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Chemoprevention of aerodigestive cancer.

Effective chemoprevention of aerodigestive tumors could have far-reaching effects. Aerodigestive cancer accounts for one-third of all cancer deaths in the United States and is the most common cancer in some areas of the world. Prognosis is poor, and a reduced quality of life remains in those who do survive. To date, there have been no effective chemopreventive agents, but many new compounds hold promise. The concepts of field carcinogenesis and multi step carcinogenesis underpin the development of chemopreventive agents for aerodigestive tract tumors. Important risk factors are tobacco use, alcohol consumption, dietary habits, genetic susceptibility, socioeconomic status, and the interaction of these. Two promising areas for surrogate biomarker development are tissue autofluorescence and DNA repair. Numerous chemoprevention trials have shown that antioxidant compounds are effective in reversing precursor lesions. Studies of the effects of chemopreventive agents on second primary tumors are ongoing. Finally, large-scale trials of the anti-oxidant beta carotene have been disappointing; they have shown that among heavy smokers and possibly heavy alcohol consumers beta carotene increases risk for lung cancer incidence and mortality. These findings underline the critical need to better understand specific mechanisms of action at a particular tissue site, and under various conditions, such as heavy smoking. Novel agents are under development: epigallacatchin gallate, or green tea, curcumin, and a new emphasis on folic acid. Studies to date show that targeting susceptible subgroups, by means of genetic or lifestyle factors, and all ethnic groups will facilitate the goals of chemoprevention studies.

Anticarcinogenic Agents↗

Adenoid cystic carcinoma metastatic to the dura: report of two cases.

Adenoid cystic carcinoma (ACC) originating in the salivary and lacrimal glands usually spreads to the intracranial space by following cranial nerves into the cavernous sinus, temporal bone and cerebellopontine angle. We present two cases in which ACC metastasized extensively to the dura, suggesting that ACC has an affinity for the dura. Case 1, a 43-year-old man, was operated on 12 years earlier for invasive ACC of the right palate. He experienced recurrence of the tumor in the left cavernous sinus and sella, and extensive involvement of the dura of both right and left temporal fossae. Case 2, a 33-year-old woman, had spread of ACC to the right convexity dura and tentorium after undergoing a resection of a left-sided ACC tumor of the lacrimal gland two years earlier. Both patients underwent multiple resections and radiation treatment. Extensive, multifocal, bilateral spread of ACC to the dura in both cases indicates that ACC has an affinity for the dura.

Adult↗

Lymphangioma involving the mandible: immunohistochemical expressions for the lymphatic proliferation.

We report a case of lymphangioma involving oral mucosa and mandible of an elderly female. The surgical and radiological examinations indicated that the lymphangioma was mainly distributed in the labial mucosa tissue, but had gradually extended into the periosteum and intrabony space of mandible. Immunohistochemical staining was also performed using antiseras of alpha-smooth muscle actin (alpha-SMA), von Willebrand factor (vWF), angiogenin, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) to elucidate the pathogenetic implications of the intraosseous lymphangioma. The present case of lymphangioma showed strong immunohistochemical reactivity of angiogenin and vWF, while it showed weak reactions of VEGF and PCNA. The immunostaining of alpha-SMA disclosed an abnormally thinned and discontinuous smooth muscle layer in the lymphatics. Both the X-rays and histological examination showed that the lymphangioma lesion was gradually extending into the adjacent osteoporotic marrow space of mandible. Therefore, we believe that the present case of intraosseous lymphangioma, which showed the harmatomatous growth of the lymphatics into the marrow space of mandible, is closely related to osteoporotic changes of old age.

Actins↗

Alcohol and cancer.

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Alcohol Drinking↗

In vitro antitumour activity of cis- and trans-5-fluoro-5,6-dihydro-6-alkoxy-uracils; effects on thymidylate synthesis.

