Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells

Sirtuin 6 (SIRT6) is a member of the NAD+-dependent class III deacetylase sirtuin family, which plays a key role in cancer by controlling transcription, genome stability, telomere integrity, DNA repair, and autophagy. Here we analyzed the molecular and biological effects of UBCS039, the first synthetic SIRT6 activator. Our data demonstrated that UBCS039 induced a time-dependent activation of autophagy in several human tumor cell lines, as evaluated by increased content of the lipidated form of LC3B by western blot and of autophagosomal puncta by microscopy analysis of GFP-LC3. UBCS039-mediated activation of autophagy was strictly dependent on SIRT6 deacetylating activity since the catalytic mutant H133Y failed to activate autophagy. At the molecular level, SIRT6-mediated autophagy was triggered by an increase of ROS levels, which, in turn, resulted in the activation of the AMPK-ULK1-mTOR signaling pathway. Interestingly, antioxidants were able to completely counteract UBCS039-induced autophagy, suggesting that ROS burst had a key role in upstream events leading to autophagy commitment. Finally, sustained activation of SIRT6 resulted in autophagy-related cell death, a process that was markedly attenuated using either a pan caspases inhibitor (zVAD-fmk) or an autophagy inhibitor (CQ). Overall, our results identified UBCS039 as an efficient SIRT6 activator, thereby providing a proof of principle that modulation of the enzyme can influence therapeutic strategy by enhancing autophagy-dependent cell death

New textile finds from Tomba dell\u2019aryballos sospeso, Tarquinia: Context, analysis and preliminary interpretation

An intact chamber tomb dated between the end of the Orientalising and early Archaic periods (terminus ante quem 630-620 BC) was discovered in 2013 in the Doganaccia necropolis of the Etruscan city of Tarquinia. Tomb 6423, nicknamed Tomba dell\u2019Aryballos sospeso, contained an inhumation of a female, as well as a cremation of a male, both accompanied by sumptuous burial gifts. Remains of several different fabrics were found inside two bronze objects associated with the inhumation, the pyxis and the basin. The bronze sheet pyxis contained both organic and mineralised fragments of threads and textiles of greenish and purplish colour, while among the organic contents of the bronze basin some open tabby fabric fragments were found. The paper presents the results of textile, fibre and dye analyses of these important new finds, and offers some preliminary thoughts regarding their possible function and significance

NEW TEXTILE FINDS FROM TOMBA DELL'ARYBALLOS SOSPESO, TARQUINIA: CONTEXT, ANALYSIS AND PRELIMINARY INTERPRETATION

An intact chamber tomb dated between the end of the Orientalising and early Archaic periods was discovered in 2013 in the Doganaccia necropolis of the Etruscan city of Tarquinia. Tomb 6423, nicknamed Tomba dell’Aryballos sospeso, contained an inhumation of a female, as well as a cremation of a male, both accompanied by sumptuous burial gifts. Exceptionally preserved remains of several different fabrics were found inside two bronze objects associated with the inhumation, the pyxis and the basin. The bronze sheet pyxis contained both organic and mineralised fragments of threads and textiles of greenish and purplish colour, while among the organic contents of the bronze basin some open tabby fabric fragments were found. The paper presents the results of textile, fibre and dye analyses of these important new finds, and offers some preliminary thoughts regarding their possible function and significance

Ricognizioni territoriali nella Conca Velina

Nel contributo sono illustrati i risultati della prima campagna di ricognizioni territoriali nell'ambito del Progetto "Conca Reatina" (Carta archeologica della Provincia di Rieti

Clinical nutrition in surgical oncology: Young AIOM-AIRO-SICO multidisciplinary national survey on behalf of NutriOnc research group

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice