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==Research== [[Caffeine]] has been speculated to inhibit paclitaxel-induced [[apoptosis]] in colorectal cancer cells.<ref name="pmid = 24173825">{{cite journal | vauthors = Mhaidat NM, Alzoubi KH, Al-Azzam SI, Alsaad AA | title = Caffeine inhibits paclitaxel‑induced apoptosis in colorectal cancer cells through the upregulation of Mcl‑1 levels | journal = Molecular Medicine Reports | volume = 9 | issue = 1 | pages = 243–248 | date = January 2014 | pmid = 24173825 | doi = 10.3892/mmr.2013.1763 | url = http://www.spandidos-publications.com/mmr/9/1/243 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20150622015153/http://www.spandidos-publications.com/mmr/9/1/243 | archive-date = 22 June 2015 }}</ref> In 2016, ''in vitro'' multi-drug resistant mouse tumor cells were treated with paclitaxel encased in [[Exosome (vesicle)|exosomes]]. Doses 98% less than common dosing had the same effect. Also, dye-marked exosomes were able to mark tumor cells, potentially aiding in diagnosis.<ref>{{cite web |date=14 January 2016 |title=Cloaking chemo drugs in cellular bubbles destroys cancer with one fiftieth of a regular dose |url=http://www.gizmag.com/drug-delivery-method-cancer-dose/41349 |url-status=live |archive-url=https://web.archive.org/web/20160224221957/http://www.gizmag.com/drug-delivery-method-cancer-dose/41349/ |archive-date=24 February 2016 |access-date=14 February 2016 |website=www.gizmag.com |vauthors=Lavars N}}</ref><ref>{{cite journal |vauthors=Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, Inskoe E, Piroyan A, Sokolsky M, Okolie O, Hingtgen SD, Kabanov AV, Batrakova EV |date=April 2016 |title=Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells |journal=Nanomedicine |volume=12 |issue=3 |pages=655–664 |doi=10.1016/j.nano.2015.10.012 |pmc=4809755 |pmid=26586551}}</ref> Aside from its direct clinical use, paclitaxel is also used extensively in biological and biomedical research as a [[microtubule]] stabilizer. In general, ''[[in vitro]]'' [[assay]]s involving microtubules, such as motility assays, rely on paclitaxel to maintain microtubule integrity in the absence of the various nucleating factors and other stabilizing elements found in the cell. For example, it is used for ''in vitro'' tests of drugs that aim to alter the behavior of microtubule [[motor proteins]], or for studies of mutant motor proteins. Paclitaxel has also been used ''in vitro'' to inhibit [[insulin]] fibrillation. In a [[molar ratio]] of 10:1 (insulin:paclitaxel), it hindered insulin fibrillation near 70%. [[Isothermal titration calorimetry]] (ITC) findings indicated a spontaneous tendency of paclitaxel to interact with insulin through [[hydrogen bond]]s and [[van der Waals force]]s.<ref>{{cite journal | vauthors = Kachooei E, Moosavi-Movahedi AA, Khodagholi F, Mozaffarian F, Sadeghi P, Hadi-Alijanvand H, Ghasemi A, Saboury AA, Farhadi M, Sheibani N | title = Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel | journal = Journal of Biochemistry | volume = 155 | issue = 6 | pages = 361–373 | date = June 2014 | pmid = 24535601 | doi = 10.1093/jb/mvu012 }}</ref> The inhibitory role of paclitaxel is attributed to its impact on the colloidal stability of protein solution, as it was observed that paclitaxel inhibited [[lysozyme]] fibrillation by inducing the formation of "off-pathway" [[oligomer]]ic intermediates, subsequently increasing the colloidal stability.<ref>{{cite journal | vauthors = Kachooei E, Mozaffarian F, Khodagholi F, Sadeghi P, Karami L, Ghasemi A, Vahdat E, Saboury AA, Sheibani N, Moosavi-Movahedi AA | title = Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability through formation of "off-pathway" oligomers | journal = International Journal of Biological Macromolecules | volume = 111 | pages = 870–879 | date = May 2018 | pmid = 29352977 | doi = 10.1016/j.ijbiomac.2018.01.072 | doi-access = free }}</ref> Paclitaxel is sometimes used for ''[[in vivo]]'' studies as well. It can be fed to test organisms, such as [[Drosophila melanogaster|fruit flies]], or injected into individual cells, to inhibit microtubule disassembly or to increase the number of microtubules in the cell. Paclitaxel induces [[remyelination]] in a [[Demyelinating disease|demyelinating]] mouse ''in vivo''<ref>{{cite journal | vauthors = Moscarello MA, Mak B, Nguyen TA, Wood DD, Mastronardi F, Ludwin SK | title = Paclitaxel (Taxol) attenuates clinical disease in a spontaneously demyelinating transgenic mouse and induces remyelination | journal = Multiple Sclerosis | volume = 8 | issue = 2 | pages = 130–138 | date = April 2002 | pmid = 11990870 | doi = 10.1191/1352458502ms776oa | s2cid = 45994154 }}</ref> and inhibits human [[PADI2|peptidylarginine deiminase 2]] (hPAD2) ''in vitro'' though its methyl [[ester]] side chain.<ref>{{cite journal | vauthors = Musse AA, Polverini E, Raijmakers R, Harauz G | title = Kinetics of human peptidylarginine deiminase 2 (hPAD2)--reduction of Ca2+ dependence by phospholipids and assessment of proposed inhibition by paclitaxel side chains | journal = Biochemistry and Cell Biology | volume = 86 | issue = 5 | pages = 437–447 | date = October 2008 | pmid = 18923545 | doi = 10.1139/o08-124 }}</ref> In 1999, Angiotech Pharmaceuticals Inc. began [[phase II clinical trials]] of micellar paclitaxel as treatment for [[Multiple sclerosis#Types and variants|secondary progressive multiple sclerosis]],<ref>{{Cite web |date=13 December 1999 |title=Phase II Clinical trial of Micellar Paclitaxel for secondary-progressive MS underway in Canada |url=http://mssociety.ca/en/research/PT991213.htm |url-status=dead |archive-url=https://web.archive.org/web/20120315095242/http://mssociety.ca/en/research/PT991213.htm |archive-date=15 March 2012 |website=[[Multiple Sclerosis Society of Canada]]}}</ref> but reported in 2002 that the results showed no statistical significance.<ref>{{Cite web |date=27 February 2002 |title=Angiotech Halts Study of Micellar Paclitaxel stating no benefit of statistical significance seen |url=http://mssociety.ca/en/research/PT020227.htm |url-status=dead |archive-url=https://web.archive.org/web/20120315095318/http://mssociety.ca/en/research/PT020227.htm |archive-date=15 March 2012 |website=[[Multiple Sclerosis Society of Canada]]}}</ref>
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