Influenza is and remains a disease to reckon with. Seasonal epidemics around the world kill several hundred thousand people every year. In the light of looming pandemics if bird flu strains develop the ability to infect humans easily, new drugs and vaccines are desperately sought. Researchers at the European Molecular Biology Laboratory (EMBL) and the joint Unit of Virus Host-Cell Interaction (UVHCI) of EMBL, the University Joseph Fourier (UJF) and the National Centre for Scientific Research (CNRS), in Grenoble, France, have now precisely defined an important drug target in influenza. In this week's Nature they publish a high-resolution image of a crucial protein domain that allows the virus to hijack human cells and multiply in them.
When the influenza virus infects a host cell its goal is to produce many copies of itself that go on to attack even more cells. A viral enzyme, called polymerase, is key to this process. It both copies the genetic material of the virus and steers the host cell machinery towards the synthesis of viral proteins. It does this by stealing a small tag, called a cap, from host cell RNA molecules and adding it onto its own. The cap is a short extra piece of RNA, which must be present at the beginning of all messenger RNAs (mRNAs) to direct the cell's protein-synthesis machinery to the starting point. The viral polymerase binds to host cell mRNA via its cap, cuts the cap off and adds it to the beginning of its own mRNA - a process known as 'cap snatching'. But exactly how the polymerase achieves this and which of the three subunits of the enzyme does what, has remained controversial.
Researchers of the groups of Rob Ruigrok at the UVHCI and Stephen Cusack at EMBL have now discovered that part of a polymerase subunit called PA is responsible for cleaving the cap off the host mRNA.
"Our results came as a big surprise, because everybody thought that the cleaving activity resides in a different part of the polymerase," explains Rob Ruigrok, Vice-Director of the UVHCI.
"These new insights make PA a promising antiviral drug target. Inhibiting the cleaving of the cap is an efficient way to stop infection, because the virus can no longer multiply. Now we know where to focus drug design efforts," adds Stephen Cusack, Head of EMBL Grenoble and Director of the UVHCI.
The researchers produced crystals of the crucial PA domain and examined them with the powerful X-ray beams of the European Synchrotron Radiation Facility (ESRF) in Grenoble. The high-resolution image of the domain reveals the individual amino acids that constitute the active site responsible for cleaving the RNA; information that could guide the design of future antiviral drugs.
Only a few months ago the same group of scientists had already identified another key part of the influenza polymerase; a domain in the subunit called PB2 that recognises and binds to the host cap. Taken together the two findings provide a close-to-complete picture of the cap snatching mechanism that allows the influenza virus to take control over human cells.
Source: Anna-Lynn Wegener
European Molecular Biology Laboratory
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вторник, 13 сентября 2011 г.
New High-Speed Internet Health Information Network To Connect Colorado's Urban, Rural Health Care Providers
The Colorado Hospital Association (CHA) and the Colorado Behavioral Healthcare Council (CBHC) today announced that they have selected Qwest Communications (NYSE: Q) to provide high-speed broadband services that will link nearly 400 of the state's urban and rural health care and behavioral health providers, and facilitate telemedicine access. Once complete, the Colorado Telehealth Network will be the among the largest health care information networks in the United States.
The Colorado Telehealth Network, managed by CHA and CBHC and powered by Qwest, will also move Colorado one step closer to achieving one of Gov. Bill Ritter's promises: to significantly expand broadband communication to rural areas of the state.
"The ability of Colorado's health care providers to accurately exchange information with each other in a timely fashion is a critical component of the state's efforts to make health care more affordable, and to improve coverage and access," Ritter said. "I am pleased to see our vision of an interconnected system move one step closer to reality."
Once completed, the Colorado Telehealth Network will connect nearly 400 hospitals, clinics and other health care and behavioral health providers in Colorado to Qwest's national fiber-optic network and enable them to provide patients-especially those in rural areas-with state-of-the-art, long-distance medical care using speeds up to 100 megabits per second.
"Too many rural communities are isolated from many of the advanced diagnosis and treatment technologies available in urban areas," said CHA President and CEO Steven J. Summer. "The Colorado Telehealth Network, when implemented, will enable Coloradans to receive the right care, at the right place and at the right time."
Telehealth and telemedicine services provide patients in rural areas with access to critically needed medical specialists, in some instances without leaving their homes or communities. Intensive care providers can monitor critically ill patients around the clock and video conferencing allows specialists and mental health professionals to care for patients in different rural locations, often hundreds of miles away. The network will enhance the delivery of health services, help control costs and make care more affordable, reduce travel time for consumers, decrease medical errors and enable health care providers to share critical information. It also will minimize the amount of time workers are away from their jobs visiting health care professionals.
"The Colorado Telehealth Network will promote better health in many ways, while greatly reducing the need for rural residents to travel long distances to receive quality care," said George DelGrosso, executive director of the Colorado Behavioral Healthcare Council. "This innovative system will save lives and scarce health care resources."
Qwest will manage metro optical Ethernet and data networking technology to provide a secure, reliable, scalable voice and data platform to health care providers of all sizes, enabling them to share critical medical information over large distances, control costs and reduce patient travel time, thereby providing a better patient care experience. The high level of security and around-the-clock network management Qwest provides will help these medical institutions meet HIPAA compliance requirements.
"The Colorado Telehealth Network is an example of how Qwest's network solutions can eliminate the obstacle of geography and revolutionize the delivery of quality health care in rural areas of the state," said Sharon Montgomery, vice president, Qwest Government and Education Solutions. "Hospitals and clinics of all sizes will be able to use this technology to extend their reach to access remote information and expertise to deliver quality patient care to every community, regardless of location or size."
