Breast Cancer Diagnosis and Classification

Breast cancer is the second most occurring cancer for women in the United States. It is estimated that there are 230,000 new cases arising in American women annually. It also occurs in men, but at a much lower rate of 2,300 annually.

Breast cancer is a form of carcinoma, cancer that originates from epithelial cells. The type of breast cancer is determined through a series of tests on breast tissue by a pathologist, a physician specialized in examining tissues in order to diagnose disease and recommend treatment. The pathologist examines the tissue through a microscope and identifies if cancer is indeed present and whether it is “in situ”, meaning non-invasive, or if it is invasive. Non-invasive cancers stay within their origin tissue, and have not yet spread to other normal tissue but invasive cancers have spread out to once noncancerous cells. For invasive cancers, the cancer is graded 1 to 3, through a comparison of the patient’s breast tissue with normal healthy tissue. The lower the grade, the less likely the patient has a cancer that will spread further. The higher the grade, the faster growing the cancer is, and therefore the larger the probability of spreading.  

Additionally, breast cancer cells can have estrogen receptors (ER+), progesterone receptors (PR+), both receptors or neither receptors. Two-thirds of breast cancer types have at least one of these hormone receptor types. The receptors allow cancer cells to obtain and utilize their respective hormones to fuel their development. Furthermore, one in five of breast cancers have too much HER2/neu, a protein that fosters cell growth. HER2/neu positive cancers are more invasive than other types. The amount of HE2/neu is usually identified through immunohistochemistry, an antibody test that changes cell color in response to an overabundance of HE2/neu, or a fluorescent in situ hybridization test (FISH) that uses fluorescent pieces of DNA to bind to the HER2/neu gene in cancer cells.  A triple negative cancer doesn’t have estrogen or progesterone hormone receptors and doesn’t have too much HER2/neu. Conversely, a triple-positive cancer is ER+, PR+ and HER2+.

A PAM50 test, working through identification of patterns of molecular features, is another classification method and divides breast cancer into 4 types. These are Luminal A, Luminal B, HER2 type and basal type. Luminal A/B cancers are ER+ cancers, but A type cancers are low grade, slow growth. B type cancers are high grade, fast growth.  HER2 type cancers are high grade and result from excessive copies of the HER2 gene in cells. Basal type cancers are triple negative type cancers, high grade, and require different treatment than the other types.

The extent the cancer has spread through the body can further be identified through more tests such as a chest x-ray, CT scan, bone scan, MRI, ultrasound and or PET scan. These tests allow the determination of the “stage” of the cancer in the body and are not usually used for early stage cancers. The most common system for “staging” used is the American Joint Committee on Cancer (AJCC) TNM system. T stands for primary tumor and is ranked zero to four, indicating the tumor size and spread to chest or skin. N stands for nearby lymph nodes and is ranked zero to 3, indicating if nearby lymph nodes have cancer and how many are cancerous. M stands for metastasis and is ranked 0 or 1, with 1 indicating the cancer has reached distant organs from the source. Combinations of the TNM ratings determine the stage of the cancer, from Stage I to Stage IV, with non-invasive cancers at Stage 0. Larger numbers for the TNM system indicate greater size, spread and severity.

Continuing research into cancer will augment our understanding of the mechanics of breast cancer and how to treat it. The fast pace of advancement in the medical field means that some of the current methods for diagnosing breast cancer may even become obsolete or new technologies may be invented. As such, the way breast cancer is diagnosed and classified is “subject to change”.

Written By: Kevin Yiu

Sources:
  1. http://www.mayoclinic.org/diseases-conditions/breast-cancer/basics/definition/con-20029275
  2. http://www.cdc.gov/cancer/breast/basic_info/what-is-breast-cancer.htm

 

Getting the Jitters?

If you’re reading this, then you’re probably part of the 54 percent of adults who drink coffee in the U.S. Why do we drink coffee? For most of us it is out of necessity to keep us awake and alert. We drink it on a daily basis and splurge an endless amount of money each year on this beverage. It’s only suitable for us to know what’s in coffee and how it affects us.

Caffeine, as we all know, is the prime ingredient of coffee. It assumes the role of a stimulant and provides a boost in alertness. Caffeine has demonstrated its efficacy whenever we wake up from little sleep, work overnight shifts, or suffer from our post-lunch laziness. There are studies that have shown that coffee does in fact improve performance when it comes to doing tedious, repetitive tasks. Caution must be taken however that too much caffeine can result in a decrease in performance.

