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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Routinely formalin-fixed and paraffin-embedded material of 123 squamous cell carcinomas of the floor of the mouth and tongue bordered by non-tumorous mucosa were immunohistochemically investigated for the expression of p53 protein using a panel of four anti-p53 antibodies (CM1, PAb 1801, DO7, PAb240) following wet autoclave antigen retrieval. p53 immunoreactivity was detected in 55-67% of the carcinomas, with the different antibodies used showing a preferential accumulation of the p53-positive tumour cells at the invasive tumour front. In dysplastic and normal epithelium focal or dispersed p53 immunopositivity could be detected in 62-72% and 57-70% of the cases, respectively, regardless of the p53 immunostatus of the carcinomas. No statistically significant correlations between p53 immunophenotype of the tumours and clinico-pathological parameters, or survival of the patients, could be detected statistically. It is concluded that immunohistochemically detectable p53 accumulation in oral cancer might indicate an early stage of carcinogenesis. The immunohistochemical detection of p53 in these tumours, however, is without prognostic significance.
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PMID:[Immunohistochemical expression of p53 protein in squamous epithelial carcinomas and normal and dysplastic epithelium of the mouth cavity]. 941 Jun 11

Descriptive epidemiology of oral and pharyngeal cancer over the last four decades is reviewed, with specific focus on Europe. Substantial rises in mortality rates have been observed for younger males, mostly in eastern Europe. The independent role of alcohol and tobacco and their interaction on oral carcinogenesis is discussed, since these factors account for about three quarters of oral cancers in Europe. The influence of dietary factors, and in particular of a diet poor in fresh fruit and vegetables on oral carcinogenesis, is also discussed, since diet may account for 10-15% of oral cancer cases in Europe. Finally, among other carcinogens, the possibility of human papillomavirus involvement in the aetiology of cancer of the oral cavity and pharynx is overviewed. Implications for prevention are discussed.
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PMID:Epidemiology and prevention of oral cancer. 941 27

We have investigated loss of heterozygosity of p53 tumor suppressor gene in Indian oral cancer patients, individuals with premalignant leukoplakia lesions, and corresponding normal mucosa, to study the status of p53 alleles in oral cancer pathogenesis. Fifty oral cancers, and 42 oral leukoplakia lesions and corresponding clinically normal oral mucosa from 18 individuals, were analysed. Peripheral blood cells (PBCs) from all the individuals and 47 normal healthy volunteers were also included in the study. Polymerase chain reaction(PCR) of p53 Exon4, followed by restriction enzyme digestion with AccII due to the enzyme polymorphic site at Exon4 codon72, was used to detect homozygosity/heterozygosity of p53 alleles, and compared with the allelic pattern in the corresponding PBC. The PCR product subjected to AccII digestion detected 259 bp, 160/99 bp fragments indicating heterozygosity of p53 alleles in 69% of the 139 individuals. On comparison of the p53 allelic distribution in the lesions or tumour tissues, and corresponding PBC, LOH was observed in 20.5% oral tumors and 22% leukoplakias. However, there was no evidence of LOH in the clinically normal mucosa available from 16 individuals with leukoplakia. Our studies demonstrated LOH of p53 allele in early and advanced stages of oral cancers, as well as leukoplakias, perhaps indicating p53 LOH as one of the early events in oral carcinogenesis. Thus, p53 LOH may be useful as a biomarker in defining a certain population of high risk leukoplakias that may progress to oral cancer.
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PMID:Loss of p53 gene as a biomarker of high risk oral leukoplakias. 942 46

An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.
Carcinogenesis 1998 Mar
PMID:Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells. 952 75

