Vitamin A derivatives in the prevention and treatment of human cancer.

Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy

Differences between the discriminatory activity of antisera raised against the total gonadotropins and the Pr-β-hCG-TT for neutralization of hCG and LH action

The effect of antibodies from four monkeys immunized with the vaccine Pr-β-hCG-TT has been investigated on LH/hCG induced progesterone synthesis by goat granulosa cells in culture. The antisera in all cases blocked the hCG induced steroidogenesis. In three out of the four cases, the antibodies did not interfere in the oLH action. One antiserum inhibited, partially but not fully, the oLH stimulated progesterone synthesis. On the other hand, antisera raised against the entire gonadotropins (hCG or oLH) neutralized without discrimination the hCG and LH stimulated progesterone synthesis in these cells. The association constants (Ka) of monkey anti-oLH antibodies for binding with hCG and hLH were of the same order (3.3×1011and 8.3×109L/M for hCG and 3.1×1011, 5.2×1010 & 1.4×109L/M for hLH). Ka of anti-Pr-β-hCG-TT sera for hCG were higher than for hLH