2013-05-24T08:03:19-04:00 Lauren Pecorino http://www.huffingtonpost.com/author/index.php?author=lauren-pecorino Copyright 2008, HuffingtonPost.com, Inc. HuffingtonPost Blogger Feed for Lauren Pecorino Good old fashioned elbow grease. tag:www.huffingtonpost.com,2013:/theblog//3.3280058 2013-05-15T12:49:16-04:00 2013-05-15T12:49:23-04:00

Lauren Pecorino http://www.huffingtonpost.com/lauren-pecorino/
It has been published that Jolie carries a BRCA1 mutation and that she has had a double prophylactic mastectomy to reduce the chance of getting cancer. The BRCA1 and BRCA2 genes are known as tumor suppressor genes. Tumor suppressor genes produce proteins that play a role in protecting the body against cancer. BRCA1 and BRCA2 are involved in DNA repair, an important self-defense mechanism to prevent mutations -- the underlying cause of cancer. So if BRCA1 and 2 become faulty because of mutation and cannot carry out its function, the body's defense system against mutations is compromised. This leads to an increased risk of breast and ovarian cancer.

The genetics

We inherit two copies of genes from our parents: one copy from our mother and one from our father. In many cases, both copies of a tumor suppressor gene need to be mutated for the development of cancer. Inheriting one mutated copy of a tumor suppressor gene leads to an increased risk of developing cancer. These patients have a "head start" in a race that no one wants to win. Note that an inherited mutation is present in all of the cells in the body because it was present in either the egg or the sperm before you were conceived. A second "hit" or acquisition of a mutation in the other copy of the gene later in life leads to cancer. This occurs in a single cell of the body. Lifestyle contributes to the risk of getting the second "hit." Inheriting a BRCA mutation leads to an increased risk of breast and ovarian cancer; not all women with one BRCA mutation will develop breast cancer.

The risks

This is the subject that can cause the most confusion and is often incorrectly communicated. In simple terms: about 12 percent (12 women out of 100) will develop breast cancer over their lifetime [1]. The lifetime risk of breast cancer rises to 60 percent (60 out of 100) if a woman has inherited a harmful mutation in BRCA1 or BRCA2. Note that these are risks of getting breast cancer and not dying from it; the arsenal of drugs to treat breast cancer has expanded in recent years and as reported in the National Cancer Institute (2012) Cancer Trends Progress Report, the trend in death rates from breast cancer is falling. It is estimated that 5-10 percent of breast cancers are due to mutations in BRCA genes.

Possible choices

There are several possible choices for reacting to a positive genetic test that increases the risk of breast cancer. Jolie has taken the most radical option -- she has chosen to have a double prophylactic mastectomy. This is still no guarantee because this procedure cannot remove all at-risk tissue.

Keeping a watchful eye by increasing cancer screening is another option for women who have an inherited BRCA mutation. The American Cancer Society recommends that women at high risk should get a mammogram and magnetic resonance imaging (MRI) scan every year and that women with BRCA gene mutations should begin this screening at age 30. Currently, 61 percent of breast cancers are diagnosed at a localized stage, for which the five-year survival rate is 98 percent.

Chemoprevention is another approach. This is the use of natural or synthetic agents to prevent, stop, or reverse the development of cancer. Tamoxifen, a drug that was the gold-standard treatment of breast cancer for decades, has also been approved by the U.S. Food and drug Administration (FDA) for breast cancer risk reduction. Some studies have shown that it may be able to help lower the risk of breast cancer in those carrying BRCA mutations. Raloxifene is another chemopreventative drug against breast cancer approved by the FDA.

Adopting evidence-based recommendations for lifestyle choices to reduce risk is important for all (note the emphasis on evidence-based). The Food, Nutrition, Physical Activity, and Prevention of Cancer report published by the American Institute for Cancer Research and World Cancer Research Fund makes 10 general recommendations for the prevention of cancer. This list includes maintaining a healthy weight, engaging in physical activity, and limiting alcohol consumption. Factors that increase lifetime exposure to estrogen are known risk factors for breast cancer that should be avoided when possible.

