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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of diabetes on the liver microsomal monooxygenase enzymes and carcinogen metabolism have been studied in rats. Treatment with streptozotocin causes a marked enhancement in microsomal N-nitrosodimethylamine (NDMA) demethylase activity. The enhancement is due mainly to the induction of a high affinity NDMA demethylase (Km, approximately 0.05 mM) which is accompanied by the induction of a protein species with mol. wt. of 50,000. The treatment also induces aniline hydroxylase whose activity is in parallel with NDMA demethylase. Streptozotocin-induced diabetes also increases the metabolism of N-nitrosomethylethylamine but not that of N-nitrosomethylaniline or N-nitrosomethylbenzylamine. On the other hand, diabetes decreases the metabolism of benzo[a]pyrene, benzphetamine, and ethylmorphine. The result suggest that diabetes causes an alteration of the composition of cytochrome P-450 isozymes; the forms efficient in metabolizing NDMA are increased while certain other forms of cytochrome P-450 are decreased.
Carcinogenesis 1983
PMID:Alterations of microsomal monooxygenase system and carcinogen metabolism by streptozotocin-induced diabetes in rats. 630 26

The effects of a single injection of streptozotocin, at a dosage of 50 mg/kg body weight, have been studied in female inbred WAG rats. The resultant diabetes in the streptozotocin treated animals was treated in one group of animals by an intraportal pancreatic islet cell transplantation whilst another group received no transplant or insulin treatment. The incidence of tumours were determined at autopsy in animals sacrificed at regular intervals. Tumours, apart from one renal adenocarcinoma, were seen only in the liver and only in streptozotocin treated animals. Liver nodules and cysts were most common in animals which had received both streptozotocin and an islet cell transplant.
Carcinogenesis 1981
PMID:Liver tumours following streptozotocin administration in rats and the effects of pancreatic islet cell transplantation. 679 61

Breast duct obliteration and periductal elastosis were studied in 100 breast carcinomas with a maximum diameter of 20 mm or less. Seventy percent of all tumours and 90% of lobular and tubular carcinomas had obliterated ducts with radial scars at the centre of the lesion. Obesity, parity and diabetes mellitus had no apparent association with duct obliteration and periductal elastosis. The striking two peaks in age distribution suggest the presence of endocrine influences. Duct obliteration with periductal elastosis occurs where the breast shows most changes during development and involution making this the high risk zone for carcinogenesis.
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PMID:A contribution to the natural history of breast cancer. I. Duct obliteration with periductal elastosis in the centre of breast cancers. 712 1

It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.
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PMID:Levels of proteolytic activities as intermediate marker endpoints in oral carcinogenesis. 754 9

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural antioxidant defences have been found to be defective in many of the same diseases. This has led to suggestions that oxidative damage and therefore disease progression may be retarded by supplementing natural antioxidant defences. Potential antioxidant therapy includes natural antioxidant enzymes and vitamins or synthetic agents with antioxidant activity. Diseases where antioxidant therapy may be beneficial include diabetes mellitus, reperfusion injury, inflammatory diseases and the prevention of chronic processes such as atherosclerosis and carcinogenesis. Further well controlled prospective clinical trials of antioxidants are required to establish the efficacy and tolerability of antioxidant therapy in the treatment of human diseases.
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PMID:Prospects for the use of antioxidant therapies. 777 11

Considering endometrial carcinoma as a natural experimental model for in vivo study of carcinogenesis, a hypothesis of endometrial type A carcinogenesis and some preventive prospects are advanced. Under the name of endometrial carcinoma two different types are considered: A) hormone dependent type, and B) autonomous type. Aging, obesity, hypertension and/or diabetes, persistent exposure to unopposed exogenous or endogenous estrogens are recognized epidemiological factors for endometrial carcinoma. Experimental and clinical studies have shown that in pregnancy associated with clinical conditions characterized by a compromised maternal circulation in the intervillous space, a state of true or relative hypoxia stimulates syncytial hyperplasia, as adaptive process, in order to increase the exchange area of the placenta. Vaginosonographic studies have shown in patients with endometrial thickness greater than or equal to 4 mm complex and atypical hyperplasia than endometrial carcinoma in a higher percentage than in patients with endometrial thickness less than 3 mm. It seems that hypoxia in endometrial thickness, greater than 3 mm promoted by estrogens, would be a supplementary proliferating factor. Immunological studies have shown, in patients with complex or atypical hyperplasia of the endometrium and/or endometrial carcinoma, a host immunological reaction (DTHS-reactivity test) to a pharmaceutical placental suspension, when injected intradermally. An extract prepared from placental suspension is also recognized in vitro, by patients' serum (Ouchterlony's technique). To conclude, hypoxic insult, as common pathophysiological factor in most predisposing diseases for endometrial cancer, leads to a persistent multicellular hyperplasia of the endometrium. Sometimes populations with an altered growth pattern develop.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothesis for endometrial carcinoma carcinogenesis. Preventive prospects. 828 9

