The aberrant expression in epithelial cells of the mesenchymal isoform of FGFR2 controls the negative crosstalk between EMT and autophagy

Signalling of the epithelial splicing variant of fibroblast growth factor receptor 2 (FGFR2b) triggers both differentiation and autophagy, while the aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells induces impaired differentiation, inhibition of autophagy as well as the induction of the epithelial-mesenchymal transition (EMT). In light of the widely proposed negative loop linking autophagy and EMT in the early steps of carcinogenesis, here we investigated the possible involvement of FGFR2c aberrant expression and signalling in orchestrating this crosstalk in human keratinocytes. Biochemical, molecular, quantitative immunofluorescence analysis and in vitro invasion assays, coupled to the use of specific substrate inhibitors and transient or stable silencing approaches, showed that AKT/MTOR and PKCε are the two hub signalling pathways, downstream FGFR2c, intersecting with each other in the control of both the inhibition of autophagy and the induction of EMT and invasive behaviour. These results indicate that the expression of FGFR2c, possibly resulting from FGFR2 isoform switch, could represent a key upstream event responsible for the establishment of a negative interplay between autophagy and EMT, which contributes to the assessment of a pathological oncogenic profile in epithelial cells

HER2-positive breast cancer and CNS metastases: Prognostic factors and clinical outcome

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Effect of raloxifene on IGF-I and IGFBP-3 in postmenopausal women with breast cancer

The effect on the IGF system of 60 mg and 600 mg daily of raloxifene administered for 2 weeks prior to surgery was investigated in 37 postmenopausal women with breast cancer. Raloxifene significantly decreased insulin-like growth factor (IGF-I) as compared to placebo (P < 0.05) with no dose–response relationship. No significant change was observed in IGFBP-3, while the IGF-I/IGFBP-3 molar ratio was decreased by treatment, with a statistically significant effect only for the higher dose. Given that high plasma levels of IGF-I have been suggested as a risk factor for breast cancer, these findings provide further support for the potential activity of raloxifene in breast cancer prevention. © 2001 Cancer Research Campaign http://www.bjcancer.co

A phase II study of primary dose-dense sequential doxorubicin plus cyclophosphamide and docetaxel in cT4 breast cancer

Background: Dose-dense chemotherapy with anthracyclines and taxanes has improved either disease free survival or overall survival in high risk patients with early breast cancer. Patients and Methods: The activity and safety of a dose-dense schedule (q14 days) of adriamycin 60 mg/sqm and cyclophosphamide 600 mg/sqm (AC) x 4 cycles followed by docetaxel 75 mg/sqm for 4 cycles with hematopoietic support in patients with stage IIIB breast cancer was explored. Patients with ER &gt;= 10% tumors received concomitant endocrine therapy with 3-month triptorelin and letrozole. Results: Fifteen patients with histologically proven cT4b (three patients) and cT4d (twelve patients) MO breast cancer were enrolled. Median age was 48 years (range 25-66). Eight clinical responses including one pathological complete remission (pCR), three stable disease (including minor responses) and four progression of disease, one during AC and three during taxotere, were observed. Four patients had grade 3-4 non hematological toxicities and all except one discontinued treatment. Conclusion: Due to the high rate of progressive disease, this schedule should not represent a standard option in cT4 breast cancer

Group Analysis of the Novikov Equation

We find the Lie point symmetries of the Novikov equation and demonstrate that it is strictly self-adjoint. Using the self-adjointness and the recent technique for constructing conserved vectors associated with symmetries of differential equations, we find the conservation law corresponding to the dilations symmetry and show that other symmetries do not provide nontrivial conservation laws. Then we investigat the invariant solutions

Perioperative serum VEGF and extracellular domains of EGFR and HER2 in early breast cancer

Background: The prognostic role of serum levels of molecular biomarkers during the perioperative period in patients with early breast cancer is not clear. Patients and Methods: Serum VEGF and extracellular domains (ECD) of EGFR and HER2 were prospectively determined in 119 consecutive patients with early breast cancer on the day before and after surgery. Results: After a median follow-up of 93 months, the preoperative value and the absolute change from pre- to postoperative serum levels of VEGF and HER2 ECD did not predict disease-free survival (DFS). A decrease after surgery of EGFR ECD correlated with a statistically significant lower DFS; each 1 ng/ml decrease in EGFR ECD serum level was associated with an increase of event risk of 15% on multivariable analysis (hazard ratio 1.15 95% confidence interval 1.04.-1.28, p=0.006). Conclusion: The perioperative absolute change of EGFR ECD significantly correlated with disease outcome of patients with early breast cancer. No correlation was found between preoperative and perioperative absolute change of serum VEGF and HER2 ECD

Numerical simulations on laser absorption enhancement in hybrid metallo-dielectric nanostructured targets for future nuclear astrophysics experiments

The linear electromagnetic interaction between innovative hybrid metallo-dielectric nanostructured targets and laser in visible and IR range is investigated through numerical simulations. The obtained results rely on the optimization of a target based on metallic nanowires (NWs) to enhance light absorption in the visible range of the electromagnetic spectrum. The NWs are grown within the ordered nanoholes of an alumina substrate, thus, forming a plasmonic lattice with triangular symmetry. The remaining volume of the nanoholes on top of the NWs is sealed with a transparent layer of aluminum oxide that is suitable to be chemically modified for containing about 25% of deuterium atoms. The study presented here is carried out within the framework of a scientific program named PLANETA (Plasmonic Laser Absorption on Nano-Engineered Targets) aiming at investigating new laser–matter interaction schemes in the ns domain and for nuclear fusion purposes, involving especially the D–D reaction

Proton therapy and src family kinase inhibitor combined treatments on U87 human glioblastoma multiforme cell line

Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy (PT) shows a ballistic precision and a higher dose conformity than conventional RT. In this study we investigated the radiosensitive effects of a new targeted compound, SRC inhibitor, named Si306, in combination with PT on the U87 glioblastoma cell line. Clonogenic survival assay, dose modifying factor calculation and linear-quadratic model were performed to evaluate radiosensitizing effects mediated by combination of the Si306 with PT. Gene expression profiling by microarray was also conducted after PT treatments alone or combined, to identify gene signatures as biomarkers of response to treatments. Our results indicate that the Si306 compound exhibits a radiosensitizing action on the U87 cells causing a synergic cytotoxic effect with PT. In addition, microarray data confirm the SRC role as the main Si306 target and highlights new genes modulated by the combined action of Si306 and PT. We suggest, the Si306 as a new candidate to treat GBM in combination with PT, overcoming resistance to conventional treatments