The role of IL-1β and TNF-α signaling in the genesis of cancer treatment related symptoms (CTRS): a study using cytokine receptor-deficient mice.

Cytotoxic chemotherapeutic agents often induce a cluster of cancer treatment related symptoms (CTRS). The purpose of this study was to develop a mouse model of CTRS to examine the role of IL-1β and TNF-α signaling in the genesis of these symptoms. CTRS (change in wheel running activity, food intake, and body weight from baseline) were examined in wild type (WT) mice or mice lacking the TNF-α p55 (type 1) receptor (TNFR1-/-) and/or IL-1β type 1 receptor (IL-1R1-/-) injected with four doses of cyclophosphamide/Adriamycin/5-fluorouracil (CAF) at 20-day intervals.

Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes.

Background: Fibroblast growth factor receptor 3 (FGFR3) inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone (T3) plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3.

Small molecule kinase inhibitors block the ZAK-dependent inflammatory effects of doxorubicin.

The adverse side effects of doxorubicin, including cardiotoxicity and cancer treatment-related fatigue, have been associated with inflammatory cytokines, many of which are regulated by mitogen-activated protein kinases (MAPKs). ZAK is an upstream kinase of the MAPK cascade. Using mouse primary macrophages cultured from ZAK-deficient mice, we demonstrated that ZAK is required for the activation of JNK and p38 MAPK by doxorubicin.

Canine fibroblast growth factor receptor 3 sequence is conserved across dogs of divergent skeletal size.

Background: Fibroblast growth factor receptor 3 (FGFR3) is expressed in the growth plate of endochondral bones and serves as a negative regulator of linear bone elongation. Activating mutations severely limit bone growth, resulting in dwarfism, while inactivating mutations significantly enhance bone elongation and overall skeletal size. Domesticated dogs exhibit the greatest skeletal size diversity of any species and, given the regulatory role of FGFR3 on growth plate proliferation, we asked whether sequence differences in FGFR3 could account for some of the size differences.