text:
HAMILTON — Democrats in the 14th district will hold a grand opening of their campaign headquarters tonight.
Residents, supporters and local officials are invited for the event, which will be hosted by state Sen. Linda Greenstein (D-Plainsboro) and Assemblymen Wayne DeAngelo and Daniel Benson (D-Hamilton).
Light refreshments will be served. The event will run from 5:30 to 8 p.m. at District 14 headquarters, 1970 Route 33.


text:
The National Motor Museum
Telephone: 01590 614650
To email us, please use the online enquiry form below.
If your enquiry is research related please see our Frequently Asked Motoring Questions and the Motoring Research Service section.
See below for Contact Names:
Chief Executive – Russell Bowman
Director of Collections – Andrea Bishop
PA to Director of Collections – Ellie De Beer
Corporate Partnership Manager – Heather Reid
Film Library Manager –Murray Weston
Picture Library Manager – Jonathan Day
Shell Art Collection Manager – Nicola Balfour Penney
Shell Art Collection Promotions Manager – Melinda McCheyne
Shell Art Collections Assistant – Emma Mackinnon
Technical Officer – Tim Woodcock
Telecine Operator – Guy Harmsworth
Curator of The Caravan Club Collection – Angela Cox
Research & Enquiries Officer – Patrick Collins
Library Officer – Caroline Johnson
Curator of Objects – Gail Stewart-Bye
Curator of Photography – Mandy Schaller
Archivist – Helen Sumping
Digital Collections Officer – Dominic Ivaldi
Vehicle Documentation Assistant – Rebecca Town/Hannah Randall
Film and Video Curator – Sarah Wyatt
Object Cataloguer – Keith Smith
Friends Membership Secretary – Theresa Browning
Volunteer Co-ordinator & Office Administrator – Helen Keisel
Education Officer – Chris Gutteridge
Outreach and Access Project Officer – Claire Weston
Site by Surface Impression

subset: commoncrawl


text:
status reports | 25-April-2015 20:14:55 |
No. 48 - Latest Operational Update |
28 February 2006 Report for period 16 January to 19 February 2006 Smart-1 suffered another Double EDAC error on 19 of January. SSC requested ESOC to compile all addresses that have been subject of double EDAC errors and sent them to SSC to check for a possible correlation with a specific chip malfunction. This time ESOC tried a new procedure that prevents loosing any data, this was done on 20 January and proved to be successful. For the rest, Smart-1 operation has been nominal during the reporting period. The RF compatibility tests for the ranging tone tests with the Chinese CLTC and India ISRO have been completed. The tests were complemented with two specific tests using ESA ground stations: Maspalomas with Cortex and Redu with Enertec. Both stations provided and excellent support although only the Cortex tests were successful. In addition an image of Crater Billy was released during this period and additional images are anticipated during the next reporting period. Future ActivitiesFuture activities are focused on the following:
Spacecraft StatusSummary AOCS TT&C EP, Power and Thermal Orbital Information
The changes since apolune 1925 are as follows:
Last Update: 19 April 2006 For further information please contact: firstname.lastname@example.com |
Status Reports ArchiveImages And VideosDocumentation |


text:
We recommend the basic water cooler Kelvin...
Kelvin the basic water cooler. Done right. $199.00 - $229.00 Love your standard water cooler, but hate the way it looks? The Kelvin is for you. Economical and stylish, it is the right match for anyone with an eye for aesthetics. Dimensions: (without bottle) LxWxH: 13"x13"x35.5" Features: - Removable drip tray - Stainless steel cold reservoir - Adjustable cold water thermostat - Universal non-spill system - Stainless steel hot reservoir - Hot water on/off switch - Child safety hot water faucet Warranty: - 5 Year Refrigeration System Warranty - 1 Year All Other Parts
Other places of interest in Orlando Sweetwater Springs Bottled Water Orlando, FL 32828 (407) 277-5331 Aqua Pure Orlando, FL 32801 (407) 521-3055
Know of a company in your city that's not listed? Let us know.


text:
Tech manufacturers usually release products as quickly as anyone can imagine. Despite launching a smartphone, companies like Samsung will have another set ready in no time. This is evident from several handsets people can choose from.
As the competition grows, there is a need for innovation. Innovation means inventing new features or technologies to make a product stand out. This is where Apple and Samsung have been long rivals. In these continuing patent wars, has one company really won over the other?
The slide-to-unlock feature on the iPhone has a patent grant under Apple. Also, the 4G network data system for Samsung Galaxy is granted under Samsung. Over the years, as both companies continue to transform their smartphone offerings, Apple and Samsung have both accused each other of infringing patents and copying technology.
According to Politicio, the two companies are yet again set to battle it out on court about patents. Apple and Samsung have been on each other's throats for almost 3 years, throwing at each other fraud and patent copying charges across four continents.
The legal battle between the two tech giants has captured the attention of the U.S. government. The government has been working on reforms helping companies to spend less money on litigation and invest most on innovative research. The tech industry has produced enough high-profile lawsuits to encourage the government to take action.
"It's just culturally unacceptable to either organization to think about settling, so they're going to continue to battle in the courts," Van Baker, a mobile technology analyst at Gartner, cited.
"They're bitter rivals in the smartphone space, and that's not going to change anytime soon. Any little competitive win or advantage is important."
Amid court battles and more patent conflicts, Apple has secured several more for its upcoming iPhone 6. Some of these patents describe technologies such as:
- Dynamic user interface - users can control devices via gestures despite the distance
- Solar charging panels
- Camera remote control
- Selfie system
Apple has not announced the official features of iPhone 6. Some of these patents may materialize with the next smartphone but some of them may not. Samsung previously released Samsung Galaxy S5 with the health monitor as its never before seen feature. Many analysts think iPhone 6 may gain more market share if Apple can push through with all of its reported patent grants.


text:
Helping you source suppliers
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Home > Indexes > HR Companies > Directory > UK > Ringwood
If you're looking for HR Companies in Ringwood then Approved Index can help! The following are all established suppliers to Ringwood who can quote for your HR Companies needs today.
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Jaluch HouseDeweys LaneRingwoodHampshire
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text:
Your donations keep RPGWatch running!
PotBS - GDC Previews
by Dhruin, 2007-03-10 10:25:00
Here's a pair of GDC previews for Pirates of the Burning Sea:
A snip from IGN:
The game starts you on the deck of your very own ship. (Each player gets their own ship here, so you won't be able to join a friend's crew.) Your 3D avatar is free to walk around the ship, observing the entire world around in real time or you can take the wheel and drive the action from an external perspective. A colored ring around the base of your ship shows which direction the wind is blowing and what the best points of sailing are for your particular ship. You can view your ship from any angle and enjoy the scenery or target an enemy to engage a padlock view.
Source: Bluesnews
Information about
PotBSSP/MP: Massive
Setting: Historical
Genre: MMORPG
Platform: PC
Release: Released


text:
Kidoumaru is another one of the Sound Four, the elite bodyguards of Orochimaru. Kidoumaru has one noticeable feature, he has 6 arms. Each of his arms is used in controlling his web type of attacks on people. He can use it to control his webs and stretch them out.
Kidoumaru is the rowdy guy of the Sound Four, he enjoys playing games and playing with his enemies before he kills them. He is the main one who uses his webs to protect the Sound Four and Orochimaru. The webs can be used defense-wise and offense-wise. Kidoumaru has a special type of metal like liquid which runs throughout his body. He can use this liquid to make his webs as well as when it reaches out side of his body it automatically starts hardening with the chakra which flows with in him.
Kidoumaru is one who likes to use spiders and their attacks in his attacks, when we see him fighting Neji he uses spiders to attack him while having the ability to summon a huge unidentified spider which attacks Neji.
Kidoumaru is a tough one from the Sound Four and his weakness is he takes too long to finish his objectives since he likes to play around which might be his down fall in future battles. Once Kidoumaru activates level 2 Curse Seal he has 120% accuracy and uses his web-made bow to strike his opponents with absolutely no chance of missing.
Kidoumaru also is a strategist who likes strategies and uses them quite often in his attacks or when he plans traps. Though he may be smart in this sense, he is still lacking any true hand to hand combat and uses a lot of long distant attacks since he is not really a taijutsu type of ninja. He doesn't mess around and his ninjutsu is an inhuman one at that, but the reason he was chosen to be one of the Sound Four is mainly because of his web type of jutsus he can use.
Soul_Dawner Comments: 10925 |
Quote by Brianbays2 THNK U! And nuh uh Kidoumaru iz kewler!
This guy is spider man lol plus, hes just trying to spread the word, no reason to get mad can't we all get along |
canibal968 Comments: 243 |
Quote by Brianbays2 u dont get it he has been saying that on a whole bunch of character biographes
This guy is spider man lol plus, hes just trying to spread the word, no reason to get mad can't we all get along |
naterman55 Comments: 1698 |
i'm with soul_dawner |
katiethingy Comments: 9 |
I ate some chicken just now |
Soul_Dawner Comments: 10925 |
Quote by canibal968 Yr point?
u dont get it he has been saying that on a whole bunch of character biographes |
spiders! Comments: 10932 |
too bad naruto shupenden never comes to the usa i rely wish thay would bring it to the us . |
kiki-inuzuka Comments: 1882 |
Quote by canibal968 how do you live in the world without news? ok, so you get the news paper, and make it into a cookie to trick soul_dawner to eating paper.
oooohh sorry |
Sasuke-KunX Comments: 552 |
Quote by spiders! well... they didn't finish naruto yet...
too bad naruto shupenden never comes to the usa i rely wish thay would bring it to the us . |
deidaraunclay Comments: 9 |
OMG Spider-man |
24itachiuchiha24 Comments: 146 |
i hate kidomaru |
naterman55 Comments: 1698 |
neji kills him |
spiders! Comments: 10932 |
his teckneckes are soooooo nasty the six arms but besides that he is ok:embarressed :embarressed :embarressed |
5ofSound Comments: 259 |
Quote by 24itachiuchiha24 ...I'd kick your ass right now if i weren't busy packing to go to Ohio.
i hate kidomaru |
trapseeker_x_x Comments: 3288 |
hello meya san |
spiders! Comments: 10932 |
hi..........hito san..:embarressed :embarressed :embarressed |


