Adipose tissue as target organ in the treatment of hormone-dependent breast cancer: new therapeutic perspectives

Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Despite many undeniable therapeutic successes obtained, breast cancer still remains, however, a major health issue. In the last few years, thanks to aromatase inhibitors, the hormone therapy for oestrogen-dependent breast cancer has evolved in terms of efficacy and tolerability; at the same time, it has enabled us to better define the role of oestrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. A more recent hypothesis suggests that adipocytes and their autocrine (paracrine and endocrine actions) are at the centre of such an etiopathogenetic mechanism. A better understanding of the main mechanisms that link together menopause, body-weight increase and hormone-dependent breast cancer is paramount to enable the identification of key molecules involved in the development of breast carcinoma and suggest new therapeutic options. The present review will discuss important findings on the therapeutic aspects of adipose tissue and adipokines as a target for treatment of hormone-dependent breast cancer.     

Cavo-portal transposition in rat: a new simple model

Background  

Liver transplantation in presence of diffuse portal vein thrombosis is possible by using caval blood as portal inflow, through cavo-portal transposition. However, clinical results are heterogeneous and experimental studies are needed, but similar hemodynamic conditions are difficult to obtain, especially in small animals. Herein we describe a new simple model of cavo-portal transposition in rat.     

Influence of subacute starvation on cardiac response to isoproterenol in rats.

Several studies have reported that the heart is severely affected by chronic malnutrition. However, the influence of these alterations on cardiac function remains unclear. The aim of this study was to evaluate the effects of subacute starvation on the heart chronotropic response to a beta-adrenergic agonist (isoproterenol). Twelve rats were fed rat chow ad libitum or a 50%-restricted diet for 17 days. The rats were killed, the right atrium was isolated and incubated, and in vitro spontaneous cardiac contractions and frequency were registered. Cumulative doses of isoproterenol were added to the solution until maximal cardiac frequency was achieved. A deficit of 25% in the weight gain was observed in study rats compared with controls (92.6 +/- 10.2 vs. 113.8 +/- 19.2 g, p less than 0.05). Mean daily food intake was 4.8 +/- 0.1 and 9.8 +/- 0.5 g/day for semistarved and control rats, respectively. The in vitro cardiac frequency of the semistarved rats was similar to that of controls (290 +/- 15 and 305 +/- 23 beats/min, respectively, NS). However, when isoproterenol was added to the solution, maximal cardiac frequency of the semistarved rats (435 +/- 51 beats/min) was lower than that of control rats (508 +/- 34 beats/min, p less than 0.005). These findings suggest that subacute starvation may alter the cardiac response to beta-adrenergic agonists.     

Evaluation of myocardial metabolism with microdialysis during bypass surgery with cold blood- or Calafiore cardioplegia.

BACKGROUND: For the first time, microdialysis was used to investigate in vivo and online the myocardial metabolism during and after cardiac surgery in patients treated with two different methods of myocardial protection. METHODS: Thirty patients underwent standard CABG with one of two different methods of myocardial protection. The patients were randomised to receive either cold blood (COLD group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis probes were implanted into the myocardium of left ventricular apical region of the heart. Cardioplegia was given antegrade only. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass and analysed for glucose, lactate, pyruvate and glycerol. RESULTS: Myocardial lactate concentrations were significantly higher in the WARM group compared with that of the COLD group, while serum lactate was comparable. Glycerol was significantly higher at the end of the clamping time in the WARM group. At the same time the glucose-lactate ratio as a marker of nutritional disorder had significantly lower levels in the WARM group. The cumulative CK-MB release over 24 h was significantly higher in those hearts protected with warm blood. CONCLUSIONS: The oxidative stress measured was significantly higher in patients undergoing CABG using modified Calafiore cardioplegia, whereas the cold cardioplegia minimised the effects of aortic clamping. The results indicate that cold cardioplegia offers superior protection of the heart, in terms of more rapid normalisation of myocardial metabolism. In elective myocardial revascularisation, intermittent antegrade warm blood cardioplegia is a comparable safe method of myocardial protection. However, in patients referring to a long clamping time, advantages of cold cardioplegia for myocardial revascularisation may be magnified.     

