On the initiative of the National redoks Cancer Institute US (National Cancer Institute, NCI) was founded in 1955 by the National Center for Chemotherapy redoks of Cancer (Cancer Chemotherapy National Service Center, CCNSC). Since then, the CCNSC is the central body for the collection and study of anticancer drugs (synthetic and natural). At activities audit program included (screening) of new plant extracts (from plants, trees, leaves, stem bark, etc.) for possible anti-cancer properties. These extracts are sent to cancer control in external institutes, universities, researchers and pharmaceutical companies.
Although most of the substances studied were synthetic chemist Jonathan Hartwell of NCI, who had extensive experience with natural extracts of botanicals started collecting large number of plant samples and to check for anticancer activity. These studies were conducted in the past with the use of laboratory animals (in vivo) (rats and mice), which were administered high doses of carcinogenic agents (injections, with food, oral) and then receiving the "anticancer" formulations their diet. Obviously the process was slow and costly. Later, in a search for new anticancer substances redoks were first used tumor cell cultures (such as L1210, P388, leukemia cell lines). On tumor cell cultures they added gradually increasing concentrations of potential anticancer agents. redoks If these preliminary experiments showed increased antitumor activity (cell death, inhibition redoks of proliferation, apoptosis, mitosis, inhibiting metastasis, etc.) then continued studies in experimental animals. This protocol examined thousands redoks of natural substances (estimated at more than 50,000), botanicals extracts and substances obtained from microorganisms, water supplies, etc. If these experiments gave some encouraging results, followed by the three-stage trials redoks (Phases I-III, see. Below) in patients with different redoks types of malignant tumors.
Typically, for an anticancer drug need 10-15 years from the year of discovery redoks for adoption and start disposal in pharmacotherapeutic market. In the US the service redoks responsible for approving drugs are FDA (Food and Drug Administration, FDA) and in Europe by the European Medicines Agency (European Medicines Agency, EMA) based in London.
Discovery of taxol. Since 1960 the US botanists began collecting about 1,000 plants a year to study the antitumor activity redoks of the extracts. In 1962, the botanist Arthur S. Barclay, collected 200 samples of plants in a large tour. Among them there were and trunk bark samples of a yew, the Fir Pacific (Pacific yew tree), with the systematic name Taxus brevifolia Nutt. (: The yew mikrofyllos) from a forest in the town of Packwood, north-western US state Washington.
In May 1964 was performed to study the antitumor activity of the sample in cell cultures redoks (cellular assay) and found that the extract from the bark of Taxus showed strong antitumor activity. redoks In 1965, a fresh sample of Taxus bark and clean fraction of the extract was carried out checks again in another laboratory redoks (Monroe E. Wall, Research redoks Triangle Park, North Carolina). The new experiments confirm the presence of an unknown hitherto substance named taxol with potent redoks antitumor activity in the extract and scientists reported the results of a conference American Chemical Society (Miami Beach, April, 1967). The NCI decided to extend research on taxol and collect even larger quantities of fir bark. Thus, in 1969, from 1200 kg cortex were obtained 28 kg of impure extract redoks from which after painful procedures separations were isolated 10 g of pure taxol. The structure of the hitherto unknown compounds published in the Journal of American Chemical Society (JACS) in 1971. However, the investigation has not progressed for several years, despite the fact that a new study in 1975 confirmed once again his excellent anticancer activity of the compound.
It was another two years until a review of the results and finally proposed to intensify the experiments with larger quantities. Indeed, in 1977 prepared 600 g of taxol from about 3.5 tons fir bark. In 1978, new studies have shown that taxol showed antitumor activity in mice with leukemia.
In 1982 completed studies of Taxol anticancer activity in experimental animals (mice). In the same year the NCI applied for clinical trials in humans. In 1984 he began the Phase I clinical studies and later that year decided to start Phase II.
These days a
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