The therapeutic potential of duloxetine in prostate cancer-related fatigue.

Cancer-related fatigue (CRF) is a common polysymptomatic syndrome with no standard therapy. The authors present the case of a prostate cancer patient in whom, during hormone therapy, disabling CRF and urinary incontinence occurred. CRF was assessed according to the brief fatigue inventory (BFI). The patient received duloxetine, 60 mg daily, due to its impact on both CRF and incontinence. After 2 months, the BFI score decreased (from 9 to 2) and urinary incontinence resolved. After duloxetine discontinuation, the patient maintained a low BFI score. The authors conclude that, as a serotonin-noradrenaline reuptake inhibitor, duloxetine could be active on prostate CRF, especially with associated urinary symptoms. Therefore, a pilot placebo-controlled trial with duloxetine to treat prostate CRF may be worthwhile

The role of docetaxel in the multimodal treatment of non-small cell lung cancer

We report the case of a 53-year-old woman with brain metastatic Non-Small Cell Lung Cancer (NSCLC). Diagnosis was made during brain surgery. Brain metastases were treated both with surgery and radiotherapy. The chemotherapy schedule was cisplatin 75 mg/m2 and docetaxel 75 mg/m2 1q21 for up to six cycles. Toxicities encountered were easily manageable. Subsequent thoracic radiotherapy improved tumor response and quality of life

Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma

Fulvestrant and trastuzumab in patients with luminal HER2-positive advanced breast cancer (ABC): an Italian real-world experience (HERMIONE 9)

Purpose The most appropriate therapy for HR+/HER2-positive (HER2+) advanced breast cancer (ABC) is a matter of debate. Co-targeting of both receptors represents an attractive strategy to overcome the cross-talk between them. Methods The HERMIONE 9 is an observational retrospective multicentric study which aimed to describe the clinical outcome of patients with HR+/HER2+ABC who received the combination of Fulvestrant (F) and Trastuzumab (T) as part of their routine treatment at 10 Italian Institutions. Results Eighty-seven patients were included. Median age was 63 (range, 35–87) years. The median number of previous treatments was 3 (range, 0–10) and F and T were administered as≥3rd line in 67 patients. Among the 86 evaluable patients, 6 (6.9%) achieved CR, 18 (20.7%) PR, and 44 (50.6%) had SD ≥24 weeks with an overall CBR of 78.2%. At a median follow-up of 33.6 months, mPFS of the entire cohort was 12.9 months (range, 2.47–128.67). No diference was observed in mPFS between patients treated after progression or as maintenance therapy (mPFS 12.9 and 13.9 months in 64 and 23 patients, respectively), neither considering the number of previous treatment lines (≤3 or<3). Conclusion The combination of F and T was active in this cohort at poor prognosis and deserves further investigations possibly in combination with pertuzumab in patients with high ER expression

Role of lung ultrasound for the etiological diagnosis of acute lower respiratory tract infection (ALRTI) in children: a prospective study

Objective and design: Our prospective study assesses the role of detailed lung ultrasound (LUS) features to discriminate the etiological diagnosis of acute lower respiratory tract infection (ALRTI) in children. Methodology: We analyzed patients aged from 1 month to 17 years admitted between March 2018 and April 2020 who were hospitalized for ALRTI. For all patients, history, clinical parameters, microbiological data, and lung ultrasound data were collected. Patients were stratified into three main groups ("bacterial", "viral", "atypical") according to the presumed microbial etiology and LUS findings evaluated according to the etiological group. Nasopharyngeal swabs were obtained from all patients. A qualitative diagnostic test developed by Nurex S.r.l. was used for identification of bacterial and fungal DNA in respiratory samples. The Seegene Allplex™ Respiratory assays were used for the molecular diagnosis of viral respiratory pathogens. In addition, bacterial culture of blood and respiratory samples were performed, when indicated. Results: A total of 186 children with suspected ALRTI (44% female) with an average age of 6 were enrolled in the study. We found that some ultrasound findings as size, number and distribution of consolidations, the position and motion of air bronchograms, pleural effusions and distribution of vertical artifacts significantly differ (p < 0.05) in children with bacterial, viral and atypical ALRTI. Conclusion: Our study provides a detailed analysis of LUS features able to predict the ALRTI ethology in children. These findings may help the physicians to better manage a child with ALRTI and to offer personalized approach, from diagnosis to treatment and follow-up

