CANCER: NOT JUST A CONSTELLATION

Amongst the first world countries cancer is one of the most common diseases and takes many lives each year. All over the world scientists work together to create therapies for all types of cancer occurring in all types of body tissue. A problem with most of these therapies is that they are still crude. There is still much work to be done in improving these treatments as well as developing new approaches to treating and detecting cancer.

Although cancer is different from tissue to tissue, the principle of how cancer occurs is, among all types, similar.
All organisms are made up out of cells; microscopic compartments that together form the tissues of our body. All cells, except blood cells, contain a nucleus; a compartment within the cell surrounded by a membrane. Within the nucleus inherited genetic information is stored in the form of DNA; a large molecule made up out of four building blocks that code for proteins according to their arrangement across the DNA molecule. In order to maintain the integrity of body tissue, cells have to renew and they do so by replicating themselves, forming a new cell and an old cell both containing a nucleus with the same genetic information. This process is called the cell cycle. The cell can signal itself or other cells to initiate the cell cycle when the proper conditions are met.

However, our bodies are exposed to many external factors that could damage our DNA, such as cigarette smoke, toxins, radiation, infections or a hereditary disposition. These factors could disrupt the arrangement of the building blocks of DNA, which is called a mutation. The cell has different mechanisms to detect these mutations, which acts as a signal to the cell prompting it to cease its cell cycle in order to repair the damage or, whenever this is not possible, destroy itself.
If a cell’s DNA is thusly damaged that the signal to initiate a cell cycle becomes incessant, uncontrolled division occurs.

A cell that divides uncontrollably eventually forms a group of uncontrollably dividing cells. This group of defective cells are called a tumour, which harms the tissue integrity and leads to loss of function of the tissue.In what type of tissue a tumour occurs, can be an important factor to the threat posed by the tumour to the individual’s health.

Between different tissues are divisive barriers. When a tumour surpasses this barrier, this is called metastasis. When this occurs it becomes more difficult to apply the proper treatment to get rid of the cancerous cells, which in turn decreases the odds of remission.

Most forms of treatment are designed to damage cancerous cells to such a degree that they will self-destruct. An example of such a treatment is chemotherapy that applies toxins in order to inflict this damage. A downside to this treatment is that toxins do not discriminate between healthy and cancerous cells. This is why chemotherapy is extremely taxing for an individual’s health, as the treatment causes healthy tissue to atrophy as well. The biggest challenge is to develop treatments that minimise the
collateral damage done to non-cancerous tissue.

It has been proven that treating cancer in an early stage significantly increases the chance of remission. A currently expanding field of research pertains the early detection of cancer by looking at tumour specific markers that indicate that an individual is developing cancer. A cancerous cell acts differently than a normal cell as it divides more frequently and thus uses more energy than a healthy cell. Screening individuals for such cancer specific markers is imperative for decreasing the mortality rate of cancer-patients.

Cancer has an impact on all of us. Statistically it either affects you directly or indirectly.
Some people do their best to avoid the external factors that have been linked to increase one’s chance of developing cancer but might develop it nonetheless, whilst some who subject themselves to such factors all their lives might not. This leaves us with more questions and shows us that we still do not know all underlying processes and machinations that lead to cancer development and how to prevent and cure this omnipresent disease.

Arend de Vos

How something small can make a huge impact

Today, as we are living in the 21th century, we are facing many medical challenges. Among these challenges are finding the cure for diseases such as cancer, malaria, aids, Alzheimer’s disease and many more diseases. Many people tend to forget that early detection of a disease such as cancer can improve treatment of the disease. Thus a good marker, for instance a certain molecule in the blood, can be of great significance in many diseases for early treatment or even curing the disease.

In the early 90’s a very small molecule was discovered in the medical biology. It is something that might even change the future of early detection of diseases! Our human body consists of many cells and they all have their own tasks. The task they have to do is noted in our genes and is regulated by the expression of these genes. The small molecule that was discovered in the 90’s is called a miRNA and it is found in plants, animals, and some viruses. The effect of this molecule is that it can regulate the expression of genes.

Recently it was found that these miRNA’s can be found in the bloodstream and that they remain very stable there. These miRNA’s in the bloodstream are called circulating miRNA’s and they have their own signature expression profile. This signature can change under different physiological and pathological conditions. For instance, a disease like cancer can change the signature expression profile of these circulating miRNA’s.

