The findings are consistent with a low prevalence of PsA among patients with psoriasis in Asia and confirm a high percentage of undiagnosed cases with active arthritis among PsA patients in dermatologist's office. Dermatologists should screen for PsA in their patients, especially those with risk characteristics and early signs.

Prohibitin (PHB) is indispensable for Ras-induced Raf-1 activation, cell migration and growth; however, the exact role of PHB in the molecular pathogenesis of cancer metastasis remains largely unexamined. Here, we found a positive correlation between plasma membrane-associated PHB and the clinical stages of cancer. The level of PHB phosphorylated at threonine 258 (T258) and tyrosine 259 (Y259) in human cancer-cell membranes correlated with the invasiveness of cancer cells. Overexpression of phosphorylated PHB (phospho-PHB) in the lipid-raft domain of the cell membrane enhanced cell migration/invasion through PI3K/Akt and Raf-1/ERK activation. It also enhanced epithelial-mesenchymal transition, matrix metalloproteinase-2 activity and invasiveness of cancer cells in vitro. Immunoprecipitation analysis demonstrated that phospho-PHB associated with Raf-1, Akt and Ras in the membrane and was essential for the activation of Raf-1 signaling by Ras. Mice implanted with cancer cells stably overexpressing PHB in the plasma membrane showed enlarged cervical tumors, enhanced metastasis and shorter survival time compared with mice implanted with cancer cells without PHB overexpression. Dephosphorylation of PHB at T258 by site-directed mutagenesis diminished the in vitro and in vivo effects of PHB. These results suggest that increase in phospho-PHB T258 in the raft domain of the plasma membrane has a role in the Ras-driven activation of PI3K/Akt and Raf-1/ERK-signaling cascades and results in the promotion of cancer metastasis.

Abstract-Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an important determinant of cardiac function. Tumor necrosis factor-␣ (TNF-␣) and angiotensin (Ang) II levels increase after MI and both factors affect fibroblast functions. The type 1 (AT 1 ) receptor that mediates most Ang II effects is upregulated after MI in cardiac fibroblasts, and there is evidence that this is caused by TNF-␣. We sought to determine if TNF-␣-induced AT 1 receptor upregulation alters fibroblast responsiveness to Ang II and if this effect differs from direct TNF-␣ effects on fibroblast functions. In cultured neonatal rat cardiac fibroblasts, TNF-␣ reduced cellular [ 3 H]-proline incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, and increased TIMP-1 protein levels. In cardiac fibroblasts with TNF-␣-induced AT 1 receptor upregulation, Ang II-stimulated [ 3 H]proline incorporation and TIMP-1 protein production was approximately 2-fold greater than in nonpretreated fibroblasts. Angiotensin II reduced MMP-2 activity and protein level only in TNF-␣-pretreated fibroblasts. Angiotensin II effects were inhibited by selective AT 1 (but not AT 2 ) receptor blockers. Thus, TNF-␣-induced AT 1 receptor upregulation enhances Ang II-mediated functions that favor fibrosis. These effects are mostly directionally opposite of direct TNF-␣ effects on cardiac fibroblasts. Key Words: collagen synthesis Ⅲ tumor necrosis factor-␣ Ⅲ matrix metalloproteinase Ⅲ tissue inhibitor of matrix metalloproteinase Ⅲ angiotensin II P ost-myocardial infarction (MI) remodeling is a complex process involving biochemical, structural, and geometric changes in the heart. The resulting alterations in ventricular size and shape are an important cause of heart failure. Although alterations in myocyte structure and function clearly play a role in remodeling, fibroblast effects on the extracellular matrix (ECM) contribute significantly to the remodeling process. 1 ECM remodeling involves tissue breakdown and formation of the replacement scar at the infarct site. Progressive accumulation of fibrous tissue including reactive perivascular/interstitial fibrosis and reparative fibrosis in response to myocyte loss also occurs in noninfarcted segments of myocardium. 1-3 Both the adequacy of replacement scar formation and the extent of fibrosis in noninfarcted myocardium are determinants of systolic and diastolic function of the heart. 4,5 Thus, better understanding of factors that influence fibroblast function during ECM remodeling should provide important insights into the pathogenesis of heart failure.After MI there is initial tissue breakdown at the infarct site followed by ECM deposition in this region and in noninfarcted myocardium. [1][2][3][4][5][6] Collagen breakdown involves the activation of degradative enzymes termed matrix metalloproteinases (MMPs). 7 These endogenous zinc-dependent enzymes are regulated by proteins known as tissue inhibitors of metalloproteinases (TIMPs). Cardiac fibroblasts and phenotypically transform...

AlignRT3C can be used as a nonionizing IGSPS with accuracy comparable to current image/marker-based systems. IGSPS and CBCT can be combined for high-precision positioning without the need for patient-attached localization devices.