Saturday, 21 September 2019

What is Cancer Cells?

Cancer

Cancer Cells


Theories of origin of cancer cells renewal and cell death. Under normal circumstances, the production of new cells is regulated so that the number of any particular type of cell remains constant. Occasionally, cells arise that no longer respond to normal growth control mechanisms. Cancer is a dreadful disease and is one of the chief killers today. It commonly originates in the tissues in which the cells are regularly replaced by mitosis. Cancer or malignant neoplasm is a disease of uncontrolled proliferation of cells without any differentiation. The cancer cells invade and destroy the surrounding tissues. Normal cells show a property called contact inhibition.

Theories of origin of cancer

Mutation theory
This theory states that the accumulation of mutations over the years cause the normal cells to turn into cancer cells.

Selective gene activation  theory
This theory states that certain gene that is not normally expressed, suddenly become active and their products cause cancer.

cancer cells
Fig.: Normal cells and cancer cells

CHARACTERISTICS OF CANCER CELLS

Cell death is inhibited so they are immortal cells.
The cancer cells do not require extracellular growth factors to grow and divide. There is no control over the cell cycle, so the cells continue to divide repeatedly.
The ability to induce blood vessel formation, known as angiogenesis is well pronounced in cancerous cells. The cells do not undergo differentiation although divide continuously. Due to repeated divisions, cells form a large undifferentiated mass called a tumour.
To support their growth, cancer cells release a growth factor that causes neighbouring blood vessels to branch into the cancer tissues. This phenomenon is called vascularisation.
The cells pass out from the tumour to new sites for forming secondary tumours. This spreading of cancerous cells from one part to other parts through circulation or by forming secondaries is called metastasis. Melanin, mucus and fat droplets are more and the mitochondrial cristae become fewer in cancer cells. The nucleus of the cancer cells become irregular, hypertrophied and granular and the number of lysosomes increases.

METASTASIS

The term tumour (undifferentiated mass of cells) is synonymous with neoplasm, especially solid neoplasm. Neoplasm is the scientific term used to describe an abnormal proliferation of genetically altered cells. Neoplasm or tumour is of two types :
(i) Benign neoplasm or tumour This is a solid neoplasm or tumour that stops growing by itself and does not invade other tissues and remains confined to a particular site. It causes limited damage to the body and is non-cancerous. It divides in an uncontrolled manner, though. Depending on its location, it can be just as life-threatening as malignant lesions. An example is a benign tumour in the brain, which can grow and occupy space within the skull, leading to increased pressure on the brain.

(ii) Malignant neoplasm or tumour – This is the actual cancerous tumour which grows and invades other tissues showing the metastasis. Malignant tumours exhibit metastasis where small clusters of cancerous cells dislodge from a tumour.


Cancer Cells

CARCINOGENESIS

Carcinogenesis, also known as oncogenesis or tumorigenesis is the process of development of cancer in the body through mutagens, i.e., chemical, physical and biological agents. This process is accomplished in 4 stages, viz., initiation, promotion, progression and metastasis.

(i) Initiation – It is caused by carcinogens which act on genetic material and produce lesions. 

(ii) Promotion – Proto-oncogenes are converted into oncogenes (cancer-causing genes). A cell with recently formed oncogenes is called latent tumour cell. Saccharin and phenobarbital are common promoters. b -carotene found in green-yellow vegetables is promoter-inhibitor as it weakens the action of promoters. Promotion is even otherwise reversible.

(iii) Progression – Intracellular changes and some external factors convert the latent tumour cell into active tumour cells. It undergoes repeated divisions and forms a neoplasm or tumour. The cancer cells do not adhere to one another and continue to divide. Angiogenic factors are produced which stimulate the development of blood vessels into the area of the tumour.

(iv) Metastasis – Cancer cells overgrow the area of the tumour and pass into blood vessels or form secondaries. They reach other parts of the body and begin to form secondary tumours. Cells capable of migrating and forming secondary tumours are called malignant cells.


Cancer Cells

Fig.: Sequential process of carcinogenesis

TYPES OF CANCER

Cancers are classified on the basis of the tissue from where they arise. They are :

(i) Sarcomas – Sarcomas are cancerous tumours of connective tissues. These tumours are common in bones, cartilages, tendons, adipose tissue, muscles, nerves, blood vessels of arms and legs.


Cancer Cells

Fig.: Types of sarcoma

Some of the examples are:
(a)Rhabdomyosarcoma – cancer of striated muscles.
(b) Osteosarcoma – cancer of bones.
(c) Liposarcoma – cancer of adipose tissue.

