UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25.3), and FOXF1-FOXC2-FOXL1 (16q24.1) loci are FOX gene clusters within the human genome. Members of FOX subfamilies A-G, I-L and Q were grouped into class 1 FOX proteins, while members of FOX subfamilies H and M-P were grouped into class 2 FOX proteins. C-terminal basic region within the FOX domain was the common feature of class 1 FOX proteins. FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. FOXA1 gene is amplified and over-expressed in esophageal and lung cancer. FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. Deregulation of FOX family genes leads to congenital disorders, diabetes mellitus, or carcinogenesis. Expression profiles, genetic alterations and epigenetic changes of FOX family genes as well as binding proteins and target genes of FOX family transcription factors should be comprehensively investigated to develop novel therapeutics and preventives for human diseases.
...
PMID:Human FOX gene family (Review). 1549 44

During the past 20 years, primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. The numbers of deaths and death rate from HCC showed a sharp increase beginning in 1975. Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes, HCV-related HCC has accounted for most of the recent increase and now represents 75% of all HCC in Japan. Geographically, HCC is more frequent in western than eastern Japan, and the death rate of HCC in each prefecture correlates with prevalence of anti-HCV. Among patients with HCV-related HCC, a history of blood transfusion was a relatively important source of infection in the 1990s, whereas community-acquired infections increased after 2000. There was a negative correlation between the duration from onset of infection to development of HCC and the age at onset. Interferon therapy for chronic hepatitis C has reduced the risk for HCC, indicating that early detection of HCV carriers and better treatment will contribute to improved outcomes. Nationwide screening for HCV and HBV began in 2002 in Japan, and reduction of HCC is anticipated. Further research should focus on mechanisms of carcinogenesis by HCV and HBV, development of more effective treatments, and establishment of early detection and treatment approaches. Better understanding of HCC unrelated to HCV and HBV and possibly because of steatohepatitis and diabetes should also be a major concern in future studies.
...
PMID:Hepatocellular carcinoma: recent trends in Japan. 1550 82

Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic effects of ethanol but does not account for the tolerance. This fact, as well as the discovery of the proliferation of the smooth endoplasmic reticulum (SER) after chronic alcohol consumption, suggested the existence of an additional pathway which was then described by Lieber and DeCarli, namely the microsomal ethanol oxidizing system (MEOS), involving cytochrome P450. The existence of this system was initially challenged but the effect of ethanol on liver microsomes was confirmed by Remmer and his group. After chronic ethanol consumption, the activity of the MEOS increases, with an associated rise in cytochrome P450, especially CYP2E1, most conclusively shown in alcohol dehydrogenase negative deer mice. There is also cross-induction of the metabolism of other drugs, resulting in drug tolerance. Furthermore, the conversion of hepatotoxic agents to toxic metabolites increases, which explains the enhanced susceptibility of alcoholics to the adverse effects of various xenobiotics, including industrial solvents. CYP2E1 also activates some commonly used drugs (such as acetaminophen) to their toxic metabolites, and promotes carcinogenesis. In addition, catabolism of retinol is accelerated resulting in its depletion. Contrasting with the stimulating effects of chronic consumption, acute ethanol intake inhibits the metabolism of other drugs. Moreover, metabolism by CYP2E1 results in a significant release of free radicals which, in turn, diminishes reduced glutathione (GSH) and other defense systems against oxidative stress which plays a major pathogenic role in alcoholic liver disease. CYP1A2 and CYP3A4, two other perivenular P450s, also sustain the metabolism of ethanol, thereby contributing to MEOS activity and possibly liver injury. CYP2E1 has also a physiologic role which comprises gluconeogenesis from ketones, oxidation of fatty acids, and detoxification of xenobiotics other than ethanol. Excess of these physiological substrates (such as seen in obesity and diabetes) also leads to CYP2E1 induction and nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), with pathological lesions similar to those observed in alcoholic steatohepatitis. Increases of CYP2E1 and its mRNA prevail in the perivenular zone, the area of maximal liver damage. CYP2E1 up-regulation was also demonstrated in obese patients as well as in rat models of obesity and NASH. Furthermore, NASH is increasingly recognized as a precursor to more severe liver disease, sometimes evolving into "cryptogenic" cirrhosis. The prevalence of NAFLD averages 20% and that of NASH 2% to 3% in the general population, making these conditions the most common liver diseases in the United States. Considering the pathogenic role that up-regulation of CYP2E1 also plays in alcoholic liver disease (vide supra), it is apparent that a major therapeutic challenge is now to find a way to control this toxic process. CYP2E1 inhibitors oppose alcohol-induced liver damage, but heretofore available compounds are too toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an innocuous mixture of polyunsaturated phosphatidylcholines extracted from soybeans (and its active component dilinoleoylphosphatidylcholine), were discovered to decrease CYP2E1 activity. PPC also opposes hepatic oxidative stress and fibrosis. It is now being tested clinically.
...
PMID:The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role. 1555 33