Inactivation of tumor suppressor genes like p53 and p16 play a key role in tumor progression, with a high incidence of mutations existing for both genes in oral squamous cell carcinomas. Previous studies have demonstrated, (i) a correlation between the prevalence of p53 mutations and tobacco use [Brennan et al. (1995) New Engl. J. Med., 332, 712-717; Lazarus et al. (1996) Carcinogenesis, 17, 733-739], and (ii) a link between genotypes in specific xenobiotic metabolizing enzymes and oral cancer susceptibility [Park et al. (1997) Cancer Epid. Biomarkers Prev., 6, 791-797). In this paper, we present results of our examination of a series of 80 oral squamous cell carcinomas for p53 exons 5-9 and p16 exons 1-2 mutations, and the potential association of these mutations with specific genotyping patterns. p53 mutation prevalence in oral tumors was linked with increased patient tobacco use using several stratification criteria. There was a significantly higher prevalence of p53 mutations in OCSCCs from patients who smoked > 30 pack-years as compared to tumors from patients who smoked < or = 30 pack-years (OR = 2.8; CI = 1.1-7.2). No significant association was observed with patient alcohol consumption. There was a significant association between the prevalence of p53 mutations in oral tumors and CYP1A1 genotyping patterns in these oral cancer patients, with the highest p53 mutation prevalence observed in subjects with the CYP1A1 [val]/GSTM1 [+] genotype (OR = 6.0; CI = 1.2-29.7). A significant association was not observed between the prevalence of p16 mutations in oral tumors and tobacco use, or CYP1A1 [val] or GSTM1 (0/0) genotypes. These data suggest that the induction of mutations in specific tumor suppressor genes or oncogenes in oral tumors may be associated with specific carcinogen exposures, and that this association may be linked to specific polymorphic genotypes in xenobiotic-metabolizing enzyme genes.
Carcinogenesis 1998 Mar
PMID:p53, but not p16 mutations in oral squamous cell carcinomas are associated with specific CYP1A1 and GSTM1 polymorphic genotypes and patient tobacco use. 952 87

Changes in the expression of keratins (Ks), indicating disturbed tissue differentiation, is one possible marker of malignant potential in stratified squamous epithelia. The presence of human papillomaviruses (HPVs) in the epithelium of the uterine cervix is increasingly regarded as a marker of risk for cervical cancer: However, a similar role in oral cancer and precancer remains controversial. To address these questions, potentially malignant oral mucosal lesions from Sudanese (9 hyperplasias/40 dysplasias) and Swedish (15 hyperplasias) snuff-dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies directed against each. HPV infection was searched for by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. For the Sudanese lesions, moderate to intense expression of both K13 (basal, basal/intermediate, basal/intermediate/superficial and intermediate/superficial cell layers) and K14 (basal, basal/intermediate cell layers) was found in 49/49 (100%). For the Swedish lesions, weak to moderate expression of K13 (basal, basal/intermediate cell layers) was found in 12/15 (80%) and 10/15 (67%), respectively. In the Sudanese lesions, expression of K13 showed a distinct pattern through the oral mucosa and its verrucous projections, with an increase towards the superficial cell layers of dysplastic, but not hyperplastic epithelium. K19 was expressed in the basal cell layer in 16/49 (33%) of the Sudanese lesions, while all the Swedish lesions were negative. HPV was found in only 2 Sudanese cases, both of which harboured both type 6 and type 11: both these cases demonstrated mild epithelial dysplasia, The present study shows that a) there is a high prevalence of expression of both K13 and K14 in oral lesions from Sudanese toombak dippers indicating dysregulation of keratinocyte maturation b) one-third of the Sudanese oral lesions expressed K19, regarded as a basal keratin representing epithelial dedifferentiation, which may prove to be a valuable risk marker in follow-up studies c) HPV genome is found infrequently in oral lesions from Sudanese toombak-dippers, suggesting that these viruses may not play a prominent role in the early stages of carcinogenesis in these subjects. These markers were less often expressed in the Swedish lesions, consistent with their much lower rate of malignant transformation.
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PMID:Expression of keratin 13, 14 and 19 in oral hyperplastic and dysplastic lesions from Sudanese and Swedish snuff-dippers: association with human papillomavirus infection. 958 46