(ii) Lymphoma – Lymphoma is the cancer of the lymphatic tissues. It appears in the lymphatic nodes, spleen and reticuloendothelial tissues. It affects a type of white blood cells known as lymphocytes, that play an important role in immunity. Hodgkin’s lymphoma is an example of human lymphoma, wherein there is chronic enlargement of the lymph nodes and enlargement of the spleen and often the liver. There is excessive production of lymphocytes by lymph nodes and spleen.

(iii) Carcinoma – Carcinoma affects the epithelial and glandular tissues. It includes breast cancer, lung cancer, pancreatic cancer, stomach cancer and skin cancer.


Cancer Cells

Fig.: Types of skin cancer

Skin cancer – Skin cancers are destructive cancerous growth of the skin. They originate from cells of the epidermis, the superficial layers of skin. The major types are :
(a) Melanoma - the cancer of the pigment-producing cells specially in the skin, (melanocytes).
(b) Squamous cell cancer – Type of skin cancer that begins in the squamous cells, the cells closest to the skin’s surface. It develops on areas of the body frequently exposed to UV radiations, such as hand, feet, ears.
(c) Basal cell cancer – It develops on areas exposed to UV rays like face and neck.


Cancer Cells

Fig.: Hodgkin’s lymphoma

Cancer Cells

Fig.: Types of breast cancer

(iv) Leukaemia – Leukemia is commonly called as blood cancer. Leukaemia results from excessive formation of WBCs in the bone marrow and lymphatic nodes, increasing their number in the blood up to 2,00,000- 10,00,000/mm 3 and also immature/myeloid stem cells. In common type of leukaemia, WBCs infiltrate the bone marrow, spleen, liver, lymph nodes and other organs causing damage and increasing their size.


Cancer Cells

Fig.: Leukemia

These cells cannot help the body fight infections.
Leukaemia can either be acute or chronic.
(a) In acute leukaemia, the abnormal blood cells are blasts that remain very immature and cannot carry out their normal functions.
(b) In chronic leukaemia, some blast cells are present which are comparatively more mature and thus can carry out some of their normal functions. The number of blasts increases at a slower pace than in acute leukaemia, as a result of which condition worsens gradually.

(v) Germ cell tumour – Tumours derived from germ cells. Germ cells normally occur in the gonads (testes and ovaries).

(vi) Myeloma (Multiple myelomas or Kahler’s disease) is a type of cancer of plasma cells (B-lymphocytes) which are immune system cells in the bone marrow and produce antibodies. But in multiple myeloma, they release too much protein into bone and blood. It builds up throughout the body and causes organ damage.


Cancer Cells

Fig.: Testicular cancer

Possible Symptoms of Cancer
(i) A persistent cough or hoarseness in a smoker.
(ii) A persistent change in digestive and bowel habits.
(iii) A change in a wart or mole.
(iv) A lump or hard area in the breast.
(v) Unexpected diminished or lost appetite.
(vi) Unexplained low-grade fever.
(vii) Unexplained loss of weight.
(viii) Any uncurable ulcer.
(ix) Bleeding in the vagina at times other than the menstruation.
(x) Non-injury bleeding from the surface of the skin, mouth or any other opening of the body.

CARCINOGENS

Cancer is neither hereditary nor a contagious disease. It can be caused by several unknown reasons. Chemical and physical agents that can cause cancer are called carcinogens. A carcinogen changes a normal cell into a cancerous cell, resulting in uncontrolled cell growth. Carcinogens cause cancer by producing changes (or mutations) in genetic material. These mutations result in uncontrolled cell division. A cancer-causing substance can alter the DNA of a cell directly or it can react with other chemicals in the body to form substances that cause gene mutations.

Types of Carcinogens

(i) Direct-acting carcinogens – Agents which do not require metabolic conversion to become carcinogenic. They directly damage DNA, leading to mutations and eventually cancer. E.g., cancer chemotherapeutic drugs (alkylating agents).

(ii) Indirect acting carcinogens – Chemicals that require metabolic activation and conversion to an ultimate carcinogen before they become active. E.g., Benzopyrene, aromatic amines, azodyes, etc.

Cancer-Causing Agents

(i) Overexposure to ionising radiations like X-rays, UV rays, gamma rays, etc., which literally punches holes in the DNA, breaking the correct genetic sequences.
(ii) Chemicals like nicotine, caffeine, steroids and arsenic air pollutants may cause cancers of lungs, brain, breast or blood.