The Colorado Telehealth Network is funded by collaborating two awards from the Federal Communications Commission (FCC). An FCC award to CHA provides up to $4.6 million in federal funds over three years. When combined with a similar award to CBHC, $9.8 million will be available for the initiative. In addition, a 15 percent match from participating health care providers will supplement the program.
CHA and CBHC expect that the Colorado Telehealth Network will connect approximately 70 percent of the 388 eligible facilities by the end of the year and will complete connectivity in early 2010.
Source
Qwest Business
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The Colorado Telehealth Network, managed by CHA and CBHC and powered by Qwest, will also move Colorado one step closer to achieving one of Gov. Bill Ritter's promises: to significantly expand broadband communication to rural areas of the state.
"The ability of Colorado's health care providers to accurately exchange information with each other in a timely fashion is a critical component of the state's efforts to make health care more affordable, and to improve coverage and access," Ritter said. "I am pleased to see our vision of an interconnected system move one step closer to reality."
Once completed, the Colorado Telehealth Network will connect nearly 400 hospitals, clinics and other health care and behavioral health providers in Colorado to Qwest's national fiber-optic network and enable them to provide patients-especially those in rural areas-with state-of-the-art, long-distance medical care using speeds up to 100 megabits per second.
"Too many rural communities are isolated from many of the advanced diagnosis and treatment technologies available in urban areas," said CHA President and CEO Steven J. Summer. "The Colorado Telehealth Network, when implemented, will enable Coloradans to receive the right care, at the right place and at the right time."
Telehealth and telemedicine services provide patients in rural areas with access to critically needed medical specialists, in some instances without leaving their homes or communities. Intensive care providers can monitor critically ill patients around the clock and video conferencing allows specialists and mental health professionals to care for patients in different rural locations, often hundreds of miles away. The network will enhance the delivery of health services, help control costs and make care more affordable, reduce travel time for consumers, decrease medical errors and enable health care providers to share critical information. It also will minimize the amount of time workers are away from their jobs visiting health care professionals.
"The Colorado Telehealth Network will promote better health in many ways, while greatly reducing the need for rural residents to travel long distances to receive quality care," said George DelGrosso, executive director of the Colorado Behavioral Healthcare Council. "This innovative system will save lives and scarce health care resources."
Qwest will manage metro optical Ethernet and data networking technology to provide a secure, reliable, scalable voice and data platform to health care providers of all sizes, enabling them to share critical medical information over large distances, control costs and reduce patient travel time, thereby providing a better patient care experience. The high level of security and around-the-clock network management Qwest provides will help these medical institutions meet HIPAA compliance requirements.
"The Colorado Telehealth Network is an example of how Qwest's network solutions can eliminate the obstacle of geography and revolutionize the delivery of quality health care in rural areas of the state," said Sharon Montgomery, vice president, Qwest Government and Education Solutions. "Hospitals and clinics of all sizes will be able to use this technology to extend their reach to access remote information and expertise to deliver quality patient care to every community, regardless of location or size."
The Colorado Telehealth Network is funded by collaborating two awards from the Federal Communications Commission (FCC). An FCC award to CHA provides up to $4.6 million in federal funds over three years. When combined with a similar award to CBHC, $9.8 million will be available for the initiative. In addition, a 15 percent match from participating health care providers will supplement the program.
CHA and CBHC expect that the Colorado Telehealth Network will connect approximately 70 percent of the 388 eligible facilities by the end of the year and will complete connectivity in early 2010.
Source
Qwest Business
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LifeSaver - A Medical Emergency Record (EMR) And Medical History Repository On A Tiny Hardware Device
LifeSaver is a complete medical emergency record (EMR) and medical history repository on a tiny hardware device, portable in a wallet, on a necklace, or on a key ring.
If the bearer of this tiny USB drive is unable to speak, for example due to an accident, physical disability, injury or any other reason, LifeSaver will speak for her or him.
It contains all the pertinent emergency medical records / information that medical emergency response teams and doctors in a hospital need to correctly treat a patient; without wasting time on routine questions and tests hindering the rescue efforts. It contains the bearer's complete medical profile plus contact information and identifying pictures.
The patient's medical history, the medications, blood group, disabilities, insurance information and much more is instantly available. It can even be printed out, right in the ambulance and be delivered with the patient.
LifeSaver can be instrumental in saving lives for accident victims, disabled persons, soldiers, Alzheimer patients, diabetics, children, persons with life threatening allergies, boyscouts, outdoors / sports enthusiasts and many more.
It also includes MD, the bonus Medical Diary, which keeps track of blood glucose levels, cholesterol levels, weight and blood pressure values; all of which can be visualized as 3D charts and also as printouts.
A journal lets the owner keep track of their progress during dieting, disease tracking, visits, or their personal notes. Additionally, measurements and values can be visualized as 3D graphs or printed out.
Another important feature is the appointment book which lets the owner keep track of medical appointments and dates.
Lifesaver is a complete personal medical records software suite which can be the difference between life and death.
To a child injured away from home it could make the difference. To a parent with Alzheimer's it could mean a save return and treatment. To a sports or outdoors person it could mean rescue and/or identification and the list goes on...
Source:
wwwvivo/Main.htm
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If the bearer of this tiny USB drive is unable to speak, for example due to an accident, physical disability, injury or any other reason, LifeSaver will speak for her or him.
It contains all the pertinent emergency medical records / information that medical emergency response teams and doctors in a hospital need to correctly treat a patient; without wasting time on routine questions and tests hindering the rescue efforts. It contains the bearer's complete medical profile plus contact information and identifying pictures.
The patient's medical history, the medications, blood group, disabilities, insurance information and much more is instantly available. It can even be printed out, right in the ambulance and be delivered with the patient.