It has been demonstrated that the light-to-moderate consumption of alcoholic beverages is associated with significant reductions in all-cause and particularly cardiovascular mortality. While the inverse association between red-wine consumption and cardiovascular risk is globally recognized as the French paradox, many epidemiological studies have concluded that beer and red wine are equally beneficial. Moderate alcohol intake improves lipoprotein metabolism and lowers cardiovascular mortality risk. The question now is whether additional health benefits associated with the non-alcohol components in beer may be expected. This article summarizes the results of the latest studies on the health benefits of beer while referring to our recent results, which demonstrate the preventive effects of beer and its components on lifestyle-related diseases. A series of studies using animal models have shown that beer may prevent carcinogenesis and osteoporosis; beer provides plasma with significant protection from oxidative stress; and isohumulones, the bitter substances derived from hops, may prevent and improve obesity and type-2 diabetes, improve lipid metabolism, and suppress atherosclerosis. Further studies are needed to clarify the components in addition to isohumulones that are responsible for these beneficial effects of beer, and the underlying mechanisms must be addressed.
...
PMID:Beer and health: preventive effects of beer components on lifestyle-related diseases. 1563 Mar 1

Mutations in one copy of the hepatocyte nuclear factors (HNF) 1alpha and 1beta homeodomain containing transcription factors predispose the carrier to maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. Moreover, previous identification of biallelic inactivation of HNF1alpha in hepatocellular adenoma identified its tumor suppressor function in hepatocarcinogenesis. The seminal observation of an ovarian carcinoma in a MODY5 patient who subsequently developed a chromophobe renal cell carcinoma, prompted us to screen for HNF1beta and HNF1alpha inactivation in a series of 20 ovarian and 35 renal neoplasms. Biallelic HNF1beta inactivation was found in two of 12 chromophobe renal carcinomas by association of a germline mutation and a somatic gene deletion. In these cases, the expression of PKHD1 (polycystic kidney and hepatic disease 1) and UMOD (Uromodulin), two genes regulated by HNF1beta, was turned off. Interestingly, in two of 13 clear cell renal carcinomas, we found a monoallelic germline mutation of HNF1alpha with no associated suppression of target mRNA expression. In normal and tumor renal tissues, we showed the existence of a network of transcription factors differentially regulated in tumor subtypes. We identified two related clusters of co-regulated genes associating HNF1beta, PKHD1 and UMOD in the first group and HNF1alpha, HNF4alpha, FABP1 and UGT2B7 in the second group. Finally, these results suggest that germline mutations of HNF1beta and HNF1alpha may predispose to renal tumors. Furthermore, we suggest that HNF1beta functions as a tumor suppressor gene in chromophobe renal cell carcinogenesis through a PKHD1 expression control.
...
PMID:Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas. 1564 45

The nuclear receptors PPARs (peroxisome proliferator-activated receptors) are transcription factors activated by specific ligands. PPARs play an important role in carcinogenesis, inflammation, atherosclerosis, lipid metabolism and diabetes. There is evidence that activation of PPARs by specific ligands is able to suppress the growth of different types of human cancer by mechanisms including the growth arrest, apoptosis and induction of differentiation, although the detailed signalling pathways have not been completely elucidated to date. The aim of our study was to determine whether synthetic ligands of PPARalpha and PPARgamma could affect the viability, proliferation, differentiation, apoptosis and expression of some cell cycle related proteins in glial tumor cell lines. The study was performed on human glioblastoma cell lines U-87 MG, T98G, A172 and U-118 MG. Cell lines were treated by ligands of PPARalpha (bezafibrate, gemfibrozil) and PPARgamma (ciglitazone). MTT, flow cytometry, TUNEL assay and immunoblotting were used for detection of changes in cell viability, proliferation, differentiation and apoptosis. Bezafibrate, ciglitazone and gemfibrozil inhibited viability of glioblastoma cell lines. The synthetic ligands significantly reduced or induced the expression of cyclins, p27Kip1, p21Waf1/Cip1, MDM-2, Bcl-2, Bax, PARP, Caspase 3, androgen receptors, etc. and did not affect the expression of the differentiation marker GFAP. Flow cytometry confirmed arrest of the cell cycle although the detection of apoptosis was controversial. Apart from hypolipidemic and hypoglycaemic effects, PPAR ligands may also have significant cytostatic effects of potential use in anticancer treatment.
...
PMID:Peroxisome proliferator-activated receptors (PPAR) agonists affect cell viability, apoptosis and expression of cell cycle related proteins in cell lines of glial brain tumors. 1580 Jul 11

