Avicena Group,
Inc. (OTC Bulletin Board: AVGOE), a late stage biotechnology company
focused on commercializing its proprietary cellular energy modulation
technology, announced today that it has filed a composition of matter
patent application with the United States Patent and Trademark Office for
Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's disease), a severe
neurodegenerative disease.
This composition of matter patent broadly covers pharmaceutical
formulations based on creatine derivatives alone or in combination with an
anti-inflammatory compound for the treatment of ALS. The Company believes
that this patent will provide additional IP protection for its current and
future generation drug candidates formulated to treat ALS which extends
beyond the existing use patents previously issued to Avicena with claims in
neurology (US Patents 6,196,115 B1 and 6,706,764 B2). This application will
further extend Avicena's intellectual property portfolio for ALS-02, a drug
candidate that has previously been granted orphan drug designation by the
US FDA.
Belinda Tsao-Nivaggioli, Ph.D., CEO of Avicena, stated, "This patent
application is another key intellectual property milestone that builds
shareholder value and will help us further protect the Company's cellular
energy franchise and the drug candidates we develop for ALS. ALS remains a
leading indication for our technology, and this additional patent
application will support our commercialization work in this important
therapeutic area."
ABOUT ALS
ALS is a neurodegenerative disease that attacks the motor neurons of
the brain and spinal cord that are responsible for voluntary muscle
movement. As these motor neurons degenerate, their ability to send impulses
to the muscle fibers is compromised. The progressive degeneration of motor
neurons eventually leads to neuron death resulting in the brain's inability
to initiate or control muscle movement. Once a patient's muscles no longer
receive the messages that they require to function, muscles begin to
atrophy. With an incidence rate of approximately 1 in 10,000, ALS affects
roughly 30,000 Americans at any given time. Each year, approximately 5,600
new cases of ALS are diagnosed. The two types of ALS are "sporadic ALS,"
which accounts for approximately 85% - 90% of all cases; and "familial
ALS," which accounts for the remaining 10% - 15% of patents.
ABOUT AVICENA
Avicena Group, Inc. (OTC Bulletin Board: AVGOE) is a late stage
biotechnology company focused on developing products based on its
proprietary understanding of the regulation of cellular energy processes.
The company's core technologies, supported by a robust IP portfolio, have
broad applications in both pharmaceuticals and dermaceuticals. Avicena's
pharmaceutical program centers on rare neurological disorders (orphan
diseases). The company is currently analyzing data from its Phase IIb/III
trial in ALS (Amyotrophic Lateral Sclerosis, or Lou Gehrig's disease). Near
term, Avicena intends to initiate a Phase III trial in Huntington's disease
to accompany its on-going Phase III trial in Parkinson's disease. Avicena's
science is well established and its products are safe and well tolerated.
Unlike traditional biotechnology companies, Avicena's clinical programs are
largely funded by government and non-profit organizations. Avicena
presently derives revenue from the sale of proprietary ingredients to skin
care manufacturers.
SAFE HARBOR
This release may contain forward-looking statements within the meaning
of the federal securities laws. Such forward-looking statements reflect,
among other things, management's current expectations, plans and
strategies, and anticipated financial results, all of which are subject to
known and unknown risks, uncertainties and factors that may cause our
actual results to differ materially from those expressed or implied by
these forward-looking statements. Many of these risks are beyond our
ability to control or predict. See "Risk Factors" under "Item 6.
Management's Discussion and Analysis of Financial Condition and Results of
Operation" from our Annual Report on Form 10-KSB for the year ended
December 31, 2005, and other descriptions in the company's public filings
with the Securities and Exchange Commission for a discussion of such risks,
including the company's need for additional funds, the company's dependence
on a limited number of therapeutic compounds, the stage of the products the
company is developing, uncertainties relating to clinical trials and
regulatory reviews, competition and dependence on collaborative partners,
the company's ability to avoid infringement of the patent rights of others,
and the company's ability to obtain adequate patent protection and to
enforce these rights. Because of these risks, uncertainties and
assumptions, you should not place undue reliance on these forward-looking
statements. Furthermore, forward-looking statements speak only as of the
date they are made. Avicena does not undertake any obligation to update or
review any such forward-looking information, whether as a result of new
information, future events or otherwise.
Avicena Group, Inc.
avicenagroup
суббота, 28 мая 2011 г.
