#WeCanICan #WorldCancerDay

A year ago tomorrow, I posted my first blog post. A year and nearly 100 posts later, I maintain the same mission I started with: to empower you with scientific knowledge so that you can make more informed decisions about your health.

February 4th is World Cancer Day, and they are running a social media campaign called “Talking Hands” so that people around the world can say how they take action to help prevent and fight cancer.  Besides what my biobanking team and the other clinical research teams are doing at St. Joseph’s Hospital and Barrow Neurological Institute to fight cancer, this blog is my personal contribution. I hope that in some way this helps you feel empowered to ask questions about yourself and your health, and in the case of a cancer diagnosis, feel better prepared to tackle your road ahead.

What can you do?

Photo Feb 02, 8 26 24 PM

The best week ever – Nobel Prize week!

nobelLast week was one of my favorite weeks of the year – Nobel Prize week. Some people wait for the Emmys or the Superbowl or Christmas.  I wait for the Nobels. To be fair, I care most about the science Nobels – Physics, Chemistry and Physiology or Medicine, though one cannot ignore the amazing accomplishments of the winners in Literature, Peace, and Economics. Every year, I try to guess who may win – though Thomson Reuters and others are far more scientific about their guesses than I am.  And each morning of Nobel Week, first thing I do is check the news on my phone to see who won, what for and whether or not I know them (this year – no).  Let’s talk about who won the science awards this year and what amazing discoveries they won for.

Physiology or Medicine. A lot of attention has been given to infectious diseases this year with the huge Ebola outbreak in western Africa.  Although tens of thousands of people were infected and died, other infectious diseases are even more widespread and affect millions of people a year. Malaria is a parasitic disease transmitted by mosquitoes that 3.4 billion people are at risk of contracting and that kills over 450,000 people per year. Parasitic worms are also rampant in the third world, can affect up to a third of the human population, and cause such diseases as river blindness.  This is the second most common cause of blindness by infection, with 17 million people infected and 0.8 million blinded by the disease.  The three winners of the Nobel for Physiology or Medicine this year discovered novel treatments for these parasitic diseases.  William C. Campbell and Satoshi Ōmura for roundworm parasites and Youyou Tu for malaria, saving hundreds of thousands of lives each year.

Chemistry. This is by far my favorite award this year because it is directly related to how humans safeguard their DNA, but also why when this safeguard does work, that we get cancer.  Awarded to Tomas Lindahl (UK), Paul Modrich (USA), and Aziz Sancar (USA), this Nobel celebrates the discovery of the mechanism of DNA repair. I’ve discussed in this blog how UV and other environmental factors can cause mutations in DNA, and with too many mutations, people can develop cancer or other diseases.  However, the genome doesn’t mutate out of control because cell contain the machinery that is always working to fix any DNA damage using DNA repair mechanisms. It’s like a NASCAR race, where the car is always being monitored, wheels replaced, and minor problems fixed by the pit crew.  DNA repair is the genome’s pit crew and these three scientists figured out three different ways that the cells monitors and fixes the DNA depending on the type of damage that has occurred.

Physics. We all know I’m not a physicist, but I’ll try my best. The Physics Nobel was awarded to Takaaki Kajita of Japan and Arthur B. McDonald of Canada for discovering that neutrinos have mass.  You may remember from high school that atoms are made up of protons, neutrons and electrons. However, scientists now know that there are even tinier parts of an atom called subatomic particles that include the neutrino, fermions and bosons (and others). Other than photons, which are the particles of light, neutrinos are the most numerous subatomic particle in the entire cosmos, so understanding how they work is incredibly important.  These researchers found that the three different types of neutrinos can convert from one to the other. It was predicted by the Standard Model of Physics that these neutrinos wouldn’t have mass, but these scientists also proved that they did. Their studies help to better understand matter and the universe. My favorite reporting of this award was by NPR.

So until next year Nobel Prizes.  I will be waiting with baited breath!

