Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral cancer has increased recently in Australia, and overall survival rates have not improved in the past 30 years. Dentists are uniquely well placed to screen their patients at regular recall examinations and detect cancers or pre-cancerous lesions at an early curable stage. Although the major risk factors--tobacco smoking and alcohol abuse--have been identified, only a minority of patients at-risk will develop oral cancer. Molecular analysis has now detected an accumulation of genetic lesions in oral cancer, but the earliest molecular changes in the oral epithelium in the progression to malignancy in at-risk patients has not yet been determined. These changes could if known be exploited for screening purposes. How long human oral carcinogenesis takes to progress from the initiated cell to an invasive tumour, and whether molecular biology can be used to identify the minority of patients who will develop cancer from the large population exposed to the risk factors, are other important unanswered questions. p53 tumour suppressor gene mutations are the most frequently found genetic errors in oral cancer and the p53 gene is a likely target for tobacco and alcohol.
 ...
PMID:A general review of the p53 gene and oral squamous cell carcinoma. 1089 14

It has been suggested that Helicobacter pylori (H. pylori) infection might be associated with not only gastric ulcers but also gastric malignancies. Recently, it was reported that the Streptococcus anginosus (S. anginosus) DNA sequence was found in DNA samples extracted from esophageal cancers. Because smoking and alcohol abuse are regarded as risk factors for both esophgeal cancer and head and neck cancer, infection of S. anginosus might be associated with carcinogenesis of head and neck cancer. To investgate the involvement of S. anginosus infection in head and neck cancer, we analyzed 217 DNA samples prepared from head and neck squamous cell carcinomas. We performed PCR analysis with S. anginosus-16S ribosomal DNA-specific primers, and Southern blot analysis. For detection of S. anginosus in the oral and pharyngeal cavities, we used oropharyngeal bacteriological culture and PCR analysis of gingival smears of the patients. By PCR analysis, the S. anginosus DNA sequence was found in 217 out of 217 (100%) DNA samples obtained from head and neck cancers. By Southern blot analysis, positive bands were detected in 41 out of 125 (33%) samples. We could find no S. anginosus colony in oropharyngeal bacteriological culture dishes of 53 patients with and without head and neck cancer. On the other hand, we found the S. anginosus DNA fragment in 8 out of 8 DNA samples obtained from gingival smears by PCR analysis. These data indicate that the upper aerodigestive environment of the patients permitting S. anginosus infection was implicated in the carcinogenesis of head and neck squamous cell carcinoma.
 ...
PMID:Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis. 1107 31

Malignancies have a distinguished role among leading causes of death around the world. As a result of more effective preventive efforts of cardiovascular diseases malignancies will reach the top of death statistics in the near future. The increased incidence of malignant tumors may be attributed to smoking, in temperate alcohol abuse, as well as inappropriate nutrition. Inappropriate nutrition is thought to be responsible for the development of about 30-50% of malignancies. In the present review the authors analyze the uniform theory of carcinogenesis and the possible mechanisms by which certain nutritive factors may interfere with the complex process of carcinogenesis. The mechanism of "oxidative stress" is detailed, in particular the impact of prooxidants (also referred to as free radicals) on tumor development and the central role of lipid peroxidation. In addition to alimentary free radicals the relevance of alcohol abuse in carcinogenesis is also studied. Against the undesirable free radical reactions a complex natural antioxidant (free radical scavenger) system exists, that is responsible for anticarcinogenesis. The authors introduce the dietary antioxidants, their known effects of mechanisms, and their possible role in chemoprevention and therapy of malignancies, based on several experimental and epidemiological data.
 ...
PMID:[The role of alimentary oxidants and antioxidants in carcinogenesis]. 1151 31

In the development of several diseases the oxidative stress is a significant aetiological or important pathogenetic factor. Its significance has been proved in the pathogenesis of several diseases, among them in arteriosclerosis and reperfusion, in inflammation and immunological disorders, as well as in toxic alterations and in carcinogenesis. The increased incidence of malignant tumors may be attributed to smoking, intemperate alcohol abuse, as well as inappropriate nutrition. Inappropriate nutrition is thought to be responsible for the development of about 30-50% of malignancies. In this paper the authors review the processes of the development of free radicals based on oxygen and nitrogen. They discuss the modalities which are able to decrease the oxidative stress, like the low oxygen tension in the tissues, the enzymatic and antioxidant protections, and the different repair mechanisms. In details the roles of ubiquinone, with other name of coenzyme Q, as well as of the selenium are discussed in the antioxidant defence processes. As a conclusion they suppose that oxidative stress in the organism and the alterations caused by them can be decreased by adequate nutrition or nutriceuticals.
 ...
PMID:[Effect of ubiquinone and other scavengers on alterations caused by oxidative stress]. 1206 56