Let’s take a disease that is very hard to detect in the very early stages of development. Alzheimer’s disease is a form of dementia that develops very early on but it is hard to detect. The very first symptoms can occur 25 years before someone can be diagnosed with Alzheimer’s disease. Early detection of the disease can be of great significance for treating the disease. Think about early prescription of medicine or even exercise to delay the onset of this disease. The very challenge in this disease is the early detection with great accuracy and little harm for the patient. Circulating miRNA’s can be the solution for the early detection of this disease. Since Alzheimer’s disease occurs normally at later age, we can take blood samples from people who are around age 50. When we screen there blood for the circulating miRNA signature we can check whether their signature might be related to a signature which occurs in Alzheimer’s disease. This is a great example for the use of circulating miRNA’s as a biomarker in Alzheimer’s disease. Several scientists are examining the circulating miRNA’s signature in Alzheimer’s disease, but there is still more research needed.

Another big medical challenge we are facing is curing cancer. Early detection of cancer can have great effect on the further development of the disease. Detecting a tumor in an early state can prevent the spreading of cancer throughout the body and can have an effect on the lifespan of a patient. For example, many women are screened for breast cancer nowadays. Other kinds of cancers are not screened while this is important too. Circulating miRNA’s can help in the detection of many kinds of cancers. In the last few years more research is done in circulating miRNA’s in several kinds of cancers.

In overall, these very small molecules can have a great impact in the medical challenges of the 21th century. In a futuristic aspect, people go to a physician once a year to have their blood checked on all their circulating miRNA’s. Comparing these miRNA’s to a huge database should indicate whether someone is developing a certain disease based on the miRNA signature profiles. With the easy and early detection of diseases, we can improve our lifetimes. We can even reduce costs of medical treatment and healthcare if we detect certain diseases such as Alzheimer’s disease in an early stage. Thus, miRNA’s could be the answer for early detection of diseases. Because the circulating miRNA’s are only recently discovered, much more research has to be done before the use of circulating miRNA’s can be implemented in the early detection of many diseases by just using the blood of a patient. Ultimately, we can alter miRNA’s ourselves to affect gene expression in treating diseases.
This is still very futuristic but kind of realistic. Because this concept is kind of new, I think the future has much more to bring. That is how something small can make a huge difference!

Michiel Konings

Antibiotic resistance: the scientific apocalyptic scenario

Caught a minor infection? Go get your miracle cure, antibiotics, from your local doctor’s office now! Receiving an antibiotic treatment seems so self-evident in modern day society, to a point that common infections are considered as harmless. But what happens if our miracle cure loses its effect?

That urinary tract infection that keeps coming back every year or that pulmonary infection you can’t quite shake off suddenly turn into something very dangerous and potentially deadly.

This sounds like a terrifying scenario.

A terrifying and real scenario.

It turns out that bacteria have caught up to our achievements in modern medicine. Many harmful bacteria have developed resistance against antibiotics. Antibiotic resistant bacteria no longer respond to drugs to which they were originally sensitive to making it harder or even impossible to cure.

What is antibiotic resistance

Antibiotic resistance is when a bacteria develops a way to incapacitate a certain antibiotic. There are four main mechanisms by which this can be achieved. The drug can be inactivated or modified by the bacteria making it harmless, the target site of the antibiotic can be altered thereby preventing the drug from binding, The bacterium can change its own metabolism to make the antibiotic target redundant for cell survival, or the antibiotic can be actively pumped out of the cell before it is able to cause any harm.

Bacteria have two ways to acquire resistance.
Bacteria are able to genetically mutate and acquire a change in the binding site of antibiotics. The bacteria is then less susceptible to the drug. This mutation is the past on to all further descendants. Although mutation occur only once in every ten billion replications, the high reproduction rate of bacteria cause this effect to still be significant.

Figure 1: Antibiotic targets and acquiring resistance

Resistance to antibiotics can also be caused by horizontal gene transfer where a resistance gene is transferred from one bacteria to another. This can happen between and within the same species. These transfers takes place by means of a special gene transfer mechanism. Most antibiotic genes are located on what is known as a plasmid. This is a small circular piece of DNA that can be easily copied and transferred through cell-cell contact via a pilus. The gene can also be transferred by bacteriophages (viruses that infect bacteria), or even release and uptake of DNA in

extracellular fluids.

Figure 2: Three ways of gene transfer between bacteria

Antibiotic resistance isn’t free

Although it seems that antibiotic resistance is of pure benefit to the bacteria, keeping itself safe from antibiotics comes with a cost. Acquiring antibiotic resistance costs energy and often interferes with normal bacterial processes. Resistance therefore comes with a fitness cost. Overall resistant bacteria are ‘weaker’ than their normal counterparts. However, this changes when the antibiotic is present.

Bacteria that carry a plasmid or mutation are better adapted to an environment where antibiotics are present, like your body during an antibiotic treatment. Following Darwin’s age old rule, survival of the fittest, the adapted bacteria survive, live and reproduce while the others die. This ultimately leads to a resistant colony.

That is when it becomes dangerous. Your suddenly faced with an infection that cannot be cured through the usual treatment. Furthermore you are an infection source for other people. 

Then why not treat it with another antibiotic?

