Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Partial least squares discriminant analysis (PLS-DA) provides a sound statistical basis for the selection of a limited number of gene transcripts most effective in discriminating different lung tumoral histotypes. The potentialities of the PLS-DA approach are pointed out by its ability to identify genes which, according to current knowledge, are considered molecular markers for colon cancer diagnostics and classification. Indeed application of PLS-DA to in vivo data allowed identification of a set of genes able to discriminate primary lung tumours from colon metastases.
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PMID:Genome-based identification of diagnostic molecular markers for human lung carcinomas by PLS-DA. 1597 38

A library of chalcones with different basic groups were synthesized and evaluated for antiproliferative activities against the human breast cancer (MCF 7) and colon cancer (HCT 116) cell lines. Structure-activity relationships were analyzed by projection methods (PCA/PLS) and multiple linear regression. Polar volume, hydrogen bonding features, HOMO energies, and charge on the beta carbon were found to be important factors. A basic group on either ring A or B of the chalcone led to a favourable increase in polar volume, but when present on ring B, it increased HOMO energies and decreased the positive charge on the beta carbon, both of which led to lower activity. Several examples showed that final activity of the chalcone was influenced by compensatory interactions among these parameters. In general, a single basic group on ring A was associated with good activity. A notable exception was compound 1-123 which had basic groups on both rings A and B but still maintained a good activity profile with IC(50)<10 microM and selectivity ratios >2.5. There was some evidence to show that structural differences in chalcones influenced not only activity but mechanism of action. Compounds 6-130 and 7-140 which had basic groups on ring A interfered with cell cycle progression, but the dibasic chalcone 1-123 had no effect.
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PMID:Antiproliferative activity of chalcones with basic functionalities. 1780 45

1,4-benzothiazines have ameliorative effects through inhibition of COX-2 mediated STAT-3 pathways at G-protein couple receptor site. As per this scenario, we recently prepared and tested novel 1,4-benzothiazine derivatives against HT-29 human colon cancer cell line. Two compounds namely AR13 and AR15 showed higher inhibitions among all the synthesized compounds. In the present context, we conducted the in vivo antiproliferative action and identified the molecular mechanism associated to cytotoxic action of AR13 and AR15 in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) model. Various physiological, oxidative stress, histopathology, ELISA, qRT-PCR, western blot and NMR-based metabolomics were accomplished to evaluate the anticancer effect of titled compounds. Both compounds were subjected to histological and biochemical tests to observe the protective action of the compounds. ELISA showed potential role of these compounds to normalize increased levels of IL-2, IL-6 and COX-2 mediators. This action was more pronounced for COX-2 rather than IL-2 and IL-6. Gene expression analyses further revealed that both of them attenuated the over-expressed COX-2 gene. Furthermore, it was confirmed that these compounds exerted antitumor potential via preventing COX-2 induced JAK-2 and STAT-3 phosphorylation. This action was substansiated by immunohistochemistry using JAK2, p-JAK2, STAT3 and p-STAT3 targets in colon tissue. Finally, score plots of PLS-DA models exhibited significant metabolic discriminations between the treated and CRC groups, and both compounds showed ability to restore the imbalance of multiple metabolites during CRC. In conclusion, our study provided the evidence towards better antiproliferative effect of AR13 and AR15 in DMH-induced CRC through the blockade of COX-2/JAK-2/STAT-3 signal transduction pathway and could be demonstrated as useful anti-CRC candidate molecules for future anticancer therapy.
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PMID:Novel 1,4-benzothazines obliterate COX-2 mediated JAK-2/STAT-3 signals with potential regulation of oxidative and metabolic stress during colorectal cancer. 2922 53

Single cell mass spectrometry (SCMS) allows for molecular analysis of individual cells while avoiding the inevitable drawbacks of using cell lysate prepared from populations of cells. Based on our previous design of the T-probe, a microscale sampling and ionization device for SCMS analysis, we further developed the device to perform online, and real time lysis of non-adherent live single cells for mass spectrometry (MS) analysis at ambient conditions. This redesigned T-probe includes three parts: a sampling probe with a small tip to withdraw a whole cell, a solvent-providing capillary to deliver lysis solution (i.e., acetonitrile), and a nano-ESI emitter in which rapid cell lysis and ionization occur followed by MS analysis. These three components are embedded between two polycarbonate slides and are jointed through a T-junction to form an integrated device. Colon cancer cells (HCT-116) under control and treatment (using anticancer drug irinotecan) conditions were analyzed. We detected a variety of intracellular species, and structural identification of selected ions was conducted using tandem MS (MS2). We further conducted statistical analysis (e.g., PLS-DA and t-test) to gain biological insights of cellular metabolism. Our results indicate that the influence of anticancer drugs on cellular metabolism of live non-adherent cells can be obtained using the SCMS experiments combined with statistical data analysis.
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PMID:Redesigning the T-probe for mass spectrometry analysis of online lysis of non-adherent single cells. 3151 34