You, but at the Cellular Level: April 2019

Cancer Treatments

Two posts ago I discussed what melanoma is, and in my most recent post I discussed cancer in general. In this post, I will talk about what treatments are available for certain cancers and there stages.

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***RECAP***
Melanoma is a form of cancer that begins in the melanocytes. The most well-known form of melanoma is cutaneous melanoma, otherwise known as skin cancer. Cancer is a general term for a variety of different genetic diseases. There are different types of cancer, such as breast cancer, lung cancer, leukemia, etc. There are a variety of risk factors, depending on the type of cancer a patient has, that can be associated with cancer, such as it being genetic, having continuous UV exposure, smoking, abnormal cell growth, and many more.

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Treatments for cancer used in modern medicine (1):

https://www.impactguru.com/blog/getting-cancer-treatment-in-india

✤ Surgery: The physical removal of the tumor if it has not metastasized too deep into other parts of the body.

✤ Radiation Therapy (2): In radiation therapy, the radiation is used to kill the cancer cells or shrink tumors in a localized area. It is able to do this because the radiation damages the DNA so that the cancer cell can no longer grow and will ultimately die. Radiation therapy can be used along with surgery if a tumor is too large to remove. The radiation therapy can be used to shrink the tumor so that the tumor is smaller and easier to remove with surgery. There are two forms of radiation therapy: external beam radiation therapy and internal radiation therapy.

External beam radiation therapy is when a machine "beams" the radiation onto a specific part
of the body that has cancer.

Internal radiation therapy is when the radiation is in the form of a liquid or solid that is placed
inside the cancer patient generally near the tumor site.

Despite the type of radiation therapy the patient undergoes, the therapy can last for several days or weeks. Based on the previous post about melanoma, how does one not get melanoma with the amount of radiation being used on the patient? Your body can tolerate a certain amount of radiation which is why every time you go outside you do not develop melanoma. There is a safe amount of radiation that can enter an individual's body, but once the maximum safe amount of radiation has been reached, that part of the body can no longer undergo radiation therapy.

✤ Chemotherapy (3): This mode of treatment is probably the most common when individuals think of cancer. Chemotherapy uses drugs to slow down the rate of rapidly growing cancer cells. Not only can this treatment potentially cure and decrease the chances of cancer from returning, but it can also be used to help shrink the tumor and lessen the pain and other symptoms that a cancer patient might experience. Some side effects associated with chemotherapy include damage to the growth of healthy cells (which is why patients on chemotherapy might experience hair loss) and extreme fatigue.

✤ Immunotherapy (4): This form of treatment targets the immune system so that it is better equipped to fight off cancer but is still not as commonly used as surgery, radiation therapy, or chemotherapy. There are several types of immune therapies such as:

Checkpoint inhibitors are drugs that help the immune system respond to tumors without
directly targeting them. Instead, they target the cancer cells ability to not be affected by the
immune system's attack.

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immune-checkpoint-inhibitor

The image above can help you better understand how the checkpoint inhibitor interacts with the
T cell and tumor cell.

Adoptive cell transfer is a type of immunotherapy that also helps the immune system to fight
off cancer cells. For this therapy, t-cells are extracted from the cancer cell itself. Out of all the t-
cells removed, the most active ones against cancer will be brought to the laboratory to greatly
multiply them so that when they are returned to the patient, there will be t-cells that are
specialized to help fight off the cancer from which they were extracted from.

There are other forms of treatments besides the ones I have listed above and there are a lot of scientists working to find new and better modes of treatments for cancer patients.

So how does one decide which treatment would be best for his or her cancer? The best way to find out which type of treatment would better your chances of fighting off cancer, is to discuss it with your doctor. Your doctor will take into consideration which cancer the patient has, what stage is the cancer at, and if the patient has had cancer previously and with what treatments.

Take a look at the two images below and compare:

https://www.slideshare.net/ronaldoquitco/defeating-colorectal-cancer-7315501

https://www.scienceofcrc.org/treat/

From the images, you can see that there is a slight variation in the "start" of certain treatments, such as chemotherapy and radiation. In the first image, chemotherapy does not begin until Stage 3, while in the second image chemotherapy can begin in Stage 2. There is not an exact or "correct" stage to begin certain treatments because cancer is very complicated. Overall you can tell that surgery is a treatment option from Stage 0 to Stage IV, even though it is more commonly used in the early stages of cancer when the tumors are easier to detect and remove without damaging too much of the surrounding tissues. Although there are risks with cancer treatments and this all may seem intimidating, talking to your doctor will make it easier and can give you a better quality of life in the long run.

