SIDA-Sport, Identità ed Adolescenza: Verso la costruzione di un nuovo protocollo di valutazione.

La psicologia dello sport ha abbracciato lo studio dell'identità atletica negli anni Novanta. L’obiettivo della nostra ricerca, dopo un’attenta revisione [Filippini et al,2023]1, è quello di creare un nuovo protocollo, che possa integrare una parte quantitativa ad una parte qualitativa, dando vita, così, ad una nuova batteria di test che vada ad individuare l’efficacia dello sport nella costruzione dell’identità nella fase adolescenzial

Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma

Innovative therapeutic agents have significantly improved outcomes, with an acceptable safety profile, in a substantial proportion of non-small cell lung cancer (NSCLC) patients in whom the malignant phenotype of the disease is determined by oncogenic molecular alterations. However, the benefit seen with these treatment models has not translated well to NSCLCs with KRAS mutations or squamous cell histology. Although efforts have been made to develop precision medicine approaches, KRAS mutant NSCLC and lung squamous cell carcinoma (LSCC) continue to display resistance to therapy. Recently, based on the results of the Phase III SQUIRE trial, the EGFR monoclonal antibody necitumumab received FDA authorization in combination with cisplatin and gemcitabine for first line treatment of patients with metastatic LSCC. Among the molecular compounds tested in KRAS mutant NSCLC patients, the MEK inhibitor, selumentinib, combined with docetaxel in second line setting, determined a progression-free survival improvement, but no overall survival advantage. Better understanding is needed in regard to signaling pathways which cooperate to induce oncogene transformation in LSCC and KRAS mutant NSCLC and could determine intrinsic or acquired resistance to necitumumab and selumetinib. Greater understanding of such pathways will provide a molecular base upon which to improve the scant clinical benefit with these compounds

BIM and mTOR expression levels predict outcome to erlotinib in EGFR-mutant non-small-cell lung cancer

Altres ajuts: Fellowship Award of the International Association for the Study of Lung Cancer i grant of the Italian Association for Cancer Research (AIRC My First AIRC Grant n° 14282).Abstract.BIM is a proapoptotic protein that initiates apoptosis triggered by EGFR tyrosine kinase inhibitors (TKI). mTOR negatively regulates apoptosis and may influence response to EGFR TKI. We examined mRNA expression of BIM and MTOR in 57 patients with EGFR-mutant NSCLC from the EURTAC trial. Risk of mortality and disease progression was lower in patients with high BIM compared with low/intermediate BIM mRNA levels. Analysis of MTOR further divided patients with high BIM expression into two groups, with those having both high BIM and MTOR experiencing shorter overall and progression-free survival to erlotinib. Validation of our results was performed in an independent cohort of 19 patients with EGFR-mutant NSCLC treated with EGFR TKIs. In EGFR-mutant lung adenocarcinoma cell lines with high BIM expression, concomitant high mTOR expression increased IC50 of gefitinib for cell proliferation. We next sought to analyse the signalling pattern in cell lines with strong activation of mTOR and its substrate P-S6. We showed that mTOR and phosphodiesterase 4D (PDE4D) strongly correlate in resistant EGFR-mutant cancer cell lines. These data suggest that the combination of EGFR TKI with mTOR or PDE4 inhibitors could be adequate therapy for EGFR-mutant NSCLC patients with high pretreatment levels of BIM and mTOR

