Cancer normalization

Progression arrays These types of arrays are used to analyze the role of protein(s) in cancer progression and consist of normal tissues from patients without cancer, normal tissue from patients with cancer, pre-invasive lesions and tumor (from local and metastatic sites). The addition of normal tissue from close to the tumor and those much further away from the tumor site might enable study of field effect . 

In further studies rats were treated with doses of THC up to 50 mg/kg and mice with up to 500 mg/kg 5 times a week for 2 years in a standard carcinogenicity test (11). After 2 years, more treated animals had survived than controls, probably because the treated animals ate less and had lower body weights. The treated animals also had a significantly lower incidence of the various cancers normally seen in aged rodents in testes, pancreas,... 

In 1969, Henry Harris, George Klein, and colleagues, reported that cancerous cells, which could produce tumours in animals, lost their tumorigenicity when they were fused with non-cancerous normal cells. The loss of tumorigenicity was then perpetuated from one generation to the next. This experiment was a landmark in cancer research. Many experiments that followed demonstrated that this condition applied to all kinds of cancers—virally induced, chemically induced, and spontaneous tumours—and to a variety of cell types—epithelial cells, fibroblasts, and lymphoc5rtes. 

Chandran, U. R., R. Dhir, C. Ma, G. Michalopoulos, M. Becich, and J. Gilbertson. 2005. Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors. BMC Cancer 5 45. 

Potent drugs against cancer normally have to fulfill a number of requirements in terms of its toxicity to tumor cells and solubility for efficient delivery. This requires a full-fledged charac-... 

The clinical symptoms of oculocutaneous albinism are of two types hypersensitivity of the skin to sunlight and photophobia. The skin is white and does not tan when exposed to ultraviolet radiation instead, the skin rapidly bums with erythema and desquamation. The incidence of skin cancer, normally high among blond individuals, is even higher among albinos. The iris has a blue-grey translucency. 

Enediynes hold substantial promise as anti cancer drugs because of their potency and selectivity Not only do they inhibit cell growth they have a greater tendency to kill cancer cells than they do normal cells The mechanism by which enediynes act involves novel chemistry unique to the C C—C=C—C C unit which leads to a species that cleaves DNA and halts tumor growth... 

The influences of herbicides on cell division fall into two classes, ie, dismption of the mitotic sequence and inhibition of mitotic entry from interphase (G, S, G2). If ceU-cycle analyses indicate increases in abnormal mitotic figures, combined with decreases in one or more of the normal mitotic stages, the effect is upon mitosis. Mitotic effects usually involve the microtubules of the spindle apparatus in the form of spindle depolymerization, blocked tubulin synthesis, or inhibited microtubule polymerization (163). Alkaloids such as colchicine [64-86-8J,viahla.stiae [865-21-4] and vincristine [57-22-7] dismpt microtubule function (164). Colchicine prevents microtubule formation and promotes disassembly of those already present. Vinblastine and vincristine also bind to free tubulin molecules, precipitating crystalline tubulin in the cytoplasm. The capacities of these dmgs to interfere with mitotic spindles, blocking cell division, makes them useful in cancer treatment. 

The immunorestorative potential of inosiplex has been evaluated in several clinical conditions, including post-surgical trauma, cancer patients with concurrent viral infections, and cancer patients receiving radiotherapy or chemotherapy. For example, most (84%) of the surgery patients remained immunologicaHy depressed, but 56% of the inosiplex-treated surgery patients had complete restoration of normal skin test reactivity (probability level < 0.0005). The use of inosiplex as an adjuvant to chemotherapy or radiotherapy appears to be valuable in the prophylaxis against opportunistic infections. 

Cancer. Cancer is a cellular malignancy characterized by loss of normal controls resulting in unregulated growth, lack of differentiation, and the abihty to invade local tissues and metastasize. Most cancers are potentially curable, if detected at an early enough stage. The ideal antineoplastic agent would destroy cancer cells without adverse effects or toxicities to normal cells. No such dmg exists. 

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

The development of so-called photodynamic therapy uses lasers for treatment of cancer. The patient is injected with a substance called hematoporphyrin derivative [68335-15-9] which is preferentially localized in cancerous tissues. The patient is later irradiated with laser light, often with a dye laser at a wavelength around 630 nm. The light energy catalyticaHy photooxidizes the hematoporphyrin derivative, releasing materials which kill the nearby cancerous tissue. Normal tissue which did not retain the chemical is not harmed. Photodynamic therapy offers promise as a new form of cancer treatment. 

Health and Safety Factors. Terephthahc acid has a low order of toxicity. Inhalation by rats for 6 h/d, 5 d/wk for 4 wk produced no fatahties at a dust exposure level of 25 mg/m. The mean acute oral toxicity for rats is over 18 g/kg (86), and for mice over 6 g/kg (87). When terephthahc acid was fed as 3% of the diet to rats, urinary calcuh formed in 90 d, some of which led to cancer. High doses of terephthahc acid lead to formation of calcium terephthalate at levels exceeding its solubihty in urine. This insoluble material leads to the calcuh and provides a threshold below which cancer is not observed (88). Normal precautions used in handling industrial chemicals should be observed with terephthahc acid. If ventilation is inadequate, a toxic-dust respirator should be used to avoid prolonged exposure. 

Health and Safety Factors. Isophthahc acid has a low order of toxicity. Inhalation by rats for 4 h at 11.4 g/m showed no toxicity. The LD -level for rats is high at 10.4 g/kg (96). As with terephthahc acid, isophthahc acid was found to form urinary tract calcuh in rats in 90 d when it constituted 3% of their diet. This led to some cancer owing to the presence of the calcuh. Some mild eye irritation is possible, so eye protection should be worn. Otherwise, normal precautions used in handling industrial chemicals should be observed with isophthahc acid. 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

Vaccine development is hampered by the fact that recurrent disease is common. Thus, natural infection does not provide immunity and the best method to induce immunity artificially is not clear. The genome of these vimses is also able to cause transformation of normal cells, thus conferring on them one of the properties attributed to cancerous cells. Vaccine made from herpes vimses must, therefore, be carefully purified and screened to eliminate the possibihty of including any active genetic material. 

Therapy with L-asparaginase is most successful against tumors exhibiting a deficiency in the synthesis of L-asparagine. Most normal cells exhibit a healthy capacity to synthesize this nonessential amino acid and are not damaged by exposure to L-asparaginase (23). This finding demonstrates that biochemical differences between normal and cancer cells can be exploited for successful cancer chemotherapy. 

Mammalian Cells Unlike microbial cells, mammalian cells do not continue to reproduce forever. Cancerous cells have lost this natural timing that leads to death after a few dozen generations and continue to multiply indefinitely. Hybridoma cells from the fusion of two mammalian lymphoid cells, one cancerous and the other normal, are important for mammalian cell culture. They produce monoclonal antibodies for research, for affinity methods for biological separations, and for analyses used in the diagnosis and treatment of some diseases. However, the frequency of fusion is low. If the unfused cells are not killed, the myelomas 1 overgrow the hybrid cells. The myelomas can be isolated when there is a defect in their production of enzymes involved in nucleotide synthesis. Mammahan cells can produce the necessary enzymes and thus so can the fused cells. When the cells are placed in a medium in which the enzymes are necessaiy for survival, the myelomas will not survive. The unfused normal cells will die because of their limited life span. Thus, after a period of time, the hybridomas will be the only cells left ahve. 

---