Postoperative treatment of intermediate-risk early stage cervical cancer: results of a survey from the Gynecology Study Group in the AIRO Gyn and MITO Groups

This survey investigated prognostic factors, treatment modalities, references followed and radiation oncologists' opinions to prescribe adjuvant therapy in early intermediate-risk cervical cancer. All but one recommended pelvic radiotherapy ± vaginal boost (45%) with or without chemotherapy (20%). 88% believed other prognostic factors could integrate classic risk criteria. 66% considered chemo-radiation indicated in case of lymphovascular invasion and suboptimal node dissection, high grade, size ≥ 4cm, non squamous histology and risk factors combination. This wide heterogeneity of treatments reflects the different guideline options due to the lack of defined indications. The need of integrating the classic prognostic factors with others factors was unanimously expressed by radiation oncologists. The best local and systemic therapy should be established through new studies. These results highlighted the need of a position paper to standardize adjuvant treatment in Italy and to design collaborative studies to clarify the controversial aspects

Immunosuppression by monocytic myeloid-derived suppressor cells in patients with pancreatic ductal carcinoma is orchestrated by STAT3

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with an overall 5-year survival rate of less than 8%. New evidence indicates that PDAC cells release pro-inflammatory metabolites that induce a marked alteration of normal hematopoiesis, favoring the expansion and accumulation of myeloid-derived suppressor cells (MDSCs). We report here that PDAC patients show increased levels of both circulating and tumor-infiltrating MDSC-like cells. Methods: The frequency of MDSC subsets in the peripheral blood was determined by flow cytometry in three independent cohorts of PDAC patients (total analyzed patients, n = 117). Frequency of circulating MDSCs was correlated with overall survival of PDAC patients. We also analyzed the frequency of tumor-infiltrating MDSC and the immune landscape in fresh biopsies. Purified myeloid cell subsets were tested in vitro for their T-cell suppressive capacity. Results: Correlation with clinical data revealed that MDSC frequency was significantly associated with a shorter patients' overall survival and metastatic disease. However, the immunosuppressive activity of purified MDSCs was detectable only in some patients and mainly limited to the monocytic subset. A transcriptome analysis of the immunosuppressive M-MDSCs highlighted a distinct gene signature in which STAT3 was crucial for monocyte re-programming. Suppressive M-MDSCs can be characterized as circulating STAT3/arginase1-expressing CD14+ cells. Conclusion: MDSC analysis aids in defining the immune landscape of PDAC patients for a more appropriate diagnosis, stratification and treatment

Induction of immunosuppressive functions and NF-\u3baB by FLIP in monocytes

Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Enforced expression of c-FLIP or viral FLIP rescues monocytes from cytotoxicity and concurrently induces potent immunosuppressive activity, in T cell cultures and in vivo models of tumor progression and immunotherapy. FLIP-transduced human blood monocytes can suppress graft versus host disease. Neither expression of FLIP in granulocytes nor expression of other anti-apoptotic genes in monocytes conferred immunosuppression, suggesting that FLIP effects on immunosuppression are specific to monocytic lineage and distinct from death inhibition. Mechanistically, FLIP controls a broad transcriptional program, partially by NF-\u3baB activation. Therefore, modulation of FLIP in monocytes offers a means to elicit or block immunosuppressive myeloid cells

