Cachexia and tumor necrosis factor-1. Overview of 1971 Old and so found to be infected mice injected with lipid more than the BCG; sugar induced tumor necrosis after the bite, 1975 Car-swell, etc. will cause the tumor necrosis factor known as tumor necrosis factor, 1984 Pennica such as TNF- obtained the DNA cloned and successfully expressed in E. coli, so that for TNF-depth study of a possible , TNF is currently a more in-depth account of a cytokine. Anti-TNF- is the host immune gram-negative bacterial infections major media, in other infections also play an important role in the process.
TNF is divided into two categories: often said that the TNF is the TNF-, and lymphotoxin as TNF-1, human TNF- gene located on chromosome 6, the activation of monocytes, T cells, NK cells, mast cells and so can be secreted, -interferon can enhance the LPS stimulated macrophages had cell synthesis of TNF function. At low concentrations, that is about 10 – 11. TNF by leukocytes and endothelial cells in a paracrine and autocrine manner to play in the local inflammation. When a large number of TNF production, to enter the blood circulation, play a variety of endocrine hormone-like effect.
Cachexia and tumor necrosis factor 2. On the appetite of TNF at low concentrations may increase neurotransmitter corticotropin-releasing hormone levels, studies have proved that TNF-1 can directly act on the hypothalamic satiety center and peripheral parts, and the next central hypothalamic regulation of food have IL-1 and TNF- receptor, IL-1. TNF- can act directly on the hypothalamus produce anorexia. Stimulate the full center, inhibitor, or to promote consumption of sugar intake on the concentration of sugar-sensitive nerves, thus reducing food intake 11k. Lee to the same degree in normal mice injected with TNF-a3 days, mice reduced food intake, cachexia in mice significantly into the state. Radioimmunoassay of tumor cachexia in serum TNF- levels were significantly higher than that of normal mice, mice with a cachexia after injection of INF- antibody, showing that mice with obvious improvement in cachexia.
3. The impact of TNF on glucose metabolism of glucose, glucose metabolism mainly for two into increased use of glucose and peripheral tissue disorder. Lactic acid into sugar and increase the role of amino acids in cancer patients abnormal glucose into the most important features of increase, this process consumes a lot of energy, thereby increasing energy consumption based on the patients, leading to the production of cachexia. TNF also can induce insulin resistance in patients with tumor membrane: mediated insulin receptor substrate-film-1 serine phosphorylation and making tyrosine kinase inhibitors, which inhibit the insulin receptor substrate-membrane – 11 Ke acid phosphorylation. reduced insulin-sensitive membrane glucose transporter (GLUT). Yang made the film, insulin stimulated glucose transport; increase the glucose uptake, feedback inhibition of the GLUT-4 in the transmembrane transport, the membrane insulin stimulated glucose uptake decreased.
4. On fat metabolism in animal and human studies show that intake of TNF induced a weight loss, rapid intake of cancer patients caused by TNF-a expression and cachexia similar increase of 80% glycerol and fatty acids into an increase of 60%, protein conversion rate increased flow of amino acids in vivo inhibition of TNF- increased lipoprotein lipase activity, animal intake of TNF could lead to a high triglyceride acidosis, the cause was believed to inhibit lipoprotein lipase activity in the liver is very low anti- density lipoprotein synthesis and secretion. If the rats were transferred to a human TNF gene, can cause cachexia, progressive weight loss occurs, anorexia, premature death. Adipose tissue loss in cachexia appear before the state of the protein consumption. TNF through the inhibition of LPL activity, reducing LPLmRNA expression, resulting in lipodystrophy cancer patients, showed increased hydrolysis of endogenous fat suits the hydrolysis of endogenous triglycerides were lower than normal, resulting in very low density lipoprotein and blood circulation glycerol Three levels of vinegar.