text:
Release Date: 1992 | Tracklist
Album Rating: 3.5Full album: http://www.youtube.com/watch?v=a6KWEcKoF7k Don't know about anyone else, but I think Deceased to be one of the most underrated death metal acts out there.
Digging: Tribulation - The Children of the Night
Album Rating: 4.0 | Sound Offi agree with that. they are one of my favs... this review is interesting. i completely disagree with the fact that at this point they were trying to do something "more" than just straight up dm ... thats true of all their albums except this one
Excellent work Robert, pos.
Digging: Aelter - IV: Love Eternal
this looks good, gotta check pos'd
Album Rating: 4.0Forgot about this one
Album Rating: 4.0Impressive album
Album Rating: 3.0its good but nothing amazing, and kinda inconsistent
Bands: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


text:
Home Celebration: A Blog Of Comfort and Joy
Saturday, December 29, 2012
Isn't It A Glorious Day?
It is when you are having so much fun, anyway.
Hope your day is just as wonderful as mine. Go out and enjoy yourself today!
(Photo by Christy Hardin Smith.)
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Post a Comment
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text:
Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast
Optics Letters, Vol. 34, Issue 13, pp. 1924-1926 (2009)
Enhanced HTML Acrobat PDF (204 KB)
We describe a full-field phase-gradient imaging method: asymmetric illumination-based differential phase contrast (AIDPC). Imaging properties of AIDPC are evaluated using the phase-gradient transfer-function approach and elucidated with experimental images of an optical fiber and a histochemical preparation of a skeletal muscle section. In comparison with full-field differential interference contrast, AIDPC does not require phase shifting for quantitative imaging of phase gradient, provides artifact-free images of birefringent specimens, requires shorter camera exposure, and has larger depth of focus. It is amenable to transfer-function engineering, simultaneous fluorescence imaging, and automated live cell imaging.
© 2009 Optical Society of America
OCIS Codes
(100.5070) Image processing : Phase retrieval
(110.0180) Imaging systems : Microscopy
(110.4850) Imaging systems : Optical transfer functions
(110.4980) Imaging systems : Partial coherence in imaging
ToC Category:
Imaging Systems
Original Manuscript: March 30, 2009
Revised Manuscript: May 22, 2009
Manuscript Accepted: May 24, 2009
Published: June 18, 2009
Virtual Issues
Vol. 4, Iss. 9 Virtual Journal for Biomedical Optics
Shalin B. Mehta and Colin J. R. Sheppard, "Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast," Opt. Lett. 34, 1924-1926 (2009)
Sort: Year | Journal | Reset
- D. K. Hamilton and C. J. R. Sheppard, J. Microsc. 133, 27 (1984). [CrossRef]
- D. K. Hamilton, C. J. R.Sheppard, and T. Wilson, J. Microsc. 135, 275 (1984). [CrossRef]
- W. B. Amos, S. Reichelt, D. M. Cattermole, and J. Laufer, J. Microsc. 210, 166 (2003). [CrossRef] [PubMed]
- M. R. Arnison, K. G. Larkin, C. J. R. Sheppard, N. I. Smith, and C. J. Cogswell, J. Microsc. 214, 7 (2004). [CrossRef] [PubMed]
- M. Shribak, J. LaFountain, D. Biggs, and S. Inoue, J. Biomed. Opt. 13, 014011-10 (2008). [CrossRef] [PubMed]
- S. B. Mehta and C. J. R. Sheppard, presented at Focus on Microscopy 2008, April 13-16, 2008, Awaji, Japan. www.focusonmicroscopy.org/2008/PDF/089_pdf.
- G. W. Ellis, "Edge enhancement of phase phenomena," U.S. patent 4,255,014 (March 10, 1981).
- B. Kachar, Science 227, 766 (1985). [CrossRef] [PubMed]
- R. Yi, K. K. Chu, and J. Mertz, Opt. Express 14, 5191 (2006). [CrossRef] [PubMed]
- T. Noda, S. Kawata, and S. Minami, Appl. Opt. 31, 670 (1992). [CrossRef] [PubMed]
- C. J. R. Sheppard and T. Wilson, J. Opt. Soc. Am. A 3, 755 (1986). [CrossRef]
- C. J. Cogswell and C. J. R. Sheppard, J. Microsc. 165, 81 (1992). [CrossRef]
- S. B. Mehta and C. J. R. Sheppard, Opt. Express 16, 19462 (2008). [CrossRef] [PubMed]
- T. Wilson and C. J. R. Sheppard, Proc. SPIE 232, 203 (1980).
- S. B. Mehta and C. J. R. Sheppard, presented at Focus on Microscopy 2009, April 5-8, 2009, Krakow, Poland, www.focusonmicroscopy.org/2009/PDF/396_Mehta.pdf.
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text:
Welcome! The Trek BBS is the number one place to chat about Star Trek with like-minded fans. Please login to see our full range of forums as well as the ability to send and receive private messages, track your favourite topics and of course join in the discussions. If you are a new visitor, join us for free. If you are an existing member please login below. Note: for members who joined under our old messageboard system, please login with your display name not your login name. |
Star Trek Movies XI+ Discuss J.J. Abrams' rebooted Star Trek here. |
Thread Tools |
March 25 2013, 07:01 PM | #31 | ||
Definitely Herbert. Maybe.
Location: Terra Inlandia
Re: Any chance...
"It is my belief that nearly any invented quotation, played with confidence, stands a good chance to deceive." Mark Twain |
March 25 2013, 07:18 PM | #32 | |
Re: Any chance...
In any case, the Shran we saw in TATV was a holographic history lesson/game and may not have been actuality. Even the novels were permitted to ignore it. And give Shran a different full name. And there's nothing in the Archer bio that precludes Shran spending time as a jewel thief.
Thiptho lapth! Ian (Entire post is personal opinion) The Andor Files @ http://andorfiles.blogspot.com/ http://therinofandor.blogspot.com/ |
March 27 2013, 11:28 PM | #33 |
Re: Any chance...
The NX Enterprise should be dragged out of mothballs and turned on. The former team is beamed aboard and the ship goes into warp. Archer screams: "Noooooooooo! I want my doggie!" Pike says: "That was a helluva thing." Scotty: "Aye, it was sir. Archer has nae a doggie at all." Porthos the Unslobbery licks Scotty face and winks at the camera. |
March 28 2013, 09:17 AM | #34 |
Rear Admiral
Re: Any chance...
Ironically, it was Archer's interaction with John Harrison that started the Federation in the Prime Universe and where Archer got the temporal communication device to guide Silik to prevent the two Daniels from acting. Out of anger, nuDaniels blows up the a transport hub in London and tries to shoot up Kirk from a helicopter, before he gets apprehended by Seven of Nine and Borg Janeway with a Defiant stolen from the Prime Universe with Picard and Sisko on board, who right until the last moment think they are being assailed by the Borg.
o= [STXI Enterprise, full scale] |
March 29 2013, 05:45 AM | #35 | |
Vice Admiral
Location: La Belle Province or The Green Mountain State (depends on the day of the week)
Re: Any chance...
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text:
Return to Transcripts main page THE SITUATION ROOM President Bush Formally Unveils Plan To Beef Up War; House Approves Minimum Wage Hike; Iraq Will Likely Dominate 2008 Agenda Aired January 10, 2007 - 16:00 ET THIS IS A RUSH TRANSCRIPT. THIS COPY MAY NOT BE IN ITS FINAL FORM AND MAY BE UPDATED.
© 2007 Cable News Network. A Time Warner Company. All Rights Reserved. Terms under which this service is provided to you. Read our privacy guidelines. Contact us. Site Map. |


text:
If I knew where they were I would be a very happy person,<quoted text>
So, where are these tables?
:::crickets chirping::
There is no evidence for your god. Why should I believe he exists?
>>>:::crickets chirping::...???
I am not asking you to believe God exists, I don't really care if you do or do not, it is not between you and I, it is between you and God.


