Archive

Posts Tagged ‘chemotherapy’

Novartis Cancer Drugs Fight Deadly Ebola Virus in Lab, Researchers Find


Two Novartis AG leukemia drugs, Gleevec and Tasigna, fought the deadly Ebola virus in laboratory experiments, suggesting the products could be used against a disease for which there are no treatments.

The two medicines stopped the release of viral particles from infected cells in lab dishes, a step that in a person may prevent Ebola from spreading in the body and give the immune system time to control it, researchers from the U.S. National Institute of Allergy and Infectious Diseases wrote in the journal Science Translational Medicine today.

There’s no cure and no vaccine for Ebola, a virus that causes high fever, diarrhea, vomiting and internal and external bleeding. Death can ensue within days, and outbreaks in Africa have recorded fatality rates of as much as 90 percent, according to the World Health Organization.

In some forms of leukemia, Gleevec and Tasigna reduce levels of a protein called Bcr-Abl that causes malignant white blood cells to multiply.

The researchers found that Ebola uses a related protein called c-Abl1 tyrosine kinase to regulate its own reproduction. They showed that by blocking c-Abl1, Tasigna may reduce the pathogen’s ability to replicate by as much as 10,000-fold. In addition to showing how the two drugs might be used to treat infected patients, the findings also suggest that new medicines could be developed to target c-Abl1, they wrote.

Gleevec and Tasigna, also known as imatinib and nilotinib, earned Basel, Switzerland-based Novartis a combined $5.45 billion in sales last year. Gleevec is sold as Glivec outside the U.S.

Source: Yahoo! Health

Advertisements

Cancer Drugs Could Halt Ebola Virus


Some cancer drugs used to treat patients with leukemia may also help stop the Ebola virus and give the body time to control the infection before it turns deadly, US researchers said on Wednesday.

The much-feared Ebola virus emerged in Africa in the 1970s and can incite a hemorrhagic fever which causes a person to bleed to death in up to 90 percent of cases.

While rare, the Ebola virus is considered a potential weapon for bioterrorists because it is so highly contagious, so lethal and has no standard treatment.

But a pair of well-known drugs that have been used to treat leukemia — known as nilotinib and imatinib — appear to have some success in stopping the virus from replicating in human cells.

Lead researcher Mayra Garcia of the US National Institute of Allergy and Infectious Diseases and colleagues reported their finding in Wednesday’s edition of the journal Science Translational Medicine.

By experimenting with human embryonic kidney cells in a lab, they found that a protein called c-Abl1 tyrosine kinase was a key regulator in whether the Ebola virus could replicate or not.

The leukemia drugs work by stopping that protein’s activity. In turn, a viral protein called VP40 stopped the release of viral particles from the infected cells, a process known as filovirus budding.

“Drugs that target filovirus budding would be expected to reduce the spread of infection, giving the immune system time to control the infection,” the study authors wrote.

“Our results suggest that short-term administration of nilotinib or imatinib may be useful in treating Ebola virus infections.”

Imatinib, which is marketed as Gleevec and Glivec, is used to treat chronic myelogenous leukemia in humans, a disease which is caused by dysregulation of c-Abl enzyme.

Nilotinib, also known as Tasigna, has been used in chronic myelogenous leukemia patients who are resistant to imatinib.

Both “have reasonable safety profiles, although some cardiac toxicity has been reported with long-term administration in a small number of patients,” the study added.

According to the UN’s World Health Organization (WHO), about 1,850 cases of Ebola, with some 1,200 deaths, have occurred since 1976.

The virus has a natural reservoir in several species of African fruit bat. Gorillas and other non-human primates are also susceptible to the disease.

Source: Bloomberg

Cancer Drugs Thwart Ebola In Lab

April 23, 2012 2 comments

The Ebola virus causes a hemorrhagic fever that can be deadly. (up)

Ebola is one virus you never want to catch. Ever.

After some aches and a fever, many infected people develop uncontrolled bleeding. The mortality rates from Ebola infection can run as high as 90 percent.

There’s no cure for Ebola. But a group of scientists is exploring whether some drugs already approved to treat cancer might help tame the virus.

Sounds wild. But there’s a reason — and now some evidence — to think it might work.

