There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

Epithelial to mesenchymal transition (EMT) is essential for driving plasticity during development, but is an unintentional behaviour of cells during cancer progression. The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them. Disturbance of a controlled epithelial balance is triggered by altering several layers of regulation, including the transcriptional and translational machinery, expression of non-coding RNAs, alternative splicing and protein stability.

Regulatory networks defining EMT during cancer initiation and progression

/pdf/about-the-national-institute-for-health-and-care-excellence-4zmiguft2a.pdf

About the National Institute for Health and Care Excellence - NICE.

Restablecimiento de la actividad en los servicios de Digestivo. Recomendaciones de la SEPD, AEEH, GETECCU y AEG

Ante un paciente diagnosticado de cáncer colorrectal, ¿cuándo debemos sospechar la presencia de mutaciones en el gen MYH?

Background: Global hypomethylation of cytosines within CpG dinucleotides is one of the distinguishing features of the neoplastic cells in human cancers. More specifically, hypomethylation of evolutionarily conserved repetitive elements (Alu and LINE-1) is associated with increased chromosomal instability in colorectal cancer (CRC). Recent data indicates that transcription start sites of certain proto-oncogenes are located within these repeat elements, and increased hypomethylation of these regions may induce the expression of illegitimate oncogenic transcripts. Primary CRCs demonstrate frequent global Alu and LINE-1 hypomethylation; however, it is unclear whether hypomethylation of these repeat sequences may be associated with a metastatic phenotype Aim: This study was aimed to determine the role of increased hypomethylation of Alu and LINE-1 sequences in CRC metastasis development. Materials and Methods: We analyzed a panel of CRC cells with different metastatic potential, as well as tissues from 50 CRC patients with matched primary colon cancer and corresponding liver metastasis tissues. Alu and LINE-1 methylation levels were determined by quantitative bisulfite pyrosequencing. Results: Lower levels of Alu and LINE-1 methylation were observed in CRC cell lines that came from metastatic foci. When we analyzed Alu and LINE-1 methylation levels in clinical specimens, the levels of Alu methylation in liver metastatis were significantly lower compared to the matched primary CRC tissues (77.2%±8.3 and 80.9%±10.7, respectively; P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 95. doi:10.1158/1538-7445.AM2011-95

Abstract 95: Increased hypomethylation of LINE-1 and Alu in human colorectal cancer metastasis

Colorectal cancer develops as a result of stepwise accumulation of genetic and epigenetic alterations, which in turn, regulate the expression of various oncogenes and tumor suppressor genes. Epigenetic alterations include DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. Data gathered in recent years clearly highlight that in contrast to genetic alterations, epigenetic alterations occur far more frequently, participate in virtually every step of colorectal cancer development, and are potentially reversible. More importantly, considering the ubiquitous nature of epigenetic alterations in human cancers, these molecular signatures have garnered significant attention for development as potential diagnostic, prognostic and predictive biomarkers in human colorectal cancer. This article reviews the current state of literature in the field, and focuses on the clinical relevance of various epigenetic alterations as potential biomarkers for the personalized treatment of patients suffering from this common malignancy worldwide.

The Epigenetics in Intestinal Tumorigenesis

https://onlinelibrary.wiley.com/doi/pdf/10.1177/2050640620901963

Deciphering the increasing incidence, special characteristics and possible aetiology of early onset colorectal cancer: A European perspective within an international effort.

Francesc Balaguer

Papers

Restablecimiento de la actividad en los servicios de Digestivo. Recomendaciones de la SEPD, AEEH, GETECCU y AEG

Ante un paciente diagnosticado de cáncer colorrectal, ¿cuándo debemos sospechar la presencia de mutaciones en el gen MYH?

Abstract 95: Increased hypomethylation of LINE-1 and Alu in human colorectal cancer metastasis

The Epigenetics in Intestinal Tumorigenesis

Deciphering the increasing incidence, special characteristics and possible aetiology of early onset colorectal cancer: A European perspective within an international effort.