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

VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Vascular endothelial growth factor D (VEGF-D) antibodies and vectors, and methods of use

A Radical View of Pathological Vasculature

VEGF-B polypeptides from the PDGF family of growth factors having the property of promoting mitosis and proliferation of vascular endothelial cells, DNA sequences encoding these polypeptides, pharmaceutical compositions containing them and antibodies which react with them. The VEGF-B polypeptides are useful in stimulating angiogenesis as well as in diagnostic applications.

Processed vascular endothelial growth factor-B polypeptides

Vascular endothelial growth factor C (VEGF-C) is the only factor known causing lymphangiogenesis We report herein the review of recent experimental studies on VEGF family and their receptors and the molecular mechanisms of the lymphangiogenesis in cancer According to our study, VEGF-C is a potent stimulator in not only the angiogenesis but also the lymphangiogenesis on the chick chorioallantoic membrane In the clinical specimens from gastric cancer, there is an intimate relationship between the VEGF receptor-3/VEGF-C tissue status and lymphagiogenesis RT-PCR and immunohistological examinations demonstrated that VEGF-C was mainly produced from cancer cells and that VEGFR-3 expression was restricted in the endothelial cells of lymphatic vessels VEGF-C and VEGFR-3 mRNA expression were positively correlated in primary gastric cancers and the number of VEGFR-3 positive lymphatic vessels in VEGF-C mRNA positive tumour was significantly larger than that in VEGF-C negative tumours The number of such vessels in tumour stroma was closely related to the grade of lymphatic invasion of gastric cancer Accordingly, we conclude that VEGF-C may induce the lymphatic neogenesis in the stroma of primary gastric cancer In these circumstances, cancer cells can easily intravasate into the lymphatic vessels, because of the increase of the contact point of cancer cells with lymphatic vessels

VEGF-C/VEGFRS and Cancer Metastasis

Transforming growth factor-ps (TGFPs) are a group of multifunctional polypeptides that regulate the proliferation, differentiation, and other functions of many cell types. The mechanism of TGFP-mediated growth inhibition of various cells is not understood. We have previously reported that the serumand phorbol ester tumor promoterregulatedjunB and c-jun transcription factors as well as platelet-derived growth factor A-chains are induced by TGFP.1.2 Recently, we have identified a TGFP-induced nuclear receptor mRNA and at least four other TGFP-responsive mRNAs of unknown function from a cDNA library made from serum-stimulated NIH/3T3 cells (Lea Sistonen, Kari Alitalo, Luisella Toshi, and Rodrigo Bravo, unpublished data). TGFB is also an efficient regulator of the secretion of plasminogen activators (both urokinase and tissue-type) and their type 1 inhibitor (PAI-1) and modulates the secretion of plasminogen activators in most fibroblastic and malignant cell lines? In the current study we propose a role for TGFP in the induction of IL-6.

Kari Alitalo

Papers

Vascular endothelial growth factor D (VEGF-D) antibodies and vectors, and methods of use

A Radical View of Pathological Vasculature

Processed vascular endothelial growth factor-B polypeptides

VEGF-C/VEGFRS and Cancer Metastasis

Regulation by TGFβ of Genes Involved in Growth Control: Interleukin‐6a