In terms of sleep, extra care should be taken if you’re going to consume caffeine. Generally, caffeine can interfere with sleep if drank by occasional drinkers, whose bodies are not accustomed to breaking down caffeine without much expenditure of energy. The stimulant might prove to be a bit too much in this population and can easily keep this group awake. Of course, for regular coffee drinkers, the effects are not as pronounced as their bodies have adapted to absorbing caffeine. No matter how frequent of a drinker you are, some ground rules should be followed for the sake of your sleeping patterns. Firstly, everyone has their limits on how much caffeine they can tolerate without overstimulation taking place. Know your limit and try not to surpass it. Second. It is not a good idea to drink coffee in the evening since you run the risk of going to sleep right around the time the caffeine kicks in.

Despite the negative portrayals of caffeine in regards to our dependence on it,  there are some bright sides to it. Regular coffee drinking can slow down age-related cognitive decline. Along with that, coffee has been shown to ward off the risk of developing Alzheimer’s Disease by as much as 20 percent. The same correlations apply between the risk of getting Parkinson’s Disease and intake of caffeine consumption. And yes, there are other possible components of caffeine that give it a neuroprotective, anti-oxidative, and anti-inflammatory effects.

Does this mean it is completely fine to ignore the criticisms of caffeine consumption and go on enjoying that Starbucks latte? Of course not. Moderation is key to anything we do and what benefits we obtain from it. Drinking coffee at responsible intervals and amounts won’t pose significant harm to your body, and at the same time, abstaining from caffeinated beverages altogether is perfectly fine too.

Written by: Ubayed Muhith

Why Some People Are More Likely To Develop Anorexia and Bulimia

Photo courtesy of Science News
Photo courtesy of Science News

Did you ever wonder why certain people are more likely to develop anxiety, eating orders or other psychiatric related conditions? Well in short, it’s in your genes. A group of scientists have done research on mice and have discovered that when a certain gene receptor in their brains is altered or mutated and its ability to function is distorted, it ultimately effects their behavior. ESRRA, the gene in question, is an estrogen related receptor and helps control anxiety and inability to adapt in these mice.

There are some connections that are drawn by human beings creating the notion that in some families, certain people are more predisposition to develop and carry on certain psychiatric-related conditions like anorexia and bulimia which are both eating disorders. We know that from society, we are thrown with unrealistic expectations and standards of extreme dieting and weight expectations for both genders. However, our ability to cope and control our decisions in overcoming these harsh and brutal standards set by the media is a result of our inherited gene receptors. Families with and without damaged mutations of the ESRRA gene have been tested and those with eating disorders had consistent results of having the mutation and families who did not have eating disorders did not have this impairment.

Consequently these studied demonstrate the connection between the gene ESRRA and the individuals who have eating disorders. From this discovery we can come to a more accurate understanding of the genetic disposition of those who develop eating disorders over the span of their lifetimes and perhaps even research further in this field. Maybe we can use this perspective of these eating disorders and treat them more like medical diseases that we can cure with medicine, therapy and surgery.

Sources:

Feltman, Rachel. “Scientists Manage to Give Mice ‘eating Disorders’ by Knocking out One Gene.” Washington Post. The Washington Post, 09 Apr. 2015. Web. 11 Apr. 2015.

Psychopath’s brains are unable to fully process punishment

“Here’s Johnny !” Jack Nicholson in film “The Shining”

According to researchers from South London and Maudsley NHS Foundation trust and the Institute of Psychiatry, Psychology and Neuroscience, adults that have psychopathic personality disorder process punishment and reward differently than normal adults because of systematic differences in their brains. The researchers’ studies involved 12 violent individuals diagnosed with anti-social personality disorder (ASPD) and psychopathy, 20 violent individuals diagnosed with ASPD but not psychopathy and 18 healthy non-offenders to serve as the control group. Those with ASPD are commonly hostile, quick to act on impulse and abysmal at decisions. Those with psychopathy are commonly characterized with a lack of empathy towards others and use aggression in order to obtain what they desire without caring about the impact of their actions on the well-being of others. The researchers’ reason for focusing on ASPD and psychopathy in individuals is due to the majority of violent criminal activity being done by people with ASPD. Additionally, half of the people in the prisons in the United Kingdom have met the diagnostic standards for having ASPD. A third of those with ASPD in prison also fit the criteria for psychopathy.

