Signet ring cell carcinoma of the gastrointestinal tract: National trends on treatment effects and prognostic outcomes.

BACKGROUND: Signet ring cell carcinoma (SRCC) is a distinct malignancy occurring across the tubular gastrointestinal tract (tGIT). We comprehensively examined the outcomes of patients diagnosed with SRCC across tGIT. METHODS: SRCC and not-otherwise-specified adenocarcinoma (NOS) patients reported to the National Cancer Database from 2004 to 2015 were included. Baseline characteristics, outcomes and site-specific adjusted hazard ratios (aHR) derived from Cox models of SRCC patients were compared to those of NOS patients. Overall survival (OS) was primary endpoint. RESULTS: A total of 41,686 SRCC (4.6%) and 871,373 NOS patients (95.4%) were included. SRCC patients were younger (63.1 ± 14.7 vs. 67.0 ± 13.4 y, p < 0.001) and more likely to present with Stage IV disease than NOS patients (42.5% vs. 24.5%, p < 0.001). Stomach (n = 24,433) and colon (n = 9,914) contributed highest frequency of SRCC. SRCC histology was associated with shorter OS (aHR = 1.377, p < 0.001) in multivariate model. There was an interaction between SRCC and chemotherapy effects on risk of death (interaction aHR = 1.072, pinteraction< 0.001) and between SRCC histology and disease site, suggesting that the effect of SRCC on OS is site-dependent, with a higher increased risk of death in patients with rectal SRCC (aHR = 2.378, pinteraction< 0.001). CONCLUSION: Significant negative prognostic effect associated with SRCC is site-dependent across the GIT. Surgical and or systemic therapy was associated with improved OS among SRCC patients, but remained lower than NOS patients. Further understanding of gastrointestinal SRCC molecular profile is needed to better inform future treatment strategies.

Systemic MCPIP1 deficiency in mice impairs lipid homeostasis.

Atherosclerosis involves interactions between inflammation system and dyslipidemia. MCPIP1 (Monocyte Chemotactic Protein induced Protein-1) is induced by proinflammatory molecules and serves as a negative feedback loop in regulating inflammatory responses. Our current study was designed to test the role of MCPIP1 in maintaining lipid homeostasis, the latter a pivotal factor that contributes to the pathogenesis of atherosclerosis. We found that MCPIP1 knockout mice displayed a decrease in levels of serum HDL-cholesterol and total triglycerides but an increase in serum LDL/VLDL-cholesterol levels when compared to wild-type mice. Additionally, ApoA-1 expression was reduced but LPL expression was upregulated in plasma from MCPIP1 knockout mice. The livers from the MCPIP1 knockout mice revealed a decrease in hepatocyte number and an increase in collagen deposition when compared to wild-type mice. These findings suggest that MCPIP1 deficiency can induce liver fibrosis, alter the expression of lipoproteins, and affect transportation and metabolism of lipids, indicating that MCPIP1 is involved in maintaining lipid homeostasis, possibly via negatively regulating inflammatory responses.