As a single agent, gemcitabine (2',2'-difluorodeoxycytidine) has shown minimal activity against gastrointestinal malignancies with only a modest improvement in survival in patients with pancreatic cancer. Recently, gemcitabine resistance has been associated with the up-regulation of mRNA and protein levels of the ribonucleotide reductase M2 subunit (RR-M2), a rate-limiting enzyme in DNA synthes...

Defects in cell cycle checkpoints can lead to chromosome abnormality, aneuploidy, and genomic instability, all of which can contribute to tumorigenesis. Recent studies and data presented in this study indicate that cells with compromised G1 checkpoint endoreduplicate and become polyploid in response to microtubule inhibitors. Previous studies have shown that polyploid cells are unstable and los...

Role of cyclin dependent kinase 9(CDK9) as a potential target in esophageal adenocarcinoma (EAC) is unknown. We investigated CDK9 protein expression in EAC and Barrett's esophagus and role of CDK9 in oncogenic processes of EAC in vitro and in murine xenografts. The CDK9 expression was significantly higher in EAC as compared to Barrett's esophagus in patient samples. Stable shCDK9 in SKGT4 reduc...

In this report, we present cyclohexylcyanine, a phthalocyanine analogue with two cyclohexane units incorporated into the backbone of the macrocycle; in the free base, the ionizable protons lie on the periphery of the ring, and when metalated with silver the macrocycle binds to the metal via these same meso nitrogen atoms.

A complete stereocontrol of 1,3-dipolar cycloaddition of N-metalated azomethine ylides onto endohedral fullerene H2@C60 is reported for the first time. The stereodivergent synthesis of either the cis or the trans endohedral cycloadduct is achieved with excellent diastereo- and enantioselectivities.

The asymmetric redox-active ligand 4,5-bis(pyridine-2-carboxamido)-1,2-catechol ((N,O)LH4) is prepared and metalated to afford the hexanuclear complex [Mn6((N,O)L)6](6-). Structural analysis and magnetic measurements reveal this complex to feature Mn(II) ions bridged by (N,O)L(3-)˙ radicals, which are antiferromagnetically coupled to give an S = 12 ground state.

Flavopiridol represents one in an ever-expanding group of compounds currently called molecularly targeted agents. Such compounds, in contrast to conventional cytotoxic drugs, which exert a more general disruptive effect on key cellular structures or processes (e.g., DNA replication, formation of the mitotic spindle, etc.), target pathways directly implicated in neoplastic transformation. The pr...

The synthesis of the CD spiroketal fragment of spongistatin 1 (altohyrtin A) has been accomplished utilizing the addition of a metalated pyrone to an aldehyde and subsequent acid-catalyzed spirocyclization. A stereoselective hydrogenation and subsequent conformational inversion establish the C19 stereocenter and the axial-equatorial spiroketal center.