This should of course be the usual course of action. However, most of the common bacteria strains have developed resistance to multiple antibiotics, making them incredibly hard to cure. For example, staphylococcus aureus strains (MRSAs) have developed resistance for multiple antibiotic agents due to its extreme pressure to adapt to antibiotics. MRSAs are therefore one of the most common causes of hospital-acquired infections infecting around 500.000 and killing about 11.000 patients in US hospitals alone.

how widespread is antibiotic resistance at the moment?

The World Health Organization (WHO) issued a global report in June 2014 on the magnitude and current surveillance of the spread. It has been observed that alarmingly high rates of resistance the seven most common pathogenic bacteria, such as E. coli, Salmonella and S. aureus, have been found throughout the world. The report also stated that tools to battle antibiotic resistant were often lacking or non-excitant in many countries. The threat was in fact so severe that a global action plan was installed to tackle actions that accelerate antibiotic resistance.  If we keep using antibiotics inappropriately and do not properly prevent and control infection, many medical treatments will fail and make common infections deadly again.

What can I do to prevent the apocalypse?

Antibiotic resistance is a complex problem, but you can be part of the solution. Small efforts like washing your hands, avoiding contact with sick people and getting vaccinated go a long way if they are applied by everyone. And when it comes to antibiotics: use only when prescribed by a doctor, always complete your treatment and never share your leftover drugs.

Coen Hanselaar

Cancer, just a case of bad luck?

We can all agree on the fact that good lifestyle choices such as avoiding smoking, eating a balanced diet and having daily exercise will offer you some protection from developing cancer. However, how much protection it will offer you exactly has never been entirely clear. Is it all worth it, or is all your good behaviour sticking to a healthy lifestyle just a waste of time and effort?

I started to ask myself these questions after reading a study from researchers from the Johns Hopskins University. This study showed that only 9 cancers from the 31 different cancers that were studied, were due to inheritance or poor lifestyle choices. So, simply put, when we manage to resist the temptation to take another snack or another cigarette it will not change the odds of developing at least 22 different cancers. But where do these cancers ‘come from’ and can we prevent them in a different way?

The answer lies in the way our bodies regenerate. A very carefully controlled process, whereby cells divide to produce new cells, allows our body to grow. During adult life it is the division of stem cells that allows our body to repair itself by replacing damaged or lost cells. Stem cells are undifferentiated cells that can differentiate into many different specialized cells and have the ability to go through numerous cycles of cell division, called self-renewal. When a stem cell divides, the DNA within this stem cell has to be copied, or replicated, and to be distributed over the two new cells, so that both will contain the same genetic information that lies in the DNA. Although it is a very carefully controlled process, random mistakes, or mutations, can occur during stem cell division. A mutation is a change in the DNA sequence; a chemical letter is incorrectly swapped for another chemical letter during replication. In the figure below you can see an example of such a random mutation in a piece of DNA sequence.

                       Fig.1: An example of a random mutation in the DNA sequence. A 

                       chemical letter is incorrectly swapped by another chemical letter 

                       during the replication process, or the copying process, of the DNA.

The more these mutations accumulate, the higher the risk that cells will grow in an uncontrolled way, which is a hallmark for cancer. During aging your stem cells keep dividing and dividing, which means more chance of random mutations and thus more chance of development of cancer stem cells. Bad luck. But how can we prevent ourselves from something so unpredictable such as bad luck?

For now, we cannot prevent ourselves from the random mutations due to bad luck by just optimizing our environmental factors and lifestyle choices, called primary prevention. However, since the study of the Johns Hopskins University says that two-thirds of cancer incidence is explained by random DNA mutations in stem cells, it is necessary that scientist focus more resources on finding ways to detect such cancers at early stage, called secondary prevention. Besides, according to the cancer stem cell theory, the stem cells in a tumour can cause relapse and spread of the cancer by giving rise to new tumours. Therefor detection at an early and curable stage is very important as well, so the tumour can be treated before it totally escalates.  

Do not misunderstand me by thinking that two-thirds of cancer cases are due to bad luck only. Cancer is always caused by a combination of many factors such as environmental factors, lifestyle choices and bad luck. But for two-third of the studied cancer types bad luck, or the random mutations, was the major contributing factor. Notice that still for one-third of the cancer cases, the environmental factors and lifestyle choices were the most involved factors.

In short, your good behaviour sticking to a healthy lifestyle is not a waste of time and effort, and is surely all worth it. Still a third of cancers, mainly skin cancer and long cancer, can be prevented by choices as quitting smoking, cutting back on alcohol, eating a healthy diet and avoiding too much sunlight. These good lifestyle choices can also prevent the other two-third of cancer cases if you are the lucky one that has no bad luck. So my advice: stay healthy & lucky!

                                                                                                                       By Dide Dijkstra