Expression of connective tissue growth factor (CTGF), a member of the CCN gene family, is known to be significantly induced by mechanical stress. We have therefore investigated whether other members of the CCN gene family, including Cyr61 and Nov, might reveal a similar stress-dependent regulation. Fibroblasts growing under stressed conditions within a three-dimensional collagen gel showed at least a 15 times higher level of Cyr61 mRNA than cells growing under relaxed conditions. Upon relaxation, the decline of the Cyr61 mRNA to a lower level occurred within 2 h, and was thus quicker than the response of CTGF. The regulation was fully reversible when stress was reapplied. Thus, Cyr61 represents another typical example of a stress-responsive gene. The level of the Nov mRNA was low in the stressed state, but increased in the relaxed state. This CCN gene therefore shows an inverted regulation relative to that of Cyr61 and CTGF. Inhibition of protein kinases by means of staurosporine suppressed the stress-induced expression of Cyr61 and CTGF. Elevated levels of cAMP induced by forskolin mimicked the effects of relaxation on the regulation of Cyr61, CTGF and Nov. Thus, adenylate cyclase as well as one or several protein kinases might be involved in the mechanoregulation of these CCN genes.
High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is applied for consolidation in myeloma and relapsing lymphoma patients. Vitamin D (VitD) exerts effects during hematopoietic stem cell proliferation, differentiation and interactions with the immune system. VitD deficiency is frequent in patients with hematological malignancies, but its prognostic relevance after ASCT remains unclear. We investigated the effect of VitD serum levels in patients with lymphomas and myeloma at ASCT on progression-free (PFS) and overall survival (OS). The cohort (n = 183) was divided into two groups: 81 (44%) had VitD levels >52 nmol/L and
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