Communicable diseases Essay Example | Topics and Well Written Essays - 750 words

Communicable diseases - Essay Example Approximately 2 billion persons in the world are infected with TB. In the United States (US) for instance, almost 15 million people are infected with TB. When it becomes active, TB kills 60% of the people who do not quest for medication. This percentage correlates with 3 million deaths experienced worldwide every year. In the US, approximately 20,000 TB infections take place every year (Denholm, Eisen, McBryde & Street, 2012). TB has treatment; when treated, about 90% of the active TB patients survive. Various governments including the federal government of Canada are working towards reducing the incidence, as well as the burden of TB. Among the efforts put by Canada include conducting investigations in order to enhance early detection as well as treatment of individuals having TB so as to control the spread of the disease. â€Å"Early detection as well as treatment of individuals with latent TB infection who are at high risk of progression to active TB disease† (Tuberculosis, 2012) is also one of the key component of not only an effective TB prevention, but also control program. The occurrence and spread of TB are highly influenced by social determinants related to health. In connection with this assertion, many governments are championing collaborative actions so as to address the risk factors for TB. According to Public Health Agency of Canada (2014), the environmental factors related to TB include overcrowding housing, poor ventilation as well as homelessness. Additionally, the Public Health Agency of Canada also claims that unsanitary living conditions, as well as lower income levels, contribute significantly to the occurrence and spread of TB. In connection with CDC assertion, it is evident that overcrowding as well as poor ventilation exposes people to fluids containing the TB bacterium. As introduced above, it is clear that TB is regarded as a â€Å"disease of the poor and socially disadvantaged† (Chandler,

BUSINESS Report Essay Example | Topics and Well Written Essays - 1000 words

BUSINESS Report - Essay Example Also we can observe that the management has redesigned the job of the workers. The hierarchical structure has been diminished and the teams hold more responsibility. Eventually, this will create new challenges for the members of the team. The jobs of the workers are enriched. The jobs of the team members are halved so that they can concentrate on the development of the team. Every fortnight the team members talk for 45 minutes to solve problems and to gather new ideas. The responsibility of the workers has been increased and the role played by the workers is changed. From mere assembly line work the job now involves various tasks such as planning, organizing, leading and directing. b) The management of BMW has taken the approach to motivate the employees as mentioned in theory Z. Theory Z mentions the major postulates of Japanese management practices and how these practices can be adopted to the environment of other countries. The major features of this theory are building trust, strong bond between the organization and employees, employee involvement and no formal structure. According to this approach, trust is the first primary factor for motivation. Trust between the members of the organization at various levels has to be built through integrity and transparency. At BMW, the work teams have been very effective in building the relationships between the employees across the organization. Another major aspect that has to be noted in this approach is the employee involvement. Any decision affecting the production practices is being done by the team members which increases the motivation of the members. Also this increases the commitment of the employees and gives due recognition to their role. Under this approach the formal structures in an organization are no longer adopted. Here, at BMW, the work teams resolve the issued irrespective of the formal hierarchical structures. The major advantages of

