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Off-energy-shell effects in p - p scattering have been investigated at p - p relative energies from 600 down to 80 keV applying the Trojan horse method (THM) to the p + d --> p + p + n reaction at 5 MeV. In contrast with the on-energy-shell case, no Coulomb-nuclear interference minimum has been found in the extracted THM p - p cross section, due to the suppression of the Coulomb amplitude as predicted by the half-off-energy shell calculations. This hypothesis is strengthened by the agreement between THM p - p data and calculated on-energy-shell n + n, n + p and nuclear p + p cross sections.

Inhibition of platelet-derived growth factor receptor (PDGFR) signaling restricts the growth of human breast cancer in the bone of nude mice. We hypothesized that osteoblast-secreted substances may alter the response capacity of breast cancer cells to the PDGFRs tyrosine kinase inhibitor imatinib mesylate. We found that osteoblast-conditioned medium (OCM) increases the proliferation rate of the estrogen receptor negative (ER-) MDA-MB-231 and of the ER+ MCF-7 human breast cancer cell lines and the growth-promoting effect on ER+ cells is independent from estrogen. OCM significantly improved the dose- and the time-dependent sensitivity of the tumor cells to the anti-proliferative effect of imatinib. We also found that MDA-MB-231 and MCF-7 cells express the two PDGFRs subtypes, PDGFR-alpha and PDGFR-beta, and OCM treatment increases the expression of the PDGFRs. Furthermore, imatinib inhibited the phosphorylation rate of its target tyrosine kinase receptors. We conclude that bone microenvironment, through osteoblast-secreted substances may cause estrogen-independent proliferation of breast cancer cells by a mechanism mediated by the induction of PDGFRs expression. The enhanced sensitivity of OCM-treated breast cancer cells to imatinib would justify investigation on the efficacy of imatinib in bone breast cancer metastasis.

Breast cancer (BC) is linked to estrogen exposure. Estradiol (E2) stimulates BC cells proliferation by binding the estrogen receptor (ER). Hormone-related cancers have been linked to estrogenic environmental contaminants. Cadmium (Cd) a toxic pollutant, acts as estrogens in BC cells. Purpose of our study was to evaluate whether Cd regulates MCF-7 cell proliferation by activating ERK1/2, Akt and PDGFRalpha kinases. Cd increased cell proliferation and the ER-antagonist ICI 182,780 blunted it. To characterize an ER-dependent mechanism, ERalpha/beta expression was evaluated. Cd decreased ERalpha expression, but not ERbeta. Cd also increased ERK1/2, Akt and PDGFRalpha phosphorylation while ICI blocked it. Since stimulation of phosphorylation was slower than expected, c-fos and c-jun proto-oncogenes, and PDGFA were analyzed. Cd rapidly increased c-jun, c-fos and PDGFA expression. Cells were also co-incubated with the Cd and specific kinases inhibitors, which blocked the Cd-stimulated proliferation. In conclusion, our results indicate that Cd increases BC cell proliferation in vitro by stimulating Akt, ERK1/2 and PDGFRalpha kinases activity likely by activating c-fos, c-jun and PDGFA by an ERalpha-dependent mechanism.

The presence of cachexia as defined by a series of clinical symptoms, such as anorexia, weight loss, muscular atrophy, tissue wasting, altered organ function, is frequently observed in cancer and makes a decisive contribution to morbidity and mortality. The onset of neoplastic cachexia is characterized by two events: the presence of primary or secondary anorexia and alterations of the host's intermediate metabolism. Among the most frequent metabolic alterations described in cancer patients is an absolute or relative increase in basal energy consumption with lack of adaptation to fasting. The causes of increased energy consumption in cancer patients are still not clear. Numerous studies on glucose, fat and protein metabolism induced by cancer have significantly contributed to our understanding of the phenomenon. The main alterations of the glucose metabolism are increased glucose turnover and reduced peripheral utilization, both of which probably depend on the presence of the tumour, as shown by their normalization after treatment. Increased gluconeogenesis, from lactate and from gluconeogenetic AA, is the main factor responsible for increased glucose turnover. The main alterations of the fat metabolism are increased mobilization of lipids from adipose tissues, reduced use of exogenous triglycerides and increased oxidation of free fatty acids that cannot be suppressed by glucose. The main alterations of protein metabolism are increased protein turnover with reduced synthesis and increased degradation of muscular proteins and increased hepatic protein synthesis. Knowledge of the pathogenesis of neoplastic cachexia represents a valuable aid for its effective prevention and treatment.