Cancer

Cancer is caused in all or almost all instances by mutation or by some other abnormal activation of cellular
genes that control cell growth and cell mitosis. The abnormal genes are called oncogenes. As many as 100 different oncogenes have been discovered.
Also present in all cells are antioncogenes, which suppress the activation of specific oncogenes. Therefore, loss of or inactivation of antioncogenes can allow activation of oncogenes that lead to cancer.

Only a minute fraction of the cells that mutate in the body ever lead to cancer.There are several reasons for this.

• First, most mutated cells have less survival capability than normal cells and simply die.
• Second, only a few of the mutated cells that do survive become cancerous, because even most mutated cells still have normal feedback controls that prevent excessive growth.
• Third, those cells that are potentially cancerous are often, if not usually, destroyed by the body’s immune system before they grow into a cancer.

This occurs in the following way: Most mutated cells form abnormal proteins within their cell bodies because of their altered genes, and these proteins activate the body’s immune system, causing it to form antibodies or sensitized lymphocytes that react against the cancerous cells, destroying them. In support of this is the fact that in people whose immune systems have been suppressed, such as in those taking immunosuppressant drugs after kidney or heart transplantation, the probability of a cancer’s developing is multiplied as much as fivefold.
Fourth, usually several different activated oncogenes are required simultaneously to cause a cancer.

For instance, one such gene might promote rapid reproduction of a cell line, but no cancer occurs because there is not a simultaneous mutant gene to form the needed blood vessels.
But what is it that causes the altered genes? Considering that many trillions of new cells are formed each year in humans, a better question might be why is it that all of us do not develop millions or billions of mutant cancerous cells? The answer is the incredible precision with which DNA chromosomal strands are replicated in each cell before mitosis can take place, and also the proofreading process that cuts and repairs any abnormal DNA strand before the mitotic process is allowed to proceed. Yet, despite all these inherited cellular precautions, probably one newly formed cell in every few million still has significant mutant characteristics.

Thus, chance alone is all that is required for mutations to take place, so we can suppose that a large number of cancers are merely the result of an unlucky occurrence.
However, the probability of mutations can be increased many fold when a person is exposed to certain chemical, physical, or biological factors, including the following:

• 1. It is well known that ionizing radiation, such as x-rays, gamma rays, and particle radiation from radioactive substances, and even ultraviolet light can predispose individuals to cancer. Ions formed in tissue cells under the influence of such radiation are highly reactive and can rupture DNA strands, thus causing many mutations.

• 2. Chemical substances of certain types also have a high propensity for causing mutations. It was discovered long ago that various aniline dye derivatives are likely to cause cancer, so that workers in chemical plants producing such substances, if unprotected, have a special predisposition to cancer. Chemical substances that can cause mutation are called carcinogens. The carcinogens that currently cause the greatest number of deaths are those in cigarette smoke. They cause about one quarter of all cancer deaths.

• 3. Physical irritants also can lead to cancer, such as continued abrasion of the linings of the intestinal tract by some types of food. The damage to the tissues leads to rapid mitotic replacement of the cells. The more rapid the mitosis, the greater the chance for mutation.

• 4. In many families, there is a strong hereditary tendency to cancer. This results from the fact that most cancers require not one mutation but two or more mutations before cancer occurs. In those families that are particularly predisposed to cancer, it is presumed that one or more cancerous genes are already mutated in the inherited genome. Therefore, far fewer additional mutations must take place in such family members before a cancer begins to grow.

• 5. In laboratory animals, certain types of viruses can cause some kinds of cancer, including leukemia. This usually results in one of two ways. In the case of DNA viruses, the DNA strand of the virus can insert itself directly into one of the chromosomes and thereby cause a mutation that leads to cancer. In the case of RNA viruses, some of these carry with them an enzyme called reverse transcriptase that causes DNA to be transcribed from the RNA. The transcribed DNA then inserts itself into the animal cell genome, leading to cancer.

Invasive Characteristic of the Cancer Cell. The major differences between the cancer cell and the normal cell are the following:

(1) The cancer cell does not respect usual cellular growth limits; the reason for this is that these cells presumably do not require all the same growth factors that are necessary to cause growth of normal cells.
(2) Cancer cells often are far less adhesive to one another than are normal cells. Therefore, they have a tendency to wander through the tissues, to enter the blood stream, and to be transported all through the body, where they form nidi for numerous new cancerous growths.
(3) Some cancers also produce angiogenic factors that cause many new blood vessels to grow into the cancer, thus supplying the nutrients required for cancer growth.

Why Do Cancer Cells Kill?

The answer to this question usually is simple. Cancer tissue competes with normal tissues for nutrients. Because cancer cells continue to proliferate indefinitely, their number multiplying day by day, cancer cells soon demand essentially all the nutrition available to the body or to an essential part of the body. As a result, normal tissues gradually suffer nutritive death.

