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This is a continuation of cancer as a metabolic disease due to mitochondrial dysfunction.  We will discuss our initial work on the Mitochondrial Organelle Transplantation.

I stated on the last post about cancer as a metabolic disease and some of the results of our mitochondrial organelle transplantation would be presented. I am sorry I am a little late in posting this but I have been on a research trip to discuss collaboration with Hebert Weissbach, PhD,  at Florida Atlantic University. 

When I initially thought that mitochondria as bacteria could be isolated from normal cells, I told my research associates what I wanted to do about isolating normal mitochondria to see if they might enter cancer cells in cell culture. They first thought that I was dreaming about something that was probably never going to happen; however, Mr. Jiang agreed to order a mitochondrial isolation kit and we decided to go ahead and isolate mitochondria from a normal human mammary epithelial cell line. We stained the cells before isolation with a stain that is a vital stain that the mitochondria will not take up unless they are functioning well. That stain is called JC-1. When Mr. Jiang initially isolated the mitochondria, and incubated them with some cancer cells lines he immediately after he looked at this under a fluorescent microscope came to get me to come into the lab to observe. We were extremely excited that yes, normal mitochondria could be isolated, stained with a vital stain JC-1, co-incubate with cancer cells and ENTER the cancer cells. This was proven by fluorescent microscopy. I next postulated that possibly if normal mitochondria would enter cancer cells they possibly may reverse their metabolism from glycolysis to oxidative phosphorylation which is normal cellular respiration. Possibly inhibit proliferation. In so doing might even make these cancer cells more responsive to chemotherapy agents.

The next procedure we did was to incubate the normal mitochondria with cancer cell lines and test for inhibited cellular proliferation. That requires a proliferation assay that requires radioactive thymidine which is involved in DNA synthesis. The final results are obtained in a radiation scintillation counter by certain amounts of counts. Knowing if you have a high count you have a lot of cellular proliferation and DNA synthesis. If you have low counts you have inhibited the proliferation. Mr. Jiang set up the procedure and as I came in one Saturday morning to do the normal Saturday morning work I decided to go into the lab to see if anything had come off of the scintillation counter and I found a large strip of data. I read the results of this data and although I do not do this very much and have not been technically associated with this procedure, it looked to me as if proliferation in the cancer cells after being co-cultured with normal mitochondria and the mitochondria entering the cancer cells had definitely inhibited proliferation. I went home that day quite excited and it was almost too hard to believe and could not wait for Monday morning to come to talk with Mr. Jiang. I left a message for him to get in touch with me Monday morning as soon as he came in.

We looked at the data and he agreed that it showed inhibition of cellular proliferation in the cancer cell line.  However, he was still doubtful and reluctant to accept this data and he said he wanted to repeat this experiment 3 more times. He did repeat it 3 more times and the exact same results were obtained; it definitely inhibited the cancer cell proliferation. What was the mechanism?

Therefore, we decided the next experiment we would repeat the same experiment but this time after so many days we could change the media and test the drug sensitivity. We found after co-incubating the cancer cells with normal mitochondria not only inhibited proliferation, but also increased tremendously drug sensitivity. In essence, it makes drugs more responsive and made the cancer cells more responsive to chemotherapy agents increasing their sensitivity indicating that in a patient possibly this would mean you could give a lot less drug, get the same effect, and maybe even a better effect, and cut down on a lot of the toxicity from chemotherapy.

This finding was extremely exciting and after repeating the experiment many more times, we decided to publish our first paper in the Breast Cancer Research and Treatment Journal on “Mitochondria organelle transplantation: introduction of normal epithelial mitochondria into human cancer cells inhibits proliferation and increases drug sensitivity” in 2012.

We have had a tremendous response to that paper, and more research has been done since that time and we will be presenting further results of this research in future posts. Thank you for reading and please if you would like to contribute to support our research, visit the Donate page on our Blog website. This is getting very exciting and it is ground breaking new research for cellular biotherapy especially in cancer. As a short note, we feel like mitochondrial organelle transplantation may also play a significant role in neurodegenerative diseases and we will mention that in later posts.

Thank you,

Robert L. Elliott, M.D., Ph.D., D.Sc.

