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Felt this was relevant considering we've talked a lot about HIV testing and infection rates during class and in the pset.
The CDC announced the results of a survey conducted in 2009 among 10,000 individuals from major urban areas that concluded that the rate of HIV infection among intravenous drug users (IDUs) fell from 18 to 9 percent as compared to 1990s. While this appears to be solid progress in the fight against HIV, the CDC cautions that the report also indicates several negative signs as well. The study shows a significant decline in testing rates(to 49%) and knowledge of one's seropositive status( half of those infected didn't know they were infected) and a large rate of high-risk behaviors such as needle-sharing(1/3 participated), unprotected sex(the majority), and multiple sex partners.
This study comes at an interesting time in our class since it's implications forces us to think about the complexities of epidemiology, especially with such a life-long infection and in these high-risk populations. Does this report mark a step forward due to the fall in prevalence, or a lack of gain/step back due to the decrease in testing and the perpetuation of high-risk behaviors that guarantee high incidence?
http://www.reuters.com/article/2012/03/02/usa-hiv-drugs-idUSL2E8E205R20120302
-Zachary Herrera
30 Eylül 2012 Pazar
Leukemia drugs can treat ebola
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Ebola is known for its terrifyingly rapid and unstoppable death. But at the National Institute of Allergy and Infectious Diseases, Mayra Garcia's lab has shown that two leukemia drugs, notlitinib and imatinib, can slow the progression of the virus. It does this by stopping the function of the oncogene Abl (a tyrosine kinase), which is necessary for viral budding through the activity of the matrix protein VP40.
This is a really weird overlap of two very different fields! And very cool! The drug can stop rapidly replicating cells and rapidly replicating viruses, though the mechanism is somewhat different. I wonder why viral budding needs Abl? The research hasn't left cell plates yet, but it sounds promising to me. The drugs are kind of toxic, but nothing beats the toxicity of ebola... Anyhow, Its a good reminder to learn everything we can about viral processes, because apparently we can use drugs we've already developed to stop them!
Article.
-Annelise
This is a really weird overlap of two very different fields! And very cool! The drug can stop rapidly replicating cells and rapidly replicating viruses, though the mechanism is somewhat different. I wonder why viral budding needs Abl? The research hasn't left cell plates yet, but it sounds promising to me. The drugs are kind of toxic, but nothing beats the toxicity of ebola... Anyhow, Its a good reminder to learn everything we can about viral processes, because apparently we can use drugs we've already developed to stop them!
Article.
-Annelise
Potential for Long-Term Flu Vaccination
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Princeton University researchers have recently developed what could be a "universal" vaccine protecting against all influenza strains. The vaccine is designed to target the relatively unchanging parts of the virus and hamper its ability to evolve rapidly. Currently, flu vaccines target the virus' most adaptable parts.
So far, the researchers have only been able to demonstrate success on a computational model, given that no humans have received their designed vaccines. James Lloyd Smith from UCLA says, "This is the first study that looks at the population consequences of the next generation of vaccines, both in terms of epidemiological impact and evolutionary impact on the virus."
Current flu vaccine focuses on the hemagglutinin proteins protruding on the cell surface. Small mutations in this area are the cause of the rapidly evolving virus family. The universal vaccine, however, ignores the hemagglutinin area, and target more commonly conserved proteins.
Pooja
http://www.sciencedaily.com/releases/2012/02/120227111536.htm
So far, the researchers have only been able to demonstrate success on a computational model, given that no humans have received their designed vaccines. James Lloyd Smith from UCLA says, "This is the first study that looks at the population consequences of the next generation of vaccines, both in terms of epidemiological impact and evolutionary impact on the virus."
Current flu vaccine focuses on the hemagglutinin proteins protruding on the cell surface. Small mutations in this area are the cause of the rapidly evolving virus family. The universal vaccine, however, ignores the hemagglutinin area, and target more commonly conserved proteins.
Pooja
http://www.sciencedaily.com/releases/2012/02/120227111536.htm
Boceprevir approved for use by Britain's state health service.
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Merck’s new hepatitis C drug, Boceprevir (Victrelis) has won recommendation for use in Britain’s state health service. It was widely discussed especially because the drug is especially expensive. This an important drug because unlike previous INV +Ribavirin combination therapy, Boceprevir can be used in the treatment of hepatitis due to HCV genotype 1, the most common form of hepatitis C. It will be used in combination with Pegylated Interferon and Ribavirin for genotype 1 hepatitis C.
Boceprevir is an NS3/4A protease inhibitor. This drug stops viral replication by binding to a protease that would work to cleave the polyprotein. Thus this drug prevents the production of functional viral protein. Pegylated interferons are used to moderate the immune system. Ribivirin is a nucleoside analog and when given with IFN, it can reduce viral replication.
Original Article from Reuters: http://www.reuters.com/article/2012/03/09/merck-britain-idUSL5E8E8AH120120309
More info on HCV Medications:
http://emedicine.medscape.com/article/177792-medication#2
--Elena Jordan
Boceprevir is an NS3/4A protease inhibitor. This drug stops viral replication by binding to a protease that would work to cleave the polyprotein. Thus this drug prevents the production of functional viral protein. Pegylated interferons are used to moderate the immune system. Ribivirin is a nucleoside analog and when given with IFN, it can reduce viral replication.
Original Article from Reuters: http://www.reuters.com/article/2012/03/09/merck-britain-idUSL5E8E8AH120120309
More info on HCV Medications:
http://emedicine.medscape.com/article/177792-medication#2
--Elena Jordan
HIV among Black Women
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At a recent conference on retroviruses, Dr. Hodder presented a study on the prevalence of HIV among American black women. In "HPTN 064 Women's HIV Seroincidence Study (ISIS)", it was found that among a study of 2,099 adult females (88% of whom were African-American), 0.24% of participants were HIV positive; this rate is 5 times higher than the rate predicted by the CDC for the general population of African-American women.
This study is getting a high amount of press because this infection rate is comparable to developing countries known for their burgeoning HIV rate - for instance, Congo at 0.28% and Kenya at 0.53% HIV-positivity.
Although the study focused on areas known to have high HIV rates and prevalent poverty, this is still a very concerning statistic for even a subpopulation. On the whole, 66% of new HIV infections among women in the US occur among African-American women, while only 14% of US women are actually African-American. This disparity is alarming and begs to be addressed by behavioral interventions. Hopefully the attention of the HIV-aware community can be directed toward black women just as intensely as it has been directed toward homosexual men in the past.
Article: http://www.medicalnewstoday.com/articles/242762.php
- Elena Higuchi
This study is getting a high amount of press because this infection rate is comparable to developing countries known for their burgeoning HIV rate - for instance, Congo at 0.28% and Kenya at 0.53% HIV-positivity.
Although the study focused on areas known to have high HIV rates and prevalent poverty, this is still a very concerning statistic for even a subpopulation. On the whole, 66% of new HIV infections among women in the US occur among African-American women, while only 14% of US women are actually African-American. This disparity is alarming and begs to be addressed by behavioral interventions. Hopefully the attention of the HIV-aware community can be directed toward black women just as intensely as it has been directed toward homosexual men in the past.
Article: http://www.medicalnewstoday.com/articles/242762.php
- Elena Higuchi
29 Eylül 2012 Cumartesi
PerkinsElmer Genomic Sequencing History
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Perkins Elmer has an extensive history in the genomic sequencing field and Dr. Craig Venter. Dr. Venter is a former researcher for The Institute for Genomic Research and founded the J. Craig Venter Institute. Find out more here: http://www.jcvi.org/
Google finance: NYSE:PKI
PerkinElmer Website
PerkinElmer Enters DNA Sequencing Market
By MATTHEW HERPER
PerkinElmer headquarters
In a move that heralds the growing importance of DNA sequencing to medical research and, eventually, diagnostics, PerkinElmer, the $1.9 billion (sales) maker of diagnostic tests, is entering the gene scanning market.
Rather than compete with makers of big DNA sequencing machines, PerkinElmer is creating a service business that will allow researchers to get human genetic data without owning their own DNA sequencers or high-powered supercomputers. Customers will be able to access and analyze DNA data on a password-protected computer cloud. The DNA sequencing and the data analysis will be compliant with regulations for lab diagnostics. Eventually, the will also comply with the Health Insurance Portability and Accountability act (HIPAA), which protects medical privacy.
Continued
The decision to enter the DNA-decoding market came about because although PerkinElmer is big player in diagnostics and in the analysis of proteins, it had no real presence in DNA sequencing.”You can’t really develop drugs without spending much more energy on the DNA side,” says Richard Begley, president of emerging technologies at Perkin, in an exclusive interview. “The absence of DNA was clearly a problem.”
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There’s a historic resonance to the move, too. The early DNA sequencers that were used in the Human Genome Project started out at Perkin-Elmer before a restructuring made the technology part of a separate company. Begley, the executive heading the DNA sequencing effort, was previously chief executive of 454 Life Sciences, the first of the current generation of faster, more powerful DNA decoders.
DNA sequencing has become a booming growth market. The machines and the chemicals that run them are a $1.5 billion market dominated by Illumina, Life Technologies, and Roche, which bought 454 in 2007. Their ascent has made Illumina one of the hottest stocks of the past five years as its sales have grown 12-fold to a projected $880 million in 2010.
PerkinElmer will focus its product on what is known as exome sequencing, a technique for looking at only the parts of the human genome that contain genes that code for proteins. (This is only 1% of the 6 billion DNA bases in a human genome; the rest either regulates the genes or is junk.) This year, researchers are expected to sequence thousands of exomes in order to understand rare diseases and cancers.
Begley says that PerkinElmer already has 20 customers for its sequencing service and that it has already delivered hundreds of exomes. The company was not able to provide any customers to be interviewed for this story.
This is hardly the first sequencing-as-service business. Complete Genomics has been in the service business for years, with clients that have included Pfizer, Eli Lilly, and the Institute for Systems Biology, and it has completed hundreds of full human genomes. Illumina has its own sequencing business, as does Knome of Cambridge, Mass. The Beijing Genomics Institute does some sequencing for other researchers. Complete has referenced per-genome prices of as low as $5,000.
Image by Getty Images via @daylife
The PerkinElmer solution will allow customers to choose between technologies made by Roche, Illumina, and Agilent to cut genomes down to exome size, but all the sequencing will be done on machines made by Illumina. In the future, Begley says, PerkinElmer will use whichever sequencing platform meets its needs or is wanted by enough customers.
The systems are automated using PerkinElmer technology and software is provided by Geospiza, a computing firm. Begley declined to provide a per exome price estimate for the new service, but said that it was competitive with other players. For more information, go here.
Jan. 24 2011 — 8:09 am
Perkin-Elmer, Dr. Craig Venter, and TIGR Announce Formation of New Genomics Company
-- Plan to Sequence Human Genome Within Three Years --
May 9, 1998
09-May-1998
PRESS RELEASE
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NORWALK, CT and ROCKVILLE, MD, May 9, 1998 -- The Perkin-Elmer Corporation (NYSE:PKN), Dr. J. Craig Venter, and The Institute for Genomic Research (TIGR) announced today that they have signed letters of intent relating to the formation by Perkin-Elmer and Dr. Venter of a new genomics company. Its strategy will be centered on a plan to substantially complete the sequencing of the human genome in three years.
The new company's goal is to become the definitive source of genomic and associated medical information that will be used by scientists to develop a better understanding of the biological processes in humans and deliver improved healthcare in the future. Using breakthrough DNA analysis technology being developed by Perkin-Elmer's Applied Biosystems Division, applied to sequencing strategies pioneered by Dr. Venter and others at TIGR, the company will operate a genomics sequencing facility with an expected capacity greater than that of the current combined world output.
Concurrently, the new company also intends to build the scientific expertise and informatics tools necessary to extract valuable biological knowledge from genomic data, including the discovery of new genes, development of polymorphism assay systems, and databases for the scientific community. Perkin-Elmer and Dr. Venter believe that this information has significant commercial value and that the new company can provide this information more rapidly and more accurately than is currently possible.
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"The fundamentals of healthcare delivery and medical practice will be transformed by molecular medicine. We believe that the information developed by this new company will become the cornerstone of this new paradigm and accelerate development of new therapies, targeted diagnostics, and individualized medicine - providing therapies tailored specifically to a disease in an individual," noted Tony L. White, Perkin-Elmer's chairman, president and chief executive officer.
