biomarkers ,

Prostate tissue kept alive and working

JOHNS HOPKINS (US) — Scientists have found a way to keep surgically removed prostate tissue alive and functioning normally for up to a week.

It’s expected that the technique—possible on both cancerous and normal prostate tissue—will not only enhance research of prostate biology and cancer, but also speed the creation of individualized medicines for prostate cancer patients.

“Our technique could help scientists more accurately predict how living prostate tissues respond to therapy,” says Marikki Laiho, director of the Division of Molecular Radiation Sciences at the Johns Hopkins University Kimmel Cancer Center. “It holds promise for testing anticancer drugs that work best.”

Previous attempts to culture live prostate tissues resulted in poor viability and lost “tissue architecture,” making them less than useful for research or therapy development.

For the study, published in the Nov. 1 issue of Cancer Research, scientists from Johns Hopkins, the University of Helsinki, and Stanford University refined a technique that Laiho piloted with Stanford researcher Donna Peehl, in a project completed in 2007.

The new work also included experiments to test tissue viability and utility in research.

Customarily, pathologists store tissue samples in paraffin wax, but that kills the tissue and results in samples that are essentially frozen in time.

In many research laboratories, scientists experiment with living prostate cancer cells grown in flasks filled with nutrients and kept under strict temperature conditions. But these cells are not connected together in the tightly knit architecture of tissue that exists in the actual prostate gland.

The new technique maintains tissue architecture while keeping the sample alive.

“Tissue architecture may hold clues to why certain therapies work and others fail, and may be a better model of the intact, in vivo prostate gland,” Laiho says.

One key to success for the international team was to work with surgeons and pathologists to speed up delivery of tissue samples from the operating room to the pathology lab.

Scientists cut thin slices of prostate specimens taken from 18 patients who had undergone surgery on the prostate gland at the Helsinki University Central Hospital or The Johns Hopkins Hospital from 2007 to 2009.

Specimen slices had to be a precise thickness to allow cells throughout the tissue to maintain a healthy exchange of gases and growth factors.

Then, Laiho and her team placed the tissues in a complex liquid mix of 64 separate ingredients to maintain the proper chemical and nutritional support for the biological functions in the tissue.

The scientists validated the presence of biomarkers specific for each type of cell within the prostate tissues to ensure that they were viable.

The scientists caution that although their method gives them a more “real-life” model of the prostate with live tissue samples, it comes at a cost.

Even with support, the tissues are short-lived, and experiments on fresh specimens must be completed within one week, which may be too short for some types of research.

Researchers have already used the tissue-culture technique to measure levels of proteins known to repair DNA damage caused by carcinogens and other environmental agents.

The tissue-culture technique was a key component of understanding which DNA repair proteins may or may not be activated in different parts of prostate tissue and could help scientists develop therapies that target these DNA repair proteins.

The Johns Hopkins and Helsinki investigators also plan to use their new tissue-culture technique to test the response of experimental drugs on prostate cancer tissues.

Funding for the study was provided by the Academy of Finland, the Patrick C. Walsh Prostate Cancer Research Fund, the K. Albin Johansson Foundation, the Biomedicum Helsinki Foundation, the Finnish-Norwegian Medical Foundation, the Finnish Medical Foundation, and Helsinki Biomedical Graduate School.

More news from Johns Hopkins University: http://releases.jhu.edu/

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