Taxol stabilizes microtubules in mouse fibroblast cells.
01 Mar 1980-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 77, Iss: 3, pp 1561-1565
TL;DR: Taxol inhibited the migration behavior of fibroblast cells, but these cells did not lose their ability to produce mobile surface projections such as lamellipodia and filopodia.
Abstract: Taxol, a potent inhibitor of human HeLa and mouse fibroblast cell replication, blocked cells in the G2 and M phase of the cell cycle and stabilized cytoplasmic microtubules. The cytoplasmic microtubules of taxol-treated cells were visualized by transmission electron microscopy and indirect immunofluorescence microscopy. More than 90% of the cells treated with 10 micro M taxol for 22 hr at 37 degrees C displayed bundles of microtubules that appeared to radiate from a common site (or sites), in addition to their cytoplasmic microtubules. Untreated cells that were kept in the cold (4 degrees C) for 16 hr lost their microtubules, whereas cells that were pretreated with taxol for 22 hr at 37 degrees C continued to display their microtubules and bundles of microtubules in the cold. Taxol inhibited the migration behavior of fibroblast cells, but these cells did not lose their ability to produce mobile surface projections such as lamellipodia and filopodia.
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01 Jan 2000
TL;DR: This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices, in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation.
Abstract: NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …
3,924 citations
TL;DR: This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases and effective drug development depends on multidisciplinary collaborations.
2,272 citations
Cites background from "Taxol stabilizes microtubules in mo..."
...promotion of the assembly of tubulin into microtubules by Schiff and Horwitz and its report in 1980 [28], was a key milestone in the lengthy development process, and it was finally approved for clinical use against ovarian cancer in 1992 and against breast cancer in 1994....
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TL;DR: Endophytic microorganisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic, which may produce a plethora of substances of potential use to modern medicine, agriculture, and industry.
Abstract: Endophytic microorganisms are to be found in virtually every plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to slightly pathogenic. Because of what appears to be their contribution to the host plant, the endophytes may produce a plethora of substances of potential use to modern medicine, agriculture, and industry. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation, culture, purification, and characterization of some choice endophytes in the recent past. The potential prospects of finding new drugs that may be effective candidates for treating newly developing diseases in humans, plants, and animals are great.
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Cites background from "Taxol stabilizes microtubules in mo..."
...The mode of action of paclitaxel is to preclude tubulin molecules from depolymerizing during the processes of cell division (50)....
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TL;DR: While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs in the future.
1,760 citations
Cites background from "Taxol stabilizes microtubules in mo..."
...In the late 1970, it was discovered as the first antimitotic agent that acted by promoting the irreversible assembly of tubulin into microtubules (Schiff et al., 1979; Schiff and Horwitz, 1980)....
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TL;DR: Taxomyces andreanae, a fungal endophyte, was isolated from the phloem (inner bark) of the Pacific yew, Taxus brevifolia, and taxol was identified by mass spectrometry, chromatography, and reactivity with monoclonal antibodies specific for taxol.
Abstract: Taxomyces andreanae, a fungal endophyte, was isolated from the phloem (inner bark) of the Pacific yew, Taxus brevifolia. The fungus is hyphomyceteous and, when grown in a semi-synthetic liquid medium, produced taxol and related compounds. Taxol was identified by mass spectrometry, chromatography, and reactivity with monoclonal antibodies specific for taxol. Both [1-14C]acetic acid and L-[U-14C]phenylalanine served as precursors of [14C]taxol in fungal cultures. No taxol was detected in zero-time cultures or in the small agar plugs used to inoculate the culture flasks.
1,575 citations
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3,761 citations
TL;DR: It is reported here that taxol acts as a promoter of calf brain microtubule assembly in vitro, in contrast to plant products such as colchicine and podophyllotoxin, which inhibit assembly.
Abstract: TAXOL (Fig. 1) was isolated from the plant Taxus brevifolia (western yew) by Wani et al., who reported that the molecule has antitumour activity in several experimental systems1. In our laboratory we have found that taxol, a low molecular weight neutral compound, completely inhibits division of exponentially growing HeLa cells at low concentrations of drug (0.25 µM) that have no significant effects on DNA, RNA or protein synthesis during a 4-h incubation with the cells. HeLa cells incubated with taxol for 20 h are blocked in late G2 and/or M (ref. 2). We report here that taxol acts as a promoter of calf brain microtubule assembly in vitro, in contrast to plant products such as colchicine and podophyllotoxin, which inhibit assembly. Taxol decreases the lag time for microtubule assembly and shifts the equilibrium for assembly in favour of the microtubule, thereby decreasing the critical concentration of tubulin required for assembly. Microtubules polymerised in the presence of taxol are resistant to depolymerisation by cold (4 °C) and CaCl2 (4 mM).
