Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidemiology and molecular biology of colorectal cancer are reviewed with a view to understanding their interrelationship. Risk factors for colorectal neoplasia include a positive family history, meat consumption, smoking, and alcohol consumption. Important inverse associations exist with vegetables, nonsteroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy, and physical activity. There are several molecular pathways to colorectal cancer, especially the APC (adenomatous polyposis coli)-beta-catenin-Tcf (T-cell factor; a transcriptional activator) pathway and the pathway involving abnormalities of DNA mismatch repair. These are important, both in inherited syndromes (familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer [HNPCC], respectively) and in sporadic cancers. Other less well defined pathways exist. Expression of key genes in any of these pathways may be lost by inherited or acquired mutation or by hypermethylation. The roles of several of the environmental exposures in the molecular pathways either are established (e.g., inhibition of cyclooxygenase-2 by NSAIDs) or are suggested (e.g., meat and tobacco smoke as sources of specific blood-borne carcinogens; vegetables as a source of folate, antioxidants, and inducers of detoxifying enzymes). The roles of other factors (e.g., physical activity) remain obscure even when the epidemiology is quite consistent. There is also evidence that some metabolic pathways, e.g., those involving folate and heterocyclic amines, may be modified by polymorphisms in relevant genes, e.g., MTHFR (methylenetetrahydrofolate reductase) and NAT1 (N-acetyltransferase 1) and NAT2. There is at least some evidence that the general host metabolic state can provide a milieu that enhances or reduces the likelihood of cancer progression. Understanding the roles of environmental exposures and host susceptibilities in molecular pathways has implications for screening, treatment, surveillance, and prevention.
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PMID:Colorectal cancer: molecules and populations. 1130 47

To develop an external preparation of oregonin (ORG) for the treatment of atopic dermatitis (AD), conventional creams (CC) and elastic liposomes (EL) containing ORG have been formulated and examined for their in vitro skin permeation properties and in vivo therapeutic efficacy assessments. EL, consisting of soybean phosphatidylcholine and Tween 80 (85 : 15 w/w %), were of flexible nanocarriers: they were about 130 nm in size and had a 4-fold greater deformability index than conventional liposomes. In a skin permeation study using a Franz diffusion cell mounted with depilated mouse skin, liposomal systems were superior to cream, revealing greater flux values. Both CC and EL were diversified with the addition of Trans-activating transcriptional activator (Tat) peptide, a sort of cell penetrating peptide, and subjected to in vivo efficacy evaluations in NC/Nga mice with AD-like lesions. On clinical observation for skin severity, rapid and profound improvement was observed in the treatment group with Tat-added liposomes (EL/T), showing a significant difference (p<0.05) versus Tat-added cream. The results indicated that EL/T treatment is effective for normalizing the immune-related responses and alleviating AD, evaluated as changes in the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-4, immunoglobulin E (IgE), and eosinophils in skin or blood.
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PMID:Facilitated skin permeation of oregonin by elastic liposomal formulations and suppression of atopic dermatitis in NC/Nga mice. 2004 44

Labor is initiated as a result of hormonal changes that are induced by the activation of the inflammatory response and a series of biochemical events. The amnion, which is the primary source of prostaglandin E2 (PGE2), plays an important role in the process of labor. In the present study, we uncovered a pathway in which c-fos, cyclooxygenase-2 (COX2) and miR-144 function as hormonal modulators in the amnions of pregnant mice and humans. miR-144 down-regulated the synthesis of PGE2 during pregnancy by directly and indirectly inhibiting COX2 expression and by directly inhibiting the expression of c-fos, a transcriptional activator of COX2 and miR-144. Estrogen (E2) activated c-fos, thus promoting the expression of miR-144 and COX2 during labor. However, the increase in COX2 resulted in the partial inhibition of COX2 expression by miR-144, thereby slightly reducing the secretion of PGE2. These observations suggest that miR-144 inhibits PGE2 secretion by section to prevent the initiation of premature labor. Up-regulated expression of miR-144, c-fos and COX2 was also observed both in preterm mice and in mice undergoing normal labor. In summary, miR-144, c-fos and COX2 play important roles in regulating PGE2 secretion in the amnion during pregnancy and labor.
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PMID:miR-144 and targets, c-fos and cyclooxygenase-2 (COX2), modulate synthesis of PGE2 in the amnion during pregnancy and labor. 2729 32