Deadly diseases

From DrugPedia: A Wikipedia for Drug discovery

Cancer: Understanding a deadly disease

Introduction

The major feature of eukaryotes is their defined life span. For example, Somatic cells, whose growth and division are highly regulated, Cancer cells are notable exceptions as they have lost their growth control, and they keep on dividing inappropriately which can be lethal for the individual. DNA is intrinsically unstable and can be altered by normal errors in DNA replication. Also, DNA is subject to extensive damage from processes associated with cellular metabolism. Within our life span our cells undergo 10 million billion cell divisions, spontaneous errors in this process leads to mutations and cancer, which accumulate with age. Fortunately, though, cells have evolved an intricate mechanism to repair genetic damage. Thus if a mutation that transforms a cell into a cancerous one can be repaired before the cell divides, the cancer eliminated. Unfortunately not all cancerous mutations are eliminated by immune system.

Cancer: a multi step process

Cancer is a disease in which cells divide uncontrollably, often invading to parts of our body. In body cancer cells grows in a similar way as normal cells, forming large growths, called tumors, that destroys vital organs of our human body and ultimately causing death. Occurrence of cancer is a multi step process in which initiation of tumor requires several steps, which is followed by further changes to strengthen the tumorigenic state. Tumor progression is further driven by selection of cancer cells which can proliferate more rapidly.

In cancer, the two major genomic changes are the

i) Conversion: accumulation of somatic mutations

The conversion of a normal cell to a cancerous one begins with a phenomenon known as mutation. Most cancer cells have more number of mutations than normal cells. Cancer progression is proportional to number of mutations, which can be caused by chemical, physical, or biological agent (a virus for example). Those agents which cause initial transformations are called as co-carcinogens. Mutation of a single gene does not result in cancer, For cancerous growth mutation must occur in 1 of the 50 genes that control the cell replication, which can release the cell from its normal growth control. Primarily release of cells from constraints of growth controls often remains dormant for long periods, presumably controlled by tissue factors. This homeostatic control keeps the cancer cells from dividing and provides an important measure of protection. Early mutations occur in the mutator genes. The inactivation of these genes decreases the repair of damaged gene and increasing the rate of mutation. The number of genes in the cancer cells reflects the genetic instability, which is a result of small duplications or deletions, translocations of material from one chromosome to another or even changes that affect entire chromosomes. As mutations are occurring at very high rate, different mutations create an opportunity to select among the population for cells with particular properties. in cancer mutations that increases the growth potential of a cell have a selective advantage. At each stage that population is selected which can proliferate aggressively and thus creating more descendants. Also later they can migrate to different locate in body and start colonies in new locations.

ii) Development and progression: Genetic instability

The second stage leading to cancer is called development and progression. It occurs by the stimulation of mutated cell by a chemical substance. Those substances influence the second stage of carcinogenesis are called promoters. Promoters stimulate to divide cells uncontrollably, as do errors in replication. A cancer progresses by multiple cycles of mutation and selection.

Types of tumors

As mentioned earlier,cancer is deadly disease in which cells divide uncontrollably, often invading to various parts of the body. But not all abnormal cellular proliferation is cancerous. Some cells forms small masses after some time of growing and then stops. These are called benign tumors. They pose no medical threat but put pressure in nerves or block vessels. Of great concerns is the malignant tumor, which continues to grow as the cells proliferate to various parts of the body via circulatory system or blood vessels or in the lymphatic system. It is spread as a result of spreading of loose cells from the original tumor, and these cells can uncontrollably to form secondary tumors. This spread of cells from one region of the body to another is called metastatis.

Tumor Cells are Immortalized and Transformed

3 types of changes occur when cells become tumorigenic

a)Immortalization describes the property of indefinite cell growth( without any other changes in the phenotype necessarily occurring).When cells are taken from a vertebrate organism and placed in a culture , after several divisions the growth ceases , which is called as senescent stage. This is followed by crisis in which most of the cells die .The number of divisions before it happens is called as hayflick limit. The survivors that emerge from crisis are able to divide indefinitely as their properties have changes in act of emerging out of crisis. This comprises the phenomenon of immortalization. Human cell enter immortalization at ~40 generations, although rarely cells emerge out of it successfully.

b)Cells cultures of tumors show different properties than the normal cells which are

          i) Anchorage dependence-a solid surface is needed for the cells to grow
         ii) Serum dependence (growth Factor dependence) - serum is needed to provide   
             essential growth factors.
        iii) Density-dependent inhibition- cells grow only to limited density, as growth is 
             inhibited, perhaps by a process involving cell cell surface contacts.
         iv) Cytoskeleton organization-cells are flat and extended on the surface have 
             elongated network of stress fibres (consisting of actin filaments).
  