 

How scientists “cured” melanoma

When talking about Personalized Medicine, one of the recent shining examples of this concept in practice is in the treatment of melanoma. Melanoma is a cancer of the pigment cells called melanocytes and is most commonly diagnosed as a skin cancer. The prognosis for melanoma is dismal when caught at later stages where the cancer cells have spread into lower layer of the skin or throughout the body (see the stats in the image below). Treatment typically involves surgery to remove the cancer cells, followed by chemotherapy and/or radiation therapy, but the response to these treatments is low.

melanoma

There are two interesting personalized medicine examples for melanoma.  The first is in determining whether a low stage (I or II) melanoma has a likelihood of spreading.  Once a low stage melanoma has been removed by surgery, there is still a 14% chance that these patients will develop metastatic (melanoma that spreads) disease. To determine which patients are more at risk, a biotech company developed DecisionDx-Melanoma. This test looks at the expression of 31 genes and separates the patients into two groups based on the gene expression profiles.  One group only has a 3% risk of developing invasive melanoma within 5 years whereas the other group has a 69% chance.

However, whether the cancer progresses or not, treatment is still an issue. That is, it was until a few years ago when scientists found that  50-60% of all melanoma patients have a mutation in the gene called “BRAF.” This mutation tells the cancer cells to grow faster, so you can imagine that if you stop this signal telling the cancer cells to GROW, then they might stop growing and die. This is exactly what the drug PLX4032 (vemurafenib) does – it inhibits this mutated BRAF and stops the cancer cells from growing in 81% of the patients with this mutation (see the photo at the bottom of the post to see how dramatic this effect is).  On the other hand, in patients without this mutation, the drug has severe adverse effects and shouldn’t be used.  Because of this, doctors don’t want to prescribe this treatment to patients without the mutation.  Therefore, scientists created a companion diagnostic.  These are tests that are used to identify specific mutations before treatment to help decide what treatment to give (see image below). In the case of melanoma, this companion diagnostic tests if the patient has the BRAF mutation, and the patient is only treated with vemurafenib if they have this mutation.

This treatment was revolutionary with an incredible ability to cure melanoma. It was like melanoma was previously being treated with the destruction of a nuclear bomb, and now it is being treated with the precision of a sniper rifle – targeting the exact source of the cancer. So why is the word “cure” so obviously in quotes? Unfortunately, after continued therapy, the cancer relapses (see the image below). Imagine treating cancer cells being like closing a road- it’ll block up traffic (kill the cancer cells), but then you’ll be able to find back roads that get you to the same place.  In the case of cancer, the drug is targeting mutations in BRAF, and BRAF finds ways to evade the drug by mutating again (effectively removing the roadblock).  Or the cancer cells themselves may have other routes besides mutated BRAF making the cancer grow. So although this drug is a life extender, scientists have been working to combine it with other targeted drugs (blocking off alternative routes) to make it a long-term life saver.

melanoma_relapse

From the Journal of Clinical Oncology

Sci Snippet – The bug that causes ulcers

Everyone can understand that bacteria can cause a disease through infection. Bacterial infections can cause huge inflammatory responses known as sepsis or result in a cut getting infected. But a bacterial infection causing ulcers? That seems weird.

Hpylori

H. Pylori under an electron microscope

This is a crazy story, but resulted in the 2005 Nobel Prize in Physiology and Medicine. In the 1980s, Dr. Barry Marshall found that the bacteria H. Pylori is often found in people with peptic ulcers. At this point, scientists didn’t even think that bacteria could survive in the acidic environment of the stomach, much less cause a disease. Ulcers were obviously caused by stress or spicy foods or too much acid. Dr. Marshall was convinced of his hypothesis and went to test his theory in pigs, but for some reason he wasn’t able to get the H. Pylori bacteria to infect the pigs.  So one night, he drank an entire petri dish of cultured H. Pylori. As a side note – it is NOT a good idea to do experiments on yourself because you have no idea what will happen (movies have confirmed this over and over). However, three days later, he felt nauseous, after a week he started vomiting and an endoscopy found massive inflammation indicative of gastritis, and two weeks later he started taking antibiotics for the H. Pylori infection. He  was the first to definitively prove that this bacterial infection caused gastritis. Although this particular experiment did not prove that H.Pylori caused ulcers, it’s now been shown by other researchers.

In fact, now scientists know that H. Pylori bacteria is found in the stomach of about 50% of the world’s population, but in most people it doesn’t cause much of an issue. 80% of people infected don’t have any symptoms and it may actually help protect against other diseases such as acid reflux and Barrett’s esophagus. However, of those infected, they have a 10-20% lifetime risk of developing an ulcer and a 1-2% risk of developing stomach cancer. What this means is that eliminating H. Pylori by antibiotics can help treat the ulcer, and can also decrease the risk of stomach cancer.

