Human diseases Cancer

JUNGBLUT, P.R., ZIMMY-ARNDT, U, ZEINDL-EBERHART, E STULIK, J., KOUPILOVA, K., PLEISSNER, K.P., OTTO, A., MULLER, E.C., SOKOLOWSKA-KOHLER, W., GRABHER, G., STOFFLER, G., Proteomics in human disease Cancer, heart and infectious disease, Electrophoresis, 1999, 20, 2100-2110. 

Jungblut, P. R., Zimny-Arndt, LF., Zelndl-Eberhart, E., Stuhk, J., Koupllova, K., Pleissner, K. P., Otto, A., Muller, E. C., Sokolowska-Kohler, W., Grabber, G., and Stoffler, G. (1999). Proteomics in human disease. Cancer, heart, and infectious diseases. Electrophoresis 20, 2100—2110. 

Qiu TH, Chandramouli GV, Hunter KW, Alkharouf NW, Green JE, Liu ET. Global expression profiUng identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice correlation to human disease. Cancer Res 2004 64 5973-5981. 

Jungblut PR, Zimny-Arndt U, Zeindl-Eberhart E, Stulik J, Koupilova K, Pleissner KP, Otto A, Muller EC, Sokolowska-Kohler W, Grabber G, Stoffler G. 1999. Proteomics in human disease Cancer, heart and infectious diseases. Electrophoresis 20 2100-2110. 

Pour, P.M., Runge, R.G., Birt, D., Gingell, R., Lawson, T., Nagel, D., Wall care, L., and Salmasi, S.S., 1981, Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to human disease. Cancer, 47 1573-1587. 

Unfortunately, excess consumption of fatty foods has been correlated with serious human disease conditions. Effects on cardiovascular disease (95), cancer (96), and function of the immune system (97) have been shown. Numerous studies have been conducted to determine the effects of saturated, monounsaturated, and polyunsaturated fatty acids on semm cholesterol and more recently high density Hpoprotein (HDL) and low density Hpoprotein... 

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

A large and rapidly growing number of clinical trials (phase I and phase II) evaluating the potential of DNA vaccines to treat and prevent a variety of human diseases are currently being performed ( http // clinicaltrials.gov) however, there is yet no licensed DNA vaccine product available for use in humans. The clinical trials include the treatment of various types of cancers (e.g., melanoma, breast, renal, lymphoma, prostate, and pancreas) and also the prevention and therapy of infectious diseases (e.g., HIV/ABDS, malaria, Hepatitis B vims, Influenza vims, and Dengue vims). So far, no principally adverse effects have been reported from these trials. The main challenge for the development of DNA vaccines for use in humans is to improve the rather weak potency. DNA vaccines are already commercially available for veterinary medicine for prevention of West Nile Vims infections in horses and Infectious Hematopoetic Necrosis Vims in Salmon. 

All three of these chnical syndromes are associated with an increased frequency of cancer. It is hkely that other human diseases resulting from disordered DNA repair capabihties will be found in the fiimre. 

There is now considerable evidence suggesting a role for free radicals in the pathogenesis of inflammatory diseases and in the development of cancer. However, the effect of benefit from specific antioxidants in human disease remains to be established. Until this is done, the question of whether free radicals are yet just another inflammatory mediator, or whether their role is more central to the understanding of disease, remains open. 

Cancer is one of the diseases in which a role has been implicated (see Table 13.1) for free radicals. Comprehensive accounts of the involvement of reactive oxygen species in human diseases may be found in Halliwell and Gutteridge (1989), Aruoma (1993) and in Cheeseman and Slater (1993). 

As stated at the beginning of this article, the liver is the most intensively studied animal tissue in biochemistry. In the context of the role of free radicals in human diseases, the liver is not obviously at centre stage, since heart disease and cancer are more important in the industrialized world than, for example, cirrhosis. Free-radical biochemistry of the liver will remain a fertile area of work, however, not least because so many original ideas and techniques are developed there and then applied to the study of other tissues. The increasing use of liver transplantation, following the acceptance of kidney and heart transplants as almost routine, will surely increase the interest in the study of ischaemia-reperfusion injury in... 

Defects have been found in these mechanisms that cause various human diseases. For example, patients with the genetic disease xeroderma pigmentosum are especially sensitive to ultraviolet light and develop skin cancer. Skin fibroblasts cultured from these patients have been shown to be defective in DNA repair. 

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

Belley, A., Keller, K., Grove, J. and Chadee, K. (1996) Interaction of LS174T human colon cancer cell mucins with Entamoeba histolytica an in vitro model for colonic disease. Gastroenterology 111, 1484—1492. 

Growing evidence suggests that PMTs play critical roles in the development of various human diseases including cancer [24,30], inflammation [31], and drug addiction [32]. For example ... 

Pharmaceuticals represent a major class of treatments for a broad array of human diseases. These chemicals are isolated from nature or, more often, synthesized chemically. They are administered to patients to kill or arrest the growth of cancer cells or infectious microbes, to stimulate faltering hearts, and to achieve a host of other specific clinical aims. It is widely recognized that not all people respond alike to these therapies, even when the diagnosis is quite specific. 

The use of BRMs to treat human disease has its origins in the use of bacterial toxins to treat cancer by William B. Coley.73 These early studies resulted in the use of microbi-ally-derived substances such as BCG, Picibanil, carbohydrates from plants or fungi such as Krestin and Lentinan, other products such as Biostim and Broncho-Vaxom, as well as thymic extracts (Table 9.4). However, the lot-to-lot variation in the manufacture of these drugs has dampened enthusiasm. Equally, the focus on MOAs in drug development strategies has also dampened developmental efforts. The particulate nature of some BRMs can also result in pulmonary thrombosis and respiratory distress following i.v. injection. However, BRMs are commonly used to treat bladder cancer and derivatives of natural products are routinely used clinically. 

Talmadge, J.E. et al., Systematic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease, Cancer Res, 47, 5725, 1987. 

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