Abstract: Methods and compositions for inhibiting PDX-1 are provided according to the present invention. An anti-PDX-1 agent included in inventive methods and compositions includes an antibody, an aptamer, an antisense oligonucleotide, a ribozyme and/or an inhibitory compound. Methods of inhibiting PDX-1 expression in a tumor cell are provided by the present invention which include contacting a tumor cell with an effective amount of an anti-PDX-1 agent highly or completely complementary to a specified region of an RNA molecule encoding PDX-1. Such an agent specifically hybridizes with the RNA molecule encoding PDX-1 and inhibits the expression of a PDX-1 gene in the tumor cell. Compositions including anti-PDX-1 siRNA and/or shRNA are described. Recombinant expression constructs encoding anti-PDX-1 siRNA or shRNA according to the present invention are described.

Abstract: The present invention provides a nucleic acid comprising a) a nucleotide sequence encoding one or more pro-apoptotic proteins, and b) a nucleotide sequence encoding one or more tumor-specific and/or tissue-specific promoters. Also provided is a method of treating cancer, comprising administering the compositions of this invention to a subject.

Abstract: In the broadest sense an inventive conjugate includes a macrocyclic scaffold moiety incorporating at least one nitrogen atom. Through linkages to the ring, nitrogen atoms are bonded to at least one therapeutic species, or one cellular trafficking species, and preferably two or more types of trafficking species. The linkages between ring nitrogen atoms and agents are formed through N—C, N—S, N—O or N—N bonds. It is appreciated that more than one agent or agent species are coupled to a ring nitrogen atom through the inclusion of a branched carbon atom or secondary amine nitrogen within the intermediate between the agent and ring nitrogen atom. A disulfide bond intermediate between an agent and a linkage to the ring nitrogen is preferred in instances where intracellular release of the agent or trafficking species is desired. An optional metal ion is coordinated by the scaffolding moiety.