LifeSaver can be instrumental in saving lives for accident victims, disabled persons, soldiers, Alzheimer patients, diabetics, children, persons with life threatening allergies, boyscouts, outdoors / sports enthusiasts and many more.
It also includes MD, the bonus Medical Diary, which keeps track of blood glucose levels, cholesterol levels, weight and blood pressure values; all of which can be visualized as 3D charts and also as printouts.
A journal lets the owner keep track of their progress during dieting, disease tracking, visits, or their personal notes. Additionally, measurements and values can be visualized as 3D graphs or printed out.
Another important feature is the appointment book which lets the owner keep track of medical appointments and dates.
Lifesaver is a complete personal medical records software suite which can be the difference between life and death.
To a child injured away from home it could make the difference. To a parent with Alzheimer's it could mean a save return and treatment. To a sports or outdoors person it could mean rescue and/or identification and the list goes on...
Source:
wwwvivo/Main.htm
wwwvivo/Specials/MedicalNewsToday50.htm
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MedImmune Receives Complete Response Letter From FDA For New Formulation Of FluMist(R)
MedImmune, Inc.
(Nasdaq: MEDI) announced today that the U.S. Food and Drug Administration
(FDA) has issued a Complete Response Letter (CRL) for a supplemental
biologics license application (sBLA) related to the new formulation of
FluMist (Influenza Virus Vaccine Live, Intranasal) for the current approved
indication. With the sBLA, MedImmune is seeking approval to use
refrigerator-stable CAIV-T (cold adapted influenza vaccine, trivalent) in
preventing influenza in healthy individuals 5 to 49 years of age. The FDA
is requesting clarification and additional information relating to data
previously submitted.
"Based on our review of the letter received, we expect to fully respond
to the agency within two to four weeks," said Linda J. Peters, senior vice
president, regulatory affairs. "We are confident that our continued
interaction with the FDA will result in approval of the new formulation of
our intranasal vaccine in advance of the 2007-2008 influenza season. CAIV-T
will bring an added level of convenience to administering the vaccine and
establish the basis upon which the company plans to expand the product's
label."
MedImmune plans to submit a separate sBLA to the FDA within the next
few weeks requesting an expanded label for FluMist. This sBLA will include
data from a Phase 3 study involving approximately 8,500 children between 6
months and 59 months of age.
Ms. Peters added, "We remain on track with our plans to launch in time
for the 2007-2008 influenza season an improved formulation of our
intranasal influenza vaccine with an expanded indication down to one year
of age."
About FluMist
FluMist is indicated for active immunization for the prevention of
disease caused by influenza A and B viruses in healthy children and
adolescents, 5 to 17 years of age, and healthy adults, 18 to 49 years of
age. There are risks associated with all vaccines, including FluMist. Like
any vaccine, FluMist does not protect 100 percent of individuals
vaccinated. In studies of people between the ages of 5 and 49 years, runny
nose was the most commonly reported side effect. Other common side effects
included various cold-like symptoms, such as headache, cough, sore throat,
tiredness/weakness, irritability, and muscle aches.
FluMist should not be used, under any circumstances, in anyone with an
allergy to any part of the vaccine, including eggs; in children and
adolescents receiving aspirin therapy; in people who have a history of
Guillain-Barre syndrome; and in people with known or suspected immune
system problems. Pregnant women and people with certain medical conditions,
asthma, or reactive airways disease should not get FluMist.
Please see the Prescribing Information at: flumist/pdf/prescribinginfo.pdf or visit
flumist
About CAIV-T
CAIV-T is an investigational intranasal, cold-adapted trivalent
influenza vaccine. It is the next-generation, refrigerator-stable
formulation of FluMist, which is a frozen, live attenuated cold-adapted
trivalent influenza vaccine. To date, the safety, tolerability and efficacy
of CAIV-T has been studied in both healthy and at-risk populations between
the ages of 6 weeks and 98 years.
About MedImmune, Inc.
MedImmune strives to provide better medicines to patients, new medical
options for physicians, rewarding careers to employees, and increased value
to shareholders. Dedicated to advancing science and medicine to help people
live better lives, the company is focused on the areas of infectious
diseases, cancer and inflammatory diseases. With more than 2,300 employees
worldwide, MedImmune is headquartered in Maryland. For more information,
visit the company's website at medimmune.
This announcement contains, in addition to historical information,
certain "forward-looking statements" regarding the regulatory approval
process and development plans for CAIV-T. Such forward-looking statements
are based on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change current
expectations and could cause actual outcomes and results to differ
materially from current expectations. In addition to risks and
uncertainties discussed in MedImmune's filings with the U.S. Securities and
Exchange Commission, no assurance exists that development efforts for
CAIV-T will succeed, that CAIV-T will receive required regulatory approval
or that, even if regulatory approval is received, CAIV-T will be
commercially successful. MedImmune undertakes no obligation to update any
forward-looking statement, whether as a result of new information, future
events or otherwise except as may be required by applicable law or
regulation.
MedImmune, Inc.
medimmune
View drug information on FluMist.
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(Nasdaq: MEDI) announced today that the U.S. Food and Drug Administration
(FDA) has issued a Complete Response Letter (CRL) for a supplemental
biologics license application (sBLA) related to the new formulation of
FluMist (Influenza Virus Vaccine Live, Intranasal) for the current approved
indication. With the sBLA, MedImmune is seeking approval to use
refrigerator-stable CAIV-T (cold adapted influenza vaccine, trivalent) in
preventing influenza in healthy individuals 5 to 49 years of age. The FDA
is requesting clarification and additional information relating to data
previously submitted.