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Defining some key terms:

Prognosis: Is when a doctor determines the probability of a patient's recovery, based on their disease and the conditions they are in (5).

https://healthhearty.com/prognosis-vs-diagnosis

5- Year Survival Rate (6): This calculates the survival percentage of patients, five years after being diagnosed with a specific cancer or stage of cancer.

Examples:

" The 5-year relative survival rate for women with cervical cancer is about 67%. This means that about 67 out of every 100 women with cervical cancer will be alive 5 years after diagnosis " (6).

" The 5-year relative survival rate for early-stage cervical cancer is 92%. This means that 92 out of every 100 women with early-stage cervical cancer will be alive 5 years after diagnosis " (6).

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https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-treatment-and-survivorship-facts-and-figures/cancer-treatment-and-survivorship-facts-and-figures-2016-2017.pdf

To view this image more clearly, please go to the website that is captioned under the image and go to page 9. The image above shows the 5-year survival percentage amongst different forms of cancer, such as thyroid cancer, prostate cancer, breast cancer, etc. The main point to get from the image is that the earlier the cancer is detected, the better the survival rate. As it metastasizes (or becomes distant, the last column on the right), you can see a great difference in survival percentages from the regional to the distant location of the cancer.

Overall, the best way to avoid the potential development of cancer is to get tested early and often.

References:

1) This website provides helpful links to cancer treatments that can be available to a cancer patient. National Cancer Institute. Types of Cancer Treatment. https://www.cancer.gov/about-cancer/treatment/types. Accessed April 24, 2019.

2) This website describes radiation therapy for early-stage cancer patients. National Cancer Institute. Radiation Therapy to Treat Cancer. https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy. Updated January 8, 2019. Accessed April 25, 2019.

3) This website describes the most well-known cancer treatment, chemotherapy. National Cancer Institute. Chemotherapy to Treat Cancer. https://www.cancer.gov/about-cancer/treatment/types/chemotherapy. Updated April 29, 2015. Accessed April 25, 2019.

4) This website describes, in depth, about how patients can use immunotherapy to treat cancer. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/types/immunotherapy. Updated November 28, 2018. Accessed April 25, 2019.

5) This website provides the definition and synonyms for the term prognosis. Merriam- Webster. Prognosis. https://www.merriam-webster.com/dictionary/prognosis. Accessed April 26, 2019.

6) This website helps its readers be able to understand the statistics of the 5-year survival rate of patients with certain diseases or cancers. Approved by Cancer.Net Editorial Board. Cancer. Net. https://www.cancer.net/navigating-cancer-care/cancer-basics/understanding-statistics-used-guide-prognosis-and-evaluate-treatment. Updated 08/2018. Accessed April 26, 2019.

Cancer

Cancer can occur in any part of the body since cells are constantly growing everywhere. Cancer occurs “when cells grow out of control” and continue “growing and making new cells” (1). The term cancer is a very general term that can be specified to a specific kind of cancer. Some examples of cancers include breast cancer, lung cancer, melanoma (skin cancer), leukemia (cancer in the blood and/or bone marrow), brain cancer, etc. Although the name can describe what kind of cancer the patient might have, that does not mean that the cancer is forever localized to that one location. If not treated or detected early enough, cancer can metastasize to other parts of the body. Before I continue to the more in-depth characteristics to developing cancer, here are some defined key terms:

Mutation (2):

A mutation is when there is a change in the DNA sequence, which could be caused by a mistake that occurred when the DNA was being created or by an environmental factor. A mutation does not always guarantee that something bad has happened, sometimes a mutation in the DNA sequence could have no effect on the individual, but it all depends on the location and what mutation actually occurred in the DNA sequence.

https://www.yourgenome.org/facts/what-types-of-mutation-are-there

The image above has one example of a mutation, a point mutation (other types of mutations include insertion, deletion, substitution, and inversion). As you can see, there is a single nucleotide change from the original sequence to the point mutation sequence. The original sequence has C →T→G while the point mutation has C→C→G.