There is always something in the pipeline

There is always something in the pipeline -- something new always in development. One new approach on the horizon for treating patients with BRCA mutations uses molecular partners to create a deadly combination in cancer cells in these patients, and not healthy cells. The agent, called olaparib, which targets a DNA repair pathway needed in BRCA deficient cells, is used to create the deadly combination. Encouraging results from early-phase clinical trials that use this "synthetic lethal" approach have been reported in the New England Journal of Medicine. Science continues to be the underlying reason why millions survive cancer.]]> tag:www.huffingtonpost.com,2013:/theblog//3.2838331 2013-03-11T09:00:57-04:00 2013-05-11T05:12:01-04:00

Lauren Pecorino http://www.huffingtonpost.com/lauren-pecorino/
Over the past few decades, stem cell science in the U.S. has had to leap over many obstacles including gaining public and governmental support, and satisfying regulators that had little experience with how to regulate this new field.

The good news is that the tide is changing. Public and governmental support has increased. A poll published in the New England Journal of Medicine has shown that a majority of Americans believe that medical research involving stem cells obtained from human embryos is morally acceptable. The U.S. Supreme Court has recently dismissed a case that had suspended government funding of projects involving embryonic stem cells. As a result, financial support from the government is now available.

The real boost is that three applications for testing embryonic stem cell therapies in clinical trials have received the go-ahead by the U.S. Food and Drug Administration (FDA). These are focused on spinal cord injury, age-related macular degeneration, and Stargardt's macular dystrophy.

The first milestone occurred when the FDA granted permission to the biotechnology company Geron to initiate the world's first human clinical trial of an embryonic stem cell-based therapy for acute spinal cord injury. This happened three years ago under the leadership of CEO Thomas Okarma.

But it has been a rollercoaster ride ever since. Soon after, the company reported the observation of non-proliferating microscopic cysts in some animals to the FDA and trials were put on hold. After additional experiments that addressed concerns, approval was granted once again. But the volume of regulatory documentation prepared for the FDA (over 21,000 pages) plus time delays and increasing financial burdens had their toll.

One year later, in 2011, a decision to halt the trials was announced due to changes in company strategy and finance. Hope for stem cell therapies overall was crushed. But Okarma, who subsequently left the firm, was not deterred. He has resurfaced at a company called BioTime with a new tactic to drive his previous efforts. In January this year, he signed a definitive agreement to obtain the intellectual property and other assets associated with Geron's discontinued human embryonic stem cell program, including the early phase clinical trial for this product. Once again Okarma is in the driver's seat.

What's the science behind the product?

Stem cells are remarkable cells. They are the crucial link between the one cell, the fertilized egg that begins a life, and the final individual. The fertilized egg divides to form embryonic stem cells. The defining properties of these cells are their ability to self renew and form more stem cells, and their ability to produce cells that are committed to a specific cell lineage such as muscle. They have the ability to form all of the cell types in the body. It is this ability that gives them great potential as a therapy.

During spinal cord injury, nerve cells are damaged and often lose an insulating material called myelin sheath. The myelin sheath is needed to transmit nerve impulses. Geron used human embryonic stem cells to produce a cell line called GRNOPC1 that is committed to produce specialized cells called oligodendrocytes. Oligodendrocytes support nerve cells and produce myelin sheath and thus should help repair spinal cord injury.

The production of stem cells as a therapy is much more complex than the production of a drug. Geron's product required three stages: growth and expansion of cells from a stem cell bank, differentiating the cells to form GRNOPC1 cells (oligodendrocyte progenitor cells), and formulation for an "off-the-shelf" quality-controlled product (cells are cryopreserved). The therapeutic application of these cells is to implant them into patients to treat spinal cord injury.

Hundreds of preclinical experiments in mice demonstrated safety and showed biological and clinical effects such as production of factors that support neurons (neurotrophic factors), improvement of movement and ability to bear weight and myelination of axons. Concerns over stem cell-derived products focus on possible contamination with undifferentiated cells and formation of tumors. But there was no evidence of tumors in over 400 treated animals. Another encouraging result was that the cells remained within the boundaries of the original site of injury. A special device to deliver the cells into humans was invented.