A cDNA representational difference analysis (cDNA-RDA) and an arrayed filter technique were used to characterize transformation-related genes in oral cancer. From an initial comparison of normal oral epithelial cells and a human papilloma virus (HPV)-immortalized oral epithelial cell line, we obtained 384 differentially expressed gene fragments and arrayed them on a filter. Two hundred and twelve redundant clones were identified by three rounds of back hybridization. Sequence analysis of the remaining clones revealed 99 unique clones corresponding to 69 genes. The expression of these transformation related gene fragments in three nontumorigenic HPV-immortalized oral epithelial cell lines and three oral cancer cell lines were simultaneously monitored using a cDNA array hybridization. Although there was a considerable cell line-to-cell line variability in the expression of these clones, a reliable prediction of their expression could be made from the cDNA array hybridization. Our study demonstrates the utility of combining cDNA-RDA and arrayed filters in high-throughput gene expression difference analysis. The differentially expressed genes identified in this study should be informative in studying oral epithelial cell carcinogenesis.
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PMID:Characterization of transformation related genes in oral cancer cells. 959 75

L-ascorbic acid is an essential dietary vitamin in humans, primates and certain mammals and is endogenously synthesised in some species. Epidemiological and ecological studies have shown that L-ascorbic acid has a protective effect against cancer, in particular non-hormone-dependent malignancies, such as oropharyngeal neoplasms. Experimental in vivo and in vitro studies, however, have yielded more controversial results, suggesting that the effects of L-ascorbic acid are dose- and perhaps, time-dependent with different effects depending on the species or organ studied. An update of the epidemiological and experimental evidence linking L-ascorbic acid to oral cancer and carcinogenesis is discussed together with a brief review of the possible mechanisms of action of L-ascorbic acid.
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PMID:The role of ascorbic acid in oral cancer and carcinogenesis. 968 Sep 1

Epidemiological evidence suggests that heavy consumption of betel quid and tobacco with areca nuts is the cause of high incidence of oral cancer in eastern part of Indian population, which is distinctly different from the etiology of oral squamous cell carcinomas (SCCs) in western countries. Here, expression of p53 and c-myc protein was studied in oral SCCs from this etiologically distinct population by immunohistochemistry. Out of 48 specimens of oral SCCs, 22 (45.8%) exhibited p53 positivity and 27 (56.3%) showed immunoreactivity with c-myc antibody. Considering the p53/c-myc expression pattern, either alone or in combination, the population was divided into four groups, i.e., both p53 and c-myc positive; p53 positive-c-myc negative; c-myc positive - p53 negative; and both p53 and c-myc negative. Tumours with both p53 and c-myc positivity were in advanced stages of the disease (poorly differentiated, tumour stage 3, nuclear grade III), whereas earliest stage of oral SCCs was detected in tumours with neither p53 nor c-myc immunoreactivity. Tumours of remaining two groups were generally restricted to early to moderate stages. These observations suggest that rapid progression of the betel- and tobacco-related oral SCCs may be associated with a simultaneous involvement of these two oncoproteins. The study also attempted to find out the relationship of p53/c-myc expression with spontaneous apoptosis. More apoptotic cells were found in c-myc positive but p53 negative tumours. This preliminary observation requires further molecular investigation of the role of p53 and c-myc genes for the progression of this epidemiologically distinct oral carcinogenesis.
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PMID:Co-overexpression of p53 and c-myc proteins linked with advanced stages of betel- and tobacco-related oral squamous cell carcinomas from eastern India. 978 19

In the United States, oral and pharyngeal cancers continue to result in significant morbidity and mortality. Dental professionals play a pivotal role in all facets of controlling the burden of oral and pharyngeal cancer-from efforts to prevent its occurrence, to ensuring that oral cancers are detected at the earliest possible stage, to treating these cancers, and to ensuring maximum quality of life and function for oral and pharyngeal cancer survivors. Individually and by making linkages within the community and beyond, dentists can help patients modify their risk of these cancers and can take steps to screen for them, thereby potentially improving survival and function of those who develop oral cancer. Creative partnerships between community dentists and academic and other research centers will help move knowledge of the biological processes involved in carcinogenesis and innovations in treatment into clinical practice. Partnerships between dental and medical professionals may also help efforts to reduce the morbidity related to oral and pharyngeal cancers. Local, state and national multidisciplinary initiatives are emerging that focus more broadly on risk factor control or oral and pharyngeal cancer issues. These many forms of cooperative approaches offer excellent opportunities to make a significant impact on reducing the incidence of and in treating these debilitating and disfiguring malignancies.
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PMID:Reducing the burden of oral and pharyngeal cancers. 979 Dec 81


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