You may not know that there are different kinds of breast cancer. Researchers call these “pathways.” There’s the well-known estrogenic (estrogen positive) breast cancer, caused by an overabundance of estrogen (much of which is from the environment). There’s also progestin positive breast cancer, and the highly publicized BRCA1 and BRCA2 genetic forms of the disease.  My cancer is HER2+, meaning that some of my cells make too much of the HER2 protein (this is termed “overexpression”).  HER2 overexpression is the culprit in about 25% of breast cancers and has been linked to nearly 10% of ovarian cancers as well.

We breast cancer patients who overexpress HER2 proteins sometimes do not respond as well as other patients to traditional treatments such as certain chemotherapy drugs.  Thankfully, the discovery of this cancer pathway allows better chemotherapy drugs to be developed and there are targeted treatments too, including Tykerb (generic name: lapatanib) and Herceptin (generic name: trastuzumab).

HER2 proteins are what is called receptor proteins, which the cells use to communicate with one another, and between the inside of the cell and the “outside.” These proteins are found on the surface of every cell and are usually exclusive; that is, if the protein doesn’t “match” the receptor it cannot bind to it. These receptors come from different “families” and work in different ways, and interact with different molecules.

This really is too intricate to get into here, so we’ll leave it at this: HER2 (also called HER2/neu) receptor molecules are signal transductors, meaning they take signals from inside the cell to the outside (or vice versa), so nearby cells can communicate with one another.

It works like this: signal—reception—transduction—response.

The reception is on the surface of the cell membrane, the transduction occurs through the cell membrane and within the cells, and the response occurs in the nucleus of the cell, in the DNA and the proteins it is told to produce. In this case, the cell is told to produce too many HER2 receptors and may not send proper signals to the cell to grow, mature and die (a process called apoptosis, which happens to of my all-time favorite words).

Finding out about these pathways is important to the increased survival in breast cancer patients, as well as to my own treatment. There are chemotherapies, called non-targeted therapy, and targeted biological therapies such as those I will be getting both in the next round of chemo and after surgery for about a year.

The latter types of therapies work in two ways. First, by binding to the HER2 receptors it “flags” them for destruction by the patient’s immune system. Next, it signals to HER2 receptors “downstream” from the one flagged that it needs to stop producing so many. Lapatanib works from inside the cell out, and herceptin from outside in, and both shrink the tumor (or so we hope!).

As I begin round two of my chemotherapy (weekly infusions of the drug Taxol) I’m also preparing to take one of the targeted therapies, lapatinib. This is part of a clinical trial, as the drug is only FDA approved for metastatic breast cancer at this point and they are researching if it works on in situ breast cancers as well. Both types of treatment provide the patient with all sorts of interesting side effects, from the really scary to the simply annoying. You’ll hear more about these soon.

Old Genes

When my father was diagnosed with squamous cell carcinoma just over a year ago, I worked with a professor who said something along the lines of "if it's any consolation, remember that your father's genes are very old and they've survived for generations." It wasn't really a consolation, because at the time I had a bad feeling about my father's diagnosis, and about how far along the cancer actually was; it was aggressive and surgery revealed substantial tumor growth in his head and neck. As it turns out, my bad feelings were right, and now I am mourning his loss.

I recount this sentiment because a little over a year later I am facing a cancer diagnosis of my own. Mine isn't skin cancer, rather it's invasive ductal carcinoma, one of the most common and most treatable forms of breast cancer. I had a terrible feeling about the lump (which is why I went to the doctor) and about the biopsy. Once again, my intuition served me well, because I got the diagnosis I did not want, but was expecting. This time, those same words that professor thought may console me actually do bring me some comfort. They have me thinking about genes (cancerous ones in particular) and the fragility of life. And unlike the bad feelings I had about my father's diagnosis and my own, I do not have bad feelings about my outcome. That may be naive, but sometimes--especially in times like these--optimism is all you've got. My genes, in various forms, have been around for centuries, and even longer. Early versions existed eons and have been passed down through entire eras. Why shouldn't they serve me well?

Life is amazing when you think about it. We start out as a hollow ball of cells called a blastulae, and if somehow we make it through that simple, silly little stage without trouble and begin to differentiate, then hey, it's nothing short of a miracle. Next, as embryos, we traverse the dangerous terrain of development, where our growth and gene expression is finely tuned, thanks to millions of years of trial and error. And if we develop as planned by our DNA, our problems aren't over yet. So many things can go wrong during these stages, and if we are lucky enough to develop as specified in the DNA blueprints, we have to go out into the real world after birth, and that isn't easy either.

We get out into the world and are bombarded by chemicals and sunlight and hormones in our food. We dodge viruses and bacteria and microbes. During all of this it is business as usual at the cellular level. Signals tell the cells when to grow, how to grow and when to divide, when to die off. If you delve deeper, into the DNA, it becomes even more detailed.