3,430 citations
TL;DR: This article summarizes the current views on the dynamic structure of the mitotic spindle and its relation to mitotic chromosome movements based on measurements of birefringence of spindle fibers in living cells, normally developing or experimentally modified by various physical and chemical agents.
Abstract: This article summarizes our current views on the dynamic structure of the mitotic spindle and its relation to mitotic chromosome movements. The following statements are based on measurements of birefringence of spindle fibers in living cells, normally developing or experimentally modified by various physical and chemical agents, including high and low temperatures, antimitotic drugs, heavy water, and ultraviolet microbeam irradiation. Data were also obtained concomitantly with electron microscopy employing a new fixative and through measurements of isolated spindle protein. Spindle fibers in living cells are labile dynamic structures whose constituent filaments (microtubules) undergo cyclic breakdown and reformation. The dynamic state is maintained by an equilibrium between a pool of protein molecules and their linearly aggregated polymers, which constitute the microtubules or filaments. In living cells under physiological conditions, the association of the molecules into polymers is very weak (absolute value of Δ F 25°C S 25°C ≃ 100 eu) or by the addition of heavy water. The spindle proteins tend to polymerize with orienting centers as their geometrical foci. The centrioles, kinetochores, and cell plate act as orienting centers successively during mitosis. Filaments are more concentrated adjacent to an orienting center and yield higher birefringence. Astral rays, continuous fibers, chromosomal fibers, and phragmoplast fibers are thus formed by successive reorganization of the same protein molecules. During late prophase and metaphase, polymerization takes place predominantly at the kinetochores; in metaphase and anaphase, depolymerization is prevalent near the spindle poles. When the concentration of spindle protein is high, fusiform bundles of polymer are precipitated out even in the absence of obvious orienting centers. The shift of equilibrium from free protein molecules to polymer increases the length and number of the spindle microtubules or filaments. Slow depolymerization of the polymers, which can be brought about by low concentrations of colchicine or by gradual cooling, allows the filaments to shorten and perform work. The dynamic equilibrium controlled by orienting centers and other factors provides a plasusible mechanism by which chromosomes and other organelles, as well as the cell surface, are deformed or moved by temporarily organized arrays of microtubules or filaments.
724 citations
TL;DR: Various aspects of the behaviour of the lamellar projections termed “ruffles” that appear at the leading end of fibroblast-like cells moving in culture are quantitatively described.
587 citations
TL;DR: A method for measurement and simultaneous analysis of DNA, protein, and cell volume in the same cell by use of a newly developed multiparameter cell analysis system which incorporates several pre-existing analytical techniques and allows all the various measurements to be performed on the samecell under conditions where large populations can be analyzed rapidly and a high degree of statistical precision obtained.
Abstract: The advent of high speed, cell analysis systems (1-5) for rapid measurement of physical and biochemical properties in single cells has provided new and useful techniques for performing a wide variety of biological experiments . Such systems recently have been used in studies related to DNA content per cell as a function of chromosome number (6, 7), effects of chemotherapeutic agents on cell cycle traverse (8), and quantitation of cell surface binding of the plant lectin concanavalin A (9) as well as immunofluorescent detection of antigen-binding cells (10) . These investigations have involved quantitative fluorescent staining of monodisperse cell populations in liquid suspension by techniques specific for biochemical components of interest and subsequent rapid analysis of the fluorescence emission signal obtained as each cell traverses a laser beam . General operating characteristics of this flow system, as well as validation of the methodology, have been presented in detail elsewhere (7, 11) . These earlier studies involved measurement of only a single cellular property. In this report we describe a method for measurement and simultaneous analysis of DNA, protein, and cell volume in the same cell by use of a newly developed multiparameter cell analysis system which incorporates several pre-existing analytical techniques and allows all the various measurements to be performed on the same cell under conditions where large populations can be analyzed rapidly and a high degree of statistical precision obtained . Electronic processing of fluorescence and volume signals from each cell provides a direct method for establishing relationships between various cellular properties reflecting specific phases of the cell cycle .
555 citations