"Based on our review of the letter received, we expect to fully respond
to the agency within two to four weeks," said Linda J. Peters, senior vice
president, regulatory affairs. "We are confident that our continued
interaction with the FDA will result in approval of the new formulation of
our intranasal vaccine in advance of the 2007-2008 influenza season. CAIV-T
will bring an added level of convenience to administering the vaccine and
establish the basis upon which the company plans to expand the product's
label."
MedImmune plans to submit a separate sBLA to the FDA within the next
few weeks requesting an expanded label for FluMist. This sBLA will include
data from a Phase 3 study involving approximately 8,500 children between 6
months and 59 months of age.
Ms. Peters added, "We remain on track with our plans to launch in time
for the 2007-2008 influenza season an improved formulation of our
intranasal influenza vaccine with an expanded indication down to one year
of age."
About FluMist
FluMist is indicated for active immunization for the prevention of
disease caused by influenza A and B viruses in healthy children and
adolescents, 5 to 17 years of age, and healthy adults, 18 to 49 years of
age. There are risks associated with all vaccines, including FluMist. Like
any vaccine, FluMist does not protect 100 percent of individuals
vaccinated. In studies of people between the ages of 5 and 49 years, runny
nose was the most commonly reported side effect. Other common side effects
included various cold-like symptoms, such as headache, cough, sore throat,
tiredness/weakness, irritability, and muscle aches.
FluMist should not be used, under any circumstances, in anyone with an
allergy to any part of the vaccine, including eggs; in children and
adolescents receiving aspirin therapy; in people who have a history of
Guillain-Barre syndrome; and in people with known or suspected immune
system problems. Pregnant women and people with certain medical conditions,
asthma, or reactive airways disease should not get FluMist.
Please see the Prescribing Information at: flumist/pdf/prescribinginfo.pdf or visit
flumist
About CAIV-T
CAIV-T is an investigational intranasal, cold-adapted trivalent
influenza vaccine. It is the next-generation, refrigerator-stable
formulation of FluMist, which is a frozen, live attenuated cold-adapted
trivalent influenza vaccine. To date, the safety, tolerability and efficacy
of CAIV-T has been studied in both healthy and at-risk populations between
the ages of 6 weeks and 98 years.
About MedImmune, Inc.
MedImmune strives to provide better medicines to patients, new medical
options for physicians, rewarding careers to employees, and increased value
to shareholders. Dedicated to advancing science and medicine to help people
live better lives, the company is focused on the areas of infectious
diseases, cancer and inflammatory diseases. With more than 2,300 employees
worldwide, MedImmune is headquartered in Maryland. For more information,
visit the company's website at medimmune.
This announcement contains, in addition to historical information,
certain "forward-looking statements" regarding the regulatory approval
process and development plans for CAIV-T. Such forward-looking statements
are based on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change current
expectations and could cause actual outcomes and results to differ
materially from current expectations. In addition to risks and
uncertainties discussed in MedImmune's filings with the U.S. Securities and
Exchange Commission, no assurance exists that development efforts for
CAIV-T will succeed, that CAIV-T will receive required regulatory approval
or that, even if regulatory approval is received, CAIV-T will be
commercially successful. MedImmune undertakes no obligation to update any
forward-looking statement, whether as a result of new information, future
events or otherwise except as may be required by applicable law or
regulation.
MedImmune, Inc.
medimmune
View drug information on FluMist.
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Carfilzomib Demonstrates Encouraging Response Rates In Patients With Relapsed And/or Refractory Multiple Myeloma In An Ongoing Phase 2 Study
Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) announced results from an ongoing Phase 2 study, known as the 004 study, of the company's lead proteasome inhibitor, carfilzomib. Results demonstrated promising overall response rates when carfilzomib was administered as a single agent in patients with relapsed and/or refractory multiple myeloma. These data were presented at the 51st annual meeting of the American Society of Hematology (ASH) in New Orleans.
Patients were divided into two populations: 73 evaluable patients with relapsed and/or refractory multiple myeloma who had not received prior bortezomib (Velcade®) treatment, classified as bortezomib-naive patients, and 33 evaluable patients with relapsed and/or refractory disease following bortezomib treatment, classified as bortezomib-treated patients.
Michael Wang, M.D., assistant professor, department of lymphoma and myeloma at the University of Texas M. D. Anderson Cancer Center and co-investigator of the study, reported that the bortezomib-naive patients when treated with carfilzomib achieved an overall response rate (ORR) of 46 percent in 54 evaluable patients at 20 mg/m2 and 53 percent in 19 evaluable patients with dose escalation to 27 mg/m2. Additionally, Dr. Wang reported interim results for secondary endpoints at the 20 mg/m2 dose, including time-to-progression (TTP) of 7.6 months and duration of response (DoR) of 8.4 months.
David Siegel, M.D., Ph.D., division chief of myeloma at the John Theurer Cancer Center and co-investigator of the study, reported that 33 evaluable patients who were previously treated with bortezomib achieved an ORR of 18 percent when administered carfilzomib. Dr. Siegel reported interim results for a secondary endpoint of TTP at 5.3 months and DoR of more than 9 months. More than 20 percent of patients were able to complete the full 12 cycles (48 weeks) of therapy in both studies without cumulative side effects.
"These interim results suggest that carfilzomib could benefit patients with multiple myeloma who are no longer responding to current therapies," said Dr. Siegel. "Additionally, given the low incidence of neuropathy and generally mild and manageable adverse events in this trial, these results suggest that increasing the dosage of carfilzomib up to 27 mg/m2 is well tolerated despite a high degree of coexisting medical conditions, such as renal insufficiency and diabetes."
Overall, treatment with carfilzomib was well tolerated and no unexpected side effects occurred. The most common grade 3 treatment-related adverse events occurred in less than 5 percent of the patients and included fatigue, pneumonia, neutropenia, lymphopenia and anemia. Peripheral neuropathy of any grade was rare and there were no grade 4 adverse events observed.