Proto-oncogene (3):

This kind of gene allows your cells to divide and grow normally.

Oncogenes (3):

This type of gene is a mutated or bad version of a proto-oncogene. An oncogene is what causes cells to grow and divide out of control which can eventually create malignant (cancerous) tumors.

https://www2.le.ac.uk/projects/vgec/highereducation/topics/cellcycle-mitosis-meiosis

The image above shows the cell cycle of a normal cell in one’s body. The G1 phase is where the cycle technically starts. In this phase, the cellular contents will be duplicated so that when the original cell becomes two daughter cells, there will be enough materials to be divided amongst them. Also in this phase, the cell will grow in size. Once the cell has completed the necessary tasks in G1, it can move on to the S-phase. This phase is where the chromosomes are duplicated and where the centrosome is created. The centrosome is an organelle that creates the spindle fibers near the nucleus so that a single sister chromatid can separate to either side of the cell. Once all of the chromosomes are duplicated, the cell will enter G2 (4). In this phase, the cell will continue to grow, make proteins and organelles, and will reorganize its materials so that it can begin the M-phase.

https://www2.le.ac.uk/projects/vgec/highereducation/topics/cellcycle-mitosis-meiosis

The M-phase, or mitosis, is where the cell actually begins dividing. Interphase (G1, S, and G2) is the necessary preparation in order for the cell to divide. The division of the cell will begin in prophase. This phase is the longest phase, taking up about half of mitosis. In this phase, the nuclear membrane will break down, the microtubules will start to appear, and the chromosomes will condense, forming a single compacted structure in the cell. Next, the cell will enter prometaphase. In this phase, the chromosomes begin lining up in the middle of the cell, preparing for metaphase. Metaphase is when the chromosomes are all aligned in the middle of the cell and the spindle fibers have attached to the kinetochore. At the end of metaphase, anaphase will begin. Anaphase is the shortest stage in mitosis and in this phase, the spindle fibers will split the sister chromatids and move them to either side of the cell. Finally, the cell will enter telophase. In this phase, two nuclear membranes will reform around each group of chromosomes and the spindle fibers will disappear. The last event to occur is the actual division and separation of the original cell to the two daughter cells. This event is called cytokinesis (4). Below is a video to give you a better representation of how the cell cycle/ division occurs:

https://youtu.be/_aQXhors-OE

Once the two daughter cells have formed, each will either restart the cell cycle at G1 and divide into two new daughter cells or will exit the cell cycle, otherwise known as G0. When a cell undergoes G0, it no longer needs to divide (even though the cell can re-enter the cell cycle at a later time if necessary) and can begin working (such as a daughter cell becoming a red blood cell). So, what actually causes cancer then? There are several risk factors associated with having cancer, such as genetics, age, diet, sunlight, tobacco, radiation, etc (5). Cancer can be caused by a mutation in the DNA, such as in melanoma (which you can read more about in my previous post), and cancer can also be caused by a mistake that occurs during the cell cycle. Generally, if a cell is formed incorrectly, it will undergo programmed cell death. Cancer forms if/when that incorrect cell continues replicating and dividing rapidly (meaning it didn't die).

https://gfycat.com/accuratewholekinglet

From the GIF above, on the left is a healthy cell dividing at a steady/constant rate, while the cancer cell on the right is dividing rapidly and on top of each other (creating a tumor). This process is the reason why cancer is so hard to treat. Cancer is not similar to a bacteria or virus infecting a specific part of the body, cancer is random and starts in different places in different people. For this reason, it’s hard to find a cure when there are too many targets to consider! Cancer results from 4-6 mutations and those mutations are different depending on the type of cancer, meaning that the mutations in melanoma are not the same as the mutations you could find in breast cancer or lung cancer. Therefore one form of cancer can have thousands of related genetic diseases.

There are two different forms of tumors: benign and malignant. A benign tumor is a non-cancerous growth of cells that will not invade neighboring tissues. A malignant tumor is cancerous and will invade neighboring tissues. This tumor will continue growing and can metastasize (spread) to other parts of the body. A tumor can help doctors determine the stage of a patients cancer. Why is knowing the stage of cancer important? Knowing the stage of the cancer can help the doctor determine a mode of treatment and prognosis for the patient. The stages of cancer are (6):

https://thetruthaboutcancer.com/understanding-four-stages-cancer/
Here is an image to help you visualize the 4 stages of cancer. Stage 0 being on the left and stage 4 being on the right.

