Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation.

Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo.

Bisphosphonate inhibitors of ATP-mediated HIV-1 reverse transcriptase catalyzed excision of chain-terminating 3'-azido, 3'-deoxythymidine: a QSAR investigation.

We report the results of an investigation of the inhibition of the ATP-mediated HIV-1 reverse transcriptase catalyzed phosphorolysis in vitro of AZT from AZT-terminated DNA primers by a series of 42 bisphosphonates. The four most active compounds possess neutral, halogen-substituted phenyl or biphenyl sidechains and have IC(50) values < 1 microM in excision inhibition assays. Use of two comparative molecular similarity analysis methods to analyze these inhibition results yielded a classification model with an overall accuracy of 94%, and a regression model having good accord with experiment (q(2)=0.

Activity of sulfonium bisphosphonates on tumor cell lines.

We investigated three series of sulfonium bisphosphonates for their activity in inhibiting the growth of three human tumor cell lines. The first series consisted of 6 cyclic sulfonium bisphosphonates, the most active species having an (average) IC50 of 89 microM. The second consisted of 10 phenylalkyl and phenylalkoxy bisphosphonates, the most active species having an IC50 of 18 microM.

Hepatic artery embolization: factors predisposing to postembolization pain and nausea.

Purpose: Analysis of preprocedural factors that may be helpful in predicting the severity of pain and nausea after hepatic arterial embolization (HAE) for liver neoplasms.

Materials And Methods: During a 2-year period, 62 patients (33 men, 29 women) underwent 130 palliative lobar HAEs for unresectable liver neoplasms. The hepatic lobe was embolized with 150-250-microm polyvinyl alcohol particulates with or without lipiodol and/or chemotherapeutic agents.

Accuracy of CO2 angiography in vessel diameter assessment: a comparative study of CO2 versus iodinated contrast material in an aortoiliac flow model.

Purpose: Precise vessel sizing prior to endovascular intervention is critical to achievement of technical success. Diameter measurements obtained with CO2 and iodinated contrast material in an aortoiliac flow model were compared.

Materials And Methods: Aortoiliac flow was simulated in a compliant, silicone elastomer phantom of the aortoiliac system using an autoperfusion pump (flow volume, approximately 1100 mL/min; mean arterial pressure, 70-80 mm Hg at 80-90 cycles/minute) and a glycerol solution (40% by weight; viscosity 3.