Malignancy proteins

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

In apoptotic cell death, several factors such as growth factors, NO, the tumor suppressor gene p53, and the protein encoded by this gene contribute to the process that leads to cell death. One of the functions of p53 protein is the activation of apoptosis if a cell is transformed to a malignant cell. Apoptosis typically leads to the formation of smaller membrane-encapsulated particles within the cell. Apoptotic cell death begins in the nucleus and proceeds to other parts of the cell. The death process may be quite advanced before it can... 

Nucleic acids in the DNA contain a high number of nucleophilic sites that can be attacked by electrophilic intermediates (metabolites) of chemical compounds. DNA adducts formed may cause alterations in the expression of a critical gene in the cell and thus lead to cell death. For example, modification of p53 tumor suppressor gene may inactivate the functions of the p53 protein and render cells sensitive to malignant transformation. Also, formation of RNA adducts may inhibit key cellular events because RNA is essential for protein synthesis. 

Interferon alfacon-1 (Inferax ), interferon alfa-2b (IntronA ), and interferon alfa-2a (Roferon -A) are applied in the treatment of chronic hepatitis B and C and some malignancies, especially hairy cell leukemia. IFN-a proteins induce the expression of antiviral, antiproliferative and immunomodulatory genes. 

Figure 49-10. Simplified scheme of the causation of malignant hyperthermia (MIM 145600). At least 17 different point mutations have been detected in the RYRl gene, some of which are associated with central core disease (MIM 117000). It is estimated that at least 50% of families with members who have malignant hyperthermia are linked to the RYRl gene. Some individuals with mutations in the gene encoding DHPR have also been detected it is possible that mutations in other genes for proteins involved in certain aspects of muscle metabolism will also be found.

Scriver CR et al (editors) The Metabolic and Molecular Bases of Inherited Disease, 8th ed. McGraw-Hill, 2001. (This comprehensive four-volume text contains coverage of malignant hyperthermia [Chapter 9], channelopathies [Chapter 204], hypertrophic cardiomyopathy [Chapter 213]> the muscular dystrophies [Chapter 216], and disorders of intermediate filaments and their associated proteins [Chapter 221].)... 

Ping YF, Yao XH, Chen JH, Liu H, Chen DL, Zhou XD, Wang JM, Bian XW (2007) The anticancer compound Nordy inhibits CXCR4-mediated production of IL-8 and VEGF by malignant human glioma cells. J Neurooncol 84 21-29 Pitcher JA, Freedman NJ, Lefkowitz RJ (1998) G protein-coupled receptor kinases. Annu Rev Biochem 67 653-692... 

Multiple myeloma is a malignancy of plasma cells that is characterized by an abnormal production of a monoclonal protein. Features of the disease include bone lesions, anemia, and... 

FIGURE 96-4. Pathophysiology of the hypercalcemia of malignancy. PTHrP, parathyroid hormone-related protein TGF-P, transforming growth factor P TNF-a, tumor necrosis factor alpha Ca2+, calcium IL-1, interleukin 1 IL-2, interleukin 2. 

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