At last, five patients have been treated in a Phase 1 clinical trial. Final data collection for the primary outcome is due later this month.

Continuing this research is a most ambitious project, but it has a record of good science and experimental evidence that give its scientists the confidence to go ahead. In so many ways, it is a success already, and has broken many barriers for others to follow. The work and determination of Thomas Okarma will be marked in the history of science.

On the horizon
The discovery that adult mature cells, such as skin cells, could be experimentally reprogrammed to form embryonic stem cell-like cells called induced pluripotent stem cells (iPSCs) in 2007 has been a great breakthrough that already has been acknowledged by a Nobel Prize. Reprogramming requires the introduction of several specific genes or small molecules into the adult specialized cells.

The ability to obtain embryonic stem cell-like cells without the need for embryos will greatly advance the understanding and application of stem cells. In addition, the generation of iPSC cells from patients with diseases will enable improved models of disease and drug testing. Such cells have been produced from patients with Huntington's Disease, juvenile diabetes, and severe combined immunodeficiency.

Pushing ahead, Advanced Cell Technology is seeking the go-ahead from the FDA to initiate the first clinical trials using the iPSC-derived cells later this year. They plan to produce platelets that can be used for blood-clotting diseases.

It is time that stem cells gain their place in medicine.


For further reading on exciting stem cell science click here.]]> tag:www.huffingtonpost.com,2013:/theblog//3.2550958 2013-01-25T11:58:51-05:00 2013-03-27T05:12:01-04:00

Lauren Pecorino http://www.huffingtonpost.com/lauren-pecorino/
It was not too long ago, as late as the 1940s, that cervical cancer was a major killer of women of childbearing years in the U.S. Fortunately in the U.S., the introduction of cervical cancer screening by the Pap test led to a 74 percent decrease in the incidence of cervical cancer from 1955 to 1992. More recently we have a new target against it. Scientists have identified that 100 percent of cervical cancers are caused by the human papillomavirus (HPV).

John Schiller, Senior Investigator at the National Cancer Institute, said "Discovering that a virus is the central cause of a cancer provides an exceptional opportunity to prevent cancer by preventing the initiating virus infection. It is certainly good news that a simple series of vaccinations now available will likely reduce a young women's risk of developing the second most frequent cause of cancer deaths in women by at least 70 percent." John Schiller, together with Douglas Lowry and colleagues, pioneered the development of the vaccine.

HPV is one of the most common types of sexually transmitted viral infections. More than 50 percent of men and women who are sexually active acquire HPV infection during their lifetimes. Usually the infection is cleared by our immune system but some women do not clear it and develop long-term (chronic) infection. Chronic HPV infection is the central risk factor for cervical cancer. Not all HPV infections lead to cancer -- of the 130 different types of HPV, two types (HPV16 and 18) account for about 70 percent of all cervical cancers. Two FDA-approved vaccines against HPV16 and 18, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are available. Note that Pap testing is still necessary to protect against the other 30 percent of cervical cancers.

According to the National Health Interview Survey (2010) only about 20 percent of 13-17 year olds in the U.S. received the three recommended doses of HPV vaccine. In contrast, by 2009, 70 percent of 12-13 year olds in the U.K. were fully vaccinated. Canada's uptake is somewhere in between the two.

Why is the uptake so poor in the U.S., a country that leads the world in medical innovation?
The only acceptable excuse is lack of education. Foremost is the question of safety. The HPV vaccine is safe. Vaccines in general are safe medical interventions which are exceptionally effective. We have eradicated smallpox and cut the incidence of mumps, measles, and polio to name a few. The public scare regarding a supposed link between the MMR vaccine and autism was unfounded and caused great damage.

Because the HPV vaccine uses virus-like particles, it is even safer than some other vaccines that use intact viruses. These virus-like particles act as the shell of a virus without any life within. The body generates antibodies against this shell. In the future, these antibodies will recognize and bind to an invading virus and stop it from infecting cells.