All these are a property of monolayer cultures (A layer that is one cell thick) on a substratum.

A Tumor cell grows in a much restricted manner. It has
         i) Reduced serum dependence
        ii) Does not need any solid surface to attach instead of growing on flat surface cells     
            "round up" to form thick mass of cells called as focus. Furthermore, The cells may 
            form tumors if injected into a host( a test animal).

c)Now fully tumorigenic cells become mobile and can migrate to start new colonies. This is known as metastasis.

Oncogenes and tumor suppressors

These are the two classes of genes in which mutations cause transformation.Oncogenes were initially are the genes carried by the viruses that can transform their target cells. A major class of the viral oncogenes has cellular counterparts that are involved in normal cell functions. the cellular genes are called as proto-oncogenes, the mutation of these genes or aberrant activation in cell to form an oncogene is associated with tumor formation. An oncogene results from a gain-of function mutation of a proto-oncogene that generates a tumorigenic product. in this a cellular proto-oncogene is inappropriately activated. Tumor suppressors represent the loss-of-function in genes that usually restrict cell cycle and impose certain growth constraints. The release of the Constraint is tumorigenic.The oncogenes represent different types of activities ranging from transmembrane proteins to transcription factors, and the definition of these functions can lead us to understand the types of changes involved in tumor formation.

      PROTO-ONCOGENE------> (Mutation converts proto-oncogene) to oncogene------->cell is transformed to tumorigenic phenotype

Some Carcinogens Exert their effect outside DNA

Chemical carcinogens induce cancer by altering the DNA of the cell . These are known as DNA-reactive carcinogens. Many carcinogens act outside the DNA, that is they do not directly interact with the DNA. These carcinogens are known as epigenetic carcinogens, operate eliciting other biological effects. By causing hormonal imbalance that lead to cellular proliferation.

Drugs and vaccines

Nowadays, fortunately, new drugs have been established for certain type of cancer, such as childhood leukemia. This helps boost the survival rates of individuals. Surgery often also works in certain types of cancers such as skin cancer. Radiation and chemotherapy is are successful in still others. One of the most advancements in cure in cancer is not a drug or a vaccine but it is the early advancement in detection of cancer. Early the detection, greater is the chances of one's survival.

Anticancer vaccine: It is actually a vaccine for lung cancer. It is not to prevent a disease but it is generally to boost the immune system of an individual. The treatment helps fight in an existing disease. In this treatment patients with early detection of cancer were treated with a plasma membrane protein extracted from lung cancer cells. When given to patients it stimulates their immune system. The immune system, in turn mounts assault on the foreign protein in the blood. as the protein is attached to the lung cancer cells the immune system attacks and kills the lung cancer cells, especially those have spread to many parts of the body. This type of vaccine could double the survival rates in patients whose lung cancers were diagnosed early.

Microspheres and monoclonal antibodies: These are the liposomes or the lipid microspheres containing cancer-killing chemicals or oncotoxins. Liposomes can be directed to kill the cancer cells, in process by giving small doses of lethal drugs at the cancer affected area and sparing the rest of the body. Targeting cancer cells is the job of the antibodies, special proteins incorporated in the lipid membrane. This antibodies bind to the proteins in the plasma membrane of the cancer cells, allowing the toxic bullet to attack its target.Oncotoxins may also be attached directly to monoclonal antibodies, which are synthesize by the immune system of test animals that have been injected with tumor cells. These antibodies can be artificially (chemically) bonded to oncotoxins and given to patients. The antibody complex then bind to cancer cells and destroys it.

Treating cancer with light: There are certain drugs invented, which on exposure of light on them can kill the cancer cells. In This therapy patients with tumors in the lining of esophagus and the bronchi of lung are given photofrin(porfimer sodium). After circulation of drug in the blood, a small optic fiber is inserted into the affected area and laser beam is trained on the cancer affected area which selectively destroys the cancer cells.

Prevention

Mutations do not manifest themselves immediately in cancer. In many cases tumor formation occurs after 20-30 years after mutation. The period between exposure and the emergence of a cancerous tumor is called the latent period. Despite many new developments in cancer, stress is given on the prevention. By quitting smoking or not taking up in the first place, by limiting exposure to x-rays and uv light, and by choosing a safe occupation and dwelling one can diminish the likelihood of cancer.