CONSEQUENCES

IN western societies one death in five is caused by cancer. The effects of tumour growth is not centred by treatment; the consequences may be obstruction of blood vessels, lymphatic’s or ducts, damage to nerves, effusions, blessing, infection, necrosis of the surrounding tissue and eventually death of the patient.
The cancer cells may secrete toxins locally or into the general circulation. Both endocrine and non-endocrine tumours may secrete hormones or other regulatory molecules.
A tumour marker is any substance which can be related to the presence or progress of a tumour.

LOCAL EFFECTS OF TUMOURS

The local growth of tumour can cause a wide range of abnormalities in commonly requested biochemical tests.
This may be a consequence of obstruction of blood vessels or ducts e.g the blockage of bile ducts by carcinoma of head of pancreas causes elevated serum alkaline phosphate activity, and sometimes jaundice. The symptoms which result from such local effects may be the first sign to the patient that something is wrong, but there may be no initial suspicion that there is an underlying malignancy.
The liver is often the site of metastatic spread of a tumour. An isolated increase in the serum alkaline phosphate or YGT is a common finding when this occurs. Even with significant liver involvement, there may be no biochemical abnormalities.

° Modest increases in the activities of the aminotransferases, ALT and AST are observed if the rate of cell destruction is high.
Metastatic spread of tumour to an important site may precipitate.
Complete system failure: for example destruction of the adrenal cortex by tumour causes impaired aldosterone and cortisol secretion, with potentially fatal consequences.
Rapid tumour growth gives rise to abnormal biochemistry; Leukaemia and Lymphoma are often associated with elevated serum urate concentration due to the rapid cell turnover.
Serum lactate dehydrogenase is often elevated in these patients reflecting the high concentration of the enzyme in the tumour and the cellular turnover.

Large tumours may not have an extensive blood supply and the tumour cells meet their energy needs via anaerogic glycolysis, this may result in the generation of a lactic acidosis.
Renal failure may occur in patients with malignancy for the following reasons:

¶Obstruction of the urinary tract.
¶Hypercalcaemia.
¶Bence-Jones proteinuria.
¶Hyperuricaemia.
¶Nephrotoxicity of cytotoxic drugs.

CANCER CACHEXIA

Cancer Cachexia describes the characteristic wasting often seen in cancer patients, the features include anorexia, lethargy, weight loss, muscle weakness, anaemia and pyrexia. The development of cancer cachexia is due to many factors and is incompletely understood.
There is an imbalance between dietary calorie intake and body energy requirements. This results from a combination of factors.

√ Inadequate food intake
√ Impaired digestion and absorption
√ Competition between the host and tumour for nutrients.
√ The growing tumour has a high metabolic rate and may deprive the body of nutrients especially if it’s large.
√ Increased energy requirements of the cancer patient. The host reaction to the tumour is similar to the metabolic response to injury, with increased metabolic rate and altered tissue metabolism.

Tumour spread may cause infection, dysphagia, persistent vomiting and diarrhoea, all of which may contribute to the overall picture seen in cancer cachexia.

Patients With Advanced Cancer & AIDS Are Usually Malnourished

Patients with advanced cancer, HIV infection and AIDS, and a number of other chronic diseases are frequently
Undernourished—the condition is called cachexia. Physically, they show all the signs of marasmus, but there is considerably more loss of body protein than occurs in starvation. The secretion of cytokines in response to infection and cancer increases the catabolism of tissue protein. This differs from marasmus, in which protein synthesis is reduced but catabolism in unaffected. Patients are hypermetabolic, ie, there is a considerable increase in basal metabolic rate. Many tumors metabolize glucose anaerobically to release lactate. This is used for gluconeogenesis in the liver, which is energy-consuming with a net cost of six ATP for each mole of glucose cycled.
There is increased stimulation of uncoupling proteins by cytokines, leading to thermogenesis and increased
oxidation of metabolic fuels. Futile cycling of lipids occurs because hormone-sensitive lipase is activated by a
proteoglycan secreted by tumors, resulting in liberation of fatty acids from adipose tissue and ATP-expensive
reesterification in the liver to triacylglycerols, which are exported in VLDL.

CONSEQUENCES OF CANCER TREATMENT..

Anti-tumour therapy can have serious effects, gonadal failure arising from radiotherapy or chemotherapy is frequently encountered.
Hypomagnesaemia and hypocalcaemia may be a consequence of the cytotoxic drugs; cisplatin.
Patients treated with methotrexate may become folate deficient.
Hyperuircemia is the consequence of the massive cell death which occurs in the treatment of some tumours with cytotoxic drugs, particularly lymphomas and some leukaemias, and is known as tumourlysis syndrome.

CONCLUSION

The measurement of oestrogen and progesterone receptors in biopsy material has been used to determine which breast cancer patients will respond to endocrine therapy. E.g. with the antioestrogen tamoxifen. As the synthesis of progesterone receptors is dependent on oestradiol, the presence of both receptors indicates the integrity of the oestrogen receptor mechanism, in the tumour cells.
The prognostic value of such receptors measurements is still controversial.

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