Is diabetes medication the cure for cancer?

The CDC estimates that in 2014 29.1 million people had diabetes, with 8.2 million people living without a diagnosis of their condition. One of the most popular medications to help those with diabetes is Metformin. One popular brand name of metformin is Glucophage, although it is marketed as part of a variety of diabetes medications. It is an oral medication given to diabetics and people that are pre-diabetic in order to help control glucose levels and increase insulin sensitivity. Some studies in the past have found diabetes medications can also help with other problems, such as preventing cardiovascular disease and polycystic ovary syndrome. While interesting these studies have limited impact on treatment options besides diabetes.

New studies, like the one linked below, are starting to test and see if metformin can help to treat cancer and decrease tumor growth. It has long been known that controlling glucose levels in diabetics is key to lower the incidence of other diseases, even some that at first do not seem related to glucose levels. The exact mechanism of metformin is unknown, and the extent of biochemical pathways it interacts with has been increased as more research has been done. This has been researched since the 1950s and things are still being discovered about the mechanisms of action exhibited in the body. One thing that has been found is that metformin activates the AMPK pathway, leading to increased glucose uptake in cells.

The AMPK pathway has also been linked antineoplastic properties, since the AMPK pathway will upregulate mRNA that degrades a long noncoding RNA called H19. H19 serves to stop methylation of some genes by inactivating an enzyme called SAHH. With H19 knocked down by the addition of metformin, SAHH will help a methyltransferase methylate many oncogenes, leading to decreased growth in cancer cells. It is hypothesized that this reaction will also serve to keep healthy cells from becoming cancerous as well.

Since metformin is near side effect free it is safe for use by people without diabetes and is much less destructive than many current cancer treatments. Hopefully, after further testing and better elucidation of all of the pathways metformin interacts with, metformin can be used to create better cancer treatments. 

Want to see articles? Check it out below:

Metformin alters DNA methylation genome wide via the H10/SAHHH axis

By: T. Zhong, Y. men, L. Lu, et al. http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016391a.html

Cellular and molecular mechanisms of metformin: an overview

By: B Viollet, B Guigas

Diabetes Stats:

http://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html

 

Miracle Berries and how we can use them

There is a particularly unique plant in west Africa that I find interesting. The Synsepalum dulcificum is a plant that grows a berry containing the aptly named glycoprotein call miraculin. When consumed miraculin makes sour foods taste sweet. While eating the berry this effect can last from thirty minutes to an hour.  The actually name miracle fruit or miracle berry can be used to describe a few different plants, but all the plants share the same characteristic of altering the perception of taste.

While the exact mechanism of miraculin is unknown it is known that it binds to taste receptors on the tongue. When miraculin is exposed to lower pH, which is typical for acidic sour foods, it will change the binding to the taste receptors, activating the sweet receptors, causing any sour foods to seem sweet. Miracle berries are safe to eat and have been consumed in west Africa for some time without any reported side effects. The properties of miraculin have led to it being tested as a food additive. The only minor drawback is that miraculin can be denatured by heat, however it is still being tested and in some places used to sweeten diet sodas.

It has not been approved in the U.S., however with no negative outcomes being linked to consumption and with additional benefits coming to light that may be subject to change. Recent studies have tested miraculin as a supplement to control uric acid, a category known as anti-hyperuricaemia agents. High uric acid levels can cause gout and kidney stones. These problems occur more often among overweight populations, and finding a way to control uric acid levels could be beneficial to many people with chronic uric acid related problems. In the study I linked below miraculin lowered uric acid levels in mice as effectively as allopurinol, a commonly used drug for gout sufferers. The name miracle berry was given long before these benefits were known, however with these new benefits coming to life it makes the name even more appropriate.

The use of natural subsatnces to make modern medical treatments is a common occurrence. Many medicines have similar origin stories. Let me know what you think in the comments below.

For more reading on how miraculin decreases uric acid levels: 

Miracle Fruit (Synsepalum dulcificum) Exhibits as a Novel Anti-Hyperuricaemia Agent

Authors: Yeu-Ching Shi

Molecules. 2016, Vol. 21 Issue 2, p1-13.