Stage 0: This stage of cancer is highly curable. In this stage, the cancer is only at the original location, meaning that surgery can easily remove the benign tumor.

Stage 1: This early stage of cancer can still be curable through means of surgery because it has not spread to nearby lymph nodes or tissues. The tumor has slightly grown since stage 0.

Stage 2 and 3: These two stages are very similar in that the tumor has grown more than stage 1 or 0 but has started to spread to nearby tissues and lymph nodes.

Stage 4: In this stage, the cancer has spread to nearby lymph nodes, tissues, and organs. This stage is when the cancer has metastasized (spread) to other parts of the body. This stage is very hard to cure because of how advanced and spread out the cancer could be.

In order for a doctor to cure any form of cancer, he or she must first determine the type of cancer the patient has, the stage at which the cancer is in, and then the best mode of treatment needed to fight that cancer. Some treatments used in modern medicine include surgery, chemotherapy, etc. In next week’s post, I will be including treatments and treatment rates on cancer patients with a primary emphasis on melanoma.

References:

1) This website provides a general understanding of cancer. American Cancer Society. What is Cancer? https://www.cancer.org/cancer/cancer-basics/what-is-cancer.html. Reviewed December 8, 2015. Accessed April 17, 2019.

2) This website provides about information about different mutations that can occur in the DNA. Your Genome. What is a Mutation? https://www.yourgenome.org/facts/what-is-a-mutation. Accessed April 17, 2019.

3) This website describes what oncogenes and tumor suppressor genes are and how they are associated with cancer. American Cancer Society. Oncogenes and tumor suppressor genes. https://www.cancer.org/cancer/cancer-causes/genetics/genes-and-cancer/oncogenes-tumor-suppressor-genes.html. Accessed April 17, 2019.

4) This website provides an in-depth evaluation of the cell cycle and its phases. Khan Academy. Phases of the cell cycle. https://www.khanacademy.org/science/biology/cellular-molecular-biology/mitosis/a/cell-cycle-phases. Accessed April 18, 2019.

5) This website describes the risk factors that can be associated with cancer. National Cancer Institute. Risk Factors for Cancer. https://www.cancer.gov/about-cancer/causes-prevention/risk. Updated December 23, 2015. Accessed April 18, 2019.

6) This website describes the different stages of cancer and how doctors are able to determine the stage of a cancer patient. Approved by the Cancer.Net Editorial Board. Cancer.Net. Stages of Cancer. https://www.cancer.net/navigating-cancer-care/diagnosing-cancer/stages-cancer. Updated 03/2018. Accessed April 20, 2019.

"But my skin never burns!"

Melanoma:

https://www.solbari.com/blogs/solbari-blog/why-should-you-use-sunscreen-everyday

Cancer is a general term for "a collection of related diseases" (1). In the cell cycle, a healthy cell will grow, divide into daughter cells, and if something is incorrect, the cell will undergo programmed cell death. In a cancer cell, if there is a mistake, whether it's in the growth or replication of chromosomes within the cell, the cell will just continue to grow and divide rapidly (as if nothing is wrong). This rapid growth and division of abnormal cells are what cause tumors to form and if they are not treated or detected early enough, they can invade and damage surrounding tissues.

https://ghr.nlm.nih.gov/condition/vitiligo

In this post, I will specifically discuss the cancer known as melanoma. The image above might be helpful in being able to visualize the parts of the skin that I am referencing. Melanoma is a type of cancer that begins in the melanocytes (which are the cells that produce melanin, which provides pigment for our skin, eyes, and hair) and has 3 different types: Cutaneous melanoma, mucosal melanoma, and ocular melanoma (2).

Cutaneous melanoma:

~ The most common form of melanoma

~ "Cutaneous" meaning skin, as in skin cancer

~ From the image below, you can see that cutaneous melanoma first appears like an abnormal and/or irregular-looking mole

https://www.nejm.org/doi/full/10.1056/NEJMra041245

Mucosal melanoma:

~ Melanoma that occurs in the parts of the body that contains a mucus membrane

~ Location examples include the mouth, nasal cavity (or nose), throat, etc.