Other findings from the two populations include:
-- Carfilzomib has substantial single-agent activity despite several prior treatments with different combination regimens.
-- Carfilzomib was well-tolerated with chronic administration, even in patients with renal insufficiency.
-- Patients were able to remain on full-dose therapy for more than 12 cycles.
"These data support our ongoing carfilzomib program in multiple myeloma, a disease that has poor long-term survival, and for which there are no alternative courses of therapy for patients who relapse following treatment or become resistant to currently approved therapies," said Michael Kauffman, M.D., Ph.D., interim chief medical officer at Onyx. "There is a clear need to provide new treatment options to patients with multiple myeloma, and we are working to potentially file a New Drug Application for carfilzomib by the end of 2010."
Trial Design
This open-label, single agent ongoing Phase 2 study is being conducted in collaboration with the Multiple Myeloma Research Consortium, and is designed to enroll approximately 150 patients with relapsed and/or refractory multiple myeloma who have received 1-3 prior treatments. Patients included two populations: bortezomib-naive patients with relapsed and/or refractory multiple myeloma and bortezomib-treated patients with relapsed and/or refractory multiple myeloma. Prior therapies include alkylating agents, stem cell transplant, thalidomide, lenalidomide and anthracyclines, and bortezomib in the bortezomib-treated patients. To date, 73 evaluable bortezomib-naive patients (54 who received 20mg/m2 and 19 who received up to 27mg/m2), and 33 evaluable patients receiving previous treatment with bortezomib have been enrolled. The primary endpoint is overall response rate and secondary endpoints include TTP, DoR, overall survival and safety.
About Carfilzomib
Carfilzomib is a selective, next generation proteasome inhibitor that has shown encouraging results in a broad clinical trial program in multiple myeloma. Carfilzomib is currently undergoing evaluation as a single agent in multiple Phase 2 and Phase 1 clinical trials in relapsed or refractory multiple myeloma. These trials include a Phase 2b monotherapy study, known as the 003 study, in patients with relapsed, refractory multiple myeloma, the pivotal trial that could support a new drug application (NDA) filing by the end of 2010. Carfilzomib is also being evaluated in advanced solid tumors.
About Multiple Myeloma
Multiple myeloma (MM) is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. In the United States, more than 50,000 people are living with MM and approximately 20,000 new cases are diagnosed annually.(i) Worldwide, more than 180,000 people are living with MM and approximately 86,000 new cases are diagnosed annually.(ii)
About Onyx Pharmaceuticals, Inc
Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals, Inc., is developing and marketing Nexavar® (sorafenib) tablets, a small molecule drug that is currently approved for the treatment of liver cancer and advanced kidney cancer. Additionally, Nexavar is being investigated in several ongoing trials in a variety of tumor types. Beyond Nexavar, Onyx has established a development pipeline of anticancer compounds at various stages of clinical testing, including carfilzomib, a next-generation proteasome inhibitor, that is currently being evaluated in multiple clinical trials for the treatment of patients with relapsed or relapsed/refractory multiple myeloma and solid tumors. ONX 0801, a targeted alpha-folate inhibitor, is currently in Phase 1 testing.
Nexavar® (sorafenib) tablets is a registered trademark of Bayer HealthCare Pharmaceuticals.
Velcade® is a trademark of Millennium Pharmaceuticals, Inc.
Revlimid® and Thalomid® are registered trademarks of Celgene Corporation.
Forward Looking Statements
This news release contains "forward-looking statements" of Onyx within the meaning of the federal securities laws. These forward-looking statements include without limitation, statements regarding the anticipated benefits of the acquisition of Proteolix and the timing, progress and results of the clinical development, safety, regulatory processes, commercialization efforts or commercial potential of carfilzomib. These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including the risk that Proteolix's operations will not be integrated successfully into Onyx's, the risk that Onyx may not realize the anticipated benefits of the acquisition and risks related to the development and commercialization of pharmaceutical products. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Reference should be made to Onyx's Annual Report on Form 10-K for the year ended December 31, 2008, filed with the Securities and Exchange Commission under the heading "Risk Factors" and Onyx's Quarterly Reports on Form 10-Q for a more detailed description of such factors. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date of this release. Onyx undertakes no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date of this release except as required by law.
(i) National Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures
(ii) International Agency for Research on Cancer , GLOBOCAN 2002 database
Source: Onyx Pharmaceuticals, Inc
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Patients were divided into two populations: 73 evaluable patients with relapsed and/or refractory multiple myeloma who had not received prior bortezomib (Velcade®) treatment, classified as bortezomib-naive patients, and 33 evaluable patients with relapsed and/or refractory disease following bortezomib treatment, classified as bortezomib-treated patients.
Michael Wang, M.D., assistant professor, department of lymphoma and myeloma at the University of Texas M. D. Anderson Cancer Center and co-investigator of the study, reported that the bortezomib-naive patients when treated with carfilzomib achieved an overall response rate (ORR) of 46 percent in 54 evaluable patients at 20 mg/m2 and 53 percent in 19 evaluable patients with dose escalation to 27 mg/m2. Additionally, Dr. Wang reported interim results for secondary endpoints at the 20 mg/m2 dose, including time-to-progression (TTP) of 7.6 months and duration of response (DoR) of 8.4 months.
David Siegel, M.D., Ph.D., division chief of myeloma at the John Theurer Cancer Center and co-investigator of the study, reported that 33 evaluable patients who were previously treated with bortezomib achieved an ORR of 18 percent when administered carfilzomib. Dr. Siegel reported interim results for a secondary endpoint of TTP at 5.3 months and DoR of more than 9 months. More than 20 percent of patients were able to complete the full 12 cycles (48 weeks) of therapy in both studies without cumulative side effects.