text:
Laviolette Gets The Flyers Back To Work
PHILADELPHIA (AP) — Flyers coach Peter Laviolette is back where he belongs, at the team's training complex, speaking to reporters and watching some of his players work out.
They're not all back yet, but they will be here soon, as the Flyers finally get a chance to wash away the sting of another short playoff run last season.
The standard group of workout regulars that included defenseman Kimmo Timonen and forwards Max Talbot and Jody Shelley were back Monday morning for a light workout in New Jersey. It was their first unofficial meeting since the NHL and the players' union reached a tentative agreement a day earlier after a lengthy lockout.
The Flyers ditched their NHLPA jerseys for their regular ones with the team logo and skated in front of a few dozen fans.
Laviolette says the short season makes it more important than ever for the Flyers to get off to a fast start.
Source: Associated Press
Laviolette Gets The Flyers Back To Work by Sports Talk FloridaTags: Philadelphia Flyers


text:
Maybe you did not know, but scarecrows used to be just that, real crows to scare off crows and other unwanted, opportunistic scavengers. This is how some farmers still do it in France, however cruel, unethical and non-pc it may seem to some people. (Don't worry,they shoot them first.)
Friday, November 18, 2011
5 comments:
- ladyfi said...
Oh gosh - great but macabre pic!
- 4:15 pm
- swenglishexpat said...
LadyFi - It almost looks medieval.
- 5:34 pm
- Zuzana said...
How interesting (albeit slightly morbid).;) Never knew that the name came from actually using a real crow.;)) Is it effective?;)
xoxo - 11:20 am
- swenglishexpat said...
Zuzana - I had heard of it before but never seen one. By the way, there were no other birds close by......
- 5:50 pm
- Zuzana said...
Just stopping by, wondering if you are still around, hope all is well.;)
- 12:04 pm
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text: "The inspiration for the illustrated arch to the children's section came from the beloved children's book The Secret Garden with a focus less on illustrating any specific children, rather to decorate and embellish the entrance with beauty found in nature; plants, trees, flowers, animals and birds. I also wanted to include the door to the garden open, with the key in the lock, and a stack of favorite books on a tree stump inviting all to enter and partake in the joy of reading and imagination."Lisa Mandle


text:
Published: November 4, 2012 Burnham-On-Sea club's float impresses crowds at Bridgwater Carnival
Burnham-On-Sea's carnival club got off to a great start at Saturday's Bridgwater Carnival, coming second in their class.
Hillview Carnival Club's entry, called Hollywood Hotel, impressed the judges and 100,000 strong crowd at the first event on the Guy Fawkes carnival circuit.
The float - which is 100ft long cart and has cost over £10,000 to build - came second in its category behind Marina Sydenham's entry, Clown Town.
The team at Hillview worked around the clock to get the entry finished in time and said they were pleased with the Bridgwater result.
The next carnival will be Weston this Friday night. The cart will come home to the Highbridge and Burnham Carnival on Monday, November 12th.
Hillview's Holywood Hotel float is pictured at Saturday's Bridgwater Carnival (courtesy of Al Crook)
Photo gallery Hundreds of photos from events across the Burnham-On-Sea area. Click here


text:
My Recent Searches
- No Recent Search.
My Tests Viewed
- No Test Viewed.
- Ordering Info
To view specimen requirements and codes please select your laboratory:
Not sure which laboratory serves your office? Call us 1-866-MYQUEST (1-866-697-8378)
Protein, Total, 24-Hour Urine with Creatinine
Test Code
CPT Code(s)
82570, 84156
Preferred Specimen(s)
10 mL aliquot from a well-mixed, 24-hour collection - no preservative
Minimum Volume
2 mL
Alternative Specimen(s)
Urinalysis transport tube (yellow-top, blue fill line, preservative tube)
Collection Instructions
Record total volume and duration of collection on test requisition and urine vial
Transport Container
Plastic urine container
Transport Temperature
Room temperature
Specimen Stability
Room temperature: 4 days
Refrigerated: 5 days
Frozen: 30 days
Reject Criteria
Acidified urine
Spectrophotometry (SP) • Colorimetric
Performing Laboratory
Quest Diagnostics-Seattle |
1737 Airport Way S Suite 200 |
Seattle, WA 98134-1636 |
Setup Schedule
Set up: Mon-Fri (Night shift); Report available: 3 days
Requires accurate 24-hour urine collection.
Reference Range(s)
Protein, Total, 24-Hour Urine | <150 | mg/24 h |
Protein/Creatinine Ratio | ≤84 | mg/g creat |
Creatinine, 24-Hour Urine | |
<36 Months | Not established |
3-8 Years | 0.11-0.68 g/24 h |
9-12 Years | 0.17-1.41 g/24 h |
13-17 Years | 0.29-1.87 g/24 h |
>17 Years | 0.63-2.50 g/24 h |
Clinical Significance
Proteinuria, mainly glomerular, is often a manifestation of primary renal disease although transient proteinuria may occur with fevers, thyroid disorders, and in heart disease. In the absence of renal disease, the degree of proteinuria is slight, usually amounting to less than 2 grams per day. In chronic glomerulonephritis and in the nephrotic syndrome including lipoid nephrosis and in some forms of hypertensive vascular disease, protein loss may vary from a few grams to as much as 30 g/day.
LOINC®' Code(s)
The Result and LOINC information listed below should not be used for electronic interface maintenance with Quest Diagnostics. Please contact the Quest Diagnostics Connectivity Help Desk for more information at 800-697-9302.NOTE: The codes listed in the table below are not orderable Test Codes.
Result Code | Result Name | LOINC Code | Component Name |
25025500 | URINE CREATININE (MG/DL) | 20624-3 | Creatinine |
25025900 | CREATININE, 24 HOUR URINE | 2162-6 | Creatinine |
50053700 | PROTEIN, TOTAL (MG/DL) | 21482-5 | Protein |
50054550 | PROTEIN/CREATININE RATIO | 13801-6 | Protein/Creatinine |
50054600 | PROTEIN, TOTAL, 24 HR UR | 2889-4 | Protein |
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.
LOINC assignment is based on a combination of test attributes, including the method used by the performing laboratory. For tests not performed by Quest Diagnostics, codes are assigned by the performing laboratory.
* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.


text:
Key things you need to know aboutDr. Luce:
Dr. Luce's Experience
Research training, expertise and qualifications
Dr. Luce's Care Philosophy
Dr. Luce's Specialties
- Obstetrics & Gynecology
- View 1 specialty and 1 board certification
Procedures Dr. Luce Performs
- Colpopexy
- Colporrhaphy
- See all 26 procedures
Conditions Dr. Luce Treats
- Asymptomatic Post-Menopausal Status
- Cervical Polyps
- See all 29 conditions
More About Dr. Luce's Background
Hospital Quality
The right hospital is as important as the right doctor
- Spectrum Health Medical Center - Butterworth Hospital
- 100 Michigan Street North East
- Grand Rapids, MI 49503
9 Facts About Hospital Quality
Patients' risk of dying during a hospital stay for heart bypass surgery could be 85.2% lower, on average, at a hospital rated 5 stars compared to a hospital rated 1 star for that procedure. Choosing the right hospital is critical to your health. View Slideshow
Patient Satisfaction
Patients' feedback on their experience with Dr. Luce
Likelihood of recommending Dr. Luce to family and friends is 5 out of 5
See More Survey Results
8 Facts About Patient Satisfaction Surveys
Patient satisfaction surveys provide a standardized way of reporting about healthcare experiences. But there can be more than meets the eye when reviewing scores. Here's what you should know
Appointments & Offices
Check insurance plans, locations and make an appointment
Accepting new patients?
- Yes
- Grand Rapids Women's Health
- Female Pelvic Medicine & Urogynecology
- 555 Midtowne St NE Ste 450
- Grand Rapids, MI 49503
- Grand Rapids Women's Health
- Grand Rapids Women's Health
- 555 Midtowne St NE Ste 400
- Grand Rapids, MI 49503
7 Tips to Prepare for Your Appointment
The key to a successful appointment is communication. To get the most out of your visit, prepare ahead of time so you can lead the conversation with your doctor. These 7 tips will get you ready


text:
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[33] But seek first God's Kingdom, and his righteousness; and all these things will be given to you as well.
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text:
Pan-Fried Brook Trout with Sage Butter
Yield: 2 servings
Community Recipe from
- 2 whole(s) trout-cleaned & de-boned;Skin left on;head & tail may be removed
- 1 stick(s) butter-softened
- 1/4 cup(s) all-purpose flour
- 8 piece(s) fresh sage leaves-minced
- 8 piece(s) fresh sage leaves-whole
- 1/4 teaspoon(s) salt
- 1/4 teaspoon(s) ground black pepper
- Combine flour with salt & pepper.
- Combine softened butter with minced sage. Place in a small plastic container and refrigerate.
- Rinse the fish under cold water and pat dry. Cut a few diagonal slashes along each side of the fish. Dredge fish in seasoned flour until coated.
- Heat 2 Tbs butter in a large heavy frying pan until it begins to bubble. Insert the whole sage leaves in the cavity of the fish and cook for about 5 minutes per side or until golden.
- Place a pat of the prepared sage butter on each fish and garnish with slices of lemon and parsley.
September 2012
This recipe is a personal recipe added by martcantor and has not been tested or endorsed by MyRecipes.
Pan-Fried Brook Trout with Sage Butter Recipe at a Glance
- COURSE: Main Dishes
- CUISINE: American
- MAIN INGREDIENT: Fish
- COOKING METHOD: Fry
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text:
Flashback [SS Remix]
Credits & Info
- Date
- 02/23/2013
- File Info
- Song
- 4 min 59 sec
- Score
- 4.71 / 5.00
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Licensing Terms
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- You must give credit to the artist.
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- You may not use this work for commercial purposes unless you make specific arrangements with the artist.
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- If you alter, transform, or build upon this image, you may distribute the resulting creation only under a license identical to this one.
- Score:
- Rated 4.71 / 5 stars
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- 846 Plays | 81 Downloads
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- Genres:
- Electronic - House
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Author Comments
HEY EVERYBODY! I'm back here on Newgrounds. Hoping to try and catch some new fans around here, I've been doing so much producing lately and just haven't been posting much.
So here is my latest remix, if you like it, there are 15 other songs available for free download! Message me if you are interested and I can send you the link to download it for free.
Hope you guys enjoy this track, I had a lot of fun making it!
Please vote, comment, and if you're interested in 14 other remixes from me, be sure to message so I can send you the link!
Rated 5 / 5 stars
I LOVE this! Amazing job dude ;D
Thanks so much! Make sure to check out the rest of the remixes! :)


