Hereditary and Inflammatory Bowel Disease-Related Early Onset Colorectal Cancer Have Unique Characteristics and Clinical Course Compared with Sporadic Disease.

Background: Early onset colorectal cancer (EoCRC), diagnosed in those <50 years old, is increasing in incidence. We sought to differentiate characteristics and outcomes of EoCRC in patients with sporadic disease or preexisting conditions.

Methods: We evaluated 2,135 patients with EoCRC in a population-based cohort from the Canadian province of British Columbia.

The impact of primary sclerosing cholangitis or inflammatory bowel disease on cholangiocarcinoma phenotype, therapy, and survival.

Background And Aim: Primary sclerosing cholangitis (PSC), with or without inflammatory bowel disease (IBD), confers the risk of cholangiocarcinoma. Isolated IBD may be an independent risk factor for cholangiocarcinoma. We sought to compare cholangiocarcinoma phenotype and outcomes between patients with PSC, IBD, and neither.

The single IgG IL-1-related receptor controls TLR responses in differentiated human intestinal epithelial cells.

Intestinal epithelial cells (IECs) are constantly exposed to enteric microbes. Although IECs express TLRs that recognize bacterial products, the activation of these TLRs is strictly controlled through poorly understood mechanisms, producing a state of hyporesponsiveness and preventing unwanted inflammation. The single IgG IL-1-related receptor (Sigirr) is a negative regulator of TLRs that is expressed by IECs and was recently shown to inhibit experimental colitis.

Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma.

Integrin-linked kinase (ILK) is a key molecule involved in mediating several biological functions including cell-matrix interactions, angiogenesis, and invasion, as well as playing a role in epithelial to mesenchymal transition (EMT) in cancer cells. In ductal pancreatic adenocarcinoma, increased expression of ILK has been linked to tumor prognosis and correlated with increased chemoresistance to drugs, such as gemcitabine. However, the precise relationship between ILK, Snail, E-cadherin, and N-cadherin expression on the stepwise development of pancreatic cancer is unknown.

Pertussis toxin promotes macrophage survival through inhibition of acid sphingomyelinase and activation of the phosphoinositide 3-kinase/protein kinase B pathway.

Apoptosis is an important mechanism involved in regulating the number of macrophages present at sites of inflammation. Several lines of evidence indicate that blocking macrophage apoptosis can increase atherosclerosis. We previously reported that oxidized LDL can inhibit apoptosis in cultured bone marrow-derived macrophages.

Ceramide-1-phosphate promotes cell survival through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway.

In this report, we show for the first time that ceramide-1-phosphate (C1P) stimulates the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB) pathway, which is a major mechanism whereby growth factors promote cell survival. Also, C1P induced IkappaB phosphorylation, and enhanced the DNA binding activity of the transcription factor NF-kappaB. Apoptotic macrophages showed a marked reduction of Bcl-X(L) levels, and this was prevented by C1P.

Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages.

It was reported previously that ceramide-1-phosphate (Cer-1-P) is mitogenic for fibroblasts (Gómez-Muñoz, A., P. A.

Sphingosine-1-phosphate inhibits acid sphingomyelinase and blocks apoptosis in macrophages.

Sphingosine-1-phosphate (Sph-1-P) regulates critical cellular functions including cell proliferation, differentiation, angiogenesis, and cell survival. However, its mechanisms of action are incompletely understood. Here, we show a novel biological effect of Sph-1-P: inhibition of acidic sphingomyelinase (A-SMase) activity in apoptotic bone marrow-derived macrophages.