The DNA double helix unwinds, the mRNA comes in to make a copy. It copies each base, or nucleotide, of the DNA one by one, and in the correct order. There are even checkpoints, like spell check or proofreading, to avoid errors. This is all built in to our bodies. The sequence of DNA nucleotides, the As, Ts, Gs and Cs, is what makes the cells what they are. The mRNA is then shuttled out of the nucleus into the cytoplasm of the cell. Once there, it is translated into the proteins which make up, well, everything in our bodies. This process is elegant, intricate, and stunning. Life goes on. But sometimes the chemicals, sunlight and viruses can cause changes in our DNA, called mutations. In the case of many cancers, it may be one slight change, as little as one nucleotide of DNA, and it is all different. A ball of cells will begin to form. They replicate themselves and grow and don't die when they should, and they stick close together like cliques in a high school cafeteria. They make a tumor. This ball of cells gone awry is what I'm planning to bring down. Beat. Survive.

Individually my cells are fragile. So very many things can go wrong and become the squeaky wheel in the well-oiled machine that is the human body. Conversely, so many things continue to go right, too, and life, in all it's fragile beauty, goes on as it should. I have faith that my body will continue on as it should, my DNA will copy and translate as it is supposed to, it will make the right protein at the right time, as these genes have been doing for eons. And I will survive.

Originally journaled 15 May 2010

Literate Scientist is taking a turn at being a patient.

As most of you who visit my blog will know, I was diagnosed with breast cancer in May. I have wanted to write about my experiences since then, but being a doctoral student, dealing with medical appointments and chemotherapy, and trying to have some down time all kept me from doing so. And if I'm being completely honest, it's taken me this long to actually believe that I have cancer. I still have days when my mind reels at the fact that I'm in chemotherapy and that I'm facing more chemotherapy, plus radiation and surgery, after the first of the year. It is unbelievable, even though it is now part of my life.

My original idea for this blog was to write about scientific literacy (or the lack thereof) and intersperse those entries with interesting sciency information. However,
I'm changing the format for now. It's going to be a blog about having breast cancer and facing the disease head on. I'm going to be honest, and try to educate you in the process.

Everyone knows someone who has cancer. I do, and it was always something that happened to SOMEONE ELSE. Tragic, awful, and yes, heartbreaking. But now it's me, and that changes the story. Now I know what it's like to have drugs dripping into me, drugs that have warning labels on the packaging that warn you not to let it come into contact with your skin. Now I know what it's like to lose my hair. Now I know what it means to be a cancer patient. Now I'm going to share my experiences with you.

Snakehead Homework

My dad gave me homework. He asked me to tell him all about snakeheads (Family Channidae) when I came down on Friday for a visit. So I did what any good daughter would do and I did a search on the greater snakehead fish (Channa micropeltes) and the northern snakehead fish (Channa argus). Turns out they are kinda cool, speaking from an ecological perspective.

They are part of a family of freshwater fish native to Asia, from China to India and down into the islands of Indonesia. There are also species native to Africa, but I don’t think those are the ones my dad heard about, as the hubbub here in the US is that they are invasive species.

Anatomically, the fish are unremarkable, with a long dorsal fin running most of the length of it’s back, and fan-shaped tail fins. Their heads are kind of flattened, I suppose like a snake head, and the mottled blotchy brown coloration reminds me of patterns on snakes bodies, like pythons or boa constrictors.

They grow quickly and can get quite large, as evidenced by this video courtesy of National Geographic.

Snakeheads were brought to America for food and as aquarium fish. However, as people are wont to do they release them in nearby ponds, rivers or streams when they get too large or they no longer need them, and the snakeheads settle and begin making more snakeheads.

They caused a stir in 2002 in Maryland, where an angler caught one in a pond. He took it to a local wildlife and fisheries office for identification. The authorities visited the pond and subsequently caught some hatchlings, indicating the population was well-established. This wouldn’t be such a problem, but the snakeheads are sneaky.

They are one of the few species of fish that need to breathe air. Yes, I said breathe, meaning they don’t use just their gills; they also have what is called a “suprabranchial organ”, which is a kind of a branch of their vascular system allowing them to oxygenate their blood via inhalation of atmospheric oxygen.

While snakeheads don’t actually walk, they do have a decidedly un-fishlike ability to scoot or flop themselves from one body of water to another. Thus, the concern of wildlife and fisheries agents.
There is plenty more I could say about invasive species but I think I should wait, or this will become a longwinded entry.

So, there you have it Dad, everything you wanted to know about snakeheads.

Warm Blooded Dinos?

I am not a paleontologist, but I am a big fan of scientific controversy. I love it when two sides argue about how flight originated or how new fossils may be related to our own hominid lineage. That’s why the recent findings that large bi-pedal dinosaurs like the beloved Tyrannosaurus rex may not have the typical large lizards we have long thought really caught my attention.