 Cancer Cells

(iii) Ultraviolet Light – Strong epidemiologic relationship to the squamous cell, basal cell and melanoma in fair-skinned people.
This type of DNA damage is repaired with the nucleotide excision repair pathway with extensive exposure to UV light, repair systems may be overwhelmed and result in skin cancer.
(iv) Chronic physical abrasions of skin produce skin cancer.
(v) Irritation to the buccal epithelium by chewing betel leaves or tobacco or irritation to lung epithelium by heavy smoking may cause cancer of mouth and lung, respectively.
(vi) Constant heat – Kashmiris have a higher frequency of abdominal-skin cancer. This is perhaps due to the irritation caused by kangri (an earthen pot containing burning coal) which they keep close to their abdomen under the gown in winter.
(vii) Jagged teeth may cause tongue cancer.
(viii) Cancer of large intestine is linked with a diet rich in animal proteins or low in cereals, dye workers have a high rate of bladder cancer and chimney sweepers tend to develop scrotum cancer.
(ix) Breast cancer has a hormonal relationship.
(x) Biological agents – Biological agents may be viral or bacterial.
Viruses that cause cancer include the human papillomavirus (implicated in cervical cancer), the human T cells lymphocytic virus (implicated in lymphoma), and hepatitis B virus (implicated in liver cancer). Known bacterial agents are Helicobacter pylori (which causes gastric ulcers), implicated in stomach cancer.


Cancer Cells

CANCER CAUSING GENES

(i) Proto-oncogenes – Encode transcription factors that stimulate expression of other genes, signal transduction molecules that stimulate cell division, cell-cycle regulators that move the cell through the cell cycle. When a proto-oncogene mutates, it gets changed into an oncogene. The process of activation of oncogenes from proto-oncogenes can include retroviral transduction or retroviral integration, point mutations, insertion mutations, gene amplification, chromosomal translocation or protein interactions. Mutated proto-oncogene becomes permanently turned on or activated when it is not supposed to be. When this happens, the cell grows out of control, which can lead to cancer.

(ii) Tumour suppressor gene – These are normal genes that slow down cell division, repair DNA mistakes and control apoptosis (programmed cell death). When tumour suppressor genes do not work properly, cells can grow out of control, which can lead to cancer.
Some of the tumour suppressor genes are :
(a) Wilms Tumour-1 appears to shut down the division of a small subset of kidney cells during development.
(b) BRCA1 and BRCA2: Inheritable breast cancer (5%) and ovarian cancer genes and code for a protein that binds strongly to DNA, inhibiting an enzyme involved in DNA breakage.
(c) p53 a transcription factor that blocks entry into S phase if there is DNA damage. If the damage is minor, p53 halts the cell cycle and hence cell division, until DNA is repaired. If damage is major and cannot be repaired, p53 triggers the cell to commit suicide by apoptosis. Proto-oncogenes cause cancer when they are activated (turned on), but tumour suppressor genes cause cancer when they are inactivated (turned off).

HEREDITY

Most forms of cancer are sporadic and have no basis in heredity. However, there are a number of recognised syndromes of cancer with a hereditary component often a defective tumour suppressor allele. Famous examples are:
(a) Certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer.
(b) Tumour of various endocrine organs in multiple endocrine neoplasias.
(c) Familial adenomatous polyposis (a condition in which numerous polyps form in an organ or tissue) is an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
(d) Hereditary non-polyposis colorectal cancer can include familial cases of colon cancer, without a preponderance of colon polyps.
(e) Retinoblastoma, when occurs in young children, is due to a hereditary mutation in the retinoblastoma gene (RB).

APOPTOSIS

It is a form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area. It maintains the health of the body by eliminating old, unhealthy and unnecessary cells. (Programmed cell death) plays an important role in controlling cancer. Cancer cells evade apoptosis, continuously divide and metastasise to other parts of the body. E.g., infection by papillomaviruses causes a viral gene to interfere with the cell’s p53 protein, an important member of the apoptotic pathway.

ANTICARCINOGENS

Anticarcinogens (Carcinopreventive agents) are substances which counteract the effects of a carcinogen or inhibit the development of cancer. Anticarcinogens occur in green-yellow vegetables, fruits and milk. They are riboflavin (milk), flavonoids (green-yellow vegetables and fruits), vitamin C, indoles (cabbage, cauliflower), retinoids (milk, carrot, butter), some synthetic oxidants in preserved foods (e.g., butylated hydroxyanisole and toluene), etc. b -carotene present in green-yellow vegetables is promotor-inhibitor which weakens the action of cancer promoters.

CANCER DETECTION AND  DIAGNOSIS

Early Detection of Cancer

Early detection of cancer greatly increases the chances of successful treatment. There are two major components of early detection of cancer: education to promote early diagnosis and screening. Increased awareness of possible warning signs of cancer, among physicians, nurses and other health care providers as well as among the general public, can have a great impact on the spread and cure of disease. Some early signs of cancer include lumps, sores that fail to heal, abnormal bleeding, persistent indigestion and chronic hoarseness. Early diagnosis is particularly relevant for cancers of the breast, cervix, mouth, larynx, colon, rectum and skin.

