Alfacell Corporation

Stanislaw M Mikulski

Wojciech J Ardelt

Kuslima Shogen

A first substance (such as the peptide aldehydes LLnL and LVP) inhibits the function of intracellular proteasome. A second substance (such as ranpirnase) inhibits intracellular protein synthesis or increases intracellular expression of a cyclin-dependent kinase (CDK) inhibitor. Both substances are administered in such a manner that the effects thereof are coincident. The cell cycle of affected tumor cells is therefore arrested and the cells die of apoptosis.

Alteration of the cell cycle in vivo, and particularly for inducing apoptosis of tumor cells

A pharmaceutical known by the trademark ONCONASE, as described in pending commonly owned application application number 07/436,141 filed Nov. 13, 1989, is combined with two forms of another drug known as Lovastatin. The combination of ONCONASE with Lovastatin has unexpected bioactivity in vitro against ASPC-1 human pancreatic adenocarcinoma cells, A-549 human lung carcinoma cells and HT-520 human squamous cell lung carcinoma cells.

Compositions comprising ONCONASE (tm) and lovastatin

A pharmaceutical to be sold under the ONCONASE trademark, as described in pending commonly owned application application Ser. No. 07/436,141 filed Nov. 13, 1989 is combined with other drugs sold under the trademarks TAMOXIFEN and STELAZINE. The combination of ONCONASE with TAMOXIFEN has unexpected bioactivity in vitro against ASPC-1 human pancreatic adenocarcinoma cells and the combination of ONCONASE with STELAZINE has unexpected bioactivity in vitro against A-549 human lung carcinoma cells.

Compositions comprising ONCONASE (TM) and STELAZINE (TM) or TAMOXIFEN

A pharmaceutical known by the trademark ONCONASE, as described in pending commonly owned application application Ser. No. 07/436,141 filed Nov. 13, 1989, is combined with drugs sold under the names cisplatin, Melphalan and Doxorubicin HCl. The combinations of ONCONASE with these drugs has unexpected bioactivity in vitro against OVCAR-3 human ovarian adenocarcinoma cells.

Compositions comprising ONCONASE(.TM.) and cisplatin, melphalan, or

Rana pipiens eggs are subjected to fertilization and the embryos are grown to a predetermined stage of development. The embryos and unfertilized eggs are then subjected to mechanical processing in the presence of a weakly acidic buffer to produce an extract. The extract is subjected to ion-exchange chromatography and size-exclusion chromatography. The resulting pharmaceutical has activity against certain cancer cells. A partial amino acid sequence of the pharmaceutical is disclosed.

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Essex Fells, NJ, United States of America

Stanislaw M Mikulski