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

https://njc.rockefeller.edu/pdf4/Class2-LeeAmbros1993.pdf

The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14

The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications.

/pdf/the-cbio-cancer-genomics-portal-an-open-platform-for-4kclcxogdw.pdf

The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data

http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_TEL/Full-Text/25.pdf

The Hallmarks of Aging

We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

/pdf/comprehensive-molecular-portraits-of-human-breast-tumours-4t6h37c9ow.pdf

Comprehensive molecular portraits of human breast tumours

Experiments described herein in which the genetic dependency on ADCK2 is shown in endocrine receptor positive cancer. Accordingly, the use of ACDK2 inhibitors for treating individuals having estrogen receptor α (ER) positive cancers, such as ER positive breast cancer, ovarian cancer, prostate cancer or endometrial cancer, are disclosed.

MATERIALS AND METHODS FOR TREATING ESTROGEN RECEPTOR α (ER) POSITIVE CANCER

Reply to 'Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study".

L'invention concerne la reconnaissance du fait que l'inhibition de la voie de reparation d'excision de base est selectivement letale dans des cellules qui sont deficientes en reparation d'ADN DSB dependant de la HR. L'invention concerne des procedes et des moyens se rapportant au traitement de cancers qui sont deficients en reparation d'ADN DSB dependant de la HR a l'aide d'inhibiteurs qui ciblent des composants de reparation d'excision de base, par exemple PARP.

Inhibiteurs de réparation d'adn endommagé pour le traitement du cancer

Endometrial cancer comprises a heterogeneous group of tumors, with distinct risk factors, clinical presentation, histopathological features and molecular characteristics. Currently, treatment of metastatic or recurrent disease is based on conventional chemotherapy combination regimens. Advances in the understanding of the molecular pathology of the two types of endometrial carcinoma—type I (endometrioid) and type II (non-endometrioid)—have underpinned the first steps in the development and testing of targeted therapies. Of the potential therapeutic targets identified to date, clinical trials have only assessed the efficacy of inhibition of the EGFR, VEGFR and PI3K/PTEN/AKT/mTOR signaling pathways; responses to these targeted therapies were modest. Despite the striking molecular differences between type I and type II endometrial cancers, most clinical trials have not taken this diversity into account. The identification of activating mutations of kinases (for example PIK3CA and FGFR2) and loss of function of genes related to DNA repair (for example PTEN) may lead to more biology-driven clinical trials exploiting the concepts of oncogene addiction and synthetic lethality.

Emerging therapeutic targets in endometrial

During the mining of sand and gravel from glacial deposits at the Three Rivers Aggregate Companies Quarry, Slippery Rock, Pennsylvania (GPS: 41.043369°, -80.150203°), wood, moss, charcoal, fungal sclerotia, Picea (spruce) needles, Salix (willow) buds, Carex (sedge) achenes, a Viola (violet) seed and beetle remains were recovered from a 0.2 -1.0 ft-thick silt and peat bed at a depth of 32.0 ft from the surface. Pollen (n=664) and spores (n=14) compiled from two samples in the silty peat (31.85 ft bls to 31.89 ft bls and 32.03 ft bls) include 53.3% Picea, 38.4% Pinus, 5.3% Cyperaceae, 1.9% Polypodiaceae, 0.6% Asteroideae, 0.3% Poaceae, 0.1% Cichoroideae, and 0.1% Selaginella selaginoides. Beetle remains found in the silty peat include species of Patrobus, Cytilus, Acidota, and either Enochrus or Cymbiodyta. The biota indicates a wetland environment (bog, fen, or lake shore) in a spruce-dominant forest similar to those found currently in central Canada. Two radiocarbon samples from this horizon have ages of 42,110±1280 BP (41006 cal BC to 45833 cal BC) (PSUAMS-8083) and 42,190±1290 BP (41029 cal BC to 45938 cal BC) (PSUAMS-8082). Below the silt and peat there is a 12.2 ft-thick sand that bears fine filaments of plant material. Within that sand at 39.2 ft bls, a pollen (n=307) and spore (n=8) assemblage has the composition 57.8% Picea, 32.4% Pinus, 7.0% Cyperaceae, 1.6% Selaginella selaginoides, and 0.9% Huperzia selago, and 0.3% Cichoroideae. Elytra (wing cases) of the ground beetle Blethisa catenaria, a ground beetle which lives exclusively on tundra, was also found at 39.2 ft bls. The sediment at 39.2 ft bls was deposited in a tundra-spruce environment similar to that today on the North Slope of Alaska and the Canadian Arctic. The faunal and floral changes indicate climatic warming from the lower to the upper organic horizons. The mean July temperature at 39.2 ft bls is estimated to be 11-12°C and at 32.0 ft bls 15-17°C compared to 21°C at Slippery Rock today. 

Alan Ashworth

Papers

MATERIALS AND METHODS FOR TREATING ESTROGEN RECEPTOR α (ER) POSITIVE CANCER

Reply to 'Comment on 'Domestic light at night and breast cancer risk: a prospective analysis of 105 000 UK women in the Generations Study".

Inhibiteurs de réparation d'adn endommagé pour le traitement du cancer

Emerging therapeutic targets in endometrial

Pleistocene beetles and plants from near slippery rock, pennsylvania, from the titusville interstade (mis 3)