Background Proposal for a Clinical Trial on Advanced Cancer based on the Chemotherapeutic Effect of Anti-Tumour Molecules of Natural Origin.

John Grinstein Ph.D.
Nutritional Medicine Research UK.

Introduction
During the twentieth century, there were two basic medical and biochemistry breakthroughs. In the first part of the century, progress in medicinal chemistry, identified a number of substances present in nature that, if deficient in the human body, can cause specific diseases.
As a result of these advances, the synthesis of many new medicinal substances took place and the large scale production of vitamins, provided the foundation of the pharmaceutical giants of today.

During the second half of the century, the synthesis of antibiotics and antibacterials, allowed the most rapid progress in the treatment of infectious diseases.
The main tools in use today for cancer chemotherapy, emerged during the time in which antibiotics were having a great impact. There is a similarity today in the rationale to treat both infectious diseases and cancer.
Cancer chemotherapy aims at the killing of malignant cells, while antibiotics aim at the killing of microorganisms.  But microorganisms are both quantitatively and qualitatively different from human cells.
Therefore, cancer should not be treated on the same basis as an infectious disease. In other words, just by killing malignant cells, we can never reach the same effective result as when killing intrusive microorganisms.

Cancer is a malformation arising within the cells of a living organism. Therefore, it is not as easy to differentiate between the normal cell and the cancer cell in the same organism, as it is, between the normal cell and the bacterial cell in that same organism.
 

DNA Damage.
Most cancers originate due to a deficiency in the capacity to repair DNA damage. DNA repair mechanisms, refer to the cellular responses associated with the restoration of the normal nucleotide sequence and chemistry of DNA following damage. 
The simplest biochemical mechanism, by which damage to DNA might be repaired, is one in which a single enzyme catalyzes a single reaction that restores the structure of the genome to its normal state. The most general DNA repair mode, observed in nature, is one in which damage or inappropriate bases are excised from the genome and replaced by the normal nucleotide sequence and chemistry. This cellular response to DNA damage is referred to as excision repair.

The enzymatic event, that characterizes the excision of free bases from DNA, is the hydrolysis of the N-glycosylic bond, linking damaged or inappropriate bases to the deoxyribose-phosphate backbone of the DNA. The enzymes that catalyze this reaction are called DNA glycosylases. At the point of the excised base, an AP endonuclease provides a prime end, from which DNA polymerase initiates synthesis to replace the excised nucleotide. The above represents just an example of a mechanism of DNA repair through the activity of three different enzymes.

DNA Repair
There is in nature, a large number of chemical compounds present in fruit and vegetables that, when taken as food, penetrate the cell and then the nucleus of the cell, interacting at specific sites of the DNA backbone.
As a result of this interaction, the synthesis of enzymatic complexes, required for DNA repair, becomes activated.
It is the activation of these DNA repair systems, that allows a cancer cell to interrupt its uncontrolled RNA synthesis and its distorted growth factors’ amplification.
Once DNA damage becomes repaired, through any of the above mentioned DNA repair mechanisms, the damaged cell will reestablish its differentiation paths. Maturation will follow through its normal stages, leading to cell programmed death. (Apoptosis)
When there is a deficiency in a food sourced molecular structure, needed for DNA repair, cell differentiation becomes impaired. A cascade of biochemical events, originating in this unrepaired DNA, leads to cell proliferation.

This graph shows the amplification of an oncogene in the nucleus of a cancer cell.

Cancer, which originates because of a deficiency in the above mentioned structures, will be much more effectively treated, through a mechanism that will compensate for the deficiency which led to DNA repair failure, than by utilizing a cytotoxic approach

Epidemiological Studies.
There are hundreds of well documented epidemiological studies, showing an inverse correlation between cancer incidence and the consumption of fruit and vegetables. Based on these results, we have undertaken the screening of a significant amount of molecular structures, isolated from a large variety of fruit and vegetables in common use.
We have used many of the standard analytical chemistry methods available today, to determine DNA-food molecular interactions. This research has guided us to identify substances, present in fruit and vegetables, which are essential for the activation of the enzymatic DNA repair mechanisms in a cancer cell.
 

Experimental observations
We added our extract formulations to the culture media of various cancer cell lines. The results led us to understand about the different anti-tumour activities present in each one of these formulations.
 

Food Biochemistry Research.
The contribution of Food Biochemistry Research in the development of new strategies to treat cancer can be divided in accordance with the activity of 3 different types of chemical compounds.

1.– Plant Kingdom Anti-tumour Molecules.
These are chemicals found in the plant kingdom from where a medicinal substance, with anti-tumour properties, can be isolated, extracted and used as a medicinal tool to treat cancer. 

2.– Mutagens in Nature and Carcinogenic Molecules in Cooked Foods.
These are chemicals present in processed food and sometimes in nature that, after being isolated, characterized and analyzed, through molecular biology methods, are found to have a carcinogenic or mutagenic effect.

3.– Anti-Tumour Molecules of Natural Origin
These are chemicals present, mainly in fruit and vegetables, in common consumption and of use in producing either a cancer chemopreventive or a cancer chemotherapeutic effect. These substances differ from the plant kingdom chemicals (category 1), in that they do not originate from rare species of plants, usually with a potent cytotoxic effect. They are, instead, present in foodstuffs of daily and common use, at micromolar concentrations, detectable only through newly developed methods of analytical, biophysical and nuclear chemistry spectroscopy.

The clinical trial we are proposing, for your consideration, is based on the use of natural substances. Most drugs in use today, reach clinicians at the final stage of development. More than 60% of all drugs in use today, to treat cancer, are based on natural compounds. However, because the substances in nature, from which they originate, are hardly ever mentioned by the manufacturers, there is a misconception about as to the contribution any natural product can provide in the struggle against cancer.  

Induction of Cell Differentiation.
While a cytotoxic compound will show an immediate decrease in tumour size, due to the direct interference with cell replication, a food chemotherapeutic compound stops proliferation by first inducing the differentiation of cancer cells.
An MRI, CAT or Ultrasound scan assessment of this treatment will show a response similar in principle to that reported by Cloughesy and Woods, with the use of a biological agent for malignant glioma. Here, there was a slow and delayed anti-tumour effect, reaching its peak response, 9 months after the treatment was initiated.
However, we have observed that, with the treatment we propose, tumours do not show any further growth in size as early as 15 days after the treatment has properly started. Cancer cells are induced to differentiate, therefore, the proliferative process ceases almost immediately.
The reduction in the size of the tumour is however, a much slower process. Cancer cells are not rapidly killed, but induced to initiate the normal maturation paths, leading to their programmed death.

We report, in the following enclosure of this presentation, the clinical history and results on 11 advanced cancer patients, in whom, a GC10-100 intervention produced a cessation in tumour growth, in various aggressive forms of cancer. 
 

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