Increased oxidative stress and lipid peroxidation (LPO) are implicated in multistage carcinogenesis. Recent studies have shown that LPO-derived reactive hydroxyalkenals can form promutagenic exocyclic etheno-DNA adducts in vivo. Such DNA damage was found to be increased in the liver of patients with metal storage diseases and in colon adenomas of familial adenomatous polyposis patients. We now have investigated the levels of 1,N(6)-ethenodeoxyadenosine (epsilon dA) in human liver samples obtained from a group of patients diagnosed with hepatitis, fatty liver, fibrosis and cirrhosis, primary hemochromatosis and Wilson's disease. Using an immunohistochemical method, the relative mean pixel intensity of randomly selected nuclei was measured by imaging software; positively stained cell nuclei (arbitrary mean pixel intensity > or =0.5) were counted. Prevalence of epsilon dA (%) was calculated from the ratio of a number of positively stained cell nuclei over a total number of cells counted. When compared with normal livers (3.1%), the percent prevalence (means) was significantly higher in specimens of alcoholic fatty liver (15%) and fibrosis patients (50%) but not in samples with hepatitis (induced by various factors) (6.2%). The percent prevalence in alcohol fibrosis was as high as in the liver from Wilson's disease (50.7%) and hemochromatosis (33%) patients. This is the first demonstration of increased epsilon dA in human liver diseases due to alcohol abuse. We conclude that excessive hepatic DNA damage, as assessed by miscoding etheno-DNA adduct in the nuclei of liver biopsies, is probably caused by alcohol-induced oxidative stress and LPO. In cancer-prone liver diseases (fatty liver, cirrhosis/fibrosis) such damage may act as a driving force towards malignancy.
Carcinogenesis 2004 Jun
PMID:Immunohistochemical detection of 1,N6-ethenodeoxyadenosine in nuclei of human liver affected by diseases predisposing to hepato-carcinogenesis. 1474 17

Chronic alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, and esophagus; breast; liver; ovary; colon; rectum; stomach; and pancreas. An understanding of the underlying mechanisms by which chronic alcohol consumption promotes carcinogenesis is important for development of appropriate strategies for prevention and treatment of alcohol-associated cancers. The National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, Office of Rare Diseases, National Cancer Institute, National Institute on Drug Abuse, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, sponsored an international symposium on Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, USA, October 2004. The following is a summary of the symposium. Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens; (3) depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; (4) induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase-mitogen-activated protein kinase signaling; (5) accumulation of iron and associated oxidative stress; (6) inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast); and (7) impairment of retinoic acid metabolism. Nicotine may promote carcinogenesis through activation of extracellular signal-regulated kinase/cyclooxygenase-2/vascular endothelial growth factor signaling pathway.
 ...
PMID:Mechanisms of alcohol-associated cancers: introduction and summary of the symposium. 1605 76

In light of recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of coagulation factors XII and XIII with increased risk for oral cancer. In DNA samples of patients with oral squamous cell carcinoma and healthy controls of comparable ethnicity, age and sex, we studied the C46T polymorphism in FXII gene which affects gene transcription and the V34L polymorphism in FXIII gene which affects enzyme activity resulting in alteration of the fibrin network structure. No significant differences were observed in genotype and mutant allele frequencies of the FXII C46T polymorphism between patients and healthy controls. On the contrary, the obtained data for FXIII V34L polymorphism revealed a significant frequency increase of the L allele, which results in thinner fibrin network, in the whole group of patients compared to controls (33.1 versus 22.2% respectively, Fischer value P=0.006). In addition, LL homozygotes had a 3-fold greater risk for developing oral cancer (OR 2.893, 95% CI 1.056-7.890), while in VL heterozygotes a 2-fold greater risk was observed (OR 1.868, 95% CI 1.126-3.101). Significantly increased frequency of L allele was also observed in sub-groups of patients without family history of thrombophilia or cancer, with and without tobacco abuse and with alcohol abuse (P<0.05). Interestingly, in comparison to controls only patients with early cancer stages I and II had significantly increased L alleles and not patients with advanced stages III and IV. These findings suggest that the presence of L allele is strongly associated with oral cancer generation but not with its progression and metastasis. In the presence of L allele, the fibrin network is composed of thinner fibers, is less porous and facilitates tumor stroma formation and therefore tumor cell proliferation. Nevertheless, this thinner and less porous fibrin network inhibits cell migration.
 ...
PMID:Increased risk for oral cancer is associated with coagulation factor XIII but not with factor XII. 1798 41