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VANCOUVER (CUP) � A UBC activist group is taking their campaign to end animal experimentation national. STOP UBC Animal Research (STOP), an animal rights group that started at the University of British Columbia's Vancouver campus, has begun working with other groups with similar goals at institutions across Canada. --
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Local News
The Josties to perform three free concerts in March
March 6, 2014SHERIDAN — The Josties, a family from Southern Alberta, Canada, will perform three free concerts March 14-16. Parents Dale and Lisa Jost along with their 11 children perform a mix of religious, acoustic country, folk and light contemporary music. The free concert is sponsored by the Pastors United in Christ but donations will be accepted. Read More
Joint horticultural conference being held March 13-15
SHERIDAN — The Wyoming Farmers Marketing Association and the Wyoming Master Gardeners will host a 2014 joint horticultural conference March 13-15. The conference is open to all and will offer a variety of activities including conference sessions, workshops, Market Manager and Master Gardener training and a two-day seed swap along with dinners and awards. Certain Read More
Whitney board fears SCSD2 trying to influence members
SHERIDAN — Members of the Whitney Benefits board fear Sheridan County School District 2 may be trying to influence the individuals the district appoints to the foundation. The Whitney Benefits board consists of 13 members who serve four-year terms and are appointed by the boards of trustees of the three county school districts — one Read More
Rawlings winner of Good Citizen award
SHERIDAN — Sarah Rawlings, a senior at Tongue River High School, was the recipient of the Sheridan Chapter Daughters of the American Revolution Good Citizen Contest award. Contestants of the contest were required to write an essay on being an American citizen. Academic performance, community service and leadership were considered in the selection of the Read More
SC women's team hosts soccer camp at YMCA
SHERIDAN — The Sheridan College women's soccer team just finished up a four week clinic with the YMCA. "The clinic was a great start to prepare these kids for their upcoming seasons this spring," SC coach Stefan Skillman said. "We had over 50 kids participate ranging from fifth through eighth grade." Each week the players Read More
SC signs Montana hitter to Lady Generals volleyball team
SHERIDAN — The Sheridan College volleyball coaching staff has announced that three-time state champion Courtney Smith from Ballantine, Mont., officially signed her National Letter of Intent to join the Lady Generals next fall. Smith is a 5-foot, 9-inch middle hitter who can be used anywhere across the net. "I am very excited to add Courtney Read More
Fuel up — gas prices lower than national average
SHERIDAN — Sheridan motorists running low on gas can take advantage of low gas prices this week. Sheridan gasoline stations are pricing unleaded gas at $3.26- $3.29 per gallon, which is lower than both the state and national average. According to gasbuddy.com, the statewide average price per gasoline in Wyoming is $3.31, while nationally, the Read More
Ash Wednesday
March 5, 2014Nicole Dillon has an ash cross marked on her forehead during the children's service on Ash Wednesday at Holy Name Catholic Church. Ash Wednesday marks the first day of Lent.
Woman gets split sentence for role in meth making
SHERIDAN — A Sheridan woman was released from the Sheridan County Detention Facility after approximately six and a half months after she pleaded guilty in 4th Judicial District Court to possessing equipment for the purpose of operating an unlawful clandestine methamphetamine laboratory. Michele Mangan, 51, was sentenced by Judge John Fenn Tuesday morning and was Read More
County votes against permit to avoid lawsuit
SHERIDAN – Keeping the peace prevailed in a 4-0 decision by County Commissioners on Tuesday against granting a conditional use permit for a Ranchester resident to build an accessory building for his cabinetry business. Bradley Wieser applied for a CUP to build a 1,500-square-foot, single-story shop next to his house in the Spirit Ridge Subdivision Read More
Man caught with pot in daydream film
SHERIDAN — A Sheridan man was cited by police at Centennial Theatre on East Alger Street Tuesday evening for being in possession of a small amount of marijuana. Darren Zimmerman, 21, admitted to having the drug on him after a fellow movie patron complained to management about the smell. Sheridan Police Sgt. Travis Koltiska said Read More
Ranchester annexes town's water, sewer facilities
RANCHESTER — Ranchester Town Council voted 4-0 to annex two separate properties that contain the town's water tank and sewer lagoon at its meeting Tuesday. The properties are owned by Ranchester but are noncontiguous to town limits. However, state statutes do allow noncontiguous property owned by a town to be annexed. Usually, annexations must be Read More
Programmers Guild research may help high school, college students
SHERIDAN — The Sheridan Programmers Guild has received funding to help them conduct research into the use of technology in remedial math education and create Web apps to encourage higher success rates among high school and college students who must take remedial courses. The Sheridan Programmers Guild received a $5,000 Phase 0 Wyoming Small Business Read More
Municipal court Febuary
From staff reports Violators under 18 and sentences under $100 and five days in jail are not reported. (Year in parentheses is defendant's birth year.) Feb. 3 • Ryan P. Perry, (1987), Sheridan, contempt of court — indirect, $100 • Michelle C. Beardman, (1989), Buffalo, failure to maintain liability insurance, $220 • Sienna E. Read More
Trail End Guilds to meet Tuesday
SHERIDAN — The Trail End Guilds will meet Tuesday. The meeting will commence at 7 p.m. at the Trail End State Historic Site. TEG sponsors at least one major event each year, the Holiday Open House during the first weekend of December. Membership dues start at $5 a year and meetings are typically held monthly Read More
Richards to take part in Alternative Spring Break
SHERIDAN — April Richards of Sheridan is one of more than 120 students from Cornell College in Iowa taking part in the college's 10th annual Alternative Spring Break. During the 10 day break, Richards will travel to Jacksonville, Tenn., on a service trip. Student groups will travel to 10 different locations and learn about topics Read More
Next Plus 50 Encore class to be held Tuesday at Main Street campus
SHERIDAN — The next Plus 50 Encore Class in the "Managing the Generational Difference" series will be held Tuesday. This series of free classes is offered to members of the community age 50 and older at the Sheridan College Main Street campus. The topic of this month's class is writing attention-grabbing resumes. The class will Read More
Crews respond to airport for potential crash; plane lands without incident
From staff reports SHERIDAN — Great Lakes Airlines called in an emergency situation to Sheridan County Airport yesterday around 2 p.m. An inbound flight carrying 18 passengers reported that their flaps were not working and requested coverage while landing in case something went wrong. The flaps of the airplane are part of the control Read More
Barron's names Dewald top advisor in Wyo.
March 4, 2014SHERIDAN — Edward Jones financial advisor Doug Dewald of Sheridan has been named the No. 1 financial advisor in Wyoming by Barron's magazine in its 2014 rankings of "top financial advisors, state-by-state." The top 1,200 financial advisors are recognized throughout the U.S. "The Barron's ranking is a widely respected list of the nation's pre-eminent financial Read More
City: Tough winter calls for new snow blower
SHERIDAN — Within a couple weeks, snow removal around the city will be able to move approximately three times faster when city streets crews begin to use a new loader mounted snow blower approved for purchase by Sheridan City Council at its meeting Monday. By a vote of 5-0, the Council approved the public works Read More
Tongue River High School to present 'Tangled' tonight
SHERIDAN — The Tongue River High School theater department will present "A Dinner Theater Event: Tangled" tonight. "Tangled," the Disney story staring Rapunzel, will be adapted and performed by TRHS students in the school auditorium. The play will be presented for free to the entire community at 7 p.m. Prior to the performance a fundraiser Read More
Sheridan College to host 'Alhazen's Carnival' this spring
SHERIDAN — The Sheridan College art department has curated an exhibit featuring artwork in digital media and video that will be displayed throughout the spring semester. "Alhazen's Carnival" will feature the work of seven artists displayed on both four-screen video monitors in the Edward A. Whitney Academic Center on a rolling loop. The display is Read More
Wear blue Friday for colon cancer awareness
SHERIDAN — March is colon cancer awareness month and Friday is National Wear Blue day. The Wyoming Cancer Resource Services office reminds everyone to wear blue for yourself, family and survivors of colon cancer. Colon cancer is a preventable, treatable and beatable disease which almost 250 Wyoming men and women are diagnosed with every year. Read More
Archaeological Society to meet Thurs. at the Holiday Inn
SHERIDAN — The Sheridan-Johnson County chapter of the Wyoming Archaeological Society will meet Thursday in the Le Gourmet Room of Holiday Inn. All members of the community are invited to this free event. At 6 p.m. attendees may order dinner off the menu, but no purchase is required to attend. Following dinner at approximately 7:15 Read More
A different grind
Dave Gundersen, left, watches as Mark Constable of England shows him a billet that the group will be making. A billet is a stack of metals — in this particular workshop, a stack of non-iron metals that are used in decorations and jewelry. Constable was one of the main demonstrators during the weekend forge-in.


