CANCER – Neoplasia


Everybody Should Know the Basics.

Uncontrolled division of abnormal cells in the body is called cancer (or neoplasia). These cells are called neoplastic cells. Neoplastic cells when collectively form a mass of recognisable size is called a tumour. Every tumour is not cancerous. Tumours can be benign or malignant. A cancer is in fact a malignant tumour (neoplasm).

There are many different types of cancers depending upon of the locality of cancer cells with respect to the biological identity of the tissue in which they do originally exist viz.: breast cancer, colon cancer, bone cancer etc.

Although there are numerous types of cancers the underlying cause of the majority of these types is the same – DNA damage. Such DNA damage is caused due to a cancer-causing genetic mutation.

Cancer is not a disease of modern-day, history of cancer dates back to 370BC or beyond. Cancer was found among the fossilized bone tumours, human mummies of ancient Egypt. Hippocrates ‘father of medicine’, was the first person who introduced the terms ‘carcinos’ and ‘carcinoma’. The Roman physician Celsus later translated Greek term into cancer. Recently it has been revealed the oldest record of cancer is found in prehistoric times as old as 1.7 million years old.

As mentioned earlier in most of the cases the common underlying factor for cancer is damage to DNA structure in the nucleus of a cancerous cell. This DNA damage can be due to many causes; inflammation, radiations, toxins, exposure to carcinogens, spontaneous deamination of methylated cytosine residues (spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process) etc. Deamination is the removal of the amine group from a molecule. Deamination primarily takes place in the liver, but glutamate is also deaminated in the kidneys. When there is an excess of protein intake, deamination occurs, during this process, amino acids are broken down. The amino group is removed from amino acid and converted into ammonia. Ammonia is harmful toxic substance for our bodies. Enzymes convert it to urea or uric acid by addition of carbon dioxide. In addition, unnecessary vaccinations may cause cancer among children and adults equally.

DNA mutation (damage) to a healthy cell can lead to loss of controlled cell cycle and formation of the tumour (known as tumorigenesis). This formation of the tumour is referred to as the primary tumour. Some of the cells in the primary tumour can undergo further mutation and detach themselves from the original tumour site to invade other sites in the body. This movement and deposition of cancer cells from their primary location to a new location is called ‘metastasis’. At this new site, these cells form new tumours called a secondary tumour. In this way, vital organs, such as the lungs and liver, are invaded by cancer cells. In this way, usually, it is metastasis that causes death.

Since DNA damage is a continuous process, therefore, we all have cancer cells in our bodies. Only a person suffers from cancer as a disease when these cancer cells find a suitable environment to propagate and further multiply. This can be due to inflammation, radiations, toxins, exposure to carcinogens, spontaneous deamination of methylated cytosine residues etc. There are 7 main steps which nature has set-up and each triggers an appropriate response in our bodies to destroy cancer cells in their path.  It is this very characteristic of a cancer cell that it by-passes or disables all these steps and become a tumour and metastasis.

APOPTOSIS (Cell suicide):

When DNA of a cell is damaged beyond its repair then a mechanism from within the cell initiates which orders the damaged cell to destroy itself. This is called APOPTOSIS (cell suicide or cell death). Since our bodies are capable of regenerating new cells on a daily basis, therefore, it is quite logical that such damaged cells should be destroyed. But in the case of cancer patients, this mechanism of cell’s self-destruction is overridden by cancer cells. The instructions about whether a damaged cell should destroy itself or not rely on the availability of a protein P53. In case of cancer patients in their cells gene TP53, which controls the production of p53 protein, is inefficient, thus these cancer cells instead of being self-destroyed remain alive and carry on multiplying in numbers.  If the activity of gene TP53 is increased, then cancer cell would self-destroy and would not be able to multiply to form a tumour.

Hence point here to remember is this, THE ACTIVITY OF GENE TP53 IS SLOW IN CASE OF CANCER PATIENTS.

CELL CYCLE CONTROL (tumour suppression):

Uncontrolled cell cycle may cause cancer. In our bodies, older cells die and new cells are regenerated. These new cells are generated by the division (proliferation) of cells within their respective tissue. There is a watertight mechanism which controls cell cycle, in order to maintain structure and function of a tissue. There are specialist proteins which are tumour suppressors and control unwanted cell proliferation. Uncontrolled cell cycle leads to the multiplication of damaged unhealthy cells, which form a tumour. A recently discovered protein encoded by gene KEAP1 plays a pivotal role in cell cycle control and inhibition of tumour formation. KEAP1 gene product also shuts off blood supply to tumours.

Food Supply Line for a Cancer Cell (Angiogenesis):

When a tumour is formed it needs a continuous supply of oxygen and nutrients to survive. For this reason, it develops a network of blood vessels to extract food for itself. Angiogenesis is controlled by many factors including optimal levels of protein p53. The protein p53 plays a vital role to hinder the development of new blood vessels, which are formed due to lack of oxygen, in tumours. Conversely suboptimal level of p53 leads to tumour growth, with the formation of unrestricted blood vessels within the tumour.

Immune Control:

The immune system plays an important role in the suppression of tumour growth. It is well understood now, that adaptive immune system (also known as an acquired immune system; evolves due to exposure to certain pathogens in a lifetime) produces cytotoxic T cells specific to kill off tumour cells. However, a link has been found between hypoxia-induced angiogenesis and generation of immune tolerance to tumours.

The protein encoded by gene OX40 has been found to interact directly with tumour-specific cytotoxic T cells to break this tolerance and make them kill tumour cells more effectively.

Metastases – the spread of cancer cells:

Some of the cancer cells within a tumour go under drastic changes. This allows them to transport themselves to a new location in the body to form secondary tumours in other organs. The protein encoded by gene TIP30 plays an important role in inhibiting the escape of cancer cells from primary tumours. By optimising the function of the gene TIP30 metastases process may be stopped in its tracks.

DNA repair:

As mentioned in the very beginning of this article. DNA damage occurs on a regular basis if DNA repair mechanism in a cell, lags behind DNA damage, then there is a possibility that a damaged cell may turn in to a cancerous cell. There are a number of genes that encode proteins to repair this damage. BRCA1 gene is one of them. If this gene BRCA1 encodes ineffective or too little gene product, DNA is not repaired effectively. If DNA damage is inflicted upon above-mentioned genes, then all sorts of calamities can possibly occur in case of a cancer patient. Ranging from the formation of tumours, angiogenesis and lethal metastases.

 Chemotherapy and Immunity:

Most of the chemo drugs work on the bases of destroying cells which are proliferating. Immune system cells are also continuously proliferating in the bone marrow to form new immune-competent cells, thus these cells also become the victim of chemotherapy drugs. Consequently, chemo drugs stop the production of immune cells, needed to attack tumour cells. Bone marrow can be stimulated to produce more immune-competent cells to kill cancer cells with the stimulation of cytokine IL7. Thus the function of gene IL7 is jeopardised with chemotherapy.

Right, Gene Product:

In cells, there is a mechanism that makes sure all the right form of products is synthesised from a particular gene. Many genes are able to produce more than one kind of biological products. The inability to make the right form of a gene product is recognised as one of the hallmarks of cancer cells. Recent studies have shown that reduced expression of RBM4 gene results in its inability to instruct cancer cells to kill themselves, control their undesirable division, arrest tumour growth, and to stop metastasis or spread of cancer.

In summary following genes and the proteins encoded by them play a crucial role to effectively control and rid the cancer cells:

KEAP1, TP53, OX40, TIP30, BRCA1, IL7, RBM4

For more information and for support through complementary healthcare contact your complementary healthcare provider.

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