The study consisted of the individuals performing a “reinforcement learning task” while in a functional MRI scanner. The researched tried to evaluate the abilities of the members of the three groups to change their behavior, exhibit “adaptive decision-making”, when they started getting punished for actions that were previously rewarded. The researchers found that those with psychopathy did not merely have a reduction in neural sensitivity to the punishment but instead had different organizational structures in the brain systems responsible for processing information on reversal learning and adaptive decision making. The researchers concluded that the current classification of adult diagnostic schemes included a too large range of individuals with varying characteristics. This included psychopaths who had structural processing differences in their brains from other individuals. Treatment should then be made to be specific instead of general.

This study reminded me of the paper “The Role of Emotion in Decision Making”.  In that study,  individuals with impairments in the brain, specifically vmPFC lesion patients, chose actions detrimental to them even with foreknowing that harm would come onto them if they performed those actions. Like those with psychopathy, their brain processes the consequences of their actions differently and unlike normal individuals, they lack the same level of ability in choosing “good” actions.

Sources:

http://www.slam.nhs.uk/media/news/psychopaths-brains-unable-to-fully-process-punishment

Naqvi N, Shiv B, Bechara A (2006) The role of emotion in decision making: a cognitive neuroscience perspective. Curr Dir Psychol Sci 15:260 –264.

HIV Immunity Due To A Gene Mutation

Courtesy of Homeomodulation

The main target of HIV is a group of human immune system cells marked with the CD4 glycoprotein. By altering these cells and using them as a host to help manufacture more of the HIV virus, the human immune system and therefore the infected person is vulnerable to infection from other harmful viruses. Without an effective immune system, even the common cold can become life-threatening.

However, individuals with a CCR5-delta 32 mutation of the CD4 gene are immune to the HIV virus. Their cells prevent HIV from entering their cells. Biologists from the the University of Liverpool discovered in 2005 why Europeans in Scandanavia had substantially higher levels of this gene than Europeans near the Mediterranean Sea. It was due to the Black Death, a series of viral haemorrhagic fevers that swept across Europe killing millions. These viruses were found to have been using CCR5 as the access into the cells. The viruses lasted much longer in Northern Europe than in the South, meaning that there was greater amount of time for there to be selective pressure on the gene.

Basically, people who were immune to the haemorrhagic viruses due to a genetic mutation were more prevalent in the Northern European populations. This immunity also applied to HIV because HIV uses a similar method of infection to that of the Black Death viruses. This is an example of natural selection within the human population. If scientists could somehow learn from this mutation to confer immunity to HIV for those who don’t naturally have the gene, it could be a great boon for the advancement of medical science.

Sources:

University Of Liverpool. “Biologists Discover Why 10 Percent Of Europeans Are Safe From HIV Infection.” ScienceDaily. ScienceDaily, 3 April 2005. <www.sciencedaily.com/releases/2005/03/050325234239.htm>.

Paoli, Julia. “HIV Resistant Mutation.” Scitable. Nature Education, 6 October 2013. Web. Accessed 21 Oct. 2014.

Food for Thought: The Size of the Universe

Courtesy of http://www.windows2universe.org/the_universe/images/galaxies/m31_small.gif

 

In our hectic lives and busy schedules, it is easy to get caught up in the massive amounts of work to be done. We sometimes barely have enough time to even think. We then miss out on many things. For example, when was the last time you looked at the moon or the stars and thought about them. They look so big and yet so small at the same time. If you just reach your hand out, you may even be able to hold them in palm. Of course, the reality is that they are massive celestial bodies and much further than you could imagine.  The Universe is much bigger than just our human civilization and even the planet Earth.

The universe is so massive that it boggles human comprehension. Light which seems almost instantaneous, actually still has a finite speed of 300,000 km/s. The fastest human spacecraft was Helios 2 and it had a top speed of 4216.6 km/s and that wasn’t due to its propulsion but instead due to the acceleration of gravity caused by it falling into the Sun. The speed of light truly is   insanely fast but still minuscule compared to the vastness of space and space deserves its name.

You may have heard of the term “light-years ahead” in comparisons as a unit of time. That is incorrect. Light-years are actually units of distance. It is the distance that light travels in a year. That is approximately 10 trillion kilometer. That is 249,532,127 times the circumference of the Earth.

