From EurekAlert!:

Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells. Two new studies advance that argument and demonstrate how shielding lung cancer cells from opiates reduces cell proliferation, invasion and migration in both cell-culture and mouse models.

The reports highlight the mu opiate receptor, where morphine works, as a potential therapeutic target.

"If confirmed clinically, this could change how we do surgical anesthesia for our cancer patients," said Patrick A. Singleton, PhD, assistant professor of medicine at the University of Chicago Medical Center and principal author of both studies. "It also suggests potential new applications for this novel class of drugs which should be explored."

The proposition that opiates influence cancer recurrence, prompted by several unrelated clinical and laboratory studies, has gradually gained support. It started with a 2002 palliative-care trial in which patients who received spinal rather than systemic pain relief survived longer. Soon after that, Singleton's colleague, anesthesiologist Jonathan Moss, noticed that several cancer patients receiving a selective opiate blocker in a compassionate-use protocol lived longer than expected. Two recent retrospective studies found that breast and prostate cancer patients who received regional rather than general anesthesia had fewer recurrences. In February, 2009, the Anesthesia Patient Safety Foundation highlighted the issue.

Moss's palliative-care patients were taking methylnaltrexone (MNTX), developed in the 1980s for opiate-induced constipation by the late University of Chicago pharmacologist Leon Goldberg. Goldberg modified an established drug that blocks morphine so that it could no longer cross the protective barrier that surrounds the brain. So MNTX blocks morphine's peripheral side effects but does not interfere with its effect on pain, which is centered in the brain. It won FDA approval in 2008.

"These were patients with advanced cancer and a life expectancy of one to two months," Moss recalled, "yet several lived for another five or six. It made us wonder whether this was just a consequence of better GI function or could there possibly be an effect on the tumors."

So Singleton, Moss and colleagues, including Joe G.N. Garcia, MD, professor of medicine at the University of Chicago, began a series of studies looking at the many peripheral effects of opiates and the potential benefits of blocking those effects.

In laboratory studies, morphine can directly boost tumor-cell proliferation and inhibit the immune response. The researchers found that opiates also promote angiogenesis, the growth of new blood vessels, and decrease barrier function--effects that may exacerbate diseases involving vascular leakiness including acute lung injury in experimental models. In a surgical setting, decreased barrier function may make it easier for tumors to invade tissue and spread to distant sites. Increased angiogenesis helps cancers thrive in a new site.

Using two different models of non-small cell lung cancer, the research teams showed that MNTX inhibited the tumor-promoting effects of opiates. In one study, using bronchioloalveolar carcinoma cells, MNTX blocked oncogenic signaling and prevented tumor-cell proliferation and migration.

In the other study, using Lewis lung carcinoma cells, mice without the mu opiate receptor did not develop the tumors that normal mice did when injected with cancer cells. The researchers further showed that MNTX reduced proliferation of cancer cells by 90 percent in normal mice. It also prevented invasion in cell culture and tumor growth and metastasis in mice.

The opioid receptor promotes Lewis lung cancer tumor growth, angiogenesis and metastasis, the authors conclude in a summary of the second study. "Methylnaltrexone attenuates these oncogenic effects."

From EurekAlert!:

Blood cholesterol levels improved, but arteries do not show it

The routine prescription of extended-release niacin, a B vitamin (1,500 milligrams daily), in combination with traditional cholesterol-lowering therapy offers no extra benefit in correcting arterial narrowing and diminishing plaque buildup in seniors who already have coronary artery disease, a new vascular imaging study from Johns Hopkins experts shows.

In tests on 145 Baltimore-area men and women with existing atherosclerosis, all over age 65, researchers found that after 18 months of drug therapy, reductions in arterial wall thickness were measurably no different between the half who took dual niacin-statin therapy and the rest who remained on statin therapy alone.

The results were the same whether they took any one of the three leading statin medications: atorvastatin (Lipitor), simvistatin (Zocor) or rosuvastatin (Crestor). Seniors on dual drug therapy had an average 5.4 cubic millimeter per month scale back in plaque buildup in the main neck artery, while those taking just a cholesterol-lowering statin medication came down by 4 cubic millimeters per month, a difference that researchers say is not statistically significant.

The team will present its findings Nov. 18 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando.

According to senior study investigator and Johns Hopkins cardiologist João Lima, M.D., the lack of any discernible advantage occurred despite promising gains in bad (LDL) and good (HDL) blood cholesterol levels in those taking vitamin B niacin. Results showed that in the group taking both niacin and a statin, blood levels of LDL-cholesterol fell 5 percent more than in the group taking only statin medications. And levels of HDL jumped 14 percent more than in the statin-only group.

"Our findings tell us that improved cholesterol levels from taking combination vitamin B niacin and statin therapy do not necessarily translate into observable benefits in reversing and stalling carotid artery disease," says Lima, a professor of medicine and radiology at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. "This does not mean that niacin therapy may not have other cardiovascular benefits, but any such benefits are independent of reducing the amount of plaque buildup and patients should be aware of that."

"Our recommendation to physicians is that current national treatment guidelines, which recommend mainly statin therapy tailored to the severity of atherosclerosis for preventing arteries from reclogging and narrowing, appear to be sufficient and accurate for physicians and patients to follow," says Lima.

However, Lima cautions that an ongoing national study of the long-term vascular benefits of dual therapy and whether extended-release niacin, also known as nicotinic acid, lowers death rates from heart disease should provide more definitive data. Hopkins is participating in that research, as well. He also notes that extended-releases niacin used in this study is a prescription medication, and that it is not sold over the counter like many other vitamin B products.