Rule of Law - UK law Essay Example | Topics and Well Written Essays - 1500 words

Rule of Law - UK law - Essay Example This drawback was recently remedied substantially, albeit not completely, by the Constitutional Reform Act 2005.1 For instance, there is now a Supreme Court under Part 3 of the law which has taken over the judicial powers of the House of Lords which used to have appellate jurisdiction. Being then all under the Queen, the rule of law was said to be hinged on her sovereignty in the parliament which makes laws and on her sovereignty in the courts which interpret and apply the law. From within this ambit was derived the structure of the so-called twin foundations. While it is true that the duties and functions of the Queen are more ceremonial, there are still aspects over which she wields power which she may exercise at will. Important examples are her needed assent for the final enactment of a bill into law and her influence over the appointment of the Prime Minister and the other members of the cabinet because of the need for the Queen's formal consent. Although reduced in the course o f history, the supremacy of the monarchy can still be felt. As a matter of fact, there were, and still there are, moves to abolish it on the strong suggestions that it is inutile and hugely expensive.2 Some claim that a democratic standard republic will be a better and effective form.3 Another aspect in the United Kingdom government worth pondering is that it does not have a complete written set of codified laws and that includes its own constitution. Case laws which are actually compilations of decided or accepted jurisprudence have a lot to do in the law-making processes which are, ironically, borne out of judicial pronouncements. This means that what the courts resolved would become laws. Stated straightforwardly, therefore, the makers of the law interpret the law in the event of a controversy or in incidents where there are doubts in construing that particular law. Incidentally, with the new Constitutional Reform Act 2005, the new Supreme Court may be able to thresh out all the possible hitches. Since the high court started working only on October 1, 2009, a lot of patience is needed until the intended reforms are made effective slowly and gradually in the mainstream of justice administration. Along this line, it can be hoped in large part that the new law for constitutional reform will bring about positive changes.4 The twin foundations of the Queen's sovereignty During one of the deliberations of the constitutional reform bill, the Law Lords had the occasion to mention the ruling in X v Morgan Gramplan (Publishers) Ltd. which enunciated the principle that the rule of law in the United Kingdom is founded on both the Queen's sovereignty in the parliament which is charged with the enactment of laws and the Queen's sovereignty over judicial proceedings particularly those administered by the House of Lords in its duties anent appellate jurisdiction.5 It has always been debated if the somewhat irregular or abnormal circumstance contradicts the precepts on separation of powers. It is like taking exceptions on one person being the prosecutor, the judge and the executioner. The notion has a direct correlation with the

BUSINESS Report Essay Example | Topics and Well Written Essays - 1000 words

BUSINESS Report - Essay Example Also we can observe that the management has redesigned the job of the workers. The hierarchical structure has been diminished and the teams hold more responsibility. Eventually, this will create new challenges for the members of the team. The jobs of the workers are enriched. The jobs of the team members are halved so that they can concentrate on the development of the team. Every fortnight the team members talk for 45 minutes to solve problems and to gather new ideas. The responsibility of the workers has been increased and the role played by the workers is changed. From mere assembly line work the job now involves various tasks such as planning, organizing, leading and directing. b) The management of BMW has taken the approach to motivate the employees as mentioned in theory Z. Theory Z mentions the major postulates of Japanese management practices and how these practices can be adopted to the environment of other countries. The major features of this theory are building trust, strong bond between the organization and employees, employee involvement and no formal structure. According to this approach, trust is the first primary factor for motivation. Trust between the members of the organization at various levels has to be built through integrity and transparency. At BMW, the work teams have been very effective in building the relationships between the employees across the organization. Another major aspect that has to be noted in this approach is the employee involvement. Any decision affecting the production practices is being done by the team members which increases the motivation of the members. Also this increases the commitment of the employees and gives due recognition to their role. Under this approach the formal structures in an organization are no longer adopted. Here, at BMW, the work teams resolve the issued irrespective of the formal hierarchical structures. The major advantages of

The impact of the Federal Reserve on the elections in 1992 Term Paper

The impact of the Federal Reserve on the elections in 1992 - Term Paper Example This led Federal Reserve board to make small reduction on short term interest rates, 1 perhaps with the confidence that such reduction was to be mild and brief. According to an News Times report, FED trimmed Federal Fund rates that banks charge one another for overnight loans from 6% to 5.75%, with the discount rate ,which Fed levies on banks for short term loans remaining constant at 5.25%.1However, the effects of interest rates are usually not realized immediately, and take time to be felt in the market.2 The delayed actions by Fed in lowering interests rates were therefore not realized immediately upon the interest cuts; recession was increasing rapidly, and as people have increasing hope in the policies of an opponent in such cases, Clinton’s economic policy in 1992 election were magnified by Fed delayed actions, with studies portraying the electorate as preferring Clinton to Bush. 3There have been discussions on the effectiveness of this intervention in the market by Fed in 1992, where many analysts have termed the intervention as too late and too little in terms of stimulating the economy; with many analysts arguing the interve ntion resulted to increasing inflationary rates in the economy as long term interest rates remained persistent.3 Despite reduced interest rates to encourage borrowing, fed interference in the economic dynamics resulted to increased inflationary rates, which were evidence after the elections. To deal with growing public spending deficit, the top marginal income tax rate was raised from 31% in 1992 to 39.6% in 1993, which was similar to a 42.55 increase when Medicare tax hikes were included. 4This was proved by the economic growth that was recorded at 4.3% annually in the last quarter of 1992, but dropped to 1.7% annual rate in first quarter of 1993. 4 This reduced growth was a result of long term interest rates that continued to haunt the economy; the high interest rates were shelved in 1992 when they were