Characterization of spontaneous metastases from autochthonous 3-methylcholanthrene-induced tumors

In mice bearing autochthonous 3-methylcholanthrene-induced tumors metastasis was rare, with only 2 out of 47 (4%) animals showing lung secondaries and 1 showing kidney lesions. Surgical excision of autochthonous growing tumors brought only a slight increase in incidence of metastasis (5 out of 42 mice, 12%). Cell lines were established by in vivo and/or in vitro passage from two kidney metastasis found in the same host (0.13-K1 and 0.13-K3) and from a spontaneous lung metastasis found in 2 mice (mR80/43 and mR80/17) and compared to lines from the respective primary tumors (0.13; R80/17; R80/43). Cell lines from metastases and primary tumors were heterogeneous in tumorigenicity, growth rate, metastatic potential (spontaneous), and colonizing capacity (i.v. inoculation). In particular, the mR80-43 line was more metastatic to lungs upon intravenous injection than the parent R80-43 primary tumor. Similarly the 013-K1 line from a kidney secondary caused more lung nodules when inoculated intravenously than the parent 0.13 line, but this was not the case with the 013-K3 line derived from another kidney secondary in the same host. The R80-17 and mR80-17 lines had similar lung-colonizing capacity. Lung colonizing ability was not strictly correlated to the capacity to form spontaneous metastases. Changes in lung-colonizing capacity occurred in part of the lines (013, 013-K1, R80-17, mR80-17) upon in vitro or in vivo passage. These findings with lines from spontaneous metastases from three autochthonous sarcomas extend previous observations on the heterogenous behavior of transplanted metastatic neoplasms.     

Differentiation of the epidermis in turtle: an immunocytochemical, autoradiographic and electrophoretic analysis

Proteins involved in the process of cornification of turtle epidermis are not well known. The present immunocytochemical, electrophoretic and autoradiographic study reports on the localization patterns and molecular weights of keratins, which are cornification proteins, and of tritiated histidine in turtle epidermis. Alpha-keratins with a molecular weight of 40-62 kDa are present in the epidermis. Beta-keratin is mainly detectable in the stratum corneum of the carapace and plastron, but is rarely present or even absent in the corneous layer of limb, tail and neck epidermis. After electrophoresis and immunoblotting with an antibody against chicken scale beta-keratin, bands at 15-17, 22-24, and 36-38 kDa appeared. This antibody recognized weaker bands at 38-40 and 58-60 kDa in the soft epidermis. After reduction and carboxymethylation of proteins extracted from carapace and plastron, but not of proteins from the soft epidermis, protein bands at 15-17 and 35-37 kDa were found when using the anti-beta 1-keratin antibody. Loricrin-, filaggrin-, sciellin-, and transglutaminase-like immunostaining was detectable only in the transitional and lowermost corneous layers of the soft epidermis. Vesicular bodies in the transitional layer were immunolabeled by the anti-loricrin antibody, and weakly by the anti-filaggrin and anti-transglutaminase antibodies. In immunoblots, the anti-loricrin antibody reacted with a major band at 50-54 kDa in both carapace-plastron and soft epidermis. The anti-sciellin antibody detected major bands at 38-40 and 50 kDa in hard epidermis, and at 50 and 54-56 kDa in soft epidermis. Filaggrin-like immunostained bands were observed at 50-55 and 62-64 kDa. This immunostaining was probably due to a common epitope in filaggrin and some keratins. Histidine was evenly incorporated in the epidermis, and the ultrastructural study showed random labeling, often associated with keratin bundles of alpha and beta-keratinocytes. Histidine-labeled protein bands were not found in the carapace-plastron. In the soft epidermis, weakly labeled bands at 15-20, 25, and 45-60 kDa were found occasionally. The latter bands probably represented neo-synthesized keratins as was also indicated by the ultrastructural autoradiographic analysis. In conclusion, our study suggests that proteins with epitopes that they have in common with cornification proteins of mammalian epidermis are also present in the epidermis of turtle.