Genes tumour cell

At present, the use of microarrays in pharmacology is especially established in the field of oncology by gene expression analysis with either tumour cell... 

Except for its narrow specificity, the ATRI gene product shares a number of properties with the higher eukaryotic MDR proteins responsible for multidrug resistance in tumour cells. The MDR gene products are also transmembrane proteins which seem to function as ATP-dependent drug-efflux pumps pumping out a variety of structurally unrelated compounds (see [25,26]). 

Nasmyth The work by Gareth Williams and Ron Laskey with the MCM proteins in cervical cancer is an example of a cell cycle gene that is presumably part of some huge battery of genes that is somehow related to whether the cell is in a proliferative state. It turns out to be rather a good marker for tumour cells. But it is nothing directly to do with proliferation itself. 

Modifying lymphocytes in order to enhance their anti-tumour activity Modifying tumour cells to enhance their immunogenicity Inserting tumour suppressor genes into tumour cells... 

An alternative anti-cancer strategy entails insertion of a copy of a tumour suppresser gene into cancer cells. For example, a dehciency in one such gene product, p53, has been directly implicated in the development of various human cancers. It has been shown in vitro that insertion of a p53 gene in some p53-dehcient tumour cell lines induces the death of such cells. A potential weakness of such an approach, however, is that 100 per cent of the transformed cells would have to be successfully treated to fully cure the cancer. Tumour suppressor-based gene therapy in combination with conventional approaches (chemotherapy or radiotherapy) may, therefore, prove most efficacious, and the sole gene-therapy-based medicine approved to date (in China only) is based upon this approach (Box 14.2). 

Yet another strategy that may prove useful is the introduction into tumour cells of a sensitivity gene. This concept dictates that the gene product should harbour the ability to convert a non-toxic pro-drug into a toxic substance within the cells - thus leading to their selective destruction. The model system most used to appraise such an approach entails the use of the thymidine kinase gene of the herpes simplex virus (Figure 14.12). 

Understanding cancer involves not only knowledge of the genetic changes that cause a normal cell to develop into a tumour cell but also the response of the whole body to a tumour, factors that increase or decrease the risk of development of a tumour and the current therapies that arrest growth of, or kill, tumour cells. These topics are discussed in this chapter, but some basic information is required first the cell cycle, the growth of a tissue, the fuels used by tumour cells and, finally, the role of genes. 

An increase in the nnmber of receptors in the membrane of the tumour cells (i.e. over-expression of the gene) allows the receptors to respond to low concentrations of growth factor. (See chapter 12 for discnssion of hormone receptors and response to hormones.)... 

Figure 21.19 Development of a secondary carcinoma from a normal epithelium by effects of activated genes, i.e. oncogenes, and inactive tumour suppressor genes. It is somatic mutations in four or five genes in a given cell plus hypomethylation changes in histones and chromatin stracture that are involved. It is the accumulation of these genetic alterations, not the sequence, that determines the progression to a tumour cell.

In many chronic inflammatory diseases, angiogenesis can be identified in the inflamed lesions. For example, in rheumatoid arthritis extensive neovascularization is present in the inflamed synovium where it is one of the earliest histopathological findings [36]. Since in RA synoviocytes exhibit characteristics of tumour cells, including somatic mutations in key regulatory genes such as H-ras and the p53 tumour suppressor, RA can be viewed as a multicentric tumour-like mass that invades and destroys its local environment [37]. Concurrent increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. 

Table 11.6. Some specific cancer types for which human gene therapy triafs have been initiated. Although several of the strategies listed in Table 11.5 are being employed in these trials, many focus upon the introduction of various cytokines into the tumour cells themselves in order to attract and enhance a tumour-specific immune response...

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