A class of new 5-fluorouracil (FU) analogues, the 5-fluoro-5,6-dihydro-6- alkoxy-uracils was synthesised with a modification at the 6-position of the pyrimidine ring. At this position the analogues have a hydroxy or alkoxy group of different chain lengths either in the cis- or trans-configuration. The antiproliferative effect of these compounds was tested on five cell lines of different origin. Generally, the analogues with a cis-configuration had a higher activity than those with a trans-configuration. The growth inhibitory effect of the compounds decreased with increasing alkoxy chain length, but the compound with a hydroxy group had the lowest growth inhibitory effect. One analogue, cis-5-F-5,6-dihydro-6-methoxy-uracil had a higher antiproliferative effect than FU in one of the cell lines. Effects on thymidylate synthase (TS), the possible target of these analogues, were evaluated by thymidine rescue of growth inhibition and incorporation of tritiated deoxyuridine (3H-UdR) into DNA. In solid tumour cell lines addition of TdR reversed the antiproliferative effect. Inhibition of TS in intact cells was determined by measuring 3H-UdR incorporation in two cell lines. The effect of cis-5-F-5,6-dihydro-6-methoxy-uracil on incorporation of 3H-UdR was 2- to 5-fold stronger than that of FU in both cell lines. All other compounds produced a higher 3H-UdR incorporation than FU both at equimolar and equi-toxic concentration. Concluding from these results we regard cis-5-F-5,6-dihydro-6-methoxy-uracil as the most promising FU analogue of this series, because of its higher antiproliferative activity than FU and marked inhibition of TS in intact cells.

Carcinoma, Squamous Cell↗

Defect in serine 46 phosphorylation of p53 contributes to acquisition of p53 resistance in oral squamous cell carcinoma cells.

To investigate whether dysregulation of p53 phosphorylation confers tumor resistance to p53, we analysed the effects of wild-type p53 on oral squamous cell carcinoma (SCC) cell lines carrying various mutations of p53. Introduction of exogenous p53 neither induced apoptosis nor suppressed colony formation in HSC-3 cells lacking any detectable p53 and HSC-4 cells expressing mutant p53R248Q protein. Consistently, exogenous p53 did not induce proapoptotic p53-target genes in these p53-resistant cells. We found that phosphorylation of exogenous p53 on serine 46 (Ser46) was severely impaired in HSC-3 but not HSC-4 cells. A mutant mimicking Ser46-phosphorylation (p53S46D) enhanced proapoptotic Noxa promoter activity, and overcame the resistance to p53-mediated apoptosis and growth suppression in HSC-3 cells. Conversely, a mutant defective for Ser46-phosphorylation (p53S46A) failed to suppress the growth of p53-sensitive HSC-2 cells. In contrast to HSC-3 cells, p53S46D had no effect on HSC-4 cells, and inhibition of endogenous p53R248Q by siRNA restored p53-mediated apoptosis in HSC-4 cells, indicating a dominant-negative effect of p53R248Q protein on wild-type p53 function. These results demonstrate that the defect in Ser46 phosphorylation accounts for the p53 resistance of HSC-3 cells, and provide evidence for a mechanism underlying the acquisition of p53 resistance in oral SCC.

Adenoviridae↗

Mandibular invasion in patients with oral and oropharyngeal squamous carcinoma.

Invasion of the mandible in squamous carcinoma of the oral cavity and oropharynx has always proved a problem for head and neck oncologists. We studied 82 patients who had mandibulectomies as part of their primary surgical treatment for cancer of these sites. In 40 patients, the tumour appeared to be invading the mandible on clinical grounds and 33 patients had tumours invading the mandible when the latter was examined histopathologically. Multivariate analysis showed that tumour was more likely to be fixed to and clinically invading the mandible in the presence of cancer of the oral cavity, compared with oropharyngeal cancer (P < 0.0001). There was a high degree of correlation between clinical invasion of the mandible and histopathological invasion of the mandible (P = 0.0059). In addition, clinical invasion of the mandible correlated with radiological findings (P = 0.0284). The 5-year survival of those patients with tumour that appeared not to be invading the mandible was 53% compared with 25% for those where tumour did appear to be invading the mandible (P < 0.02). The sensitivity and specificity of clinical evidence of mandibular invasion was calculated with the final arbiter of invasion being the histopathological findings. The sensitivity of clinical examination was 91% and the specificity 80%. The positive predictive value was 75% and the negative predictive value 93%. Mandibular invasion is a poor prognostic sign in cancer of the oropharynx and oral cavity. Detection of invasion prior to operation is obviously extremely important and it appears that clinical findings are an accurate method of predicting invasion.