~ The image below contains one example of an individual with mucosal melanoma in his or her mouth

https://www.researchgate.net/figure/Primary-oral-mucosal-melanoma-affecting-the-lower-gingival-and-lip-mucosa_fig1_319342373

Ocular melanoma:

~ Also known as uveal melanoma or choroidal melanoma

~ Found in the eye

~ Rare form of melanoma

~ As you can see in the image below, ocular melanoma can occur in different parts of the eye, such as in the iris, ciliary gland, and the choroid

https://newsnetwork.mayoclinic.org/discussion/living-with-cancer-melanoma-can-begin-in-the-eye/

Melanoma can often be detected early compared to other cancers. Melanocytes form moles, which can sometimes indicate that melanoma is present, but not ALL moles turn into melanoma.

https://www.emergemedicaldayspa.com/2017/07/27/know-your-abcs/skin-cancer-chart/

Above, you can see how to detect if a mole is cancerous. You need to take a good look at your mole(s) or have your dermatologist take a look at it before jumping to any cancerous conclusions. The key difference to look out for is an asymmetrical shape or if it continues to grow. Determining a difference in shape might be difficult to conclude if you haven’t determined the original size of the mole. While examing a mole, remember the A, B, C, D, E acronym that is provided in the image above.

There are several risk factors associated with having any kind of cancer, especially melanoma. These are some of the risks that can increase an individual’s chances of getting melanoma (3):

Sun exposure: This is probably the most well-known risk factor associated with skin cancer. This factor is the reason why your mom keeps telling you to put sunscreen on. The reason for this is because of the two types of UV radiation: UVA and UVB.

UVA: Stands for ultraviolet A. This type of radiation is able to pass through glass, meaning that when you are in the car or near a window in the middle of the day, this form of radiation can pass through the glass which can cause skin cancer, aging, and wrinkling.

UVB: Stands for ultraviolet B. This type of radiation is also from the sun and can cause melanoma to form, but the key difference between UVA and UVB is that UVB can cause sunburns but cannot pass through glass. Therefore, you would actually need to be outside in the hottest hours of the day to be exposed to this UVB radiation.

Tanning beds: You might think that getting your tan via a tanning bed is safer than getting a tan from the natural sun but that is not correct. Artificial tanning beds are also associated with putting an individual at risk of getting melanoma. The reason for this is because tanning beds use ultraviolet radiation similar to the radiation you're getting from the sun. Despite what salons say, tanning beds are harmful to your health and can increase your chances of getting melanoma (4).

Genetics: When you think of a direct relative (such as a parent or grandparent) having a type of cancer, you might automatically assume that you will get that cancer, but that is not always the case. Cancers are found in the somatic cells (body cells, not sex cells), this means that the mutation will not be directly passed on to the next generation. The mutations in these types of cells just increase the probability (or chances) of the next generation getting that same mutation. Basically, the next generation is ABLE to get that mutation but are NOT positively going to get it. Only about 10% of individuals who have melanoma have had relatives with (or who have had) melanoma.

Skin type: If you have a lighter complexion and often get burned rather than tanned, this means that you are more likely to get melanoma than someone with darker skin. Furthermore, people with darker skin can also get melanoma without proper safety precautions. It's just that there are a greater percentage and risk factor for lighter skinned people being exposed to the formation of melanoma.

There are many other risk factors associated with skin cancer, such as aging and the number of moles you already have and produce but the thing to take away from these risks is that you need to protect and watch out for any unusual moles that spontaneously appear on your body and wear sun protection!

Previously, I have described cancer as being the abnormal growth of cells that rapidly undergo cell growth, even when a mistake has occurred. This might cause you to wonder how UV radiation can affect our skin and cause cancer. Below I have provided some very interesting videos that describe this process:

https://www.youtube.com/watch?v=Cf7Ar3nEUmw

In this video, a YouTuber questions How UV causes cancer and aging with Dr. Hayley Goldbach who is a dermatologist. She describes how the UV radiation wave causes covalent bonding between adjacent thymine or cytosine bases (or pyrimidine dimers), rather than what the bases would original bond to, such as thymine with adenine and cytosine with guanine. The first few times that this irregular covalent bonding occurs, our DNA can be repaired which prevents the skin cancer from forming every time you are exposed to sunlight. Towards the end of the video, they discuss how the sun’s UV radiation can also cause aging because of the breaking down of collagen in our dermis (middle layer of skin).

https://youtu.be/FjewT1jDNw8

In this video, Dr. Ankit discusses How UV rays damage our skin. This video is a bit shorter than the previous one I linked above and it also has a bit more approachable images and animations (for the more visual learners). Dr. Ankit discusses very similar topics as the previous video but includes that the DNA can be repaired after being affected by the UV radiation but after a prolonged amount of time, too much damage can be caused to the cell in which case just causes skin cancer to form in that skin cell.

