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

Life-style variables, especially those relating to metabolic overload, are significantly linked to risk for human cancer. Although the roles of tobacco use, alcohol abuse, sunlight, and select occupations are well established, the impact of nutrition on human carcinogenesis, and particularly that of excessive intake of fat and low intake of fiber, is less recognized. This article summarizes the essential evidence, recommends optimal fat and fiber intake, and suggests ways in which comprehensive clinical cancer centers can effectively participate in cancer prevention.
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PMID:Cancer prevention: optimizing life-styles with special reference to nutritional carcinogenesis. 161 16

Disulfiram, widely used in avoidance therapy for alcohol abuse, has been shown to have protective effects against chemically induced toxicity and carcinogenesis. The purpose of this work was to elucidate the biochemical mechanisms of this protective action by examining its effects on cytochrome P450IIE1 and other related microsomal enzyme activities. When a dose of disulfiram was given intragastrically to rats, a very rapid decrease of N-nitrosodimethylamine (NDMA) demethylase activity, possibly due to the inactivation of P450IIE1, was seen. The loss of P450IIE1 protein from the microsomal membrane was observed at 18 hr after receiving disulfiram, but not within the first 5 hr after the treatment. P450IIB1, on the other hand, was induced markedly between 15 and 72 hr after the disulfiram treatment. The treatment, however, caused only moderate changes in some other P450 isozymes. Carbon disulfide, a putative metabolite of disulfiram, produced similar effects on P450IIE1, but with shorter duration. Carbon disulfide, however, did not induce P450IIB1. Diethyldithiocarbamate, a reductive product of disulfiram, was an inhibitor of P450IIE1 activity in vitro, and upon preincubation with microsomes, it produced an NADPH-dependent inactivation of NDMA demethylase activity. The results suggest that this or other metabolites of disulfiram are inhibitors of P450IIE1 and are responsible for the inactivation of P450IIE1 in vivo. Hepatotoxicity of NDMA or CCI4 in rats was blocked by pretreatment with disulfiram. The present work demonstrates that P450IIE1 was inhibited and inactivated by disulfiram, and this mechanism can account for many of the reported inhibitory actions of disulfiram against chemically induced toxicity and carcinogenesis.
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PMID:Effects of disulfiram on hepatic P450IIE1, other microsomal enzymes, and hepatotoxicity in rats. 185 Jan 73

Serum levels of estrogens and testosterone were measured in 25 male patients with hepatocellular carcinoma and associated cirrhosis of the liver and in another 25 male patients with cirrhosis only. The two groups were statistically comparable in terms of age distribution, duration of liver disease, incidence of alcohol abuse, incidence of hepatitis B surface antigenemia, and grade of hepatic dysfunction. Estrone was significantly elevated in both groups of patients. Estradiol concentrations were above normal in 10 patients with hepatocellular carcinoma and in 11 with cirrhosis only. All patients had normal concentrations of estriol. There were no statistical differences between the two groups in either individual or total estrogen levels (estrone 0.05 less than p less than 0.1). Eight of the patients with hepatocellular carcinoma and 5 of the cirrhotics had lower testosterone levels than normal, but this difference was not significant. However, the estrone to testosterone ratios were significantly higher in the hepatocellular carcinoma group than in the cirrhosis group (p less than 0.05). The present study seems to indicate that hyperestrogenemia commonly seen in male patients with liver cirrhosis may play some role in hepatic carcinogenesis of cirrhotic livers. Further studies are needed to determine if the estrone to testosterone ratio is implicated in hepatocarcinogenesis in cirrhotic men.
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PMID:Serum levels of estrogens and testosterone in cirrhotic men with and without hepatocellular carcinoma. 298 53

The biological characteristics of hepatocellular cancer vary appreciably in different parts of the world, but especially between regions with very high and low incidences of the tumour. Hepatocellular cancer is multifactorial in origin, and the pattern of its aetiological associations differs between populations at high and low risk. In Africans and Chinese, who have the highest incidences of hepatocellular cancer, the hepatitis B virus is the most important causal association. The viral carrier state is acquired during early childhood, and carries a relative risk for the development of the tumour of over 200. Integration of hepatitis B virus DNA probably acts as a genotoxic initiator in the multistep process of hepatocarcinogenesis, although the precise mechanisms involved have not been determined. Aflatoxin ingestion may also have an aetiological role in high incidence regions, probably as a genotoxic or epigenetic promoter to hepatitis B virus-initiated carcinogenesis. In low risk populations cirrhosis is the most important causal association of hepatocellular cancer. The cirrhosis is often the result of alcohol abuse, but the tumour may complicate all aetiological forms of this disease. Whether neoplasia is an inevitable consequence of the hyperplasia of cirrhosis, or the increased hepatocyte turnover rate acts as a promoter is not known. Hepatitis B virus infection plays a lesser part, and aflatoxin no part at all.
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PMID:The development of hepatocellular cancer in humans. 304 Feb 42

Certain types of cancer are clearly associated with alcohol abuse, although the role of ethanol in carcinogenesis--as a carcinogen, co-carcinogen, promoter, or "innocent bystander"--is not known with certainty. The impact of alcohol abuse on the management of the patient with cancer is also discussed.
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PMID:Alcohol, alcoholism, and cancer. 636 11