Adult↗

The role of neck dissection in head and neck mucosal squamous cancer.

The most clinically useful system of classification of neck lymph nodes is grouping into levels I-V. Anatomical, clinical and pathological studies demonstrate that although generally lymphatic flow is from above downwards, level I is often bypassed and level V is seldom involved. Neck dissection is classified into radical, modified radical, selective and extended radical neck dissections. Recent studies demonstrate that elective neck dissection is beneficial to the outcome of oral cancer patients, but not necessarily to laryngeal and pharyngeal cancer patients. Modified radical neck dissection is as effective as radical neck dissection when performed in the elective situation. Selective neck dissection in the form of supra-omohyoid neck dissection is useful as a staging procedure. Modified radical neck dissection is acceptable for the N1 neck provided postoperative radiotherapy is given.

Carcinoma, Squamous Cell↗

Ameloblastic carcinoma: report of an aggressive case with multiple bony metastases.

Ameloblastic carcinoma is a rare primary tumor of the maxillofacial skeleton with a distinct predilection for the mandible. These lesions may initially show histologic features of ameloblastoma that dedifferentiate over time. Other ameloblastic carcinomas initially present with morphologic features suggestive of ameloblastoma with areas of epithelial dedifferentiation. We herein report a rare case of aggressive ameloblastic carcinoma in a 22-year-old white man who developed widespread bony metastases and expired 4 years after initial diagnosis.

Adult↗

Dentascan in oral imaging.

In the past, dental disease and lesions involving the jaw were either evaluated by plain radiography or tomography. The advent of spiral computed tomography (CT) and DentaScan is changing the imaging trend. It is now not only used for pre-implant assessment but also in the diagnosis of lesions affecting the jaw. This pictorial review discusses the role of DentaScan in the various abnormalities that may affect the mandible and maxilla.

Ameloblastoma↗

Oral metastasis of renal cell carcinoma in a horse.

A 14-year-old hunter gelding presented with an ulcerated mass on the left premaxilla. Biopsy of the mass revealed a poorly differentiated carcinoma. Surgical excision was attempted, but local regrowth followed several months later, at which point radiotherapy was carried out. An initial improvement was followed by marked deterioration and the animal was humanely killed. Post-mortem examination revealed a massively enlarged right kidney and associated widespread metastases. A metastatic clear cell renal carcinoma was identified by histological examination.

Animals↗

Functional and aesthetic results of various lip-splitting incisions: A clinical analysis of 60 cases.

PURPOSE: This study retrospectively evaluated the functional and aesthetic results of various types of lip-splitting incisions in a group of patients in whom this approach was used to treat intraoral tumors. PATIENTS AND METHODS: Between 1992 and 1998, 87 consecutive patients were subjected to either mandibulotomy or mandibulectomy using a lip-splitting incision. During this period, 4 types of incisions were sequentially used: straight midline incision, lateral lip-splitting incision, midline splitting with extension around the contour of the chin, and the chevron chin-contour incision. Sixty patients with a follow-up of at least 6 months were included in the study. The patients were asked to answer a questionnaire regarding the degree of satisfaction with the cosmetic result of the procedure and were clinically assessed for sensory and functional impairment resulting from the incision. The remaining 27 patients were lost to follow-up or had died of their disease. RESULTS: The lateral lip-splitting incision caused the fewest postoperative problems in patients subjected to either mandibulotomy or mandibulectomy. The best overall results were achieved by the chevron-chin contour incision. The incision that followed the contour of the chin and the straight midline incision showed less satisfactory results. CONCLUSION: The chevron chin-contour incision, along with meticulous soft tissue closure, produces the best aesthetic and functional results.

Aged↗