Volume 2, issue 3
The most human protein pharmaceuticals are available in only limited quantities. They are costly to produce and in a number of cases, their biological mode of action is not well-characterized. Many infectious and fatal diseases such as AIDS, Cancer etc are very difficult to be treated by those pharmaceuticals. By recombinant DNA technology, these fatal and infectious diseases can be cured satisfactory.
Cancer:-
Normal development is the consequence of a highly regulated cellular proliferation coupled with programmed cell death (apoptosis). The cancer cells are altered self-cells that do not heed to normal growth regulating mechanisms; as a result, they continue to divide and produce a tumor or neoplasm. A tumour may be benign (i.e. incapable of indefinite growth and invasion of healthy surrounding tissues) or malignant (i.e. have the abilities to grow indefinitely and invade surrounding healthy tissues). The term cancer refers specially to malignant tumours. Cancers invade healthy tissues by a process called metastasis, in which small clusters of cancerous cells dislodge from a primary tumour, invade the blood or lymphatic vessels, and are carried to other tissues where they continue to proliferate and give rise to secondary tumour Origin of Cancer:-
Cancer is induced by a variety of agents, such as, chemical carcinogens, irradiation and certain viruses. A number of DNA and RNA viruses induce cancer. The RNA viruses that induce cancer are called transforming viruses, they are retroviruses, some of which carry oncogens or cancer genes. The oncogenes present in retroviruses are denoted as V-onc (Viral oncogenes). These V-onc genes have homologues are called cellular oncogenes (C-Onc) or protooncogenes.
p53 tumor suppressor protein:-
The p53 tumor suppressor protein, encoded by the TP53 gene, lies at the center of an elaborated circuit controlling cell proliferation and interconnecting with many cellular functions. In response to various forms of stress, p53 is activated and accumulates in the nucleus, where it regulates the transcription of numerous target genes using specific DNA response elements. From the p53 activation, several biological responses occur including apoptosis, cell cycle arrest, DNA repair, differentiation or senescence. The nature of the p53-induced response depends on the type of stress and cell/tissue in which it occurs. Beyond its nuclear role, p53 regulates some mitochondrial functions. Thus, p53 is the archetype of a truly multifunctional protein, in which a small number of structural domains is specifically involved in vast arrays of complex interactions with various species (DNA, RNA, proteins and cell metabolites).
The TP53 gene is often mutated in cancer with a high proportion of missense mutations, leading to the production of a protein expressed at high levels that differs from wild-type p53 by just one amino acid residue. This feature is a characteristic of p53, as many ‘classical’ suppressor genes, such as APC or BRCA1, are mainly altered through nonsense or frameshift mutations leading to the expression of inactive truncated proteinse. Today, a large body of knowledge has accumulated on mutant p53 GOF, which appears as a major contender in human cancer.
Mutant p53 have yielded remarkable progress in understanding their specific functions. It is now clear that GOF mutant p53 is not a single and generic property. In a manner reminiscent of wild-type p53, mutant p53 is a multifunctional factor, of which the effects may differ according to the cancer cells in which the mutation occurs. Two main avenues for further research may be identified. First, accumulation of mutant p53 at higher levels than those normally found in healthy cells, may allow mutant proteins to interact with a larger panel of DNA and proteins than wild-type p53. Second, it should be considered that mutant p53 may exert particular effects depending on its structure and its affinity for defined DNA or protein targets. The respective importance of this dosage effect and these specific structural effects induced by the mutation should be further investigated, but a combination of these two properties may account for the wide diversity of mutant p53 effects.
It is becoming clear that all cancers have a defective p53 pathway, either by TP53 mutation or by deregulation of another determinant of the p53 pathway. Despite this increased complexity, the field of mutant p53 research is now swiftly moving towards translation in the clinics.
Cancer Therapy:-
Following measures should be taken in cancer treatment.
(1) Use of tumour cells transformed with B7 gene to induce T cell activation
(2) Enhancement of antigen processing cell activity, it can be achieved in several ways. e.g. dendritic cells may be proliferated in vitro, exposed to the tumour antigen fragments, and reintroduced into the patient.
(3) Use of TNF-α and TNF-β that exhibit direct antitumour activities.
(4) Monoclonal antibodies have been targeted to a number of tumour-associated antigens. A “humanized” hybrid monoclonal antibody targeting against HER 2, an EGF- like receptor, has been approved for the treatment of HER 2-receptor-bearing breast cancers; this antibody is called Herceptin.
(5) Immunotoxins specific for tumour antigens in a variety of cancers e.g. melanomas leukaemias, lymphomas etc have been evaluated in phase Ι and phase ΙΙ clinical trials with variable success.
(6) Several tumour-specific antigens have been identified. e.g. tyrosinase in melanomas, MAG-1 in several types of cancers, CEA in Colon cancer, HER2 in breast and ovarian cancers etc.
It is hoped that viral and bacterial vaccine vectors carrying the tumour antigens gene would be
expressed in appropriate cellular compartments leading to regression of the tumours.
By:
Sabir Hussain Shah (Ph.D. Plant Genomics & Biotechnology)
E-mail: sabir_shah81@yahoo.com
Contact number: - 03327245844
Address: - Room No.11, NARC Hostel-I, Park Road, Chak Shahzad, Islamabadhttp://www.technologytimes.pk/mag/2011/jan11/issue03/role_of_recombinant_dna_technology.php
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