the role of adjuvant therapy in resectable sba a different clinicians attitude with a relevant impact on outcome

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Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Unexpected response to palliative radiotherapy for subcutaneous metastases of an advanced small cell pancreatic neuroendocrine carcinoma: A case report of two different radiation schedules

Background: Skin metastases from pancreatic neuroendocrine carcinoma (PNEC) are rare and their palliative treatment is challenging. We report our experience in the multimodal management of one of the few reported cases of metastatic PNEC with multiple visceral and subcutaneous secondary lesions, focusing on the effectiveness of palliative radiotherapy for skin metastases. Case presentation: A 61-years old woman affected by a metastatic PNEC-with subcutaneous growing and bleeding secondary lesions (at the scalp, right scapular region and at the back of the left thoracic wall, respectively)-obtained a successful control of visceral metastases with the use of chemotherapy and an unexpected local response of her skin metastases with palliative radiotherapy. In particular, two subsequent radiation treatments were performed using different fractionation schedules (30 Gy in 10 fractions and 20 Gy in 5 fractions, respectively). Both radiation treatments were well-tolerated and patient's quality of life was improved. Local response was maintained until patient's death-that occurred due to cachexia. Conclusions: The presented case highlights the effectiveness and the good tolerance of radiotherapy in the treatment of subcutaneous metastases; nevertheless, further knowledge of the optimal local palliative approach for PNEC metastatic sites is necessary. The experience gained in this work is the occasion to encourage a routine integrated multidisciplinary team management of metastatic PNECs because of their clinical complexity. The aim is to guarantee the optimization of the care with personalized and more effective systemic and local treatments-also including supportive cares and treatment-related side effects management

Pratiche di partecipazione. Teorie e metodi di intervento con bambini e adolescenti

Il volume è il risultato di un lavoro di ricerca SUI Diritti di partecipazione dei bambini e degli adolescenti. Il tema fondamentale è la promozione della partecipazione sociale dei bambini e degli adolescenti. L’indagine è stata effettuata individuando ed esaminando i progetti e gli interventi realizzati in Italia tra il 1998 ed il 2001 nel quadro previsto dalla Legge 28 agosto 1997, n. 285, Disposizioni per la promozione di diritti ed opportunità per l’infanzia e l’adolescenza. Il volume presenta un'analisi di come i progetti che promuovono la partecipazione sociale dei minori vengono tradotti in interventi. I saggi riguardano quattro aree tematiche fondamentali, tra loro correlate: 1) il problema dell’attuazione dei diritti di cittadinanza dei bambini e degli adolescenti ed il collegamento tra la partecipazione di tipo giuridico in senso stretto e la promozione giuridica della partecipazione sociale; 2) la prospettiva di una concezione dell'infanzia di tipo nuovo, caratterizzata sia dall’idea di bambino come soggetto attivo e attore sociale, sia dalla nozione di infanzia come categoria sociale autonoma; 3) le forme di comunicazione tra adulti e bambini e l'osservazione di come la comunicazione condizioni la promozione della partecipazione sociale, riducendola o incentivandola; 4) i significati della cultura dell’infanzia e dell’adolescenza che possono sostenere oppure ostacolare la partecipazione sociale. L'analisi così realizzata porta ad un'ampia ricognizione delle principali forme in cui la partecipaizone è stata promossa nell'applicazione della legislazione

VEGFA Status as a Predictive Marker of Therapy Outcome in Metastatic Gastric Cancer Patients Following Ramucirumab-Based Treatment

Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy. Following this insight, our study aims to examine the role of VEGFA status as a predictive biomarker for the outcome of second-line therapy with Ramucirumab and paclitaxel in mGC patients. To this purpose, the copy number of the VEGFA gene, by fluorescence in situ hybridization experiments, and its expression in tumor tissue as well as the density of micro-vessels, by immunohistochemistry experiments, were assessed in samples derived from mGC patients. This analysis found that amplification of VEGFA concomitantly with VEGFA overexpression and overexpression of VEGFA with micro-vessels density are more represented in patients showing disease control during treatment with Ramucirumab. In addition, in the analyzed series, it was found that amplification was not always associated with overexpression of VEGFA, but overexpression of VEGFA correlates with high micro-vessel density. In conclusion, overexpression of VEGFA could emerge as a potential biomarker to predict the response to anti-angiogenic therapy