mismatch repair deficiency mmrd in glioma patients pts frequency and correlation with clinical histological and molecular characteristics

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Anaplastic astrocytoma (AA) and glioblastoma (GBM): a real-life experience in Padua Neuro-Oncology Center

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Mismatch-repair protein expression in high-grade gliomas: A large retrospective multicenter study

Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). Materials and Methods: We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein. Results: We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders. Conclusions: MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients

Characterization of seed proanthocyanidins of thirty-two red and white hybrid grape varieties

Grape seed extracts are known for their beneficial effects on health and on cardiovascular diseases due to antioxidant activity and the free radical-scavenging properties of proanthocyanidins (PAs). Moreover, grape seed tannins are used in oenology as additives to improve the organoleptic characteristics of wines, and for the clarification of must and wines. PAs in seed extract of 32 hybrid and three V. vinifera grape varieties were characterized by MALDI-TOF mass spectrometry. Signals of 148 compounds were identified as [M+H]+, [M+Na]+ and [M+K]+ adducts of B-type and A-type PAs formed from catechin/epicatechin subunits up to undecamers and with galloylation degree 0-7. The number-average molecular weight (Mn) of the samples, a parameter correlated with the molecular weight of polymers, and the polyphenolic content of extract, were also determined. Profiles of the hybrid grape varieties were compared with those of three V. vinifera samples studied as references. 'Terzi 108-6' showed high content of antioxidant polyphenols and 'Seyve Villard 12-390' higher content of higher oligomers. These two grape varieties are therefore potentially very interesting as sources of antioxidants and tannins for nutraceutical and oenological uses

A morfologia dos vasos Jê na produção de cauim de milho em Vereda III: uma proposição

An archaeobotanical analysis focused on starch granules extracted from ceramic vessels and a lithic artifact exhumed in Vereda III, MG revealed the widespread presence of corn (Zea mays sp). A previous study of the artifacts detected typical marks of fermentation in some vessels, thus, raised the possibility that more vessels have been used in the production of corn cauim (a fermented alcoholic beverage). The aim of the current research was to understand the production of this drink/food in its multiple possibilities through historical accounts, ethnographies, technological information and tests with fermentation. The taphonomical effects of the various stages of the process on the corn starch granules were investigated in literature and through tests. Here a proposition is made about the morphology of Je vessels used in the preparation of corn cauim, thought from the intersection of two types of evidence: the study of microtrace contained in archaeological artifacts and the trademarks in the vessels.A análise arqueobotânica focada em grânulos de amido extraídos de vasos cerâmicos e um artefato lítico exumados em Vereda III, MG revelou a presença generalizada do milho (Zea mays sp). Um estudo prévio realizado com os artefatos havia detectado marcas de uso típicas da fermentação em alguns vasos, assim, levantou-se a possibilidade de que mais vasos teriam sido utilizados na produção de cauim de milho. Tratou-se de compreender a produção dessa bebida/alimento nas suas múltiplas possibilidades através de relatos históricos, etnografias, informações tecnológicas e testes com fermentação. Os efeitos tafonômicos das distintas etapas do processo sobre os grânulos de amido de milho foram pesquisados em literatura e através de testes. Faz-se aqui uma proposição quanto à morfologia dos vasos Jê utilizados na elaboração do cauim de milho, pensada a partir do cruzamento de 2 tipos de evidências: o estudo dos microvestígios contidos nos artefatos arqueológicos e as marcas de uso nos vasos.&nbsp

‘Verdello’, ‘Verdicchio’ and ‘Verduschia’: an example of integrated multidisciplinary study to clarify grapevine cultivar identity

‘Verdello’, ‘Verdicchio’ and ‘Verduschia’ are registered in the official Italian Catalogue as three distinct grapevine varieties. Twenty-five accessions of these cultivars, encompassing known or presumed synonyms, coming from CRA repositories and from vineyards where they are traditionally cultivated, have been genotyped with eleven SSR markers. For morphological comparison, one accession for each variety has been described with 57 characters of OIV 2009 list; phenological and yield traits have also been recorded. In addition, the phenotypic comparison has been extended to the literature descriptions. The same DNA profile has been obtained for all 25 accessions; moreover, present and historical ampelographic data showed a very high similarity. All this information leads to the conclusion that these three varieties are, in fact, the same cultivar

