BRONX, NY — Researchers at Albert Einstein College of Medicine of Yeshiva University have developed a therapy for pancreatic cancer that uses Listeria bacteria to selectively infect tumor cells and deliver radioisotopes into them. The experimental treatment dramatically decreased the number of metastases (cancers that have spread to other parts of the body) in a mouse model of highly aggressive pancreatic cancer without harming healthy tissue. The study was published in the online edition of the Proceedings of the National Academy of Sciences.

“We’re encouraged that we’ve been able to achieve a 90 percent reduction in metastases in our first round of experiments,” said co-senior author Claudia Gravekamp, Ph.D., associate professor of microbiology & immunology at Einstein who studies new approaches to treating metastatic cancer. “With further improvements, our approach has the potential to start a new era in the treatment of metastatic pancreatic cancer.”

Pancreatic cancer is among the deadliest of cancers, with a five-year survival rate of only 4 percent. The National Cancer Institute predicts that this year, 45,220 new cases of pancreatic cancer will be diagnosed and 38,460 people will die from the disease. Pancreatic cancer confined to the pancreas can be treated through surgery. But early pancreatic cancer is difficult to detect, since it rarely causes noticeable signs or symptoms. Most pancreatic cancer cases are diagnosed only after the cancer has spread (metastasized), typically resulting in jaundice, pain, weight loss and fatigue. But there is no cure for metastatic pancreatic cancer, and treatment focuses mainly on improving quality of life.

Several years ago, scientists observed that an attenuated (weakened) form of Listeria monocytogenes can infect cancer cells, but not normal cells. In a 2009 study, Dr. Gravekamp discovered the reason: The tumor microenvironment suppresses the body’s immune response, allowing Listeria to survive inside the tumors. By contrast, the weakened bacteria are rapidly eliminated in normal tissues. (Listeria in its wild form causes foodborne illnesses, particularly in immunocompromised people.)

Scientists later showed that Listeria could be harnessed to carry an anti-cancer drug to tumor cells in laboratory cultures, but this concept was never tested in an animal model. These findings prompted Dr. Gravekamp to investigate Listeria-tumor interactions and how Listeria could be used to attack cancer cells.

The idea of attaching radioisotopes (commonly used in cancer therapy) to Listeria was suggested by Ekaterina Dadachova, Ph.D., professor of radiology and of microbiology & immunology at Einstein and the paper’s co-senior author. Dr. Dadachova, who is also the Sylvia and Robert S. Olnick Faculty Scholar in Cancer Research, is a pioneer in developing radioimmunotherapies —patented treatments in which radioisotopes are attached to antibodies to selectively target cells including cancer cells, microbes or cells infected with HIV. When the antibodies bind to antigens that are unique to the cells being targeted, the radioisotopes emit radiation that selectively kills the cells.

Working together, Drs. Gravekamp and Dadachova coupled a radioactive isotope called rhenium to the weakened Listeria bacteria. “We chose rhenium because it emits beta particles, which are very effective in treating cancer,” said Dr. Dadachova. “Also, rhenium has a half-life of 17 hours, so it is cleared from the body relatively quickly, minimizing damage to healthy tissue.”

Mice with metastatic pancreatic cancer were given intra-abdominal injections of the radioactive Listeria once a day for seven days, followed by a seven-day “rest” period and four additional daily injections of the radioactive bacteria. After 21 days, the scientists counted the number of metastases in the mice. The treatment had reduced the metastases by 90 percent compared with untreated controls. In addition, the radioactive Listeria had concentrated in metastases and to a lesser extent in primary tumors but not in healthy tissues, and the treated mice did not appear to suffer any ill effects.

The treatment may have the potential for clearing an even higher percentage of metastases. “We stopped the experiment at 21 days because that’s when the control mice start dying,” said Dr. Dadachova. “Our next step is to assess whether the treatment affects the animals’ survival.”

“At this point, we can say that we have a therapy that is very effective for reducing metastasis in mice,” Dr. Gravekamp noted. “Our goal is to clear 100 percent of the metastases, because every cancer cell that stays behind can potentially form new tumors.” The researchers expect the treatment could be improved by fine-tuning the treatment schedule, using higher doses of radiation, or by piggybacking additional anti-cancer agents onto the bacteria. Einstein has filed a patent application related to this research that is currently available for licensing to partners interested in further developing and commercializing this technology.

- MFP Wire Services
- 04-24-2013

ANN ARBOR, MI — Alternative therapies such as aerobic exercise, resistance or strength training, and isometric hand grip exercises may help reduce your blood pressure, according to the American Heart Association.

In a new scientific statement published in its journal Hypertension, the association said alternative approaches could help people with blood pressure levels higher than 120/80 mm Hg and those who can’t tolerate or don’t respond well to standard medications.

However, alternative therapies shouldn’t replace proven methods to lower blood pressure — including physical activity, managing weight, not smoking or drinking excess alcohol, eating a low sodium balanced diet and taking medications when prescribed, the association said.

High blood pressure — a major risk factor for heart attack and stroke — affects more than 26 percent of the population worldwide and contributes to more than 13 percent of premature deaths.

An expert panel assessed three alternative remedy categories: exercise regimens; behavioral therapies such as meditation; and non-invasive procedures or devices including acupuncture and device-guided slow breathing. The panel did not review dietary and herbal treatments.