For more Sci Snippets, click here.

What is that? A beautiful image of deadly tumor cells

the eye

Thanks to Dr. Roberto Fiorelli of Barrow Neurological Institute for sharing this stunning image

It looks like an eye.  Perhaps a terrifying pink eye, like the Eye of Sauron, coming out of the darkness. It’s not an eye, but it is a bit terrifying. This is an image of a slice of the brain showing tumor cells (in green and red) surrounding a blood vessel.  How does this type of image get made?  How does this type of image help scientists? What does it mean that these tumor cells are near a blood vessel?

This image is created with a microscope – specifically a confocal microscope. I’m going to use a very weird analogy to explain why confocal microscopy is so cool, so stick with me. Imagine that you have a jello mold with an object it and you want to know exactly what the object looks like.  Now imagine a regular microscope is like a flashlight.  When you point the flashlight at the jello mold the whole thing lights up including what’s in front of the object, and if the object is translucent, the jello behind the object lights up too.  This gives you an idea of what the object is, but it may be kind of fuzzy because of all the jello you see in front and behind the object.  Confocal microscopy, on the other hand, is designed to turn that wide flashlight beam into a single pinpoint of light so only one part of the object is illuminated at a time.  So when you move this single pinpoint around (back and forth and up and down) over the object, you can get a clear a crisp image of what is inside the jello.

confocal_microscopy

To bring this analogy back into the science-verse, the jello is a cell or a piece of human tissue with layers of many cells.  The objects inside the jello are certain proteins marked so that they light up in different colors (what we call fluorescence) when excited by the light from the laser (flashlight). When confocal microscopy is used to look at these proteins, you can see clear crisp images of exactly where the proteins are in the cells.  And if you take enough images up and down through the cells and the tissue, you can even create a 3D image of the cell or a piece of tissue. Check out this neat video of a 3D rendering of a piece of the brain called the hippocampus.

Now back to the image above.  This is a piece of tissue taken from a patient with an ependymoma, a tumor derived from brain tissue and is primarily found in younger patients.  The colors you see are:

  1. Blue: a chemical called DAPI (or 4′,6-Diamidino-2-Phenylindole, Dihydrochloride) that binds to DNA. Since DNA is found in the nucleus of every cell, staining cells with DAPI helps you to locate each cell in the image – each blue dot is one cell.
  2. Red: stains a protein called GFAP (Glial Fibrillary Acidic Protein) that is found in different cells of the brain, but is also a marker of particular brain tumors, like ependymomas
  3. Green: stains a protein called vimentin that is also found in different cells of the brain, including cells that make up large blood vessels and brain tumors like ependoymomas

So what are we able to learn from this beautiful picture?  See how there are a lot of red and green cells surrounding an empty round space.  That round space is a blood vessel. Cancer cells need food and oxygen to grow, so the green and red cancer cells are clustering around the blood vessel to get the nutrients they need. Even though this is a beautiful image, it helps scientists to understand how these deadly tumors function within the brain and how they find the resources to grow.

If you want to look at more amazing images taken using confocal microscopy and fluorescently tagged proteins, check out these links

Wellcome Image Awards 2015
The Cell: An Image Library

Thanks to Dr. Roberto Fiorelli of Barrow Neurological Institute for sharing this stunning image from his postdoctoral work in Dr. Nadar Sanai’s Laboratory, the Barrow Brain Tumor Research Center

For more “What is That?”, click here.

What happens when chromosomes rearrange? Sometimes cancer.

There are so many different kinds of genetic mutations.  So far, we’ve only discussed small single nucleotide changes and insertions and deletions.  But entire pieces of chromosomes can also be rearranged in what’s called a translocation. The prefix “trans” shows up a lot in science.  It comes from Latin and means “across” or “on the opposite side”.  “location” is physically talking about the chromosomal location.  So “translocation” mean s pieces of chromosomes moving to another location.

translocation

You can think of it as two different pieces of DNA that aren’t usually right next to each other, being put next to each other. Kind of like a centaur – the top of a human attached to the bottom of the horse – a human/horse translocation.  Of course, in the case of chromosome, genes or regulatory pieces of DNA are moved next to each other, and although it may not seem nearly as dramatic as a centaur, the effects can be just as surprising.

philadelphia chromosomeOne example of a translocation that has dramatic consequences is the translocation that causes the blood cancer Chronic Myelogenous Leukemia (abbreviated as CML).  In this case, part of Chromosome 9 and part of Chromosome 22 break off and swap.  So now, Chromosome 9 has part of chromosome 22 attached, and vice versa.  The part of chromosome 22 and the broken off part of chromosome 9 are called the Philadelphia chromosome, and this is what causes the leukemia.