Axon guidance cue SEMA3A promotes the aggressive phenotype of basal-like PDAC

Objective: The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression. Design: We integrated bulk and single-cell transcriptomic datasets of human PDAC with in situ hybridisation analyses of patients’ tissues to evaluate SEMA3A expression in molecular subtypes of PDAC. Gain and loss of function experiments in PDAC cell lines and organoids were performed to dissect how SEMA3A contributes to define a biologically aggressive phenotype. Results: In PDAC tissues, SEMA3A is expressed by stromal elements and selectively enriched in basal-like/squamous epithelial cells. Accordingly, expression of SEMA3A in PDAC cells is induced by both cell-intrinsic and cell-extrinsic determinants of the basal-like phenotype. In vitro, SEMA3A promotes cell migration as well as anoikis resistance. At the molecular level, these phenotypes are associated with increased focal adhesion kinase signalling through canonical SEMA3A-NRP1 axis. SEMA3A provides mouse PDAC cells with greater metastatic competence and favours intratumoural infiltration of tumour-associated macrophages and reduced density of T cells. Mechanistically, SEMA3A functions as chemoattractant for macrophages and skews their polarisation towards an M2-like phenotype. In SEMA3Ahigh tumours, depletion of macrophages results in greater intratumour infiltration by CD8+T cells and better control of the disease from antitumour treatment. Conclusions: Here, we show that SEMA3A is a stress-sensitive locus that promotes the malignant phenotype of basal-like PDAC through both cell-intrinsic and cell-extrinsic mechanisms

An overview of the Italian forest biodiversity and its conservation level, based on the first outcomes of the 4th Habitat Report ex-Art. 17

In 2019 the 4th Report ex-Art. 17 on the conservation status (CS) of Annex I Habitats of the 92/43/EEC Directive was expected by every EU/28 country, with reference to the period 2013-18. In Italy, the process was in charge to the Italian Institute for Environmental Protection and Research (ISPRA), on behalf of the Ministry for Environment, Land and Sea Protection (MATTM), with the scientific support of the Italian Botanical Society (SBI). A large group of thematic and territorial experts elaborated the available data concerning the 124 types of terrestrial and inland water Habitats present in Italy, 39 of which are represented by Forest Habitats (Group 9),. The main aim of the work was the evaluation of the overall CS of each Habitat by Biogeographic Region (Mediterranean, Continental and Alpine), for a total amount of 294 assessments. A high proportion of these (92, corresponding to 31% of the total) referred to Forest Habitats, including 20 marginal types for which the CS was not requested. The analysis was carried out at different scales: a) administrative territory, through the data contained in the ISPRA database, whose compilation was in charge to the Regions and Autonomous Provinces; b) Natura 2000 site, with the latest updates available (Standard Data Forms updated to 2018); c) national scale, implementing the distribution maps for each Habitat based on the European grid ETRS89-LAEA5210 (10x10 km2 mesh); d) Biogeographic Region, scale of the final assessment. Cartographic outcomes, associated databases and additional data used for the assessments will be available online on the ISPRA Portal as soon as the validation process by the European Commission will be completed. A dedicated archive named "HAB_IT" has been created in the national database "VegItaly" (1), managed by the Italian Society of Vegetation Science, where the phytosociological relevés representative of the various Annex I Habitats in Italy will be archived and freely accessible. An overview of the results regarding the Forest habitats is here provided, including a comparison with the outcomes of the former reporting cycle, the 3rd Report ex-Art. 17 (2). In several cases (e.g. 9120, 91L0), the distribution maps have been remarkably improved due to better knowledge and more fitful interpretation. The conservation status resulted as Favourable (FV) for 6,7%, Inadequate (U1) for 58,7% and Bad (U1) for 32,0% of the 72 assessed forest Habitat types. In no case there was an improvement of the conservation status, while in 6 cases a worsening of the conditions resulted from the data analysis, pointing out the Habitats types with a higher need of action. Similarly to other projects carried out as a team by the network of Annex I Habitat experts of the Italian Botanical Society and the Italian Society for Vegetation Science (e.g. 3, 4), this is another step in the direction of supporting the implementation of the 92/43/EEC "Habitat" Directive in Italy and Europe. On this ground, the high biodiversity of the Italian forest Habitats could be emphasized, however results pointed out that some rare or endemic types (e.g. Alnus cordata or Betula aetnensis-dominated forests) are still scarcely acknowledged by the most prominent EU conservation tools such as the Annex I to the "Habitat" Directive. 1) F. Landucci et al. (2012) Plant Biosyst., 146(4), 756-763 2) P. Genovesi et al. (2014) ISPRA, Serie Rapporti, 194/2014 3) E. Biondi et al. (2009) Società Botanica Italiana, MATTM, D.P.N., http://vnr.unipg.it/habitat/ 4) D. Gigante et al. (2016) Plant Sociology, 53(2), 77-8