Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.
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PMID:Screening for pregnancy risk-drinking. 784 99

Up-regulation of phosphatidylinositol-3-kinase (PI3K)-AKT signaling facilitates tumor cell growth and inhibits cell demise. The AKT-pathway also plays an important role in cytostatic therapy resistance and response to hypoxia and angiogenesis. Using real-time cell proliferation assay we examined the potency of triciribine in three distinct neuroendocrine gastrointestinal tumor cell lines. Also we investigated triciribine's induction of apoptosis and effects on a broad range of cancer-associated gene products. Furthermore, we characterized the role of PTEN as a possible predictor of sensitivity to triciribine in GEP-NETs. We also looked for additive anti-neoplastic effects of triciribine when combined with conventional cytostatic drugs or other targeted drugs, affecting different molecules of the PI3K-AKT-pathway and we assessed the potency of triciribine to inhibit tumor growth in vivo, by using the chick chorioallantoic membrane assay. Treatment of insulinoma (CM) or gut neuroendocrine tumor cells (STC-1) with triciribine significantly reduced tumor cell growth by 59% and 65%, respectively. By contrast, the highly expressing PTEN carcinoid cell line BON did not respond, even at higher doses. Combinations of triciribine with classic cytostatic drugs as well as drugs targeting other molecules of the PI3K-AKT-pathway led to synergistic anti-proliferative effects. Additional in vivo-evaluations confirmed the anti-neoplastic potency of triciribine. Thus, our data show that inhibition the AKT-pathway potently reduces the growth of GEP-NET cells alone or in combination therapies. AKT inhibition may provide a rationale for future evaluations.
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PMID:AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors. 2207 56

Promoters and enhancers are key cis-regulatory elements, but how they operate to generate cell type-specific transcriptomes is not fully understood. We developed a simple and robust method, native elongating transcript-cap analysis of gene expression (NET-CAGE), to sensitively detect 5' ends of nascent RNAs in diverse cells and tissues, including unstable transcripts such as enhancer-derived RNAs. We studied RNA synthesis and degradation at the transcription start site level, characterizing the impact of differential promoter usage on transcript stability. We quantified transcription from cis-regulatory elements without the influence of RNA turnover, and show that enhancer-promoter pairs are generally activated simultaneously on stimulation. By integrating NET-CAGE data with chromatin interaction maps, we show that cis-regulatory elements are topologically connected according to their cell type specificity. We identified new enhancers with high sensitivity, and delineated primary locations of transcription within super-enhancers. Our NET-CAGE dataset derived from human and mouse cells expands the FANTOM5 atlas of transcribed enhancers, with broad applicability to biomedical research.
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PMID:NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements. 3147 27

Small bowel neuroendocrine tumors (SBNETs) are rare cancers originating from enterochromaffin cells of the gut. Research in this field has been limited because very few patient derived SBNET cell lines have been generated. Well-differentiated SBNET cells are slow growing and are hard to propagate. The few cell lines that have been established are not readily available, and after time in culture may not continue to express characteristics of NET cells. Generating new cell lines could take many years since SBNET cells have a long doubling time and many enrichment steps are needed in order to eliminate the rapidly dividing cancer-associated fibroblasts. To overcome these limitations, we have developed a protocol to culture SBNET cells from surgically removed tumors as spheroids in extracellular matrix (ECM). The ECM forms a 3-dimensional matrix that encapsulates SBNET cells and mimics the tumor micro-environment for allowing SBNET cells to grow. Here, we characterized the growth rate of SBNET spheroids and described methods to identify SBNET markers using immunofluorescence microscopy and immunohistochemistry to confirm that the spheroids are neuroendocrine tumor cells. In addition, we used SBNET spheroids for testing the cytotoxicity of rapamycin.
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PMID:Establishment and Characterization of Small Bowel Neuroendocrine Tumor Spheroids. 3165 1