Welfare Myths and Realities Essay Example for Free

Welfare Myths and Realities Essay Society has continued to undergo evolution and change throughout the history of civilization. These are the factors that spell out the dividing line between social classes and castes that are redrawn on an almost daily basis by mankind. This is why there will always be a mixture of fact and fiction surrounding the way present day society views those people who were unlucky enough to end up at the bottom of the societal class chain. These are the people who are forced to survive using welfare to keep food on the table, money in their pockets, and clothes on their backs. It is highly unfortunate that the word Welfare has come to mean a person who does not want to work unless he is forced to work. But this is not always what defines a person on welfare. In todays world, the workplace is a highly competitive environment where people no longer have security of tenure in their jobs. People want to work. The problem is, there are not enough jobs to go around. The reality is that when a person loses his job these days, it is highly unlikely that he will be able to get new regular employment anytime in the short-term future. So, he is forced to take what odd jobs he can while trying his luck at landing regular employment. Realistically speaking, temp jobs wont pay the rent nor keep food on the table. In order to stay afloat, the person must take welfare assistance. This is a not a permanent set up for most, it is just financial aid until the person can get back on his feet. Hey, he paid his taxes and his Social Security dues. Therefore, it is only proper that the system helps him get back on his feet. Nobody in his right mind would want to make welfare his way of life. Welfare tends to affect a person both psychologically and emotionally as he struggles to try to go back to the way of life that he has become accustomed to. Even though they try to get off welfare at the soonest possible time, sometimes, he is forced to go back on welfare for one reason or another. The last thing he wants to become is a welfare cyclist but he is left with no other choice. Psychologically, a man unable to support himself is thrown into despair and self-pity. He thinks less of himself and wishes to feel better by being able to support himself without the aid of welfare. The last thing he wants for himself is to get involved in welfare cycling. This is the act of going on welfare for short periods of time during which a person has lost his job. It is totally unfair to say, the federal welfare program encourages people to stay poor. (Margaret L. Andersen Howard F. Taylor, 2003, p. 200) Man is an ambition driven entity. He pursues lofty goals and ambitions in life and does not deem himself a success or a complete individual unless he has something to show for his existence. It can be in the form of finances, or something solid like real estate. Whatever it may be, there is nothing that can drive a man to have a desire to stay poor. The government does not give enough financial support to the welfare organizations for one to believe that those on welfare would be getting enough welfare checks or food coupons to sustain any kind of lifestyle. These benefits are available only to a limited number of families who must pass a stringent interview and verification process. Neither is it true that only Blacks or Hispanic families benefit from welfare. There are also White families who are down on their luck and also move from place to place or even state to state in search of the elusive jobs. The welfare myth about women is proves to be even most unfair. Women are the light that guides a family. While husbands work and bring home what pay then can in the lower middle class society, the women are left at home to tend to the children. Most of them cannot afford child-care and therefore help their husband earn income in order to improve their basic lifestyle. This is why most women collect welfare for their families. If there were proper child-care assistance provided to these families, both parents would have a chance to work instead of having to line up collecting unemployment checks just to make ends meet. Of the 100% of the total federal budget, only 60% of this it spent on assisting poor families. This provides subsidies for the lowest income families basic living and medical assistance. There is absolutely no truth to the belief that certain welfare recipients are paid benefits that they no longer qualify for. Though the system is not foolproof, as some payments errors are done due to human error, there are still safety measures in place to make sure that overpayments are limited and that any fraudulent transactions are weeded out in the process. Going on welfare was never meant to make any man rich. It is not a status symbol that will make you the envy of others either. Often times, the amount of the checks given to the people involved are below the poverty level. It is really meant only to be a stop gap measure for those who have had a stroke of financial bad luck. It was not meant to sustain any person throughout life. The myths that were created by the fear of going on welfare gave the deserving welfare beneficiaries a bad name. It has branded them in such a way that society tends to be judge and jury of the way they conduct their lives and personal businesses. Welfare was meant to be a helping hand when one needs it the most. Welfare was envisioned, developed and meant to help a person get back on his feet after a devastating financial setback. To believe all these myths that have been handed down from generation to generation would be a disservice to such a humane undertaking that is done for and on behalf of your fellowman. Works Cited Andersen, Margaret L. Taylor, Howard R. (2003). Sociology The Essentials (2nd Ed. ) Welfare Myths: Fact or Fiction? Exploring the Truth about Welfare. 1996. December 22, 2006, Retrieved from http://hcom. csumb. edu/welfare/resources/myths_facts. html Irons, Meghan Erica. Dispelling Myths About Welfare. December 21, 2006, Retrieved from http://www. voice. neu. edu/960215/welfare. html

