Cancer, Respiration and the Peril of the Heart in Cancer Patients
Author and Curator: Larry H Bernstein, MD FCAP
and
Curator: Aviva Lev-Ari, PhD, RN
Cancer and Respiration
Otto Heinrich Warburg, a German physiologist, observed that tumor cells utilize glycolysis more than their normal counterpart cells despite being in normal oxygen conditions (the “Warburg Effect”). In 1931, Warburg won a Nobel Prize for his work on mitochondria. Subsequently he formulated the Warburg Hypothesis, that the cause of cancer is defective mitochondria.
- The hypothesis focused on the measurement of RESPIRATION
- Mitochondrion was not then known and referred to as grana
- He referred to work by Pasteur – 60 years earlier, and the Meyerhof ratio
the discovery of “oncogenes” that directly caused cancer led researchers to believe that the Warburg Hypothesis for cancer causation was simply wrong. As the data on cancer-causing genes became both more comprehensive and more productive, cancer research switched to decoding genes, and a generation of researchers began ignoring metabolism as a factor. This was unfortunate. The genetic code is the template for cellular synthesis. The cell function is carried out by proteins and the membranes have a lipoprotein structure that includes all organelles. The proteins carry out the cellular function through interaction with substrates that fit to an active site like a lock and key. Moreover, the same protein (or enzyme) can have pleiotropic actions because of three dimensional structure and folding. In addition, there are increasing instances of multiple molecular forms of the same protein or enzyme that have minor changes in amino acid sequence, but have different functional activity based on the cell type and based on substrate interactions.
We are including an article on DM and cancer. The e-Reader attention is drawn to the fact that the mediated relations between Type 2 DM and Cancer are explained by the fact that Type 2DM is a systemic disease that affects lipid metabolism, the kidney, and is a risk factor for heart disease.
The connection – LKB1, a gene causing 30% of lung cancers and 25% of cervical cancers was directly activating the enzyme AMPK, known to modulate diabetes and metabolism.
Dr. Shaw asked himself two seminal questions:
- “What did a diabetes gene have to do with cancer?
- did the cancer gene have anything to do with diabetes?”
AMPK responds to caloric restriction, exercise, hypoxia, low glucose, and metabolic hormones such as ghrelin or adiponectin.
The drug metformin operates through LKB1 and AMPK to lower blood glucose. Since it is well-tolerated, it is the frontline treatment for type 2 diabetes with more than 120 million people taking it every day. However, as Dr. Shaw had postulated, at this time it was also becoming known that metformin reduces the risk of cancer in diabetic patients.
AMPK directly shuts off a major oncogene called TOR, but it only does so when nutrients are low. This oncogene is the causal biochemical event in a number of human cancers, including kidney cancer, tuberous sclerosis, and LAM.
Metformin and phenformin both inhibit mitochondria; however, phenformin is nearly 50 times as potent as metformin. Dr. Shaw and his postdoctoral fellows tested both metformin and phenformin as chemotherapeutic agents in mice genetically engineered to mutate different cancer genes in adult lung cells, which results in the mice developing advanced-stage lung tumors. Only in mice lacking the LKB1 cancer gene did Dr. Shaw and his team observe that, after three weeks of treatment with phenformin, there was a major reduction in tumor burden in the mice.
Knowledge of this leads to a profound impact on therapies for cancer because, as Dr. Shaw now knew, it was possible to interfere pharmacologically with this pathway. Disruptions of the “fuel sensing” mechanism means that with cancer cells, they could cause nutrient and oxygen deprivation. This had the medically important effect of signaling AMPK to arrest cell growth. The cancer cells would be influenced to cease proliferating.
Is this perhaps a key to the arrested apoptosis of cancer cells? Cancer cells do have autophagy without apoptosis. This gives malignant cells the ability to seek eternal life. This is quenched when the host expires.
The heart. Myxomas…metastatic other. Myxosarcomas? Not myocardiosarcomas. Myocardiocyte is absolutely dependent on oxygen. Apoptosis is not impaired, even though autophagy is needed for repair.
From Our Cardiovascular Disease – Volume Three
Heart – Correlation between Cancer and Cardiovascular Diseases
Causes
2.1.6.1 Reuben Shaw, Ph.D., a geneticist and researcher at the Salk
Institute: Metabolism Influences Cancer
Aviva Lev-Ari, PhD, RN
2.1.6.2 Heart Tumors: Etiology and Classification
Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2014/01/08/heart-tumors-etiology-and-c lassification/
2.1.6.3 Amyloidosis with Cardiomyopathy
Author: Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/03/31/amyloidosis-with-cardiomyop athy/
Biomarkrs
2.1.6.4 Stabilizers that prevent Transthyretin-mediated Cardiomyocyte
Amyloidotic Toxicity
Larry H. Bernstein, MD, FCAP
2.1.6.5 Cancer Symptom Science: On the Mechanisms underlying the Expression
of Cancer-related Symptoms
Aviva Lev-Ari, PhD, RN
Therapies
2.1.6.6 Cardio-oncology and Onco-Cardiology Programs: Treatments for Cancer
Patients with a History of Cardiovascular Disease
Aviva Lev-Ari, PhD, RN
2.1.6.7 Radiation and Chemotherapy Therapy: The Pharmacological Risk for
Developing Cardiovascular Disease
Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2014/01/08/20316/
2.1.6.8 3rd Annual Canadian Cardiac Oncology Network Conference, June 20 –
21, 2013, Ottawa Convention Centre
Aviva Lev-Ari, PhD, RN
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