Mr. White continued, "We see our exciting new sequencing technology as the catalyst for this new genomics initiative - allowing us to take another step in the redefinition of Perkin-Elmer. When combined with the talents and resources of Dr. Venter and other TIGR scientists who would be employed by the new company, we believe we have the ability to quickly and cost-effectively sequence whole genomes. Together, we intend to build a new business that satisfies the rapidly growing need for genomic information and gene discovery."
Since the inception of the Human Genome Project (HGP) in 1990, a major shift in technology has been anticipated that would allow the entire sequence to be completed. To date, scientists have constructed detailed genetic and physical maps and sequenced approximately three percent of the three billion base pairs of DNA that comprise the human genome and contain the inherited instructions for human development and function.
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"The Human Genome Project has been a technology-driven quest," said Dr. Michael W. Hunkapiller, senior vice president of Perkin-Elmer and president of its Applied Biosystems Division. "We're near the end of our technology development phase and about to implement a new sequencing strategy. We believe we can provide the anticipated advance that greatly expedites the sequencing phase of the entire human genome."
The new company plans to make sequencing data publicly available to ensure that as many researchers as possible are examining it and that applications, such as the development of diagnostic tests and new drug discovery, are as broad as possible.
Commenting on the proposed new venture, J. Craig Venter, Ph.D., TIGR's president and director, said, "By linking techniques that have been used by TIGR scientists with Perkin-Elmer's genetic analysis technologies, we pave the way for a new era of post-genomic discovery. The sooner researchers can access the information contained in the complete human genome, the sooner new therapies can be developed for the thousands of disorders in which genes play a role."
Dr. Venter will serve as the president of the proposed new company. Mr. White will serve as the new firm's chairman, and Perkin-Elmer's vice president of corporate planning and business development, Peter Barrett, Ph.D., will be appointed an executive vice president. Perkin-Elmer will retain ownership of approximately 80 percent of the new company, with the balance being held by TIGR, Dr. Venter, other members of management, and employees of the new company in the form of common shares and options. The company will be located in Rockville, MD.
Additional terms of the letters of intent were not disclosed, and the agreement is subject to final documentation and the approval of the boards of Perkin-Elmer and TIGR.
The Perkin-Elmer Corporation is a leading supplier of systems for life science research and related applications. It develops, manufactures, and markets life science systems and analytical instruments used in markets such as pharmaceutical, biotechnology, environmental testing, foods, agriculture, and chemical manufacturing. Headquartered in Connecticut, Perkin-Elmer had revenues of nearly $1.4 billion in fiscal 1997 and employs more than 6,000 people worldwide.
TIGR, headquartered in Rockville, MD is an independent, not-for-profit research institute founded in 1992 by Dr. Venter that employs 170 faculty and staff. TIGR has interest in structural, functional and comparative analysis of genome and gene products in viruses, eubacteria, pathogenic bacteria, archaea, and eukaryotes, both plant and animal, including humans. In its brief history, TIGR has fully sequenced seven organisms. Most recently, TIGR released the DNA sequence for H. pylori, the bacteria that causes stomach ulcers and B. burgdorferi, the pathogen that causes Lyme disease.
Perkin-Elmer will hold a conference call, at 10:00 a.m. ET on Monday, May 11, to discuss this press release. To participate in this call, those interested should phone (203) 761-2617 to receive the conference number. This and other information about the Company is also available on the World Wide Web at www.perkin-elmer.com or by phoning (800) 762-6923.
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Sequencing Technologies
The Scientist 1995, 9(20):18
Published 16 October 1995
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Genome
Author: Holly Ahern
SIDEBAR: Selected Suppliers of DNA Sequencing Equipment and Supplies
Since the Human Genome Project (HGP) was launched five years ago, human geneticists working to decipher the code of nucleotides in the DNA of human cells have enthralled the public with discoveries of numerous genes that are responsible for human diseases, such as cancer-related genes. Different groups of scientists in laboratories all over the world are participating in this project, taking apart the human genome right down to the constituent DNA nucleotides. The ultimate goal of the HGP is to determine the exact order, or DNA sequence, of the nucleotide bases that make up all 23 pairs of human chromosomes, some 3 billion bases in all.
As high-profile as the project may be, HGP researchers aren't the only molecular geneticists who are attracting fame and glory. In July, a research team headed by Nobel laureate Hamilton Smith of Johns Hopkins University and Craig Venter of The Institute for Genomic Research in Gaithersburg, Md., published the first complete genomic sequence of the bacterium Haemophilus influenzae, a laboratory organism and potential pathogen. H. influenzae gained the "honor" of becoming the first free-living organism whose genetic composition is completely known. (R.D. Fleischmann et al., Science, 269:496-512, 1995).
"This is a notable effort," comments Barton Slatko, director of the DNA sequencing core facility at New England BioLabs Inc. in Beverly, Mass. "The Human Genome Project gains a lot of attention, but this shows that there are many other applications of DNA sequencing technology that are just as noteworthy."
SEQUENCING BY CAPILLARY ELECTROPHORESIS: the ABI Prism 310 Genetic Analyzer from Perkin-Elmer Biosystems is a sequencing and DNA-fragment znalyzing system using capillary electrophoresis.
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The implications of Venter and Smith's research are far- reaching. With the sequence data generated from this effort and from sequencing the genomes of other microbes and eukaryotes, researchers might find answers to the question of how microorganisms and higher creatures evolved. Additionally, investigators sorting through the 1,743 genes in H. influenzae's genome have found genes of unknown function as well as counterparts to known genes in other organisms. Knowing the identity of all of H. influenzae's genes will also aid medical microbiologists studying the organism's natural pathogenicity.
New sequencing methods, along with automated instruments and computerized analysis of the sequencing data, are the tools that researchers such as Venter and Smith are using to generate genomic sequences in a fraction of the time it takes to achieve the same results manually. The techniques used by Venter's group to sequence the bacterial genome may have direct bearing on the HGP if their methods are applicable to pieces of human DNA. Because Venter and Smith's method involves less initial cloning, sequencing time -- and, thus, the cost -- are greatly reduced.
With conventional methods, in order to determine the nucleotide sequence of something as big as an organism's full contingent of DNA, researchers first must painstakingly clone the genomic DNA piece by piece in large (approximately 40 kilobases), overlapping segments. Each segment is "shotgunned," or broken into smaller fragments, which serve as templates for sequencing. The order of bases in each fragment is determined with a series of chemical reactions followed by electrophoresis to separate the resulting DNA pieces, which differ in length by only one base. Once the order is determined, the shotgunned fragments are ordered according to overlaps in their sequence. Then the larger segments are put back into place in the genome using the same type of analysis -- not a trivial accomplishment, and one that requires powerful computing capabilities.
This approach was used successfully by Venter's team. They shotgunned the entire 1,800-kilobase H. influenzae genome, sequenced each fragment, and then reassembled the genome by lining up overlapping ends. To reassemble the genome from the tens of thousands of fragments generated by shotgunning, the research group relied on their own program, called TIGR Assembler, to put the genome back together again. Although the human genome is roughly 1,500 times larger than that of the bacterium, the researchers are optimistic that this new method can be adapted for sequencing human DNA.
When the HGP began in 1990, sequencing was a manual effort that was both labor-intensive and expensive, which prompted former HGP director James D. Watson and his associates to propose that the genome be divvied up among several laboratories all over the world. Manually sequencing even a small fragment of DNA is a complicated process in itself, requiring special electrophoresis equipment and an extensive array of reagents and chemicals for purifying DNA, pouring gels, and performing the sequencing reactions. Talent and patience are also necessary. Pouring a good sequencing gel, which is a very thin slab of acrylamide poured between two long glass plates, can be more of an art than a science.
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"In general, pouring gels is something that many people find technically difficult," notes Randall Collura, a molecular biologist at the State University of New York, Albany. Collura runs a DNA sequencing facility for members of the molecular biology core group at the university. "With all of the available kits and enzymes, conventional sequencing chemistry is quite straightforward. but the quality of the data really depends on how well the DNA fragments separate in the gel," he says.
Anomalies commonly encountered with sequencing gels, such as compressed bands (bands that are squeezed together) and "smiling" gels (occurring when genes at the beginning and end of the band travel more slowly through the gel than the ones in the middle, causing the gel to look like a smile), make it difficult to read long stretches of sequence. Investigators may be able to read only 100 bases rather than the 300 or 400 they would normally read from a very good gel. To generate further sequence data, more cloning and sequencing steps must be performed. This translates into lost time and money.
Advances in sequencing technology stemming from HGP research have led to improvements in gel polymers, gel pouring techniques, and the requisite electrophoresis equipment. The gel polymer most often used in sequencing, polyacrylamide, can be purchased from companies such as Bio-Rad Laboratories in Hercules, Calif., which offers several different formulations of acrylamide powders and solutions, and Pharmacia Biotech Inc. of Piscataway, N.J. Pharmacia's PlusOne acrylamide products offer researchers a range of acrylamide mixtures and come as powders or as solutions, depending on the investigator's preference.
Electrophoresis "rigs" for sequencing -- which include gel assembly and support components, glass plates, combs for sample loading, and a power supply -- are improving, as well. Many electrophoresis units come complete with temperature controls that allow investigators to regulate the temperature of the gel, which generally goes way up as the applied voltage is increased. With this feature, gels can be run faster without worries of "cooking" the gel, or ending up with smiles or compressed bands.
Electrophoresis instruments, such as Pharmacia's Macrophor system, feature a thermostatic plate that keeps the entire gel at a uniform temperature. Using the MacroMould Gel Casting Unit (also from Pharmacia), researchers create ultrathin gels (100 mm thick) that can be cast in less than one minute. Bio-Rad's Sequi-Gen II Sequencing Cell incorporates an upper buffer chamber that extends over the entire length of the gel to dissipate heat and maintain the gel at a constant temperature.
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The Model SA Sequencing Gel Electrophoresis System from Life Technologies Inc. of Gaithersburg, Md., is an adjustable system for gels of different heights. For sequencing reactions, for example, a researcher would choose the longest gel configuration (88 cm). The system also includes an integral aluminum plate design that distributes heat evenly across the gel to minimize electrophoretic anomalies.
"With DNA sequencing, there are essentially five areas of consideration," explains New england BioLab's Slatko. The first of these considerations are the DNA-based steps of cloning to mass-produce the area of DNA to be sequenced and purifying the target to be sequenced. For example, the targets may be templates such as single-stranded or double- stranded DNA, messenger RNA, or polymerase chain reaction products. Researchers must also choose both the type of sequencing chemistry (Maxam-Gilbert, Sanger, or thermal cycling) and an isotopic or nonradioactive labeling and detection system. A fourth consideration, for separating the fragments generated by the sequencing reactions, is the electrophoresis rig and the method of gel process, usually autoradiography or gel-scanning devices that read bands directly from an electrophoresis gel. The final consideration is the interpretation of gel patterns to obtain the DNA-sequence information, which is usually performed with the aid of a computer and dedicated software.
Each of these areas has seen advancements, many of which are related to the HGP and other genome-sequencing efforts. "The Human Genome Project has dedicated large amounts of money and resources for developing new and advanced sequencing technologies," says Collura. Research aimed at developing techniques that will decrease the length of the project as well as project costs is generally well funded. "Any improvement that makes sequencing faster, cheaper and easier to perform will pay off in the end," Collura notes.
Cycle-sequencing chemistry, sequencing based on DNA amplification, is an example. Most conventional sequencing strategies are based on the dideoxy chain-termination method developed by Fred Sanger (F. Sanger et al., Proceedings of the National Academy of Sciences, 74:5463, 1977). It uses a radioactive isotope as the label to create visible bands on an X-ray film after electrophoresis of the chain-terminated DNA fragments. Cycle sequencing combines conventional dideoxy-sequencing reactions with thermal-cycling conditions, and involves a thermostable DNA polymerase, such as Taq, and a thermal cycler for repeated rounds of DNA denaturation, annealing, and primer extension. This offers many advantages over a single-cycle method, because the reactions can be performed at higher temperatures (preventing false-priming reactions) and less template is required, since the product is linearly amplified over several cycles. Bacterial colonies or phage plaques, as opposed to highly purified DNA, can be used as template in this type of reaction.
Several cycle-sequencing kits that contain all of the necessary reactants (a thermal-cycling instrument is also required) are commercially available. The Cycle Sequencing Kit from Pharmacia generates approximately 500 bases of readable sequence data from as little as 50 femtomoles (10- 15 moles) of DNA. The Cyclist Taq DNA Sequencing kit from Stratagene Cloning Systems in La Jolla, Calif., is similarly based on thermal cycle-sequencing chemistry.
