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Granular cell leiomyoma of the oral cavity.

Granular cytoplasmic change is a reported but uncommon finding in leiomyoma. Leiomyoma in the oral cavity is also uncommon, and granular cell change in oral leiomyomas, to the best of our knowledge, has not been previously reported in the English literature. Two cases of oral leiomyomas with significant granular cell change are presented. These tumors may be confused with the more common granular cell tumor, however, routine histology and immunohistochemistry aided in establishing the diagnosis. Ultrastructural studies were done for one case. Both tumors were immunoreactive for muscle markers, namely, smooth muscle actin and desmin. One of the tumors (case 2) reacted postiviely for HHF-35 and alpha-1 antitrypsin. The tumors were unreactive for S-100 protein, pancytokeratin, myoglobin, and factor VIII related antigen (case 2).

Actins↗

Cell-mediated immune responses to COPV early proteins.

Cell-mediated immunity plays a key role in the regression of papillomavirus-induced warts and intra-epithelial lesions but the target antigens that induce this response are not clear. Canine oral papillomavirus (COPV) infection of the oral cavity in dogs is a well-characterized model of mucosal papillomavirus infection that permits analysis of the immune events during the infectious cycle. In this study we show that during the COPV infectious cycle, systemic T cell responses to peptides of several early proteins particularly the E2 protein, as assayed by delayed type hypersensitivity, lymphoproliferation and IFN-gamma ELISPOT, can be detected. The maximal response occurs in a narrow time window that coincides with maximal viral DNA replication and wart regression: thereafter, systemic T cell responses to early proteins decline quite rapidly. Vaccination using particle-mediated immunotherapeutic delivery (PMID) of codon-modified COPV E2 and E1 genes induces strong antigen-specific cell-mediated immune responses in the vaccinated animals. These data show that therapeutic immunization by PMID with codon-modified E2 is completely effective, that to E1 is partially protective, that this correlates with the intensity of antigen-specific cell-mediated immune responses and, further, they emphasize the importance of these responses and the route of immunization in the generation of protective immunity.

Animals↗

NF-kappaB and COX-2 during oral tumorigenesis and in assessment of minimal residual disease in surgical margins.

Oral cancer is a major health problem in many parts of the world including India. The molecular mechanisms involved in oral tumorigenesis are not completely understood. Although surgery continues to be the most common treatment modality for this cancer, survival rates of oral cancer patients have still not significantly improved over the last few decades. Classical diagnostic methods are still not sensitive enough in detecting completeness of surgery and assessing minimal residual disease. This study investigated the role of NF-kappaB and COX-2 both in oral cancer progression and assessment of minimal residual disease. Expression of NF-kappaB proteins and its inhibitory protein IkappaB-alpha was evaluated using immunohistochemistry, ELISA and EMSA, while RT-PCR was used to detect COX-2 expression. Cytoplasmic expression as well as nuclear translocation of NF-kappaB proteins increased with histological progression of oral cancer (from normal to leukoplakia to cancer). A similar pattern of expression was observed for COX-2 also. NF-kappaB proteins, both cytoplasmic and nuclear, had a significant negative correlation from tumor to surgical margin to extra margin; COX-2 paralleled the expression of NF-kappaB proteins. Our results thus point to NF-kappaB and COX-2 as participants in oral tumor progression and also to the validation of these two molecular markers in assessing minimal residual disease.

Blotting, Western↗

Recurrent chromosomal imbalances detected in biopsy material from oral premalignant and malignant lesions by combined tissue microdissection, universal DNA amplification, and comparative genomic hybridization.

Biopsies routinely performed for the histopathological diagnosis of oral epithelial lesions before treatment were screened for chromosomal imbalances by comparative genomic hybridization. Comparative genomic hybridization was performed on 12 oral premalignant lesions (OPLs; dysplasias and carcinomas in situ) and 14 oral squamous cell carcinomas (OSCCs). Eight biopsies displayed areas of different histopathological appearance, so that OPLs and OSCCs from the same patient were analyzed. To avoid contamination with nonneoplastic cells, defined cell populations were isolated by micromanipulation with a glass needle. Before comparative genomic hybridization analysis, universal DNA amplification was performed using the DOP-polymerase chain reaction protocol. In the 14 OSCCs examined, the average number of chromosomal imbalances was significantly higher than in the 12 OPLs (mean +/- SEM: 11.9 +/- 1.9 versus 3.2 +/- 1.2; P = 0.003). The DNA copy number changes identified in more than one OPL were gains on 8q (3 of 12) and 16p (2 of 12), as well as losses on 3p (5 of 12); 5q (4 of 12); 13q (3 of 12); and 4q, 8p, and 9p (2 of 12 each). In more than 30% of OSCCs, gains of chromosomal material were identified on 20q (8 of 14); 8q, 11q, 22q (7 of 14 each); 3q, 15q, and 17p (6 of 14 each); and 14q, 17q, and 20p (5 of 14 each), and losses were identified on 3p and 4q (9 of 14 each), 5q (7 of 14), 13q (6 of 14), and 2q and 9p (5 of 14 each). These results were validated by positive and negative control comparative genomic hybridization experiments and microsatellite analysis for the detection of allelic loss. The vast majority of genomic alterations found in OPLs were again identified in OSCCs from the same biopsy, supporting the hypothesis that multiple lesions in the same patient are clonally related. In summary, we show that comprehensive information on the genomic alterations in oral epithelial lesions can be obtained from small biopsies. Such data may identify prognostic indicators that could eventually assist in designing therapeutic strategies.