"These interim results suggest that carfilzomib could benefit patients with multiple myeloma who are no longer responding to current therapies," said Dr. Siegel. "Additionally, given the low incidence of neuropathy and generally mild and manageable adverse events in this trial, these results suggest that increasing the dosage of carfilzomib up to 27 mg/m2 is well tolerated despite a high degree of coexisting medical conditions, such as renal insufficiency and diabetes."
Overall, treatment with carfilzomib was well tolerated and no unexpected side effects occurred. The most common grade 3 treatment-related adverse events occurred in less than 5 percent of the patients and included fatigue, pneumonia, neutropenia, lymphopenia and anemia. Peripheral neuropathy of any grade was rare and there were no grade 4 adverse events observed.
Other findings from the two populations include:
-- Carfilzomib has substantial single-agent activity despite several prior treatments with different combination regimens.
-- Carfilzomib was well-tolerated with chronic administration, even in patients with renal insufficiency.
-- Patients were able to remain on full-dose therapy for more than 12 cycles.
"These data support our ongoing carfilzomib program in multiple myeloma, a disease that has poor long-term survival, and for which there are no alternative courses of therapy for patients who relapse following treatment or become resistant to currently approved therapies," said Michael Kauffman, M.D., Ph.D., interim chief medical officer at Onyx. "There is a clear need to provide new treatment options to patients with multiple myeloma, and we are working to potentially file a New Drug Application for carfilzomib by the end of 2010."
Trial Design
This open-label, single agent ongoing Phase 2 study is being conducted in collaboration with the Multiple Myeloma Research Consortium, and is designed to enroll approximately 150 patients with relapsed and/or refractory multiple myeloma who have received 1-3 prior treatments. Patients included two populations: bortezomib-naive patients with relapsed and/or refractory multiple myeloma and bortezomib-treated patients with relapsed and/or refractory multiple myeloma. Prior therapies include alkylating agents, stem cell transplant, thalidomide, lenalidomide and anthracyclines, and bortezomib in the bortezomib-treated patients. To date, 73 evaluable bortezomib-naive patients (54 who received 20mg/m2 and 19 who received up to 27mg/m2), and 33 evaluable patients receiving previous treatment with bortezomib have been enrolled. The primary endpoint is overall response rate and secondary endpoints include TTP, DoR, overall survival and safety.
About Carfilzomib
Carfilzomib is a selective, next generation proteasome inhibitor that has shown encouraging results in a broad clinical trial program in multiple myeloma. Carfilzomib is currently undergoing evaluation as a single agent in multiple Phase 2 and Phase 1 clinical trials in relapsed or refractory multiple myeloma. These trials include a Phase 2b monotherapy study, known as the 003 study, in patients with relapsed, refractory multiple myeloma, the pivotal trial that could support a new drug application (NDA) filing by the end of 2010. Carfilzomib is also being evaluated in advanced solid tumors.
About Multiple Myeloma
Multiple myeloma (MM) is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow. In the United States, more than 50,000 people are living with MM and approximately 20,000 new cases are diagnosed annually.(i) Worldwide, more than 180,000 people are living with MM and approximately 86,000 new cases are diagnosed annually.(ii)
About Onyx Pharmaceuticals, Inc
Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals, Inc., is developing and marketing Nexavar® (sorafenib) tablets, a small molecule drug that is currently approved for the treatment of liver cancer and advanced kidney cancer. Additionally, Nexavar is being investigated in several ongoing trials in a variety of tumor types. Beyond Nexavar, Onyx has established a development pipeline of anticancer compounds at various stages of clinical testing, including carfilzomib, a next-generation proteasome inhibitor, that is currently being evaluated in multiple clinical trials for the treatment of patients with relapsed or relapsed/refractory multiple myeloma and solid tumors. ONX 0801, a targeted alpha-folate inhibitor, is currently in Phase 1 testing.
Nexavar® (sorafenib) tablets is a registered trademark of Bayer HealthCare Pharmaceuticals.
Velcade® is a trademark of Millennium Pharmaceuticals, Inc.
Revlimid® and Thalomid® are registered trademarks of Celgene Corporation.
Forward Looking Statements
This news release contains "forward-looking statements" of Onyx within the meaning of the federal securities laws. These forward-looking statements include without limitation, statements regarding the anticipated benefits of the acquisition of Proteolix and the timing, progress and results of the clinical development, safety, regulatory processes, commercialization efforts or commercial potential of carfilzomib. These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including the risk that Proteolix's operations will not be integrated successfully into Onyx's, the risk that Onyx may not realize the anticipated benefits of the acquisition and risks related to the development and commercialization of pharmaceutical products. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Reference should be made to Onyx's Annual Report on Form 10-K for the year ended December 31, 2008, filed with the Securities and Exchange Commission under the heading "Risk Factors" and Onyx's Quarterly Reports on Form 10-Q for a more detailed description of such factors. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date of this release. Onyx undertakes no obligation to update publicly any forward-looking statements to reflect new information, events, or circumstances after the date of this release except as required by law.
(i) National Cancer Institute, Surveillance Epidemiology and End Results, 2007 Facts and Figures
(ii) International Agency for Research on Cancer , GLOBOCAN 2002 database
Source: Onyx Pharmaceuticals, Inc
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Interaction Between Lymph And Liver Cells May Affect Immune Response
A new study on the ability of liver cells to interact with T cells (lymph cells that play a role in regulating the immune response) found that such interactions do occur and demonstrated the mechanism by which they may take place. The results may help explain the altered immune responses that occur with aging and other conditions and may be useful in developing therapies for viral hepatitis and autoimmune diseases.