New England BioLabs uses a highly thermostable polymerase (Vent exo- DNA polymerase) in its CircumVent Thermal Cycle DNA Sequencing kit. Combining this product with the CircumVent Phototope Detection kit for chemiluminescent detection of DNA bands, researchers can sequence DNA without radioactivity.
For scientists who prefer the nonradioactive sequencing strategies, Tropix Inc. of Bedford, Mass., markets a chemiluminescence-based DNA sequencing product, the SEQ- Light DNA-sequencing system, that combines standard dideoxy- sequencing chemistry with chemiluminescent detection. Boehringer Mannheim Corp. of Indianapolis also carries a sequencing kit for those who prefer the nonradioactive approach. The Genius Nonradioactive DNA Sequencing kit can be used for both standard or cycle-sequencing with chemiluminescent detection.
Most of the recent sequencing developments are aimed at speeding up the sequencing process and increasing the length of "read," or how many bases in a row a researcher can accurately read after a single electrophoretic run. The most direct way to achieve these goals is to automate some or all of the sequencing steps.
Preparing templates for sequencing, for example, can be automated with the Vistra DNA Labstation 625, manufactured by Molecular Dynamics Inc. of Sunnyvale, Calif. The unit reportedly performs all of the steps required to prepare samples for sequencing-gel loading. The starting material can be purified DNA, or simply the cells or virus particles containing the target template. For loading gels, Bio-Rad carries an automatic gel loader (GS Gene Loader II) that adds radiolabeled or fluorescently labeled samples onto sequencing gels in semiautomated sequencing systems, such as those offered by Perkin-Elmer Corp. Applied Biosystems Division in Foster City, Calif., and Pharmacia.
The GS Gene Reader from Bio-Rad is an automated film scanner that simplifies one of the most tedious sequencing steps -- reading the order of bases. When connected to a computer workstation, the scanning system delivers more bases in less time and allows the researcher to process images, assign bases, and edit sequence data. To read sequence data directly from gels, Molecular Dynamics markets two systems: the FluorImager SI, for fluorescent labels; and the PhosphorImager 445 SI, which captures images produced by radioactive emissions from isotopes. Molecular Dynamics also carries software (DNAscan) for computer-assisted DNA sequencing of images from films and gels.
Companies such as Molecular Dynamics; Genomyx Corp. of Foster City, Calif.; Perkin-Elmer Applied Biosystems; and Pharmacia market semiautomated sequencing instruments that reportedly sequence more bases in less time and at a fraction of the cost of manual sequencing (according to the company, as low as 5 to 10 cents a base). Additionally, Hyseq Inc. of Sunnyvale, Calif., is currently developing -- but has not yet made available -- its sequencing-by-hybridization (SBH) technology, whereby sequencing is performed directly on a microchip. The chip serves as a physical platform where target sequences hybridize with immobilized oligonucleotides (eight bases long). Computerized analysis of the hybrids then provides the researcher with the unknown sequence, at a rate of up to 64,000 bases of DNA in less than two hours, according to the company.
Speedy sequences don't come cheap, however. You have to buy the instrument first, a one-time investment of $10,000 to $100,000 or more, depending on the instrument.
ALL IN ONE: The Genomyx genomyxLR DNA Sequencer replaces the conventional electrophoresis "rig", including the power supply and gel drier.
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The genomyxLR DNA Sequencer from Genomyx Corp., priced slightly less than $10,000, is a completely integrated system that replaces the conventional electrophoresis "rig," including the power supply and gel drier (along with the associated cold trap and vacuum pump). This system, which is semiautomated (investigators pour and load gels, as with manual methods), features air-impingement technology that uniformly distributes air over the glass plates, eliminating temperature gradients or differences in the gel. Sequencing gels can be run at higher temperatures or higher voltage with good resolution of the DNA fragments.
The genomyxLR also has a unique incorporated radionucleotide capture cartridge for processing radioactive buffer left over at the end of an electrophoresis run. This feature decreases the amount of liquid radioactive waste to nearly nonexistent, because the radioactivity is collected in the cartridge. Next year Genomyx plans to introduce a fluorescent sequencer as a nonradioactive alternative to conventional sequencing protocols.
Molecular Dynamics' Vistra DNA Sequencer 725 is a mid-range semiautomatic sequencing instrument, priced at $49,500 without a computer workstation and at $54,900 with a workstation.
Pharmacia and Applied Biosystems both carry semiautomated sequencing systems for their higher-end users. Priced at $75,000, Pharmacia's ALF DNA Analysis System (ALF DNA Sequencer) and Pharmacia's newer, less costly system, the ALFexpress, utilize a single fluorescent dye with LIF (laser-induced fluorescence) detection. The ALF system incorporates an electrophoresis module that includes the argon laser for detection, a power module with both electrophoretic and laser power supplies, and a PC-based computer system with system-management software. Three dedicated reagent kits -- the AutoRead Sequencing kit, AutoRead 1000 Sequencing kit, and the AutoCycle Sequencing Kit for thermal cycle sequencing-support the system.
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The ABI Prism 377 DNA sequencer from Perkin-Elmer Applied Biosystems, which succeeds ABI's model 373 instrument, is a high-throughput DNA sequencer that runs in a slab-gel format (referring to the type of gel, in this case a thin polyacrylamide slab). Like the 373 model, the 377 is based on the company's four-color fluorescent labeling technology. With four fluorescent dyes (for the four bases in DNA), all of the sequencing reactions can be run in one lane. This increases the number of bases that can be read from a single gel and generates sequencing data faster, at a rate of up to 7,200 bases per hour. However, with a price tag of more than $100,000, this instrument is largely relegated to core facilities that support a large number of researchers. Users of the core facility generally pay to have their DNA sequenced, usually at a per-base rate.
Newer to the market is the ABI Prism 310 Genetic Analyzer from Perkin-Elmer Applied Biosystems, a near fully automated sequencing and DNA-fragment analyzing system priced at less than half the cost of the model 377. With the ABI Prism 310, sequences are determined by capillary electrophoresis, whereby the DNA pieces generated in the sequencing reactions are separated in a polymer gel contained within a glass capillary tube. With the exception of purifying the DNA and performing the chemical reactions, the model 310 is fully automated. Prepared samples are injected into the capillary from a sample tray, and the fragments are separated and analyzed by four-color LIF detection.
"Four-color LIF DNA sequencing utilizes four different [fluorescent] color labels, one for each DNA nucleotide," explains J. William Efcavitch, genetic-analysis research and development section leader at Perkin-Elmer. "All four reactions are loaded into the systems' single capillary, where the differently sized fragments are separated" and then analyzed, at a rate of 400 to 450 bases every two hours. "The second generation of this instrument [due out in January] is expected to sequence 600 to 650 nucleotides in the same amount of time," he adds.
Image via Wikipedia
"When you are sequencing DNA, it's a simple choice," according to Efcavitch. "You can read a fewer number of bases at ultra-high speed, or you can read more bases but at a slower rate." To sequence a genome, investigators are interested in as much throughput as possible. For smaller projects, such as in the applied sciences of forensics and diagnostics, where only bits of genome are examined, Efcavitch concludes, "the greater need is for total automation and longer read, as opposed to faster throughput."
Holly Ahern is a science writer and an assistant professor of biology at Adirondack Community College in Queensbury, N.Y
Image via Wikipedia
Read more: Sequencing Technologies Helping - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/article/display/16721/#ixzz1CZTrRIL3
Image via WikipediaPerkins Elmer has an extensive history in the genomic sequencing field and Dr. Craig Venter. Dr. Venter is a former researcher for The Institute for Genomic Research and founded the J. Craig Venter Institute. Find out more here: http://www.jcvi.org/
Google finance: NYSE:PKI
PerkinElmer Website
PerkinElmer Enters DNA Sequencing Market
By MATTHEW HERPER
PerkinElmer headquarters
In a move that heralds the growing importance of DNA sequencing to medical research and, eventually, diagnostics, PerkinElmer, the $1.9 billion (sales) maker of diagnostic tests, is entering the gene scanning market.
Rather than compete with makers of big DNA sequencing machines, PerkinElmer is creating a service business that will allow researchers to get human genetic data without owning their own DNA sequencers or high-powered supercomputers. Customers will be able to access and analyze DNA data on a password-protected computer cloud. The DNA sequencing and the data analysis will be compliant with regulations for lab diagnostics. Eventually, the will also comply with the Health Insurance Portability and Accountability act (HIPAA), which protects medical privacy.
Continued
The decision to enter the DNA-decoding market came about because although PerkinElmer is big player in diagnostics and in the analysis of proteins, it had no real presence in DNA sequencing.”You can’t really develop drugs without spending much more energy on the DNA side,” says Richard Begley, president of emerging technologies at Perkin, in an exclusive interview. “The absence of DNA was clearly a problem.”
Image via WikipediaThere’s a historic resonance to the move, too. The early DNA sequencers that were used in the Human Genome Project started out at Perkin-Elmer before a restructuring made the technology part of a separate company. Begley, the executive heading the DNA sequencing effort, was previously chief executive of 454 Life Sciences, the first of the current generation of faster, more powerful DNA decoders.
DNA sequencing has become a booming growth market. The machines and the chemicals that run them are a $1.5 billion market dominated by Illumina, Life Technologies, and Roche, which bought 454 in 2007. Their ascent has made Illumina one of the hottest stocks of the past five years as its sales have grown 12-fold to a projected $880 million in 2010.
PerkinElmer will focus its product on what is known as exome sequencing, a technique for looking at only the parts of the human genome that contain genes that code for proteins. (This is only 1% of the 6 billion DNA bases in a human genome; the rest either regulates the genes or is junk.) This year, researchers are expected to sequence thousands of exomes in order to understand rare diseases and cancers.
Begley says that PerkinElmer already has 20 customers for its sequencing service and that it has already delivered hundreds of exomes. The company was not able to provide any customers to be interviewed for this story.
This is hardly the first sequencing-as-service business. Complete Genomics has been in the service business for years, with clients that have included Pfizer, Eli Lilly, and the Institute for Systems Biology, and it has completed hundreds of full human genomes. Illumina has its own sequencing business, as does Knome of Cambridge, Mass. The Beijing Genomics Institute does some sequencing for other researchers. Complete has referenced per-genome prices of as low as $5,000.
Image by Getty Images via @daylifeThe PerkinElmer solution will allow customers to choose between technologies made by Roche, Illumina, and Agilent to cut genomes down to exome size, but all the sequencing will be done on machines made by Illumina. In the future, Begley says, PerkinElmer will use whichever sequencing platform meets its needs or is wanted by enough customers.
The systems are automated using PerkinElmer technology and software is provided by Geospiza, a computing firm. Begley declined to provide a per exome price estimate for the new service, but said that it was competitive with other players. For more information, go here.
Jan. 24 2011 — 8:09 am
Perkin-Elmer, Dr. Craig Venter, and TIGR Announce Formation of New Genomics Company
-- Plan to Sequence Human Genome Within Three Years --
May 9, 1998
09-May-1998
PRESS RELEASE
Image via WikipediaNORWALK, CT and ROCKVILLE, MD, May 9, 1998 -- The Perkin-Elmer Corporation (NYSE:PKN), Dr. J. Craig Venter, and The Institute for Genomic Research (TIGR) announced today that they have signed letters of intent relating to the formation by Perkin-Elmer and Dr. Venter of a new genomics company. Its strategy will be centered on a plan to substantially complete the sequencing of the human genome in three years.
The new company's goal is to become the definitive source of genomic and associated medical information that will be used by scientists to develop a better understanding of the biological processes in humans and deliver improved healthcare in the future. Using breakthrough DNA analysis technology being developed by Perkin-Elmer's Applied Biosystems Division, applied to sequencing strategies pioneered by Dr. Venter and others at TIGR, the company will operate a genomics sequencing facility with an expected capacity greater than that of the current combined world output.
Concurrently, the new company also intends to build the scientific expertise and informatics tools necessary to extract valuable biological knowledge from genomic data, including the discovery of new genes, development of polymorphism assay systems, and databases for the scientific community. Perkin-Elmer and Dr. Venter believe that this information has significant commercial value and that the new company can provide this information more rapidly and more accurately than is currently possible.
Image via Wikipedia"The fundamentals of healthcare delivery and medical practice will be transformed by molecular medicine. We believe that the information developed by this new company will become the cornerstone of this new paradigm and accelerate development of new therapies, targeted diagnostics, and individualized medicine - providing therapies tailored specifically to a disease in an individual," noted Tony L. White, Perkin-Elmer's chairman, president and chief executive officer.
