Role of SIRT-3, p-mTOR and HIF-1\u3b1 in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin

The incidence of hepatocellular carcinoma deriving from metabolic dysfunctions has increased in the last years. Sirtuin- (SIRT-3), phospho-mammalian target of rapamycin (p-mTOR) and hypoxia-inducible factor- (HIF-1\u3b1) are involved in metabolism and cancer. However, their role in hepatocellular carcinoma (HCC) metabolism, drug resistance and progression remains unclear. This study aimed to better clarify the biological and clinical function of these markers in HCC patients, in relation to the presence of metabolic alterations, metformin therapy and clinical outcome. A total of 70 HCC patients were enrolled: 48 and 22 of whom were in early stage and advanced stage, respectively. The expression levels of the three markers were assessed by immunohistochemistry and summarized using descriptive statistics. SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients. Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Moreover, our results describe a slight, albeit not significant, benefit of high SIRT-3 and a significant benefit of high nuclear HIF-1\u3b1 expression in early-stage patients, whereas high levels of p-mTOR correlated with worse prognosis in advanced-stage patients. Our study highlighted the involvement of SIRT-3 and p-mTOR in metabolic dysfunctions that occur in HCC patients, and suggested SIRT-3 and HIF-1\u3b1 as predictors of prognosis in early-stage HCC patients, and p-mTOR as target for the treatment of advanced-stage HCC

The impact of the Hippo pathway and cell metabolism on pathological complete response in locally advanced Her2+ breast cancer: the TRISKELE multicenter prospective study

The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies

Role of gonadotropin-releasing hormone analogues in metastatic male breast cancer: Results from a pooled analysis

Background: Male breast cancer is a rare malignancy. Despite the lack of prospectively generated data from trials in either the adjuvant or metastatic setting, patients are commonly treated with hormone therapies. Much controversy exists over the use of gonadotropin-releasing hormone analogues in metastatic male breast cancer patients. We conducted this study to provide more concrete ground on the use of gonadotropin-releasing hormone analogues in this setting. Methods: We herein present results from a pooled analysis including 60 metastatic male breast cancer patients treated with either an aromatase inhibitor or cyproterone acetate as a monotherapy (23 patients) or combined with a gonadotropin-releasing hormone analogue (37 patients). Results: Overall response rate was 43.5 % in patients treated with monotherapy and 51.3 % with combination therapy (p = 0.6). Survival outcomes favored combination therapy in terms of median progression-free survival (11.6 months versus 6 months; p = 0.05), 1-year progression-free survival rate (43.2 % versus 21.7 %; p = 0.05), median overall survival (29.7 months versus 22 months; p = 0.05), and 2-year survival rate (64.9 % versus 43.5 %; p = 0.05). Conclusions: In metastatic male breast cancer patients, the combined use of gonadotropin-releasing hormone analogues and aromatase inhibitors or antiandrogens seems to be associated with greater efficacy, particularly in terms of survival outcomes, compared with monotherapy. Collectively, these results encourage considering these agents in the metastatic setting

Effects of soil warming and nitrogen foliar applications on bud burst of black spruce

Key message: In mature black spruce, bud burst process is anticipated by soil warming, while delayed by foliar applications of nitrogen; however, the effects depend on growth conditions at the site. Abstract: The observation of phenological events can be used as biological indicator of environmental changes, especially from the perspective of climate change. In boreal forests, the onset of the bud burst is a key factor in the length of the growing season. With current climate change, the major factors limiting the growth of boreal trees (i.e., temperature and nitrogen availability) are changing and studies on mature trees are limited. The aim of this study was to investigate the effects of soil warming and increased nitrogen (N) deposition on bud burst of mature black spruce [Picea mariana (Mill.) BSP]. From 2008 onwards, an experimental manipulation of these environmental growth conditions was conducted in two stands (BER and SIM) at different altitudes in the boreal forest of Quebec, Canada. An increase in soil temperature (H treatment) and a canopy application of artificial rain enriched with nitrogen (N treatment) were performed. Observations of bud phenology were made during May–July 2012 and 2013. In BER, H treatment caused an anticipation (estimated as 1–3 days); while N treatment, a delay (estimated as 1–2 days but only in 2012) in bud burst. No treatments effect was significant in SIM. It has been demonstrated that soil temperature and N availability can play an important role in affecting bud burst in black spruce but the effects of these environmental factors on growth are closely linked with site conditions

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: A real-world experience

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-na\uc3\uafve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-na\uc3\uafve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-na\uc3\uafve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p < 0.0001), while overall survival was positively affected by lower ECOG PS (p < 0.0001), absence of brain metastases (p 0.05), and clinical benefit (p < 0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order

Fedeltà ai quartieri di maschi di stambecco ( Capra ibex ) nella colonia della Marmolada

Monitoraggio di stambecco e analisi della fedeltà ai quartieri estiv

SCA.LE-UP Utilizzo innovativo degli scarti lignei

Il progetto SCA.LE-UP - Utilizzo innovativo degli scarti lignei, nasce per rispondere alla necessit\ue0 delle aziende della filiera legno di valorizzare direttamente i residui prodotti durante le fasi di lavorazione per la produzione di energia. L\u2019articolo descrive obiettivi, azioni e risultati preliminari del progetto

Influence of soil warming and N‐addition on sap flux density and stem radius variation in boreal stands in Quebec, Canada

Climate change is projected to intensify the global hydrological cycle and increase temperatures. Excess N deposition could limit plant productivity because of a lack of plant–soil system efficiency with reduced water availability. However, the effects of soil warming and N-addition on tree water transport and water use remain poorly understood. This study aimed to quantify the effects of soil warming and N-addition associated with meteorological variables on the sap flux density and stem radius variation in black spruce (Picea mariana [Mill.] B.S.P.). From 2008 to 2014, we conducted a long-term experiment on mature trees growing in two stands (Bernatchez [BER] and Simoncouche [SIM]) at different latitudes to evaluate the effect of soil warming (H) and N-addition. During 2014, we investigated soil and plant water status between May and August, sap flux density from July to August and stem radius variation over the whole year. At the colder, northern site (BER), we detected a significant increase in sap flux density with the H-treatment, whereas no effect was observed at the warmer, southern site (SIM). At BER, diurnal sap flux density in H × N-addition treatment showed a significant effect in the afternoon near the peak of day compared with the other treatments. We found no significant effects of independent single or combined factors on soil and plant water status and stem radius variation at either site. Under climate change, black spruce at more northern sites could have a better water use and storage for wood productivity than those at more southern sites