The results of this study appear in the November 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.
The liver possesses an unusual ability to stimulate immune tolerance, possibly due to its distinctive architecture that allows T cells normally activated in the lymph system to become activated by liver cells. Normally, endothelial cells that line blood vessels form a physical barrier that prevents naГЇve (unactivated) T cells from accessing surrounding tissue; these cells must typically be activated by specialized cells known as professional antigen presenting cells (APCs) before they are able to migrate across the endothelium and interact with organ cells. Recent studies have shown that the liver is an exception in that liver cells may be able to act as APCs, activating T cells independently of the lymph system, a process which makes them less efficient. However, the question remains as to how T cells can cross the endothelial barrier to interact with liver cells.
A collaborative work between Alessandra Warren and David Le Couteur of the Centre for Education and Research on Ageing (CERA), Concord RG Hospital and Patrick Bertolino of the Centenary Institute, University of Sydney, Australia, has led to the first study investigating the interactions between lymphocytes (T cells), liver sinusoidal endothelial cells (LSECs) and hepatocytes (liver cells) using electron microscopy. LSECs are highly specialized endothelial cells that line the walls of hepatic sinusoid cells (gossamer-like structures that form the rich capillary network of the liver) and are perforated by fenestrations, or openings. The researchers hypothesized that the fenestrations could provide a portal through which liver cells and T cells could interact or that the interaction could take place across gaps between LSECs.
The study was conducted using mice whose livers had been injected with lymphocytes. The mouse livers were examined with two types of electron microscopy. Analysis of the images showed a large number of intrahepatic lymphocytes (IHLs) that had extensions similar to the dimensions of the fenestrations of the LSECs. These extensions were seen within the fenestrations and were observed to be in contact with minute projections on liver cells (hepatocyte microvilli). There were no observable gaps between LSECs and hepatocyte microvilli did not seem to interact with circulating lymphocytes. Further investigation showed that naive T cells displayed the same extensions as IHLs and were also able to interact with liver cells through LSEC fenestrations. The authors propose the term "trans-endothelial hepatocyte-lymphocyte interactions" (TEHLI) to describe these interactions.
The discovery of TEHLI is the first demonstration by electron microscopy of the interaction between naive T cells and liver cells in a living organism, which shows that the liver is an exception to the rule that T cells need to be activated by professional APCs in order to cross the endothelial barrier, and that hepatocytes can function as APCs. In fact, this T cell activation in the liver during early hepatitis C infection may contribute to the impaired immune response seen in chronic hepatitis C.
"As well as providing insight into the normal immune system, our observations might have implications for liver conditions associated with altered LSEC morphology and in particular those conditions associated with loss of fenestrations such as cirrhosis and old age," the authors conclude. "We have shown [in previous studies] that old age is associated with dramatic reductions in the fenestrations of LSECs therefore the altered immune responses of older people might in part be mechanistically linked to reduced opportunity for TEHLI in old age."
In an accompanying editorial in the same issue, Erin F. McAvoy and Paul Kubes of the University of Calgary in Alberta, Canada note that although the authors did not observe any interaction between hepatocyte microvilli and circulating lymphocytes, it is possible that this type of transient interaction is difficult to capture using electron microscopy. They suggest that the hepatocyte microvilli could function as a rapid screen for circulating lymphocytes, which might then decide to adhere and start the TEHLI process. "The notion that naive T lymphocytes are capable of directly interacting with hepatocytes contradicts the dogma that naive T cells cannot gain access to peripheral non-lymphoid tissues," the authors state, adding that the study furthers the notion that liver cells may be involved in hepatic immune tolerance. "Like any good study," they conclude, "the work of Warren et al., answers important questions but also raises some new and intriguing areas for further exploration."
Article: "T Lymphocytes Interact With Hepatocytes Through Fenestrations in Murine Liver Sinusoidal Endothelial Cells," Alessandra Warren, David G. Le Couteur, Robin Fraser, David G. Bowen, Geoffrey W. McCaughan, Patrick Bertolino, Hepatology; November 2006 (DOI: 10.1002/hep.21378).
Editorial: "Holey Endothelium: Gateways for Naive T Cell Activation," Erin F. McAvoy, Paul Kubes, Hepatology; November 2006 (DOI: 10.1002/hep.21421).
Contact: David Greenberg
John Wiley & Sons, Inc.
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The results of this study appear in the November 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.
The liver possesses an unusual ability to stimulate immune tolerance, possibly due to its distinctive architecture that allows T cells normally activated in the lymph system to become activated by liver cells. Normally, endothelial cells that line blood vessels form a physical barrier that prevents naГЇve (unactivated) T cells from accessing surrounding tissue; these cells must typically be activated by specialized cells known as professional antigen presenting cells (APCs) before they are able to migrate across the endothelium and interact with organ cells. Recent studies have shown that the liver is an exception in that liver cells may be able to act as APCs, activating T cells independently of the lymph system, a process which makes them less efficient. However, the question remains as to how T cells can cross the endothelial barrier to interact with liver cells.
A collaborative work between Alessandra Warren and David Le Couteur of the Centre for Education and Research on Ageing (CERA), Concord RG Hospital and Patrick Bertolino of the Centenary Institute, University of Sydney, Australia, has led to the first study investigating the interactions between lymphocytes (T cells), liver sinusoidal endothelial cells (LSECs) and hepatocytes (liver cells) using electron microscopy. LSECs are highly specialized endothelial cells that line the walls of hepatic sinusoid cells (gossamer-like structures that form the rich capillary network of the liver) and are perforated by fenestrations, or openings. The researchers hypothesized that the fenestrations could provide a portal through which liver cells and T cells could interact or that the interaction could take place across gaps between LSECs.