text:
THE SQL Server Blog Spot on the Web
A new date is available for the PowerPivot workshop I and Marco are delivering all over Europe.
On September 19-20, 2011 we will be in Lisbon (Portugal) to present the workshop to Excel users and BI professionals.
Moreover, as Denali CTP3 of PowerPivot is now disclosed, we will present, for the first time, an enhanced version of the workshop with a new set of slides and demos aimed to understand what's new in Denali for all the PowerPivot users.
In the meantime, we are organizing a community event on the evening of the 19th, where we are going to speak about the roadmap from UDM to BISM and how to shape your data and skills for the incoming version of Analysis Services. We will publish all the details of the event as soon as we will know them.
You can find more information and the registration page at www.powerpivotworkshop.com.
I know from personal experience that Lisbon is a wonderful city and the food is simply great. Moreover, I have been assured that the weather will be nice too in that period. Thus, I look forward to see many of you at the workshop and at the community event, even from outside of Portugal!
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What Tight End on the Chiefs Current Roster Will Fans Be Raving About Come the End of the Season?
By: William Bruno Not too long ago, if you were to listen to Mitch Holthus on The Kansas City Chiefs broadcast you would hear him yell "TOUCHDOWN, Kansas City Chiefs" which was quite often followed by, "TOUCHDOWN, Tony Gonzalez!!!" Since those days ...After Charles, Who Will Stand Out On Offense In 2014?
By: Nathan Shellstein Anyone who followed the Kansas City Chiefs last year understood that Jamaal Charles was the bulk of the offense. He figures to be a huge part again in 2014, but the team is hoping for a bit more help. Here is a look at the 3 be ...
By Darin Gantt
The guy Chip Kelly replaced as the coach of the Eagles might have helped cost him the guy he wanted most in this draft. According to Peter King of Sports Illustrated, a conversation between Titans coach Ken Whisenhunt and Chiefs coach Andy Reid last week helped convince Whisenhunt to hold onto the second pick in…
Read more…
PAC 12 and ACC top all conferences with 9 first round picks
First time SEC hasn't led since 2010 they had 7
6 receivers in the First round Cooper, White, Parker, Agholor, Perriman and Dorset
So much for no first round RB Todd Hurley and Melvin Gordon
No TE picked
3 corners Trae Waynes, Kevin Johnson, Marcus Peters and Byron Jones
1 Safety Damarious Randall
4 OLB Dante Fowler, Vic Beasley, Bud Dupree and Shaw Thompson
1 ILB Stephone Anthony
1 NT Danny Shelton
2 DT Malcolm Brown and Erik Farmstead
2 DE Leonard Williams and Shane Ray
3 OG Brandon Scherff, Ereck Flowers and Laken Tomlinson
3 OT Andrus Peat, Cedric Read more…
DE Randy Gregory
S Landon Collins
OT T.J. Clemmings
CB Jalen Collins
DT Eddie Goldman
WR Dorial Green Beckham
OG La'el Collins
LB Eli Harold
OT Jake Fisher
CB Eric Rowe
WR Jalen Strong
DE Preston Smith
DE Owamagbe Odighizuwa
WR Devin Smith
TE Maxx Williams
LB Eric Kendricks
DT Jordan Phillips
DT Michael Bennett
QB Brett Hundley
CB Ronald Darby
WR/TE Devin Funchess
CB P.J. Williams
The biggest names on Guard that stick out at me are
A.J. Gann
Ali Marpet
Tre' Jackson
John Miller
Arie Kouandjio
Jeremiah Poutasi
Mitch Morse
Josue Matias
Jamil Douglas
OT Remaining
Jake Fisher
La'el Collins
Ty Sambrailo
Rob Havenstein
Sean Hickey
Centers Remaining
Hroniss Grasu
B.J. Finney
Reece Dismukes
WR Remaining
Jaelen Strong
Devin Smith
Rashad Greene
Sammie Coates
Tyler Lockett
Chris Conley
Justin Hardy
Stefon Diggs
Tony Lippett
Ty Montgomery Read more…
The Kansas City Chiefs have added perhaps the most talented defensive back in this year's draft. At No. 18 overall, the Chiefs drafted Marcus Peters, a cornerback from Washington. There's no doubt that Peters has the ability to play in the NFL, but there are doubts about whether he has the makeup to coexist with…
Read more…
By brdempsey69
Since nobody has started the official draft day thread, as of yet, I'll do it here.
Post your responses to the draft as it transpires here.
With 10 picks, this is a great opportunity for Dorsey/Reid to bring a stable of good football players to the Chiefs team. Let's get it done.
Go over here to follow the draft live if you wish:
Read more…
Had a dream last night I was checking Twitter and saw that the Chiefs drafted Phillip Dorset in the first. ???? I am not a huge fan of this pick lol but it is what it is. The name of our second round pick is no one I have ever heard of so Ill assume he doesn't exist. Lol. But here's to hoping this particular dream of mine does not come true. Read more…
Arrowhead Pride says Chiefs like Darby Read more…
By brdempsey69
Just saw a report by Peter King that "the Chiefs love DeVante Parker". It's not out of the realm that if he falls far enough that the Chiefs trade up to take him. He fits Andy Reid's Offense perfectly. It may depend on what Minnesota does at #11, assuming Parker is still on the board. If the Vikes pass on Parker & the Chiefs can move up for a reasonable cost — say to #12 in a trade with Cleveland –, then I don't believe anybody could rightfully complain.
Of course, the best case scenario is to have Parker fall right Read more…
- For new Kansas City Chiefs CB Marcus Peters, trick is learning how and when to ... - FOXSports.com
- Jamell Fleming a near-lock for Kansas City Chiefs roster - Tulsa World
- There's a wide range of opinions on Chiefs - ESPN (blog)
- Breaking Down Kansas City Chiefs Roster After the 2015 NFL Draft - Bleacher Report
- Kansas City Chiefs release QB Terrelle Pryor - NFL.com
- Chiefs' 2015 draft class: Video highlights, grades, best picks - ESPN
- NFL RUMORS: Kansas City Chiefs, Mychal Kendricks Trade With Eagles Eyed ... - Headlines & Global News