But how?  We  imagine that Chromosome 9 and Chromosome 22 are both train tracks.  On those train tracks are trains that can either be going or not going depending on the upstream signals.  On Chromosome 22 there is a green signal that is stuck at green so the train is always going.  On Chromosome 9, there is a more sensitive signal – some times it’s green, but most of the time it’s red so the train isn’t going.

train_anaolgy

What happens now is that there is a switch (or a translocation) that attaches the Chromosome 9 and 22 train tracks together.   But when it does this, the green signal from Chromosome track 22 is telling the train on the chromosome 9 track to go – even though it usually doesn’t always go.  This is nearly exactly what happens in the case of the Philadelphia chromosome, except the trains are genes that are making protein (if the signal is green) or are not made into protein (if the signal is red). The signals are parts of DNA that regulate the “expression” of the gene (in other words, whether or not the gene makes the protein).

train_analogy_switch

In the case of the translocation in CML, what happens is a gene of Chromosome 22, called BCR is attached to part of the Abl gene on chromosome 9.  In this configuration, the BCR-Abl fusion gene makes a protein that is always “on”.   What does this protein do?  Essentially, it tells the blood cells to keep growing and dividing.  This makes too many blood cells and causes leukemia.

There are many different chromosomal translocations that cause a number of different diseases, but what they have in common is either creating a protein that is always on or changing the upstream signal that tells a gene to make more protein.  Most of the time, this results in signalling the cell to keep growing and dividing, which is why translocations are often associated as a cause of cancer.

What is risk? Absolute versus Relative

riskMy mom and I were talking this afternoon – we talk every day on my drive home from work (I celebrated the day I got Bluetooth in my car) – about Angelina Jolie.  It was difficult to miss the news this past week about her New York Times opinion piece describing why she decided to remove her ovaries and Fallopian tubes.  There have been a number of interesting articles both praising (here or here or here) or criticizing or clarifying her choice.  That’s not what I want to talk about and it’s not what my mom and I talked about.  What we talked about was risk.  Most stories talking about Angelina Jolie mention that because of the gene mutation she had, there was an 87% risk of her developing breast cancer.  Despite the fact that 87% is awfully specific (and based on limited data from a certain number of women with this mutation that were studied over time), what I want to focus on isn’t the number, but what the number refers to.  In particular, I want to point out that there are different ways of talking about risk – and this is important when reading about any scientific information in the news.

coin_flipLet’s start with a quick definition – risk is the chance that something will happen.  These are usually percentages.  There is a 50% chance when you flip a coin that it will land on heads.  The risk is 50%.  Of course, when applied to the chance of developing a disease, or having a particular treatment outcome, or surviving an accident, the numbers are a lot more difficult to calculate than a coin flip.  But they are also more confusing when describing the risk as well.

 

rosk_tableI’m sure you’ve read news stories that say something like “Drinking more than 3 caffeinated drinks a day increases your risk of a heart attack by 50%” (this is a completely fictional example!!!) Fifty percent. What a HUGE risk.  Except what they don’t tell you is that without drinking caffeinated drinks, your risk of having a heart attach is only 1%.  So a 50% increase means your risk only increases to 2%.  This is the difference between relative versus absolute risk.  50% is the risk relative to what the actual baseline risk, whereas the absolute risk tells you the actual chance of something happening.

Let’s look at another example.  “This new drug decreases the risk of blindness in diabetic patients by 50% over 5 years”.  This is promising news!  Except, again, the 50% is relative risk – what you want to know is what the chance of a diabetic patient going blind?  If the chance that a diabetic patient goes blind is 60%, then a decrease of 50% is huge. There is only a 30% chance of blindness now.  Ont he other hand, if like the previous example, the actual chance of going blind is 2%, the 50% decrease is less impressive.  This makes the decrease in risk no less important to the patients who take the drug and don’t go blind – but it does affect how you read a news story describing the effect of the drug and whether or not you may want to take an expensive drug.