Mr. White continued, "We see our exciting new sequencing technology as the catalyst for this new genomics initiative - allowing us to take another step in the redefinition of Perkin-Elmer. When combined with the talents and resources of Dr. Venter and other TIGR scientists who would be employed by the new company, we believe we have the ability to quickly and cost-effectively sequence whole genomes. Together, we intend to build a new business that satisfies the rapidly growing need for genomic information and gene discovery."
Since the inception of the Human Genome Project (HGP) in 1990, a major shift in technology has been anticipated that would allow the entire sequence to be completed. To date, scientists have constructed detailed genetic and physical maps and sequenced approximately three percent of the three billion base pairs of DNA that comprise the human genome and contain the inherited instructions for human development and function.
Image via Wikipedia"The Human Genome Project has been a technology-driven quest," said Dr. Michael W. Hunkapiller, senior vice president of Perkin-Elmer and president of its Applied Biosystems Division. "We're near the end of our technology development phase and about to implement a new sequencing strategy. We believe we can provide the anticipated advance that greatly expedites the sequencing phase of the entire human genome."
The new company plans to make sequencing data publicly available to ensure that as many researchers as possible are examining it and that applications, such as the development of diagnostic tests and new drug discovery, are as broad as possible.
Commenting on the proposed new venture, J. Craig Venter, Ph.D., TIGR's president and director, said, "By linking techniques that have been used by TIGR scientists with Perkin-Elmer's genetic analysis technologies, we pave the way for a new era of post-genomic discovery. The sooner researchers can access the information contained in the complete human genome, the sooner new therapies can be developed for the thousands of disorders in which genes play a role."
Dr. Venter will serve as the president of the proposed new company. Mr. White will serve as the new firm's chairman, and Perkin-Elmer's vice president of corporate planning and business development, Peter Barrett, Ph.D., will be appointed an executive vice president. Perkin-Elmer will retain ownership of approximately 80 percent of the new company, with the balance being held by TIGR, Dr. Venter, other members of management, and employees of the new company in the form of common shares and options. The company will be located in Rockville, MD.
Additional terms of the letters of intent were not disclosed, and the agreement is subject to final documentation and the approval of the boards of Perkin-Elmer and TIGR.
The Perkin-Elmer Corporation is a leading supplier of systems for life science research and related applications. It develops, manufactures, and markets life science systems and analytical instruments used in markets such as pharmaceutical, biotechnology, environmental testing, foods, agriculture, and chemical manufacturing. Headquartered in Connecticut, Perkin-Elmer had revenues of nearly $1.4 billion in fiscal 1997 and employs more than 6,000 people worldwide.
TIGR, headquartered in Rockville, MD is an independent, not-for-profit research institute founded in 1992 by Dr. Venter that employs 170 faculty and staff. TIGR has interest in structural, functional and comparative analysis of genome and gene products in viruses, eubacteria, pathogenic bacteria, archaea, and eukaryotes, both plant and animal, including humans. In its brief history, TIGR has fully sequenced seven organisms. Most recently, TIGR released the DNA sequence for H. pylori, the bacteria that causes stomach ulcers and B. burgdorferi, the pathogen that causes Lyme disease.
Perkin-Elmer will hold a conference call, at 10:00 a.m. ET on Monday, May 11, to discuss this press release. To participate in this call, those interested should phone (203) 761-2617 to receive the conference number. This and other information about the Company is also available on the World Wide Web at www.perkin-elmer.com or by phoning (800) 762-6923.
Image via WikipediaSequencing Technologies
The Scientist 1995, 9(20):18
Published 16 October 1995
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Genome
Author: Holly Ahern
SIDEBAR: Selected Suppliers of DNA Sequencing Equipment and Supplies
Since the Human Genome Project (HGP) was launched five years ago, human geneticists working to decipher the code of nucleotides in the DNA of human cells have enthralled the public with discoveries of numerous genes that are responsible for human diseases, such as cancer-related genes. Different groups of scientists in laboratories all over the world are participating in this project, taking apart the human genome right down to the constituent DNA nucleotides. The ultimate goal of the HGP is to determine the exact order, or DNA sequence, of the nucleotide bases that make up all 23 pairs of human chromosomes, some 3 billion bases in all.
As high-profile as the project may be, HGP researchers aren't the only molecular geneticists who are attracting fame and glory. In July, a research team headed by Nobel laureate Hamilton Smith of Johns Hopkins University and Craig Venter of The Institute for Genomic Research in Gaithersburg, Md., published the first complete genomic sequence of the bacterium Haemophilus influenzae, a laboratory organism and potential pathogen. H. influenzae gained the "honor" of becoming the first free-living organism whose genetic composition is completely known. (R.D. Fleischmann et al., Science, 269:496-512, 1995).
"This is a notable effort," comments Barton Slatko, director of the DNA sequencing core facility at New England BioLabs Inc. in Beverly, Mass. "The Human Genome Project gains a lot of attention, but this shows that there are many other applications of DNA sequencing technology that are just as noteworthy."
SEQUENCING BY CAPILLARY ELECTROPHORESIS: the ABI Prism 310 Genetic Analyzer from Perkin-Elmer Biosystems is a sequencing and DNA-fragment znalyzing system using capillary electrophoresis.
Image via Wikipedia------------------------------------------------------- The implications of Venter and Smith's research are far- reaching. With the sequence data generated from this effort and from sequencing the genomes of other microbes and eukaryotes, researchers might find answers to the question of how microorganisms and higher creatures evolved. Additionally, investigators sorting through the 1,743 genes in H. influenzae's genome have found genes of unknown function as well as counterparts to known genes in other organisms. Knowing the identity of all of H. influenzae's genes will also aid medical microbiologists studying the organism's natural pathogenicity.
New sequencing methods, along with automated instruments and computerized analysis of the sequencing data, are the tools that researchers such as Venter and Smith are using to generate genomic sequences in a fraction of the time it takes to achieve the same results manually. The techniques used by Venter's group to sequence the bacterial genome may have direct bearing on the HGP if their methods are applicable to pieces of human DNA. Because Venter and Smith's method involves less initial cloning, sequencing time -- and, thus, the cost -- are greatly reduced.
With conventional methods, in order to determine the nucleotide sequence of something as big as an organism's full contingent of DNA, researchers first must painstakingly clone the genomic DNA piece by piece in large (approximately 40 kilobases), overlapping segments. Each segment is "shotgunned," or broken into smaller fragments, which serve as templates for sequencing. The order of bases in each fragment is determined with a series of chemical reactions followed by electrophoresis to separate the resulting DNA pieces, which differ in length by only one base. Once the order is determined, the shotgunned fragments are ordered according to overlaps in their sequence. Then the larger segments are put back into place in the genome using the same type of analysis -- not a trivial accomplishment, and one that requires powerful computing capabilities.
This approach was used successfully by Venter's team. They shotgunned the entire 1,800-kilobase H. influenzae genome, sequenced each fragment, and then reassembled the genome by lining up overlapping ends. To reassemble the genome from the tens of thousands of fragments generated by shotgunning, the research group relied on their own program, called TIGR Assembler, to put the genome back together again. Although the human genome is roughly 1,500 times larger than that of the bacterium, the researchers are optimistic that this new method can be adapted for sequencing human DNA.
When the HGP began in 1990, sequencing was a manual effort that was both labor-intensive and expensive, which prompted former HGP director James D. Watson and his associates to propose that the genome be divvied up among several laboratories all over the world. Manually sequencing even a small fragment of DNA is a complicated process in itself, requiring special electrophoresis equipment and an extensive array of reagents and chemicals for purifying DNA, pouring gels, and performing the sequencing reactions. Talent and patience are also necessary. Pouring a good sequencing gel, which is a very thin slab of acrylamide poured between two long glass plates, can be more of an art than a science.
Image via Wikipedia"In general, pouring gels is something that many people find technically difficult," notes Randall Collura, a molecular biologist at the State University of New York, Albany. Collura runs a DNA sequencing facility for members of the molecular biology core group at the university. "With all of the available kits and enzymes, conventional sequencing chemistry is quite straightforward. but the quality of the data really depends on how well the DNA fragments separate in the gel," he says.
Anomalies commonly encountered with sequencing gels, such as compressed bands (bands that are squeezed together) and "smiling" gels (occurring when genes at the beginning and end of the band travel more slowly through the gel than the ones in the middle, causing the gel to look like a smile), make it difficult to read long stretches of sequence. Investigators may be able to read only 100 bases rather than the 300 or 400 they would normally read from a very good gel. To generate further sequence data, more cloning and sequencing steps must be performed. This translates into lost time and money.
Advances in sequencing technology stemming from HGP research have led to improvements in gel polymers, gel pouring techniques, and the requisite electrophoresis equipment. The gel polymer most often used in sequencing, polyacrylamide, can be purchased from companies such as Bio-Rad Laboratories in Hercules, Calif., which offers several different formulations of acrylamide powders and solutions, and Pharmacia Biotech Inc. of Piscataway, N.J. Pharmacia's PlusOne acrylamide products offer researchers a range of acrylamide mixtures and come as powders or as solutions, depending on the investigator's preference.
Electrophoresis "rigs" for sequencing -- which include gel assembly and support components, glass plates, combs for sample loading, and a power supply -- are improving, as well. Many electrophoresis units come complete with temperature controls that allow investigators to regulate the temperature of the gel, which generally goes way up as the applied voltage is increased. With this feature, gels can be run faster without worries of "cooking" the gel, or ending up with smiles or compressed bands.
Electrophoresis instruments, such as Pharmacia's Macrophor system, feature a thermostatic plate that keeps the entire gel at a uniform temperature. Using the MacroMould Gel Casting Unit (also from Pharmacia), researchers create ultrathin gels (100 mm thick) that can be cast in less than one minute. Bio-Rad's Sequi-Gen II Sequencing Cell incorporates an upper buffer chamber that extends over the entire length of the gel to dissipate heat and maintain the gel at a constant temperature.
Image via WikipediaThe Model SA Sequencing Gel Electrophoresis System from Life Technologies Inc. of Gaithersburg, Md., is an adjustable system for gels of different heights. For sequencing reactions, for example, a researcher would choose the longest gel configuration (88 cm). The system also includes an integral aluminum plate design that distributes heat evenly across the gel to minimize electrophoretic anomalies.
"With DNA sequencing, there are essentially five areas of consideration," explains New england BioLab's Slatko. The first of these considerations are the DNA-based steps of cloning to mass-produce the area of DNA to be sequenced and purifying the target to be sequenced. For example, the targets may be templates such as single-stranded or double- stranded DNA, messenger RNA, or polymerase chain reaction products. Researchers must also choose both the type of sequencing chemistry (Maxam-Gilbert, Sanger, or thermal cycling) and an isotopic or nonradioactive labeling and detection system. A fourth consideration, for separating the fragments generated by the sequencing reactions, is the electrophoresis rig and the method of gel process, usually autoradiography or gel-scanning devices that read bands directly from an electrophoresis gel. The final consideration is the interpretation of gel patterns to obtain the DNA-sequence information, which is usually performed with the aid of a computer and dedicated software.
Each of these areas has seen advancements, many of which are related to the HGP and other genome-sequencing efforts. "The Human Genome Project has dedicated large amounts of money and resources for developing new and advanced sequencing technologies," says Collura. Research aimed at developing techniques that will decrease the length of the project as well as project costs is generally well funded. "Any improvement that makes sequencing faster, cheaper and easier to perform will pay off in the end," Collura notes.
Cycle-sequencing chemistry, sequencing based on DNA amplification, is an example. Most conventional sequencing strategies are based on the dideoxy chain-termination method developed by Fred Sanger (F. Sanger et al., Proceedings of the National Academy of Sciences, 74:5463, 1977). It uses a radioactive isotope as the label to create visible bands on an X-ray film after electrophoresis of the chain-terminated DNA fragments. Cycle sequencing combines conventional dideoxy-sequencing reactions with thermal-cycling conditions, and involves a thermostable DNA polymerase, such as Taq, and a thermal cycler for repeated rounds of DNA denaturation, annealing, and primer extension. This offers many advantages over a single-cycle method, because the reactions can be performed at higher temperatures (preventing false-priming reactions) and less template is required, since the product is linearly amplified over several cycles. Bacterial colonies or phage plaques, as opposed to highly purified DNA, can be used as template in this type of reaction.
