University of Turin

About: University of Turin is a education organization based out in Turin, Piemonte, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29607 authors who have published 77952 publications receiving 2480900 citations. The organization is also known as: Universita degli Studi di Torino & Università degli Studi di Torino.

Relative validity and reproducibility of a food frequency dietary questionnaire for use in the Italian EPIC centres.

Abstract: A pilot questionnaire was developed for the EPIC centres of northern Italy, and validated in the feasibility part of the cohort project. The questionnaire was self-administered and of the food frequency type with portion size estimated by means of pictures. It was structured by courses within a meal characteristic of Italian dietary habits. Dietary intake estimated by the questionnaire was compared to the corresponding estimates obtained from 8-14 24-hour recall interviews administered over a 1-year period. The reference method was validated by means of urinary nitrogen in 4-6 repeated 24-hour urine collections. One hundred and ninety-seven volunteers (47 men and 150 women) were enrolled and completed the study lasting 1 year. They filled out two questionnaires at the beginning and at the end of the study, and had a 24-hour recall interview once a month. Twenty-four-hour urine samples were collected at regular intervals. Usual intake of energy, the major nutrients and some vitamins were estimated for the questionnaires and the reference method by means of food composition tables compiled for this study. The agreement between the questionnaire and the 24-hour recalls was only good for alcohol consumption: Pearson's correlation was 0.73 and 0.77 in men and women respectively. Otherwise the relative validity of the questionnaire ranged between 0.28 for fat to 0.52 for carbohydrates in men and 0.25 and 0.50 in women for the same nutrients. The validity of the two interview methods in estimating protein intake, compared to mean urinary nitrogen was 0.24 (M) and 0.18 (W) for the questionnaire and 0.63 (M) and 0.48 (W) for 24-hour recalls. The main causes of low performance of the questionnaire were identified to be the estimated intake of dressing and cooking fats, vegetables and meat. Remedies were devised and introduced in the final version of the questionnaire currently in use in the EPIC project.

Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders

Abstract: The European Myeloma Network (EMN) organized two flow cytometry workshops. The first aimed to identify specific indications for flow cytometry in patients with monoclonal gammopathies, and consensus technical approaches through a questionnaire-based review of current practice in participating laboratories. The second aimed to resolve outstanding technical issues and develop a consensus approach to analysis of plasma cells. The primary clinical applications identified were: differential diagnosis of neoplastic plasma cell disorders from reactive plasmacytosis; identifying risk of progression in patients with MGUS and detecting minimal residual disease. A range of technical recommendations were identified, including: 1) CD38, CD138 and CD45 should all be included in at least one tube for plasma cell identification and enumeration. The primary gate should be based on CD38 vs. CD138 expression; 2) after treatment, clonality assessment is only likely to be informative when combined with immunophenotype to detect abnormal cells. Flow cytometry is suitable for demonstrating a stringent complete remission; 3) for detection of abnormal plasma cells, a minimal panel should include CD19 and CD56. A preferred panel would also include CD20, CD117, CD28 and CD27; 4) discrepancies between the percentage of plasma cells detected by flow cytometry and morphology are primarily related to sample quality and it is, therefore, important to determine that marrow elements are present in follow-up samples, particularly normal plasma cells in MRD negative cases.

Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth

Abstract: Molecular alterations in genes involved in DNA mismatch repair (MMR) promote cancer initiation and foster tumour progression. Cancers deficient in MMR frequently show favourable prognosis and indolent progression. The functional basis of the clinical outcome of patients with tumours that are deficient in MMR is not clear. Here we genetically inactivate MutL homologue 1 (MLH1) in colorectal, breast and pancreatic mouse cancer cells. The growth of MMR-deficient cells was comparable to their proficient counterparts in vitro and on transplantation in immunocompromised mice. By contrast, MMR-deficient cancer cells grew poorly when transplanted in syngeneic mice. The inactivation of MMR increased the mutational burden and led to dynamic mutational profiles, which resulted in the persistent renewal of neoantigens in vitro and in vivo, whereas MMR-proficient cells exhibited stable mutational load and neoantigen profiles over time. Immune surveillance improved when cancer cells, in which MLH1 had been inactivated, accumulated neoantigens for several generations. When restricted to a clonal population, the dynamic generation of neoantigens driven by MMR further increased immune surveillance. Inactivation of MMR, driven by acquired resistance to the clinical agent temozolomide, increased mutational load, promoted continuous renewal of neoantigens in human colorectal cancers and triggered immune surveillance in mouse models. These results suggest that targeting DNA repair processes can increase the burden of neoantigens in tumour cells; this has the potential to be exploited in therapeutic approaches.

Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression.

Abstract: Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.