Patients with diabetes frequently suffer from various postoperative complications, especially infection. Diabetic patients also have a high incidence of uterine endometrial cancer. The nature of the intrauterine bacterial flora may be related to both infection and carcinogenesis. Therefore, identification of the intrauterine bacterial flora in diabetic patients may be useful. Bacteria were detected in the uterine endometrial cavity of 100% of ten diabetic patients with myoma uteri. However, among 20 non-diabetic control patients with myoma uteri, only three 15% harbored bacteria. Members of the Enterobacteriaceae (Escherichia coli, Proteus spp., Enterobacter cloacae, and Klebsiella pneumoniae) were the predominant bacteria. We speculate that bacterial products contribute to carcinogenesis, as has been proposed for colon carcinoma. Antimicrobial agents active against Enterobacteriaceae should be used to prevent postoperative infections in gynecologic procedures in diabetic patients.
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PMID:Bacterial flora detected of the uterine endometrial cavity of diabetic patients with myoma uteri. 836 May 20

Diabetes mellitus has been suggested as a possible risk factor for the development of pancreatic cancer in humans. Previous studies in our laboratory have shown, however, that streptozotocin (STZ) diabetes inhibits the development of cancer of the exocrine pancreas in hamsters when STZ is administered prior to treatment with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). It has been reported by others that the concurrent administration of BOP and STZ enhances pancreatic carcinogenesis in hamsters. The purpose of the present study was to determine the effect of STZ diabetes on the development of BOP-induced pancreatic carcinoma when STZ is given following exposure to BOP. Groups of Syrian golden hamsters were treated with either BOP only (single s.c. injection, 40 mg/kg body wt at week 0), BOP (single s.c. injection, 40 mg/kg body wt at week 0) plus STZ (50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30), STZ only (50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30), or neither BOP nor STZ. The experiment was terminated at 40 weeks after BOP treatment. No significant difference was seen in the incidence of pancreatic cancer between those animals receiving BOP only at week 0 and those receiving BOP at week 0 plus STZ at weeks 10, 20 or 30 of the study. The results would appear to indicate that STZ diabetes, established after BOP tumor initiation, plays no apparent role in the modulation of pancreatic carcinogenesis.
Carcinogenesis 1993 May
PMID:Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure. 850 90

Endocrine organs, such as the pancreatic islets of Langerhans, contain permeable, fenestrated endothelium that allows direct access of endocrine cells to the blood stream. Factors that control differentiation and maintenance of this highly specialized endothelium remain unknown. Vascular endothelial growth factor (VEGF) is a multifunctional growth factor that may be responsible for the homeostasis of endocrine endothelium; it is a selective mitogen for endothelial cells and is able to permeabilize endothelium. We have analyzed the expression of VEGF mRNA and protein in pancreatic islet cells of normal mice and during the different stages of tumor progression in a transgenic mouse model of beta-cell carcinogenesis. The 120-amino acid and the 164-amino acid isoforms of VEGF are expressed in normal islets of Langerhans and are moderately up-regulated during the stages of tumor development. Two high-affinity receptors for VEGF, flt-1 and flk-1, are expressed by endothelial cells both in normal islets and in the stages of tumorigenesis; these receptors are not up-regulated during this process. Our data raise the possibility that VEGF is involved in the maintenance of permeable endothelium in islets of Langerhans, an observation that may have implications for islet cell physiology and diabetes. While VEGF may also play an important role in the growth of new blood vessels during islet cell tumorigenesis, it cannot be the only factor required for the activation of tumor angiogenesis.
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PMID:Vascular endothelial growth factor and its receptors, flt-1 and flk-1, are expressed in normal pancreatic islets and throughout islet cell tumorigenesis. 861 12

Cancers of many types are major chronic diseases with a high fatality rate and a high cost to society. In the USA, the Delaney Clause was implemented in 1958 because the public believed that many cancers stem from food additives and food contaminants. In the intervening years, research has provided key information about the mechanisms of carcinogenesis and demonstrated that there are two major classes of carcinogens, genotoxic and non-genotoxic. Two case reports are presented, of sodium saccharin and ethylenebisdithiocarbamates that were banned based on the Delaney Clause in an unjustified manner, based on the underlying mechanisms not relevant for non-genotoxic carcinogens. Also, the causes of major cancers have been discovered. Most cancers are associated with lifestyle, specifically tobacco and excessive alcohol use, inappropriate nutritional traditions, and lack of exercise. These lifestyle components involve now known genotoxic carcinogens and importantly, non-genotoxic carcinogens. The effect of non-genotoxic carcinogens is highly dose dependent and also reversible upon lowering the dose below a threshold. Thus, it is quite possible to lower human cancer risk, and also the risk of related chronic diseases such as coronary heart disease, hypertension and stroke, adult on-set diabetes, by proper lifestyle adjustments. Clearly, the Delaney Clause plays no role in disease prevention.
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PMID:Human protection against non-genotoxic carcinogens in the US without the Delaney Clause. 867 78


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