text:
Systematic (IUPAC) name | |
(2α,4α,5β,7β,10β,13α)-4,10-Bis(acetyloxy)-13-{[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate | |
Clinical data | |
Trade names | Abraxane, Taxol |
AHFS/Drugs.com | monograph |
Pharmacokinetic data | |
Bioavailability | 6.5% (oral)[1] |
Protein binding | 89 to 98% |
Metabolism | Hepatic (CYP2C8 and CYP3A4) |
Half-life | 5.8 hours |
Excretion | Fecal and urinary |
Identifiers | |
33069-62-4 | |
L01CD01 L01CD03 (paclitaxel poliglumex) |
PubChem | CID 36314 |
IUPHAR ligand | 2770 |
DrugBank | DB01229 |
ChemSpider | 10368587 |
ChEBI | CHEBI:45863 |
ChEMBL | CHEMBL428647 |
PDB ligand ID | TA1 (PDBe, RCSB PDB) |
Chemical data | |
Formula | C47H51NO14 |
853.906 g/mol | |
(what is this?) (verify) |
Paclitaxel is a medication used to treat a number of types of cancer including: ovarian cancer, breast cancer, lung cancer and pancreatic cancer among others.[2] It and docetaxel represent the taxane family of drugs. Paclitaxel's mechanism of action involves interference with the normal breakdown of microtubules during cell division.
Common side effects include: hair loss, muscle and joint pains, and diarrhea, among others.[2] It results in a greater risk of infections which can be potentially serious.[2] Use during pregnancy often results in problems in the infant.[2]
Paclitaxel was discovered in 1962[3] as a result of a U.S. National Cancer Institute-funded screening program; being isolated from the bark of the Pacific yew, Taxus brevifolia, thus its name "taxol". Developed commercially by Bristol-Myers Squibb, the generic name has changed to "paclitaxel" with a trademark becoming Taxol. Other trademarks include Abraxane. Clinicians sometimes use the abbreviation "PTX" for paclitaxel, which is discouraged, because it is not a unique identifier.
Paclitaxel is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[4] There was initially concern over the environmental impact of its initial sourcing from the slow growing Pacific yew. In addition, both the assignment of rights to Bristol-Myers Squibb and the product name were subject to public debate and Congressional hearings.
Medical use[edit]
Paclitaxel is approved in the UK for ovarian, breast and lung, bladder, prostate, melanoma, esophageal, and other types of solid tumor cancers as well as Kaposi's sarcoma.[5] It is recommended in NICE guidance of June 2001 that it should be used for nonsmall cell lung cancer in patients unsuitable for curative treatment, and in first-line and second-line treatment of ovarian cancer. In September 2001, NICE recommended paclitaxel should be available for the treatment of advanced breast cancer after the failure of anthracyclic chemotherapy, but that its first-line use should be limited to clinical trials. In September 2006, NICE recommended paclitaxel should not be used in the adjuvant treatment of early node-positive breast cancer.[6] In 2005, its use in the United States for the treatment of breast, pancreatic, and non-small cell lung cancers was approved by the FDA.[7]
Similar compounds[edit]
Albumin-bound paclitaxel (trade name Abraxane, also called nab-paclitaxel) is an alternative formulation where paclitaxel is bound to albumin nano-particles. Much of the clinical toxicity of paclitaxel is associated with the solvent Cremophor EL in which it is dissolved for delivery.[8] Abraxis BioScience developed Abraxane, in which paclitaxel is bonded to albumin as an alternative delivery agent to the often toxic solvent delivery method. This was approved by the U.S. Food and Drug Administration in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy.[9]
Synthetic approaches to paclitaxel production led to the development of docetaxel. Docetaxel has a similar set of clinical uses to paclitaxel and is marketed under the name of Taxotere.
Recently the presence of taxanes including paclitaxel, 10-deacetylbaccatin III, baccatin III, paclitaxel C, and 7-epipaclitaxel in the shells and leaves of hazel plants has been reported.[10] The finding of these compounds in shells, which are considered discarded material and are mass-produced by many food industries, is of interest for the future availability of paclitaxel.
Paclitaxel is used as an antiproliferative agent for the prevention of restenosis (recurrent narrowing) of coronary and peripheral stents; locally delivered to the wall of the artery, a paclitaxel coating limits the growth of neointima (scar tissue) within stents.[11] Paclitaxel drug eluting coated stents for coronary artery placement are sold under the trade name Taxus by Boston Scientific in the United States. Paclitaxel drug eluting coated stents for femoropopliteal artery placement are sold under the trade name Zilver PTX by Cook Medical, Inc.
Side effects[edit]
Common side effects include nausea and vomiting, loss of appetite, change in taste, thinned or brittle hair, pain in the joints of the arms or legs lasting two to three days, changes in the color of the nails, and tingling in the hands or toes. More serious side effects such as unusual bruising or bleeding, pain/redness/swelling at the injection site, Hand-foot syndrome, change in normal bowel habits for more than two days, fever, chills, cough, sore throat, difficulty swallowing, dizziness, shortness of breath, severe exhaustion, skin rash, facial flushing, female infertility by ovarian damage[12] and chest pain can also occur. A number of these side effects are associated with the excipient used, Cremophor EL, a polyoxyethylated castor oil. Allergies to drugs such as cyclosporine, teniposide and drugs containing polyoxyethylated castor oil may indicate increased risk of adverse reactions to paclitaxel.[13] Dexamethasone is given prior to beginning paclitaxel treatment to mitigate some of the side effects.[citation needed] Leuprolide, a GnRH analog may prevent ovarian damage, according to mice studies.[12]
Mechanism of action[edit]
Paclitaxel is one of several cytoskeletal drugs that target tubulin. Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin-targeting drugs such as colchicine that inhibit microtubule assembly, paclitaxel stabilizes the microtubule polymer and protects it from disassembly. Chromosomes are thus unable to achieve a metaphase spindle configuration. This blocks progression of mitosis, and prolonged activation of the mitotic checkpoint triggers apoptosis or reversion to the G-phase of the cell cycle without cell division.[14][15]
The ability of paclitaxel to inhibit spindle function is generally attributed to its suppression of microtubule dynamics,[16] but recent studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher therapeutic concentrations, paclitaxel appears to suppress microtubule detachment from centrosomes, a process normally activated during mitosis.[17] Paclitaxel binds to beta-tubulin subunits of microtubules.[18]
Research use[edit]
Aside from its direct clinical use, paclitaxel is used extensively in biological and biomedical research as a microtubule stabilizer. In general, in vitro assays 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 is sometimes used for in vivo studies as well; it can be fed to test organisms, such as 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 mouse in vivo[19] and inhibits hPAD2 in vitro though its methyl ester side chain did not.[20] Angiotech Pharmaceuticals Inc. began phase II clinical trials in 1999[21] as a multiple sclerosis treatment but in 2002, reported that the results showed no statistical significance.[22]
This section relies largely or entirely upon a single source. (June 2014) |
This section is outdated. (June 2014) |
In recent years, extensive research has been done to find a way to mitigate the side effects of paclitaxel, by altering its administration. DHA-paclitaxel, PG-paclitaxel, and tumor-activated taxol prodrugs are undergoing continued testing, and are actually on the way to being introduced into widespread clinical use.
Protarga has linked paclitaxel to docosahexaenoic acid (DHA), a fatty acid easily taken up by tumor cells; the DHA-paclitaxel "appears not to be cytotoxic until the bond with DHA is cleaved within the cell."[23] The advantage of DHA-paclitaxel over paclitaxel is DHA-paclitaxel's ability to carry much higher concentrations of paclitaxel to the cells, which are maintained for longer periods in the tumor cells, thus increasing their action. With increased activity, DHA-paclitaxel, also known as Taxoprexin, may have a more successful response in cancer patients than paclitaxel, and it may be able to treat more types of cancer than paclitaxel has been able to treat.
Cell Therapeutics has formulated PG-paclitaxel, which is paclitaxel bonded to a polyglutamate polymer; tumor cells are significantly more porous to polyglutamate polymers than normal cells, due to the leaky endothelial membranes of tumor cells. PG-paclitaxel has been introduced into clinical use, and has proven to initiate very mild side effects and to effectively treat many patients who were not responsive to the action of Taxol. The PG-paclitaxel may be a very promising anticancer drug, as it is much more selective than paclitaxel for which cells it targets.[23]
ImmunoGen has been introducing tumor-activated prodrug (TAP) technology in recent years, and is now working to apply this technology to paclitaxel. Tumor-activated paclitaxel prodrugs are designed for accurate targeting, by the action of a monoclonal antibody that is very specific to certain cells. Tumor-activated Taxol prodrugs research is progressing, and, in mice, the "taxane-based TAP completely eradicated human tumour xenografts at non-toxic doses."[23]
ANG1005 is made up of one molecule of a peptide called angiopep-2 joined with three molecules of paclitaxel. It is in phase I clinical trials for some types of cancer.[citation needed]
This section needs additional citations for verification. (June 2014) |
This article or section appears to contradict itself about endophyte production of taxol (compare to lede). (June 2014) |
From 1967 to 1993, almost all paclitaxel produced was derived from bark from the Pacific yew, the harvesting of which kills the tree in the process.[citation needed] The processes used were descendants of the original isolation method of Wall and Wani;[who?] by 1987, the NCI had contracted Hauser Chemical Research of Boulder, Colorado, to handle bark on the scale needed for Phase II and III trials.[citation needed] While both the size of the wild population of Taxus brevifola and the magnitude of the eventual demand for taxol were uncertain, it was clear for many years[vague] that an alternative, sustainable source of supply of the natural product would be needed. Initial attempts to broaden its sourcing used needles from the tree, or material from other related Taxus species, including cultivated ones,[citation needed] but these attempts were challenged by the relatively low and often highly variable yields obtained. Early in the 1990s, coincident with increased sensitivity to the ecology of the forests of the Pacific Northwest, taxol was successfully extracted on a clinically useful scale from these sources.[24]