Warburg and cancer as a metabolic disease due to mitochondrial dysfunction

I have decided to post information on the exciting research that has consumed us the past seven years.  This research was stimulated by the wonderful work of Otto Warburg. He is one of my research heroes. He stated that cancer was caused by a defect in cellular respiration due to mitochondrial dysfunction. In the 1920’s he showed cells produced their energy by fermenting glucose in the cytoplasm producing large amounts of lactic acid. Normal cells produced energy in the mitochondria by oxidative phosphorylation. This involves the inner membrane (electron transport chain) of the mitochondrion. Cancer cells crave large amounts of glucose and this craving is the rationale of using the PET scan to diagnose and stage disease in cancer patients. Cancer cells use glycolytic metabolism even in the presence of adequate oxygen. This is known as aerobic glycolysis and the “Warburg Effect”. Warburg made his own equipment to perform these experiments and won the Nobel Prize in 1931. He later won another but Hitler would not let him go to receive the award. Although Warburg was of Jewish decent, Hitler left Warburg alone knowing he worked on cancer and Hitler had a tremendous fear of cancer.

What about the origin of mitochondria? Well, most know it as the powerhouse of the cell. The cellular organelle involved in cellular respiration and energy production. Few laymen know its evolution of origin. It is postulated and there is strong genetic evidence that mitochondria are evolutionary bacteria that were engulfed by eukaryotic cells 3-4 billion years ago. This created a symbiotic relationship and thus we and many forms of life developed.

We have worked on cancer iron metabolism and cancer immunology for many years, but Warburg’s and recent work of Thomas Seyfried, Ph.D., inspired me to look at mitochondria in our breast cancer patients. We had studied the ultrastructure of breast cancer specimens in in many patients by electron microscopy. Therefore, I decided to review these electron micrographs. I found that mitochondrial appearance in these micrographs could be divided into 3 groups:

1. mitochondrial plentiful and normal
2. mitochondria sparse and abnormal
3. mitochondria essentially absent

After defining these 3 groups, the patient’s charts were reviewed. The patients in group one (mitochondria plentiful and normal) were found to have low grade tumors and good overall survival. The patients in group two (mitochondria sparse and abnormal) had more aggressive tumors, poor outcome and survival. The patients in group three (mitochondria absent), had very aggressive tumors with much poorer outcome and survival. This observation impressed me that Warburg was correct about cancer cell metabolism being caused by defective mitochondrial leading to aerobic glycolysis.

One night as I thought and prayed about this problem and how to approach it; I soon realized if mitochondria are evolutionary bacteria, then they may act like bacteria. I thought why can’t we isolate normal mitochondria from normal cells and see if they can enter cancer cells and reverse the “Warburg Effect”? This led to our work on mitochondria organelle transplantation in breast cancer cells. These results will be presented in the next posting.

We welcome comments and questions!

Thank you,

Robert L. Elliott, M.D., Ph.D., Dsc

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Any type of cancer immunotherapy works better when there is less tumor burden.  In other words, a cancer vaccine is most effective when there are minimal cancer cells in the body, such as after a cancer tumor is removed or after chemotherapy. There is rationale of using immunotherapy after standard of care therapy and when there is no evidence of disease. Using immunotherapy in this setting is advantageous because sometimes it is possible to have micrometastatic disease that is undetectable by modern imaging, but these cancer cells can cause a recurrence years later.

We have been using our cancer vaccine for over 20 years in our practice.  We have used this cancer vaccine for solid epithelial tumors such as breast, prostate, colon, and lung.  The prostate cancer vaccine ProscaVax (OncBioMune Pharmaceuticals) is currently enrolling patients to begin a Phase II trial. As we have previously published, there has been minimal side effects with the cancer vaccine, and there has been improvement in the survival of our cancer patients.

We will now show you the results of our breast cancer vaccine in a group of patients that were vaccinated from 1994 to 2006. There were 37 women with breast cancer in this study. A patent on the vaccine was granted in 1994. The results of this study were published in a peer review journal in 2013 (the full reference is listed below). The image below is taken from this article and shows there is an improvement in survival when our breast cancer patients had the cancer vaccine to boost their immune system.  The cancer patients with a weakened or depressed immune system are shown in red and had a decrease in their survival.  The cancer patients who got the cancer vaccine are shown in blue and they had a better survival as compared to the red line.

