Tumours various

Tumours induced by chemical carcinogens/irradiation Each tumour usually displays distinct antigen specificity Virally induced tumours Various tumour types display identical tumour-... 

CYP1B1 (chromosome 5) has been linked to primary congenital glaucoma. CYP1B1 is not regularly expressed in liver but is often found in various kinds of tumours. It metabolizes retinoids and many aromatic amines and PAHs to potentially carcinogenic products. 

Concentrations of PCBs in fish from each of the Great Lakes currently exceed the GLWQA objectives for the protection of aquatic life. Similarly, concentrations of some substances (e.g., PCBs, Hg, mirex, toxaphene) in Great Lakes fish continue to exceed acceptable guidelines for human consumption. Documented effects in the Great Lakes include reproductive failure, congenital abnormalities and induction of tumours in various aquatic, terrestrial and avian species (23). 

Additional products Tumour necrosis factor (TNF), therapeutic enzymes 18 Various chapters... 

Interferons induce a wide range of biological effects. Generally, type I interferons induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

Various malignancies can also induce an anaemic state. This is often associated with decreased serum EPO levels, although iron deficiency, blood loss or tumour infiltration of the bone marrow can be complicating factors. In addition, chemotherapeutic agents administered to this patient group often adversely affect stem cell populations, thus rendering the anaemia even more severe. 

The enzyme urate oxidase has also found medical application for the treatment of acute hype-ruricaemia (elevated plasma uric acid levels), associated with various tumours, particularly during their treatment with chemotherapy. 

NK cells, which, like some T-cells, can induce lysis of tumour cells. The tumouricidal activity of NK cells is potentiated by various cytokines (e.g. IL-2 and TNF). 

AFP is a 70 kDa glycoprotein found in the circulatory system of the developing foetus. It is synthesized primarily by the yolk sac and (foetal) liver. AFP is present only in vanishing low quantities in the serum of adults (where it is replaced by serum albumin). Elevated adult serum levels of this marker are often associated with various cancers of the liver, as well as germ cell tumours. It is also sometimes expressed by gastric and pancreatic cancer cells. Although a useful tumour marker, increased serum AFP levels also often accompany cirrhosis and some other non-cancerous liver diseases. 

Although several of the strategies listed in Table 14.5 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. 

Intratumoural injection is believed to facilitate vector uptake and expression of p53 in the adjacent tumour cell, leading to cell cycle arrest and apoptosis. Company data showed complete regression of tumours in 64 per cent of patients treated with Gendicine in combination with radiation therapy, with few associated side effects. By 2006 the product was believed to have been administered to some 50 000 patients in China, and is in late-stage clinical trials for various other cancers. 

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). 

An interesting study of the relative rates of reduction of N,N-bis(2-chloroethyl)-aminoazobenzene and various monosubstituted derivatives (3.27) was initiated because of the ability of such dyes to inhibit the growth of animal tumours [23], even though some... 

In addition to directly eliciting cell chemotaxis and free-radical production, PAF can also induce the release of various inflammatory cytokines, amongst which tumour necrosis factor (TNF) is of particular importance [ 312 ]. We have recently shown that PAF stimulates TNF production from peripheral blood derived monocytes and at picomolar concentrations amplifies lipopoly-saccharide (LPS)-induced TNF production, effects inhibited by various PAF antagonists [313]. PAF also acts synergistically with interferon-y (IFN-y) to increase the monocyte cytotoxicity. Furthermore, PAF can modulate the production of both interleukin 1 and interleukin 2 (IL-1, IL-2) from rat monocytes and lymphocytes, respectively [222, 223], cytokines which in turn elicit the release of other mediators and growth factors. 

Figure 21.7 Control of the activity of Ras by a balance of the activities of guanine nucleotide exchange factor and GTPase. GAP is the abbreviation for GTPase-activating factor and GEF for guanine nucleotide exchange factor. Both are enzymes. Both the activities are controlled by stimuli from various cell surface receptors. Ras oncogenes are present in about 30% of all human tumours.

It has been hypothesized that folate receptor-mediated endocytosis can be exploited for the selective delivery of drugs by covalent attachment to folate via its y-carboxyl group. This concept was primarily designed for the targeting of various biomolecules to solid tumours. For a... 

The success of treating tumours, especially solid tumours, by systemic therapy depends on various characteristics of the tumour. Besides the importance of intrinsic drug activity and the potential targets within the tumour cells, drug pharmacokinetics and whole body distribution, site of delivery and the ability of site-specific targeting (affinity) are important features. 

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