Tick saliva could hold cancer cure: Brazilian scientists

View of an Amblyomma cajennense. Brazilian reasearchers have identified a protein in the saliva of the South American tick that apparently reduces and can even eradicate cancerous cells while leaving healthy cells alone.

SAO PAULO (AFP) - - It may be one of nature's repulsive little blood-sucking parasites, but the humble tick could yield a future cure for cancers of the skin, liver and pancreas, Brazilian researchers have discovered.

They have identified a protein in the saliva of a common South American tick, Amblyomma cajennense, that apparently reduces and can even eradicate cancerous cells while leaving healthy cells alone.

"This is a radical innovation," said Ana Marisa Chudzinski-Tavassi, the molecular biologist at the Instituto Butantan in Sao Paulo who is leading the research.

"The component of the saliva of this tick... could be the cure for cancer," she told AFP.

She said she stumbled on the properties of the protein, called Factor X active, while testing the anti-coagulant properties of the tick's saliva -- the way it stops blood thickening and clotting so the tick can keep gorging itself on its host.

The protein shares some characteristics with a common anti-coagulant called TFPI (Tissue Factor Pathway Inhibitor), specifically a Kunitz-type inhibitor which also has been shown to interfere with cell growth.

A theory that the protein might have an effect on cancerous cells led to laboratory tests on cell cultures -- which exceeded all expectations.

"To our surprise it didn't kill normal cells, which were also tested," Chudzinski-Tavassi said. "But it did kill the tumorous cells that were being analyzed."

In her modest lab in the institute, housed in a rundown building, a line of immobile bloated ticks could be seen lined up with straws under their heads.

The small amounts of saliva captured that way was reproduced many times over in yeast vats so that tests could be carried out on lab rats with cancer.

The results have been more than promising.

"If I treat every day for 14 days an animal's tumor, a small tumor, this tumor doesn't develop -- it even regresses. The tumor mass shrinks. If I treat for 42 days, you totally eliminate the tumor," the scientist said.

Producing a medicine from the find, though, will require years of clinical tests and a significant financial investment -- neither of which Brazil is geared to provide.

Chudzinski-Tavassi has applied for a patent on the tick protein, and is presenting her team's discovery in medical journals and conferences around the world.

But she says moving beyond her lab "proof of concept" will be frustratingly difficult.

"To discover this is one thing. To turn it into a medicine is a whole other thing entirely," she said. link....

