Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.

PURPOSE: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients. METHODOLOGY: This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time. RESULTS: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups (P-value < 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups (P-value < 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 (P-value < 0.01). For TF, there was a significant association with age (P-value < 0.01). CONCLUSIONS: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied.

Altered Lamin A/C splice variant expression as a possible diagnostic marker in breast cancer.

BACKGROUND: Lamin A/C alternative splice variants (Lamin A, Lamin C, Lamin AΔ10 and Lamin AΔ50) have been implicated in cell cycle regulation, DNA replication, transcription regulation, cellular differentiation, apoptosis and aging. In addition, loss of Lamin A/C expression has been observed in several cancers, including breast cancer, and it has been found that Lamin A/C suppression may lead to cancer-like aberrations in nuclear morphology and aneuploidy. Based on these observations, we hypothesized that Lamin A/C transcript variant quantification might be employed for the diagnosis of breast cancer. METHODS: Newly designed TaqMan qRT-PCR assays for the analysis of Lamin A/C splice variants were validated and their use as biomarkers for the diagnosis of breast cancer was assessed using 16 normal breast tissues and 128 breast adenocarcinomas. In addition, the expression levels of the Lamin A/C transcript variants were measured in samples derived from seven other types of cancer. RESULTS: We found that the expression level of Lamin C was significantly increased in the breast tumors tested, whereas the expression levels of Lamin A and Lamin AΔ50 were significantly decreased. No significant change in Lamin AΔ10 expression was observed. Our data also indicated that the Lamin C : Lamin A mRNA ratio was increased in all clinical stages of breast cancer. Additionally, we observed increased Lamin C : Lamin A mRNA ratios in liver, lung and thyroid carcinomas and in colon, ovary and prostate adenocarcinomas. CONCLUSIONS: From our data we conclude that the Lamin C : Lamin A mRNA ratio is increased in breast cancer and that this mRNA ratio may be of diagnostic use in all clinical stages of breast cancer and, possibly, also in liver, lung, thyroid, colon, ovary and prostate cancers.