Kansas Bridges To Future: Minorities With Potential For Biomedical Sciences
Kansas Bridges to the Future is a research training grant funded by the National Institutes of Health. It partners Kansas State University with Seward County, Dodge City, Garden City and Kansas City Kansas community colleges and Donnelly College in Kansas City, Kan., in a grassroots effort to identify, mentor and guide minority students with potential for biomedical science careers.
Denis Medeiros, head of K-State's department of human nutrition, is the grant's principal investigator. Medeiros wrote the grant after establishing the partnership with the five schools during the last three years. More than 20 minority students have transferred to K-State since the program began in 2003, with more students in the pipeline.
"We proposed a grassroots effort beginning at the community college level to develop biomedical career awareness, enhance the academic preparation skills of selected Bridges' students, seek parental involvement, and devote resources to the community colleges to allow for sufficient academic advisement of these students," Medeiros said. "The overall goal is to increase the number of Kansas minority students pursuing graduate degrees in the biomedical field."
Medeiros said the schools participating in the partnership were selected because their enrollments reflect the diverse population in their parts of Kansas: Seward County, Garden City and Dodge City community colleges have high enrollments of Hispanic students, while Donnelly College and Kansas City Kansas Community College each have a high percentage of African-American students enrolled.
"Many of the community colleges are the first choice of underrepresented minorities in pursuing their higher education goals," Medeiros said. "Many of these students are the first in their families to go to college."
Students identified for the Bridges program receive dual admission to the community college and K-State, with tuition waivers. The students attend a one-week summer institute to make them more aware of scientific investigation and opportunities after their freshman year.
After the second year in the program, the students will have the opportunity to work for eight weeks at K-State in the laboratory of a scientific investigator. Community college instructors also will be given an opportunity to work at a K-State laboratory for an eight-week summer period to help bridge gaps in research training and curriculum development. All students will be prepared in a rigorous foundation of science, chemistry and math, Medeiros said.
The students who come to K-State also take part in the Developing Scholars Program and continue their mentoring with a professor. Other K-State faculty involved with the project include Anita Cortez, co-director of the Developing Scholars Program, and Farrell Webb, associate professor of family studies and human services and associate director of the Developing Scholars Program.
Contact: Denis Medeiros
Kansas State University
Denis Medeiros, head of K-State's department of human nutrition, is the grant's principal investigator. Medeiros wrote the grant after establishing the partnership with the five schools during the last three years. More than 20 minority students have transferred to K-State since the program began in 2003, with more students in the pipeline.
"We proposed a grassroots effort beginning at the community college level to develop biomedical career awareness, enhance the academic preparation skills of selected Bridges' students, seek parental involvement, and devote resources to the community colleges to allow for sufficient academic advisement of these students," Medeiros said. "The overall goal is to increase the number of Kansas minority students pursuing graduate degrees in the biomedical field."
Medeiros said the schools participating in the partnership were selected because their enrollments reflect the diverse population in their parts of Kansas: Seward County, Garden City and Dodge City community colleges have high enrollments of Hispanic students, while Donnelly College and Kansas City Kansas Community College each have a high percentage of African-American students enrolled.
"Many of the community colleges are the first choice of underrepresented minorities in pursuing their higher education goals," Medeiros said. "Many of these students are the first in their families to go to college."
Students identified for the Bridges program receive dual admission to the community college and K-State, with tuition waivers. The students attend a one-week summer institute to make them more aware of scientific investigation and opportunities after their freshman year.
After the second year in the program, the students will have the opportunity to work for eight weeks at K-State in the laboratory of a scientific investigator. Community college instructors also will be given an opportunity to work at a K-State laboratory for an eight-week summer period to help bridge gaps in research training and curriculum development. All students will be prepared in a rigorous foundation of science, chemistry and math, Medeiros said.
The students who come to K-State also take part in the Developing Scholars Program and continue their mentoring with a professor. Other K-State faculty involved with the project include Anita Cortez, co-director of the Developing Scholars Program, and Farrell Webb, associate professor of family studies and human services and associate director of the Developing Scholars Program.
Contact: Denis Medeiros
Kansas State University
How Precursors Of Gene-Regulating Small RNAs Are Sorted By Cellular Machinery
A team of scientists at Cold Spring Harbor Laboratory (CSHL) has determined a hierarchical set of criteria that explain how the molecular precursors of gene-regulating small RNAs are sorted by the cellular machinery.