And yet the nearest stars to the Earth are multiples of light-years away. The closest star system to our own solar system is Alpha Centauri and that is 4.22 light years away from the Earth or 40.22 trillion kilometers away.

Even more shocking is the fact that the light, the image, of the stars we’ve seen are merely the light that star emitted in the distance past. For example the light of a star that is 15 light-years away from us is actually 15 years old. On greater scales like billions of light years away, it is possible that such stars have already ceased to exist but the image of their destruction won’t reach us for billions of years.

Furthermore, although space truly is full of empty space, the amount of things in the observable universe is absolutely staggering.

There are an estimated 100 billion stars in the Milky Way. 100 billion stars. In the observable universe, there is  an estimated 100 billion galaxies. 100 billion galaxies! mind = blown

Source

Bennett, J. O. (2008). The cosmic perspective. San Francisico, CA: Pearson Addison-Wesley.

What is…Ebola?

We in the United States of America and other developed countries are fortunate to have fully functional healthcare systems. Building upon years of experience and advances and technology and countermeasures such as antibiotics and vaccinations, entire diseases have been exterminated.  However we often forget that among the rest of the world, we are in the minority. A majority of the world is unable to receive the same level of medical treatment we have come to expect, some people don’t even have doctors to go to.  This lack of healthcare infrastructure results in disastrous consequences.  The epidemic of Ebola in Western Africa is a prime example of what happens to people without a working healthcare system.

Courtesy of WHO, CDC

Courtesy of WHO, CDC

 

The Ebola virus, Zaire ebolavirus,is transmitted through contact with the bodily fluids of the infected through direct contact or indirect contact like through tainted objects.  There is an incubation period of 2 to 21 days with symptoms showing at 8-10 days after the initial infection.  These symptoms include fever greater than 38.6 C or 101.5 F, severe headaches, muscle pains and weakness, diarrhea, vomiting, abdominal pain, and lack of appetite.  The fatality rate, when left untreated, can reach 90%.  This is further compounded by the fact that there are no cures or vaccinations for Ebola. (Although there have been experimental serums being worked on and have been quickly pushed through experimental trials due to the severity of the problem.) The only treatment currently available for these people is isolation, bed rest and nutrition in the hope that they are able to fight off the disease with their own immune system.

The Ebola virus is believed to be primarily carried by bats and transferred to other mammals, collectively known as bush meat. Humans in West Africa ate this bush meat, contracting the virus. Initial attempts to prevent the eating of bush meat failed as the general public refused to believe that Ebola could be spread through bush meat or even that Ebola itself was real.

There have been Ebola hemorrhagic fever outbreaks previously but the current outbreak in 2014 is the worst one yet. Cases have been reported in Guinea, Liberia, Nigeria, and Sierra Leone. There have been 519 suspected and confirmed cases of Ebola with 380 deaths in Guinea. In Liberia, there have been 786 suspected and confirmed cases with 413 deaths. In Nigeria, there have been 12 suspected and confirmed cases with 4 deaths. In Sierra Leone, there has been 810 suspected and confirmed cases with 348 deaths.  Among these deaths have been physicians, nurses, and other medical care professionals. Unable to cope with the deaths or even to stop the spread of Ebola, these nations have begun to close off borders in desperate attempts to stop it. The most poignant  aspect of these epidemic is the fact that in modern industrialized countries, Ebola would be easily contained and treated. Modern medical science would have been able to stop Ebola from spreading if only it was available.  Unfortunately, in West Africa, due to corruption and neglect of the healthcare system, the medical apparatus was unable to stop Ebola. Making the situation worse is the pervasive culture of superstition,  mistrust of doctors, and ignorance.

Many of the public believe that Ebola is fake, a hoax, and any attempts to treat the Ebola-infected was instead a conspiracy to harm them. To West Africans, bush meat has been a critical component of African diet for millennia. Furthermore, the isolation of the infected separates people from their family, something nobody would want and it often appears to the family of the infected that the doctors were murderers and not helpers.  Not trusting modern medicine, many turn to traditional medicine which have no effect and only serve to help spread the illness.  They also attack the very people trying to stop the disease, again believing that those who wish to save them are actually cannibals.  Armed men and mobs have attacked and looted Ebola treatment centers, in attempts to loot the centers or to take out their family members. These acts of violence have caused infected patients to escape, further spreading Ebola to more people.  The inability of the West African governments to control the situation means the situation will only worsen. Faced with a lack of medical supplies and workers,  experts fear that this epidemic may last months before any hope of  a resolution and before that happens, many more people will die.

