The ideal therapy would target cancer cells while sparing normal tissue. However, in most conventional chemotherapies normal cells are damaged together with cancer cells resulting in the unfortunate side effects. The principle underlying enzyme/prodrug therapy is that a prodrug-activating enzyme is delivered or expressed in tumor tissue following which a non-toxic prodrug is administered system...

BACKGROUND Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargi...

The selective activation of prodrug(s) in tumor tissues by exogenous enzyme(s) for cancer therapy can be accomplished by several ways, including gene-directed enzyme prodrug therapy (GDEPT), virus-directed enzyme prodrug therapy (VDEPT), and antibody-directed enzyme prodrug therapy (ADEPT). The central part of enzyme/prodrug cancer therapy is to deliver drug-activating enzyme gene or functional...

PURPOSE Antibody-directed enzyme prodrug therapy is a two-stage treatment whereby a tumor-targeted antibody-enzyme complex localizes in tumor for selective conversion of prodrug. The purpose of this study was to establish optimal variables for single administration of MFECP1, a recombinant antibody-enzyme fusion protein of an anti-carcinoembryonic antigen single-chain Fv antibody and the bacter...

The mechanisms behind protein PEGylation are complex and dictated by the structure of the protein reactant. Hence, it is difficult to design a reaction process which can produce the desired PEGylated form at high yield. Likewise, efficient purification processes following protein PEGylation must be constructed on an ad hoc basis for each product. The retention and binding mechanisms driving ele...

Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex) and DTPA-indium-tagged liposomes were chara...

PURPOSE The success of enzyme/prodrug cancer therapy is limited by the uncertainty in the delivery of the enzyme in vivo. This study shows the use of noninvasive magnetic resonance (MR) and optical imaging to image the delivery of a prodrug enzyme. With this capability, prodrug administration can be timed so that the enzyme concentration is high in the tumor and low in systemic circulation and ...

PEGylated sequence-controlled macromolecules using supramolecular binding motifs effectively disrupt Taspase1 interaction with Importin α in a concentration-dependent manner, thereby exploiting novel inhibition mechanism for this protease.

background rapid virological response (rvr) strongly predicts sustained virological response (svr) in patients with chronic hepatitis c (chc), and abbreviates antiviral therapy in some patients. objectives to identify factors predicting virological relapse (vr) in chc patients who attained rvr. patients and methods medical records of 133 chc patients with an rvr after completing 24 weeks of ant...

Dual therapy with pegylated interferon and ribavirin is recommended for patients with chronic hepatitis C virus infection who meet criteria for treatment, but it is unclear whether pegylated interferon alfa-2a or pegylated interferon alfa-2b is more effective or associated with fewer adverse events. Because data from head-to-head trials of pegylated interferon regimens are sparse, we performed ...