Currently Available Therapeutics

The traditional principle of tumour histogenesis is that neoplasms characterized by a certain phenotype arise from normal cells of similar phenotype. Considerable evidence has accumulated in recent years which indicates that this histogenetic assumption is incorrect. Most, if not all, neoplasms arise from immature cells, which in the course of neoplastic transformation acquire phenotypic features equivalent to those of one or more normal ceU types. Often this differentiation develops along lines analogous to those expected under normal conditions for that particular cell. 

The characterization and genesis of neoplasms on the basis of morphological (shape-related) features is needed for the evaluation of the common traits and differences among the many types of neoplasms that can affect the human body. Such identification and classification confirms that many different cell types can be involved in cancer. 

The number of grades varies from system to system, but in general the three-grade system (well differentiated, moderately differentiated, and poorly differentiated, or undifferentiated or grades I, II and III, respectively) has proved to be the most reproducible and the best suited to prediction of survival. 

For more detailed information about cancer pathology readers are referred to De Vita et al. [7]. 

Non-surgical methods of cancer treatment, primarily radiation therapy and chemotherapy, rely almost exclusively on procedures that kill cells. The main problem with these treatments is that they do not provide specificity for cancer cells. In the case of radiation therapy, a degree of specificity is achieved by localizing the radiation to the tumour and its immediate surrounding normal tissue. For anti-cancer drugs, it is primarily the rapid proliferation of many of the cancer cells that makes them more sensitive to cell killing than their normal counterparts. However, both modalities are limited by their cytotoxic effects on normal cells. In the case of radiotherapy, normal tissue surrounding the tumour limits the radiation dose, where- 

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List the currently available therapeutic antagonists of leukotrienes and prostaglandins and their targets (receptors or enzymes). 

Currently available therapeutic options include no treatment, conservative treatment, palliative or definitive endovascular treatment, surgery, a combination of endovascular treatment and surgery, and radiosurgery. As detailed in Sections 4.2.2 and 4.2.3, the natural history of DAVM may vary from spontaneous cure (Magidson and Weinberg 1976 Bitoh and Sakaki 1979 Endo et al. 1979 Luciani et al. 2001) (Fig. 4.18) to fatal hemorrhage (Awad et al. 

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

It follows that drugs that selectively inhibit COX-2 should cause fewer side effects than those that inhibit both COX-1 and COX-2. At therapeutic doses, all currently available NSAIDs, with the excqrtion of celecoxib, etoricoxib, lumiracoxib and parecoxib (the prodrug of valdecoxib), are non-selective and inhibit both COX isoforms. 

From these studies it is clear that the progression of PAR-based therapy relies upon the future development of new specific agonists and antagonists for PARs 2-4 with much higher potencies than those currently available, with an efficient mode of delivery to target sites. However despite these problems the PARs still rqiresent one of the most attractive therapeutic targets for a number of disease states. 

Much has been discovered recently regarding the molecular mechanisms and pathways involved in sleep and its associated disorders. It is hoped that this knowledge will lead to improved therapeutics lacking the side effects of currently available drugs. 

The relevance of experimental pharmacology to currently available sleep-wake therapeutics... 

Persons expressing 5 per cent or above of the normal complex levels experience less severe clinical symptoms. Treatment normally entails administration of factor VIII complex purified from donated blood. More recently, recombinant forms of the product have also become available. Therapeutic regimens can require product administration on a weekly basis, for life. About 1 in 10 000 males are born with a defect in the factor VIII complex and there are approximately 25 000 haemophiliacs currently resident in the USA. 

Determining the genes that promote survival, especially those under CBP s control, could facilitate the development of novel drugs and specific therapeutic strategies with lower adverse side effects than those currently available. 

Selective COX-2 inhibitors are currently being investigated in cancer patients in phase I and early phase II clinical trials. The currently available data would suggest that specific inhibitors of COX-2 have the potential to increase the therapeutic ratio of radiotherapy in tumors that express COX-2, and that clinical investigation of this interaction is warranted. 

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