(Elliott & Head, 2013)

The vaccine improved the disease specific survival of the patients that had depressed lymphocyte immunity to their own tumor.

We believe that probably all patients with any kind of cancer should have an autologous vaccine in the adjuvant setting after completion of standard of care therapy.

Adjuvant cancer immunotherapy may possibly prevent recurrence and improve survival in certain patients with cancer.

Robert L. Elliott, M.D., Ph.D. and Catherine C. Baucom, M.D., Ph.D.

 

(Elliott RL and Head JF. 2013. Adjuvant breast cancer vaccine improves specific survival of breast cancer patients with depressed lymphocyte immunity. Surgical Oncology. 22:172-177.)

Here is the link to purchase the journal article:

http://www.sciencedirect.com/science/article/pii/S0960740413000601

 

Last week we discussed the importance of host immunity in survival of the cancer patient and how we evaluate that immunity.

Now we want to briefly tell you what we do with that information about a cancer patients immune system.

Cancer vaccines may be used as additional (adjuvant) treatment after completion of the standard of care therapy to help prevent cancer recurrence, or in a combination with chemotherapy and sometimes radiation in the Stage IV patients.

After the patient completes standard of care therapy which may be a combination of surgery, chemotherapy and radiation all of which are immunosuppressive; they should be rested 3-4 months before the immune system is tested.  (Please see the previous blog on Understanding your immune system on July 19, 2017 for the blood tests we use to evaluate a person’s immune system.) If a patient has a depressed lymphocyte immunity, an adjuvant cancer vaccine is indicated.

The use of a cancer vaccine in a Stage IV patient can be done, but the timing of the vaccine depends on other treatment protocols.  For instance, what type of chemotherapy cycle and is radiation involved? The type of drugs used in chemotherapy are very important, as some complement immunotherapy by causing cancer cells to die an immunogenic cell death.  This promotes better tumor cell antigen presentation to dendritic cells that then drain to the lymph nodes to stimulate effector T-cells.  The vaccine is timed and given during the chemotherapy cycle based on parameters to be discussed later.

Sometimes a great immune cascade occurs causing marked tumor reduction and a tremendous host response.

Stay tuned…….

Robert L. Elliott, M.D., Ph.D.

Catherine C. Baucom, M.D., Ph.D.

Now that we have discussed the importance of evaluating a cancer patient’s immune system before any treatment is started, we will discuss the specific blood tests we use to get a detailed summary of a person’s immune system.

1. Complete Blood Count (CBC) – this blood test gives information on a person’s red blood cells (RBC), white blood cells (WBC), and platelets.  The red blood cells carry oxygen to all parts of the body.  White blood cells are the cells that fight off infection.  There are several types of white blood cells, and each has a unique purpose.  Chemotherapy usually makes the white blood cells very low.  The platelets help with clotting to prevent too much bleeding when someone hurts themselves.
2. Total Serum Immunoglobulins (IgG, IgM, IgA, & IgE) – this blood test measures several antibodies in the blood that are responsible for defending us against infection.  Each immunoglobulin or antibody has a certain job such as IgA tends to help fight infections throughout the entire gastrointestinal tract and in the lungs. IgG has the ability to enter certain tissues to fight infections. IgE is associated with allergic reactions.  IgM is the first one on the scene of an infection and also helps stimulate other immune cells to fight off foreign bodies.
3. Lymphocyte Phenotyping– the most common lymphocytes are the T cell and the B cells.  The T cell has several subtypes of cells that help stimulate a person’s immune system to fight infection or a foreign body.  The B cell makes antibodies and can help stimulate more T cells to help fight infection or foreign bodies.
4. Lymphocyte Blastogenesis Assay (LBA) – this assay determines if a patients immune system can recognize certain cancer proteins or even a patient’s own cancer.  It is helpful to have a small sample of the person’s actual cancer to put in this test to determine if a person’s immune system can determine the cancer is a “foreign body”.

These blood tests help us in understanding your immune system.  We can figure out if the immune system has the components to adequately put up a “fight.” We ultimately want to make the body think the cancer is a foreign body and to fight it.  Most cancer’s disguise themselves and fly under the radar of the immune system and that’s why they can grow and spread throughout the body.  Our immune system is constantly fighting every day.