ISSN: 1420-3049

DOI: 10.3390/molecules21020140

Autophagy: The Newest Nobel Prize

The newest Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi for his work on understanding and elucidating the mechanisms of autophagy. He has a doctorate of science from the University of Tokyo and has had professorships at multiple colleges in Japan. Much of his work has been on the vacuole of simple yeast. His decades of research have led to wide ranging advances in the understanding of autophagy and its relation to bodily processes. He also characterized many of the genes that code for the proteins involved in autophagy, as well as some mutations of the same genes.

Autophagy is the mechanism by which cells degrade and reuse cellular components that are no longer necessary. It involves the sequestration, transport, degradation, and recycling of material.  The body recycles components through the use of lysosomes, one part of the autophagy process. Autophagy is an important part of many biochemical processes and has been linked to many different causes and outcomes in cells from a variety of species. There are three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy is commonly triggered in response to physical stresses on the body, that forces it to efficiently clean and reuse cell materials. Some of these physical stresses include starvation and disease.

The degradation caused by autophagy helps power the cell in these trying times and it can also protect against infection and viruses. It has a role in a multitude of disease responses and can cause programmed cell death. Having said that there are many diseases that occur because of malfunctions in the autophagy process. When the mechanism malfunctions because of mutations in the genes that code for proteins involved in the process there has been linked to osteoarthritis, cancer, and Parkinson disease.

I highly recommend reading the interview of Yoshinori Ohsumi that I linked below. He talks about how he followed his interests to continue his research and at the end he shares some advice to younger scientists.

For more reading:

An interesting interview of Professor Ohsumi where he talks about the progression of his work:

Yoshinori Ohsumi: Autophagy from beginning to end

By: Caitlin Sedwick

J Cell Biol. 2012 Apr 16; 197(2): 164–165

http://jcb.rupress.org/content/197/2/164

Some more in depth information on autophagy:

Autophagy: process and function

By: Noboru Mizushima

http://genesdev.cshlp.org/content/21/22/2861.long

Developments in HIV Research

As a little introduction to the topic I will explain how Human Immunodeficiency Virus (HIV) works. HIV is a retrovirus, meaning that it infects cells and uses reverse transcriptase to infect normal cells with the genetic material of the virus. HIV creates RNA then uses a reverse transcriptase protein to integrate a complimentary DNA strand into the DNA of the host cell. HIV is particularly deadly because it attacks macrophages, dendritic cells, and CD4 helper T-cells, an integral part of the immune system. It can be spread through the transfer of many bodily fluids such as blood, semen, breast milk, or vaginal secretions. The virus has a long incubation period and is also known as a lentivirus. It infects CD4 cells, using them to replicate and over time it lowers the amount of CD4 cells in the blood to levels too low to stop infections. People with the lowest CD4 count are diagnosed as having stage 4 HIV infection, often called AIDS, or Acquired Immune Deficiency Syndrome.  

HIV is a relatively new disease, only being discovered in 1983. There is not a cure widely available and most treatments are a combination of drugs designed to limit the viral load in fluids to undetectable levels, which reduces transmission rates and increases the life span. If treatment is stopped the virus will begin replicating back to pre-treatment levels. Only one man has been cured of HIV, by being giving a bone marrow transplant from someone with natural immunity to the disease. It was a rare circumstance that cannot be replicated readily since bone marrow transplants are expensive and matches are hard to find, particularly since immunity to HIV is rare.  A few days ago a new series of treatments also produced a patient with no viral load, although further observation is needed to if this was a permanent solution.  

This research paper focuses on some of the inner workings of the cells that have been infected by HIV. It was thought that when a cell was infected with HIV it did not realize it was infected and the cell did not attempt to fight the infection. In reality this paper shows that the cells recognize HIV replication products and produce type 1 interferon. This would normally fight off many types of infections, however HIV produces accessory proteins that regulate interferon production. In many cases interferon is ineffective at fighting HIV and causes inflammation that is detrimental to the patient.  