Several cycle-sequencing kits that contain all of the necessary reactants (a thermal-cycling instrument is also required) are commercially available. The Cycle Sequencing Kit from Pharmacia generates approximately 500 bases of readable sequence data from as little as 50 femtomoles (10- 15 moles) of DNA. The Cyclist Taq DNA Sequencing kit from Stratagene Cloning Systems in La Jolla, Calif., is similarly based on thermal cycle-sequencing chemistry.
New England BioLabs uses a highly thermostable polymerase (Vent exo- DNA polymerase) in its CircumVent Thermal Cycle DNA Sequencing kit. Combining this product with the CircumVent Phototope Detection kit for chemiluminescent detection of DNA bands, researchers can sequence DNA without radioactivity.
For scientists who prefer the nonradioactive sequencing strategies, Tropix Inc. of Bedford, Mass., markets a chemiluminescence-based DNA sequencing product, the SEQ- Light DNA-sequencing system, that combines standard dideoxy- sequencing chemistry with chemiluminescent detection. Boehringer Mannheim Corp. of Indianapolis also carries a sequencing kit for those who prefer the nonradioactive approach. The Genius Nonradioactive DNA Sequencing kit can be used for both standard or cycle-sequencing with chemiluminescent detection.
Most of the recent sequencing developments are aimed at speeding up the sequencing process and increasing the length of "read," or how many bases in a row a researcher can accurately read after a single electrophoretic run. The most direct way to achieve these goals is to automate some or all of the sequencing steps.
Preparing templates for sequencing, for example, can be automated with the Vistra DNA Labstation 625, manufactured by Molecular Dynamics Inc. of Sunnyvale, Calif. The unit reportedly performs all of the steps required to prepare samples for sequencing-gel loading. The starting material can be purified DNA, or simply the cells or virus particles containing the target template. For loading gels, Bio-Rad carries an automatic gel loader (GS Gene Loader II) that adds radiolabeled or fluorescently labeled samples onto sequencing gels in semiautomated sequencing systems, such as those offered by Perkin-Elmer Corp. Applied Biosystems Division in Foster City, Calif., and Pharmacia.
The GS Gene Reader from Bio-Rad is an automated film scanner that simplifies one of the most tedious sequencing steps -- reading the order of bases. When connected to a computer workstation, the scanning system delivers more bases in less time and allows the researcher to process images, assign bases, and edit sequence data. To read sequence data directly from gels, Molecular Dynamics markets two systems: the FluorImager SI, for fluorescent labels; and the PhosphorImager 445 SI, which captures images produced by radioactive emissions from isotopes. Molecular Dynamics also carries software (DNAscan) for computer-assisted DNA sequencing of images from films and gels.
Companies such as Molecular Dynamics; Genomyx Corp. of Foster City, Calif.; Perkin-Elmer Applied Biosystems; and Pharmacia market semiautomated sequencing instruments that reportedly sequence more bases in less time and at a fraction of the cost of manual sequencing (according to the company, as low as 5 to 10 cents a base). Additionally, Hyseq Inc. of Sunnyvale, Calif., is currently developing -- but has not yet made available -- its sequencing-by-hybridization (SBH) technology, whereby sequencing is performed directly on a microchip. The chip serves as a physical platform where target sequences hybridize with immobilized oligonucleotides (eight bases long). Computerized analysis of the hybrids then provides the researcher with the unknown sequence, at a rate of up to 64,000 bases of DNA in less than two hours, according to the company.
Speedy sequences don't come cheap, however. You have to buy the instrument first, a one-time investment of $10,000 to $100,000 or more, depending on the instrument.
ALL IN ONE: The Genomyx genomyxLR DNA Sequencer replaces the conventional electrophoresis "rig", including the power supply and gel drier.
Image via Wikipedia--------------------------------------------------------------------------------
The genomyxLR DNA Sequencer from Genomyx Corp., priced slightly less than $10,000, is a completely integrated system that replaces the conventional electrophoresis "rig," including the power supply and gel drier (along with the associated cold trap and vacuum pump). This system, which is semiautomated (investigators pour and load gels, as with manual methods), features air-impingement technology that uniformly distributes air over the glass plates, eliminating temperature gradients or differences in the gel. Sequencing gels can be run at higher temperatures or higher voltage with good resolution of the DNA fragments.
The genomyxLR also has a unique incorporated radionucleotide capture cartridge for processing radioactive buffer left over at the end of an electrophoresis run. This feature decreases the amount of liquid radioactive waste to nearly nonexistent, because the radioactivity is collected in the cartridge. Next year Genomyx plans to introduce a fluorescent sequencer as a nonradioactive alternative to conventional sequencing protocols.
Molecular Dynamics' Vistra DNA Sequencer 725 is a mid-range semiautomatic sequencing instrument, priced at $49,500 without a computer workstation and at $54,900 with a workstation.
Pharmacia and Applied Biosystems both carry semiautomated sequencing systems for their higher-end users. Priced at $75,000, Pharmacia's ALF DNA Analysis System (ALF DNA Sequencer) and Pharmacia's newer, less costly system, the ALFexpress, utilize a single fluorescent dye with LIF (laser-induced fluorescence) detection. The ALF system incorporates an electrophoresis module that includes the argon laser for detection, a power module with both electrophoretic and laser power supplies, and a PC-based computer system with system-management software. Three dedicated reagent kits -- the AutoRead Sequencing kit, AutoRead 1000 Sequencing kit, and the AutoCycle Sequencing Kit for thermal cycle sequencing-support the system.
Image via WikipediaThe ABI Prism 377 DNA sequencer from Perkin-Elmer Applied Biosystems, which succeeds ABI's model 373 instrument, is a high-throughput DNA sequencer that runs in a slab-gel format (referring to the type of gel, in this case a thin polyacrylamide slab). Like the 373 model, the 377 is based on the company's four-color fluorescent labeling technology. With four fluorescent dyes (for the four bases in DNA), all of the sequencing reactions can be run in one lane. This increases the number of bases that can be read from a single gel and generates sequencing data faster, at a rate of up to 7,200 bases per hour. However, with a price tag of more than $100,000, this instrument is largely relegated to core facilities that support a large number of researchers. Users of the core facility generally pay to have their DNA sequenced, usually at a per-base rate.
Newer to the market is the ABI Prism 310 Genetic Analyzer from Perkin-Elmer Applied Biosystems, a near fully automated sequencing and DNA-fragment analyzing system priced at less than half the cost of the model 377. With the ABI Prism 310, sequences are determined by capillary electrophoresis, whereby the DNA pieces generated in the sequencing reactions are separated in a polymer gel contained within a glass capillary tube. With the exception of purifying the DNA and performing the chemical reactions, the model 310 is fully automated. Prepared samples are injected into the capillary from a sample tray, and the fragments are separated and analyzed by four-color LIF detection.
"Four-color LIF DNA sequencing utilizes four different [fluorescent] color labels, one for each DNA nucleotide," explains J. William Efcavitch, genetic-analysis research and development section leader at Perkin-Elmer. "All four reactions are loaded into the systems' single capillary, where the differently sized fragments are separated" and then analyzed, at a rate of 400 to 450 bases every two hours. "The second generation of this instrument [due out in January] is expected to sequence 600 to 650 nucleotides in the same amount of time," he adds.
Image via Wikipedia"When you are sequencing DNA, it's a simple choice," according to Efcavitch. "You can read a fewer number of bases at ultra-high speed, or you can read more bases but at a slower rate." To sequence a genome, investigators are interested in as much throughput as possible. For smaller projects, such as in the applied sciences of forensics and diagnostics, where only bits of genome are examined, Efcavitch concludes, "the greater need is for total automation and longer read, as opposed to faster throughput."
Holly Ahern is a science writer and an assistant professor of biology at Adirondack Community College in Queensbury, N.Y
Image via WikipediaRead more: Sequencing Technologies Helping - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/article/display/16721/#ixzz1CZTrRIL3
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Genome study brings blood cancer into sharp focus
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Image via Wikipedia(Reuters) -
By Julie SteenhuysenCHICAGO |
Scientists have mapped out the full genetic code of 38 people with multiple myeloma, uncovering never-before suspected genes that play a role in the blood cancer and showing that a promising new drug might help.
Studying the genetic blueprint of so many people with this cancer allows researchers to have a much more comprehensive picture of what drives the cancer, and it gives drug companies much better clues about how to shut down the disease.
"If we compare the tumor genome to the normal genome, that gives us great clues about what makes a normal cell into a cancer cell," said Todd Golub of the Broad Institute and the Dana-Farber Cancer Institute, who helped lead the study published on Wednesday in the journal Nature.
Golub said the findings revealed many new avenues for future treatments for the cancer, including several genes that have never before been implicated in any cancer.
"We have a number of examples of genes that were not thought to play a role, but they must be important," Golub said in a telephone interview. "It sends the field in a new direction that they couldn't have anticipated before." Most immediately, the results suggest that about 4 percent of patients with multiple myeloma have mutations in the BRAF gene -- the same type of mutations found in some people with the skin cancer melanoma.
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So far, melanoma patients with this mutation have shown a strong response to an experimental drug being developed by Roche and Daiichi Sankyo's newly acquired Plexxikon, and the hope is the drug or others like it might also help a small subset of multiple myeloma patients.
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"An important next phase will be to explore that hypothesis in a clinical trial," Golub said.
The Multiple Myeloma Research Foundation hailed the study as "a major step forward" in efforts take a personalized medicine approach in multiple myeloma, a cancer that starts in bone marrow cells and has a five-year survival rate of less than 40 percent.
Golub said the study showcases the power of new gene-sequencing technology that allows researchers to look at the whole genetic makeup of a cancer, something that was not possible even five years ago.
"This has been made possible not by our brilliance but by advances in new gene sequencing technology," said Golub, who is an investigator at Howard Hughes Medical Institute, and professor of pediatrics at Harvard Medical School.
The latest machines from companies like Illumina Inc and Life Technologies Corp can map out a patient's whole DNA code in just a few weeks for as little as $5,000, a far cry from 13 years and $3 billion it took to get the first human genome a decade ago.
Golub said the study signals a new approach that is coming in cancer research.
"It is a very positive development that will enable the field to see things that were previously not imaginable," he said.
Image via Wikipedia
"Five years from now, we will have the genetic landscape of all common human cancers mapped out."
(Editing by Paul Simao)
ScienceHealth
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| Bio Technician demonstrates the loading of the high tech 454 Life Science sequencing machine in the sequencing laboratory at the J. Craig Venter Institute in Rockville, Maryland, in this March 29, 2010 file photo. Credit: Reuters/Larry Downing (UNITED STATES - Tags: SCI TECH) |
Image via Wikipedia(Reuters) - By Julie SteenhuysenCHICAGO |
Scientists have mapped out the full genetic code of 38 people with multiple myeloma, uncovering never-before suspected genes that play a role in the blood cancer and showing that a promising new drug might help.
Studying the genetic blueprint of so many people with this cancer allows researchers to have a much more comprehensive picture of what drives the cancer, and it gives drug companies much better clues about how to shut down the disease.
"If we compare the tumor genome to the normal genome, that gives us great clues about what makes a normal cell into a cancer cell," said Todd Golub of the Broad Institute and the Dana-Farber Cancer Institute, who helped lead the study published on Wednesday in the journal Nature.
Golub said the findings revealed many new avenues for future treatments for the cancer, including several genes that have never before been implicated in any cancer.
"We have a number of examples of genes that were not thought to play a role, but they must be important," Golub said in a telephone interview. "It sends the field in a new direction that they couldn't have anticipated before." Most immediately, the results suggest that about 4 percent of patients with multiple myeloma have mutations in the BRAF gene -- the same type of mutations found in some people with the skin cancer melanoma.
Image via Wikipedia So far, melanoma patients with this mutation have shown a strong response to an experimental drug being developed by Roche and Daiichi Sankyo's newly acquired Plexxikon, and the hope is the drug or others like it might also help a small subset of multiple myeloma patients.
Image via Wikipedia"An important next phase will be to explore that hypothesis in a clinical trial," Golub said.
The Multiple Myeloma Research Foundation hailed the study as "a major step forward" in efforts take a personalized medicine approach in multiple myeloma, a cancer that starts in bone marrow cells and has a five-year survival rate of less than 40 percent.
Golub said the study showcases the power of new gene-sequencing technology that allows researchers to look at the whole genetic makeup of a cancer, something that was not possible even five years ago.
"This has been made possible not by our brilliance but by advances in new gene sequencing technology," said Golub, who is an investigator at Howard Hughes Medical Institute, and professor of pediatrics at Harvard Medical School.