Led by Benjamin Czech, a group working in the laboratory of CSHL Professor Gregory Hannon posed the question: can distinct patterns be observed in the process that unfolds when double-stranded RNAs enter the RNAi pathway? Shorthand for RNA interference, RNAi is a biological response to double-stranded RNA that can culminate in the regulation of gene expression. It has been observed in a vast range of organisms ranging from plants to worms to flies to man.
An enzyme called Dicer cuts double-stranded RNAs into smaller double-stranded pieces called duplexes. Czech, Hannon and colleagues propose rules governing the next step in the RNAi pathway, in which duplexes are sorted to proteins called Argonautes which are at the core of a molecular complex called RISC (the RNA-Induced Silencing Complex).
"Only one strand of each duplex is chosen," explains Czech, "and which one makes all the difference. In the fruit flies that we used as models for this series of experiments, the selection of one or another strand effectively determines whether the short RNA will seek out and regulate a gene, or whether it will perform another function such as protecting a cell against a viral invader."
The rules determining how a duplex is processed and sorted are discussed in a paper the team published recently in Molecular Cell. These include the overall arrangement of the nucleotides in the duplex; how many bases are paired; where they're paired and unpaired; and how tightly the ends of the duplex are stuck together.
"These rules for sorting are important for two reasons," according to Hannon, who is also an Investigator of the Howard Hughes Medical Institute. "One is that since small RNAs play critical biological roles in nearly every process, understanding which strands of the small RNAs entering RISC act as regulators of gene expression is critical for our fundamental understanding.
"The rules are also important because scientists are hoping to use small RNAs one day as therapeutics. By understanding the rules by which small RNAs are processed and sorted, we move closer to the goal of being able to manipulate the RNAi pathway, bend it to the purpose of addressing disease."
"Hierarchical Rules for Argonaute Loading in Drosophila" appeared in Molecular Cell, Vol. 36, No. 3. The authors are: Benjamin Czech, Rui Zhou, Yaniv Erlich, Julius Brennecke, Richard Binari, Christians Villalta, Assaf gordon, Norbert Perrimon and Gregory J. Hannon.
Source: Peter Tarr
Cold Spring Harbor Laboratory
Led by Benjamin Czech, a group working in the laboratory of CSHL Professor Gregory Hannon posed the question: can distinct patterns be observed in the process that unfolds when double-stranded RNAs enter the RNAi pathway? Shorthand for RNA interference, RNAi is a biological response to double-stranded RNA that can culminate in the regulation of gene expression. It has been observed in a vast range of organisms ranging from plants to worms to flies to man.
An enzyme called Dicer cuts double-stranded RNAs into smaller double-stranded pieces called duplexes. Czech, Hannon and colleagues propose rules governing the next step in the RNAi pathway, in which duplexes are sorted to proteins called Argonautes which are at the core of a molecular complex called RISC (the RNA-Induced Silencing Complex).
"Only one strand of each duplex is chosen," explains Czech, "and which one makes all the difference. In the fruit flies that we used as models for this series of experiments, the selection of one or another strand effectively determines whether the short RNA will seek out and regulate a gene, or whether it will perform another function such as protecting a cell against a viral invader."
The rules determining how a duplex is processed and sorted are discussed in a paper the team published recently in Molecular Cell. These include the overall arrangement of the nucleotides in the duplex; how many bases are paired; where they're paired and unpaired; and how tightly the ends of the duplex are stuck together.
"These rules for sorting are important for two reasons," according to Hannon, who is also an Investigator of the Howard Hughes Medical Institute. "One is that since small RNAs play critical biological roles in nearly every process, understanding which strands of the small RNAs entering RISC act as regulators of gene expression is critical for our fundamental understanding.
"The rules are also important because scientists are hoping to use small RNAs one day as therapeutics. By understanding the rules by which small RNAs are processed and sorted, we move closer to the goal of being able to manipulate the RNAi pathway, bend it to the purpose of addressing disease."
"Hierarchical Rules for Argonaute Loading in Drosophila" appeared in Molecular Cell, Vol. 36, No. 3. The authors are: Benjamin Czech, Rui Zhou, Yaniv Erlich, Julius Brennecke, Richard Binari, Christians Villalta, Assaf gordon, Norbert Perrimon and Gregory J. Hannon.