Swine flu looms over global economic recovery

Swine flu looms over global economic recovery

WASHINGTON (AFP) - – Markets around the globe have started to celebrate the first signs of economic recovery, but experts have warned that a possible resurgent swine flu could still take a toll of productivity and financial systems.
First reported four months ago, the new A(H1N1) influenza virus spread by June into a global pandemic with some 1,800 deaths and now affects more than 170 countries, according to the World Health Organization.
Though the number of cases reported to WHO has topped 182,000, the United Nations health watchdog cautions the real number is higher because countries are no longer required to test and report individual cases.
Health officials are gearing up for a resurgence in cases as the northern hemisphere enters winter. So far swine flu infections generally have been relatively mild, with typical flu symptoms that last about a week.
However, the pandemic virus could mutate into a more deadly form. Officials are projecting a shortfall in vaccines being rushed to market in hopes of warding off a potential global health disaster.
Faced with the unpredictable nature of flu viruses, economists say it is difficult to assess the impact of swine flu on the delicate global economic recovery taking shape amid the worst world recession since World War II.
"As the severity of A(H1N1) is so far not severe, we would not expect the magnitude of the shock to the economy to be large relative to GDP (gross domestic product)," said Simonetta Nardin, a spokeswoman at the International Monetary Fund.
"The main threat to financial stability is the risk that high levels of absenteeism could lead to breakdowns in the functioning of key financial systems," she told AFP.
School closures would exacerbate absenteeism, further reducing workplace productivity.
Nardin said that the effects of swine flu on global financial stability and the world economy would be covered in future updates of the IMF's Global Financial Stability Report and World Economic Outlook (WEO), "as warranted by events."
World Bank experts have estimated the potential economic costs of a global influenza pandemic could range from 0.7 percent to 4.8 percent of global GDP depending on the severity of the outbreak.
The lower estimate was benchmarked on the Hong Kong flu of 1968-1969, while the upper bound was based on the devastating 1918-1919 Spanish flu, which infected an estimated one third of the world's population and is estimated to have caused 50 million or more deaths.
Based on the IMF estimate of 2009 global GDP of 54.863 trillion dollars, the swine flu pandemic, using the World Bank simulation, could cost the global economy between 384 billion dollars and 2.633 trillion dollars.
"In the case of a serious flu, 70 percent of the overall economic cost would come from absenteeism and efforts to avoid infection," World Bank experts wrote in the Global Development Finance report released in June.
"Generally speaking, developing countries would be hardest hit, because higher population densities, relatively weak health care systems, and poverty accentuate the economic impacts in some countries."
The swine flu virus was first identified in California in late April and officials linked the new virus to an outbreak of illnesses in Mexico.Mexico has borne the brunt of the economic costs of the pandemic, particularly in the transportation and tourism sectors.
"While we expect these effects to dissipate quickly following the peak of the epidemic in May, we estimate that the swine flu epidemic will have lowered GDP growth in Mexico on the order of 0.5 to 1.0 percent in 2009," an IMF official said, on condition of anonymity.
"These effects are already factored into our baseline outlook for growth in Mexico of negative 7.3 percent in 2009, as released in the July 2009 WEO," the official said. link....

Lung cancer genetics unravelled

Smoking is the cause of most lung cancers.

The genetics underpinning a smoker's risk of developing lung cancer have been further unpicked by UK scientists.
Three areas of DNA were found to be linked with lung cancer risk in smokers, two of them influencing the type of cancer which develops.
It supports previous studies which have suggested a family link, even after taking smoking into account, a report in the Cancer Research journal says.
Smoking is responsible for nine out of 10 cases of lung cancer.
The Institute of Cancer Research team compared the DNA of 1,900 lung cancer patients and 1,400 healthy individuals.

Information gathered on areas of genetic risk was then tested further in another 2,000 patients with lung cancer and a similar number of healthy volunteers.
Specific differences associated with lung cancer risk were found on chromosomes 5, 6 and 15.
Those with certain genetic changes on chromosome 5 were more likely to get a type of cancer called adenocarcinoma and the region highlighted on chromosome 6 seemed to influence whether a patient developed adenocarcinoma or another type called squamous cell carcinoma.
On chromosome 15, they pinpointed two independent sites that have a role in whether or not a smoker develops lung cancer.
These areas of the genome contain a family of genes that influence smoking behaviour but also cell growth and cell death.Current or former smokers who carry one copy of each of these genetic variants increase their risk of lung cancer by 28%.
That increases to 80% in smokers who carry two copies.Those who had the genetic changes but did not smoke had no increased risk of lung cancer.
Trigger
Study leader Professor Richard Houlston said the findings confirmed earlier research.
"The next step is to dig deeper to pinpoint which gene, or genes in these regions, cause the increased risk of developing lung cancer and how they actually trigger this increase."
Dr Lesley Walker, director of cancer information at Cancer Research UK who partly funded the research, said smoking was responsible for the vast majority of lung cancers.
"This research shows that inherited genetic variation accounts for some of this risk and the type of lung cancer that develops."
She added: "The best thing a smoker can do to reduce their risk of lung cancer, and a range of other life-threatening conditions, is to quit."
Dr Noemi Eiser, honorary medical director of the British Lung Foundation, said: "This research is very interesting as it provides further clues as to why some smokers are more prone to developing certain types of lung cancer.
"We now hope that with more research this discovery will lead to the development of early screening techniques and treatments for lung cancer, which is currently the UK's biggest cancer killer." link....