The latest machines from companies like Illumina Inc and Life Technologies Corp can map out a patient's whole DNA code in just a few weeks for as little as $5,000, a far cry from 13 years and $3 billion it took to get the first human genome a decade ago.
Golub said the study signals a new approach that is coming in cancer research.
"It is a very positive development that will enable the field to see things that were previously not imaginable," he said.
Image via Wikipedia"Five years from now, we will have the genetic landscape of all common human cancers mapped out."
(Editing by Paul Simao)
ScienceHealth
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- Genome study brings blood cancer into sharp focus (reuters.com)
- A Genomic Blueprint for Cancer (technologyreview.in)
- Multiple Myeloma Genome Sequencing Provides Breakthrough (friendshipland.wordpress.com)
- Researchers sequence multiple myeloma genome in landmark study (physorg.com)
- Researchers sequence multiple myeloma genome in landmark Nature study (eurekalert.org)
- Hackensack University scientists catalogue, study DNA of deadly bone marrow cancer (nj.com)
- Multiple Myeloma Research Foundation Announces Publication Of First Whole-Genome Sequence Analysis For Multiple Myeloma (medicalnewstoday.com)
- A Genomic Blueprint for Cancer (technologyreview.com)
Bristol melanoma drug extends survival in study
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By Bill BerkrotNEW YORK |
(Reuters) - Bristol-Myers Squibb Co's eagerly anticipated experimental drug ipilimumab extended survival of previously untreated patients with advanced melanoma in a late stage study, the company said.
Details of how much longer patients who were suffering from the deadly skin cancer lived after taking the highly promising Bristol drug will be unveiled at a major medical meeting in June.
Bristol-Myers shares were up 4.3 percent at $27.10 in extended trading from their New York Stock Exchange close at $26. They initially jumped 5.7 percent after news of the clinical trial's success was reported.
Extending overall survival -- the primary goal of the study -- is considered the gold standard for cancer drug trials.
U.S. health regulators are expected to approve ipilimumab this week based on results of a different study of patients who had received prior treatment for advanced melanoma. In that study the Bristol-Myers drug extended survival by an average of four months, which was seen as a major advance for a disease littered with drug failures and for which there are really no effective treatment options.
The Food and Drug Administration in November delayed its approval decision to give it more time to review data on the medicine, setting a new action date of March 26. "Ipilimumab is an exciting drug, especially given the dearth of effective therapies for this bad form of cancer," Sanford Bernstein analyst Tim Anderson said in a research note.Advanced melanoma is one of the deadliest cancers and can quickly spread from the skin to internal organs, such as the brain. Once melanoma spreads to other organs the average survival is typically only six to nine months.
The Phase III study of previously untreated patients compared ipilimumab in combination with chemotherapy against chemotherapy alone.
Patients in the study had stage III or stage IV melanoma. Stage IV is the most advanced form of the disease.
"If prior results are any gauge, then the drug likely gives a meaningful two-year survival benefit compared with monotherapy treatment and will likely show again that a smaller proportion of patients (15 percent of so) have a near-cure like response, said Anderson, who forecast worldwide ipilimumab sales reaching $1.7 billion in 2015.
Stocks Bristol Myers Squibb Co
BMY.N$27.29+0.86+3.25%03/25/2011 The promise of ipilimumab has created new hope for desperately ill patients, many of whom in the earlier study survived well beyond the four-month average. At the time those results were unveiled last June, more than 20 percent of those who took the drug were still alive after two years.
A consensus forecast of four analysts compiled by Thomson Reuters calls for ipilimumab sales to reach about $820 million by 2015.
(Reporting by Bill Berkrot and Lewis Krauskopf; Editing by Richard Chang, Bernard Orr)
Health
Image via Wikipedia
By Bill BerkrotNEW YORK |
(Reuters) - Bristol-Myers Squibb Co's eagerly anticipated experimental drug ipilimumab extended survival of previously untreated patients with advanced melanoma in a late stage study, the company said.
Details of how much longer patients who were suffering from the deadly skin cancer lived after taking the highly promising Bristol drug will be unveiled at a major medical meeting in June.
Bristol-Myers shares were up 4.3 percent at $27.10 in extended trading from their New York Stock Exchange close at $26. They initially jumped 5.7 percent after news of the clinical trial's success was reported.
Extending overall survival -- the primary goal of the study -- is considered the gold standard for cancer drug trials.
U.S. health regulators are expected to approve ipilimumab this week based on results of a different study of patients who had received prior treatment for advanced melanoma. In that study the Bristol-Myers drug extended survival by an average of four months, which was seen as a major advance for a disease littered with drug failures and for which there are really no effective treatment options.
The Food and Drug Administration in November delayed its approval decision to give it more time to review data on the medicine, setting a new action date of March 26. "Ipilimumab is an exciting drug, especially given the dearth of effective therapies for this bad form of cancer," Sanford Bernstein analyst Tim Anderson said in a research note.Advanced melanoma is one of the deadliest cancers and can quickly spread from the skin to internal organs, such as the brain. Once melanoma spreads to other organs the average survival is typically only six to nine months.
The Phase III study of previously untreated patients compared ipilimumab in combination with chemotherapy against chemotherapy alone.
Patients in the study had stage III or stage IV melanoma. Stage IV is the most advanced form of the disease.
"If prior results are any gauge, then the drug likely gives a meaningful two-year survival benefit compared with monotherapy treatment and will likely show again that a smaller proportion of patients (15 percent of so) have a near-cure like response, said Anderson, who forecast worldwide ipilimumab sales reaching $1.7 billion in 2015.
Stocks Bristol Myers Squibb Co
BMY.N$27.29+0.86+3.25%03/25/2011 The promise of ipilimumab has created new hope for desperately ill patients, many of whom in the earlier study survived well beyond the four-month average. At the time those results were unveiled last June, more than 20 percent of those who took the drug were still alive after two years.
A consensus forecast of four analysts compiled by Thomson Reuters calls for ipilimumab sales to reach about $820 million by 2015.
(Reporting by Bill Berkrot and Lewis Krauskopf; Editing by Richard Chang, Bernard Orr)
Health
Image via WikipediaRelated articles
- BREAKING NEWS: FDA approves Bristol's Yervoy (ipilimumab) for melanoma (fiercebiotech.com)
- FDA clears first melanoma drug to extend survival (msnbc.msn.com)
- First Melanoma Drug Approved, Hailed As Cancer 'Breakthrough' (huffingtonpost.com)
- FDA clears first melanoma drug to extend life (cbsnews.com)
Pfizer's To Present Lung Cancer Data July 3-7
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Image via CrunchBase Pfizer Inc. will present early and mid-stage data from its lung cancer portfolio, including PF-00299804 (PF-299) an investigational, oral, pan-HER inhibitor;1 and crizotinib, an investigational, oral, first-in-class compound that inhibits the anaplastic lymphoma kinase, or ALK,2 at the International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), July 3-7 in Amsterdam, The Netherlands.
“While lung cancer remains a difficult-to-treat disease, we’re learning more about how therapies like crizotinib and PF-299 may be able to specifically target ALK or the HER pathway, respectively, and how this may lead to more rationally selected and personalized therapy,” said Maurizio Voi, MD, Thoracic Tumor Strategy Lead, Pfizer Oncology. “Data being presented show survival outcomes for PF-299 and crizotinib, as well as quality-of-life or patient-reported outcomes after treatment for patients with non small cell lung cancer, which represent important considerations in determining the best treatment option for these patients.”
First Presentation of PF-299 Preliminary Overall Survival Data
Continued....
Pfizer will present, for the first time, preliminary overall survival data from a Phase 2 study evaluating PF-299 vs erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after progression on at least one chemotherapy regimen (oral presentation, Abstract #745, Monday, July 4).1
Pfizer also will present patient-reported outcomes (PRO) from clinical trials of PF-299 in refractory and second-/third-line NSCLC, which provide a better understanding of the patient’s perspective of the burden of adverse events associated with treatment and how it may change over time.3,4
PF-299 targets multiple receptors of the HER pathway. PF-299 is an irreversible inhibitor of HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases. 6
Crizotinib Data to be presented:
At the WCLC, data on the anti-tumor activity, safety, overall survival, patient-reported and quality-of-life outcomes observed in clinical trials of Pfizer’s crizotinib will be presented.2,7,8
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. Pfizer Oncology has biologics and small molecules in clinical development and more than 100 clinical trials underway. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. For more information please visit www.Pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of June 28, 2011. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about various oncology product candidates, including their potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by regulatory authorities regarding whether and when to approve any drug applications that have been or may be filed for any such oncology product candidates as well as their decisions regarding labeling and other matters that could affect their availability or commercial potential; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and in its reports on Form 10-Q and Form 8-K.
1 World Lung Accepted Abstract #745. Overall Survival (OS) Results of a Randomized Phase 2 Trial of PF299804 versus Erlotinib in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) After Failure of Chemotherapy. Oral Session, Monday July 4, 2011: 3:35 PM – 3:45 PM CEST. M. Boyer – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
2 World Lung Accepted Abstract #1618. Phase 2 Data for Crizotinib (PF-02341066) in ALK-Positive Advanced Non-Small Cell Lung Cancer (NSCLC): PROFILE 1005. Oral Session, Wednesday July 6, 2011: 3:10 PM – 3:20 PM CEST. G. Riely – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
3 World Lung Accepted Abstract #957. Gastrointestinal Toxicity of the Pan-HER Tyrosine Kinase Inhibitor (TKI) PF299804: Assessment by Patient-Reported Outcomes in 2nd/3rd-Line and Refractory Non-Small Cell Lung Cancer (NSCLC). Poster Session, Wednesday July 6, 2011: 12:15 PM – 2:15 PM CEST. A. Campbell – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
4 World Lung Accepted Abstract #702. Dermatologic Adverse Events of the Pan-HER Tyrosine Kinase Inhibitor (TKI) PF299804: Assessment by Patient-Reported Outcomes in 2nd/3rd-line and Refractory Non-Small Cell Lung Cancer (NSCLC). Poster Session, Wednesday July 6, 2011: 12:15 PM – 2:15 PM CEST. A. Campbell – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
5 Clinicaltrials.gov. ARCHER 1009: A Phase 3 Study of PF-00299804, a Pan-HER Inhibitor, Vs. Erolotinib in the Treatment of Advanced Non-Small Cell Lung Cancer. Available here: http://www.clinicaltrials.gov/ct2/show/NCT01360554?term=ARCHER&rank=1. Accessed June 21, 2011.
6 Gonzales AJ, Hook KE, Althaus IW et al. Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbBreceptor tyrosine kinase inhibitor. Mol Cancer Ther. 2008;7:1880-89.
7 World Lung Accepted Abstract #1510. PROFILE 1005: Preliminary Patient-Reported Outcomes (PROs) from an Ongoing Phase 2 Study of Crizotinib (PF-02341066) in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC). Oral Session, Wednesday July 6, 2011: 3:30 PM – 3:40 PM CEST. F. Blackhall – Presenter. Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
8 World Lung Accepted Abstract #1207. Crizotinib improves overall survival of ALK-positive patients with advanced NSCLC compared with historical controls. Oral Session, Wednesday July 6, 2011: 3:20 PM – 3:30 PM CEST. A. Shaw – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
9 World Lung Accepted Abstract #1349. Efficacy of Crizotinib in Retrospective Comparisons with Standard-Of-Care (SOC) Regimens from Three Pfizer-Sponsored Clinical Trials in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC). Poster Session, Wednesday July 6, 2011: 12:15 PM – 2:15 PM CEST. Y. Tang – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
10 Bang Y et al. Clinical Activity of the Oral ALK Inhibitor, Crizotinib (PF-02341066), in Patients with ALK-positive Non-Small Cell Lung Cancer. Accepted Plenary Presentation at the American Society of Clinical Oncology Annual Meeting, June 4-8, 2010. Chicago, IL.
11 Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of c-MET,
PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007;67:4408-4417.
12 Chiarle R, Voena C, Ambrogio C et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1): 11-23.
Image via CrunchBase Pfizer Inc. will present early and mid-stage data from its lung cancer portfolio, including PF-00299804 (PF-299) an investigational, oral, pan-HER inhibitor;1 and crizotinib, an investigational, oral, first-in-class compound that inhibits the anaplastic lymphoma kinase, or ALK,2 at the International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), July 3-7 in Amsterdam, The Netherlands. “While lung cancer remains a difficult-to-treat disease, we’re learning more about how therapies like crizotinib and PF-299 may be able to specifically target ALK or the HER pathway, respectively, and how this may lead to more rationally selected and personalized therapy,” said Maurizio Voi, MD, Thoracic Tumor Strategy Lead, Pfizer Oncology. “Data being presented show survival outcomes for PF-299 and crizotinib, as well as quality-of-life or patient-reported outcomes after treatment for patients with non small cell lung cancer, which represent important considerations in determining the best treatment option for these patients.”