The majority of modern hormone replacement therapy (HRT) regimens contain estrogen and progestogens, given either in a cyclical or continuous manner. About 15% of the endometrial biopsies taken from women on sequential HRT show proliferative activity including atypical endometrial hyperplasia in up to 1% of the cases. The majority of biopsies from women under continuous combined HRT show an endometrial atrophy. About 2-3% of these women will present proliferative activity, usually without atypical hyperplasia. Contrary to breast cancer, an increased risk of endometrial cancer has not been reported in the WHI- and HERS-studies. However, endogenous factors, such as obesity, diabetes mellitus, the distribution of estrogen receptors alpha and beta and genetic polymorphisms for receptors and enzymes might alter the endometrial stimulation under different types of HRT. There should be a liberal indication for endometrial biopsies in Hereditary Non-Polyposis Colorectal Cancer (HNPCC). HNPCC-patients under HRT as well as for ultrasonographic evaluation of the endometrium. The risk of atypical hyperplasias or carcinoma under unopposed estrogen-therapy varies from 2 to 10%. So, this kind of HRT should not be used in non-hysterectomised women. As far as the risk of endometrial cancer under any kind of HRT is concerned, the different molecular pathways of endometrial carcinogenesis (type 1 and 2 cancers) should be taken into account. The use of tibolone leaves the endometrium unaffected.
...
PMID:Hormone replacement therapy (HRT) and endometrial morphology under consideration of the different molecular pathways in endometrial carcinogenesis. 1592 47

Conjugated linoleic acid (CLA) has been shown to exert beneficial effects against carcinogenesis, atherosclerosis and diabetes. It has been demonstrated that CLA modulates lipid metabolism through the activation of peroxisome proliferator-activated receptors (PPARs). The PPAR family comprises 3 closely related gene products, PPAR alpha, beta/delta and gamma, differing for tissue distribution, developmental expression and ligand specificity. It has also been demonstrated that activated PPARgamma results in growth inhibition and differentiation of transformed cells. These observations stimulated a great interest toward PPARgamma ligands as potential anticancer drugs to be used in a differentiation therapy. Glioblastomas are the most commonly diagnosed primary tumors of the brain in humans. The prognosis of patients with high-grade gliomas is poor and only marginally improved by chemotherapy. The aim of this work was to study the effects of CLA and of a specific synthetic PPARgamma ligand on cell growth, differentiation and death of a human glioblastoma cell line as well as on parameters responsible for the metastatic behavior of this tumor. We demonstrate here that CLA and PPARgamma agonist strongly inhibit cell growth and proliferation rate and induce apoptosis. Moreover, both treatments decrease cell migration and invasiveness. The results obtained show that CLA acts, directly or indirectly, as a PPARgamma activator, strongly suggesting that this naturally occurring fatty acid may be used as brain antitumor drug and as a chemopreventive agent. Moreover, the gamma-agonist, once experimented and validated on man, may represent a useful coadjuvant in glioblastoma therapy and in the prevention of recurrences.
...
PMID:PPARgamma-dependent effects of conjugated linoleic acid on the human glioblastoma cell line (ADF). 1598 37

Glycated hemoglobins are minor components of human hemoglobin (Hb). These are formed nonenzymatically by condensation of glucose or other reducing sugars with alpha- and beta-chains of hemoglobin A. The subfraction HbA1c, a nonenzymatic glycation at the amino-terminal valines of the beta-chain, was identified by the author in the 1960s as a minor "abnormal fast-moving hemoglobin band" in diabetic patients during routine screening for hemoglobin variants. This finding later turned out to be an important biomolecular marker with clinical and pathological applications. Measurement of HbA1c in diabetic patients is an established procedure for evaluating long-term control of diabetes, and the introduction of this measurement represents an outstanding contribution to the quality of care of diabetic patients in this century. More importantly, HbA1c is the first example of in vivo nonenzymatic glycation of proteins, and its discovery opened new and still-growing avenues of research on Maillard reactions in biological systems, including the concept of advanced glycation/lipoxidation end products (AGEs/ALEs) and the development of diabetic complications and various diseases associated with aging. Although interest in the Maillard reaction is growing rapidly, much remains to be done in this field, including detection and characterization of all in vivo AGEs/ALEs, development and clinical applications of AGE inhibitors and breakers, as well as investigations into the possible roles of the Maillard reaction in regulatory biology and carcinogenesis.
...
PMID:The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems. 1603 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

<< Previous 1 2 3 4 5 6 7 8 9 10