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

Potentially, one of the most useful warning signals for the detection of environmental hazards is an unusually early age at onset of disease. Animal studies have shown age effects of this type with co-carcinogens. A clearcut example of a downward age shift in humans is provided by a study of the consumption of alcoholic beverages and cigarettes in women with oral concer. Using data on 145 white females with intraoral cancer, and 1973 non-neoplastic controls from patients seen at Roswell Park Memorial Institute between 1957 and 1966, it can be shown that exposure to both alcohol and tobacco can lead to onset of oral cancer 15 or more years earlier than would occur in women who do not use either alcohol or tobacco. Exposure to smoking only produces a smaller age shift, but exposure to alcohol only does not produce any clear shift in age of onset. Implications for co-carcinogenesis and for early detection of co-carcinogens in the environment are suggested.
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PMID:Early onset of oral cancer among women who drink and smoke. 101 47

Oral squamous cell cancer is the most common malignant tumour in Papua New Guinea. We have found that oral cancer in this region is concentrated at the corner of the mouth and cheek, by striking contrast with western populations, and corresponds precisely with the site of application of lime in 77% of 169 cases. Powdered slaked lime applied to the chewed Areca nut with Piper betle inflorescence at the corner of the mouth causes the mean pH to rise to 10, at which reactive oxygen species are generated from betel quid ingredients in vitro. Reactive oxygen species, together with sustained lime-induced cell proliferation, suggest a possible mechanism of carcinogenesis for this tumour.
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PMID:Slaked lime and betel nut cancer in Papua New Guinea. 136 76

Human head and neck squamous cell carcinogenesis (SCC) is a common malignancy that appears to be related to continuous exposure to putative carcinogens or promoters such as tobacco and alcohol. To understand the mechanisms of the development of head and neck cancer and to test the efficiency of new therapeutic approaches, the characterization of an animal model system is necessary. The check-pouch carcinogenesis model in Syrian golden hamsters is probably the best known animal system that is most closely comparable with the development of premalignant and malignant lesions in human oral cancer. Furthermore, it is one of the most well-characterized animal system models for SCC. Our first approach to understanding the cellular and molecular changes that occur in the hamster cheek-pouch carcinogenesis process was to compare this model to the mouse-skin system, in which a number of critical events have been well characterized. We examined the sequential expression of hyperplasia, micronucleated cells, ornithine decarboxylase activity, polyamine levels, transglutaminase I activity, epidermal growth factor receptor levels, expression of several keratins, gamma-glutamyl transpeptidase, and nucleolar organizer regions. We suggest that these markers can be used to understand mechanisms of carcinogenesis and, in addition, can serve as alternative shorter end points in studies of chemoprevention. We also present preliminary molecular studies in the experimental oral model. We obtained a partial sequence of exon 2 of the Ha-ras gene and detected an A182----T transversion in codon 61 in hamster cheek-pouch SCC induced by 7,12-dimethylbenz(a)anthracene.
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PMID:An animal model for oral cancer. 138 4

The inhibitory effect of oral administration of betel-leaf extract (BLE) and 2 of its constituents, beta-carotene and alpha-tocopherol, as single agents or in combination with dietary turmeric on methyl(acetoxymethyl)nitrosamine (DMN-OAC)-induced oral carcinogenesis in Syrian hamsters was studied. DMN-OAC was administered twice monthly for 6 months. The chemopreventive effect of BLE or its constituents with turmeric was determined by comparing tumor incidence observed in treated groups with that seen in control animals. The apparent site-specific chemopreventive effect of BLE or its constituents was demonstrated by inhibition of tumor incidence, reduction of tumor burden, extension of the tumor latency period and regression of established, frank tumors. The inhibitory effect of BLE or its constituents combined with turmeric was higher than that of the individual constituents. The study suggests that BLE could be developed as a potential chemopreventive agent for human oral cancer.
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PMID:Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine-induced hamster oral carcinogenesis. 159 32

