Radiotherapy and Its Side Effects: Chapter 2 - Side Effects of Radiotherapy

PART II

Chapter 2

Side Effects of Radiotherapy (Cont'd)

2. Damage to cell renewal

      The following side effects are under a class called cell renewal effects.

Damage to bone marrow 

Bone marrow is the flexible tissue in the hollow interior of bones. It is responsible for the production of blood cells, including RBCs, WBCs, and platelets. If a person is exposed to a high dose of radiation for too long (especially on pelvis, chest and other bones), one can suffer bone marrow damage. As a result of radiotherapy, a patient may suffer from low WBC count (neutropenia or leukopenia), low RBC count (anemia), and/or low platelet count (thrombocytopenia). As explained in the previous chapter, neutropenia may increase a patient’s chance of infection, anemia may cause fatigue, and thrombocytopenia can increase a patient’s risk of bruising and bleeding.

 On the other hand, radiation damage to bone marrow is not completely negative. For patients that require bone marrow transplantation, a high dose TBI becomes a positive tool in that unhealthy bone marrow cells are “wiped out” by high-dose radiation before a patient receives healthy bone marrow cells or cord blood cells. 

Hair loss (alopecia)

        Radiotherapy often causes hair loss on the body part being treated [35, 36]. However, hair loss from radiotherapy is usually limited to the area treated by the radiation. For patients who receive radiotherapy for brain cancer, the most pronounced side effect may be hair loss. In this case, radiation-induced hair loss could be permanent; this is different from chemotherapy on other part of the body wherein hair loss is more likely temporary.

Anemia  

        Depending on the dose and the time of treatment, radiotherapy may or may not cause anemia for cancer patients. Many patients experience anemia at some point during treatment; in serious situations, it may cause aplastic anemia.

 Aplastic anemia is when the hematopoietic stem cells in bone marrow are seriously damaged. As a result, all blood cells are not adequately produced, and could be fatal in some cases. One of the most important pioneers in radioactivity, Marie Curie, died from aplastic anemia which was believed to have resulted from her long-term exposure to the radioactive materials she studied.

Diarrhea

 

  When the lining of mouth, stomach, and intestines are injured by radiotherapy, it may cause diarrhea. It is common to have diarrhea during or after radiotherapy treatment on the stomach or abdomen. The diarrhea can gradually get worse as the treatment goes on.  Once the treatment ends, the diarrhea normally goes away gradually over a couple of weeks, but for some people it may take a little bit longer.

Skin damage

        Radiotherapy can induce tanned (hyperpigmentation), irritated, peeling or burned skin. Because recent radiotherapy technology utilizes higher radiation doses, skin damage becomes a problem that happens more often. On the other hand, in the most recent radiosurgery, such as stereotactic radiotherapy, because radiation is applied from different direction, skin damage is significantly reduced.  

© Jiajiu Shaw, 2021

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Chemotherapy and Its Side Effects: Chapter 3 - Side Effects of Chemotherapy

Part I

Chapter 3

Side Effects of Chemotherapy

      Chemotherapy can result in a wide range of side effects; many of them are due to its adverse activity on the fast-growing normal cells of the body such as bone marrow cells, hair follicle cells, and crypt epithelial cells on the small intestine lining. Other effects are due to its adverse activities on vital organs such as liver, kidney, and heart. Although the side effects induced by individual drugs can be different from drug to drug, they can be generalized and described below.

A.    Bone Marrow

Because most anticancer drugs tend to damage fast-growing bone marrow cells, which produce new blood cells, blood-related side effects are not unexpected as a result of chemotherapy. Basically, there are three major blood-related side effects resulted from bone marrow damage by chemotherapy; they are briefly described below:

A.1. Neutropenia

Neutropenia is defined as an abnormal decrease in the number of neutrophils, an abundant type of granular WBC that is highly destructive of microorganisms. A low WBC count may leave a patient vulnerable to bacterial infection and the chemotherapy regimen has to be put on hold until the WBC count is back to an acceptable level for the chemotherapy to resume. This is often a problem that interferes with the chemotherapy regimen.

A.2. Anemia

Anemia is defined as a deficiency of hemoglobin (Hb), which is an iron-containing protein that carries oxygen from the lungs to the body’s brains, muscles, tissues, and other organs; oxygen is critical to the health of tissues and organs. Symptoms of anemia include light headedness, tiredness, or dizziness when a patient stands up suddenly from a crouching position.