Source: Peter Tarr
Cold Spring Harbor Laboratory
Researchers Use Light In MRSA Fight
New treatment using a light-activated drug could revolutionise the fight
against hospital "superbug", MRSA (otherwise known as meticillin resistant
staphylococcus aureus) it was revealed at the British Pharmaceutical
Conference (BPC) in Manchester.
MRSA can sometimes live on the skin or in the nose and has no harmful
effects unless it gets under the skin, for example in wounds, where it can
cause infection. If MRSA gets into the bloodstream it can cause serious
infections, for example pneumonia, septicaemia, or osteomyelitis (in the
bones).
Doctors do not apply antibiotics directly to MRSA-infected wounds as they
do not penetrate deep enough into the wound to have an effect, or can
irritate the surrounding skin, slowing down wound healing. Worryingly, MRSA
is now resistant to most types of standard antibiotics.
Investigations underway by Corona Cassidy and co-workers at the School of
Pharmacy, Queen's University of Belfast, move away from the antibiotic
approach. The treatment would involve delivering a drug known as a
'photosensitiser' to infected wounds and activating it using a special type
of light, triggering it to kill the MRSA. The concept is known as
photodynamic antimicrobial chemotherapy or 'PACT'.
In laboratory studies, the team has examined a hydrogel that holds and
then releases the light-reacting drug. The system was effective in killing
the bacteria when the drug was released from the hydrogel.
Miss Cassidy said: "PACT is an exciting potential treatment of
MRSA-infected wounds. More laboratory work must be carried out to optimise
our treatment conditions to ensure that all exposed bacteria are killed."
The British Pharmaceutical Conference 2008 (BPC)
BPC 2008: Pharmacy in the 21st Century: Adding years to life and life to
years. In 2008, as the NHS marks its 60th anniversary year, BPC will examine
how pharmacy and the pharmaceutical services are helping to add years to life
and life to the year of the UK population. The profession of pharmacy plays
an important role in meeting the healthcare challenges associated with the
UK's ageing population.
How can pharmacists contribute to caring for the population as well as
ensuring quality of life? Increasingly, scientists and practitioners have to
consider the cost implications of this conundrum, and the evidence base for
all interventions is becoming of paramount importance: BPC 2008 will debate
these issues and open up discussion on them. Visit: bpc2008
The main sponsors of BPC 2008 are: Boots The Chemists (Lead Sponsor),
AstraZeneca (Associate Sponsor and BPC-PJ Careers Forum Platinum Sponsor),
Pharmacists' Defence Association (PDA) (Associate Sponsor) and GSK (BPC-PJ
Careers Forum Platinum Sponsor).
British Pharmaceutical Conference
View drug information on Photodynamic Therapy.
against hospital "superbug", MRSA (otherwise known as meticillin resistant
staphylococcus aureus) it was revealed at the British Pharmaceutical
Conference (BPC) in Manchester.
MRSA can sometimes live on the skin or in the nose and has no harmful
effects unless it gets under the skin, for example in wounds, where it can
cause infection. If MRSA gets into the bloodstream it can cause serious
infections, for example pneumonia, septicaemia, or osteomyelitis (in the
bones).
Doctors do not apply antibiotics directly to MRSA-infected wounds as they
do not penetrate deep enough into the wound to have an effect, or can
irritate the surrounding skin, slowing down wound healing. Worryingly, MRSA
is now resistant to most types of standard antibiotics.
Investigations underway by Corona Cassidy and co-workers at the School of
Pharmacy, Queen's University of Belfast, move away from the antibiotic
approach. The treatment would involve delivering a drug known as a
'photosensitiser' to infected wounds and activating it using a special type
of light, triggering it to kill the MRSA. The concept is known as
photodynamic antimicrobial chemotherapy or 'PACT'.
In laboratory studies, the team has examined a hydrogel that holds and
then releases the light-reacting drug. The system was effective in killing
the bacteria when the drug was released from the hydrogel.
Miss Cassidy said: "PACT is an exciting potential treatment of
MRSA-infected wounds. More laboratory work must be carried out to optimise
our treatment conditions to ensure that all exposed bacteria are killed."
The British Pharmaceutical Conference 2008 (BPC)
BPC 2008: Pharmacy in the 21st Century: Adding years to life and life to
years. In 2008, as the NHS marks its 60th anniversary year, BPC will examine
how pharmacy and the pharmaceutical services are helping to add years to life
and life to the year of the UK population. The profession of pharmacy plays
an important role in meeting the healthcare challenges associated with the
UK's ageing population.