Sustainability of grape-ethanol energy chain

The aim of this work is to evaluate the sustainability, in terms of greenhouse gases emission saving, of a new potential bio-ethanol production chain in comparison with the most common ones. The innovation consists of producing bio-ethanol from different types of no-food grapes, while usually bio-ethanol is obtained from matrices taken away from crop for food destination: sugar cane, corn, wheat, sugar beet. In the past, breeding programs were conducted with the aim of improving grapevine characteristics, a large number of hybrid vine varieties were produced and are nowadays present in the Viticulture Research Centre (CRA-VIT) Germplasm Collection. Some of them are potentially interesting for bio-energy production because of their high production of sugar, good resistance to diseases, and ability to grow in marginal lands. Life cycle assessment (LCA) of grape ethanol energy chain was performed following two different methods: i) using the spreadsheet BioGrace, developed within the Intelligent Energy Europe program to support and to ease the Renewable Energy Directive 2009/28/EC implementation; ii) using a dedicated LCA software. Emissions were expressed in CO2 equivalent (CO2eq). These two tools gave very similar results. The overall emissions impact of ethanol production from grapes on average is about 33 g CO2eq MJ–1 of ethanol if prunings are used for steam production and 53 g CO2eq MJ–1 of ethanol if methane is used. The comparison with other bio-energy chains points out that the production of ethanol using grapes represents an intermediate situation in terms of general emissions among the different production chains. The results showed that the sustainability limits provided by the normative are respected to this day. On the contrary, from 2017 this production will be sustainable only if the transformation processes will be performed using renewable sources of energy

PO-338 Recurrent glioblastoma: a complex scenario dominated by loss of MMR proteins

Introduction Glioblastoma (GBM) is the most common primary brain tumour in adults and the Stupp protocol represents the standard of care. However, the tumour invariably relapses suggesting marked intra-tumour genetic heterogeneity enabling rapid adaptation to therapy. In-depth characterisation of recurrent GBM (rGBM) might contribute to better understand mechanisms behind tumour progression and enable rGBM treatment with targeted drugs. Material and methods Matched GBM samples have been collected at diagnosis and recurrence from adult patients (n=57) treated with the Stupp protocol. Expression of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6) was evaluated by IHC, followed by exome sequencing of 3 pairs showing loss of MSH6 reactivity as well as of 3 MSH6 positive pairs. In addition, established genetic and epigenetic markers of GBM were investigated along with their correlation with loss of MMR proteins and patients' survival. Results and discussions According to IHC results, 13 out of 52 rGBM samples (25%) lacked expression of MMR proteins. In particular, 11 among the 13 samples (85%) showed partial or total reduction of MSH6 expression. Conversely, almost all GBM samples at diagnosis (96.4%) stained positive for the 4 MMR markers. Consistent with IHC data, exome sequencing disclosed lack of variants in MMR genes in primary samples whereas rGBM samples lacking MSH6 expression were mutated in the abovementioned genes and shared a c.3438+1G>A* splicing variant in MSH6 with a potential loss of function effect. Moreover, MSH6 negative relapsed specimens were characterised by 30 to 100-fold more variants compared to the matched primary ones and lacked microsatellite instability. Notably, MMR deficiency was associated with significant telomere shortening. Conversely, the tumour pairs expressing MMR proteins showed an almost comparable number of mutations in primary versus relapsed samples and absence of variants in MMR genes both in the initial tumours and in their recurrent counterpart. Conclusion Our study shows that IHC staining is a valuable tool to identify a subset of rGBM patients with alterations in MMR genes linked to high mutational burden and, hence, potentially eligible for drugs targeting immune checkpoint inhibitors