Concurrently, synthetic chemists in the US and France had been interested in taxol, beginning in the late 1970s.[citation needed] As noted, by 1992 extensive efforts were underway to accomplish the total synthesis of paclitaxel, efforts motivated by the desire to generate new chemical understanding rather than to achieve practical commercial production. In contrast, the French group of Pierre Potier at the Centre national de la recherche scientifique (CNRS) addressed the matter of overall process yield, showing that it was feasible to isolate relatively large quantities of the compound 10-deacetylbaccatin from yew, Taxus baccata, which grew on the CNRS campus and whose needles were available in large quantity.[citation needed] By virtue of its structure, 10-deacetylbaccatin was seen as a viable starting material for a short semisynthesis to produce taxol. By 1988 Poitier and collaborators had published a semisynthetic route from needles of T. baccata to taxol.[25]
The view of the NCI, however, was even this route was not practical.[citation needed] The group of Robert A. Holton had also pursued a practical semisynthetic production route; by late 1989, Holton's group had developed a semisynthetic route to paclitaxel with twice the yield of the Potier process.[citation needed] Florida State University, where Holton worked, signed a deal with Bristol-Myers Squibb to license their semisynthesis and future patents.[citation needed] In 1992, Holton patented an improved process with an 80% yield, and BMS took the process in-house and started to manufacture paclitaxel in Ireland from 10-deacetylbaccatin isolated from the needles of the European yew.[citation needed] In early 1993, BMS was able to announce that it would cease reliance on Pacific yew bark by the end of 1995, effectively terminating ecological controversy over its use.[citation needed] This announcement also made good their commitment to develop an alternative supply route, made to the NCI in their CRADA application of 1989.
Currently, all paclitaxel production for BMS uses plant cell fermentation (PCF) technology developed by the Ithaca, New York biotechnology company Phyton Biotech, Inc. and carried out at their plant in Germany.[26][better source needed][neutrality is disputed] PCF uses a specific Taxus cell line propagated in aqueous medium in large fermentation tanks with the endophytic fungus Penicillium raistrickii. Paclitaxel is then extracted directly, purified by chromatography and isolated by crystallization.[citation needed] Compared to the semisynthesis, PCF eliminates the need for many hazardous chemicals and saves a considerable amount of energy.[27]
In 1993, taxol was discovered as a natural product in a newly described endophytic fungus living in the yew tree.[28] It has since been reported in a number of other endophytic fungi, including Nodulisporium sylviforme,[29] Alternaria taxi, Cladosporium cladosporioides MD2, Metarhizium anisopliae, Aspergillus candidus MD3, Mucor rouxianus sp., Chaetomella raphigera, Phyllosticta tabernaemontanae, Phomopsis, Pestalotiopsis pauciseta, Phyllosticta citricarpa, Podocarpus,Fusarium solani, Pestalotiopsis terminaliae, Pestalotiopsis breviseta, Botryodiplodia theobromae Pat., Gliocladium sp., Alternaria alternata var. monosporus, Cladosporium cladosporioides, Nigrospora sp., Pestalotiopsis versicolor, and Taxomyces andreanae. However, there has been contradictory evidence for its production by endophytes, with other studies finding independent production is unlikely.[30][31]
The core synthetic route is via a terpenoid pathway, parts of which having been successfully transplanted into production strains of E.coli[32] and yeast.[33]
By 1992, at least thirty academic research teams globally were working to achieve a total synthesis of this natural product, with the synthesis proceeding from simple natural products and other readily available starting materials.[34] This total synthesis effort was motivated primarily by the desire to generate new chemical understanding, rather than with an expectation of the practical commercial production of paclitaxel. The first laboratories to complete the total synthesis from much less complex starting materials were the research groups of Robert A. Holton, who had the first article to be accepted for publication, and of K. C. Nicolaou who had the first article to appear in print (by a week, on 7 February 1994). Though the Holton submission preceded the Nicolaou by a month (21 December 1993 versus 24 January 1994),[35] the near coincidence of the publications arising from each of these massive, multiyear efforts—11-18 authors appearing on each of the February 1994 publications—has led the ending of the race to be termed a "tie"[36] or a "photo finish",[34] though each group has argued that their synthetic strategy and tactics were superior.[36]
As of 2007,[dated info] five additional research groups have joined the initial two in successful total syntheses: Wender et al. in 1997, and Kuwajima et al. and Mukaiyama et al. in 1998 with further linear syntheses, and Danishefsky et al. in 1996 and Takahashi et al. in 2006 with further convergent syntheses. All strategies aim to prepare a 10-Deacetylbaccatin-type core containing the ABCD ring system, followed generally by last stage addition of the "tail" to the 13-hydroxyl group.[34]
While the "political climate surrounding taxol and Taxus brevifolia in the early 1990s… helped bolster [a] link between total synthesis and the [taxol] supply problem", and though total synthesis activities were a requisite to explore the structure-activity relationships of taxol via generation of analogs for testing, the total synthesis efforts were never seen "as a serious commercial route" to provide significant quantities of the natural product for medical testing or therapeutic use.[37]
Paclitaxel was discovered as a part of a U.S. National Cancer Institute screening program, by Monroe E. Wall and Mansukh C. Wani at the Research Triangle Institute, Research Triangle Park, North Carolina, in 1967.[38] These scientists isolated the natural product from the bark of the Pacific yew tree, Taxus brevifolia, determined its structure and named it "taxol", and arranged for its first biological testing.[citation needed] The compound was then developed commercially by Bristol-Myers Squibb (BMS), who had the generic name assigned as "paclitaxel".[citation needed]
Plant screening program[edit]
In 1955, the National Cancer Institute (NCI) in the United States set up the Cancer Chemotherapy National Service Center (CCNSC) to act as a public screening center for anticancer activity in compounds submitted by external institutions and companies.[39] Although the majority of compounds screened were of synthetic origin, one chemist, Jonathan Hartwell, who was employed there from 1958 onwards, had had experience with natural product derived compounds, and began a plant screening operation.[40] After some years of informal arrangements, in July 1960, the NCI commissioned USDA botanists to collect samples from about 1000 plant species per year.[41] On 21 August 1962, one of those botanists, Arthur S. Barclay, collected bark from a single Pacific yew tree, Taxus brevifolia, in a forest north of the town of Packwood, Washington as part of a four-month trip to collect material from over 200 different species.[42] The material was then processed by a number of specialist CCNSC subcontractors, and one of the Taxus samples was found to be cytotoxic in a cellular assay on 22 May 1964.[42]
Accordingly, in late 1964 or early 1965, the fractionation and isolation laboratory run by Monroe E. Wall in Research Triangle Park, North Carolina, began work on fresh Taxus samples, isolating the active ingredient in September 1966 and announcing their findings at an April 1967 American Chemical Society meeting in Miami Beach.[43] They named the pure compound taxol in June 1967.[42] Wall and his colleague Wani published their results, including the chemical structure, in 1971.[44]
The NCI continued to commission work to collect more Taxus bark and to isolate increasing quantities of taxol. By 1969, 28 kg of crude extract had been isolated from almost 1,200 kg of bark, although this ultimately yielded only 10g of pure material,[45] but for several years, no use was made of the compound by the NCI. In 1975, it was shown to be active in another in vitro system; two years later, a new department head reviewed the data and finally recommended taxol be moved on to the next stage in the discovery process.[46] This required increasing quantities of purified taxol, up to 600 g, and in 1977 a further request for 7,000 lbs of bark was made.
In 1978, two NCI researchers published a report showing taxol was mildly effective in leukaemic mice.[47] In November 1978, taxol was shown to be effective in xenograft studies.[48] Meanwhile, taxol began to be well known in the cell biology, as well as the cancer community, with a publication in early 1979 by Susan B. Horwitz, a molecular pharmacologist at Albert Einstein College of Medicine, showing taxol had a previously unknown mechanism of action involving the stabilization of microtubules. Together with formulation problems, this increased interest from researchers meant that, by 1980, the NCI envisaged needing to collect 20,000 lbs of bark.[49] Animal toxicology studies were complete by June 1982, and in November NCI applied for the IND necessary to begin clinical trials in humans.[49]
Early clinical trials, supply and the transfer to BMS[edit]
Phase I clinical trials began in April 1984, and the decision to start Phase II trials was made a year later.[50] These larger trials needed more bark and collection of a further 12,000 pounds was commissioned, which enabled some phase II trials to begin by the end of 1986. But by then it was recognized that the demand for taxol might be substantial and that more than 60,000 pounds of bark might be needed as a minimum. This unprecedentedly large amount brought ecological concerns about the impact on yew populations into focus for the first time, as local politicians and foresters expressed unease at the program.[51]
The first public report from a phase II trial in May 1988 showed an effect in melanoma patients and a remarkable response rate of 30% in patients with refractory ovarian cancer.[52] At this point, Gordon Cragg of the NCI's Natural Product Branch calculated the synthesis of enough taxol to treat all the ovarian cancer and melanoma cases in the US would require the destruction of 360,000 trees annually. For the first time, serious consideration was given to the problem of supply.[51] Because of the practical and, in particular, the financial scale of the program needed, the NCI decided to seek association with a pharmaceutical company, and in August 1989, it published a Cooperative Research and Development Agreement (CRADA) offering its current stock and supply from current bark stocks, and proprietary access to the data so far collected, to a company willing to commit to providing the funds to collect further raw material, isolate taxol, and fund a large proportion of clinical trials. In the words of Goodman and Welsh, authors of a substantial scholarly book on taxol, "The NCI] was thinking, not of collaboration, ... but of a hand-over of taxol (and its problems)".[51]