Cancer Screening

Screening refers to the use of simple tests across a healthy population in order to identify individuals who have the disease but do not yet have symptoms. Examples include breast cancer screening using mammography and cervical cancer screening using cytology screening methods, including Pap smears. Other screenings include :
(i) Bone marrow biopsy and abnormal count of WBCs in leukaemia.
(ii) Biopsy of tissue, direct or through endoscopy.
(iii) Techniques such as radiography (use of X-rays), CT Scan (computed tomography), MRI Scan (magnetic resonance imaging) In CT Scan, X-rays are used to generate a three-dimensional image of internal organs. In MRI, strong magnetic fields and non-ionizing radiations are used to detect pathological and physiological changes in the living tissue. 
(iv) Monoclonal antibodies coupled to appropriate radioisotopes can detect cancer-specific antigens and hence cancer.

A vaccine that prevents cancer

A low-cost, easily delivered and effective vaccine to prevent high-frequency cancer has tremendous potential to save lives throughout the world. Recent studies are being carried on a vaccine to prevent human papillomavirus (HPV), the causative agent in cervical cancer. In the United States, cervical cancer ranks about seventh among lethal cancers. The U.S. Food and Drug Administration (FDA) has approved two vaccines to prevent HPV infection viz. Gardasil and Cervarix. Both cervical cancer vaccines prevent infection with two high-risk HPV strains which cause nearly 70% of cervical cancers. Gardasil also prevents infection with two HPV strains that cause nearly 90% of genital warts.

TREATMENT OF CANCER

Since cancer is not a single disease but causes widespread effects, so far there is no single treatment and number of therapies are used simultaneously. Cancer is at present treated in many ways on the basis of the type of cancer, location of tumours and extent or stage of the disease.
The therapies are:

(i) Chemotherapy – In chemotherapy, a variety of anti-cancer drugs are used that produce more injury to cancer cells than to normal cells. These drugs interfere with the cell division and growth and affect both normal and cancerous cells. Chemotherapy may lead to hair loss or anaemia but both get corrected after the treatment is stopped. Vincristine and vinblastin from Catharanthus roseus (Vinca rosea) are effective in leukaemia control. Taxol is another anticancer drug obtained from Taxus baccata. Tetrathiomolybdate is the new anticancer drug. It arrests the tumour growth by starving cancer cells of copper.

(ii) Radiotherapy – It is used in addition to chemotherapy. The basic principle of radiotherapy is to bombard cancer cells with rays that damage or destroy the ability of cancer cell to grow and divide by damaging the DNA within the tumour cells but produce minimal damage to the surrounding normal tissue. Both normal and cancer cells are affected by radiations, but most normal cells recover or repair themselves. Radiation therapy can treat tumours located in a specific area. Sometimes, radiation helps to control the symptoms from a tumour that has spread. Radiation can also be used in certain instances for whole-body irradiation, such as for bone marrow transplantation.

(iii) Surgery – It is the removal of the cancerous cells surgically and has only limited usefulness. In breast tumour and uterine tumour,

it is most effective but other treatments are also given to kill any cells that may have been left.
(iv) Supportive therapy – As the cancer cells progress and various therapies are tried, the patient becomes increasingly prone to infection, anaemia or haemorrhage. In supportive therapy, the antibiotics are used to prevent infection or transfusions are given to check anaemia.

(v) Immunotherapy – Immunotherapy is a form of treatment that enhances the body’s ability to recognise cancer cells and destroy them. The body’s immune system can usually destroy or help destroy most infections or the invaders like cancer cells. It can be given intravenously or by subcutaneous injection.

(vi) Blood and marrow transplant – High dose chemotherapy or radiation therapy can destroy bone marrow’s ability to make blood cells. A blood or marrow transplant can be used to replace marrow stem cells which produce blood cells. The procedure of bone marrow transplantation is usually performed either because a patient has cancer that is particularly aggressive or because they have cancer that has relapsed after being treated with conventional therapy.

(vii) Hormone therapy – The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumours include certain types of breast and prostate cancers. Removing or blocking estrogen or testosterone is often an important additional treatment. In certain cases, the administration of hormone agonists such as progestogens may be therapeutically beneficial.

(viii) Angiogenesis inhibitor – Angiogenesis inhibitors prevent the extensive growth of blood vessels (angiogenesis) that tumours require to survive. E.g. monoclonal antibody bevacizumab, has been approved as an angiogenesis inhibitor.

Role of Yoga in Cancer Recovery

Individuals diagnosed with cancer, receiving chemotherapy or radiation treatment, recovering from surgical tumour removal or in remission may be dealing with symptoms or side effects, anxiety or emotional issues. Depending on what parts of the body are affected, what type of cancer the body has (or had) and physical abilities; yoga helps an adjunct to medical treatment by:
(i) ease the symptoms
(ii) give more energy
(iii) calm the mind; and
(iv) give tools for accepting, loving and motivation.

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