Adult↗

Detection of squamous neoplasia by fluorescence imaging comparing porfimer sodium fluorescence to tissue autofluorescence in the hamster cheek-pouch model.

BACKGROUND: Early neoplastic changes in the oral cavity may be difficult to detect. Fluorescence imaging using porphyrin-derived drugs has been used to enhance detection of neoplasia. Autofluorescence has also been used for this purpose. This paper compares autofluorescence to porfimer sodium-induced fluorescence in the detection of neoplasia in the hamster cheek-pouch model. MATERIALS AND METHODS: Neoplasia was induced in the hamster cheek pouch by the application of 9,10-dimethyl-1,2-benzanthracene. Animals were imaged either with injection of drug (porfimer sodium) or without drug (autofluorescence). Imaging was carried out using a laser-induced fluorescence detection system. Biopsies were performed on imaged sections and histologic grades were assigned. RESULTS: Porfimer sodium fluorescence provided 100% sensitivity and specificity in detection of neoplasia. The sensitivity and specificity with autofluorescence was 76% and 83%, respectively. CONCLUSIONS: Autofluorescence provides an accurate means of detecting early neoplastic changes in the hamster cheek-pouch model; however, porfimer sodium imaging does improve detection rates.

9,10-Dimethyl-1,2-benzanthracene↗

Expression of bone sialoprotein in mineralized tissues of tooth and bone and in buccal-pouch carcinomas of Syrian golden hamsters.

The expression of bone sialoprotein (BSP) is normally restricted to mineralized connective tissues of bones and teeth where it has been associated with mineral crystal formation. However, recent studies have revealed ectopic expression of BSP in various lesions, including oral and extraoral carcinomas, in which it has been associated with the formation of microcrystalline deposits and the metastasis of cancer cells to bone. To develop a model to study the induction of BSP in carcinoma development, BSP expression in squamous-cell carcinomas induced by chemical carcinogen in the hamster cheek-pouch epithelium was investigated. Hamster BSP cDNA was first isolated and characterized, then used to prepare probes for Northern and in situ hybridization. The protein sequence of hamster BSP displayed 86% amino acid identity with a consensus mammalian BSP sequence and retained polyglutamate sequences, the RGD sequence and sites of phosphorylation, glycosylation and sulphation. The tissue-specific expression of hamster BSP mRNA and protein was confirmed by in situ hybridization and immunolocalization in developing tissues. Squamous-cell carcinomas induced in the buccal pouches of 5-week-old male Syrian golden hamsters treated with chemical carcinogen had BSP mRNA and BSP in the proliferating neoplastic epithelium. In contrast, neither BSP mRNA nor the protein could be detected in the stroma within which islands of the transformed tissue had formed. Thus, the hamster cheek pouch is a well-characterized model that can be used to study the induced expression of BSP in association with the development of squamous-cell carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

The role of nitric oxide in oral diseases.

Although previously regarded as a toxic pollutant gas, nitric oxide (NO) is a short-lived molecule that plays a key role in many physiological and pathological processes. It is produced in vivo from the amino acid L-arginine by a complex family of enzymes termed nitric oxide synthase (NOS). Since its discovery as a biological messenger in 1987, NO has been implicated in many disease processes, ranging from septic shock to cancer. It is a highly reactive free radical and causes concentration-dependent conformational changes in proteins, enzymes and DNA, predominantly by its reaction with transition metals and thiol residues. Although high concentrations of NO are cytotoxic, the levels produced in many human cancers possibly facilitate tumour growth and dissemination. The interest in this molecule by scientists and clinicians involved with the oral cavity and head and neck regions is fairly recent, and only a tiny minority of 50,000 papers currently cited on NO relate to diseases in this anatomical area. This review gives an overview of NO, outlining its basic chemistry, formation by NOS and its possible roles in the oral diseases studied to date. The implications for possible therapeutic manipulation of NO are also discussed.

Humans↗

Combined therapy of oral cancer bleomycin and radiation: a clinical trial.

