Alpha-fetoprotein-mediated targeting--a new strategy to overcome multidrug resistance of tumour cells in vitro.

The possibility of overcoming the multidrug resistance of human malignant cells by using doxorubicin conjugated to alpha-fetoprotein (AFP) was studied. It was shown that this type of antitumour drugs, penetrating the cell by receptor-mediated endocytosis with AFP as a vehicle, raises the sensitivity of the tumour cells that are resistant due to the expression of the multidrug resistance gene mdr1. The sensitivity of antibiotic-resistant cell lines SKVLB (a human ovarian carcinoma) and MCF-7 AdrR (a human breast carcinoma) increased by 10- and 4-fold, respectively, when AFP-conjugated doxorubicin was used.

Hypersensitization of multidrug resistant human ovarian carcinoma cells by pluronic P85 block copolymer.

The chemosensitizing effect of Pluronic P85 block copolymer were studied using two human ovarian carcinoma sublines: the glycoprotein P (P-gp) multidrug resistant (MDR) SKVLB cells and non-MDR SKOV3 cells. The dramatic increase (up to 700 times) in the daunorubicin cytotoxic activity was observed in the presence of 0.01% (22 microM) to 1% (2.

Alpha-fetoprotein-mediated targeting of anti-cancer drugs to tumor cells in vitro.

An oncofetal protein, human alpha-fetoprotein, was selected as a vector molecule for targeted delivery of antitumor substances. Conjugates of alpha-fetoprotein with doxorubicin, daunomycin, calichemicin, carboxyphosphamide, bleomycetin, chlorbutin, cis-platinum, methotrexate were synthesized. All conjugates displayed a highly selective antitumor cytotoxic activity towards human cell cultures.

Identification of functionally active fragments of staphylococcal enterotoxin B.

It has been found that staphylococcal enterotoxin B contains a proteolysis-sensitive sequence in the cysteine loop formed by two half-cystines located in the middle of the toxin polypeptide chain. Fragments of the enterotoxin formed as a result of its digestion in this region have been isolated, their N-terminal sequences have been determined and sites of proteolysis have been identified. It has been demonstrated that the N-terminal fragment of staphylococcal enterotoxin B is capable of activating T cell proliferation in the culture of human mononuclear cells practically to the same degree as the intact enterotoxin.

Platelet-activating factor stimulates receptor-mediated formation of reactive oxygen intermediates in human monocytes.

Stimulation of production of reactive oxygen intermediates (ROI) was examined in human peripheral blood monocytes by luminol-dependent chemiluminescence. The dose-response curve characterizing the dependence of ROI production on the concentration of platelet-activating factor (PAF) showed that stimulation occurred within a concentration range of 2 x 10(-9)M to 5 x 10(-6)M. Transformation of the dose-response curve to an Eadie-Hofstee plot indicated that the process is characterized by two Km values.

The effect of Staphylococcus aureus enterotoxin A on proliferation of lymphoid and nerve cells.

The effects of Staphylococcus aureus enterotoxin A (SEA) on proliferative activities of human peripheral blood lymphocytes, B-lymphoma cells of the Namalva line, and nerve cells of the PC12 line have been studied. It has been shown that SEA affects these cells in identical ways, producing either a mitogenic or an antiproliferative effect. Studies on the dynamics of cellular responses to the action of SEA have demonstrated that the effects of the toxin are mediated by its interaction with different binding sites on the membranes of target cells.