Molecular Genetics of Cancer

Molecular Genetics of Cancer INTRODUCTION It has been established that cancer is a genetic disease, characterized by interplay of mutant form of the oncogenes and tumour suppressor genes leading to the uncontrolled growth and spread of cancer cells. While some of the mutant genes may be inherited, others occur in the somatic cells of the individuals, which can divide and form tumour. Completion of Human Genome Sequencing Project has generated a wealth of new information about the mutations that trigger a cell to become cancerous. It has now been possible to understand to great extent the relationship between genes and cancer, and how mutations, chromosomal changes, viruses and environmental agents play a role in the development of cancer. In this chapter current understanding of the nature and cause of cancer has been presented. CELL CYCLE AND CANCER During mitotic cell division, in every cell, all chromosomes must duplicate faithfully and a copy of the each has to be distributed to progeny cells. Progression through the cell cycle is controlled by the activities of many genes. At different stages in the cell cycle there exist control points (G1, G2, S, and M stages) at which the cell cycle is arrested if there is damage to the genome or cell-cycle machinery. Such mechanism helps to repair the damage or destroy the cell. Through this process it is possible to prevent the possibility of dividing a defective cell and from becoming cancerous. Proteins and enzymes called cyclines and cycline-dependent kinases (Cdks) respectively are the key components that are involved in the regulation of events in the checkpoints. At the G1-to-S checkpoint, two different G1 cycline/Cdks complex forms, resulting in activation of the kinase. The kinase catalyzes a series of phosphorylations (addition of phosphate group) of cell-cycle control proteins, affecting the functions of those proteins and leading to translation into the S phase. Similarly, at the G2-to-M checkpoint, a G2 cycline binds to a Cdk to form a complex. Phosphorylation of the Cdk by another kinase keeps the Cdk inactive. Removal of a phosphate group from Cdk by a phosphataes enzyme activates the Cdk. Thereafter, the cell moves from S to M phase, due to phosphorylation of proteins by Cdk. Regulation of Cell Division in Normal Cells Division of normal cells is regulated by both extracellular and cellular molecules that operate in a complicated signal system. Steroids and hormones made in other tissues are extracellular molecules, which influence the growth and division of some other tissues. These extracellular molecular are known as growth factors, which bind to specific receptors on their target cells. The receptors are proteins that span the plasma membrane, and the growth factor binds to the part of the receptor which lies outside of the cell. The signal is then transmitted to an intracellular part through the membrane-embedded part of the receptor. Thereafter, the signal is relayed through a series of proteins, which ultimately activate nuclear genes involved in stimulation and division of cells through transcription factors (Fig 13.1a). In the opposite direction, inhibition of cell growth and division is regulated by growth-inhibiting factors (Fig 13.1b). The process which involves either growth-stimulator y or growth-inhibitory signal after binding of the extracellular factor to the receptors is called signal transduction, and the proteins involved in such process are called signal transducers. Cell division in normal cells takes place only when there exist balance between stimulatory and inhibitory signals from outside the cells. Any mutation either in the stimulatory or inhibitory genes or genes encoding cell surface receptors involved in cell cycle control may cause imbalance and loss of control of cell division. CANCERS ARE GENETIC DISEASE Clinically, cancer is defined as a large number of complex diseases that behave differently depending on the cell types from which they originate. However, at the molecular level, all cancers exhibit common characteristics, and thus they can be grouped as a family. All cancer cells share two fundamental properties: unregulated cell proliferation, characterized by abnormal growth and division, and metastasis, a process that allow cancer cells to spread and invade other parts of the body. When a cell loses its genetic control over its growth and division, it may give rise to a benign tumour, a multicellular mass. Such tumours may cause no serious harm and can often be removed by surgery. However, if cells of the tumour also acquire the ability to break loose, enter the