Radioactive Bacteria:1 – Pancreatic Cancer:0

pancreatic cancer facesYears ago, when I was just starting my healthcare career, I worked with a team specializing in the management of patients with pancreatic cancer.  Despite the dedication and compassion of our team, revolutionary surgical techniques, and top-notch palliative care, all too often our patients died. Even today, some 30 years later, pancreatic cancer has a poor prognosis. It’s seldom detected in its early stages, and often spreads rapidly. Signs and symptoms frequently don’t appear until the disease is advanced and surgical removal isn’t possible.

Pancreatic cancer touches so many people. It killed my childhood mentor and one of my best friends. It’s taken the lives of many household names, from astronauts to actors, entrepreneurs to opera singers.  For example, Patrick Swayze, Randy Pausch, Luciano Pavarotti, Dizzy Gillespie, Count Basie, Michael Landon, Joan Crawford, Sally Ride and of course, Apple CEO – Steve Jobs.

So, I was excited to hear about new research into a targeted anti-cancer therapy that promised limited side effects. The study, published April 22 in the Proceedings of the National Academy of Sciences found that treating mice with an attenuated, radioactively labeled bacteria –  Listeria monocytogenes – drastically reduced the number of metastases, while leaving normal tissue unscathed.

The notion of using bacteria to attack tumors is not new. Robert Hoffman, a cancer biologist at the University of California, San Diego, who was not involved in the current study, has shown that Salmonella can kill mouse cancer cells, including metastases of pancreatic cancer.

Other research has shown that a Listeria strain known as CRS-207 has the ability to stimulate an immune response in Phase 1 and 2 trials.

listeria.monocytogenesIn the new study, researchers at Albert Einstein College of Medicine have paired this technique with a radioactive isotope to selectively kill tumor cells, focusing on the metastatic cells that so often elude current treatment regimens.

It’s this combination of approaches that synergistically target metastases, that’s new. Claudia Gravekamp, an immunologist at Albert Einstein College of Medicine who led the study with nuclear medicine researcher Ekaterina Dadachova had previously demonstrated that an attenuated strain of Listeria monocytogenes, a type of bacterium that penetrates host cells during infection, selectively killed breast cancer cells without damaging normal tissue. The bacteria’s ability to target only diseased cells raised the possibility that it could be used to treat metastatic cancer by both directly killing cells and by carrying anti-tumor therapies—like radiation—to cancer cells.

pancreatic_cancerGravekamp and Dadachova tested the bacteria against highly metastatic pancreatic cancer in mice. First, they demonstrated that the bacteria proliferated well in the animals’ metastases, but poorly in the primary tumor, and not at all in normal tissues like spleen, suggesting the bacteria would be good candidates for delivering a therapy to far-flung metastases.

Then, the researchers armed the Listeria with the Rhenium-188, a radionuclide that kills cells by releasing DNA-damaging. Sure enough, regular injections of the Rhenium-188 labeled bacteria decreased metastases by 90% versus controls.

While this implies that bacteria have to potential to be used to deliver therapeutic radiation doses to metastases, the bacteria were administered before metastases were established, notes Donald Buchsbaum, a radiation biologist at the University of Alabama at Birmingham who was not involved in the study.  “So to some extent it’s a prevention model.”

Future work will need to focus on targeting established metastases, possibly by exploring other radioisotope options.  Gravekamp and Dadachova are currently refining their protocol and examining alternative radioisotopes to achieve a 100% reduction of metastases, but have high hopes for their bacteria.

Though primary tumors are often removed surgically, even small pieces left behind can produce new metastases. It might be possible that one day radioactive Listeria could be part of an “early second-line treatment after surgery to prevent further metastases,” says Gravekamp.

ListeriaWhich is great news in the war against cancer and not a bad deal for the Listeria bacteria which normally gets a bad rap for causing the infection listeriosis  – the leading cause of death among food-borne bacterial pathogens – responsible for approximately 2,500 illnesses and 500 fatalities annually in the United States.

Exciting stuff!