Poor 'lacking lung cancer help'

Nine out of ten lung cancers are caused by smoking.

The poorest people in the UK are least likely to receive treatment when they get lung cancer, a study suggests.
Analysis of data from 35,000 lung cancer patients in northern England found living in a deprived area cut the chance of treatment such as surgery.
The problem was exacerbated further if patients lived a long distance from a specialist hospital, the British Journal of Cancer reported.Cancer Research UK said there were "unacceptable variations" in care.
Researchers looked at treatment of patients between 1994 and 2002.Overall 17% had chemotherapy, 40% had radiotherapy and 10% had surgery.
Looking in more detail, they found that those living in deprived areas were less likely to have their disease confirmed with a biopsy.And the most deprived were overall 21% less likely to have received chemotherapy, radiotherapy or surgery than the most affluent group.This became more apparent the further the patient lived from the hospital offering the treatment - so the worst cared for group seemed to be the poorest people living in rural areas with a 45% lower chance of treatment.
Diagnosis
Study leader Dr Michael Crawford, a medical oncologist at Airedale Hospital in West Yorkshire, said to have a chance at beating lung cancer, patients really needed to undergo surgery.
Early diagnosis is key, he added, because if the disease was picked up too late, patients would be too sick to undergo treatment to try and beat the disease.
"The question is how patients get into the system.
"So do patients feel they can go to the GP and do they manage to convince the GP that they should be tested for lung cancer."
He said GPs in deprived practices would see a lot of smokers with coughs and they have to decide who warrants an X-ray.
"GPs are gatekeepers of the health service and the message has been 'don't do too many X-rays'.
"We need to make it easier for GPs to say 'you need to have an X-ray'."
Hilary Tovey, Cancer Research UK's policy manager, said: "This study adds to the evidence that despite lung cancer being the UK's biggest cancer killer, there are still unacceptable variations in diagnosis and treatment across the UK.
"It's particularly worrying that people living in the poorest areas are less likely to receive treatment for lung cancer.
"More work needs to be done to understand why this is happening and where improvements should be made." link....

Vaccine Testing On Track

Testing of the vaccine against the pandemic H1N1 influenza virus is on track and there have been "no red flags" for adverse effects, said Dr. Antonhy Fauci, director of the National Institute of Allergy and Infectious Diseases, at a news conference today. The only observed problems have been some redness, swelling and soreness at the injection site -- the same as observed with seasonal flu and other vaccines. The first data on the immunogenicity of a single dose of the vaccine should be available by the middle of the September and data from two doses should be available a month later, he said.based on the lack of adverse effects in vaccination of the elderly, tests in children age 6 months to 17 years began Wednesday and Thursday, he said. Data from those trials should be available about two weeks after data from the first trials.
The United States expects to have 45 million to 52 million doses of the vaccine available by mid-October and as many as 195 million by the end of the year, said Dr. Jay Butler, director of the Centers for Disease Control and Prevention's H1N1 vaccine test force, in the same news conference. The vaccine will be distributed to the states on the basis of population, he said, and distribution will be coordinated in the same manner as the government's Vaccines for Children program -- although the program will have to enroll many more providers to ensure adequate distribution.
Butler said that there have so far been 7,963 hospitalizations and 522 deaths from laboratory-confirmed infections of pandemic H1N1 in the United States. About 75% of those hospitalized are under the age of 49, as are 60% of those who died. The current round of infection is slowing, he added, with only sporadic cases in all states except Alaska and Maine, which have widespread activity. "Reports of widespread influenza activity in August are very unusual," Butler noted, and emphasize how little is still known about the new virus. Officials believe there have been more than 1 million cases of swine flu in the United States to date.
Worldwide, nearly 1,800 people have died from complications of the virus, with more than 1,200 of them in Latin America, according to the World Health Organization. But flu activity is decreasing in the Southern Hemisphere, Butler said, as the conventional flu season winds down. Activity is also declining in the United Kingdom, which has had a severe outbreak of the virus, but is increasing in Japan -- for reasons that are not clear. A WHO official said earlier this week in China that there could be an "explosion" of new cases this fall with cases doubling every three to four days for several months. Fauci said that the U.S. should expect an upsurge in new cases this fall as children return to school, but Butler said that an explosion of new cases is a "worst case scenario. Whether it will occur, I don't think any of us know."
Agricultural officials in Chile said this week that pandemic H1N1 virus has been found in two flocks of turkeys and that the animals were quarantined and have fully recovered. Officials have been wary about such infections because of the risk that the pandemic H1N1 virus could recombine with the H5N1 avian flu virus, which is much more deadly but not as readily transmissible in humans. Such a recombinant could theoretically possess the easy transmission of the current swine flu virus with the lethality of the bird flu. It could also recombine with seasonal flu, which is resistant to antiviral drugs such as Tamiflu -- thereby limiting options for treating and preventing swine flu infections.
Butler noted, however, that the isolation of the virus from turkey "is not that surprising" because attributes of swine flu viruses help them infect turkeys. The virus was discovered because of a drop in egg production, not because turkeys were dying, and officials have seen no evidence of recombination. "The report did not raise any great concerns among us," he concluded. link....

