Cdc42 is involved in basal cell carcinoma carcinogenesis.

Basal cell carcinoma (BCC) is the most common type of skin cancer in older persons and is a rapidly rising incidence. E-cadherin-mediated cell-cell adhesion activates Cdc42, a Rho GTPase essential for cell polarity in numerous settings. No study has yet addressed a biological significance of Cdc42 alterations in BCC pathogenesis. Our aim was to investigate E-cadherin-dependent cell-cell contacts and Cdc42 activity in BCC formation. We evaluated E-cadherin and Cdc42 expression by immunohistochemistry and Western blot analysis in samples of 15 normal skin (NS) and 30 BCC (10 superficial, 9 nodular and 11 infiltrative subtypes). Low E-cadherin and high Cdc42 immunohistochemical expression were found in BCC samples compared with NS. E-cadherin staining was significantly reduced in infiltrative BCC compared with superficial and nodular. A significantly greater Cdc42 expression was observed in BCC compared with NS; moreover, superficial BCC had a significantly lower Cdc42 expression in respect to the other subtypes. Western blot analysis confirmed the significantly decreased E-cadherin expression in infiltrative BCC as well as Cdc42 reduction in superficial BCC in respect to the other subtypes. In BCC the increased Cdc42 in association with reduced E-cadherin might contribute to the disruption of adhesion mechanisms and to the loss of cell polarity, thus explaining a mechanism by which cancer cells can escape from the control of adjacent normal keratinocytes. Our study also showed that Cdc42 and E-cadherin expression differed according to aggressive behaviour of BCC subtypes and suggested important functions of these molecules in regulating tumour demarcation and progression.

Psychological, neuroendocrine and immune measures in non spousal carers of disabled elderly in Italy.

OBJECTIVES: The purpose of this study was to determine whether psychological well being as well as metabolic, neuroendocrine and immune functions were different in non spousal primary caregivers of disabled elderly than in controls. SETTING AND DESIGN: We randomly recruited 38 primary family carers of over 65 year old recipients of health home care services and 37 controls stratified according to sex and age. METHOD: Data were collected on psychological wellbeing (including anxiety, depression and self-perceived quality of life), on neuroendocrine and immune conditions (haemanalysis and metabolic signs, plasma ACTH, cortisol, prolactin, intra-lymphocyte content of beta-endorphins, NK cell activity and number), as well as on the incidence and severity of influenza disease during previous winter. RESULTS: Caregivers showed greater anxiety, although mean scores did not reach pathological levels. Neither depression nor satisfaction on quality of life did differ significantly, nor differences in haemanalisis and metabolic signs were found, apart from leukocyte and lymphocyte number, which was significantly lower in carers. Plasma levels of ACTH, cortisol and prolactin, the intra-lymphocyte content of beta-endorphins as well as the NK cell number and cytotoxicity did not show significant differences. Incidence and severity of influenza episodes was also similar, whereas the duration of influenza disease showed to be significantly longer. CONCLUSIONS: Non spousal caregivers of disabled elderly suffer from only slight alterations of psychological, endocrine and immune parameters, and do not respond very differently to influenza disease. This does not support therefore any generic privilege for them in the allocation of public support or respite services.

Local rh-VEGF administration enhances skin flap survival more than other types of rh-VEGF administration: a clinical, morphological and immunohistochemical study.

The aim of the present study was to evaluate experimentally whether administration of recombinant (rh) vascular endothelial growth factor (VEGF) can protect skin flaps from necrosis and to study the optimum mode of rh-VEGF administration. We used rats to study the effects of local or systemic administration of rh-VEGF on skin flap during surgery; we also tested preoperative systemic administration of rh-VEGF to assess whether it may prepare the tissue to respond to the hypoxic injury better than previously tested methods. The animals were 30 male Sprague-Dawley rats. Group I rats received multiple systemic injections of rh-VEGF in the tail artery prior to flap dissection. Group II rats were injected with rh-VEGF in the clamped left epigastric artery during flap dissection; in this group, the left flaps thus received rh-VEGF locally (via incubation for 10 min during hypoxia) and the right flaps systemically, after blood flow restoration. Group III received saline solution instead of VEGF in the same way as group II. Skin samples from the distal portion of the flaps were collected on day 7 for morphological and immunohistochemical analysis. The flaps exhibiting the least necrosis were those treated with local rh-VEGF, followed by those treated with systemic rh-VEGF. The flaps that received rh-VEGF locally showed a strong VEGF expression on keratinocytes and endothelial cells, the greatest amount of mature and newly formed vessels and strong survivin expression in endothelial cells. Local rh-VEGF administration should thus be considered as an effective therapeutic option to enhance the survival of a tissue at risk for perfusion.