Although the offer was widely advertised, only four companies responded to the CRADA, including the American firm Bristol-Myers Squibb (BMS), which was selected as the partner in December 1989. The choice of BMS later became controversial and was the subject of Congressional hearings in 1991 and 1992. While it seems clear the NCI had little choice but to seek a commercial partner, there was also controversy about the terms of the deal, eventually leading to a report by the General Accounting Office in 2003, which concluded the NIH had failed to ensure value for money.[53] In related CRADAs with the USDA and Department of the Interior, Bristol-Myers Squibb was given exclusive first refusal on all Federal supplies of Taxus brevifolia. This exclusive contract lead to some criticism for giving BMS a "cancer monopoly".[54] Eighteen months after the CRADA, BMS filed a new drug application (NDA), which was given FDA approval at the very end of 1992. [51] Although there was no patent on the compound, the provisions of the Waxman-Hatch Act gave Bristol-Myers Squibb five years exclusive marketing rights.
In 1990, BMS applied to trademark the name taxol as Taxol(R). This was controversially approved in 1992. At the same time, paclitaxel replaced taxol as the generic (INN) name of the compound. Critics, including the journal Nature, argued the name taxol had been used for more than two decades and in more than 600 scientific articles and suggested the trademark should not have been awarded and the BMS should renounce its rights to it.[55] BMS argued changing the name would cause confusion among oncologists and possibly endanger the health of patients. BMS has continued to defend its rights to the name in the courts.[56] BMS has also been criticized for misrepresentation by Goodman and Walsh, who quote from a company report saying "It was not until 1971 that ... testing ... enabled the isolation of paclitaxel, initially described as 'compound 17".[57] This quote is, strictly speaking, accurate: the objection seems to be that this misleadingly neglects to explain that it was the scientist doing the isolation who named the compound taxol and it was not referred to in any other way for more than twenty years.
Annual sales peaked in 2000, reaching US$1.6 billion; paclitaxel is now available in generic form.
The nomenclature for paclitaxel is structured on a tetracyclic 17-carbon (heptadecane) skeleton. There are a total of 11 stereocenters. The active stereoisomer is (−)-paclitaxel (shown here).
(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Diacetoxy-15-{[(2R,3S)-3- (benzoylamino)-2-hydroxy-3- phenylpropanoyl]oxy}-1,9- dihydroxy-10,14,17,17-tetramethyl -11-oxo-6-oxatetracyclo [18.104.22.168~3,10~.0~4,7~] heptadec-13-en-2-yl rel-benzoate |
The cost to the NHS per patient in early breast cancer, assuming four cycles of treatment, is about £4000 (approx. $6000).[58]
A recent study suggested that caffeine may act inhibitory on paclitaxels' pro-apoptotic effect in colorectal cancer cells.[59]
Additional images[edit]
Space-filling model of paclitaxel
- ^ Peltier, Sandra; Oger, Jean-Michel; Lagarce, Frédéric; Couet, William; Benoît, Jean-Pierre (2006). "Enhanced Oral Paclitaxel Bioavailability After Administration of Paclitaxel-Loaded Lipid Nanocapsules". Pharmaceutical Research 23 (6): 1243–50. doi:10.1007/s11095-006-0022-2. PMID 16715372.
- ^ a b c d "Paclitaxel". The American Society of Health-System Pharmacists. Retrieved Jan 2, 2015.
- ^ National Cancer Institute: http://dtp.nci.nih.gov/timeline/flash/success_stories/S2_taxol.htm
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ Saville, M.W.; Lietzau, J.; Pluda, J.M.; Wilson, W.H.; Humphrey, R.W.; Feigel, E.; Steinberg, S.M.; Broder, S. et al. (1995). "Treatment of HIV-associated Kaposi's sarcoma with paclitaxel". The Lancet 346 (8966): 26–8. doi:10.1016/S0140-6736(95)92654-2. PMID 7603142.
- ^ "British National Formulary".
- ^ "Paclitaxel, Protein-Bound Suspension". Paclitaxel, Protein-Bound Suspension. Cancer.Org. January 6, 2015. Retrieved January 24, 2015.
- ^ "Cremophor EL". European Journal of Cancer 37: 1590–1598. doi:10.1016/S0959-8049(01)00171-X.
- ^ "Abraxane Drug Information." Food and Drug Administration. January 7, 2005. Retrieved on March 9, 2007.
- ^ Ottaggio, Laura; Bestoso, Federica; Armirotti, Andrea; Balbi, Alessandro; Damonte, Gianluca; Mazzei, Mauro; Sancandi, Monica; Miele, Mariangela (2008). "Taxanes from Shells and Leaves ofCorylus avellana". Journal of Natural Products 71 (1): 58–60. doi:10.1021/np0704046. PMID 18163585.
- ^ Heldman, AW; Cheng, L; Jenkins, GM; Heller, PF; Kim, DW; Ware Jr, M; Nater, C; Hruban, RH et al. (2001). "Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis". Circulation 103 (18): 2289–95. doi:10.1161/01.CIR.103.18.2289. PMID 11342479.
- ^ a b Ozcelik, Bulent; Turkyilmaz, Cagdas; Ozgun, Mahmut Tuncay; Serin, Ibrahim Serdar; Batukan, Cem; Ozdamar, Saim; Ozturk, Ahmet (2010). "Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist". Fertility and Sterility 93 (5): 1609–14. doi:10.1016/j.fertnstert.2009.02.054. PMID 19339002.
- ^ "Medline Plus Entry for Paclitaxel Injection." MEDLINE. Last Reviewed 09/01/2008. Accessed 10-2-21.
- ^ Bharadwaj, Rajnish; Yu, Hongtao (2004). "The spindle checkpoint, aneuploidy, and cancer". Oncogene 23 (11): 2016–27. doi:10.1038/sj.onc.1207374. PMID 15021889.
- ^ Brito, D. A.; Yang, Z.; Rieder, C. L. (2008). "Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied". The Journal of Cell Biology 182 (4): 623–9. doi:10.1083/jcb.200805072. PMC 2518701. PMID 18710927.
- ^ Jordan, MA; Wilson, L (2004). "Microtubules as a target for anticancer drugs". Nature reviews. Cancer 4 (4): 253–65. doi:10.1038/nrc1317. PMID 15057285.
- ^ Ganguly, A; Yang, H; Cabral, F (2010). "Paclitaxel-dependent cell lines reveal a novel drug activity". Molecular cancer therapeutics 9 (11): 2914–23. doi:10.1158/1535-7163.MCT-10-0552. PMC 2978777. PMID 20978163.
- ^ Lowe, J; Li, H; Downing, KH; Nogales, E (2001). "Refined structure of $alpha;$beta;-tubulin at 3.5 p resolution1". Journal of Molecular Biology 313 (5): 1045–57. doi:10.1006/jmbi.2001.5077. PMID 11700061.
- ^ Moscarello, MA; Mak, B; Nguyen, TA; Wood, DD; Mastronardi, F; Ludwin, SK (2002). "Paclitaxel (Taxol) attenuates clinical disease in a spontaneously demyelinating transgenic mouse and induces remyelination". Multiple sclerosis (Houndmills, Basingstoke, England) 8 (2): 130–8. doi:10.1191/1352458502ms776oa. PMID 11990870.
- ^ Musse, AA; Polverini, E; Raijmakers, R; Harauz, G (2008). "Kinetics of human peptidylarginine deiminase 2 (hPAD2)--reduction of Ca2+ dependence by phospholipids and assessment of proposed inhibition by paclitaxel side chains". Biochemistry and cell biology = Biochimie et biologie cellulaire 86 (5): 437–47. doi:10.1139/o08-124. PMID 18923545.
- ^ MS Society of Canada Phase II Clinical trial of Micellar Paclitaxel for secondary-progressive MS underway in Canada
- ^ MS Society of Canada Angiotech Halts Study of Micellar Paclitaxel stating no benefit of statistical significance seen
- ^ a b c Whelan, Jo (2002). "Targeted taxane therapy for cancer". Drug Discovery Today 7 (2): 90–2. doi:10.1016/S1359-6446(01)02149-3. PMID 11790612.
- ^ Goodman & Walsh 2001, pp. 172–5
- ^ Goodman & Walsh 2001, pp. 100–1
- ^ "Phyton news release".
- ^ "2004 Greener Synthetic Pathways Award: Bristol-Myers Squibb Company: Development of a Green Synthesis for TAXOL Manufacture via Plant Cell Fermentation and Extraction".
- ^ Stierle, A; Strobel, G; Stierle, D (1993). "Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew". Science 260 (5105): 214–6. doi:10.1126/science.8097061. PMID 8097061.
- ^ Zhao K. et al. (2004). "Study on the Preparation and Regeneration of Protoplast from Taxol-producing Fungus Nodulisporium sylviforme'" (PDF). Nature and Science 2 (2): 52–9.
- ^ Staniek, A; Woerdenbag, H; Kayser, O (2009). "Taxomyces andreanae: A Presumed Paclitaxel Producer Demystified?". Planta Med 75 (15): 1561–6. doi:10.1055/s-0029-1186181.
- ^ Heinig, U; Scholz, S; Jennewein, S (2013). "Getting to the bottom of taxol biosynthesis by fungi". Fungal Divers 60: 161–170. doi:10.1007/s13225-013-0228-7.
- ^ Boghigian, Brett A.; Myint, Melissa; Wu, Jiequn; Pfeifer, Blaine A. (2011). "Simultaneous production and partitioning of heterologous polyketide and isoprenoid natural products in an Escherichia coli two-phase bioprocess". Journal of Industrial Microbiology & Biotechnology 38 (11): 1809–1820. doi:10.1007/s10295-011-0969-9.
- ^ Engels, Benedikt; Dahm, Pia; Jennewein, Stefan (2008). "Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (Paclitaxel) production". Metabolic Engineering 10 (3–4): 201–6. doi:10.1016/j.ymben.2008.03.001. PMID 18485776.
- ^ a b c Nina Hall, 2003, Creating complexity: The beauty and logic of synthesis, Chem. Commun., 661 - 664, doi:10.1039/b212248k
- ^ See N. Hall, ibid. See also the American Chemical Society publication Chemical and Engineering News (C&EN), Feb. 21, 1994, page 32, and primary citations appearing at Holton and Nicolaou taxol total synthesis articles.
- ^ a b Flam Faye (1994). "Race to synthesize Taxol ends in a tie". Science 263 (5149): 911. doi:10.1126/science.7906053. PMID 7906053.
- ^ Jordan Goodman & Vivien Walsh, 2001, The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug, Cambridge University Press, 179-182, esp. p. 181; ISBN 9780521561235. See [books.google.com/books?isbn=052156123X], accessed 2 June 2014
- ^ ME, WALL; MC, Wani (Feb 15, 1995). "amptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture.". Cancer Res. 55 (4): 753–60. PMID 7850785.
- ^ Goodman, Jordan; Walsh, Vivien (2001). The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug. Cambridge University Press. p. 17. ISBN 0-521-56123-X.
- ^ Goodman & Walsh 2001, p. 22
- ^ Goodman & Walsh 2001, pp. 25,28
- ^ a b c Goodman & Walsh 2001, p. 51
- ^ Wall, ME; Wani, MC (1995). "Camptothecin and taxol: Discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture". Cancer Research 55 (4): 753–60. PMID 7850785.
- ^ Wani M, Taylor H, Wall M, Coggon P, McPhail A (1971). "Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia". J Am Chem Soc 93 (9): 2325–7. doi:10.1021/ja00738a045. PMID 5553076.
- ^ Goodman & Walsh 2001, p. 81
- ^ Goodman & Walsh 2001, pp. 79,81
- ^ Fuchs, David A and Johnson, Randall K (1978). "Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison". Cancer Treatment Reports 62 (8): 1219–22. PMID 688258.
- ^ Goodman & Walsh 2001, p. 95
- ^ a b Goodman & Walsh 2001, p. 97
- ^ Goodman & Walsh 2001, p. 115
- ^ a b c d Goodman & Walsh 2001, p. 120
- ^ Rowinsky, EK and others (1988). "Phase II study of taxol in advanced epithelial malignancies". Proceedings of the Association of Clinical Oncology 7: 136.
- ^ "Technology Transfer: NIH-Private Sector Partnership in the Development of Taxol" (PDF).
- ^ Nader, Ralph; Love, James. "Looting the medicine chest: how Bristol-Myers Squibb made off with the public's cancer research." The Progressive. February 1993. Retrieved on March 9, 2007.
- ^ "Names for hi-jacking". Nature 373 (6513): 370. 1995. doi:10.1038/373370a0. PMID 7830775.
- ^ Goodman & Walsh 2001, p. 170
- ^ Bristol-Myers Squibb, The development of TAXOL (paclitaxel), March 1997, as cited in Goodman & Walsh 2001, p. 2
- ^ "NICE Guidance TA108".
- ^ Mhaidat NM (Jan 2014). "Caffeine inhibits paclitaxel‑induced apoptosis in colorectal cancer cells through the upregulation of Mcl-1 levels". J Mol Med Rep 9 (1): 243–8. doi:10.3892/mmr.2013.1763. PMID 24173825.
External links[edit]
- NCI Drug Information Summary for Patients.
- NCI Drug Dictionary Definition
- Molecule of the Month: TAXOL by Neil Edwards, University of Bristol.
- A Tale of Taxol from Florida State University.
- Berenson, Alex (October 1, 2006). "Hope, at $4,200 a Dose". The New York Times. Retrieved 2007-03-31.
- U.S. National Library of Medicine: Drug Information Portal - Paclitaxel


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