To reproduce, the Ebola virus needs the help of cells it invades. And a couple of cancer drugs tweak a human protein that new copies of the virus use to leave their host cells so they can infect others.

The tested drugs — Gleevec and Tasigna, both sold by Novartis — are called tyrosine kinase inhibitors. Tyrosine kinases are enzymes that put a phosphate group on a particular amino acid. Amino acids, as you might remember from high school biology, are the building blocks of proteins.

When a phosphate group gets attached to the right tyrosine block on the right protein, it changes the shape and function of the protein. And that might change everything when it comes to Ebola.

“Proteins are like little machines,” says Emory University’s Dan Kalman, one of the researchers. “As with a machine, they can be turned or turned off. The switch for turning things on or off is a modification. And one of those modifications is a phosphate group.”

In some cancers, the tyrosine kinases help trigger the uncontrolled division of cells. Gleevec and Tasigna help stop that.

When it comes to Ebola, the researchers think drugs like these could turn off a transport protein and could keep new viruses bottled up inside cells.

The Ebola lab work using collections of human cells was published in the latest issue of Science Translational Medicine. It showed that the drugs dramatically decrease the ability of Ebola to replicate. “The effect was quite pronounced,” Kalman told Shots.

And, if the theory holds, such a reduction might be enough to allow an infected person’s immune system to mop up the Ebola viruses.

“Ebola is a very nasty infection,” Kalman says. “The whole concept of containing the disease in a local group before it spreads all over the planet is something clearly we want to do.”

The next step will be to see if the drugs can make a difference in animal experiments.

Source: npr.org

Breakthrough in Malaria Treatment in the Run Up to World Malaria Day


Ahead of World Malaria Day (25 April), EU-funded researchers have discovered that drugs originally designed to inhibit the growth of cancer cells can also kill the parasite that causes malaria. They believe this discovery could open up a new strategy for combating this deadly disease, which, according to World Health Organisation statistics, infected around 225 million and killed nearly 800,000 people worldwide in 2009.

Efforts to find a treatment have so far been hampered by the parasite’s ability to quickly develop drug resistance. The research involved four projects funded by the EU (ANTIMAL, BIOMALPAR, MALSIG and EVIMALAR) and was led by laboratories in the UK, France and Switzerland with partners from Belgium, Germany, Denmark, Greece, Spain, Italy, Netherlands, Portugal, and Sweden, along with many developing nations severely affected by malaria.

Research, Innovation and Science Commissioner Máire Geoghegan-Quinn said: “This discovery could lead to an effective anti-malaria treatment that would save millions of lives and transform countless others. This demonstrates yet again the added value both of EU-funded research and innovation in general and of collaboration with researchers in developing countries in particular. The ultimate goal is the complete eradication of the global scourge of malaria and collaborative work across many borders is the only way of confronting such global challenges effectively.”

Cancer drugs to kill malaria parasite

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites reproduce in the liver, and then infect and multiply in red blood cells. Joint research led by EU-funded laboratories at the Inserm-EPFL Joint Laboratory, Lausanne, (Switzerland/France), Wellcome Trust Centre for Molecular parasitology, University of Glasgow (Scotland), and Bern University (Switzerland) showed that, in order to proliferate, the malaria parasite depends upon a signalling pathway present in the host’s liver cells and in red blood cells. They demonstrated that the parasite hijacks the kinases (enzymes) that are active in human cells, to serve its own purposes. When the research team used cancer chemotherapy drugs called kinase inhibitors to treat red blood cells infected with malaria , the parasite was stopped in its tracks.

A new strategy opens up

Until now the malaria parasite has managed to avoid control by rapidly developing drug resistance through mutations and hiding from the immune system inside liver and red blood cells in the body of the host, where it proliferates. The discovery that the parasite needs to hijack some enzymes from the cell it lives in opens up a whole new strategy for fighting the disease. Instead of targeting the parasite itself, the idea is to make the host cell environment useless to it, by blocking the kinases in the cell. This strategy deprives the parasite of a major modus operandi for development of drug resistance.