blood stream, invade other cells, they may induce formation of secondary tumours elsewhere in the body. Such tumours are called malignant, which are difficult to treat and may become life threatening. A benign tumour may become malignant through multiple steps and genetic mutations. Mutations in three kinds of genes can leads to cancer. These are proto-oncogenes, tumour suppressor genes and mutator genes. Mutant proto-oncogenes are called oncogenes, are usually more active than normal cells. The product of oncogenes stimulates cell proliferation. The normal tumour suppressor genes inhibit cell proliferation, while the mutants found in tumour cells have lost their inhibitory function. The normal mutator genes are required to ensure fidelity of replication and maintenance of genome integrity, while mutant mutator genes in cancer cells make the cells prone to accumulate mutational errors. RETROVIRUS AND ONCOGENES Most cancer causing animal viruses are RNA viruses known as retroviruses, and the oncogenes carried by RNA tumour viruses are altered forms of normal animal host cell genes. Infection with retroviruses can transform normal host cells to the neoplastic state, and such cells proliferate in an uncontrolled manner to produce tumour. Examples of retroviruses include human immunodeficiency virus (HIV-1), mouse mammary tumour virus, felin leukemia virus, and Rous sarcoma virus. A typical retrovirus particle has a protein core, which often is icosahedral in shape, with two copies of plus-sense (means directly translatable) single stranded RNA molecule (7kb and 10 kb). The core is surrounded by an envelope with virus-encoded glycoproteins inserted into it (Fig 13.2). The virus enters the host cell by interacting with the host cell surface receptor through its glycoproteins present in the envelope. To understand how retroviruses cause cancer in animals, it is essential to know their life cycle. Rous sarcoma virus (RSV) is one of the earliest retrovirus studied on induction of cancer. When a retrovirus like RSV infect a cell, the RNA genome is released from the viral particle, and a double stranded DNA copy of the genome is made by reverse transcriptase (Fig 13.3). This is known as proviral DNA. The proviral DNA then enters the nucleus of the infected cell, and integrates into the host chromosome at random locations. The integrated DNA copy is called provirus. At the left end of all retroviral RNA genomes consists of the sequence R and U5, and U3 and R at the right end. Powerful enhancer and promoter elements are located in the U5 and U3 sequences (Fig 13.3). During proviral DNA synthesis by reverse transcriptase, the end sequences are duplicated to produce long terminal repeats of U3-R-U5 (LTRs in Fig 13.3), which contain many of the transcription regulatory signals for the vir al sequence. The two ends of the proviral DNA are ligated to produce a circle, a double stranded molecule in which the two LTRs are next to each other. Staggered nicks are made in both viral and cellular DNAs, and integration of the viral DNA begins. The viral DNA ends joined through recombination. Integration occurs at this point, and single stranded gaps are ligated. The integration of retrovirus proviral DNA results in a duplication of DNA at the target site, producing short, direct repeats in the host cell DNA flanking the provirus. The proviral DNA is transcribed by host RNA polymerase II, after integration into the host DNA. The retroviruses have three protein- coding genes for the virus life cycle: gag, pol, and env (Fig 13.3). The gag gene encodes a precursor protein that is cleaved to produce virus particle protein. The pol gene encodes a precursor protein which produces an enzyme called reverse transcriptase, required for the integration of the proviral DNA into the host chromosome. The env gene encodes the precursor to the envelop glycoprotein. The progeny virus particles are produced when transcription products of the entire integrated viral DNA are packed into new viral particles. The new virus particles are released and can infect new host cells. A retrovirus may induce cancer in the host cells through two different ways. First, the proviral DNA may integrate by chance near one of the cell’s normal proto-oncogenes. The strong enhancers and promoters in the provirus then stimulate transcription of proto-oncogenes present in the host cell at high levels or at inappropriate timing. This leads to stimulation of host-cell proliferation. Second, a retrovirus may pick-up a copy of a host proto-oncogene and integrates it into its genome (Fig 13.4). The integrated oncogene may mutate during the process of