Engineered Protein-like Molecule Protects Cells Against HIV Infection

With the help of the human immunodeficiency virus (HIV) and molecular engineering, researchers have designed synthetic protein-like mimics convincing enough to interrupt unwanted biological conversations between cells.
Interactions between proteins are fundamental to many biological processes, including some less-than-desirable ones like infections and tumor growth. For example, HIV and several other human viruses — including influenza, Ebola and the severe acute respiratory syndrome (SARS) virus — rely on interactions both among their own proteins and with host cell proteins to infect the cells.
"There's a lot of information transfer that occurs when proteins come together, and one would often like to block that information flow," says Samuel Gellman, a chemistry professor at the University of Wisconsin-Madison.In a fundamental study of how to control protein shape, Gellman's UW-Madison research team, including former postdoctoral fellow W. Seth Horne, now at the University of Pittsburgh, and graduate student Lisa Johnson, created a set of peptide-like molecules that successfully blocked HIV infection of human cells in laboratory experiments.By interacting with a piece of a crucial HIV protein called gp41, the synthetic molecules physically prevent the virus from infecting host cells.
The idea shows promise as a new avenue for targeting other unwanted protein interactions as well, Gellman says. The work, performed with a group led by John Moore and Min Lu at the Weill Medical College of Cornell University, is described in a paper appearing online the week of Aug. 17 in the Proceedings of the National Academy of Sciences.Past attempts to prevent infection by selectively interfering with these interactions have had limited success, he says. Most drugs are small molecules and are not very effective at blocking most protein-protein interactions, which involve large molecular surfaces. Short snippets of proteins, or peptides, can be more effective than small molecules but are easily broken down by enzymes in the body and so require large and frequent doses that are difficult for patients to manage.
The new synthetic approach avoids these pitfalls by creating peptide-like molecules with a modified structure that degrading enzymes have trouble recognizing."We want to find an alternate language, an alternate way to express the information that the proteins express so that we can interfere with a conversation that one protein is having with another," Gellman explains.
Like engineers adjusting molecular blueprints, Gellman and his colleagues made structural tweaks to the backbones of their synthetic molecules to improve stability while retaining the three-dimensional shape necessary to recognize and interact with the HIV gp41 protein. The resulting molecules — dubbed "foldamers" — are hybrids of natural and unnatural amino acid building blocks, a combination that allows the scientists to control shape, structure and stability with much greater precision than is currently possible with natural amino acids alone.In addition to adopting a shape that can interrupt the protein-protein dialogue, the novel foldamer has the additional advantage of being highly resistant to degradation by naturally occurring enzymes, which are stymied by the foldamer's unusual structure. This means the molecule can remain effective for a longer time and at lower doses.
Several of the synthetic foldamers showed potent antiviral activity against HIV when applied to cultured human cell lines in a dish. Although it is not clear that the foldamers themselves could ever be used as anti-HIV drugs, Gellman emphasizes, the results show that this type of approach has great potential to lead to new ways to think about designing molecules for antiviral therapies and other biomedical applications.
"You don't have to limit yourself to the building blocks that nature uses," Gellman says. "There's a huge potential here because the strategy we use is different from what the pharmaceutical and biotech industries now employ." link....

