March 2008

By Prachi Petal-Predd
Published: Friday, Jun 25, 2010
UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER

Protein-Mimetic Kills Lung Cancer Cells

A synthetic molecule that mimics a suicide-triggering protein called Smac can cause human lung cancer tumors grown in mice to regress or disappear. The new findings, which appear in the November issue of Cancer Cell, suggest that the compound could one day be used as a targeted therapy for lung and other cancers.

Howard Hughes investigator Xiaodong Wang, PhD, professor of biochemistry at the University of Texas Southwestern Medical Center in Dallas, Texas who led the study, first announced the discovery of the cell protein Smac in 2000. Smac, which is released by mitochondria, plays a role in the normal apoptosis of cells, a process that is turned off in tumor cells. Dr. Wang and his colleagues developed molecules that mimicked Smac and could enter cells and trigger apoptosis without requiring the mitochondria to release Smac. The mimetic, however, only killed cancer cells when introduced together with another molecule called Tumor Necrosis Factor-α or TNF-α.

In the new study, Dr. Wang and his colleagues found that some human non–small cell lung cancer cell lines reacted to the Smac mimic without requiring TNF-α. Of the 50 non–small cell lung cancer cell lines the researchers tested, 22% were sensitive to the Smac mimic alone. These sensitive cell lines, the researchers found, produced their own TNF-α.

This is paradoxical, said Dr. Wang, because TNF-a signaling is part of a complex pathway that gives cancer cells a survival signal. “Thus, in these cancer cell lines, the TNF-α survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics,” said Dr. Wang. He added that in the future, Smac mimics could be used to treat some cancers and that the presence of TNF-α could serve as a marker to tell doctors which tumors would respond to the Smac mimetic alone.





DUKE UNIVERSITY MEDICAL CENTER

Obesity Decreases Effectiveness of PSA Test

Researchers at the Duke University Medical Center have found that high blood volumes linked to obesity can dilute levels of Prostate Specific Antigen (PSA). The results indicate that doctors need to adjust the current PSA test when screening obese patients for prostate cancer.

“Physicians need to take increased body weight into consideration when interpreting PSA results in obese men,” Lionel Banez, MD, of Duke University Medical Center in Durham, North Carolina, told Oncology & Biotech News. “Failure to do so may lead to a large number of missed cancers.”

In a November 21 Journal of the American Medical Association paper, Dr. Banez and his colleagues state that higher body mass index (BMI) in men was associated with higher blood plasma volume, which in turn means lower PSA levels.

The researchers looked at more than 13,000 men who had undergone radical prostectomy between 1988 and 2006. They found that men with a BMI of at least 35 had 21%–23% larger plasma volumes than men with normal weight. After adjusting for clinicopathological variables, men with a BMI of 35 or greater had 11%–21% lower PSA concentrations as compared with normalweight men. “It is reasonable then, when caring for obese patients, to lower the threshold or assign a lower PSA cut-off point which prompts a diagnostic prostate biopsy,” said Dr. Banez.

Several other studies have shown that obese men have lower PSA concentrations than nonobese men, but there have been two hypotheses to explain this observation. One was that obese men make less PSA because of lower levels of testosterone, which is related to PSA production. The other was that obese men create more blood to support their size, which effectively dilutes PSA levels. The purpose of the new study was to determine which of two hypotheses is true and the latter is very clearly the answer, said Alan Partin, MD, chief of the Department of Urology at Johns Hopkins’ Brady Urological Institute and one of the study’s authors.

Stephen Freedland, MD, professor of Urology at Duke University, said that many new tests for cancer and other diseases that are being developed currently rely on the concentrations of disease markers, similar to PSA tests. “For these other tests just starting down the development pipeline, we need to think about the actual total amount of a biological marker rather than concentration,” he said.





Rhode Island Hospital

Microwave Ablation Safe for Lung Cancer

In a new study, researchers at Rhode Island Hospital have shown that microwave energy can be safely used to shrink or eliminate malignant lung tumors. The researchers presented their results on microwave ablation at the Radiological Society of North America meeting. Rhode Island Hospital in Providence is one of 10 facilities in the country that offer microwave ablation—physicians at the hospital were the first in the United States to treat cancer with the technique.

During microwave ablation, radiologists use computed tomography–imaging guidance to place a thin microwave electrode into the tumor. A microwave generator emits electromagnetic waves that excite water molecules in the tumor tissue, creating intense heat and friction that destroys the tumor.


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