Finding new things about HIV infections opens up new avenues of research. This research could lead to effective cures that work quicker and cheaper than those being researched now. It also shows that the understanding of this disease is not complete. What do you think about this ongoing research? Do you think HIV will be effectively cured sometime in the future?  

For more reading on research about HIV here is the journal article I started on:  

HIV Triggers a cGAS-Dependent, Vpu- and Vpr- Regulated Type I Interferon Response in CD4+ T Cells 

By: Jolien Vermeire, Bruno Verhasselt, et. al

GMO’s: Harder, Better, Faster, Stronger

As the world’s population increases the demand for sustainable and efficient agriculture has grown and many companies are competing to make ever better genetically modified crops.

 

Many genetically modified organisms (GMOs) are being improved in ways that have just been discovered. Older GMOs exist and have for some time, but the methods used to make the older generation of GMOs had many limits on what advantaged could be added to crops. Research has found programmable DNA binding proteins such as ZFP, TALEN, and CRISPR/Cas that allow for the input of specific DNA sequences in specific spots on chromosomes. These new techniques allow scientist to create widely improved crops and even add in totally new attributes that do not belong to those crops.

 

These newer crops can be changed in ways that were impossible by the older methods, creating crops that are disease resistant, protected from pests, and do not require as much sun. These are just three of many attributes that are closely targeted by scientist. There have also been some sensational news reports about odd but useful modifications being made in some places, and not all are related to this research. In Japan watermelons are being grown in square shaped containers, originally to decrease later shipping costs of the fruit. These watermelons are now highly prized and sold for more than regular watermelons because of this new shape. It is possible that the future holds GMOs created to not only be better for growing but also more ascetically pleasing.

 

The advantage to these techniques is that they are some of the only methods that have real potential to raise food production to the levels needed to meet demand. Crops will not spoil as fast and are better in every way than tradition crops, or even older GMOs.

 

Some of the disadvantages include patent protection on GMOs by the companies that make them, which are used to artificially increase seed prices for farmers and stop these great crops from ruining company profit margins. But while good for the company the prices can have negative impact on medium sized farms that have a hard time selling their produce at higher prices. There has also been some concern about lack of diversity in the crops. The lack of diversity is both in types of crops grown and the diversity among a single crop. With natural breeding no longer being a factor crops do not have the range of immunity to diseases that are seen in the wild nor the lucky mutations that prove advantageous in the face of adversity. As certain crops are more heavily modified and profitable than others the diversity of what is grown to meet the food supply will decrease. We have already seen evidence of this by the decreasing numbers of apple varieties available at super markets. Having diverse food sources helps grow food security since it is unlikely that that any one mishap will be able to ruin every type of crop. Decreased diversity will allow one type of mold, bacteria, or natural disaster to disproportionally affect the food supply if there are only a few types of crops being grown.

 

Let me know what you think about GMO’s. Are they good, great, or horrible for the future? Are the conspiracy theorists right about them being unhealthy?

 

Precision genetic modifications: a new era in molecular biology and crop improvement

By: Franziska Fichtner, Reynel Urrea Castellanos, Bekir Ülker

DOI 10.1007/s00425-014-2029-y

 

Nanotechnology vs. HIV: The fight of the future

Most HIV treatments focus on the use of anti-retroviral drugs to decrease the amount of virus in the body to almost undetectable levels. These drugs frequently target the enzymes that HIV needs to replicate itself inside of cells in order to slow replication and decrease viral load.

HIV has a high rate of mutation compared to a mammal such as ourselves, and it will often mutate in enough to develop resistance to certain anti-retroviral drugs. Mutations in viral RNA that change the proteins produced in cells or mutations that change how HIV enter the cell can lead to drug resistance. In order to slow down the development of drug resistance many patients are put on combination therapies, which use multiple medications to keep the viral load in a person low and stop virus replication at many steps.

With combination therapies the development rate of resistance is slowed, however there are worries that viruses will still mutate fast enough to outpace our ability to develop new drugs. As HIV drug resistance becomes more common it is likely that this will eventually be the case. New treatments that attack HIV in radically different ways are being developed to hopefully find a long lasting and safe treatment for HIV. One such treatment involves the use of RNAi or RNA interference. This involves using microRNA and siRNA to target conserved genes in HIV with little mutation, binding and destroying the viral mRNA to stop production of the virus effectively and efficiently. The only problem with this research is delivering the RNA necessary for interference to every cell that needs it.