Metastatic Cancer And Macrophages: Cells Thought To Protect Against Cancer May Actually Promote It

Macrophages (green) are shown attaching to a metastatic tumor cell (blue) in the lung -- a process that promotes metastatic growth.

The deadliest part of the cancer process, metastasis, appears to rely on help from macrophages, potent immune system cells that usually defend vigorously against disease, researchers at Albert Einstein College of Medicine of Yeshiva University report.

In a new study published online in PLoS ONE, Einstein cancer research specialist Jeffrey W. Pollard, Ph.D., and seven colleagues analyzed the movement of breast cancer cells in mice to show that a distinct population of macrophages helps malignant cells set up shop at distant sites. This process, known as metastasis, is the main reason cancer patients die. Dr. Pollard and his colleagues propose that their discovery offers a potentially useful new target for anti-cancer therapy. What they've found is a vulnerable step in the cancer process that might be blocked by drug treatments. In three different ways, the scientists showed that metastatic tumor growth is inhibited if these unusual macrophages are killed.
They also showed that even after breast cancer cells have lodged in the animals' lungs and started aggressive growth, erasing the special macrophages dramatically slowed growth of the metastasized tumors. "This suggests that anti-macrophage therapy will have an impact in patients even with metastatic disease," Dr. Pollard said.Based on this new work, he added, "macrophages themselves, or their unique signaling pathways, represent new therapeutic targets that may be efficacious in reducing cancer mortality."
Ordinarily, macrophages are vital for maintaining health as an integral arm of the immune system, one of the body's main lines of defense. Their assigned tasks include cleaning up debris in the wake of disease or injury, alerting other immune system cells when an infection begins, and helping identify viruses and bacteria that need to be killed.
The findings of this study build on earlier cancer research by Dr. Pollard and his team that shows macrophages can act at the primary tumor site to enhance tumor progression and malignancy. Thus, they've now shown that macrophages can become traitors, enhancing the worst aspect of the disease – metastatic tumor growth.
"This new study is important because it definitively shows the effects of macrophages at distant sites, as well as the identity of the macrophage population," Dr. Pollard explained. "This is the first proof that they have impact at this location, at the site of metastatic tumor growth."
Dr. Pollard noted that "metastatic disease is the major cause of cancer mortality," in part because the distant tumors tend to resist chemotherapy and radiation treatments. Unfortunately, "the biological mechanisms that underlie metastatic disease are poorly understood," so continuing research is needed. And if metastasis can somehow be blocked -- particularly through influencing cells of the metastatic microenvironment -- the impact on cancer mortality would be enormous.
The paper, "A Distinct Macrophage Population Mediates Metastatic Breast Cancer Cell Extravasation, Establishment and Growth," was published August 10 in PLoS ONE, a journal of the Public Library of Science. The lead author is post-doctoral fellow Binzhi Qian, Ph.D., Einstein. Other co-authors are Yan Deng and Yiyu Zou, Einstein; Jae Hong Im and Ruth J. Muschel, University of Oxford Churchill Hospital in England; and Richard A. Lang, Children's Hospital Research Foundation, in Cincinnati, Ohio.
Dr. Pollard is the director of the Center for the Study of Reproductive Biology and Women's Health, deputy director of the Albert Einstein Cancer Center, professor of developmental and molecular biology, and of obstetrics & gynecology and women's health. He is also the Louis Goldstein Swan Chair in Women's Cancer Research at Einstein. link....