The Harvey ras locus was examined for restriction fragment polymorphism and loss of allelic heterozygosity in 62 oral cancer patients. Southern blot analysis on BamHI digests of the tumour tissue DNA, revealed 23 patients with H-ras-1 heterozygosity. The probes used to study the polymorphism were the BamHI 6.6-kb fragment encoding the complete H-ras-1 sequence plus the variable tandem repeat (VTR) region, and the 1-kb MspI fragment encoding the VTR region. The allelic heterozygosity was better resolved by PvuII and further confirmed by TaqI. In addition, TaqI digestion demonstrated a unique VTR rearrangement indicated by 2.1-kb, 0.9-kb and 0.6-kb fragments, implying additional TaqI sites, in three of the patients. Further analysis of matched tumor tissue and peripheral blood cell DNA from the same patient demonstrated tumor-associated loss of one of the allelic fragments in 7/23 (30%) of the patients with H-ras-1 heterozygosity. However, the loss was not significantly correlated to clinicopathological parameters staging the disease. Thus, our data showing loss of H-ras-1 alleles and VTR rearrangement, with relatively high incidence (9/23; 39%) in the oral cancer patients at various stages of the disease, implies H-ras-1 involvement as an early event in the process of oral carcinogenesis.
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PMID:Loss of allelic heterozygosity at the harvey ras locus in human oral carcinomas. 167 60

Eosinophilia in tissues and/or circulating blood is known to be associated with a wide variety of malignancies but the role of the eosinophil in neoplastic conditions is not known. Using the cheek pouch of the Syrian hamster as an experimental model for oral carcinogenesis, it has recently been shown that eosinophils at sites of developing oral cancer express the multifunctional cytokine, transforming growth factor alpha (TGF-alpha). This study investigated the time course of eosinophil infiltration, tissue eosinophilia associated with malignant epithelium, and eosinophil-derived TGF-alpha mRNA during the 16-week 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral cancer development process. The results reveal that the occasional eosinophil is normally present in the lamina propria of hamster oral mucosa. With progressive DMBA treatments, there is an increase of eosinophils infiltrating into the lamina propria. By weeks 12-16, the number of eosinophils is significantly higher in DMBA-treated pouches than in control pouches treated with the vehicle mineral oil alone. Analysis of the infiltrating eosinophils into fully developed hamster oral carcinomas reveals that tissue eosinophilia is associated with 78% of the stromal areas associated with malignant epithelium, while only 7% of sites associated with non-tumor oral epithelium (normal, hyperplastic-dysplastic) exhibited eosinophilia. Furthermore, the majority of the eosinophils associated with malignant epithelium were found to contain TGF-alpha mRNA. The number of TGF-alpha mRNAs containing eosinophils associated with malignant oral epithelium is significantly higher than that associated with nonmalignant oral epithelium. Together, these results suggest that eosinophils are recruited to tumor-developing sites, that they predominantly associate with malignant epithelium, and that most tumor-associated eosinophils express the cytokine TGF-alpha.
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PMID:Eosinophils, tissue eosinophilia, and eosinophil-derived transforming growth factor alpha in hamster oral carcinogenesis. 172 10

This paper examines the evidence for an aetiological role for viruses in the development of oral carcinoma. Several viruses have been sought in oral cancer and evidence found for some, particularly herpes simplex and human papillomavirus. However, the evidence also suggests that these viruses are ubiquitous agents and a number of criteria must be met before these potentially oncogenic agents can reliably be implicated in human carcinogenesis. In contrast, there is no evidence that viruses such as adenovirus, Epstein-Barr virus, and retroviruses play any role in oral carcinogenesis.
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PMID:Viruses in the aetiology of oral carcinoma? Examination of the evidence. 177 58