Personally, I recommend watching both videos because they are both informative about how UV radiation can generate skin cancer. Also, one video might answer some of the questions you might still have after watching the other video. So, in order to prevent getting melanoma, make sure to use sunscreen every 2 hours, limit direct exposure during the hottest times of the day in your area, avoid tanning beds and lamps, and check your skin regularly to ensure nothing new has popped up (3).

Before I conclude this post I want to discuss the different stages of melanoma (5):

https://www.yervoy.com/metastatic/what-is-metastatic-melanoma

Stage 0: Is when the benign tumor has just surfaced on the epidermis (outer-most layer) and has not spread to the lower layers of the skin or to other parts of the body.

Stage 1: Is when the malignant tumor has begun to enter the dermis (middle skin layer) region. There are two types of stage 1: 1a and 1b. Stage 1a and 1b are differentiated by the thickness of the tumor. By this point, the tumor could be around 2mm thick but there will still be no signs that the cancer has metastasized (meaning that it hasn't spread to other parts of the body).

Stage 2: In this stage, the cancer still would not have spread to the lymph nodes or other parts of the body, but it would have become slightly bigger and could even be ulcerated (meaning that could have an ulcer surrounding it).

*An ulcer is a sore that is slow to heal and can be painful. Oftentimes, that occurs when an individual has an infection, disease, or injury that does not heal well. These ulcers, if not treated, can cause serious issues like an infection, a leg or foot amputation (if it is a diabetic ulcer), or osteoporosis (6).

Stage 3: At this stage, the melanoma has undergone a regional spread. This means that the cancer has spread to nearby lymph nodes and nearby skin, but has not yet spread far enough from the original site of the tumor.

Stage 4: At this stage, the cancer has spread beyond the regional area of the lymph nodes and nearby skin and has metastasized to other organs. This is the most severe and most difficult stage to treat in any type of cancer, especially if the cancer has spread to the vital organs, such as the lungs or brain.

Just like with lung cancer, skin cancer can be an easily preventable cancer if the correct safety precautions are taken. Make sure to use sunscreen when going outside during the day, don't use tanning beds, and be aware of the moles you have around your body and get them checked often. In a later post, I will be discussing the treatments and treatment rates associated with melanoma!

http://gakkomom.com/blog/its-sunscreen-time

References:

1) This website gives information to be able to better understand cancer (in general). National Cancer Institute. What is Cancer? https://www.cancer.gov/about-cancer/understanding/what-is-cancer. Updated February 9, 2015. Accessed April 1, 2019.

2) This website describes what melanoma is and the 3 types of melanoma that I described above. Melanoma Research Foundation. What is melanoma? https://www.melanoma.org/understand-melanoma/what-is-melanoma. Accessed April 1, 2019.

3) This website describes in great detail the risk factors that are associated with melanoma. Approved by the Cancer.Net Editorial Board. Cancer.Net. Melanoma: Risk Factors and Prevention. https://www.cancer.net/cancer-types/melanoma/risk-factors-and-prevention. Updated 06/2017. Accessed April 2, 2019.

4) This website briefly describes the radiation used in tanning beds and why they are considered to be a risk factor to melanoma. Skin Cancer Foundation. Tanning. https://www.skincancer.org/prevention/tanning. Accessed April 3, 2019.

5) This website describes each individual stage in melanoma and provides links to a more in-depth evaluation of each of the stages. At Melanoma Foundation. Understanding Melanoma: Stages of Melanoma. https://www.aimatmelanoma.org/stages-of-melanoma/. Accessed April 14, 2019.

6) This website describes what an ulcer is and how one can get one. Web MD. What is an Ulcer? https://www.webmd.com/skin-problems-and-treatments/what-is-an-ulcer#1. Accessed April 14, 2019.