First Presentation of PF-299 Preliminary Overall Survival Data
Continued....
Pfizer will present, for the first time, preliminary overall survival data from a Phase 2 study evaluating PF-299 vs erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after progression on at least one chemotherapy regimen (oral presentation, Abstract #745, Monday, July 4).1
Pfizer also will present patient-reported outcomes (PRO) from clinical trials of PF-299 in refractory and second-/third-line NSCLC, which provide a better understanding of the patient’s perspective of the burden of adverse events associated with treatment and how it may change over time.3,4
- Gastrointestinal toxicity of the pan-HER tyrosine kinase inhibitor (TKI) PF299804: Assessment by patient-reported outcomes in second-/third-line and refractory NSCLC (poster session, Abstract #957, Wednesday, July 6)3
- Dermatologic adverse events of the pan-HER tyrosine kinase inhibitor (TKI) PF299804: Assessment by patient-reported outcomes in second-/third-line and refractory NSCLC (poster session, Abstract #702, Wednesday, July 6)4
PF-299 targets multiple receptors of the HER pathway. PF-299 is an irreversible inhibitor of HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases. 6
Crizotinib Data to be presented:
At the WCLC, data on the anti-tumor activity, safety, overall survival, patient-reported and quality-of-life outcomes observed in clinical trials of Pfizer’s crizotinib will be presented.2,7,8
- Phase 2 data for crizotinib in ALK-positive advanced NSCLC: PROFILE 1005 (oral presentation, Abstract #1618, Wednesday, July 6)2
- PROFILE 1005: Preliminary patient-reported outcomes (PROs) from an ongoing Phase 2 study of crizotinib in ALK-positive advanced NSCLC (oral presentation, Abstract #1510, Wednesday, July 6)7
- Crizotinib improves overall survival of ALK-positive patients with advanced NSCLC compared with historical controls (oral presentation, Abstract #1207, Wednesday, July 6)8
- Efficacy of crizotinib in retrospective comparisons with standard-of-care (SOC) regimens from three Pfizer-sponsored clinical trials in patients with advanced NSCLC (poster session, Abstract #1349, Wednesday, July 6)9
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. Pfizer Oncology has biologics and small molecules in clinical development and more than 100 clinical trials underway. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. For more information please visit www.Pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of June 28, 2011. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about various oncology product candidates, including their potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by regulatory authorities regarding whether and when to approve any drug applications that have been or may be filed for any such oncology product candidates as well as their decisions regarding labeling and other matters that could affect their availability or commercial potential; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2010 and in its reports on Form 10-Q and Form 8-K.
1 World Lung Accepted Abstract #745. Overall Survival (OS) Results of a Randomized Phase 2 Trial of PF299804 versus Erlotinib in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) After Failure of Chemotherapy. Oral Session, Monday July 4, 2011: 3:35 PM – 3:45 PM CEST. M. Boyer – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
2 World Lung Accepted Abstract #1618. Phase 2 Data for Crizotinib (PF-02341066) in ALK-Positive Advanced Non-Small Cell Lung Cancer (NSCLC): PROFILE 1005. Oral Session, Wednesday July 6, 2011: 3:10 PM – 3:20 PM CEST. G. Riely – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
3 World Lung Accepted Abstract #957. Gastrointestinal Toxicity of the Pan-HER Tyrosine Kinase Inhibitor (TKI) PF299804: Assessment by Patient-Reported Outcomes in 2nd/3rd-Line and Refractory Non-Small Cell Lung Cancer (NSCLC). Poster Session, Wednesday July 6, 2011: 12:15 PM – 2:15 PM CEST. A. Campbell – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
4 World Lung Accepted Abstract #702. Dermatologic Adverse Events of the Pan-HER Tyrosine Kinase Inhibitor (TKI) PF299804: Assessment by Patient-Reported Outcomes in 2nd/3rd-line and Refractory Non-Small Cell Lung Cancer (NSCLC). Poster Session, Wednesday July 6, 2011: 12:15 PM – 2:15 PM CEST. A. Campbell – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
5 Clinicaltrials.gov. ARCHER 1009: A Phase 3 Study of PF-00299804, a Pan-HER Inhibitor, Vs. Erolotinib in the Treatment of Advanced Non-Small Cell Lung Cancer. Available here: http://www.clinicaltrials.gov/ct2/show/NCT01360554?term=ARCHER&rank=1. Accessed June 21, 2011.
6 Gonzales AJ, Hook KE, Althaus IW et al. Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbBreceptor tyrosine kinase inhibitor. Mol Cancer Ther. 2008;7:1880-89.
7 World Lung Accepted Abstract #1510. PROFILE 1005: Preliminary Patient-Reported Outcomes (PROs) from an Ongoing Phase 2 Study of Crizotinib (PF-02341066) in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC). Oral Session, Wednesday July 6, 2011: 3:30 PM – 3:40 PM CEST. F. Blackhall – Presenter. Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
8 World Lung Accepted Abstract #1207. Crizotinib improves overall survival of ALK-positive patients with advanced NSCLC compared with historical controls. Oral Session, Wednesday July 6, 2011: 3:20 PM – 3:30 PM CEST. A. Shaw – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
9 World Lung Accepted Abstract #1349. Efficacy of Crizotinib in Retrospective Comparisons with Standard-Of-Care (SOC) Regimens from Three Pfizer-Sponsored Clinical Trials in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC). Poster Session, Wednesday July 6, 2011: 12:15 PM – 2:15 PM CEST. Y. Tang – Presenter. International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), Amsterdam, The Netherlands. July 3-7, 2011.
10 Bang Y et al. Clinical Activity of the Oral ALK Inhibitor, Crizotinib (PF-02341066), in Patients with ALK-positive Non-Small Cell Lung Cancer. Accepted Plenary Presentation at the American Society of Clinical Oncology Annual Meeting, June 4-8, 2010. Chicago, IL.
11 Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of c-MET,
PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007;67:4408-4417.
12 Chiarle R, Voena C, Ambrogio C et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1): 11-23.
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- Benefit of targeted lung cancer therapy confirmed (eurekalert.org)
- Pfizer drug shows double survival time for certain lung cancer patients (nj.com)
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Amgen submits BLA for XGEVA
To contact us Click HERE
Image via WikipediaTHOUSAND OAKS, Calif., June 27, 2011 /PRNewswire/ --
Amgen (NASDAQ: AMGN) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) to expand the indication for XGEVA® (denosumab) to treat men with castrate-resistant prostate cancer to reduce the risk of developing bone metastases. If approved, XGEVA would be the first therapy licensed to prevent or delay the spread of cancer to the bone.
The sBLA submission is based on a pivotal Phase 3 Study ('147) evaluating XGEVA versus placebo in 1,432 men with castrate-resistant prostate cancer. Results of the '147 study demonstrate that XGEVA significantly prolonged bone metastasis-free survival by more than four months compared with placebo (29.5 versus 25.2 months, respectively) in men with castrate-resistant prostate cancer that had not yet spread to the bone.
Bone metastasis-free survival is a composite measure of the development of bone metastases or death.
"The successful outcome of this study provides clinical evidence supporting the view that tumors activate the RANK Ligand pathway to penetrate bone," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "XGEVA has the potential to become a significant advance for patients with castrate-resistant prostate cancer who currently have no treatment options to help prevent the spread of cancer to their bones."
Continued
Bone is one of the most common places for cancer to spread. In fact, up to 90 percent of men with advanced prostate cancer will have their tumor spread to the bone.(i),(ii),(iii) With effective therapies now in place for both early (castrate-sensitive) prostate cancer and advanced (castrate-resistant) metastatic prostate cancer, there is a gap in the treatment plan for those patients who are castrate-resistant but have not yet developed metastatic disease.
In the '147 trial, adverse events and serious adverse events were relatively similar between the XGEVA and placebo arms. Hypocalcemia and osteonecrosis of the jaw (ONJ) were reported with increased frequencies in the XGEVA treated patients. The yearly rate of ONJ in the XGEVA arm was similar to prior XGEVA trial results. Back pain was the most common adverse event reported in the XGEVA arm of the trial.
About XGEVA
XGEVA is the first and only RANK Ligand inhibitor approved by the FDA indicated for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the FDA. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. XGEVA is the first novel bone metastases treatment for advanced cancer patients in nearly a decade. Delivered as an every four week 120 mg subcutaneous injection, XGEVA provides a unique option for urologists and oncologists to prevent SREs in patients with advanced cancer.
XGEVA is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). XGEVA prevents RANK Ligand from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction.
XGEVA has been studied in over 7,000 patients with cancer. In clinical trials, XGEVA demonstrated a clinically meaningful improvement compared to the previous standard of care in preventing bone complications. XGEVA is also being investigated for the potential use to delay the onset of bone metastasis in adjuvant breast cancer.
XGEVA Skeletal-Related Events Regulatory Status
XGEVA is currently approved in the U.S. for the prevention of SREs in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the FDA. In the U.S., XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.(iv) XGEVA is also approved in Canada for reducing the risk of developing SREs in patients with bone metastases from breast cancer, prostate cancer, non-small cell lung cancer, and other solid tumors. In Canada, XGEVA is not indicated for reducing the risk of developing SREs in patients with multiple myeloma.
Amgen has also submitted marketing applications for XGEVA in Australia, Mexico, Russia, Switzerland and the European Union. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited and a marketing application was submitted in August. In addition,Amgen and GlaxoSmithKline (GSK) have a collaboration agreement for the commercialization of XGEVA in a number of countries where Amgen does not currently have a commercial presence. In these countries, marketing applications are filed by GSK.
For more information on XGEVA, please visit www.XGEVA.com.
Denosumab is also marketed as Prolia® in other indications.
XGEVA Important Safety Information
XGEVA can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
ONJ can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
The most common adverse reactions in patients receiving XGEVA were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction in patients receiving XGEVA was dyspnea. The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis and hypocalcemia. Please visit www.amgen.com for full prescribing information.
Bone Metastases and Skeletal-Related Events: Prevalence and Impact
Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 90 percent of patients with metastatic disease.(v),(vi),(vii),(viii)
Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.(ix),(x),(xi) Events considered to be SREs include fractures, spinal cord compression and severe bone pain that may require surgery or radiation.(xii) Such events can profoundly disrupt a patient's life and can cause disability and pain.(xiii),(xiv),(xv)
About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
Image via WikipediaTHOUSAND OAKS, Calif., June 27, 2011 /PRNewswire/ --Amgen (NASDAQ: AMGN) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) to expand the indication for XGEVA® (denosumab) to treat men with castrate-resistant prostate cancer to reduce the risk of developing bone metastases. If approved, XGEVA would be the first therapy licensed to prevent or delay the spread of cancer to the bone.
The sBLA submission is based on a pivotal Phase 3 Study ('147) evaluating XGEVA versus placebo in 1,432 men with castrate-resistant prostate cancer. Results of the '147 study demonstrate that XGEVA significantly prolonged bone metastasis-free survival by more than four months compared with placebo (29.5 versus 25.2 months, respectively) in men with castrate-resistant prostate cancer that had not yet spread to the bone.
Bone metastasis-free survival is a composite measure of the development of bone metastases or death.
"The successful outcome of this study provides clinical evidence supporting the view that tumors activate the RANK Ligand pathway to penetrate bone," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "XGEVA has the potential to become a significant advance for patients with castrate-resistant prostate cancer who currently have no treatment options to help prevent the spread of cancer to their bones."
Continued
Bone is one of the most common places for cancer to spread. In fact, up to 90 percent of men with advanced prostate cancer will have their tumor spread to the bone.(i),(ii),(iii) With effective therapies now in place for both early (castrate-sensitive) prostate cancer and advanced (castrate-resistant) metastatic prostate cancer, there is a gap in the treatment plan for those patients who are castrate-resistant but have not yet developed metastatic disease.
In the '147 trial, adverse events and serious adverse events were relatively similar between the XGEVA and placebo arms. Hypocalcemia and osteonecrosis of the jaw (ONJ) were reported with increased frequencies in the XGEVA treated patients. The yearly rate of ONJ in the XGEVA arm was similar to prior XGEVA trial results. Back pain was the most common adverse event reported in the XGEVA arm of the trial.
