Many malignant solid tumors generally develop a higher interstitial fluid pressure (IFP) than normal tissue. High IFP in tumors may cause a reduced uptake of chemotherapeutic agents and resistance to radiation therapy. In addition, a high IFP has been found to promote metastatic spread.
"Currently, an imaging method for noninvasive assessment of the IFP of tumors is needed to evaluate the potential of IFP as a biomarker for cancer aggressiveness and, hence, to identify patients with cancer who may benefit from particularly aggressive treatment because of highly elevated tumor IFP," said Einar K. Rofstad, Ph.D., of the department of radiation biology at the Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway.
Rofstad and colleagues tested the use of dynamic contrast-enhanced magnetic resonance imaging (MRI) to evaluate the velocity of fluid flow from tumors in human cell lines of cervical carcinoma and melanoma implanted in mice. Researchers hypothesized that the velocity of fluid flow from tumor tissue into adjacent tissue was determined by the IFP drop at the tumor surface.
Results indicated that the velocity of the fluid flow at the tumor surface strongly correlated with the magnitude of the tumor IFP and that dynamic contrast-enhanced MRI with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as a contrast agent can be used to noninvasively measure the fluid-flow velocity. In addition, primary tumors of mice with metastases had a significantly higher IFP and fluid-flow velocity at the tumor surface compared with the primary tumors of metastasis-free mice, confirming that the development of lymph node metastases strongly correlated to the IFP of the primary tumor and the velocity of fluid flow as measured by Gd-DTPA-based dynamic contrast-enhanced MRI.
"Our findings establish that Gd-DTPA-based dynamic contrast-enhanced MRI can noninvasively visualize tumor IFP," Rofstad said. "This reveals the potential for the fluid-flow velocity at the tumor surface determined by this imaging method to serve as a novel general biomarker of tumor aggressiveness."
Rofstad said that comprehensive prospective clinical investigations in several types of cancer are needed to assess the value of fluid-flow velocity at the tumor surface level assessed by Gd-DTPA-based dynamic contrast-enhanced MRI as a general biomarker for interstitial hypertension-induced cancer aggressiveness.
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Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR's membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
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