A concurrent randomised controlled clinical trial to evaluate a combination of Bleomycin and radiation as against radiation only in the treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras, since 1971. All T3 and T4 previously untreated oral squamous cell carcinomas with N0, N1 and N2 regional nodes, or N3 nodes confined to the submandibular region, without systemic metastases or gross infiltration of the temporal and infratemporal fossa producing total trismus, and in decent general health were eligible for the trial. Patients with gross active pulmonary tuberculosis were excluded, as were recurrent carcinomas. Age, external fungation of growth or radiological bone invasion were no bar. Randomisation was done by the sealed envelope technique. The study group received concurrent fractionated cobalt 60 teletherapy using two opposing fields and 10-15 mg of Intra-arterial or Intravenous Bleomycin. The controls received fractionated cobalt teletherapy and i.v. or i.m. distilled water on the same protocol as the Bleomycin cases. All cases were evaluated double blind 8 weeks after the end of radiation therapy, and were classified as 'favourable response' or 'failure'. The criterion of 'favourable response' was 'total clinical healing of the tumour within the volume of irradiation with no subsequent recurrence within that volume, whatever the length of follow up'. Anything else was reported as a failure. A long term follow up of 3 years is also available. 136 cases have completed the trial. The favourable response in the study group was 77% as against 20.9% in the control group. The differential response is statistically significant. The present study is the fourth in the series of combined therapeutic trials conducted in advanced oral squamous cell carcinoma since 1958. (Krishnamurthi and Shanta, 1963, 1965, 1967 and 1971). A concurrent randomised controlled clinical trial to evaluate the combination of Bleomycin and radiation as against radiation only in treatment of advanced oral cancer has been conducted at the Cancer Institute, Madras since 1971.

Bleomycin↗

Combined bleomycin and radiotherapy in oral cancer.

A clinical trial comparing Bleomycin (BLM) plus radiation against radiation alone is reported. One hundred and fifty-seven previously untreated T3 and T4 and N0, N1 or N2 buccal squamous cell carcinomas were entered. Eighty-four of these received the combined therapy and 73 were controls. Cobalt-60 teletherapy using two opposing fields was employed. BLM was administered intra-arterially in 42 patients, intravenously in 22 patients and intramuscularly in 20 patients. The 73 controls received physiological saline as a placebo. Total clinical healing of the lesion within the volume of irradiation eight weeks after the end of radiotherapy was termed a favourable response. Anything else was a failure. Five-year recurrence-free rates and disease-free survival were also evaluated. The favourable response rate in the study group was 78.6% and in the control 19.1%. The corresponding recurrence-free rates and five-year survival rates were 71.8% and 17%, and 65.5 and 23.5% respectively. The main toxic features were acute mucositis, pneumonitis and dermatitis.

Bleomycin↗

The effect of chlorhexidine and benzydamine mouthwashes on mucositis induced by therapeutic irradiation.

A variety of mouthwashes are frequently used in the management of irradiation-induced mucositis. Benzydamine has recently been introduced for alleviating this condition. Its efficacy as a mouthwash was compared with chlorhexidine in two groups of patients receiving radiotherapy for oral carcinoma. Mucositis and pain were recorded over a 6 week period and oral carriage of Candida species, coliforms and Staphylococcus aureus was assessed using an oral rinse technique. There was no significant difference in the mucositis scores, overall pain scores or the yeast and bacterial species isolated between the two treatment groups. However, 58% (7 out of 12) and 92% (12 out of 13) patients reported oral discomfort when rinsing the mouth with chlorhexidine and benzydamine, respectively. In both groups, the most common coliform isolated was Klebsiella pneumoniae and the carriage of yeasts was significantly greater than that of coliforms. These results indicate that, although the individual patient acceptance of chlorhexidine is better than benzydamine, there is little difference between the two mouthwashes both in controlling pain and mucositis or in the oral carriage of the micro-organisms studied.

Aged↗

Complete mandibular subperiosteal implants for edentulous mandibles.

The complete mandibular subperiosteal implant is one of the oldest implant modalities. It has been serving thousands of people for over 25 years. All failures and problems created in the past have been due to the inadequate support and improper architectural design of the implant substructure. Through the mistakes made in experimentation over the years, better results have been achieved because of the improvement of the implant design. Proper evaluation and utilization of the available bone is essential for a successful prognosis for the edentulous mandible. The crossbar attachment that joins the four implant posts of the substructure provides better force distribution and less potential for resorption below the primary struts of the complete mandibular subperiosteal implant. The cast substructure rests on the bone and is covered by the mucoperiosteum. Satisfactory retention and stability is given to the definitive overdenture which is fitted over the protruding posts and crossbar design. The complete mandibular subperiosteal implant is a definite solution to the problem mandibular edentulous patient. Proper, careful, and conservative diagnosis is important. Skill, experience, and accuracy are major criteria for the success of a dental implant.

Chromium Alloys↗