Risorse personali e Leadership: l’impatto della proattività sul benessere

Introduzione. A seguito dell’emergenza pandemica numerosi cambiamenti hanno stravolto le organizzazioni incidendo sul benessere delle persone, alle quali è richiesto un pervasivo adattamento alle nuove modalità di lavoro. La letteratura ha dimostrato la rilevanza delle risorse personali nella gestione dei cambiamenti. Studi precedenti hanno dimostrato che le capacità agentiche facilitano i comportamenti proattivi di Job Crafting - attraverso la previsione dei possibili scenari futuri, il conseguente modellamento delle strategie per perseguire le proprie mete e la finale capitalizzazione dalle esperienze passate - contribuendo al raggiungimento di performance elevate e promuovendo il benessere percepito. Tuttavia, nessun contributo approfondisce il ruolo differenziato dei comportamenti di Task e Relational Crafting su tali esiti. Infine, le organizzazioni possono creare le condizioni facilitanti per lo sviluppo del Job Crafting attraverso uno stile gestionale come la Coaching Leadership, capace di valorizzare le risorse personali e le potenzialità dei collaboratori. Obiettivi. Indagare la relazione di influenza positiva delle capacità agentiche sugli esiti organizzativi di Task Performance e Benessere attraverso la mediazione, rispettivamente, del Task e del Relational Crafting; esplorare il possibile ruolo di moderazione della Coaching Leadership sulla relazione di influenza positiva delle capacità agentiche su entrambi Task e Relational Crafting. Metodo. I dati sono stati raccolti tramite un questionario online somministrato in due tempi, a distanza di sei mesi, finalizzato a rilevare le dimensioni sopracitate. Le analisi sono state condotte su un campione di 180 dipendenti di un’organizzazione italiana, leader nel settore delle telecomunicazioni. È stato testato un modello di mediazione moderata utilizzando il Software Mplus. Risultati. I risultati confermano complessivamente quanto ipotizzato. Limiti. Legati alla generalizzabilità dei risultati e all’utilizzo di dati self-report. Ricadute applicative. Percorsi formativi e di coaching possono accrescere il Job Crafting capitalizzando dalle risorse personali (capacità agentiche) e di contesto (Coaching Leadership) al fine di migliorare la prestazione e il benessere

Other targeted drugs in melanoma

Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are "targeted" to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other "druggable" kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials

Melanoma: oncogenic drivers and the immune system

Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches

Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC

Background: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non- small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals.We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response. Methods: We used MTT and clonogenic assays, immunoblotting, and quantitative polymerase chain reaction to evaluate the efficacy of EGFR TKI alone and in combination with STAT3 and Src inhibition in three EGFR-mutant NSCLC cell lines. The Chou-Talalay method was used for the quantitative determination of drug interaction. We examined tumor growth inhibition in one EGFR-mutant NSCLC xenograft model (n¼4 mice per group). STAT3 and YAP1 expression was evaluated in tumors from 119 EGFR-mutant NSCLC patients (64 in an initial cohort and 55 in a validation cohort) by quantitative polymerase chain reaction. Kaplan-Meier and Cox regression analyses were used to assess the correlation between survival and gene expression. All statistical tests were two-sided. Results: We discovered that lung cancer cells survive initial EGFR inhibitor treatment through activation of not only STAT3 but also Src-YAP1 signaling. Cotargeting EGFR, STAT3, and Src was synergistic in two EGFR-mutant NSCLC cell lines with a combination index of 0.59 (95% confidence interval [CI] ¼ 0.54 to 0.63) for the PC-9 and 0.59 (95% CI¼0.54 to 0.63) for the H1975 cell line. High expression of STAT3 or YAP1 predicted worse progression-free survival (hazard ratio [HR] ¼ 3.02, 95% CI¼1.54 to 5.93, P ¼ .001, and HR¼2.57, 95% CI¼1.30 to 5.09, P ¼ .007, respectively) in an initial cohort of 64 EGFR-mutant NSCLC patients treated with firstline EGFR TKIs. Similar results were observed in a validation cohort. Conclusions: Our study uncovers a coordinated signaling network centered on both STAT3 and Src-YAP signaling that limits targeted therapy response in lung cancer and identifies an unforeseen rational upfront polytherapy strategy to minimize residual disease and enhance clinical outcomes

First-Line Osimertinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer: Outcome and Safety in the Real World: FLOWER Study

Osimertinib has confirmed effectiveness in this real-world population of patients with EGFR-mutant advanced non-small cell lung cancer population. Thromboembolic events occur more frequently than previously reported, suggesting a thrombotic diathesis that requires further investigation. Patients with at least three metastatic sites, brain metastases, and symptoms at diagnosis seem to have a worse prognosis

Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s41030-016-0013-3">https://link.springer.com/article/10.1007/s41030-016-0013-3</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p