A selective COX-2 inhibitor differentially modulates tumor angiogenesis and growth in COX-2 expressing and COX-2 lacking pancreatic cancer in vivo: Abstract No. 4792
A popular drug used to treat arthritis worldwide has been found to promote tumor growth in specific types of human pancreatic cancer cells, according to a study presented by investigators with the UCLA David Geffen School of Medicine.
In their studies, the researchers found that the anti-inflammatory drug nimesulide triggered the growth of blood vessels, or angiogenesis, in human pancreatic cells that do not express an enzyme called COX-2.
Nimesulide belongs to a class of so-called "super aspirins" that primarily work by blocking COX-2, thus inhibiting inflammation seen a variety of ailments including arthritis and even some cancers.
In fact, the UCLA study confirmed that nimesulide actually inhibited angiogenesis and tumor growth in pancreatic tumors that express COX-2.
"Basically, for the first time, we have shown that a selective COX-2 inhibitor can simulate tumor growth," said Guido E. Eibl, M.D., a researcher in the Hirshberg Pancreatic Cancer Laboratory at the UCLA School of Medicine.
"However, its effects, depend on whether the tumor expresses COX-2 or not," he added. Depending on the study, roughly 10-40 percent of all pancreatic tumor cells are considered COX-2 negative, while all others express COX-2.
"These studies suggest that patients can be treated with selected COX-2 inhibitors, but only based on the COX-2 expression profile of their pancreatic tumor," said Eibl.
Such findings are significant for a disease that is considered among the most lethal of all tumors, with a mortality rate in excess of 95 percent. In the United States, pancreatic cancer now ranks fourth and fifth as a cause of cancer death in men and women respectively, with about 25,000 new cases of pancreatic cancer diagnosed each year.
Chemotherapy has not resulted in significant survival benefit, suggesting the need for new molecular targets for prevention and treatment of this disease.
In the UCLA study, COX-2 negative and positive human pancreatic tumor cells were injected in the flanks of nude mice, which were then treated with nimesulide. The scientists found that in the COX-2 positive mice, the drug inhibited a factor needed for the growth of blood vessels (VEGF), but actually increased human VEGF levels in the COX-2 negative mice. The results showed widespread growth of blood vessels in the COX-2 negative mice, along with increased production of pancreatic cancer cells.
"The increase in VEGF production has predominantly only an effect in vivo, where it can act on endothelial cells," said Eibl. "So it may very well be possible that the overall effects of nimesulide, or any other COX-2 inhibitor for that matter in vivo, reflects a balance between direct effects on the cancer cells and indirect effects on the interaction between the cancer cells and host tissue."
Eibl said his team plans to test other COX-2 inhibitors in animals to see if other drugs in this class have the same impact on tumor growth as nimesulide.
"Based on in vitro data, we feel confident that we would find comparable results in vivo, although the studies still must be done," said Eibl.
Sun Exposure, Sexual Behavior and Cervical Human Papilloma Virus: Abstract No. 2924
If, as Ecclesiastes says, there's a season for everything, then spring is the season for love, but summer is the season for increased venereal infections from human papilloma virus … at least in the southern part of Holland.
According to an analysis of nearly a million Pap smears collected over 16 consecutive years in southern Holland, women are about twice as likely to be infected with HPV during the longer, sunnier days of August than the shorter, bleaker days of winter. Studies have linked HPV with human cervical cancer.
The results are somewhat surprising since, according to three centuries of birth records in this region of Holland, the highest rate of conceptions, and presumably heterosexual activity, occurs during the spring.
As an alternate explanation for the increased incidence of HPV infections seen during the summer months, scientists suggest quite a distinct biological process: suppressed immunity triggered by a specific band of ultraviolet rays found in sunlight.
"There is a clear relationship between the detection of HPV-positive cervical smears and extent of potential sunlight exposure," said William H. M. Hrushesky, M.D., VA Professor, Cell & Developmental Biology and Anatomy with the University of South Carolina School of Medicine; Senior Clinician Investigator at the WJB Dorn VA Medical Center; and Adjunct Professor of Epidemiology and Biostatistics in the Arnold School of Public Health, at the University of South Carolina, Columbia, South Carolina.
"We speculate that the well-known phenomenon of UV-mediated suppression of immune surveillance may be causally related to this unusual increase in active HPV infections during the summer months in northern countries such as Holland," he added.
In the course of their study, Hrushesky's team evaluated 920,359 consecutive screening Pap smears obtained between 1983 and 1998 in a well-established screening program, headquartered in Leiden. The population represented in this database constitutes about one-third of the adult female population of southern Holland. Daily sunlight data for the 192-months encompassed by the study was provided by the Royal Netherlands Meteorological Institute.
The results showed that the highest average monthly rate for both HPV infection and sunlight availability each occurred during the month of August for every year of the study. Over the entire span and during each year of the study, pathological evidence of infection was about twice as frequent from May through August, falling off abruptly every September.
"We conclude that the screening Pap smear detect ability of venereal HPV infection is rhythmic during each year," said Hrushesky. "This rhythmicity may occur, at least in part, in response to annual differences in sunlight exposure."
He added the results should generate future work to determine if sunlight exposure is a meaningful worldwide risk factor for the initiation and progression of cervical cancer.
"Confirming this relationship elsewhere may be important, because whatever risk is conferred by sunlight is, in principle, behaviorally avoidable," said Hrushesky.
Modulation of gene expression in murine lung tissue by tobacco smoke exposure: Abstract No. 1527
A genetic alteration that occurs 13 times more frequently in lung tissue of mice exposed to tobacco smoke has been identified by researchers at the Fox Chase Cancer Center in Philadelphia, Pa. The frequency of this genetic alteration and its role in estrogen metabolism could help researchers understand why women who smoke are more susceptible to lung cancer.
The researchers found 53 smoking-induced genetic alterations in mice exposed to tobacco smoke compared to unexposed controls. The most notable finding was the 13-fold overexpression of the enzyme CYP1B1.
"Our research demonstrates that this alteration isn't present in the lung tissue prior to tobacco exposure," said Fox Chase researcher Sibele I. Meireles, Ph.D., lead author of the research. "Since we know this alteration is present in human lung tissues, it could be a target for chemopreventive intervention in people at high risk for lung cancer – in particular, active smokers.
Because CYP1B1 activates estradiol, one of the body's natural estrogen hormones, this finding could also help researchers understand more about why female smokers are more susceptible to lung cancer than male smokers.
"The overexpression of CYP1B1 poses an interesting question about gender differences in the development of lung cancer," said Meireles. "We hadn't intended to look at gender differences in the study, but this finding about an enzyme so important to estrogen metabolism once again raises the issue of whether estrogen has a role in promoting lung cancer, as it does in breast and ovarian cancer."
Founded in 1907, the American Association for Cancer Research is a professional society of more than 22,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.