Attempts have been made to create viral vectors to do this, however the results were often underwhelming and at times dangerous. This brings me to nanotechnology. The latest research is delving into multiple types of nanotechnology to safely deliver RNA to targeted cells. This technology includes artificial liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. Finding something that can deliver the RNA will allow for advances in many medications and may help to put a major dent in the spread of HIV worldwide.

Let me know what you think. Will nanotechnology be able to advance fast enough to find a transport system for RNAi? If you want to do more research on this topic you can start on the article below.

Nanotechnology Approaches for the Delivery of Exogenous siRNA for HIV Therapy

Simeon K. Adesina and Emmanuel O. Akala

Mol. Pharmaceutics

DOI: 10.1021/acs.molpharmaceut.5b00335

http://pubs.acs.org.ezproxy.shsu.edu/doi/10.1021/acs.molpharmaceut.5b00335

The evolution of disease

Some diseases are caused by a person’s genetics. In many cases diseases can be predicted by looking at DNA for specific genes that predispose someone to a disease. Having said that DNA is also connected to evolution, in that genomes that confer an advantage to a person will increase the probability of that person reproducing. Over time well adapted and healthy genomes will become prominent in a species.

            Why is it that so many diseases can be passed genetically when the theory of evolution claims that only the fittest will survive? Would that not mean that genetic based diseases should have died out long before the modern day? In truth it is much more complicated than that and there are many factors at play. Genetic diseases could always occur in a later generation through mutation in reproductive cells, being passed in that way. Or a series of other advantages will allow someone to still be fit enough to pass along a disease. Some diseases hide as recessive traits, only appearing when two carriers of the recessive trait mate.

            Then there are some diseases that are relics of a different time. Some diseases are still prevalent because they conferred an advantage in the past, and even with the significant side effects of a disease the advantage proved invaluable. Once this advantage was selected for it became prevalent in certain populations over time. Fast forward generations later and people still have these diseases in different circumstances that no longer provide a benefit, yet medical science has advanced enough that even without the advantage the disease will still be a permanent part of the population.

            One interesting example is Type 1 diabetes. People born with Type 1 diabetes have an autoimmune response that prevents them from producing enough insulin. Without insulin the person will have unusually high amounts of glucose in the blood. It has been found that Type 1 diabetes is most prevalent in northern Europeans, occurring at a frequency that is more common than random chance would suggest possible, showing signs of having been selected for in that area in the past. What advantage would that give? As it turns out high amounts of glucose in blood will depress the freezing point, increasing the tolerance for cold in humans. In the past minor ice ages and unseasonably cold weather would kill those unprepared for it, selecting those with Type 1 diabetes because of their tolerance for the cold. Trading a healthy amount of insulin for this advantage proved invaluable in the past and modern northern Europeans still suffer today as a result.

This leaves an interesting new avenue for understanding the epidemiology of disease. People with sickle cell trait have a higher resistance to malaria because of their malformed hemoglobin. Iron deficiency improves the chances of surviving infection by Yersinia Pestis, the bacteria that causes the plague, better known as the Black Death.

Finding how many diseases conferred an advantage in the past would also lead to better understanding of what diseases may give advantages in the modern day. A more holistic view of disease could also lead to new treatment ideas as well.

Want to learn more? I have an article about the prevalence of Type 1 diabetes listed below. A well written book on the subject of advantageous diseases that I have read in the past is also below. The book is much more interesting than any textbook and I highly recommend it for some casual reading.

For further reading please see:

The sweet thing about Type 1 diabetes: A cryoprotective evolutionary adaptation

By: S. Moalema, K.B. Storeyb, M.E. Percyc, M.C. Perose, D.P. Perl

http://www.sciencedirect.com.ezproxy.shsu.edu/science/article/pii/S030698770500054X

A more in depth novel on the subject:

Survival of the sickest: A medical maverick discovers why we need disease

By: Sharon Moelem