At our center, our goal is to help boost the immune system so it can fight off cancer.

Until next time,

Robert L Elliott, M.D., Ph.D.

Catherine C Baucom, M.D., Ph.D.

 

As we have previously written, most patients with cancer are treated with some combination of either surgery, chemotherapy, or radiation treatment. The patient’s immune system is often ignored during the current treatment of cancer.  We have published numerous papers on the importance of studying and treating the cancer patients immune system also know as host immunity.

As previously published in an editorial in 2005, a cancer patient’s immune system should be evaluated before any treatment is started.  There are several ways to measure the immune system and measure the response of the immune system after treatment (Elliott et al., 2005):

1. DTH (delayed-type hypersensitivity)
2. Proliferation assays
3. Chromium release assay
4. Elispot
5. Cytokine flow cytometry (CFR)
6. Tumor antigen peptide tetramer-binding assay
7. Clinical observation of response

It is important to determine if a cancer patient has an overall good immune system, especially to their own tumor-associated antigens (TAA).  If a patient has a good immune system and their immune system is able to recognize their tumor, then they have a better outcome (Head et al., 1993). This concept applies not only to breast, but several cancers including lung, stomach, pancreas, and colon.

Our research as well as previous studies support the finding that evaluating a cancer patient’s immune system before, during, and after treatment is important to determine if there was a response to treatment.  Two independent researchers decades apart demonstrated the positive relationship between a person’s immune system and survival. Riesco et al., 1970 demonstrated that measuring a cancer patients total lymphocyte count before treatment could determine a patient’s survival. Fumagalli et al, 2003 also showed how a cancer patient’s lymphocyte count determines their overall survival.

At our center, we believe in supporting a cancer patient’s immune system.  In our cancer patients, we measure a total immune profile and a lymphocyte blastogenesis assay.  These two tests give us detailed information on a cancer patients own immune system including the number of T cells and B cells which are important cells to fight infection and cancer.  These tests also lets us know if the cancer patient’s immune system can recognize certain cancer markers.  In some cases, we are actually able to see if a cancer patient’s immune system can recognize their own cancer!

While we are a breast center, we see and treat patients with other cancers.  Our goal is to help support a patient’s immune system so that they can use their own immune system to help fight off their current cancer and prevent any recurrence of cancer.  We believe immunologic therapy can compliment traditional treatment for cancer, but evaluating a cancer patient’s immune system is important and should not be ignored!

Stay tuned……..more to come on understanding a cancer patient’s immune system!

Robert L Elliott M.D., Ph.D.

Catherine Baucom M.D., Ph.D.

 

REFERENCES:

Elliott RL & Head JF. 2005. Host Immunity Ignored in Clinical Oncology: A Medical Opinion. Cancer Biotherapy & Radiopharmaceuticals. 20(2):119.

Head JF, Wang F, Elliott RL, et al. 1993. Assessment of Immunological competence and host reactivity against tumor antigens in breast cancer patients: Prognostic value and rationale of immunotherapy development. Ann NY Acad Sci-Fi. 690:340.

Riesco A. 1970. Five-year cancer cure: Relation to total amount of peripheral lymphocytes and neutrophils. Cancer. 25:135.

Fumagalli LA, Vinke J, Hoff W, et al. 2003. Lymphocyte counts independently predict overall survival in advanced cancer patients: A biomarker for IL-2 immunotherapy. J Immunotherapy. 26:394.

 

 

A cancer treatment that has recently received a lot of attention in medical reports and even to the public by TV ads. Some great results have been achieved in some patients, but in my opinion there is still much to be done. We are still too much involved with treating the disease and often forgetting the host with the disease. Many believe cancer immunotherapy is a new modality, but as you will see later in this and future posts, the concept has been around for quite some time.

In 2005, I published an editorial entitled “Host Immunity Ignored in Clinical Oncology: A Medical Opinion.” At that time, I emphasized the importance of host immunity cancer survival. Cancer immunotherapy was still considered experimental and was not part of the Big Three Cancer Treatments: (1) Surgery, (2) Chemotherapy, and (3) Radiation; all of which are in themselves immunosuppressive and damage the host’s immune system.

