Salicylate inhibition of rat mammary carcinogenesis and angiogenesis in female rat compatible with misoprostol administration.

Epidemiological data suggest that non-steroidal anti-inflammatory drugs prevent colon cancer. The evidence for other types of tumour is less conclusive, though animal and in vitro studies indicate that they may be effective against mammary cancer cells. We assessed the effect of dietary acetylsalicylic and salicylic acid against dimethylbenzanthracene-induced rat tumours.

Oxysterol mixtures prevent proapoptotic effects of 7-ketocholesterol in macrophages: implications for proatherogenic gene modulation.

Oxysterols are common components of oxidized low-density lipoprotein and accumulate in the core of fibrotic plaques as a mixture of cholesterol and cholesteryl ester oxidation products. The proapoptotic effects of a biologically representative mixture of oxysterols was compared with equimolar amounts of 7-ketocholesterol and unoxidized cholesterol. The oxysterol mixture in a concentration range actually detectable in hypercholesterolemic patients did not stimulate programmed cell death in cultivated murine macrophages.

Mice lacking TNFalpha receptors 1 and 2 are resistant to death and fulminant liver injury induced by agonistic anti-Fas antibody.

The liver is particularly susceptible to Fas-mediated cytotoxicity. Mice given an adequate parenteral dose of agonistic anti-Fas antibody (aFas) or of FasL are known to develop a devastating liver injury and to die in a few hours. The present work shows that mice lacking TNFR1 and TNFR2 (R(-)) both survive a single dose of aFas, otherwise rapidly lethal, and develop a mild form of hepatic damage, compared to the much more severe liver injury that in a few hours strikes wild-type mice (R(+)), eventually involving increased activity of proteases of different families (caspase 3-, 8-, and 9-like, calpains, cathepsin B).

4-hydroxynonenal and transforming growth factor-beta1 expression in colon cancer.

In vivo studies on human colon adenocarcinoma showed decreased transforming growth factor-beta1 (TGF-beta1) antiproliferative cytokine content in tumour tissue related to malignancy progression, with a corresponding decrease in lipid peroxidation aldehydic end-product, 4-hydroxynonenal (HNE). The tumour mechanism to escape TGF-beta1-mediated growth inhibition may be due to an altered TGF-beta1 receptor system. Subsequent in vitro analyses showed a differential distribution of TGF-beta1 receptors depending on the human colon cancer cell line considered (CaCo-2 or HT-29): compared to HT-29 cells, CaCo-2 cells showed a decrease of the two main TGF-beta1 receptors, RI and RII.

Associated changes of lipid peroxidation and transforming growth factor beta1 levels in human colon cancer during tumour progression.

Background: During neoplastic progression, alterations in transforming growth factor beta1 (TGF-beta1) dependent control of cell growth may be an important mechanism of selective proliferation of transformed cellular clones. Defective regulation of TGF-beta1 receptors has been reported to occur in a number of human malignant tumours while little is known of the actual levels of this growth inhibitory cytokine in cancer. On the basis of the demonstrated ability of major lipid peroxidation products such as 4-hydroxynonenal to modulate TGF-beta1 expression and synthesis, we speculated that decreased lipid oxidation, as frequently observed in neoplastic tissues, would contribute to the selective promotion of tumour growth through decreased expression of the cytokine within the tumour mass.