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New anticancer drug - paclitaxel

Paclitaxel is a kind of tetracyclic two nitric acid amines compounds, which isolated from Taxus--taxus chinensis bark and needles. It can be effectively treating advanced ovarian cancer, breast cancer and other cancers, and is said to be the best anti-cancer drugs discovered in past decades.

In 1992, FDA approved paclitaxel as a new cancer drug for treating advanced ovarian cancer (its brand name is Pach-taxel). Because paclitaxel content in the plant body is quite low, it only can be extracted about 1g paclitaxel from 3~6 60-100 years old trees bark, for treating a cancer patient. Currently, global annual consumption of paclitaxel is 200kg, meaning it should cut 1 million yew trees. Along with the application of paclitaxel extended, the demand will increase year by year, but yew grows quite slowly, 20cm diameter trees need to grow for 100 years. Therefore, felling trees to produce paclitaxel is not only seriously destroying the long-term survival and distribution of tree, but also cannot meet the people's demand for paclitaxel. The current findings suggest that the major source of paclitaxel is still yew bark, this evergreen tree grows very slowly, and large-scale deforestation must be seriously damaged the plant resources. While about the paclitaxel total synthesis, although organic chemists have been success in laboratory, but from the point of mass production view, it is infeasible.

Paclitaxel has a unique mechanism of action, can induce and promote tubulin polymerization, microtubules assembly and microtubule stable, thereby preventing the tumor cells grow. Pharmacological experiments shown that paclitaxel has broad-spectrum anti-cancer effect, its anti-cancer effect derives that it roles in the tubulin which form of spindle during cell division process. The effect is opposite of the other usual spindle poisons such as vinblastine, new vinblastine, colchicine, podophyllotoxin, which stop the microtubules gathered, paclitaxel in low concentrations (0.25g/m) will catalyze tubulin rapidly synthesize microtubule and combined with microtubule to play the role of stability and preventing microtubule depolymerization. Normal microtubules in the presence of Ca2+ or under 4 low temperature will occur depolymerization, but microtubules treated by paclitaxel would not occur depolymerization. So the activity of paclitaxel manifests in two ways: First, for the rapidly divisive tumor cells, paclitaxel will freeze the mitotic spindle, thereby stopping the tumor cells in the G2 phase and M phase, until death. Second, inhibit tumor cell migration.

Pharmacyeutical raw materials suppliers claimed that paclitaxel is a kind of new novel mechanism of action anticancer drug. Clinical studies have shown that it has effects on the ovary cancer, breast cancer, esophageal cancer, cell carcinoma of head and neck and many other tumors, be known as broad spectrum antitumor drugs. But in clinical application, paclitaxel still has a lot of aspects to be further studied.

Some patients treated with paclitaxel appear severe acute allergic reactions, so that disturbed the necessary treatment or must be stopped treating. In clinical trials, some patients treated with paclitaxel were occurred significant cardiovascular adverse reactions, including myocardial infarction, mild congestive heart failure, ventricular and supraventricular tachycardia, ventricular arrhythmia and so on. Other adverse reactions which associated with paclitaxel including almost all patients are losing hair; 4% to 30% of the patients suffer catarrh; the most important is mild nausea, vomiting, and local phlebitis (4% to 64%). AgeFree Articles, previous treatment or the received total cumulative dose of paclitaxel drug seems to be no effect on the drug tolerance.


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