There is now much attention on cancer immunotherapy, but this attention is on patients that have metastatic Stage IV disease. Why don’t we support the immune system early in the disease and in the early stages of standard of care therapy? After completion of therapy, why don’t we evaluate the patient’s host immunity? If there is specific depressed lymphocyte immunity to the patients own tumor; why don’t we then offer an autologous vaccine to that patient in the adjuvant setting?

This vaccine may be what is needed to delay or prevent recurrence.  We have done that in a group of patients that had depressed lymphocyte immunity to their own tumor after standard of care therapy. Those patients were vaccinated with an autologous vaccine containing their modified cancer cells, proteins, and biologic adjuvants targeted to their own tumor. The results were published in 2012 and showed the vaccine improved disease specific survival in the vaccinated patients. This vaccine was for breast cancer, but this technology will probably be beneficial solid epithelial tumor.

Our vaccine stimulates the adaptive immune system, while most of the newer therapies are passive immunity. We will explain in later posts, but these are monoclonal antibodies given by infusion to a certain tumor target.  Checkpoint inhibitor drugs are similar and are targeted to immunosuppressed elements in the tumor microenvironment. These are great and help patients with metastatic disease.  The point is why don’t we try harder to prevent metastatic disease and eliminate the need for expensive other cancer immunotherapies? This would be cost effective and much better for the cancer patient and their families.

In upcoming posts, I will explain the types of cancer immunotherapy in more detail, and also other measures that can be done to support the immune system during therapy. We will emphasize things neglected, what you should look out for and how you might improve your odds. I will quote some passages from our papers on the subject.  Hope you enjoy and get something from this post; and we eagerly await your comments and questions.

God Bless,

Robert L. Elliott, M.D., Ph.D., DSc. &

Catherine C. Baucom, M.D., Ph.D

Here are some of the videos we have published on Facebook:

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Celebrating 45 years of the Elliott Breast Center!

 

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The best way to evaluate and screen for breast cancer is using contrast enhanced digital mammography- we have been using this technology for several years and have had great results!

 

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1 in 8 women will be diagnosed with breast cancer. It is very important to get evaluated for breast cancer. We offer a one stop shop at our center – you will walk out of the office knowing the results of your mammogram and ultrasound (performed by a physician)!

This site is being launched and dedicated to all people that have been diagnosed and treated for cancer and their families. It makes no difference what type of cancer, it is still cancer and to the person receiving that diagnosis it is devastating. In fact at the time of diagnosis, no matter how minimal the disease to the patient it is a death sentence. It is also a death sentence to the family.

The moment one hears that diagnosis of cancer emotions run wild. They are immediately overwhelmed with fear, anxiety, hopelessness, the unknown, and severe stress. This stress impacts the patient’s immune system which may impact how they handle treatment for the disease. Frequently, host immunity is ignored in treating cancer. Physicians treat the disease, but forget the host with the disease. At the Elliott Breast Center, we have a unique approach that focuses treatment on both the patient and the disease. We will have more to say about our treatment approach in later postings.

Your body, your cancer is here for you to express your fears and to learn how to support your immune system, educate you about your cancer, and how you can improve your chance of cure, survival, and quality of life.

I am a Surgical Oncologist that started a comprehensive breast cancer research and treatment center in 1973, with an emphasis on early detection of cancer. In 1994, I published a book entitled “Breast Cancer, Anger at the Enemy.” Since then much has been learned about new cancer therapies, tumor biology, genomic-proteomic testing, and targeted therapy. However, the impact on host immunity created by the disease and its treatment are frequently ignored. My practice has been limited to surgery and treatment of breast cancer for 44 years and chapters in my book are still true today and apply to all types of cancer. I and my partner, Dr. Catherine Baucom, will post from this book and new emerging technology and treatment for all types of cancer. We hope we can convey knowledge and hope to patients with this disease, lessen their burden and eliminate immuno-suppressive stress. We want our followers to share their feelings, post questions, fears, their experiences, immediate and long term needs, and how we can help. We are here to share and educate you more about your disease, after all it is your body, your cancer.

Welcome to yourbodyyourcancer.com

Best of luck and God Bless,

Robert L Elliott, M.D., Ph.D. & Catherine C Baucom, M.D.,Ph.D