The study was conducted using mice whose livers had been injected with lymphocytes. The mouse livers were examined with two types of electron microscopy. Analysis of the images showed a large number of intrahepatic lymphocytes (IHLs) that had extensions similar to the dimensions of the fenestrations of the LSECs. These extensions were seen within the fenestrations and were observed to be in contact with minute projections on liver cells (hepatocyte microvilli). There were no observable gaps between LSECs and hepatocyte microvilli did not seem to interact with circulating lymphocytes. Further investigation showed that naive T cells displayed the same extensions as IHLs and were also able to interact with liver cells through LSEC fenestrations. The authors propose the term "trans-endothelial hepatocyte-lymphocyte interactions" (TEHLI) to describe these interactions.
The discovery of TEHLI is the first demonstration by electron microscopy of the interaction between naive T cells and liver cells in a living organism, which shows that the liver is an exception to the rule that T cells need to be activated by professional APCs in order to cross the endothelial barrier, and that hepatocytes can function as APCs. In fact, this T cell activation in the liver during early hepatitis C infection may contribute to the impaired immune response seen in chronic hepatitis C.
"As well as providing insight into the normal immune system, our observations might have implications for liver conditions associated with altered LSEC morphology and in particular those conditions associated with loss of fenestrations such as cirrhosis and old age," the authors conclude. "We have shown [in previous studies] that old age is associated with dramatic reductions in the fenestrations of LSECs therefore the altered immune responses of older people might in part be mechanistically linked to reduced opportunity for TEHLI in old age."
In an accompanying editorial in the same issue, Erin F. McAvoy and Paul Kubes of the University of Calgary in Alberta, Canada note that although the authors did not observe any interaction between hepatocyte microvilli and circulating lymphocytes, it is possible that this type of transient interaction is difficult to capture using electron microscopy. They suggest that the hepatocyte microvilli could function as a rapid screen for circulating lymphocytes, which might then decide to adhere and start the TEHLI process. "The notion that naive T lymphocytes are capable of directly interacting with hepatocytes contradicts the dogma that naive T cells cannot gain access to peripheral non-lymphoid tissues," the authors state, adding that the study furthers the notion that liver cells may be involved in hepatic immune tolerance. "Like any good study," they conclude, "the work of Warren et al., answers important questions but also raises some new and intriguing areas for further exploration."
Article: "T Lymphocytes Interact With Hepatocytes Through Fenestrations in Murine Liver Sinusoidal Endothelial Cells," Alessandra Warren, David G. Le Couteur, Robin Fraser, David G. Bowen, Geoffrey W. McCaughan, Patrick Bertolino, Hepatology; November 2006 (DOI: 10.1002/hep.21378).
Editorial: "Holey Endothelium: Gateways for Naive T Cell Activation," Erin F. McAvoy, Paul Kubes, Hepatology; November 2006 (DOI: 10.1002/hep.21421).
Contact: David Greenberg
John Wiley & Sons, Inc.
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Advanced Pancreatic Cancer Patients May Benefit From Bacteriolytic Therapy
The aim of cancer immunotherapy is the stimulation of immune mechanisms to recognize malignant cells and may be a useful complementary therapy to conventional anticancer therapy. Immunotherapy was initiated over 100 years ago when New York surgeon William B. Coley inoculated a bacterial vaccine consisting of Streptococcus pyogenes and Serratia marcescens. Several patients experienced a beneficial effect on malignancy and were finally cured of their tumours by the development of a potent immune response.
A research article published in the World Journal of Gastroenterology worked on this old idea. The research team led by Dr. Michael Linnebacher from the University of Rostock treated pancreatic carcinoma with Clostridium novyi-spores. In their experimental model they analyzed animals with tumours of different sizes. Treatment success depended on tumour size. Small tumours were completely unaffected whereas the treatment was toxic in cases of very large tumours. Most interestingly, tumours of a defined medium size completely disappeared and animals remained free of tumour recurrence. The authors showed that immune mechanisms were responsible for this success.
The bacterial spores germinate and grow in the oxygen-free tumour centres where they damage surrounding tumour cells. This together with an infection-driven infiltration of tumours by cells of the innate immune system leads to significant damage to tumours.
These data indicate that the application of bacteria may be a promising treatment strategy for patients with advanced pancreatic cancer and warrants further investigation.
Reference:
Maletzki C, Gock M, Klier U, Klar E, Linnebacher M. Bacteriolytic therapy of experimental pancreatic carcinoma. World J Gastroenterol 2010; 16(28): 3546-3552
Source:
Lin Tian
World Journal of Gastroenterology
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A research article published in the World Journal of Gastroenterology worked on this old idea. The research team led by Dr. Michael Linnebacher from the University of Rostock treated pancreatic carcinoma with Clostridium novyi-spores. In their experimental model they analyzed animals with tumours of different sizes. Treatment success depended on tumour size. Small tumours were completely unaffected whereas the treatment was toxic in cases of very large tumours. Most interestingly, tumours of a defined medium size completely disappeared and animals remained free of tumour recurrence. The authors showed that immune mechanisms were responsible for this success.
The bacterial spores germinate and grow in the oxygen-free tumour centres where they damage surrounding tumour cells. This together with an infection-driven infiltration of tumours by cells of the innate immune system leads to significant damage to tumours.
These data indicate that the application of bacteria may be a promising treatment strategy for patients with advanced pancreatic cancer and warrants further investigation.
Reference:
Maletzki C, Gock M, Klier U, Klar E, Linnebacher M. Bacteriolytic therapy of experimental pancreatic carcinoma. World J Gastroenterol 2010; 16(28): 3546-3552
Source:
Lin Tian
World Journal of Gastroenterology
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