Now let’s get back to Angelina Jolie. The actual risk for breast cancer in the general population over a lifetime is ~12%.  If you have the mutations in the genes (called BRCA1/BRCA2) that Angelina Jolie has, it increases the risk to 40-80%. This is the absolute increase in the chance of getting breast cancer.  And as you may notice – the risk has a range (based on a number of factors – family history, health history, etc that we’ll get into in another post).

So how can you be a more savvy reader? You can be tipped off to relative risk by phrases like “increased by”, “decreased by”, “more than” or “less than”.  This only tells us the difference compared to baseline, but gives NO indication of what that baseline risk is. Absolute risk, on the other hand, provides the best estimate of what the overall likelihood of something happening will be.

risk_cartoon

Book Club – Cancer: The Emperor of All Maladies

cancermaladies

The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukerjee is a brilliant book that combines masterful storytelling with the story of the history and biological underpinnings of cancer.  I was planning on suggesting this book when I started talking about cancer on this blog, but Ken Burns has partnered with Barak Goodman and PBS to transform this book into a three night miniseries “Cancer: The Emperor of All Maladies” starting tonight (see the trailer and visit the website).

In lieu (or in advance) of reading the book and our discussion here on the blog about cancer, I encourage you to watch this film.  I read the book quite a while ago, but some of the stories still stick with me.  Stories about massive, disfiguring surgeries to remove breasts, lymph nodes, and chest muscles to treat breast cancer before trials were done to prove that smaller surgeries had the same effectiveness.  Stories about the discovery of the first chemotherapy – from work in a dye factory.  Stories about scientists and physicians who pushed the bounds of knowledge to find better ways to treat patients.

Use this as a backdrop as you think about genes, hereditary, and biology as we move (soon – very soon!) into our discussions about cancer, it’s causes and cures.

For more Book Club books, click here.

You’re what kind of scientist?

I was one of those people who wrote in their college application essay that since I was seven years old I wanted to cure cancer.  And I truly did (long story for another post).  Somehow, I thought it would happen by the time I graduated from college.  I was convinced that all cancer needed as a “fresh pair of eyes” and it would just come to me.  Looking back, I want to pat my teenage head and sigh at what a cute idea that was while being incredible proud of my idealism.

BU terriers

So with this goal in mind, I thought I should be a pharmacist so that I could do pharmaceutical research, until I asked a pharmacist what they did all day and decided that would be incredibly dull.  So I started Boston University as a biomedical engineering major – it included the words “bio” and “medical” so I assumed that it would be perfect for me.  This was a fabulous plan until I took physics.  This was the first time I realized that not every scientist was the same kind of scientist.  I was a scientist who had a lot of trouble understanding physics – specifically electromagnetism.  I still don’t understand why the electromagnetic vector was sometimes going into and sometimes coming out of the board.

I distinctly remember the day I decided to switch my major to biochemistry and molecular biology. I called my parents and they told me to tell them 10 reasons why I should switch major.  They understood what a person could do with a degree in biomedical engineer (create prosthesis or design medical devices), but what in the world would a biochemistry and molecular biologist do?  And so I explained…

Cells are the building blocks of living organisms and molecules (whether DNA, RNA or proteins) are inside of the cells essentially either doing things (in the case of proteins) or directing the creation of these proteins (in the case of DNA and RNA).  Biochemistry explains the mechanisms of how these molecules function. So by understanding how cells and molecules work through research, I could better understand how life works.  And even more interesting, you can study what happens when these mechanisms break down to cause changes in the cells that result in diseases like cancer.  Cells and molecules are also what are targeted by drugs, which fit right in with my goal of developing a cure for cancer.

As I reflect on this early “scientist” moment, I’m thinking about how the public views scientists and how it could be confusing that different kinds of scientists are not at all interchangeable.  Do people lump all scientists together?  Is it confusing that as a biochemist, cell and molecular biologist I know so very little about physics? Or climate change? Or medicine? And even though I’ve taken classes in neuroscience (and neurons are cells that are filled with molecules), I’m no neuroscientist?  There’s so much information and scientific knowledge, that I’m actually grateful that there are experts in other fields…if for no other reason than so I don’t have to understand physics.

[espro-slider id=69]