A.3. Thrombocytopenia

Thrombocytopenia refers to the condition of lower than normal platelet count. Platelets play a fundamental role in hemostasis (a complex process that causes the blood to clot and bleeding to stop) and are a natural source of growth factors including platelet-derived growth factor (PDGF), which plays a significant role in the repair and regeneration of connective tissues. A low platelet count may cause a person to experience bruising more easily or excessive bleeding. Patients with acute myeloid or lymphocytic leukemia often experience low platelet count. This is especially true when patients with acute leukemia are treated with chemotherapy

All of these three side effects are related to bone marrow damage and they can be diagnosed through the complete blood count (CBC) which represents the three types of cells in blood.

Currently, there are several drugs approved by the FDA to reduce individual side effects resulted from bone marrow damage. These drugs will be discussed later. In addition, some natural products have been claimed to have certain protective effects on bone marrow damage. However, one needs to look into the scientific evidence before making any conclusion or decision.

© Jiajiu Shaw, 2020

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen.

Chemotherapy and Its Side Effects: Chapter 1

Chapter 1

Introduction

     Mutation is not uncommon in our daily lives. Most mutated cells either keep their normal cellular functions or undergo a programmed cell death (apoptosis) and die at some point in time. In addition, many mutated cells are recognized and rapidly removed by the body’s immune system. Only a very small portion of mutated cells will evolve further and become cancerous cells with uncontrollable proliferation; this behavior is different from that of normal cells. For adult, most normal cells are well differentiated except for certain types of cells, such as epithelial cells and bone marrow hematopoietic progenitor cells, which are capable of continuous proliferation; unlike cancerous cells, the growth of normal cells is highly regulated and controlled.

Cancer is a group of various diseases in that some cells are mutated in certain ways so that they grow and divide continuously. Currently, there are more than 200 known cancers that afflict humans.

For the treatment of cancer, there are generally three conventional strategies: surgery, chemotherapy, and radiotherapy. In this book, we will focus on chemotherapy, radiotherapy, and their side effects.

Chemotherapy is a systemic treatment of cancer patients with one or more anticancer drugs (chemical agents) to kill cancer cells and/or slow down their growth. The name “chemotherapy” comes from chemical agents being used as a therapy for treating cancer. Chemotherapy plays a critical role in cancer treatment; it is estimated that more than half of all cancer patients receive chemotherapy.

Depending on the dosage form, cancer drugs may be administered through several different routes, including intravenous injection/infusion, oral (mouth) delivery, or a slow release dosage form embedded in a tissue by implantation. A chemotherapy regimen (a treatment plan including the dosing and schedule) usually includes the administration of at least one drug to fight cancer at a predetermined dose according to a suitable schedule, usually daily, weekly, or every several weeks. Due to the different characteristics of individual cancer drugs, the chemotherapy regimen for each drug may be different. Because cancer treatment is a delicate process, it is important to know that staying on the chemotherapy regimen gives a patient the optimal chance for a successful result.

Many times, additional supplementary drugs are used simultaneously in a chemotherapy regimen in order to achieve a better outcome to either increase the anticancer potency or reduce the side effects of chemotherapy; these drugs are often called adjuvant medications. Adjuvant drugs that are used to reduce the side effects of cancer therapy, including chemoprotective and radioprotective agents, will be discussed in Part III.

Most cancer drugs work by killing cancer cells or slowing down the growth of cancer cells. Unfortunately, most of the cancer drugs are not able to clearly distinguish between cancer cells and normal cells. Therefore, most cancer drugs will damage not only the fast-growing cancer cells but also the fast-growing normal cells, which include bone marrow cells, crypt epithelial cells (lining of small intestine), and hair follicles. In addition, a number of organs (e.g., liver, kidney, and heart) are often injured by chemotherapy.

In order to have a better understanding on how anticancer drugs work and what kind of side effects they can cause, let’s take a look at some anticancer drugs in different categories. 

© Jiajiu Shaw, 2018

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. All contents posted are extracted from the book, "SIDE EFFECTS OF CHEMOTHERAPY AND RADIOTHERAPY", prepared by Dr. Jiajiu Shaw, Dr. Frederick Valeriote, and Dr. Ben Chen. 

Novel/Unconventional Methods for Cancer Treatment (6)

(6) Stem Cells and Related Treatments

Remember we talked about stem cells in the beginning of this book?  The stem cells are very powerful ancestors of all cells; normal cells that show specific functions are all essentially derived (differentiated) from stem cells.  Therefore, it makes sense to attempt to utilize the natural power of stem cells to treat different diseases including cancer.  Generally, there are several ways to utilize stem cells for cancer treatment.  They are briefly described as follows:

Using Stem Cells Directly

On type of stem-cell therapy is to inject stem cells directly into the blood stream for them to fight against cancer and other diseases.  Stem cell based strategy has been shown to be very promising.  A well know example is to use stem cell transplantation for leukemia.  