“There aren’t many large well-designed studies lasting longer than a few weeks looking at alternative therapies, yet patients have a lot of questions about their value,” said Robert D. Brook, M.D., Chair of the panel and an associate professor of medicine at the University of Michigan in Ann Arbor. “A common request from patients is, ‘I don’t like to take medications, what can I do to lower my blood pressure?’ We wanted to provide some direction.”

The alternative therapies rarely caused serious side effects and posed few health risks, but the analysis revealed some approaches were more beneficial than others and could be part of a comprehensive blood pressure-lowering treatment plan.

Brook and colleagues reviewed data published in 2006-11, including 1,000 studies on behavioral therapies, non-invasive procedures and devices, and three types of exercise (aerobic, resistance or weight training and isometric exercises, most commonly handgrip devices).

The studies also examined the effects of yoga, different styles of meditation, biofeedback methods, acupuncture, device-guided breathing, relaxation and stress reduction techniques.

The panel found:
•All three types of exercise reduced blood pressure. Walking programs provided modest benefit while, somewhat surprisingly, four weeks of isometric hand grip exercises resulted in some of the most impressive improvements – a 10 percent drop in systolic and diastolic blood pressure. However, isometric exercise should be avoided among people with severely-uncontrolled high blood pressure (180/110 mm Hg or higher).
•Behavioral therapies such as biofeedback and transcendental meditation may help lower blood pressure by a small amount. However, there’s not sufficient data to support using other types of meditation.
•Strong clinical evidence is also lacking to recommend yoga and other relaxation techniques for reducing blood pressure.
•There isn’t enough evidence to recommend acupuncture for lowering blood pressure, particularly given the complexities involved in employing this treatment. However, device-guided slow breathing did prove effective in lowering blood pressure when performed for 15-minute sessions three to four times a week.

“Most alternative approaches reduce systolic blood pressure by only 2-10 mm Hg; whereas standard doses of a blood pressure-lowering drug reduce systolic blood pressure by about 10-15 mm Hg,” Brook said. “So, alternative approaches can be added to a treatment regimen after patients discuss their goals with their doctors.”

Given the global public health burden of high blood pressure more research is needed to look at the long-term cardiovascular health impact of alternative therapies and the effects of combining them together or adding them to other proven lifestyle measures, Brook said.

- MFP Wire Services
- 04-23-2013

SYDNEY, NEW SOUTH WALES, AUSTRALIA – The proportion of young women diagnosed with genital warts in Australia has seen a significant decline thanks to the HPV vaccine, suggests a paper published at Britsish Medical Journal online.

In 2007, Australia became one of the first countries to implement a nationally funded quadrivalent human papillomarivus (HPV) vaccination programme for girls and young women, which offers free vaccinations to girls aged 12-13 years in schools. From 2007 – 2009 there were a further two catch-up programmes: for 13-18 year olds and 18-26 year olds. The vaccine protects against the types of HPV that cause 90% of genital warts, as well as the cancer-causing HPV types.

Early data suggest two years after the vaccine was introduced, the proportion of genital warts diagnoses declined by 59% in vaccine eligible women aged 12-26 years and by 39% in heterosexual men. In the same two year period, there was a significant decrease in the incidence of high-grade cervical abnormalities in females under 18 years.

Researchers from the University of New South Wales and Melbourne Sexual Health Centre therefore looked to describe the ongoing population effect of the vaccination programme, five years after it was established.

Data were taken from eight sexual health services across Australia. Australian-born patients who attended any of the services for the first time between January 2004 and December 2011 were included in the analysis.

The study period was divided into the pre-vaccination period (2004-2007) and the vaccination period (2007-2011). The findings were also separated into three age groups: those under 21, 21-30 year olds and those 30 and older.

Between 2004 and 2011, 85,770 patients were seen for the first time. Of these, 7686 (9%) were diagnosed with genital warts. Overall, the proportion of women diagnosed with genital warts increased during the pre-vaccination period from 9% in 2004 to 10% in 2007, which then decreased in the vaccination period to 3%. In men the proportion remained relatively stable in the pre-vaccination period from 13% in 2004 to 12% in 2007 and then decreased during the vaccination period to 7%.

In women under 21, results showed that 9% were diagnosed with genital warts in 2004 and 11% in 2007. During the vaccination period the proportion declined dramatically to 0.85% (13 cases altogether).

In 2011, none of the vaccinated women under 21 were diagnosed with genital warts. In the same year, 7% of unvaccinated women under 21 (out of 161) were diagnosed with genital warts.

Significant declines in genital warts were also seen in women aged 21-30 and heterosexual men under 21 and aged 21-30 years, during the vaccination period.

No significant trends were seen in women or heterosexual men over the age of 30.

The authors say this result in men is probably due to herd-immunity (immunity that occurs when the vaccination of a portion of the population provides a measure of protection for individuals who have not developed immunity).

In an accompanying editorial, Clinical Director Simon Barton and Sexual Health and HIV Consultant Colm O’Mahony say that it is “worth celebrating the extraordinary success” of this public health achievement, adding that it will probably have a major impact on the cost of sexual healthcare. They hope that this trend will be mirrored in the UK which will help reduce the workload in sexual health clinics but say it is also important to vaccinate boys. They say these are “exciting times in the science of HPV” and we can look forward to the “virtual elimination of genital warts […] most genital cancers and some 60% of head and neck cancers”.

In this week’s BMJ podcast, Professor Donovan talks about the HPV vaccination and the paper’s findings. He says that the researchers found the fact that there were no cases of genital warts in 2011 was “striking”.

- MFP Wire Services
- 04-22-2013