Neoadjuvant Therapy in Pancreatic Cancer: An Emerging Strategy

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths among men and women, being responsible for 6% of all cancer-related deaths. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. In recent years, increasing evidences support the use of neoadjuvant strategies in pancreatic cancer in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC in order to allow early treatment of micrometastatic disease, tumour regression, and reduced risk of peritoneal tumour implantation during surgery. Furthermore, neoadjuvant treatment allows evaluation of tumour response and increases patient’s compliance. However, most evidences in this setting come from retrospective analysis or small case series and in many studies chemotherapy or chemoradiation therapies used were suboptimal. Currently, prospective randomized trials using the most active chemotherapy regimens available are trying to define the real benefit of neoadjuvant strategies compared to conventional adjuvant strategies. In this review, the authors examined available data on neoadjuvant treatment in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC and the future directions in this peculiar setting

Toll like receptors and pancreatic diseases: From a pathogenetic mechanism to a therapeutic target

Toll-like receptors (TLRs) mediate interactions between environmental stimuli and innate immunity. TLRs play a major role in the development of numerous pancreatic diseases, making these molecules attractive as potential therapeutic targets. TLR2, TLR7 and TLR9 are involved in the initiation of type 1 diabetes mellitus (T1DM), whereas TLR2 and TLR4 play a major role in the onset of type 2 diabetes mellitus (T2DM). Furthermore, TLRs cause derangements in several tumor suppressor proteins (such as p16, p21, p27, p53 and pRb), induce STAT3 activation and promote epithelial-mesenchymal transition as well as oncogene-induced senescence. In this review we will focus on the contribution of TLRs in pancreatic disease including cancer and we describe recent progress in TLR-modulation for the treatment of these patients

Behavioural equivalences and interference metrics for mobile ad-hoc networks

Abstract Connectivity and communication interference are two key aspects in mobile ad-hoc networks (MANETs). This paper proposes a process algebraic model targeted at the analysis of both such aspects. The framework includes a probabilistic process calculus and a suite of analytical techniques based on a probabilistic observational congruence and an interference-sensitive preorder. The former enables the verification of behavioural equivalences; the latter makes it possible to evaluate the interference level of behaviourally equivalent networks. The result is a comprehensive and effective framework for the behavioural analysis and a quantitative assessment of interference for wireless networks in the presence of node mobility. We show our techniques at work on two realistic case studies

Connectivity and energy-aware preorders for mobile ad-hoc networks

Network connectivity and energy conservation are two major goals in mobile ad-hoc networks (MANETs). In this paper we propose a probabilistic, energy-aware, broadcast calculus for the analysis of both such aspects of MANETs. We first present a probabilistic behavioural congruence together with a co-inductive proof technique based on the notion of bisimulation. Then we define an energy-aware preorder over networks. The behavioural congruence allows us to verify whether two networks exhibit the same (probabilistic) connectivity behaviour, while the preorder makes it possible to evaluate the energy consumption of different, but behaviourally equivalent, networks. In practice, the quantitative evaluation of the models is carried out by resorting to the statistical model checking implemented in the PRISM tool, i.e., a simulation of the probabilistic model. We consider two case studies: first we evaluate the performance of the Location Aided Routing protocol, then we compare the energy efficiency of the Go-Back-N protocol with that of the Stop-And-Wait in a network with mobility

Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage

FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome

The Risk Assessment in Low Grade Gliomas: An Analysis of European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) criteria

<p></p><p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s40487-018-0063-9"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> 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.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p><br><p></p

Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC

none8siThe introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented. Although first approvals of ICI therapy have been recently granted in SCLC and MPM (in combination with chemotherapy and different ICIs), results remain somewhat modest and limited to a small proportion of patients. This work reviews the trial results of ICI therapy in mesothelioma, SCLC, and TETs and discusses the potential of combining ICIs with old drugsrestrictedCantini, Luca; Pecci, Federica; Merloni, Filippo; Lanese, Andrea; Lenci, Edoardo; Paoloni, Francesco; Aerts, Joachim G.J.V.; Berardi, RossanaCantini, Luca; Pecci, Federica; Merloni, Filippo; Lanese, Andrea; Lenci, Edoardo; Paoloni, Francesco; Aerts, Joachim G. J. V.; Berardi, Rossan

Trattamento del carcinoma del pancreas. Attualità e prospettive

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest solid malignancies, with an extremely poor prognosis, with a 1-year survival rate of approximately 20%. Low survival rates of PDAC mainly derive from late diagnosis, with only a minority of patients amenable to surgery, as well as high rates of relapse and lack of effective treatments for advanced disease stages. As a result, there is an urgent need for the development of new effective therapies. At present, the greatest step towards an improvement of treatment has been made with the introduction of two combination chemotherapy regimens, namely FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab-paclitaxel. However, current research is also taking a multidirectional approach aiming at developing new treatment options, such as the use of agents targeting the oncogenic network signaling of KRAS or the extracellular matrix, as well as immune therapies