The vaccine is preventative and NOT therapeutic which means that it must be given before exposure to the virus so that the body has time to trigger an immune response. The vaccine is recommended for girls at an age before engaging in any sexual activity. Having the vaccine does not imply, in any way, that the child is sexually active. Parents can weigh the risks and benefits of any medical procedure. In this case, one must weigh the tears due to a few injections at the age of 13 against the tears due to possible cervical cancer some years later.

Coincidentally there is an unexpected bonus. It has been discovered that the same strains of HPV which the vaccines protect us against is also responsible for an increase in head and neck cancers (probably transmitted by oral sex). So the same vaccine also guards against a second type of cancer.

The U.S. needs to have a national organized vaccination program similar to that of the U.K. which implements a national school-based vaccination program. This has proven to yield high coverage compared to on-demand provision. Parents, health professionals, teachers, and government need to get the message heard. Public advertisements and broadcasts should support such a campaign.

Come on USA, let's make use of the years of research that yielded the first cervical cancer vaccine. The vaccine is safe. Prevention is better than a cure.]]> tag:www.huffingtonpost.com,2012:/theblog//3.2384650 2012-12-30T21:46:12-05:00 2013-03-01T05:12:01-05:00

Lauren Pecorino http://www.huffingtonpost.com/lauren-pecorino/
The American Institute for Cancer Research recommends that men should limit their intake to two drinks per day and women should limit their intake to one drink per day. The reason for limiting our alcohol intake is simple -- alcohol is a listed carcinogen, an agent that causes cancer, by the International Agency for Research on Cancer. The mechanism of how it causes cancer is similar to that of cigarette smoke. Alcohol is metabolized in the body to form acetaldehyde, which like many carcinogens of cigarette smoke, stick to DNA and mask the genetic code. The masking of the code causes errors because the code cannot be read properly by the cell's machinery during cell division. The errors become permanent changes to the sequence of the genetic code called mutations. Just as changes of single notes in a musical score effects the melody of a tune, the altered genes produce faulty enzymes. It is the accumulation of mutations over time which can lead to cancer. Some women may ask why there is an inequality in recommendations between women and men. The answer is because alcohol also increases the amount of circulating estrogen and increases in estrogen are a risk factor for breast cancer. So drink with your friends this holiday season but keep within the limits.

Uncle Bob may be able to drink his Asian colleague Mingyan under the table. The reason for differences in alcohol tolerance is due to variations in metabolic enzymes produced by your genes. This underlies the observation that many Asians are unable to drink alcohol without becoming ill. There is a common genetic variant among this population that produces an enzyme with a low ability to metabolize acetaldehyde, a step that helps rid the body of this carcinogen. In these people, acetaldehyde accumulates and leads to facial flushing and nausea.

Include fruit and vegetables in your feast

The antioxidants found in fruit and vegetables offer more than acting as molecular sponges to soak up dangerous free radicals in the body. One of the most startling facts we have learned about fruit and vegetables is that they contain components that can turn on genes that produce detox enzymes. Yes, food affects your genes. This is not nature versus nurture but rather nature hand-in-hand with nurture. The detox enzymes carry out important roles that help protect us from agents that cause cancer by playing a role in repairing DNA damage and modifying carcinogens so that they can be excreted quickly. Scientists have shown that people who drank fruit juices daily had less detectable DNA damage than those who did not. The protective affect disappears when the fruit juice intake was halted. Unfortunately we cannot store up the effects of fruit and vegetables and this is the reason that the recommendation states that intake must be daily.

Let's dance

Holidays are a break from the chains that bind us to a desk. So it is a time to dance, take a walk, or just move around. Exercise is a vital ingredient of good health and in many ways is medicinal. It also has several effects that help prevent cancer. Obviously it helps to maintain a healthy weight. As stated in a report by the World Cancer Research Fund and the American Institute for Cancer Research, maintaining a healthy lifestyle throughout life may be one of the most important ways to protect against cancer. Physical activity has other effects such as boosting the immune system, stimulating defense enzymes, and reducing circulating hormones such as estrogen.

As a population, we "got the message" not to smoke. The message to limit alcohol intake and increase fruits and vegetable intake should be heeded during and after the holidays.

Wishing you all a very happy and healthy New Year.]]>