p53/FBXL20 axis negatively regulates the protein stability of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase.

We have previously reported an important role of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase, in the support of critical oncogenic pathways required for oncogenesis and the malignant phenotype of pancreatic cancer. The studies in this report reveal a novel mechanism by which the p53 tumor suppressor inhibits the protein-stability of PR55α via FBXL20, a p53-target gene that serves as a substrate recognition component of the SCF (Skp1_Cullin1_F-box) E3 ubiquitin ligase complex that promotes proteasomal degradation of its targeted proteins. Our studies show that inactivation of p53 by siRNA-knockdown, gene-deletion, HPV-E6-mediated degradation, or expression of the loss-of-function mutant p53 results in increased PR55α protein stability, which is accompanied by reduced protein expression of FBXL20 and decreased ubiquitination of PR55α.

Biological Evaluation of a Potential Anticancer Agent Methyl -[5-(3'-Iodobenzoyl)-1-Benzimidazol-2-yl]Carbamate.

Resistance of cancer to chemo- and radiotherapy remains a major clinical problem. This study contributes to the ongoing search for agents that can bypass this resistance by developing a novel antimitotic theranostic. Methyl -[5-(3'-iodobenzoyl)-1-benzimidazol-2-yl]carbamates and were synthesized from a common precursor or its 3'-stannylated derivative.

Radiolabeled cyclosaligenyl monophosphates of 5-iodo-2'-deoxyuridine, 5-iodo-3'-fluoro-2',3'-dideoxyuridine, and 3'-fluorothymidine for molecular radiotherapy of cancer: synthesis and biological evaluation.

Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies.

Radiolabeled 5-iodo-3'-O-(17beta-succinyl-5alpha-androstan-3-one)-2'-deoxyuridine and its 5'-monophosphate for imaging and therapy of androgen receptor-positive cancers: synthesis and biological evaluation.

High levels of androgen receptor (AR) are often indicative of recurrent, advanced, or metastatic cancers. These conditions are also characterized by a high proliferative fraction. 5-Radioiodo-3'-O-(17beta-succinyl-5alpha-androstan-3-one)-2'-deoxyuridine 8 and 5-radioiodo-3'-O-(17beta-succinyl-5alpha-androstan-3-one)-2'-deoxyuridin-5'-yl monophosphate 13 target AR.

Radioactive drugs in drug development research: quality assurance issues.

Increasing number of new drugs, drug formulations and drug delivery systems is evaluated using noninvasive imaging methods. A successful use of new drugs and radiopharmaceuticals depends on their proven quality. This review provides a brief outline of the quality control procedures required for radiolabeled drugs within the context of the existing regulations.