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The “unnatural” history of colorectal cancer in Lynch syndrome : lessons from colonoscopy surveillance

2021

Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alon…

Epidemiological, clinical and molecular characterization of Lynch‐like syndrome: A population‐based study

2019

Colorectal carcinomas that are mismatch repair (MMR)‐deficient in the absence of MLH1 promoter methylation or germline mutations represent Lynch‐like syndrome (LLS). Double somatic events inactivating MMR genes are involved in the etiology of LLS tumors. Our purpose was to define the clinical and broader molecular hallmarks of LLS tumors and the population incidence of LLS, which remain poorly characterized. We investigated 762 consecutive colorectal carcinomas operated in Central Finland in 2000–2010. LLS cases were identified by a stepwise protocol based on MMR protein expression, MLH1 methylation and MMR gene mutation status. LLS tumors were profiled for CpG Island Methylator Phenotype (…

No evidence of EMAST in whole genome sequencing data from 248 colorectal cancers.

2021

Microsatellite instability (MSI) is caused by defective DNA mismatch repair (MMR), and manifests as accumulation of small insertions and deletions (indels) in short tandem repeats of the genome. Another form of repeat instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), has been suggested to occur in 50% to 60% of colorectal cancer (CRC), of which approximately one quarter are accounted for by MSI. Unlike for MSI, the criteria for defining EMAST is not consensual. EMAST CRCs have been suggested to form a distinct subset of CRCs that has been linked to a higher tumor stage, chronic inflammation, and poor prognosis. EMAST CRCs not exhibiting MSI have b…

Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer

2023

Abstract Background The CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint interaction may promote cancer progression, but the expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised. Methods We used a custom 9-plex immunohistochemistry assay to quantify the expression patterns of PD-L1 and PD-1 in macrophages, T cells, and tumour cells in 910 colorectal cancer patients. We evaluated cancer-specific mortality according to immune cell subset densities using multivariable Cox regression models. Results Compared to PD-L1– macrophages, PD-L1+ macrophages were more likely M1-polarised than M2-polarised and located close…

KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer

2022

Background: KRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting. Methods: Patients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demog…

Genome-wide diversity of Pagliarola sheep residual population and its conservation implication

2021

Local breeds represent an underestimated resource in terms not only of their important cultural and economical role in marginal areas, but also because they often own a potential genetic pool well adapted to extreme conditions. This fact is of increasing interest, especially when considering climate global challenges where peculiar and uncommon traits could be advantageous. In this study, we genotyped 24 individuals belonging to the small residual Pagliarola sheep population using the OvineSNP50K array, in order to compare its genomic architecture with other 21 Italian local breeds. Moreover, we performed the fixation index (FST) outlier analysis to identify genes most differentiated betwee…

Más allá del voto

2007

Construction sequence analysis of long-span cable-stayed bridges

2018

Abstract In cantilever construction of long-span cable-stayed bridges the stressing sequence of stays is fundamental for establishing the final configuration of the bridge. The structural behaviour of these bridges is usually evaluated through a forward staged construction analysis, in which the values of the prestressing forces to be applied to stays are the main unknowns. A unified procedure for determining the initial cable forces and for analyzing the entire sequence is presented here, considering the geometric nonlinearity of stays through the Dischinger equivalent elastic modulus. The target is the simultaneous determination of the initial cable forces with the simulation of the const…

Los límites exteriores del capitalismo en la «crítica de la economía política» de Marx. Sobre la interpretación de César Ruiz Sanjuán de la articulac…

2019

The Outer Limits of Capitalism in Marx's «Critique of Political Economy». On César Ruiz Sanjuán's Interpretation of the Articulation of History and System in Marx.
 
 Resumen: Se ha publicado recientemente en castellano una investigación rigurosa y pionera acerca de la compleja articulación que mantienen la historia y la exposición del sistema capitalista en el proyecto de una «crítica de la economía política» de Marx. Este trabajo pretende exponer y discutir las aportaciones interpretativas abiertas por el libro deCésar Ruiz Sanjuán: Historia y sistema en Marx. Hacia una teoría crítica del capitalismo, publicado en 2019 en la editorial Siglo XXI España. Al final de nuestra exposi…

Caracciolo ed il superamento del piano funzionalista

2014

Viene esaminato il contributo di Edoardo Caracciolo al superamento del piano funzionalista di matrice razionalista, attraverso l'esame dei piani da lui redatti per Caltanissetta, Trapani e Marsala