It’s generally consensus these days that some dinosaurs were birds rather than lizards, and the lineage has been split to include non-avian and avian branches. But there is still controversy among experts as to whether or not these dinos were warm-blooded like their birdy brethren or cold-blooded like their lizardy links. A new study published in the online scientific journal PLoS ONE on Nov. 11th brings to light some new information.

Say the study authors, endothermy, or warm-bloodedness, was widespread “in at least larger non-avian dinosaurs.” The results of their study seem to indicate that the ability to maintain a constant internal temperature may have originated earlier than previously believed.

What this essentially means is that once again we are rethinking how these extinct giants behaved. For the longest time, large dinosaurs like the T-rex were considered unwieldy, hulking and awkward. Now there’s evidence that there was more power and precision behind their lumbering movements.

So why is this such a point of contention? Because being warm-blooded and cold-blooded are very different and require different energy expenditures, different rates of respiration, and different natural histories altogether.

Cold-blooded animals (termed ectothermic), such as amphibians, reptiles and the ilk, rely on the environment to maintain body heat. They generally adapt behaviors to soak up as much heat and sun as possible to run their metabolic processes.

Warm-blooded animals are everything else—including birds (or avian dinosaurs). We can maintain homeostasis (i.e., regulate and maintain a constant body temperature through metabolism). But doing this requires much more energy consumption and output, and requires different anatomical and physical traits. It also means we can live anywhere, hunt for food anytime, and not have to worry about the environment to meet our temperature regulation needs.

So the fact that there is evidence for endothermy among dinosaurs has huge ramifications. We may need to reconsider how we classify them, and even how they became extinct.

Reptiles, a lineage of animals dating back over 300 million years, include organisms such as the extinct dinosaurs and the extant (still living) species of lizards, crocodilians, turtles. It was later expanded to include birds, based on genetic and molecular evidence. These new findings could also lead to more accurate phylogenies, or evolutionary trees.

Your DNA damage looks great, did you get just get back from the beach?

My students in Biology 101 are learning about DNA right now and one asked me how UV radiation causes damage to our genetic material. I know the basics, but was unfamiliar with the process. So I, of course, was intrigued, and had to look it up. Bear with me, I’ve tried to make this as simple and bare-bones as possible, so don’t let your eyes glaze over (like those of some of my students) when you see big scientific words.
DNA structure consists of a backbone molecule made up of sugar (a deoxyribose sugar, what the D in it’s name stands for) paired with phosphate molecules. Attached to each of those sugars is a nitrogenous base: adenine (A), thymine (T), guanine (G) or cytosine (C). It’s the complimentary pairing nature of these bases that allows for such perfect replication of our genetic material; A pairs with T, and G pairs with C, and that is what gives DNA it’s structure, chemical properties, and it’s ability to replicate so faithfully.
DNA replicates, or copies itself, in a process that is nothing short of amazing. The double-helix structure unwinds (with the help of an enzyme) and each parent strand is faithfully copied via complimentary base pairing. Throughout the process are “checkpoints” to prevent errors and proofreaders that won’t allow the DNA to code for protein unless things are correct.
Most DNA damage interferes with the ability to proofread or prevent incorrect proteins from being made, which is the case with UV radiation. UVB light causes one of the nitrogenous bases, thymine, to pair with itself instead of with adenine. These thymine base pairs next to each other in genetic sequences bond together into thymine dimers, an incorrect sequence which disrupts replication in the strand and which enzymes cannot read or copy. This leads to the production of melanin--a tan, or in severe cases, sunburn. Sunburn is the body’s way to get rid of cells damaged by UV radiation.
Direct DNA damage is reduced by sunscreen, which prevents sunburn; it won’t necessarily keep you from getting a tan. On the skin’s surface, sunscreen filters the UV-rays, decreasing their intensity. When sunscreen molecules penetrate the skin, they protect against direct DNA damage because the UV-light is then absorbed by the sunscreen and not by DNA.
So, that beautiful golden color you get when you lay out in the sun, the one you think makes you look so good? Yeah, not so good. That damage accumulates in your DNA, and over time can lead to skin cancer.
We do need some sun, so I’m not advocating staying inside on beautiful afternoons, just be careful and use sunscreen to decrease your risks of skin cancer.

Fueling my new obsession with mitochondira

I'm currently reading a fabulous book that I found just laying all by it's lonesome (i.e., in the wrong place) in Barne's and Noble a couple of weeks ago. It's entitled Power, Sex, and Suicide (now do you see why I had to have it?). And, if a fabulous title isn't enough it's about my newest favorite organelle--the mitochondria.
Dr. Nick Lane, a British science writer, does a very admirable job with this subject, especially in light of all the research being done in this area. Unfortunately, I am not very far along in the book, but it's one of those I can't put down so far. It's interesting and inspiring (as a wanna be science writer), as Lane says things like "the living cell is a minute universe" (p. 8) and he calls mitochondria the "clandestine rulers of the world" (introduction). I love these descriptions!
As I get further in to it, I will share more, but I wanted to share the title and the fact that it's a good read, at least thus far.