 

Sources:

http://www.bbc.com/news/world-africa-28841040

http://www.cdc.gov/vhf/ebola/outbreaks/guinea/index.html

http://www.cdc.gov/vhf/ebola/

http://www.cnn.com/2014/04/11/health/ebola-fast-facts/

Linus Pauling and Vitamin C, a lesson

Every morning, waiting for the delicious sweet and sour fizzy orange vitamin C tab to dissolve in the glass of water was part of the breakfast ritual. Maybe I should emphasize that this 1000mg Vitamin C was given in addition to a fresh squeezed orange juice, bananas and whatever other fruits of the season that the Carribbean island I am from had to offer. Having our daily quota of vitamins growing up was a must for my parents. Today, I seldom skip my “Emergen-C drink” before starting my day, attributing to vitamin C my capacity  to balance social life with long work-study days. Praising to others the importance of vitamin C in my every day diet, and stating from my own observations that it even reduces the chances for cold sores to occur, I tried to find in literature some support for my claims. After all, it could simply be a placebo for me, especially given the psychological dimension of  it given its link to my childhood…
Even though I could not find much data in renowned journals about vitamin C and Herpex Simplex (a.k.a. cold sore), I was a little comforted to see that somehow, somewhere on the planet, it had been researched. However, the one thing that made me feel happily satisfied was to discover that the person who would had given the strongest support to my beliefs (aside from my own father), was none other than Dr. Linus Pauling.
Yes, the same Pauling whose principle will inevitably be learned by anyone taking a General Chemistry class. The same Linus Pauling who set the path for Watson and Crick in their discovery of the double helix (actually named after Pauling’s α-helix protein structure!). Pauling, who on top of being one of the greatest chemists of the 20th century, was also a great humanitarian and earned not only one but two unshared Nobel Prizes! One for Chemistry (at 30 years old), and one for Peace (he was a fearless peace activist)… Well, here it is! Pauling has also pioneered research on  vitamins!
Sadly, reading further, I also learned that it was this same research on vitamin C that caused his reputation as scientist to go down the drain, as he became considered more like a mad man, blinded by his obsession. Recent findings have undermined the widespread beliefs in the benefits of vitamins.
Many questions since then remain in my mind. First of all, isn’t obsession needed for research? My answer is yes. In fact, whole communities of researchers are needed to question results to not only weed out bias, but also further a cause. On the other hand, where is the line between criticism and ridicule? How much more objective is the other party that wants to prove the scientist wrong? It seems that Pauling went a little far with his claims regarding Vitamin C, even arguing that it was the cure to cancer and could prolong lifespans to 150 years. Could his age (70 years old at the time) be to blame for such a great thinker to loose rationality? It is hard to believe that a person who relied for most of his life on proven facts, would not have some rational basis to consider that deficiency in diet is linked to diseases.

One might reply that, despite his  achievements, Pauling was not invincible. After all, he was convinced that genetic material was made of protein and not nucleic acid. Nevertheless, his conclusions were based on facts and even though his research did not lead to the final result on the discovery of DNA, it has certainly highly contributed to it.
Pauling’s contemporaries from the research field have deconstructed his beliefs through leading studies. Results have even shown that high doses of vitamin C can increase mortality and disease occurrence (the “antioxidant-paradox”). However, some of Pauling’s followers argue that many of theses studies have been poorly designed and do not properly assess the effects of vitamins on individuals…

Although I wish I had the time and skills to go through all these pro or against vitamins papers and evaluate how each study was conducted to build my own opinion, what I believe there is to learn from this is that critical thinking in whatever we read and the actions we take are essential; no matter how great our achievements can be in a lifetime, our views and beliefs are never infallible.

Reference:

Offit, Paul. “The Vitamin Myth: Why We Think We Need Supplements.” The Atlantic. Atlantic Media Company, 19 July 2013. Web. 21 July 2014.

