Problematiche geoambientali del territorio veneziano

Venezia, la sua laguna ed il territorio circostante sono un patrimonio artistico, storico, culturale ed ambientale tra i più noti al mondo. Il fragile equilibrio, tipico delle lagune, è per Venezia particolarmente vulnerabile; essa infatti risulta modellata da un forte contributo antropico, iniziato secoli or sono con le note deviazioni fluviali, ed è oggi esposta ad azioni antropiche di particolare rilevanza, quali quelle derivanti dalla presenza della zona industriale di Marghera che s'affaccia proprio sulla laguna. Questo delicato equilibrio è legato al particolare assetto geologico-territoriale dell'area veneziana. In questa relazione, forzatamente molto schematica in quanto sintetizza decenni di studi ed indagini a livello sia scientifico che tecnico-applicativo, si vuole indicare l'insostituibile apporto della geologia anche in un'area urbana, quale quella Veneziana. Questo "complesso urbano" è composto da una serie di centri: insulari (centro storico, Murano, Burano, Torcello, ecc.), litorali (Lido, Chioggia, Jesolo), di terraferma ed industriali (Mestre, Scorzè, Marghera, Malcontenta, Fusina, ecc.). Altra caratteristica del complesso veneziano è l'interazione dei vari centri urbani che, malgrado la dislocazione geografica, interagiscono nelle varie problematiche geoambientali con strette relazioni causa-effetto. Questa nota, frutto della collaborazione tra Enti di Ricerca, Pubbliche Amministrazioni e Liberi Professionisti, evidenzia la necessità di lavorare in modo sinergico per affrontare al meglio le complesse tematiche geologico-ambientali che si riscontrano in questo tipo di studi

PO-502 A potential role for HSP90 in HER2-driven breast cancer (BC)

Introduction HER2 (amplified in 30% of BC) is involved in the activation of many pathways and its function is regulated by HSP90. Thus, HSP90 co-targeting is emerging as a potential molecular target for HER2-directed BC therapy. Material and methods We analysed HER2 and HSP90 expression in a panel of BC cell lines, including MCF7 cells stably transfected with a constitutively active HER2. HER2/HSP90 expression and growth inhibition were monitored over time upon exposure to trastuzumab (T) and docetaxel (D), in the presence or absence of HSP90 silencing. We also retrospectively evaluated a series of 24 locally advanced/operable BC patients (pts) who underwent neoadjuvant T+D for HSP90 expression and correlated it with pathological complete response (pCR). Results and discussions In the BC cell lines analysed there was no clear-cut correlation between HSP90 and HER2 expression. HER2 transfection into MCF7 cells increased HSP90 mRNA and protein expression; however, treatment with T further increased HSP90 levels. Conversely D increased HER2, but did not affect HSP90, expression. In HER2 +BC cell lines, simultaneous T+D combination resulted in synergistic growth inhibition in vitro , while their staggered combination, particularly T followed by D, did not afford synergistic effects. Effects of simultaneous and staggered treatments on HSP90 and HER2 expression were analysed by WB: HER2 expression decreased in the simultaneous and staggered combination (D followed by T), while HSP90 expression did not change upon combined treatment. The effects of HSP90 silencing and overexepression on functional response to T+D are being analysed in HER2 +BC models: preliminary results indicate that HSP90 silencing in HER2 +BC decreases the therapeutic synergism of the simultaneous T+D combination. Accordingly, in locally advanced/operable pts undergoing neoadjuvant T+D, pCR occurred more frequently in pts with a baseline HSP90 score of 3+, as compared to 2+and 1+ (50.0% vs. 14.3% vs. none, p=0.05). These results suggest the possibility to classify HER2-positive pts into HSP90 defined subgroups and elaborate specific therapeutic strategies. Conclusion Preclinical data indicate that constitutive HER2 activation induces HSP90 expression and HSP90 modulation influences the functional response to combined treatment. Baseline HSP90 expression may potentially represent a pre-requisite of pharmacological response in HER2-addicted BC

Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis

In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC

preliminary results of principe predictors of resistance to immunotherapy with nivolumab niv study in advanced pretreated non small cell lung cancer apnsclc investigating the role of an immune genomic signature igs including jak2 jak3 pias4 ptpn2 stat3 ifnar2 alterations

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a propensity score analysis exploring the impact of the addition of adjuvant chemotherapy act to hormone therapy aht in a multi center series of resected luminal early stage pure invasive lobular breast carcinoma ilc

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Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade >= 3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure

Flood Protection in Venice under Conditions of Sea-Level Rise: An Analysis of Institutional and Technical Measures

It is widely acknowledged that in times of climate change loss of coastal resources and risk for human life can be minimized by implementing adaptation strategies. Such strategies need to encompass a balanced mix of non-structural (institutional) and structural (technical) measures based on sound scientific knowledge. This article discusses measures carried out to protect the city of Venice, Italy from flooding (locally known as “high water”), and reflects on their ability to anticipate a possible acceleration of sea-level rise as induced by climate change. It is based on scientific literature, legislative and policy documents of key institutions, reports and documents of organizations working on Venice issues, newspaper articles, and interviews. Our analysis shows that the synergic action of the hydraulic defense infrastructure under construction is in principle adequate to withstand a broad range of sea-level rise scenarios for the next 100 years. However, when the goal is to use these investments effectively major changes in the existing institutional arrangements will be required in the years to come. The Venice findings point out the difficulties and yet the importance of identifying and implementing both non-structural and structural measures to adapt to climate change

Real-world ANASTASE study of atezolizumab+nab-paclitaxel as first-line treatment of PD-L1-positive metastatic triple-negative breast cancer

The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, ‘real-world’ data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program. A retrospective analysis was conducted in 29 Italian oncology centers among patients who completed at least one cycle of treatment. Data from 52 patients were gathered. Among them, 21.1% presented de novo stage IV; 78.8% previously received (neo)adjuvant treatment; 55.8% patients had only one site of metastasis; median number of treatment cycles was five (IQR: 3–8); objective response rate was 42.3% (95% CI: 28.9–55.7%). The median time-to-treatment discontinuation was 5 months (95% CI: 2.8–7.1); clinical benefit at 12 months was 45.8%. The median duration of response was 12.7 months (95% CI: 4.1–21.4). At a median follow-up of 20 months, the median progression-free survival was 6.3 months (95% CI: 3.9–8.7) and the median time to next treatment or death was 8.1 months (95% CI: 5.5–10.7). At 12 months and 24 months, the overall survival rates were 66.3% and 49.1%, respectively. The most common immune-related adverse events included rash (23.1%), hepatitis (11.5%), thyroiditis (11.5%) and pneumonia (9.6%). Within the ANASTASE study, patients with PD-L1-positive mTNBC treated with first-line atezolizumab plus nab-paclitaxel achieved PFS and ORR similar to those reported in the IMpassion130 study, with no unexpected adverse events

Palbociclib plus fulvestrant or everolimus plus exemestane for pretreated advanced breast cancer with lobular histotype in er+/her2 12 patients: A propensity score-matched analysis of a multicenter retrospective patient series

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO\u2013FUL) with everolimus plus exemestane (EVE\u2013EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO\u2013FUL and 26 with EVE\u2013EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE\u2013EXE compared with PALBO\u2013FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35\u20130.96; p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE\u2013EXE compared to PALBO\u2013FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE\u2013EXE is more effective than PALBO\u2013FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence