Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to α-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110α upregulates GPT2 gene expression through an AKT-independent, PDK1–RSK2–ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations.

Background— The South Bay Heart Watch is a prospective cohort study designed to appraise the value of coronary calcium and risk factors for predicting outcomes in asymptomatic adults. Two factors that may be related to subsequent cardiovascular events are coronary calcium (CAC, a manifestation of subclinical atherosclerosis) and high-sensitivity C-reactive protein (CRP, a measure of chronic inflammation). Methods and Results— Between December 1990 and December 1992, 1461 participants without coronary heart disease underwent baseline risk factor screening, computed tomography for CAC, and measurement of CRP. Participants were followed up for 6.4±1.3 years. Cox regression analyses were conducted for the 967 nondiabetics with CRP levels ≤10 mg/L to estimate the risk-factor–adjusted relative risks of CAC and CRP for the occurrence of (1) nonfatal myocardial infarction (MI) or coronary death and (2) any cardiovascular event (MI, coronary death, coronary revascularization, or stroke). CAC was a predictor of both end points ( P <0.005), and CRP was a predictor of any cardiovascular event ( P =0.03). Risk group analysis defined by tertiles for CAC (<3.7, 3.7 to 142.1, >142.1) and the 75th percentile for CRP (>4.05 mg/L) indicated that there was increasing risk with increasing calcium and CRP. Relative risks for the medium-calcium/low-CRP risk group to high-calcium/high-CRP risk group ranged from 1.8 to 6.1 for MI/coronary death ( P =0.003) and 2.8 to 7.5 for any cardiovascular event ( P <0.001). Conclusions— Participants without diabetes and those at intermediate risk may benefit from risk stratification based on high-sensitivity CRP levels and CAC, because both factors contribute independently toward the incidence of cardiovascular events.

OBJECTIVE -The South Bay Heart Watch is a cohort study designed to determine the significance of coronary calcium in high-risk asymptomatic patients. This is a report of the relative risk (RR) for outcomes of coronary artery calcium in diabetic and nondiabetic subjects.RESEARCH DESIGN AND METHODS -A total of 1,312 diabetic and nondiabetic subjects underwent risk factor screening and computed tomography testing for coronary calcium at baseline and were followed clinically for 6.3 Ϯ 1.4 years. End points were either 1) hard events of nonfatal myocardial infarction (MI) or coronary death or 2) any cardiovascular event (nonfatal MI, coronary death, coronary revascularization, or stroke).RESULTS -The incidence rates of a hard event and any cardiovascular event for diabetic and nondiabetic subjects were 14.5 and 6.1% and 23.8 and 12.2%, respectively (P Ͻ 0.001). Cox regression analyses of the combined risk relationship of diabetes status and calcium score demonstrated that relative to nondiabetic subjects with low calcium scores (Ͻ2.8), diabetic subjects with calcium scores Ն2.8 exhibited at least a fourfold increase in the risk of either a hard or any cardiovascular event (P Ͻ 0.001). Cox regression analyses conducted separately for nondiabetic and diabetic subjects revealed that coronary calcium score risk groups were significantly associated with events in nondiabetic subjects (RR Ն 2.6, P Յ 0.01), but not in diabetic subjects (RR Յ 1.7, P Ͼ 0.05).CONCLUSIONS -The risk of coronary heart disease increases with increasing calcium scores and diabetes status. Calcium scores have less prognostic value in diabetic subjects. Diabetes Care 26:905-910, 2003

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Pooled analyses of these geographically diverse case-control data indicate a reduced thyroid cancer risk associated with current smoking. A reduced risk associated with alcohol was eliminated after adjustment for smoking, and caffeinated beverages did not alter thyroid cancer risk.

BackgroundPlant allelochemicals act as toxins, inhibitors of digestion, and deterrents that affect the fecundity of insects. These compounds have attracted significant research attention in recent decades, and much is known about the effects of these xenobiotic plant secondary metabolites on insect development. To date, although ecological interactions between xenobiotic plant secondary chemicals that retard insect growth have been observed in many species, it remains unclear how particular allelochemicals influence insect development in a life stage-dependent manner.ResultsWe found that 2-tridecanone can affect insect development; this effect appears similar to the symptoms induced by the physiological imbalance between juvenile and molting hormones in cotton bollworm. We later detected that a decrease in the concentration of 20-hydroxyecdysone occurred alongside the observed symptoms. We next identified the transcriptome of Helicoverpa armigera and eightdigital gene expression libraries for shading light on how 2-tridecanone retarded the development of cotton bollworm. The expression of CYP314A1, CYP315A1, CYP18A1, CYP307A1, and CYP306A1 (unigenes 16487, 15409, 40026, 41217, 35643, 16953, 8199, 13311, and 13036) were found to be induced by 2-tridecanone; these are known to be related to the biosynthesis or metabolism of 20-hydroxyecdysone. Expression analysis and RNA interference studies established that the retardant effect of 2-tridecanone on the development of cotton bollworm is mediated by P450 genes.ConclusionsThe candidate P450 gene approach described and exploited here is useful for identifying potential causal genes for the influence of plant allelochemicals on insect development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3277-y) contains supplementary material, which is available to authorized users.

The study evaluated the ability of long intergenic noncoding RNA LINC00312 (LINC00312) to influence the proliferation, invasion, and migration of thyroid cancer (TC) cells by regulating miRNA-197-3p. TC tissues and adjacent normal tissues were collected from 211 TC patients. K1 (papillary TC), SW579 (squamous TC), and 8505C (anaplastic TC) cell lines were assigned into a blank, negative control (NC), LINC00312 overexpression, miR-197-3p inhibitors, and LINC00312 overexpression + miR-197-3p mimics group. The expression of LINC00312, miR-197-3p, and p120 were measured using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation was assessed via CCK8 assay, cell invasion through the scratch test, and cell migration via Transwell assay. In comparison with adjacent normal tissues, the expression of LINC00312 is down-regulated and the expression of miR-197-3p is up-regulated in TC tissues. The dual luciferase reporter gene assay confirmed that P120 is a target of miR-197-3p. The expression of LINC00312 and p120 was higher in the LINC00312 overexpression group than in the blank and NV groups. However, the expression of miR-197-3p was lower in the LINC00312 overexpression group than in the blank and NC groups. The miR-197-3p inhibitors group had a higher expression of miR-197-3p, but a lower expression of p120 than the blank and NC groups. The LINC00312 overexpression and miR-197-3p inhibitor groups had reduced cell proliferation, invasion and migration than the blank and NC groups. These results indicate that a LINC00312 overexpression inhibits the proliferation, invasion, and migration of TC cells and that this can be achieved by down-regulating miR-197-3p.

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