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Blood pressure drugs could help halt pancreatic cancer spread, Jefferson researchers find
December 08, 2006(PHILADELPHIA) Common blood pressure medications might help block the spread of pancreatic cancer, researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found. The scientists showed in laboratory studies that two types of pressure-lowering drugs - ACE inhibitors and AT1R blockers - may help reduce the development of tumor-feeding blood vessels, a process called angiogenesis. Such drugs, they say, may become part of a novel strategy to control the growth and spread of cancer.
According to Hwyda Arafat, M.D., Ph.D., assistant professor of surgery at Jefferson Medical College, previous studies have linked a lower cancer incidence with the inhibition of the pancreas hormone angiotensin II (Ang II) by either ACE (Angiotensin I converting enzyme) inhibitors or AT1R (Ang II type 1 receptor) blockers. Ang II increases the production of VEGF, a vascular factor that promotes blood vessel growth in a number of cancers. High VEGF levels have been correlated with poor cancer prognosis and early recurrence. ACE is the enzyme that converts Ang I to Ang II.
Dr. Arafat and her co-workers examined the protein of both invasive pancreatic cancer and normal pancreatic tissue, analyzing the expression of ACE and AT1R in relation to VEGF. They also looked at the effects of blood pressure drugs captopril, an ACE inhibitor, and losartan, an AT1R blocker, on VEGF production in cancer cell lines.
They found that protein levels in ACE and AT1R were significantly higher in 75 percent of the cancer tissue examined. VEGF expression was higher in cases where there was strong ACE and AT1R levels. In the test tube, Ang II significantly enhanced VEGF production in AT1R-positive cells. Captopril and losartan both blocked this effect.
"Our data show for the first time that both ACE and AT1R are functionally expressed in pancreatic ductal adenocarcinoma and suggest their involvement in tumor angiogenesis," Dr. Arafat says. She presents her results December 5, 2006 at the Southern Surgical Association meeting in Palm Beach, FL.
"High VEGF levels correspond with lymph node metastasis and worse prognosis in many cancers," Dr. Arafat says. "High levels of angiotensin II might mean high levels of VEGF and pancreatic cancer. We have a treatment to block it."
"We are continuing to analyze how angiotensin affects VEGF, and the signaling pathways involved," she says. Her team is looking at the effect of angiotensin on cell proliferation and programmed cell death, and would like to develop an animal model.
"Patients have chemotherapy and radiation sometimes before surgery," she says. "I would imagine this would be useful either for unresectable tumors or after surgical removal of the pancreatic cancer. It might be used in maintenance."
"These are well tested, safe drugs," Dr. Arafat notes, "so the translation of our work from the animal model to the clinical trial can be fast. This is very promising." Pancreatic cancer is the fourth leading cause of cancer death in the United States, with some 32,000 deaths a year. Only five percent of patients live at least one year after diagnosis.
Thomas Jefferson University
They found that protein levels in ACE and AT1R were significantly higher in 75 percent of the cancer tissue examined. VEGF expression was higher in cases where there was strong ACE and AT1R levels. In the test tube, Ang II significantly enhanced VEGF production in AT1R-positive cells. Captopril and losartan both blocked this effect.
"Our data show for the first time that both ACE and AT1R are functionally expressed in pancreatic ductal adenocarcinoma and suggest their involvement in tumor angiogenesis," Dr. Arafat says. She presents her results December 5, 2006 at the Southern Surgical Association meeting in Palm Beach, FL.
"High VEGF levels correspond with lymph node metastasis and worse prognosis in many cancers," Dr. Arafat says. "High levels of angiotensin II might mean high levels of VEGF and pancreatic cancer. We have a treatment to block it."
"We are continuing to analyze how angiotensin affects VEGF, and the signaling pathways involved," she says. Her team is looking at the effect of angiotensin on cell proliferation and programmed cell death, and would like to develop an animal model.
"Patients have chemotherapy and radiation sometimes before surgery," she says. "I would imagine this would be useful either for unresectable tumors or after surgical removal of the pancreatic cancer. It might be used in maintenance."
"These are well tested, safe drugs," Dr. Arafat notes, "so the translation of our work from the animal model to the clinical trial can be fast. This is very promising." Pancreatic cancer is the fourth leading cause of cancer death in the United States, with some 32,000 deaths a year. Only five percent of patients live at least one year after diagnosis.
Thomas Jefferson University
Pancreatic Cancer Current Events and Pancreatic Cancer News RSSRare pancreatic cancer patients may live longer when treated with radiation therapy
Radiation therapy is effective in achieving local control and palliation in patients with pancreatic neuroendocrine tumors (PNTs), despite such tumors being commonly considered resistant to radiation therapy.
African-Americans with colorectal cancer have poorer outcomes, lower survival rates
New research published in the November issue of the Journal of the American College of Surgeons shows that African-American patients with colorectal cancer are more likely to be diagnosed with advanced disease and are less likely to undergo surgical procedures compared with Caucasians, suggesting that improvements in screening and rates of operation may reduce differences in colorectal cancer outcomes for African-Americans.
Discovery offers potential new pancreatic cancer treatment
Tiny particles that can carry drugs and target cancer cells may offer treatment hope for those suffering with pancreatic cancer. New research to be presented in November at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting in Los Angeles reveals that tumor-penetrating microparticles (TPM) have been specifically designed to break through hard-to-infiltrate barriers and deliver drugs more effectively and efficiently than the standard form of chemotherapy such as those injected through a vein.
Hepatitis B does not increase risk for pancreatic cancer
A Henry Ford Hospital study found that hepatitis B does not increase the risk for pancreatic cancer - and that only age is a contributing factor.
M. D. Anderson examines use of toad venom in cancer treatment
Huachansu, a Chinese medicine that comes from the dried venom secreted by the skin glands of toads, has tolerable toxicity levels, even at doses eight times those normally administered, and may slow disease progression in some cancer patients, say researchers from The University of Texas M. D. Anderson Cancer Center.
Pancreatic cancer: Researchers find drug that reverses resistance to chemotherapy
For the first time researchers have shown that by inhibiting the action of an enzyme called TAK-1, it is possible to make pancreatic cancer cells sensitive to chemotherapy, opening the way for the development of a new drug to treat the disease.
Endothelin-1 inhibitors in chronic pancreatitis
Fibrosis is a key feature of chronic pancreatitis and pancreatic cancer. The extensive deposition of extracellular matrix proteins fosters the development of an exocrine and endocrine organ insufficiency, and accelerates progression of the tumour.
Autoimmune response can induce pancreatic tumor rejection
Immune responses are capable of killing tumors before they can be directed toward normal body tissue, according to new scientific findings published in Cancer Research, a journal of the American Association for Cancer Research.
MicroRNAs circulating in blood show promise as biomarkers to detect pancreatic cancer
A blood test for small molecules abnormally expressed in pancreatic cancer may be a promising route to early detection of the disease.
Blood-flow metabolism mismatch predicts pancreatic tumor aggressiveness
Researchers from Turku, Finland, have identified a blood-flow glucose consumption mismatch that predicted pancreatic tumor aggressiveness, according to results of a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
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