The expression of transforming growth factor alpha (TGF-alpha) is consistently associated with the malignant transformation of oral mucosal tissues in both hamster and human. The cheek pouch of the Syrian hamster represents an ideal model to elucidate the role of TGF-alpha in epithelial cancer development. A prerequisite for such investigations at the molecular level is to obtain hamster-specific TGF-alpha molecular probes. Here we report the successful cloning of the hamster TGF-alpha cDNA from a hamster oral cancer cell line (HCPC-1) by the polymerase chain reaction technique using synthetic oligonucleotide primers based on human TGF-alpha cDNA sequence. Analysis of the nucleotide sequence of the newly isolated hamster cDNA encoding the portion of the mature TGF-alpha peptide revealed that it is 92.6% (139/150) homologous to that of the rat and 93.3% (140/150) homologous to that of the human sequences. The predicted hamster TGF-alpha amino acid sequence is 96% (48/50) similar to that of human, while 94% (47/50) similar to that of rat. Using this hamster TGF-alpha cDNA as a probe, molecular hybridization experiments revealed that it detects hamster TGF-alpha mRNA with approximately 40 times and approximately 5 times greater sensitivity than similar probes from human and rat origin respectively. This hamster TGF-alpha cDNA should be of great value as a probe to evaluate the role of TGF-alpha in the normal and pathological processes using the hamster as an experimental model.
Carcinogenesis 1991 Mar
PMID:Molecular cloning of the complementary DNA encoding for the hamster TGF-alpha mature peptide. 200 97

Designs of intervention trials are based on results from a multitude of disciplines. In this study, a comparative analysis of various chewing mixtures used by groups from different geographical locations (Guam, Peru, Taiwan, the Philippines, and India) and their link to oral cancer incidences was used to trace the ingredients responsible for oral carcinogenesis among chewers. The usefulness of applying intermediate endpoints in intervention trials was examined by comparing the response of micronucleated mucosal cells and oral leukoplakia of chewers of tobacco-containing betel quids to the twice weekly administration of beta-carotene (180 mg/week), vitamin A (100,000 IU/week or 200,000 IU/week), and beta-carotene (180 mg/week) plus vitamin A (100,000 IU/week). A reduced frequency of micronucleated mucosal cells and remission of leukoplakias resulted following a 3- to 6-month treatment. The development of new leukoplakias was also inhibited. The various endpoints differed in degree and time course to the administration of beta-carotene and vitamin A. Following termination of the beta-carotene or vitamin A administration, micronucleated cells and leukoplakia recurred in the oral cavity of chewers who continued this habit throughout the trial period. Attempts were made to maintain the protective effect achieved by the treatment with relatively high doses of the chemopreventive agents. Vitamin A given at a level of 50,000 IU/week was able to keep the frequency of micronucleated mucosal cells at low levels for at least a 12-month post-treatment period, whereas beta-carotene administered at 60 mg/week was less effective in maintaining the protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Remission of oral precancerous lesions of tobacco/areca nut chewers following administration of beta-carotene or vitamin A, and maintenance of the protective effect. 203 61

The aim of these studies was to determine the levels of carcinogenic tobacco specific nitrosamines (TSNA) in Sudanese oral snuff (toombak) as recent retrospective epidemiological studies suggested an association between the use of toombak and subsequent development of oral cancer. We have analyzed the TSNA levels in 20 samples of Sudanese toombak, of four different quality levels, collected from five different vendors. Using GC coupled with thermal energy analysis, four TSNA were quantified in snuff extracts: N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Unusually high levels of these TSNA (mean; range, mg/g snuff, dry wt) were detected; NNN (1.13; 0.50-3.08); NAT (0.08; 0.02-0.29); NAB (0.22; 0.02-2.37); and NNK (2.31; 0.62-7.87). Previously, the highest levels of NNN and NNK reported in any snuff were 0.154 and 0.014 mg/g dry wt respectively. In comparison, the levels in Sudanese toombak were up to 20 and 560 times higher respectively. As the public health implications of these findings are significant, attempts should be made to reduce exposure to TSNA in oral snuff users in Sudan.
Carcinogenesis 1991 Jun
PMID:Unusually high levels of carcinogenic tobacco-specific nitrosamines in Sudan snuff (toombak). 204 92


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