Lymphocytes, retinoids

Recidivation is generally due to undetected small intra-hepatic foci. Especially in cirrhosis, the recurrence rate is very high as a result of this factor. A further cause of recidivation after primary RO resection is attributed to the multicentricity of the HCC, i. e. synchronic or metachronic development of additional tumours which are independent of the primary tumour. Therefore, the secondary prophylaxis takes on a special meaning (systemic or intra-arterial chemotherapy, interferon, retinoids, autologous lymphocyte transfusion, etc.). An increase in ornithine decarboxylase and spermidine is apparently a high risk factor for recurrence. Even after recidivation, repeated resection or interventional procedures (e.g. RFTA) are sometimes successful. 

Clinical studies in the use of retinoic add for the treatment or chemoprevention of cancers are becoming more common. Of particular interest has been the use of natural retinoids for the treatment of APL [101,102,193,194,236-241], also called acute non-lymphocytic leukaemia type M3 (ANLL-M3) and French-American-British criteria for M3 leukaemia (FAB M3). The incidence of reports of attainment of complete remissions in patients treated with RA has dramatically increased over the past few years. The following paragraphs describe some of the results obtained to date. Lastly, a brief summary of other studies on the effect of RA in cancer prevention/treatment will be given. 

Phorbol esters. Phorbol esters are an interesting class of compounds which are synthesized by plants of the Euphorbiaceae family. (See also the article by Berry and Helms in this vo1-ume.) They promote skin tumors and also affect the immune system. They stimulate some subpopulations of human T-lymphocytes to divide (Kaplan et al., 1982) and alter the activity of natural killer cells (Kolb et al., 1981). The effect may be adjuvantlike, since the phorbol esters have a macrophage-replacing activity in some culture systems (Koretzky et al., 1982). Vitamin A derivatives appear to inhibit the mitogenic activity of phorbols (Skinnider and Giesbrecht, 1981), but it is not clear whether this is related to the immunopharmacological effects of retinoids discussed above. 

The greater cytotoxic activity of LAK cells compared to NK or unstimulated cytotoxic T lymphocytes may contribute to the antitumor activity of RA and various retinoids. 

Recent cellular and molecular studies have pointed to numerous mechanisms by which VA and related retinoids can potentially regulate the immune system. Evidence exists for retinoid-modulation of antigenic activation of T lymphocytes, activation of monocytes, and B cell differentiation. Retinoids are likely to be involved in a direct manner in regulating the production of... 

---