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City of Hope researchers offer hope for less invasive prostate cancer diagnosis
DUARTE, Calif.—Researchers at City of Hope have published a study validating their use of a nanodevice that can distinguish between prostate cancer and benign enlarged prostate, offering a potential solution to the difficulties usually presented by prostate cancer diagnosis.
When testing patients for prostate cancer, clinicians are looking for prostate specific antigen (PSA), a glycoprotein that is present in small quantities in the serum of men with healthy prostates, but often elevated in the presence of prostate cancer or other prostate disorders. If PSA levels are abnormal, clinicians will check for cancer with an expensive—and sometimes painful—biopsy procedure. If the biopsy shows no cancer, but PSA levels remain high over time, the physician will repeat the biopsy at further expense and more patient discomfort.
What's more, these tests are not precise enough, says Dr. Jennifer Linehan, a urologic oncologist at City of Hope who specializes in robotic surgery, mostly for patients with kidney, bladder and prostate cancer.
"On the research side, I have been focusing on differentiating prostate cancer from benign prostate tissue, as well as differentiating prostate cancer from more aggressive cancers that are going to develop faster, in an effort to achieve better outcomes for patients," says Linehan, a surgical fellow in City of Hope's Division of Urology and Urologic Oncology.
In 2006, the City of Hope team published a report in the journal Nano Letter describing their use of a bacterial enzyme known as methyltransferase to attach as many as three different targeting molecules to a piece of Y-shaped DNA. The researchers engineered the Y-shaped DNA so that it contains a specific nucleic acid, known as 5-fluorocytosine, at the end of each arm. 5-Fluorocytosine tricks the enzyme into forming a chemical bond between the enzyme itself and the DNA molecule. The researchers also created so-called "fusion" proteins between methyltransferase and proteins, such as thioredoxin, that bind to malignant cells. The investigators then tested whether a nanoscale device could target prostate cancer cells expressing the thioredoxin receptor on their surfaces and distinguish among those cells and those not expressing this particular receptor. Fluorescence imaging showed that this nanoscale construct did bind only to those cells expressing the thioredoxin receptor, suggesting to the investigators that their nanoscale device could be useful in histological tumor typing assays.
Following up on these findings, Linehan and her colleagues presented data at the American Urological Association's 2012 Annual Meeting in Atlanta comparing how the nanodevice binds to stromal tissue found in prostate cancers and tissue from benign prostatic hyperplasia. Using this nanodevice to test the stroma in a biopsy sample could make the first biopsy all that is necessary, according to the researchers.
The study's sample size was relatively small, notes Linehan, but the results of this study are mighty. The research team collected frozen tissue samples of prostates that were surgically removed from 45 patients, 18 of which contained prostate cancer and 17 of which contained benign prostatic hyperplasia. The samples were incubated with varying concentrations of the nanodevice, and then the intensity of their glow was measured.
"We had a small study sample and couldn't use all of the specimens, but as far as how the device works, we established that very well," says Linehan.
City of Hope's report has commercial opportunities beyond prostate cancer, Linehan notes. The methods the researchers developed can be tailored to attach a different molecule to each arm of the Y-shaped DNA molecule. In addition, because the scaffold designed by the researchers is readily absorbed into cells, it can be used to deliver chemotherapeutic or other therapeutic agents, Linehan suggests.