Our concept of enzyme‐mediated cancer imaging and therapy aims to use radiolabeled compounds to target hydrolases over‐expressed on the extracellular surface of solid tumors. A data mining approach identified extracellular sulfatase 1 (SULF1) as an enzyme expressed on the surface of pancreatic cancer cells. We designed, synthesized, and characterized 2‐(2′‐sulfooxyphenyl)‐6‐iodo‐4‐(3H)‐quinazolinone (IQ2‐S) as well as its radioiodinated form (125IQ2‐S) as a prodrug with potential for hydrolysis by SULF1. IQ2‐S was successfully docked in silico into three enzymes – homolog of SULF1, alkaline phosphatase, and prostatic acid phosphatase. The incubation of 125IQ2‐S and 125IQ2‐P with the three enzymes in solution confirms the docking results and enzyme selectivity for the analogs. The hydrolysis of both radioactive compounds produces the water‐insoluble, fluorescent product 2‐(2′‐hydroxyphenyl)‐6‐[125I]iodo‐4‐(3H)‐quinazolinone (125IQ2‐OH). The in vitro incubation of 127IQ2‐S and 127IQ2‐P with pancreatic, ovarian, and prostate cancer cells expressing studied hydrolases also results in their hydrolysis and the precipitation of 127IQ2‐OH fluorescent crystals on the cell surface. To our knowledge, these findings are the first to report the targeting of a radioactive substrate to SULF1 and that this prodrug may be potentially useful in the imaging (123I/124I/131I) and radiotherapy (131I) of pancreatic cancer.
We identified extracellular sulfatase 1 as an enzyme that is appropriate for our concept of Enzyme‐Mediated Cancer Imaging and Therapy, which aims to use radiolabeled compounds to target hydrolases over‐expressed on the extracellular surface of pancreatic tumor cells. Fluorescent products of the hydrolysis of the newly designed and synthesized sulfurylated quinazolinone derivative suggest its potential for use in imaging and radiotherapeutic treatment of pancreatic cancer.
We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation‐carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis co ... more
Flavonoids have well‐known antioxidant, anti‐inflammatory, and anti‐cancer activities. Isoflavone genistein is considered a potent antioxidant agent against oxidative stress. Although several mechanisms have been proposed, a clear antioxidant mechanism of genistein is still remain ... more
People can get oral cancers from UV (290‐400 nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV‐emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to or ... more
A new study from the University of Southern California (USC) has found a link between recreational marijuana use and an increased risk of developing subtypes of testicular cancer that tend to carry a somewhat worse prognosis. Published in CANCER the findings suggest that the potential cance ... more
Researchers in the United States have developed a medical model for regenerating bladders using stem cells harvested from a patient’s own bone marrow. The research, published in STEM CELLS, is especially relevant for paediatric patients suffering from abnormally developed bladders, but also ... more
The journal Stem Cells has announced Dr. Cinzia Rota as the winner of the annual Stem Cells Young Investigator Award. Co-sponsored by the International Stem Cell Symposium, the $10,000 prize is annually given to a young scientist who is the principal author of a research paper published in ... more