transfer into the virus, or it may be expressed at abnormal levels, due to action of the viral promoters. Retroviruses that carry these viral oncogenes can infect and transform normal cells into tumour cells. Different oncogenic retroviruses carry different oncogenes. Most oncogenic retroviruses cannot replicate as they do not have a full set of life-cycle genes. Thus they cannot change growth properties of the host cells. They are called nononcogenic retroviruses. HIV-1 is a nononcogenic retrovirus. On the contrary, RSV is an oncogenic retrovirus as it can replicate its oncogenes and can affect the growth and division of the infected host cells. Viral oncogenes, genetically called v-oncs are responsible for many different cancers. The v-oncs of RSV is called v-src. Unlike RNA tumour viruses, DNA tumour viruses do not carry oncogenes. Their mechanism for transforming cells is completely different. They transform normal cells to cancerous state through the action of genes present in the viral chromosome. DNA tumour viruses are found in five major families of DNA viruses which include: papovaviruses, pox viruses, hepatitis B viruses, herpes viruses and adenoviruses. After infection, the DNA tumour viruses produce a viral protein that activates DNA replication in the host cell. Then, utilizing host proteins, the viral genome is replicated and transformed. After producing large number of progeny viruses, they lyses the host cell and the viruses thus released can infect other cell. Rarely, the viral genome instead of replicating gets integrated into the host genome. Thereafter if the viral protein that activates DNA replication of the host cell is synthesized, this will lead to division and proliferation of the host cell converting normal cell to cancerous state. Basically, the cells move from G0 phase to the S phase of the cell cycle. The DNA viruses which induces cancers are papillomaviruses (HPV 16 and 18), human T-cell leukemia virus (HTLV-1), hepatitis B virus, human herpesvirus 8, and epstein-barr virus. Some of these viruses cause benign tumours such as skin and venereal warts in humans. Transformation is caused by the key viral genes, E6 and E7, which encode proteins that activate progression through the cell cycle. However, in most of the cases, virus infection alone is not sufficient to trigger human cancers. Other factors like DNA damage, accumulation of mutants in cell’s oncogenes and tumour suppressor genes, are required to induce cancer in multiple pathways. Some transducing retroviruses, their viral oncogenes, viral protein and type of cancer induced is presented in Table 13.1. CANCER AND GENOME STABILITY Cancer cells are characterized by the presence of chromosomal translocations, deletions, aneuploidy, and DNA amplification. Cultured cancer cells also show similar genomic instabilities. Study of the specific chromosomal defects can be used to diagnose the type and stage of the cancer. For example, chronic myelogenous leukemia (CML) gene C-ABL from chromosome 9 is translocated to the chromosome 22 in the region of gene BCR. The fused ABL-BCR gene encodes for a chimeric ABL-BCR protein, which produces an abnormal signal transduction molecule that stimulates the CML cells to proliferate. The normal ABL protein (protein kinase) acts within signal transduction pathway, transferring growth factor signals from the external environment to the nucleus, thereby control cell division. Defect in the DNA repair genes can also induce cancer. For example, Xenoderma pigmentosum (XP), a disease in which the skin becomes extremely sensitive to UV light and other carcinogens. Patients with XP often develop skin cancer. Cells of XP are defective in nucleotide excision repair, with mutations appearing in any one of the seven genes whose products are required to carry out DNA repair. Hereditary nonpolyposis colorectal cancer (HNPCC) is also caused by mutations in genes controlling DNA repair. Patients affected by HNPCC have an increased risk of developing colon, ovary, uterine, and kidney cancers. At least eight genes are associated with HNPCC, and four of these genes (MSH2, MHS6, MLH1, and MLH3) control DNA mismatch repair. Mutations in any one of these genes can lead to development of cancer. EPIGENETICS AND CANCER Epigenetics includes those factors that affect heritable gene expression but do not alter the nucleotide sequence of DNA. Examples of epigenic modifications are DNA methylation, acetylation and phosphorylation of histones etc. Modifications caused through these processes can be inherited and affect gene expression. X-chromosome inactivation, heterochromatin gene expression are such