The paper presents results of the epidemiological, clinical and experimental data regarding the link between alcohol abuse and cancer that demonstrate an important role of ethanol in stomach cancerogenesis. The role of ethanol is more evident in stomach as it is the organ exposed more directly and often to higher ethanol concentrations. Ethanol may develop its detrimental activity in carcinogenesis through several mechanisms: by its solvent effects, by inducing alimentary and immunological deficiencies, by acting as a vehicle for carcinogens, by facilitating their activation or by inhibiting DNA repair.
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PMID:[Ethanol as a risk factor in the pathogenesis of precancerous states and changes in the gastric mucous membrane]. 759 92

The modern concept of oncogenesis is based upon the interaction between factors which modulate cellular growth and differentiation, in particular oncogenes and tumor suppressor genes. The molecular events which induce laryngeal carcinogenesis are not yet known. Protoncogenes seem to be the target of the risk factors (cigarette smoking, alcohol abuse, ionizing radiations and, not least HPV-DNA) that are commonly considered related to laryngeal squamous cell carcinoma. New information on the role of alterations of oncogenes and/or their proteic products in laryngeal cancer will be useful in identifying new diagnostic and clinical therapeutical applications. The Authors investigated Epidermal Growth Factor Receptor (EGFR) expression in 103 primary laryngeal squamous cell carcinoma and 42 normal laryngeal tissue specimens in order to assess its clinical significance in primary laryngeal cancer. Significantly higher EGFR levels were found in cancer specimens compared with normal mucosa (p < 0.001). EGFR expression did not correlate with age, tumor localization, T classification, cervicallymphonode involvement or surgery, whereas in G3 tumors it was significantly higher than in G1-G2 (p < 0.05). Follow-up data were available for 74 cases: EGFR levels resulted significantly higher in patients who had a recurrence of the disease than those in recurrence-free patients (p < 0.05). The 24-month disease-free survival (DFS) was 58% for EGFR+ patients and 82% for EGFR-subjects. Multivariate analysis permitted identification of EGFR status and tumor localization as significant independent prognostic factors. Data reported here suggest that EGFR expression probably plays a role not only by regulating the growth of laryngeal cancer, but also by identifying a sub-set of laryngeal cancer patients at a higher degree of relapse risk and with an unfavorable prognosis. Furthermore, in this study p21-ras expression in 43 primary laryngeal cancers and in 7 normal laryngeal mucosa specimens was evaluated. Scattered p21 levels, expressed as optical density (O.D), were found in normal mucosa (median = 1.94) and in primary laryngeal tumours (median = 1.74). Higher p21 levels were found in neoplastic tissue than in normal laryngeal tissue (median = 2.54 vs median = 1.94; p = 0.023). The correlation between p21 ras protein and EGFR levels was also investigated. EGFR+ cases do not show any difference in p21 expression with respect to EGFR- cases (median = 1.52 O.D. vs median = 1.84). Our findings suggest that overexpression of p21 is associated with malignant phenotype in laryngeal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Oncogenes and cancer of the larynx. EGFR, p21 ras and HPV-DNA infections]. 779 43

The authors report 4 patients, without a history of tobacco or alcohol abuse, who developed squamous cell carcinoma of the esophagus secondary to mediastinal irradiation. Carcinoma of the esophagus developed in 3 women 8-11 years after mediastinal radiotherapy for breast cancer and in a man 9 years after mediastinal radiotherapy for Hodgkin's disease. Three patients underwent resection, with intrathoracic anastomosis in 2 and cervical in 1. No fistulae were observed despite the presence of esophageal fibrosis. No mediastinal lymph node was metastatic. Patients survived 7, 16, and 26 months, respectively, after resection. This study confirms the concept of radiation-induced carcinogenesis. We conclude that patients with dysphagia and a history of previous mediastinal radiotherapy should undergo repeated endoscopy for biopsy.
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PMID:Esophageal cancer after mediastinal irradiation. 801 Oct 16

The authors report 4 patients, without a history of tobacco or alcohol abuse, who developed squamous cell carcinoma of the esophagus secondary to mediastinal irradiation. Carcinoma of the esophagus developed in 3 women 8-11 years after mediastinal radiotherapy for breast cancer and in a man 9 years after mediastinal radiotherapy for Hodgkin's disease. Three patients underwent resection, with intrathoracic anastomosis in 2 and cervical in 1. No fistulae were observed despite the presence of esophageal fibrosis. No mediastinal lymph node was metastatic. Patients survived 7, 16, and 26 months, respectively, after resection. This study confirms the concept of radiation-induced carcinogenesis. We conclude that patients with dysphagia and a history of previous mediastinal radiotherapy should undergo repeated endoscopy for biopsy.
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PMID:Esophageal cancer after mediastinal irradiation. 800 9

Little is known about syncarcinogenic effects of occupational and environmental substances although it is supposed that different exogenous factors may play critical roles in the development of many human tumors. Epidemiologic results prove syncarcinogenesis for asbestos exposure and smoking (lung cancer), radon exposure and smoking (lung cancer), exposure to aromatic amines and smoking (bladder cancer) and alcohol abuse and smoking (oral, larynx and oesophagus cancer). Animal experiments point to additive effects in carcinogenesis for different nitrosamines and substances like benzo(a)pyrene, carbon tetrachloride, ethanol, vinyl chloride and ionising radiation. It can be concluded from modern concepts of carcinogenesis that syncarcinogenic mechanisms may not only result from genotoxicity but also from influences on cell proliferation and mitogenesis as well as toxicokinetics, DNA repair, intercellular communication, immune system and hormonal effects. New methods of molecular epidemiology seem very promising to study syncarcinogenic effects in animals and humans.
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PMID:[New data on syncarcinogenesis in tumors of exogenous origin]. 940 98


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