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

Lymph vessels are essential for the maintenance of tissue fluid homeostasis and immune surveillance and are involved in the pathogenesis of several human diseases, such as lymphoedema, inflammation and tumour metastasis. The identification of lymphangiogenic growth factors and their receptor, and of transcription factors that control lymphangiogenesis, have provided significant insight into the biology of lymphatic vasculature. Another important advance has been the recent development of mouse, frog and fish models that allow the study of lymphangiogenesis and diseases affecting lymph vessels. In this review we discuss some of the major molecular players involved in regulation of lymphangiogenesis and lymph vessel remodelling, and the role of lymph vessels and their regulators in human disease.

Molecular Players in Lymphangiogenesis

454: Targeting Lymphatic Vessel CCL21 Production by VEGFR-3 Inhibition Prevents Cardiac Allograft Rejection and Arteriosclerosis

Growth factors and lymphangiogenesis

During embryogenesis, the formation of new blood vessels occurs via two processes: vasculogenesis and angiogenesis. Vasculogenesis involves the de novo differentation of endothelial cells from mesoderm-derived precursors called angioblasts, which then cluster and reorganize to form capillary-like tubes (Risau and Flamme, 1995). Once the primary vascular plexus is formed, new capillaries form by sprouting or by splitting (intussusception) from preexisting capillaries in the processes called sprouting or nonsprouting angiogenesis, respectively (Risau, 1997). In postnatal life, the growth of normal as well as neoplastic tissues depends on angiogenesis. Angiogenesis is particularly important for normal reproductive function, including the cyclical growth of capillaries within the ovary (required for ovulation and corpus luteum formation) and the endometrium (required for regeneration following menstruation). Angiogenesis also occurs following implantation of the blastocyst, and is required for the formation of the placenta (Findlay, 1986). This chapter discusses the role of physiologic angiogenesis and angiogenic growth factors in relation to mammary gland function.

Growth Factor Regulation of Physiologic Angiogenesis in the Mammary Gland

PDGF-D, a new member of the PDGF/VEGF family of growth factors, as well as the nucleotide sequence encoding it, methods for producing it, antibodies and other antagonists to it, transfected and transformed host cells expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications, including methods for stimulating growth of a connective tissue or healing a wound in a mammal, which methods comprise administering to the mammal an effective amount of PDGF-D polypeptides or polynucleotides encoding the PDGF-D polypeptides.

Kari Alitalo

Papers

Molecular Players in Lymphangiogenesis

454: Targeting Lymphatic Vessel CCL21 Production by VEGFR-3 Inhibition Prevents Cardiac Allograft Rejection and Arteriosclerosis

Growth factors and lymphangiogenesis

Growth Factor Regulation of Physiologic Angiogenesis in the Mammary Gland

Antibodies to PDGF-D