Information from a preceding lipid study contributed to the pathobiological assessment of laryngeal squamous cell carcinoma (LSCC). Lipid-driven signaling pathways are responsible for laryngeal carcinogenesis and immunodeficiency. The construction of fatty acid (FA) profiles for LSCC allowed the identification of FA role players. The integration of lipid and clinicomolecular information encountered in the literature, in turn, allowed the identification of biological prognostic markers to distinguish between early (less aggressive) and advanced (more aggressive) LSCCs. High arachidonic acid (AA) and cyclooxygenase (COX-2) activities are criteria for less aggressive growth, whilst low AA and COX-2 activities occur during more aggressive growth. Excessive tobacco use and environmental smoke or human papillomavirus (HPV) infection and alcohol abuse can, respectively, elicit cumulative oxidative stress and an oxidative burst or interfere with signaling pathways during essential fatty acid (EFA) metabolism, all factors and events which may cause LSCC. Research revealed that enhanced COX-2 activity and Bcl-2 expression prevent apoptosis and, hence, LSCCs become resistant to radiotherapy. It was also observed that recurrent laryngeal cancers become more aggressive after radiotherapy failure. It is predicted that manipulation of AA activity and consequently a cascade of downstream factors that include COX-2 and Bcl-2 expression responsible for LSCC may have therapeutic potential to improve radiotherapy outcome during early LSCC. Adjuvant FA therapy to improve early LSCC management by counteracting radiotherapy failure and unwanted complications for further management is proposed. FA therapeutic strategies before and during radiotherapeutic courses need to be evaluated.
 ...
PMID:Rationale for adjuvant fatty acid therapy to prevent radiotherapy failure and tumor recurrence during early laryngeal squamous cell carcinoma. 1805 75

Cervical cancer is a major cause of cancer mortality in women worldwide and is initiated by infection with high-risk human papillomaviruses (HPVs). High-risk HPVs, especially HPV-16, are associated with other anogenital cancers and a subgroup of head-and-neck cancers. Indeed, HPV infection could account for the development of head-and-neck cancer in certain individuals that lack the classical risk factors for this disease (tobacco and alcohol abuse). This Review summarizes the main events of the HPV life cycle, the functions of the viral proteins, and the implications of HPV infection on their hosts, with an emphasis on carcinogenic mechanisms and disease outcomes in head-and-neck cancer. The demonstration that HPVs have a role in human carcinogenesis has allowed the development of preventive and therapeutic strategies aimed at reducing the incidence and mortality of HPV-associated cancers.
 ...
PMID:Human papillomavirus in cervical and head-and-neck cancer. 1809 54

Mutations in oncogenes or tumor suppressor genes, as well as environmental factors such as tobacco chewing or smoking, poor oral hygiene, ill-fitting dental appliances, infection by certain HPV types, or alcohol abuse, seem to be involved in the multifactorial process of carcinogenesis in head and neck. Recently, several genetic association studies have indicated that common DNA polymorphisms in low penetrance genes may affect the susceptibility of an individual to malignancy. Cytokines are an important group of proteins that regulate and mediate inflammation and angiogenesis. Tumor growth, invasion and metastasis are facilitated when there is a deregulation in their production. Cytokines include interleukins (ILs), tumor necrosis factors (TNFs) and certain growth factors (GFs). A number of genetic association studies have recently investigated the putative correlation between functional DNA polymorphisms in cytokine genes and head and neck carcinomas. This review discusses the findings of such studies in oral, nasopharyngeal and esophageal squamous cell carcinomas. Extensive research has indicated that functional polymorphisms affecting gene expression of IL-4,-6,-8,-10 as well as TNF-alpha are strongly associated with increased risk for oral cancer. Gene expression of TNF-alpha seems to be associated also with esophageal carcinomas, while for nasopharyngeal cancer the picture is yet unclear. It is generally believed that such genetic association studies will gradually increase our knowledge regarding the predisposed manifestation and advancement of these malignancies in the head and neck region.
 ...
PMID:Genetic association of cytokine DNA polymorphisms with head and neck cancer. 1848 34


<< Previous 1 2 3 4 5 Next >>