Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family of serine/threonine kinases, is a key regulator of multiple steps in mitosis. Herewe report on the pharmacological profile of volasertib, a potent and selective Plk inhibitor, in multiple preclinical models of acute myeloid leukemia (AML) including established cell lines, bone marrow samples from AML patients in short-term cultu...

Approaches to improving the selectivity of drugs for the treatment of patients with cancer are discussed, with em phasis on folate antagonists as prototype compounds. The useof metabolites (leucovorin, 5-methyltetrahydrofolate)as “rescue' †̃ agents following methotrexate treatment with appropriate monitoring of blood levels of methotrexate has led to the safe use of this antimetabolite in hi...

Bendamustine (Treanda, Cephalon) is a unique compound composed of an alkylating agent (a nitrogen mustard derivate) and a benzimidazole ring (similar to a purine analog).1 Originally developed in the 1960s, the rationale behind the drug was to use both its antimetabolite activity and alkylating properties to produce an effective drug with a lower toxicity profile than other alkylating agents.2 ...

BACKGROUND Chemotherapy in cancer patients can be associated with serious short- and long-term adverse neurological effects, such as leukoencephalopathy and cognitive impairment, even when therapy is delivered systemically. The underlying cellular basis for these adverse effects is poorly understood. RESULTS We found that three mainstream chemotherapeutic agents--carmustine (BCNU), cisplatin,...

infectious agents cause disease in virtually any susceptible hosts. in the poultry production and medicine, pathogens were eliminated from a line of a breeder by injection of antibiotics into hatching eggs. there is little information available describing the safety of the folate antimetabolite/sulfonamide class of antibiotics on the game birds embryonated eggs. the objective of this study was ...

Previous work has shown that 6-thioguanine (TGua) is an effective inducer of differentiation of Friend and HL-60 leukemia cells which lack hypoxanthine-guanine phosphoribosyltransferase but is at best only weakly active in inducing maturation in parental wild-type cells. Studies in wild-type and mutant HL-60 cells have provided evidence that the free-base TGua is the form of this drug that indu...

PURPOSE We hypothesized that chemotherapy synergizes with VEGF/VEGFR (VEGF/R) inhibitors in patients with advanced solid malignancies. EXPERIMENTAL DESIGN Patients treated on phase I protocols between December 2004 and July 2013 (n = 1,498) were included in this analysis. The primary outcome was clinical benefit, defined as stable disease ≥ 6 months, complete response, or partial response. Tw...

Purpose: We hypothesized that chemotherapy synergizes with VEGF/VEGFR (VEGF/R) inhibitors in patients with advanced solid malignancies. Experimental Design: Patients treated on phase I protocols between December 2004 and July 2013 (n1⁄4 1,498)were included in this analysis. The primary outcomewas clinical benefit, defined as stable disease 6 months, complete response, or partial response. Two o...

The combination of Interferon (IFN) and conventional chemotherapeutic agents offers a promising therapeutic approach for the treatment of cancer. However, there is as yet no consensus on optimal strategies for combining this family of compounds with other cancer therapies. While in vitro studies have demonstrated both direct cytotoxic and cytokinetic effects for IFN, a more interesting role der...

The combination of interferon (IFN) and conventional chemotherapeutic agents offers a promising therapeutic approach for the treatment of cancer. However, there is as yet no consensus on optimal strategies for combining this family of compounds with other cancer therapies. While in vitro studies have demonstrated both direct cytotoxic and cytokinetic effects for IFN, a more interesting role der...