A phase 1 study of mTORC1/2 inhibitor BI 860585 as a single agent or with exemestane or paclitaxel in patients with advanced solid tumors

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5-300 mg/day; Arm A), BI 860585 (40-220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80-220 mg/day; Arm C) with 60-80 mg/m(2)/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD. Forty-one, 25, and 24 patients were treated (Arms A, B, and C). DLTs were observed in four (rash (n= 2), elevated alanine aminotransferase/aspartate aminotransferase, diarrhea), four (rash (n= 3), stomatitis, and increased gamma-glutamyl transferase), and two (diarrhea, increased blood creatine phosphokinase) patients in cycle 1. The BI 860585 MTD was 220 mg/day (Arm A) and 160 mg/day (Arms B and C). Nine patients achieved an objective response (Arm B: Four partial responses (PRs); Arm C: Four PRs; one complete response). The disease control rate was 20%, 28%, and 58% (Arms A, B, and C). The most frequent treatment-related adverse events (AEs) were hyperglycemia (54%) and diarrhea (39%) (Arm A); diarrhea (40%) and stomatitis (40%) (Arm B); fatigue (58%) and diarrhea (58%) (Arm C). The MTD was determined in all arms. Antitumor activity was observed with BI 860585 monotherapy and in combination with exemestane or paclitaxel

IAU Office of Astronomy for Education, OAE Center Italy - Annual Report 2022

Annual report 2023 of the the IAU OAE Center Italy, an international office addressed to education and hosted and financed by Inaf. OAE Center Italy was established on the 3rd of March 2021, thanks to a Memorandum of Understanding signed by three parties: IAU, the Office of Astronomy for Education and INAF. OAE Center Italy is a joint project of a consortium of Italian partners, led and represented by INAF and of the IAU OAE, and is operated by INAF. The Italian partners are INAF, the Italian Astronomical Society (SAIt) and the University of Rome Tor Vergata (ToV). Index of contents 1. Professionalize astronomy education 11 1.1 The 4th Shaw-IAU workshop of Astronomy for Education 12 1.2 “Officina degli Errori” Pilot Programme 14 1.3 Educational path for transversal skills and professional orientation through Game-Based Learning 16 2. Provide access to good resources 18 2.1 astroEDU 19 2.2 Shared astronomical Glossary 21 2.3 Astrophotography contest 23 3. Promote astronomy in curricula 24 3.1 MIRTO - Mediterranean Informal Round Table – online 25 3.2 STEAM-MED - Lampedusa workshop on Astronomy Education 2022 27 3.3 Teacher Training Pilot Program (TTPP) 35 3.4 Organisation and delivery of the 16 hour-course for PhD students "Designing innovative public-engagement activities", at the University of Padova. 36 3.5 Castellaro Lagusello Astronomy Festival 37 4. OAE Networking 38 4.1 Participation in Expo 2020, Dubai, Italian Pavilion 39 4.2 Under the same Moon: building bridges through sky and astronomy 40 5. Spread the news 41 5.1 Under the same sky: an exhibition in Rome 42 5.2 Il Cielo itinerante – Italy shines 42 5.3 Universe World / EduINAF column 43 5.4 Time machines, an astronomy exhibition 43 5.5 Workshops 43 5.6 Press release, announcements and new

Apple Polyphenol Diet Extends Lifespan, Slows down Mitotic Rate and Reduces Morphometric Parameters in Drosophila Melanogaster: A Comparison between Three Different Apple Cultivars

Plant-derived polyphenols exhibit beneficial effects on physiological and pathological processes, including cancer and neurodegenerative disorders, mainly because of their antioxidant activity. Apples are highly enriched in these compounds, mainly in their peel. The Tuscia Red (TR) apple variety exhibits the peculiar characteristic of depositing high quantities of polyphenols in the pulp, the edible part of the fruit. Since polyphenols, as any natural product, cannot be considered a panacea per se, in this paper, we propose to assess the biological effects of TR flesh extracts, in comparison with two commercial varieties, in a model system, the insect Drosophila melanogaster, largely recognized as a reliable system to test the in vivo effects of natural and synthetic compounds. We performed a comparative, qualitative and quantitative analysis of the polyphenol compositions of the three cultivars and found that TR flesh shows the highest content of polyphenols, and markedly, anthocyanins. Then, we focused on their effects on a panel of physiological, morphometrical, cellular and behavioral phenotypes in wild-type D. melanogaster. We found that all the apple polyphenol extracts showed dose-dependent effects on most of the phenotypes we considered. Remarkably, all the varieties induced a strong relenting of the cell division rate

