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

Atherosclerosis, the principal cause of heart attack, stroke and gangrene of the extremities, is responsible for 50% of all mortality in the USA, Europe and Japan. The lesions result from an excessive, inflammatory-fibroproliferative response to various forms of insult to the endothelium and smooth muscle of the artery wall. A large number of growth factors, cytokines and vasoregulatory molecules participate in this process. Our ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.

The pathogenesis of atherosclerosis: a perspective for the 1990s

http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

TGF-beta signal transduction.

Dose-dependent kinetics of all-trams-retinoic acid in rats:Plasma levels and excretion into bile, urine, and faeces

Combination chemoprevention of cancer.

Growth factors and cytokines in health and disease

In vitro and in vivo metabolism of all-trans- and 13-cis-retinoic acid in hamsters. Identification of 13-cis-4-oxoretinoic acid.

Summary The pathogenesis of epithelial hyperplasia and squamous metaplasia of the tracheobronchial epithelium, induced by polynuclear hydrocarbons, was studied, with the Syrian golden hamster as a suitable animal model. The acute cellular changes in the tracheobronchial epithelium, produced by intratracheal instillations of benzo[ a ]pyrene carried by ferric oxide particles, included focal replacement of the columnar cells with pleomorphic cells. These had the ultrastructural features of atypical squamous cells, i.e. , cytoplasmic filaments, widened intercellular spaces, abnormal desmosomes, and increased number of lysosomal derivatives. Polylobulated nuclei and pleomorphic nucleoli were prominent findings after multiple instillations of benzo[ a ]pyrene:ferric oxide. Intratracheal instillations of ferric oxide alone or pyrene:ferric oxide produced basal cell hyperplasia, which was reversible. The atypical squamous cells induced by benzo[ a ]pyrene:ferric oxide had ultrastructural features similar to hyperplastic epithelial cells described in the bronchi of smoking dogs and neoplastic squamous cells described in human bronchogenic carcinoma. This investigation is one of a series of studies to clarify the histogenesis of squamous cell carcinoma of the lung.

/pdf/acute-ultrastructural-effects-of-benzo-a-pyrene-and-ferric-3k64ai8g1l.pdf

Michael B. Sporn

Papers

Dose-dependent kinetics of all-trams-retinoic acid in rats:Plasma levels and excretion into bile, urine, and faeces

Combination chemoprevention of cancer.

Growth factors and cytokines in health and disease

In vitro and in vivo metabolism of all-trans- and 13-cis-retinoic acid in hamsters. Identification of 13-cis-4-oxoretinoic acid.

Acute ultrastructural effects of benzo[a]pyrene and ferric oxide the hamster tracheobronchial epithelium.