Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyamines are of great importance in several biological processes, such as cell proliferation, and differentiation. The ingestion of spermine by suckling rats induces the precocious maturation of their small intestine. This phenomenon is preceded by a cell elimination at the villus tip. We hypothesize that these two phenomena could be mediated by the immune system and thus inhibited by an immunosuppressive agent such as cyclosporine A. Cyclosporine A inhibits, at least partially, the spermine-induced increase of the maltase- and sucrase-specific activities in the small intestine but failed to inhibit lactase-specific activity decrease and cell loss. Spermine does not act by the same mechanism in differentiation and in cell loss. Moreover, spermine acts in a different way on lactase-specific activity compared to maltase- or sucrase-specific activity. We hypothesize that spermine acts on differentiation by a T-cell/IL-2-dependent mechanism.
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PMID:Cyclosporine A inhibits partially spermine-induced differentiation but not cell loss of suckling rat small intestine. 1075 46

Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.
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PMID:Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. 2232 54