examples. Cancer cells contain major alterations in DNA methylation. In general, there is much less DNA methylation in cancer cells compared to normal cells. On the other hand promoters of some genes are highly methylated in cancer cells. Apparently these changes lead to the release of transcription repression over the bulk of genes that would otherwise remain silent, while at the same time repressing transcription of genes that would normally regulate functions such as DNA repair, cell cycle, and cellular differentiation. The genes MLH1 and BRCA1, involved in DNA repair mechanism, are transcriptionally si lenced by hypermethylation in many cancer cells. Methylation profiles can be used to diagnose types of tumours and their possible course of development. It has also been observed that histones are also modified in the cancer cells. These modifications are due to mutations in the genes that encode histone acetylases, deacetylases, methyltransferases, and demethylases. Since the epigenetic modifications are reversible, epigenetic- based therapies may be useful for cancer treatments. APOPTOSIS AND CANCER If a normal cell encounters defective processing in DNA replication, DNA repair or chromosome assembly, they do not allowed to continue through the cell cycle, till the conditions are corrected and thereby reduces the chances of accumulation of defective cells. In case the damage of the DNA is irreparable, the cell may go through a second line of defence called programmed cell death or apoptosis. Apoptosis is controlled genetically, and is an inherent process to eliminate certain cells that are not required for by the final adult organism. In this process, the nuclear DNA becomes fragmented, internal cellular structures are disrupted, and cell dissolves into small spherical (apoptotic) bodies. Thereafter, these bodies are engulfed by the phagocytic cells of the immune system. The products of the genes Bcl2 and BAC can trigger or prevent apoptosis. In the cancer cells these genes are mutated, and as a result normal checkpoints in the cell cycle are inactivated. Such cells remain defec tive and cannot undergo apoptosis. TUMOUR SUPRESSOR GENES Henry Harris in late 1960’s observed that some cell lines, derived from the somatic hybrid of normal rodent cells and cancer cells, did not form tumours, instead established a normal growth pattern. He speculated that products of some genes present in the normal cells had the ability to suppress the uncontrolled proliferation of cancer cells. These genes are called tumour suppressor genes. Inactivation of tumour suppressor genes has been linked to the development of a wide variety of human cancer, including colon, lung and breast cancers. With the development of positional cloning technique, it has become possible to isolate tumour suppressor genes. In this technique, variations in the genetic characters present in the cancer cells and/or in cells of patients with inherited cancer predisposition are identified. Existence of variations indicate occurrence of mutations and help to study such mutations through cloning. Through this technique several tumour suppressor genes are identified in humans (Table 13.2). The p53 Tumour-Suppressor Gene In human cancer cells p53 is the most frequently mutated gene. The nuclear protein encodes by the gene p53 acts as a transcription factor. It can stimulate transcription or repress more than 50 different genes. Although the p53 protein is continuously synthesized, it is rapidly degraded and thus is present in low levels. When p53 protein binds to another protein called Mdm2, it induces degradation and sequesters the transcriptional activation domain of p53. It also prevents conversion of inactive p53 protein to active form. In case Mdm2 protein gets dissociated from p53 protein then rapid increase in the activated p53 protein takes place at nuclear level. Such dissociation is induced due to creation of dsDNA breaks, chemical damage in DNA and presence of DNA-repair intermediates. Increase in the level of p53 protein leads to increased protein phosphorylation, acetylation, and other post translational modifications. The products of p53 gene control the movement of the normal cells through different phases of the cell cycle. Activated p53 proteins can: i) stimulate transcription of p21 protein (which arrests progression from G1-S checkpoint of mitotic cycle), ii) regulate gene expression that retard replication of DNA (this helps in repair of the damaged DNA before replication), and iii) block damaged cells (DNA damage occurred during S phase) from progression from G2 to M checkpoint by regulating expression of other genes.