Cancer necrosis, mechanism

Mier, J.W. et al., Induction of circulating tumor necrosis factor (TNF-alpha) as the mechanism for the febrile response to interleukin-2 (IL-2) in cancer patients, J. Clin. Immunol., 8, 426, 1988. 

The mechanisms of the necrosis of the cancer tissue by electrochemical treatment (ECT) are complex and not fully understood although the nature of several factors involved has been indicated. Nordenstrom pointed out the importance of electroosmosis, electrophoresis, electrode reactions, pH changes and the general drastic change in the microenvironment of the cancer tissue10,18 during ECT this and related work has been reviewed by Nilsson and coworkers.19... 

The traumatic changes brought by ECT would also tend to break and dismantle the hydrogen-bonding network of DNA of the tissue thus suggesting another mechanism for necrosis.25 The following other possible contributions to the necrosis of the cancer tumor during ECT may also be noted ... 

There is a great deal of evidence that AmB can exert a number of effects directly on cells of the immune system, and particularly on macrophages to increase nonspecific defense mechanisms against pathogens and cancer cells. These mechanisms include the production of nitric oxide (NO) (32) and tumor necrosis factor alpha (TNF-a) (33), which could contribute to the antifungal and antiparasitic activity of AmB. However, excess TNF-a production could also be responsible for some of the side effects associated with AmB treatment, such as fever and chills. 

The rate of growth of human and experimental cancers is initially quite rapid (exponential) and then slows until a plateau is reached. The decrease in growth rate with increasing tumor size is related both to a decrease in the proportion of cancer cells actively proliferating (termed the growth fraction) and to an increase in the rate of cell loss due to hypoxic necrosis, poor nutrient supply, immunological defense mechanisms, and other processes. 

Our understanding on the underlying mechanism of this novel cancer treatment was significantly advanced by the discovery in 1975 that bacterial endotoxin induced the production and release of an anti-tumor activity from host cells like macrophages. This activity caused hemorrhagic necrosis of transplanted tumors in mice and killed transformed cell lines (Carswell et al, 1975). The promise of TNF as a cancer cure prompted many laboratories to search the molecular identity of TNF, which eventually led to the purification, characterization and cloning of TNF (Beutler and Cerami, 1986 Pennica et al., 1984 Shirai et al., 1985 Wang et al, 1985). 

Celiptinium is useful in the treatment of metastatic breast cancer and is useful in combination therapy because of minimal hematotoxicity. Acute and chronic renal failures have been detected in patients treated with celiptinium. Acute renal failure is dose dependent, while chronic effects appear to be cumulative in nature. The primary manifestation of celiptinium nephrotoxicity is tubular necrosis with celiptinium-induced lipid peroxidation in proximal tubular cells proposed as the mechanism of toxicity. 

Immunostimulant effects of garlic include an increase in proliferation of lymphocyte and macrophage phagocytosis, induction of the infiltration of lymphocytes and macrophages in transplanted tumors, induction of splenic hypertrophy, increased release of interleukin (IL)-2, interferon-y, and tumor necrosis factor-a, and enhancement of natural killer cell activity. It is thought that these effects may be mechanisms of cancer prevention (49). Lau and colleagues tested an aqueous garlic extract from Japan, the protein fraction isolated from this same extract, and three additional extracts obtained from health food stores in Loma Linda, CA, for ability to stimulate murine T-lym-... 

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