Several kinase-inhibiting chemotherapy drugs are already used clinically in cancer therapy, and many more have already passed phase-I and phase II clinical trials. Even though these drugs have toxic side-effects, they are still being used over extended periods for cancer treatment. In the case of malaria, which would require a shorter treatment period, the problem of toxicity would be less acute. Researchers are proposing therefore that these drugs should be evaluated immediately for anti-malarial properties, drastically reducing the time and cost required to put this new malaria-fighting strategy into practice.

The next steps will include mobilising public and industrial partners to verify the efficacy of kinase inhibitors in malaria patients and to adjust the dose through clinical trials, before the new treatments can be authorised and made available to malaria patients worldwide.

Journal Reference:

  1. Audrey Sicard, Jean-Philippe Semblat, Caroline Doerig, Romain Hamelin, Marc Moniatte, Dominique Dorin-Semblat, Julie A. Spicer, Anubhav Srivastava, Silke Retzlaff, Volker Heussler, Andrew P. Waters, Christian Doerig. Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytesCellular Microbiology, 2011; DOI:10.1111/j.1462-5822.2011.01582.x
  2. The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by European Commission, Research & Innovation DG, viaAlphaGalileo.

Malaria’s Weakest Link: Class of Chemotherapy Drugs Also Kills the Parasite That Causes Malaria


A group of researchers from EPFL’s Global Health Institute (GHI) and Inserm (Institut National de la Santé et de la Recherche Médicale, the French government agency for biomedical research) has discovered that a class of chemotherapy drugs originally designed to inhibit key signaling pathways in cancer cells also kills the parasite that causes malaria. The discovery could quickly open up a whole new strategy for combating this deadly disease.

The research, published online in the journal Cellular Microbiology, shows that the malaria parasite depends upon a signaling pathway present in the host — initially in liver cells, and then in red blood cells — in order to proliferate. The enzymes active in the signaling pathway are not encoded by the parasite, but rather hijacked by the parasite to serve its own purposes. These same pathways are targeted by a new class of molecules developed for cancer chemotherapy known as kinase inhibitors. When the GHI/Inserm team treated red blood cells infected with malaria with the chemotherapy drug, the parasite was stopped in its tracks.

Professor Christian Doerig and his colleagues tested red blood cells infected with Plasmodium falciparum parasites and showed that the specific PAK-MEK signaling pathway was more highly activated in infected cells than in uninfected cells. When they disabled the pathway pharmacologically, the parasite was unable to proliferate and died. Applied in vitro, the chemotherapy drug also killed a rodent version of malaria (P. berghei), in both liver cells and red blood cells. This indicates that hijacking the host cell’s signaling pathway is a generalized strategy used by malaria, and thus disabling that pathway would likely be an effective strategy in combating the many strains of the parasite known to infect humans.

Malaria infects 250 million and kills 1-3 million people every year worldwide. Efforts to find a treatment have been marred by the propensity of the parasite to quickly develop drug resistance through selection of mutations. Once in the body, it hides from the immune system inside liver and blood cells, where it proliferates. The discovery that the parasite hijacks a signaling pathway in the host cell opens up a whole new strategy for fighting the disease. Instead of targeting the parasite itself, we could make the host cell environment useless to it, thus putting an end to the deadly cycle. Because this strategy uniquely targets host cell enzymes, the parasite will be deprived of a major modus operandi for development of drug resistance — selection of mutations in the drug target.

Several kinase-inhibiting chemotherapy drugs are already used clinically, and many more have passed stage 1 and stage 2 clinical trials. Even though these drugs have toxic effects, they are still being used or considered for use over extended periods for cancer treatment. Using them to combat malaria would involve a much shorter treatment period, making the problem of toxicity less acute. The authors of the study suggest evaluating these drugs for antimalarial properties, thus drastically reducing the time and cost required to put this new malaria-fighting strategy into practice.

Journal Reference:

  1. Audrey Sicard, Jean-Philippe Semblat, Caroline Doerig, Romain Hamelin, Marc Moniatte, Dominique Dorin-Semblat, Julie A. Spicer, Anubhav Srivastava, Silke Retzlaff, Volker Heussler, Andrew P. Waters, Christian Doerig. Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytesCellular Microbiology, 2011; DOI:10.1111/j.1462-5822.2011.01582.x
  2. The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ecole Polytechnique Federale de Lausanne (EPFL), viaAlphaGalileo.