Analysis of SF3B1 mutations in monoclonal B-cell lymphocytosis

[No abstract available

Saliva is a reliable and practical source of germline DNA for genome-wide studies in chronic lymphocytic leukemia

High-throughput genomics requires tumor DNA matched to germline DNA, that cannot be easily obtained in the context of leukemia. Using chronic lymphocytic leukemia as a model, saliva DNA was frequently devoid of tumor DNA also during overt disease, and passed quality controls for SNP-array (77/102, 75.4%) and next generation sequencing (71/102, 69.6%). Compared to saliva, urine provides germline DNA of similar quality but in lower amounts. Saliva DNA was successfully run on SNP 6.0 arrays, and passed quality control call rate thresholds. On these bases, saliva represents a useful source of germline DNA for high-throughput genomic studies of hematologic neoplasia. (C) 2011 Elsevier Ltd. All rights reserved

A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer

Abstract Background This phase Ib study (NCT00960960) evaluated pictilisib (GDC-0941; pan-phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without bevacizumab or trastuzumab, or in combination with letrozole, in patients with locally recurrent or metastatic breast cancer. Methods This was a three-part multischedule study. Patients in parts 1 and 2, which comprised 3 + 3 dose escalation and cohort expansion stages, received pictilisib (60–330 mg) plus paclitaxel (90 mg/m2) with and without bevacizumab (10 mg/kg) or trastuzumab (2–4 mg/kg). In part 3, patients received pictilisib (260 mg) plus letrozole (2.5 mg). Primary objectives were evaluation of safety and tolerability, identification of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of pictilisib, and recommendation of a phase II dosing regimen. Secondary endpoints included pharmacokinetics and preliminary antitumor activity. Results Sixty-nine patients were enrolled; all experienced at least one adverse event (AE). Grade ≥ 3 AEs, serious AEs, and AEs leading to death were reported in 50 (72.5%), 21 (30.4%), and 2 (2.9%) patients, respectively. Six (8.7%) patients reported a DLT, and the MTD and recommended phase II pictilisib doses were established where possible. There was no pictilisib–paclitaxel drug–drug interaction. Two (3.4%) patients experienced complete responses, and 17 (29.3%) patients had partial responses. Conclusions Combining pictilisib with paclitaxel, with and without bevacizumab or trastuzumab, or letrozole, had a manageable safety profile in patients with locally recurrent or metastatic breast cancer. The combination had antitumor activity, and the additive effect of pictilisib supported further investigation in a randomized study. Trial registration ClinicalTrials.gov, NCT00960960. Registered on August 13, 2009

A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer

BACKGROUND: This phase Ib study (NCT00960960) evaluated pictilisib (GDC-0941; pan-phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without bevacizumab or trastuzumab, or in combination with letrozole, in patients with locally recurrent or metastatic breast cancer. METHODS: This was a three-part multischedule study. Patients in parts 1 and 2, which comprised 3 + 3 dose escalation and cohort expansion stages, received pictilisib (60-330 mg) plus paclitaxel (90 mg/m2) with and without bevacizumab (10 mg/kg) or trastuzumab (2-4 mg/kg). In part 3, patients received pictilisib (260 mg) plus letrozole (2.5 mg). Primary objectives were evaluation of safety and tolerability, identification of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of pictilisib, and recommendation of a phase II dosing regimen. Secondary endpoints included pharmacokinetics and preliminary antitumor activity. RESULTS: Sixty-nine patients were enrolled; all experienced at least one adverse event (AE). Grade ≥ 3 AEs, serious AEs, and AEs leading to death were reported in 50 (72.5%), 21 (30.4%), and 2 (2.9%) patients, respectively. Six (8.7%) patients reported a DLT, and the MTD and recommended phase II pictilisib doses were established where possible. There was no pictilisib-paclitaxel drug-drug interaction. Two (3.4%) patients experienced complete responses, and 17 (29.3%) patients had partial responses. CONCLUSIONS: Combining pictilisib with paclitaxel, with and without bevacizumab or trastuzumab, or letrozole, had a manageable safety profile in patients with locally recurrent or metastatic breast cancer. The combination had antitumor activity, and the additive effect of pictilisib supported further investigation in a randomized study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00960960 . Registered on August 13, 2009.status: publishe