About XGEVA
XGEVA is the first and only RANK Ligand inhibitor approved by the FDA indicated for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the FDA. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. XGEVA is the first novel bone metastases treatment for advanced cancer patients in nearly a decade. Delivered as an every four week 120 mg subcutaneous injection, XGEVA provides a unique option for urologists and oncologists to prevent SREs in patients with advanced cancer.
XGEVA is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). XGEVA prevents RANK Ligand from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction.
XGEVA has been studied in over 7,000 patients with cancer. In clinical trials, XGEVA demonstrated a clinically meaningful improvement compared to the previous standard of care in preventing bone complications. XGEVA is also being investigated for the potential use to delay the onset of bone metastasis in adjuvant breast cancer.
XGEVA Skeletal-Related Events Regulatory Status
XGEVA is currently approved in the U.S. for the prevention of SREs in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the FDA. In the U.S., XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.(iv) XGEVA is also approved in Canada for reducing the risk of developing SREs in patients with bone metastases from breast cancer, prostate cancer, non-small cell lung cancer, and other solid tumors. In Canada, XGEVA is not indicated for reducing the risk of developing SREs in patients with multiple myeloma.
Amgen has also submitted marketing applications for XGEVA in Australia, Mexico, Russia, Switzerland and the European Union. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited and a marketing application was submitted in August. In addition,Amgen and GlaxoSmithKline (GSK) have a collaboration agreement for the commercialization of XGEVA in a number of countries where Amgen does not currently have a commercial presence. In these countries, marketing applications are filed by GSK.
For more information on XGEVA, please visit www.XGEVA.com.
Denosumab is also marketed as Prolia® in other indications.
XGEVA Important Safety Information
XGEVA can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
ONJ can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
The most common adverse reactions in patients receiving XGEVA were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction in patients receiving XGEVA was dyspnea. The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis and hypocalcemia. Please visit www.amgen.com for full prescribing information.
Bone Metastases and Skeletal-Related Events: Prevalence and Impact
Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 90 percent of patients with metastatic disease.(v),(vi),(vii),(viii)
Approximately 50-70 percent of cancer patients with bone metastases will experience debilitating SREs.(ix),(x),(xi) Events considered to be SREs include fractures, spinal cord compression and severe bone pain that may require surgery or radiation.(xii) Such events can profoundly disrupt a patient's life and can cause disability and pain.(xiii),(xiv),(xv)
About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
Related articles
- Amgen Receives Positive Opinion for XGEVA(TM) (Denosumab) in the European Union (biospace.com)
- Xgeva: new drug for bone mets: answers to recent questions (donnapeach.com)
- Is Amgen the Right Stock to Retire With? (fool.com)
- Amgen says it will pay dividend starting in 2Q (sfgate.com)
- A Quick Roundup Of The New Drugs Presented At This Weekend's Huge Oncology Conference (CELG, AMGN, AVEO, MDVN) (businessinsider.com)
28 Eylül 2012 Cuma
Saturday spring thing
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Gentle Reader, whatever are you doing on this warm sunny day?
No need to ask. You're reading a silly blog post written by someone who is most likely a stranger to you. May we benevolently suggest that you STOP. READING. NOW. PLEASE. Go, go away! Have a hula hoop off with your favorite five year old, write poetry on the patio, bicycle-race friends to the beach.
Hmph. Someone's not listening.
Fine: go ahead. Dismiss our direction. Do not keep reading; do not harvest your neighbor's unsprayed lavender; and do not see the Herb Farm Cookbook recipe for lavender shortbread. Halt! Do not read Margaret Atwood's Encouragement to the Young while the shortbread bakes and by all means do not share the shortbread with friends distressed from unemployment or academic-related anxiety.
Perhaps you are reading this because you yourself suffer student writer's block or are stranded sans paid work. If so we send you a sympathetic smile and we hope that someone special bakes for you.
For the rest of you: do not ever, ever return to read GAP.
Machine magnifica
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What might Pam Beesly see in the Espresso Book Machine?
Photo via The Guardian
What might Pam Beesly see in the Espresso Book Machine?
Photo via The Guardian
An Espresso Book Machine, whose name is more sophisticated than its appearance, just debuted at Blackwell's Charing Cross Road branch in London. Creators of the 2007 Time Invention of the Year say that their machine enables smaller bookstores to have the opportunity to compete with stock-holding shops and Amazon. A contentious claim. What is certain is that Blackwell's customers can now access almost half a million books including a fascimile of the original manuscript of Alice in Wonderland. Lucky Londoners! The company is working with publishers in the UK to increase access to in-copyright writings. It hopes to have over a million titles by the end of the summer, or an astounding alleged equivalent of 23.6 miles of shelf space. That is just a few more than the 200 titles the World Bank's InfoShop inaugurated in April 2006. Libraries as well are employing the Espresso as a major space saver: in September the University of Michigan proudly announced itself as the first university to purchase the machine. Mind you, the library's offering is limited to printed and out-of-copyright books from its digitized collection of nearly 2 million, and thousands of books from the Open Content Alliance and other digital sources.* Let's hope this dream-machine isn't ultimately corrupted to a nightmare of self-publishing?
*The Espresso purchase PR is since dwarfed by highlights on self-healing concrete, a spine-tingling vest, and how a baby mammoth study validated a researcher.
Robots versus Poachers
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National Geographic is running an interesting article on the efforts of wildlife officials in the US to catch poachers using robotic decoy animals as bait. The robots mimic the behavior of wild animals and are much more resilient than their non-metallic counterparts. The obvious next step here is to make robotic animals that actually arrest the poachers themselves.
On a related note Talk of the Nation's Science Friday had a good segment on animal CSI yesterday.
On a related note Talk of the Nation's Science Friday had a good segment on animal CSI yesterday.
What diplomats!
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LYSISTRATA: Good day, Lampito, dear friend from Lacedaemon! How well and handsome you look! what a rosy complexion! and how strong you seem; why, you could strangle a bull surely!
LAMPITO: Yes, indeed I really think I could. 'Tis because I do gymnastics and practice the 'kick dance.
LYSISTRATA: And what superb bosoms!
LAMPITO: La! You are feeling me as if I were a beast for sacrifice.
Lysistrata, Act I, Scene I
Lysistrata reminds us how to get a good start in terms of solidarity: a warm greeting that affirms strength and beauty (and also attracts the audience) but doesn't take offense at a smart retort. On this subject of solidarity --and attention, now that we caught yours-- various news agencies have been reporting on the week-long Kenyan women's political protest that is a "sex strike," organized by women's NGOs such as Women's Development Organisation. A male Kenyan legislator is reported to be upset. Moving on... International news media coverage of similar protests in the recent past highlights diverse agents and causes. Headlines have featured Cameroonian women angered by crop destruction (2003), Pereiran (Colombian) wives and girlfriends of "gang members" appalled by violence (2006), and Naples women opposed to men using dangerous fireworks (2008). Radical, longer-term activisms, such as the one based upon the booklet Love Your Enemy?, have taken their own place in history and the present. The anti-misogyny that roots such a (sub-)movement brings to mind the great risk some women assume to participate in attention-getting abstinence. Looking ahead, it will be interesting to see how changes in economic status and the general social construction of reality are reflected in the motivation, composition, strategy and achievement of these (in)actions that can be ever so diplomatic.
LAMPITO: Yes, indeed I really think I could. 'Tis because I do gymnastics and practice the 'kick dance.
LYSISTRATA: And what superb bosoms!
LAMPITO: La! You are feeling me as if I were a beast for sacrifice.
Lysistrata, Act I, Scene I
Lysistrata reminds us how to get a good start in terms of solidarity: a warm greeting that affirms strength and beauty (and also attracts the audience) but doesn't take offense at a smart retort. On this subject of solidarity --and attention, now that we caught yours-- various news agencies have been reporting on the week-long Kenyan women's political protest that is a "sex strike," organized by women's NGOs such as Women's Development Organisation. A male Kenyan legislator is reported to be upset. Moving on... International news media coverage of similar protests in the recent past highlights diverse agents and causes. Headlines have featured Cameroonian women angered by crop destruction (2003), Pereiran (Colombian) wives and girlfriends of "gang members" appalled by violence (2006), and Naples women opposed to men using dangerous fireworks (2008). Radical, longer-term activisms, such as the one based upon the booklet Love Your Enemy?, have taken their own place in history and the present. The anti-misogyny that roots such a (sub-)movement brings to mind the great risk some women assume to participate in attention-getting abstinence. Looking ahead, it will be interesting to see how changes in economic status and the general social construction of reality are reflected in the motivation, composition, strategy and achievement of these (in)actions that can be ever so diplomatic.
What's your Drinking Personality?
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The BBC is running a fluffy piece on peoples drinking personalities. It seems a psychologist, Dr. Glenn Willson, has observed the behavior of 500 Brits while at bars and pubs and found that their body language belies their personality. The good doctor has determined that their are eight distinct "drinking personalities". No more, no less.
From the article:
Image via the BBC.
From the article:THE JACK-THE-LADSo, what's your drinking personality? I think I am clearly the "Ice Queen."This "peacock" is conscious of his image and will drink a bottled beer, or cider.
He is inclined to be confident and arrogant, and can be territorial in his gestures, spreading himself over as much space as possible, for example, pushing the glass well away from himself and leaning back in his chair.
If he is drinking with friends, he would be unlikely to welcome approaches from outside the group, unless sycophantic and ego-enhancing.
Image via the BBC.
27 Eylül 2012 Perşembe
Safe medicine For Genital Herpes - Are Over-the-Counter Drugs Safe and Effective?
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The content is good quality and useful content, That is new is that you just never knew before that I know is that I have discovered. Prior to the distinctive. It is now near to enter destination Safe medicine For Genital Herpes - Are Over-the-Counter Drugs Safe and Effective?.
Do you know about - Safe medicine For Genital Herpes - Are Over-the-Counter Drugs Safe and Effective?
Treatment For Hpv! Again, for I know. Ready to share new things that are useful. You and your friends.Many healing experts were left dumbfounded by how covertly this Hsv-2 virus, the one responsible for causing genital herpes spreads. Until now miniature is known why this virus cannot be cured. It is only known that this virus can be "latent" for a very long time, but what is the cause of its latency is still vague. It seems that this aspect of the virus itself is not very about that the trend among healing experts was to find a treatment that could cure it or at least counter its effects.
What I said. It is not outcome that the real about Treatment For Hpv. You look at this article for info on a person need to know is Treatment For Hpv.How is Safe medicine For Genital Herpes - Are Over-the-Counter Drugs Safe and Effective?
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A handful of over-the-counter medicines are already ready right now in the market. Each of them claiming and trying to incorporate them-selves with the highest reputation that herpes antidote has reached by now. All of them claiming to be the most victorious but the examine that is frequently raised towards these breakthrough medicines is that, how sufficient are they in combating herpes virus? And, are they safe?
Well the most likely who can answer these questions are the ones prescribing and assessing the victims directly, the doctors, together with the firsthand accounts of those victims who had already experienced the healing power of such medicines.
The effectiveness of a treatment is directly proportional to the tolerance or resistance of a sick person towards that sure treatment prescribed to him by his physician. It also depends on the current corporal situation and the current state or extent of the damage caused by the infection, as in the case of genital herpes that the treatment would prove successful. In other words, the safeness and effectiveness of each of the over-the-counter anti-herpes drugs is very subjective. A treatment regimen intended for those herpes victims having a compromised immune law would be very dangerous or otherwise no consequent at all when used to treat those with general body conditions, and vice versa.
Over-the-counter Safety
As the term implies, over-the-counter drugs could be purchased even without prescribe from a doctor per se. It doesn't need any permission also from anybody that's why any herpes victim can effortlessly get his/her treatment without any restriction at all. The reckon for these kinds of medicines to be unrestricted is that they all passed a minimum safety requirement, the set thorough of safety for the majority of people, that's why they were commonly safe at all.
When it comes to its effect, over-the-counter drugs for genital herpes depend on how bad the extent of the infection itself. Some infected persons plainly heal faster than others that's why it is relative to say that safety and effectiveness of this kind of drug in relation to herpes depends greatly on the current infection state, the more early the infection is treated, the more sufficient and safe the treatment is.
I hope you get new knowledge about Treatment For Hpv. Where you can put to easy use in your day-to-day life. And just remember, your reaction is Treatment For Hpv.View Related articles associated with Treatment For Hpv. I Roll below. I have suggested my friends to assist share the Facebook Twitter Like Tweet. Can you share Safe medicine For Genital Herpes - Are Over-the-Counter Drugs Safe and Effective?.Related Articles
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