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Stopping Herpes From Going Viral

herpes-simplex-virusOn Wednesday SRxA’s Word on Health reported on a link between memory loss and cognitive decline and the herpes virus.  Today, we bring a glimmer of hope to the 65% – 90% of people worldwide affected with either type 1 or Type 2 herpes simplex virus.

In the US alone, it’s estimated that nearly 60 percent of U.S. men and women between the ages of 14 and 49 carry the HSV-1 virus, while >16.2% are infected with herpes simplex virus type 2 (HSV-2).

HSV-2 is a lifelong and incurable infection that can cause recurrent and painful genital sores and can make those infected with the virus two-to-three times more likely to acquire HIV.

Now, according to a study just published in the Journal of the Federation of American Societies for Experimental Biology (FASEB), researchers from Albert Einstein College of Medicine of Yeshiva University have discovered a novel strategy for preventing, treating or suppressing herpes virus infections.

molecule_key_chains-We’ve essentially identified the molecular “key” that herpes viruses use to penetrate cell membranes and infect cells of the human body,” said Betsy Herold, MD of The Children’s Hospital at Montefiore.

Dr. Herold and her colleagues had previously shown that infection by the herpes viruses depends on calcium released within the cells. In this study, they found that calcium release occurs because the viruses activate a critical cell-signaling molecule called Akt [also known as Protein Kinase B (PKB) ] at the cell membrane.

As part of their investigation of Akt’s role in herpes infections, the researchers took laboratory cultures of human cell and mixed them for 15 minutes with four different drugs known to inhibit Akt. The cells were then exposed for one hour to herpes simplex virus 2.

The drugs tested were:

  • MK-2206 – an experimental drug being studied as adjunct therapy for cancer
  • Akt Inhibitor VIII
  • Miltefosine, a drug licensed for treatment of leishmaniasis and other protozoal infections
  • Perifosine, an experimental agent in phase 3 clinical trials for treatment of several cancers

STOPAll four of the drugs significantly inhibited HSV infection in each of the cell types.  Miltefosine was the most potent and reduced viral plaques by 90% in all cell types.

By contrast, cells not pre-treated with the Akt inhibitors were readily infected on exposure to the virus.

For people infected with herpes, the drug acyclovir helps prevent herpes outbreaks from recurring and lowers the risk of transmitting the infection to others,” said Dr. Herold. “But some people have herpes infections that don’t respond to acyclovir, and unfortunately there is no effective vaccine. So new approaches for suppressing and treating herpes infections are badly needed, and our findings indicate that inhibiting Akt should be a useful therapeutic strategy to pursue.”

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Tick-tock, tick-tock…we’ll explain your biological clock!

If, like me, you’re one of those people who wake up at exactly the same time every morning without ever setting an alarm clock you’ve no doubt had people ask how you do it? Well, now you can tell them!

According to researchers at the Salk Institute for Biological Studies it’s all in our genes.  Recently they identified a gene responsible for starting our biological clock every morning.

The biological clock ramps up our metabolism early each day, initiating important physiological functions that tell our bodies that it’s time to rise and shine. Discovery of this new gene and the mechanism by which it starts the clock everyday may help explain the genetic underpinnings of sleeplessness, aging, and chronic illnesses such as cancer and diabetes.  Better still, it could eventually lead to new therapies for these illnesses.

The body is essentially a collection of clocks,” says Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory, who led the research along with Luciano DiTacchio, a post-doctoral research associate. “We roughly knew what mechanism told the clock to wind down at night, but we didn’t know what activated us again in the morning. Now that we’ve found it, we can explore more deeply how our biological clocks malfunction as we get older and develop chronic illness.”

In a report just published in Science, the Salk researchers and their collaborators at McGill University and Albert Einstein College of Medicine describe how the gene encodes a protein that serves as an activation switch in the biochemical circuit that maintains our circadian rhythm. The discovery fills in a missing link in the molecular mechanisms that control our daily wake-sleep cycle.

It turns out that the molecular bugle call for cells and organs to get back to work each morning is an enzyme known as JARID1a.

Now that scientists understand why we wake each day, they can explore the role of JARID1a in sleep disorders and chronic diseases, possibly using it as a target for new drugs.

SRxA’s Word on Health looks forward to these developments and to a good night’s sleep!