The Sunshine Vitamin and Prostate Cancer

Virtually every pre-health student has to read a journal article at least once during his/her undergraduate years. Often, students find them intimidating, boring, or just plain dense. But these articles can also be incredibly fascinating, and they can be a great window into the research world.

One of the goals that I have with this website is to expose students to these journal articles by having our members post summaries of particular articles here.

Below is a summary that I wrote this past semester for one of my biology classes at Hunter.

The journal article can be found here.


In a 2005 scientific journal article entitled “Molecular mechanisms mediating the anti-proliferative effects of Vitamin D in prostate cancer”, researchers at Stanford University School of Medicine describe the effects of calcitriol (the biologically active form of vitamin D that acts as a hormone) on tumorigenesis in the prostate. Their findings show that calcitriol affects the production of cyclooxygenase-2 (COX-2) and 15-prostaglandin dehydrogenase (15-PGDH), which are both involved in prostaglandin metabolism. Also, when paired with NSAIDS, calcitriol becomes an even more effective treatment in cancer.

Studies in the past have shown a possible link between prostate cancer and calcitriol. Prostate cancer is usually treated with radiation or surgery, and if it turns metastatic, it is treated with androgen blockers. However, blocking the production of androgens is only a temporary solution because the cancer goes from being androgen-dependent to androgen-independent, which is much harder to treat. Calcitriol has been shown to inhibit tumorigenesis in both types of prostate cancer, which is what makes it of such interest. Also, UV light is integral to the production of vitamin D in the body, and studies have shown that low levels of calcitriol in the body increase the risk of developing prostate cancer. Lastly, polymorphisms in the gene that encodes the vitamin D receptor may contribute to the development of this kind of cancer.

Two other points of interest are that 25-Hydroxyvitamin D3-1-α-hydroxylase, the enzyme that makes calcitriol in the kidney, and 24-Hydroxylase, the enzyme that helps catabolize calcitriol are both made in the prostate. Because the first enzyme converts 25(OH)D3 to calcitriol, it was thought that giving patients 25(OH)D3 could be an effective treatment, but it was discovered that cancer cells have low levels of 1-α-hydroxylase, and normal cells have high levels of the enzyme. Therefore, giving 25(OH)D3 wouldn’t be helpful to people who already have prostate cancer but would be helpful as a chemopreventative drug. 24-Hydroxylase is an enzyme that catabolizes calcitriol and is actually activated by calcitriol itself. In cells that are resistant to the anti-proliferative properties of calcitriol, there is a high level of this enzyme. However, when calcitriol is paired with a P450 inhibitor, then it’s effective against cancer in these types of cells.

At the time the article was written, the precise mechanism(s) behind the inhibitory effects of calcitriol on cancer cells were not known. However, the researchers cited evidence that calcitriol causes cell cycle arrest in the G1/G0 phase. “The growth arrest appears to be due to an increase in the expression of cyclin-dependent kinase inhibitors p21Waf/Cip1 and p27Kip1, a decrease in cyclin-dependent kinase 2 (Cdk2) activity, accompanied by a reduction in the nuclear fraction of this molecule and the hyperphosphorylation of the retinoblastoma protein (pRb)” (Moreno, et al). Calcitriol can also cause apoptosis of certain cells and decreases the expression of bcl-2, an anti-apoptotic gene. These are all effects that are commonly seen in anti-cancer agents.

The researchers did cDNA microarray analyses of normal cells and prostate cancer cells in order to find other molecular pathways. The analyses revealed that calcitriol is involved in the regulation of two genes involved in prostaglandin metabolism. It decreases the expression of COX-2, which is a gene that is involved in prostaglandin synthesis and increases the expression of 15-PGDH, which is a gene that is involved in the inactivation of prostaglandins. Studies have shown that prostaglandins play a role in the development of prostate cancer. Prostaglandins are made from arachidonic acid with the help of COX. COX-2 is activated by a host of molecules that are also involved in cancer including a host of mitogens and cytokines. Elevated levels of the enzyme have been shown to be present in multiple kinds of cancers. It’s been shown that high levels of COX-2 lead to the stabilization of survivin, which acts to block caspase activation, a key step in apoptosis. The mechanisms through which calcitriol decreases the expression of COX-2 were unknown at the time the article was published.

