https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

The hallmarks of cancer.

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

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.

https://science.sciencemag.org/content/sci/235/4785/177.full.pdf

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene

The present invention provides VEGF-D polypeptides, which among other things stimulate endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as fragments, dimers, and methods of using the same.

Vascular endothelial growth factor D (VEGF-D) polypeptides and methods of use

Meningeal lymphatic vessels promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelium growth factor-C (VEGF-C) is essential for meningeal lymphatic development and maintenance and has therapeutic potential for treating neurological disorders, including ischemic stroke. We have investigated the effects of VEGF-C overexpression on brain fluid drainage, single cell transcriptome in the brain, and stroke outcomes in adult mice. Intra-cerebrospinal fluid administration of an adeno-associated virus expressing VEGF-C (AAV-VEGF-C) increases the CNS lymphatic network. Post-contrast T1 mapping of the head and neck showed that deep cervical lymph node size and drainage of CNS-derived fluids were increased. Single nuclei RNA sequencing revealed a neuro-supportive role of VEGF-C via upregulation of calcium and brain-derived neurotrophic factor (BDNF) signaling pathways in brain cells. In a mouse model of ischemic stroke, AAV-VEGF-C pretreatment reduced stroke injury and ameliorated motor performances in the subacute stage. AAV-VEGF-C thus promotes CNS-derived fluid and solute drainage, confers neuroprotection, and reduces ischemic stroke damage. Short abstract Intrathecal delivery of VEGF-C increases the lymphatic drainage of brain-derived fluids confers neuroprotection, and improves neurological outcomes after ischemic stroke.

/pdf/vegf-c-promotes-brain-derived-fluid-drainage-confers-2asmq5gh.pdf

VEGF-C promotes brain-derived fluid drainage, confers neuroprotection, and improves stroke outcomes

Regulatory or structural alterations of cellullar oncogenes have been implicated in the causation of various forms of cancer. Oncogene alteration by point mutations can result in a protein product with strongly enhanced tumorigenic potential. Aberrant expression of cellular oncogenes may result from tumor-specific chromosomal translocations that dysregulate the normal function of a proto-oncogene. The amplification of cellular oncogenes can also enhance their expression by increasing the amount of DNA template available for the production of mRNA. It appears that the amplification of certain oncogenes is both a common correlate of the progression of some tumors and occurs as a rare sporadic event affecting various oncogenes in different types of cancer. Amplified copies of oncogenes may or may not be associated with chromosomal abnormalities that signify DNA amplification.

Amplification of Cellular Oncogenes in Colon and Lung Cancer Cells

L'invention concerne VEGF-D, nouveau membre de la famille PDGF (facteurs de croissance d'origine plaquettaire) des facteurs de croissances qui stimule, entre autres, la proliferation et l'angiogenese des cellules endotheliales et favorise la permeabilite vasculaire, ainsi que des sequences nucleotidique codant pour ledit facteur, des methodes de fabrication dudit facteur, ses anticorps et autres antagonistes, des cellules hotes transfectees ou transformees exprimant ledit facteur, des compositions pharmaceutiques comprenant ledit facteur et ses utilisations dans des applications medicales et diagnostiques.

Facteur d recombinant de croissance des cellules endotheliales vasculaires (vegf-d)

We would like to thank Dr Toska for pointing out an inaccuracy pertaining to Figure 1 in our recent review article.1 Indeed, the figure reflects outdated textbook knowledge on the physiology of fluid exchange between the various compartments (arteries, capillaries, veins, lymphatic vessels, and the interstitium). According to current …

Kari Alitalo

Papers

Vascular endothelial growth factor D (VEGF-D) polypeptides and methods of use

VEGF-C promotes brain-derived fluid drainage, confers neuroprotection, and improves stroke outcomes

Amplification of Cellular Oncogenes in Colon and Lung Cancer Cells

Facteur d recombinant de croissance des cellules endotheliales vasculaires (vegf-d)

Response to Letter Regarding Article, “Biological Basis of Therapeutic Lymphangiogenesis”