Briefly, stem cells can be collected from the bone marrow, circulating (peripheral) blood, and umbilical cord blood.  In a stem cell transplant, healthy stem cells are infused into the body.  Basically, there are two types of stem cell transplants.  Autologous stem cell transplant is when stem cells are collected from the patients themselves.  When stem cells are taken from a matching donor, the transplant is called allogenic stem cell transplant.  In order to find the right match, a human leukocyte antigens test needs to be conducted on the patient and the potential donor. 

Although stem cell therapy has been used successfully in many cases, there are also many cases of failures.  Research and studies in this area are continuing.

Converting Cancer Cells Back into Stem Cells or Normal Cells

A number of studies are focusing on converting cancer cells into stem cells.  The origin of this type of research started from a Japanese scientist, Shinya Yamanaka, who won Nobel Prize in 2012 year for his discovery showing that mature cell (differentiated) can be reprogrammed to become pluripotent (similar to stem cells).   He successfully identified a few critical genes in mice; when these genes were activated, mice skin cells were re-programmed and became stem cells (now referred to as iPS cells or induced pluripotent stem cells) by using several key ingredients and a delicate process.  Theoretically, these iPS cells can be differentiated into all types of cells.   

Since then, many studies indicated that, if the condition is right, it is indeed possible to artificially convert normal cells back into stem cells.  At the present time, a lot of research activities are ongoing to hopefully convert cancer cells back into stem cells or normal cells.

Use of Exosomes

Stem cells, normal cells, and cancer cells all produce a variety of biological molecules and one type of very important vesicles, exosomes, for inter-cellular communication and other functions.  Exosomes are cell-derived vesicles; exosomes from different types of cells contain a common group of molecules, as well as cell type-specific components.  Once released from the cells, exosomes act as messengers to carry and transfer their biomolecules to proximal and also distant cells.  Indeed, this general description is correct.  However, there is a very important point not being well characterized: some contents of exosomes can also be cellular environment-dependent. 

Exosomes are present in all biological fluids (blood, urine, and even cell culture medium).  Their diameters are from 0.04 to 0.1 µM, much smaller than RBC (diameter 6-8 µM) and WBC (diameter 12-15 µM).  Fig. 6.1 shows a schematic size comparison of a WBC, a RBC, and exosomes. 

Exosomes have been shown to have specialized functions.  For example, exosomes play a key role in intercellular signaling and waste management. Among other functions, exosomes work like messengers to carry a variety of RNA, proteins, sugar etc.  As mentioned before, stem cells have the amazing power to grow and differentiate.  It is therefore reasonable to assume that stem cells utilize exosomes to carry important biomolecules to normal cells and cancer cells to deal with many different cellular issues. 

 Exosomes are like micro-packages of important biomolecules to be shipped from one cell to another.  Let’s use an analogy in our daily lives to explain the roles of exosomes as follows.  

In our daily lives, we all use the post office to mail letters and, sometimes, we use FedEx or UPS to ship packages.  The letters or packages all contain useful information or materials that may be useful to the receiving parties.  If you still remember, inter-cellular communication is very important and normal cells communicate better than cancer cells.  However, cancer cells do release specific exosomes to be conveyed to other cancer or normal cells.  Therefore, it will be very important to figure out what are in the exosomes that are released by cancer cells.  If we know the answers, it will be very useful in finding a better way to deal with cancer.   In short, exosomes are becoming a very important area for cancer research. 

In recent years, uses of exosomes for diagnostics and for treatment of diseases have become a hot area of research.  Because individual exosomes contain different RNAs and proteins and the fact that exosomes can stay in the circulation for a long time, it is possible to trace back to the tissues that produce them.  As a result, it is possible to develop certain diagnostics to detect cancers at early stages.  On the other hand, there are some real hurdles making the diagnostics at the present time.  For example, because of its small size as compared to RBC and WBC, it is not easy to fish out exosomes out of blood or urine.  In addition, there are a great number of exosome exist in plasma.  All these make it a real challenge to develop new diagnostic employing exosomes.  As to the use of exosomes in therapeutics, intense research activities are ongoing in many labs. 

In short, let’s use another analogy to make it easier to understand exosomes.  Exosomes released from normal cells are similar to missionaries in real life; exosomes carries a lot of important ingredients to deal with cancer cells whereas missionaries carry a lot of information to carry out missions such as religion, education, and health care.

© Jiajiu Shaw, 2016

Disclaimer: This blog is written solely for informational purposes. It does not constitute the practice of any medical, nursing or other medical professional health care advice, diagnosis, or treatment. Although some commercial products, publications, and services are mentioned in this blog, the author does not endorse any specific products, publications, or services.  None of the contents in this blog represents or warrants that any of the products, publications, or services is appropriate or effective for their intended purposes. Readers shall always seek the advice of their physicians or other medical practitioners with any questions regarding personal health or medical conditions and shall be solely responsible for their own decisions and/or actions.