A second gene that calcitriol affects is 15-PGDH, which is involved in inactivating prostaglandins. The enzyme, 15-PGDH, inactivates prostaglandins by converting them to 15-keto derivatives. It has previously been shown that 15-PGDH is downregulated in colon cancer. This is because 15-PGDH expression is activated by TGFβ, and cancer cells have mutations in the TGFβ receptor. When 15-PGDF was transfected into these cancer cells, the tumors didn’t develop or were slowed down in their development. The researchers in this study show that calcitriol upregulates 15-PGDH in prostate cancer cells, which would prevent the accumulation of prostaglandins and the progression of the cancer.

Because calcitriol is involved in calcium homeostasis and bone metabolism, one side effect of excess calcitriol in the body is hypercalcemia. Scientists have tried to use calcitriol analogs as a substitute, and this has helped reduce side effects. However, towards the end of the article, the researchers suggest that another way to mediate side effects and to more effectively repress tumorigenesis is to use calcitriol with NSAIDS. NSAIDS have been shown to suppress the development of prostate cancer as well as other kinds of cancers. They do this by inhibiting both COX-1 and COX-2. However, NSAIDS have cardiovascular side effects, which can be life- threatening. If calcitriol and NSAIDS are used together, then lower concentrations of both drugs can be used, and the risk of hypercalcemia and cardiovascular issues would be reduced. Since calcitriol affects the expression of COX-2, lower levels of the enzyme will be made in the body so lower levels of NSAIDS will be needed to counteract COX-2.

Overall, this article gives a thorough overview of the current knowledge of how calcitriol impacts cancer cells as well adding in new experimental material that shows the link between calcitriol and prostaglandin metabolism. What’s most exciting about this link is that calcitriol is naturally synthesized by the body so giving patients more calcitriol would result in less side effects than giving them other types of treatment. Also, the researchers’ suggestion of using calcitriol in conjunction with NSAIDS seems like an effective combination that would produce good results with few side effects.

References

Moreno, J., Krishnan, A. V., & Feldman, D. (2005). Molecular mechanisms mediating the anti-proliferative effects of Vitamin D in prostate cancer. The Journal of steroid biochemistry and molecular biology, 97(1), 31-36.

Your neural reward system and its relationship to drug addiction and obesity.

The reward system in our brain provides us with feelings of pleasure and happiness that occur when dopamine, a type of neurotransmitters (chemical substances that acts as a signal), is released. Due to this desire to feel pleasure and happiness , we are more motivated to go after things that provide us with these feelings. Consequently, this motivation for pleasure is a contributor to drug addiction as well as obesity.

Cocaine is an example of a drug that affects the reward system. As cocaine was sniffed by the participants in the experiment conducted by McGill University Health Centre and McGill University, the amount of dopamine released increased. As the increase of dopamine led to the increase of pleasure and happiness, drug users then desired the pleasant feelings again which could have led to a desire for more cocaine resulting in an addiction. The researchers correlated the “intensity of the reward-circuit response” to the “increased susceptibility to addiction.” What is surprising is that drugs are not the only things that affect our neural reward system. Sugars and, recently discovered, lipids also influences our neural reward system.

Photo courtesy by drugabuse.gov
Photo courtesy by drugabuse.gov

Can we all agree that most of the time, it is easier to get up to get a snack when the snack is chocolate versus when it’s a healthy snack? The motivation that we have to go get chocolate is due to the dopamine, triggered to release by the sugar in chocolate onto our reward system. The pleasurable feeling created when food is consumed motivates us to eat more; however as triglycerides, fat substances in food, build up in our brain, the motivation to physically get more food reduces. This was proven by a group of researchers who induced small amounts of lipids into brains of mice in order to mimic a good meal consumed. As the amount of lipids increased, the physical motivation to push a lever for food decreased. This stopped the mice from eating. Removing the enzyme from the reward circuit of the brain that breaks down these triglycerides led to a continuous increase in food uptake which may have led to obesity. 

As more research slowly display the correlation between increases in dopamine release and drug addictions as well as the role our reward system play in what we eat, further steps can then be identified to tackle issues within these areas of concern. 

Sources:

http://www.sciencedaily.com/releases/2014/04/140415084200.htm – Obesity: Are lipids hard drugs for the brain?

http://www.sciencedaily.com/releases/2011/08/110830193855.htm – Faulty signaling in brain increases craving for sugar and drugs

http://www.sciencedaily.com/releases/2009/05/090519134706.htm – Cocaine: Perceived as a reward by the brain?