastomoses between 1988 and 1999. PATIENTS AND METHODS: Recipient arteries of the head and neck region from 100 patients who had undergone ablative surgery requiring microvascular tissue reconstruction were examined histologically. Past illnesses believed to be risk factors included hypertension, myocardial disease, and diabetes. Blood vessels chosen for microsurgical anastomoses were examined using histological staining, scanning electron microscopy, and immunofluorescence. RESULTS: Of the patients undergoing microvascular surgery, 51% showed histologic vessel abnormalities. Marked thickening of the blood vessel wall and severe exfoliation of the endothelial cells were observed in most arteries. Thickening of the intima was evaluated using scanning electron microscopy (Friedman's method; Microvasc Res 3:416, 1971). Values higher than twice the ratio of wall thickness-to-lumen diameter were observed in 9 recipient arteries. Six graft failures were correlated with both technical errors and pre-existing vessel lesions. CONCLUSIONS: This study revealed that most patients undergoing microsurgery in the head and neck region had pre-existing damage to vessels that hindered anastomoses. Pre-existing changes in the recipient arteries may cause technical difficulties and must be regarded as additional factors contributing to graft failure.

Allelic loss of chromosome 2 in human oral squamous cell carcinoma: correlation with lymph node metastasis.

To evaluate the role of chromosome 2 deletions in human oral squamous cell carcinoma (SCC) progression and to define the precise location of putative tumor suppressor genes, we examined 40 primary tumors and seven lymph node metastatic tumors from 40 patients with oral SCC by the polymerase chain reaction (PCR)-loss of heterozygosity (LOH) assay, using 10 different polymorphic loci on the long arm of chromosome 2. LOH was observed in 67.5% of the patients at one or more loci on the chromosome 2q. Two commonly deleted regions with high frequency of LOH, D2S1327 region at 2q32-35 (31.6%) and D2S206 region at 2q36 (36.7%), were identified by the deletion mapping of chromosome 2q, suggesting the presence of putative tumor suppressor genes associated with oral SCC. Examination of seven metastatic tumors also revealed four commonly deleted regions, D2S436, D2S1327, D2S155, and D2S164. Of these four regions D2S1327 region has no significant increase in the frequency of LOH between in primary tumors and in metastatic tumors. However, at other three regions the frequencies were much increased in metastatic tumors, comparing the results in primary tumors. Especially, very high frequencies of LOH in metastatic tumors were detected at two regions on 2q35, 100.0% at D2S155 and 57.1% at D2S164, suggesting the significant relationship between lymph node metastasis and LOH at these two regions. Our results indicate that LOH on chromosome 2q is a common event in oncogenesis and/or progression of oral SCC, and also suggest that the LOH at 2q35 play a significant role in the lymph node metastasis.

Lesions related to the formation of bone, cartilage or cementum arising in the oral area: a statistical study and review of the literature.

This report contains a statistical review of 559 cases of lesions forming hard tissues that were diagnosed by the departments of Clinical Pathophysiology and of Pathology at Tokyo Dental College from 1966 to 2001. Sixteen kinds of lesions which were related to the formation of bone, cartilage or cementum were analysed: osteoma, osteo-chondroma, chondroma, osteoid osteoma, osteoblastoma, ossifying fibroma, cemento-ossifying fibroma, cementifying fibroma, so-called cementoma, cementoblastoma, gigantiform cementoma, periapical cemental dysplasia, osteosarcoma, chondrosarcoma, fibro-osseous lesion, and fibrous dysplasia of bone. The most common lesion was osteoma (203 cases). There is a marked tendency for this condition to occur in females (201 males cases and 358 female cases). The patients' ages ranged from 3 to 84 years, and the mean was 40.1 years old. Lesions with hard tissue formation were observed most frequently in the third decade and in the mandibular molar region.

Anterolateral thigh flap.

A 64-year-old Japanese male had a squamous cell carcinoma (T4N1M0) in the left gingival and buccal mucosa, so a radical wide resection involving left radical neck dissection was performed. An anterolateral thigh flap measuring 15 x 8 cm was raised from the left thigh and transferred to the defect. The postoperative course was eventful. There was no postoperative flap necrosis, infection, not even a cervical fistula.

Fracture of mandibular reconstruction plates used after tumor resection.

PURPOSE: We assessed the incidence of fractured plates after primary temporary AO plate reconstruction of the mandible following tumor resection. PATIENTS AND METHODS: One hundred ten patients were retrospectively evaluated according to the extent of the tumor, anatomic location of the reconstruction, type of plate, additional use of radiotherapy or flap surgery (or both), and the incidence of fractured plates. RESULTS: Fractured plates occurred in 8 of 110 patients. Most occurred less than 6 months after surgery. All of the 8 patients had a malignant tumor; 2 had received radiation therapy and 4 had skin flaps placed. The fractured plate was the straight type in 1 patient and the angular type in 7 patients. Among patients who had fractured plates, the average number of remaining teeth was 12.8 in the maxilla and 9.5 in the mandible. CONCLUSIONS: Fractured plates were more common among patients with oral cancer with a segmental defect that did not cross the midline in whom an angular-type plate was used and no bone grafting was performed.

Oral cancer research with an emphasis on genomic analysis.

Ablative surgery has been a standard procedure for many years, but during the past few years there has been a significant improvement in our understanding of invasion and metastasis in oral cancer. Each procedure has to be planned individually. Before surgery, every attempt must have been made to arrive at a proper diagnosis, including the exact nature and aggressiveness of the tumor and an analysis of the patient's genetic background. These procedures and the prognosis will be discussed.

The presence of candidate tumor suppressor gene loci at chromosome 3p for oral squamous cell carcinomas.

We investigated the short arm of chromosome 3 (3p) for allelic imbalances, including loss of heterozygosity (LOH) and microsatellite instability (MSI) in 40 primary oral squamous cell carcinomas (SCCs) using 10 microsatellite markers and constructed a deletion map for this chromosome arm. We examined 40 primary tumor tissues, 40 corresponding normal tissues, and seven lymph node metastatic tissues. LOH at one or more loci was found in 24/40 (60%) of tumors. Deletion mapping of these tumors revealed at least three discrete, commonly deleted regions on the chromosome arm. Furthermore, we detected MSI in six of those tested cases (15%). We compared our results with the clinicopathologic features. A number of sites displaying LOH at 3p could be detected in early stage lesions, and the frequencies of LOH tended to be higher in later clinical stages. Thus, the frequent LOH was observed from early stage in pTNM classification. An unknown tumor suppressor gene in the genesis of oral squamous cell carcinoma may exist in 3p.