1,487 research outputs found
New Treatment Opportunities in Phosphatase and Tensin Homolog (PTEN)-Deficient Tumors: Focus on PTEN/Focal Adhesion Kinase Pathway
No full textDeep genetic studies revealed that phosphatase and tensin homolog (PTEN) mutations or loss of expression are not early events in cancer development but characterize tumor progression and invasion. Loss of PTEN function causes a full activation of the prosurvival phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, but the treatment with specific inhibitors of PI3K/AKT/mTOR did not produce the expected results. One of the alternative targets of PTEN is the focal adhesion kinase (FAK) kinase, mainly involved in the control of cancer cell spread. The connection between PTEN and FAK has been demonstrated in different tumor types, with reduced PTEN activity often correlated with increased expression and phosphorylation of FAK. FAK inhibition may thus represent a promising strategy, and some clinical trials are testing FAK inhibitors alone or combined with other agents in a number of solid tumors. However, only few preclinical and clinical data described the effects of the combination of PI3K/AKT/mTOR and FAK inhibitors. Increasing knowledge on the PTEN/FAK connection could confirm PTEN as a good prognostic marker for a combination strategy based on concomitant inhibition of PI3K/AKT and FAK signaling, in advanced metastatic malignancies with altered or reduced PTEN expression
Meccanismi cellulari e molecolari coinvolti nella risposta di adattamento di cellule endoteliali all’ ipertonicità
No full textL’inibizione dei proteasomi ripristina l’espressione del gene HSP70 in fibroblasti umani senescenti
No full text
New therapeutic strategies for malignant pleural mesothelioma
No full textMalignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. Therapeutic actions are limited due to the late stage at which most patients are diagnosed and the intrinsic chemo-resistance of the tumor. The recommended systemic therapy for MPM is cisplatin/pemetrexed regimen with a mean overall survival of about 12months and a median progression free survival of less than 6months. Considering that the incidence of this tumor is expected to increase in the next decade and that its prognosis is poor, novel therapeutic approaches are urgently needed. For some tumors, such as lung cancer and breast cancer, druggable oncogenic alterations have been identified and targeted therapy is an important option for these patients. For MPM, clinical guidelines do not recommend biological targeted therapy, mainly because of poor target definition or inappropriate trial design. Further studies are required for a full comprehension of the molecular pathogenesis of MPM and for the development of new target agents. This review updates pre-clinical and clinical data on the efficacy of targeted therapy and immune checkpoint inhibition in the treatment of mesothelioma. Finally, future perspectives in this deadly disease are also discussed
Stabilization of hsp70 mRNA on prolonged cell exposure to hypertonicity
No full textAbstractProlonged exposure of 3T3 cells to 0.5 osM hypertonic medium induced the accumulation of hsp70 mRNAs. This increase in mRNA levels required active protein synthesis. A weak and transient activation of heat shock factor 1 (HSF1) was noted, but it was temporally uncoupled to the accumulation of the hsp70 mRNAs. Nuclear run-on assay and transfection experiments showed that hsp70 gene transcription was not affected by hypertonicity. ActD chase experiments showed that during hypertonic treatment, degradation of hsp70 mRNAs was markedly reduced. This effect did not appear to be a general phenomenon since the increase in mRNA level of another gene induced by hypertonicity (ATA2 transporter) was scarcely due to RNA stabilization. These findings suggest that hypertonic treatment increases the production of hsp70 protein in 3T3 cells via a stabilization of its corresponding mRNA
The ethical and moral-based dimension of leadership in CSR-oriented strategies and sustainable entrepreneurship
No full textThis chapter addresses the theme of leadership and its influence on corporate social
responsibility (CSR) and sustainability-oriented strategies. Specifically, it aims to analyse,
through a deductive and literature-based approach, the relevance of the ethical and moral
leadership models with respect to the diffusion of CSR and sustainable entrepreneurship. Linking ethical and moral-based leadership to the CSR and sustainable entrepreneurship discourse allows us to point out the relevance of an authentic orientation in supporting
change and fostering sustainable entrepreneurship The theoretical construct of responsible and sustainable leadership derives from the
intersection of the moral-based leadership concepts with those of CSR and sustainable
entrepreneurship..Drawing from these premises, this chapter seeks to identify leadership models and
attributes consistent with (and necessary to develop) an authentic CSR-oriented strategy
and able to foster sustainable entrepreneurship.
Accordingly, in this chapter, we argue that leadership represents a key aspect that
warrants more research within both CSR and sustainable entrepreneurship studies. The
research questions that orients this study can be summarised as follows: Which leadership
models favour authentic CSR practices? Are moral, ethical-based and virtues-based models
of leadership effective in developing CSR and fostering sustainable entrepreneurship?
These questions guide the critical review of the different leadership approaches, bringing
attention to the models that are most coherent in regard to the actual socio-economic
context which requires managers and entrepreneurs to govern the internal and external
complexity and actively contribute to sustainability. The methodological approach is
mainly based on a literature review that surveys critical points in current literature that is
relevant to the topic.
The work is structured as follows. First, we offer an analysis of the leadership theoretical
framework in the context of the CSR debate. We begin with a brief methodological
note, followed by an analysis of the antecedents of CSR and sustainable entrepreneurship
in terms of values and virtues.
Second, a review of relevant literature on leadership approaches and models consistent
with the CSR and sustainable entrepreneurship discourse is presented, emphasising the relationship between transformational, moral and virtues-based leadership and
CSR-oriented strategies and sustainable entrepreneurship. Drawing from the analysis,
four main propositions are introduced. The final sections illustrate the propositions and
summarise the implications and limitations of the study
Heat-induced proteasomic degradation of HSF1 in serum-starved human fibroblasts aging in vitro
No full text- …