5. Qiang on bone metabolism in muscle protein consumption is due to TNF-a induced oxidative stress and nitric oxide (NO) synthesis, resulting in myosin, muscle kinase activity decreased. Rat weight loss, muscle consumption, cell abnormalities, by giving the same or NO inhibitors and antioxidants to prevent; rats after the inoculation of tumor was significantly higher TNF- level, these phenomena are confirmed by TNF- in the pathogenesis of cachexia effect. Recent consumption of muscle protein loss and muscle made great progress, Tisdale is also the author of Science on the results of such genetic Guttridge comment. Guttridge and so on through a large number of experimental studies show that TNF-a with or without IFN dry coordinating role, through the inhibition of nuclear factor KB, and inhibit C2C12 muscle cell sarcoplasmic protein family of transcription factors MyoD bHLH protein transcription, myogenic differentiation of bone marrow suppression, muscle consumption. When using the antagonist of NF-KB after IKBaSR MyoD was restored. TNF-a protein can also inhibit the synthesis of the Pan-26s protein precursor enzymes the body produces, and thus inhibit protein synthesis in pan. In humans, TNF- antibody partially prevented weight loss, but can not keep their weight normal. In addition to these phenomena are prompted to TNF-, there are other factors involved in the formation of cachexia.
6. TNF- can be used to predict the prognosis of lung cancer in recent years, TNF- and tumor prognosis attention by everyone, including TNF- and lung cancer more. Chen Lin observed 73 cases of primary lung cancer and other patients with TNF- value was found TNF was significantly higher than a control group TNF- levels increased with tumor stage and, in the period of increased lung W most obvious, but and lung cancer tissue type. Tip TNF- values as a predictor of lung cancer can be an indicator of the disease. Liu Zenglin of soluble tumor necrosis factor receptor (sTNFRI) in the pathogenesis of lung cancer by enzyme-linked immunosorbent assay (ELISA) assay in 30 patients with lung cancer TNFRI levels. Results: The patients with lung cancer TNFRI (3.54 2.68) Q significantly higher than the control group (1.52 0.65) P <0.OO1. sTNFRI value of state failure in patients with increasing high. sTNFRl with the staging of lung cancer and increasing the value of high. STNFRI in lung cancer that play a major role, can be used as indicators of lung cancer.
Cachexia and tumor necrosis factor: Many researchers also observed that TNF- value with changes in treatment. HU Chi-Ding for propionate Nandrolone and nutritional support therapy in 19 patients with cachexia in patients with treatment for 3 weeks, the concept of cheong before and after treatment of serum TNF-, weight, right arm middle circumference, triceps skin fold garnet thickness, KPS, total protein, albumin changes, and with 17 healthy control group for comparison. Results Before treatment, disease TNF- significantly in the control group (P <O.01), TNF- after treatment than before treatment significantly decreased the value (P <O.01), and close to the control group, remaining after treatment Additional indicators were compared before treatment, her condition improved and TNF- when the value is down. Concluded that TNF- could be involved in the process of cachexia one of important cytokines, the level of severity level associated with the disease.
Zhang Bin, 15 cases of advanced lung cancer patients with tumor necrosis child (TNF- value) the dynamic changes before and after surgery, were analyzed in parallel. Satisfied that the results of preoperative patients with lung cancer in peripheral serum levels of TNF- values were significantly higher than normal people p <0.05. 17 days after patients with lung cancer serum TNF- level was significantly lower than that before operation (P <0.
05). Liu Jifu 14 cases of lung cancer patients detected TNF-a value of preoperative and postoperative changes, and were followed up, found that 10 cases had decreased to normal values of TNF-, survival 10-33 months, the median survival of 20, 4 postoperative value but increased TNF-, and 1 were not reduced to normal in 5 patients suffering from recurrence within 6 months after surgery and metastasis. The results above shows, TNF- in patients with lung cancer staging, cachexia status, progress of the disease is almost the same as a predictor of lung cancer can be an indicator of the disease.