How can pharmacists contribute to caring for the population as well as
ensuring quality of life? Increasingly, scientists and practitioners have to
consider the cost implications of this conundrum, and the evidence base for
all interventions is becoming of paramount importance: BPC 2008 will debate
these issues and open up discussion on them. Visit: bpc2008
The main sponsors of BPC 2008 are: Boots The Chemists (Lead Sponsor),
AstraZeneca (Associate Sponsor and BPC-PJ Careers Forum Platinum Sponsor),
Pharmacists' Defence Association (PDA) (Associate Sponsor) and GSK (BPC-PJ
Careers Forum Platinum Sponsor).
British Pharmaceutical Conference
View drug information on Photodynamic Therapy.
Common Pain Relievers May Dilute Power Of Flu Shots
With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers -- Advil, Tylenol, aspirin -- at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.
Richard P. Phipps, Ph.D., professor of Environmental Medicine, Microbiology and Immunology, and of Pediatrics, has been studying this issue for years and recently presented his latest findings to an international conference on inflammatory diseases.
"What we've been saying all along, and continue to stress, is that it's probably not a good idea to take common, over-the-counter pain relievers for minor discomfort associated with vaccination," Phipps said. "We have studied this question using virus particles, live virus, and different kinds of pain relievers, in human blood samples and in mice -- and all of our research shows that pain relievers interfere with the effect of the vaccine."
A study by researchers in the Czech Republic reported similar findings in the Oct. 17, 2009, edition of The Lancet. They found that giving acetaminophen, the active ingredient in Tylenol, to infants weakens the immune response to vaccines.
Phipps' research has tested whether production of antibodies using a cell culture system was blunted by over-the-counter pain relievers. He found that a variety of pain relievers -- even though Tylenol and Advil have different ingredients -- seemed to dilute the production of necessary antibodies to protect against illness.
Many of the pain relievers in question are classified as NSAIDs or nonsteroidal anti-inflammatory drugs, which act in part by blocking the cyclooxygenase-2 (cox-2) enzyme. Blocking the cox-2 enzyme is not a good idea in the context of vaccination, however, because the cox-2 enzyme is necessary for the optimal production of B-lymphocytes.
Therefore, when a person takes a medication to reduce pain and fever, he or she might also inadvertently reduce the ability of B cells to make antibodies.
Phipps and colleagues also demonstrated that timing of the administration of pain relievers is important as well, according to the study published earlier this year in the journal Cellular Immunology.
They exposed human cells and mice to ibuprofen, Tylenol, aspirin and naproxen (Aleve) in amounts comparable to doses commonly used by millions of Americans every day to prevent or treat pain and fever, or arthritis, or to prevent heart attack and stroke.
Treatment during the earliest stages of inflammation - or when the first signs of pain, swelling, redness or fever would occur - had the most detrimental effects on the immune system, the study noted.
The connection between NSAIDs and antibody production is still being actively pursued. Phipps said researchers believe ibuprofen, in particular, affects lymphocytes' ability to produce antibodies.
Meanwhile, until a full clinical trial provides a clearer picture, Phipps urges regular users of NSAIDs to be aware of the risks.
"NSAIDs are one of the most commonly used drugs; they are recommended for all age categories, are prescribed for relieving transient pain or in cases of serious inflammatory diseases," Phipps said. "By decreasing antibody synthesis, NSAIDs also have the ability to weaken the immune system which can have serious consequences for children, the elderly and the immune-compromised patients."
The U.S. Public Health Service has funded Phipps' studies. URMC co-investigators on the study in Cellular Immunology include: David Topham, Ph.D., an expert in the immune response to influenza and a principal investigator in the David H. Smith Center for Vaccine Biology and Immunology, and Simona Bancos and Matthew P. Bernard, of the Department of Environmental Medicine, Lung Biology and Disease Program.
One of the nation's top academic medical centers, the University of Rochester Medical Center forms the centerpiece of the University's health research, teaching, patient care, and community outreach missions. The Medical Center receives more than $230 million in external research funding per year and the University of Rochester School of Medicine and Dentistry ranks in the top one-quarter of U.S. medical centers in federal research funding. The University's health care delivery network is anchored by Strong Memorial Hospital - a 739-bed, University-owned teaching hospital. As upstate New York's premier health care delivery network, patients benefit from the Medical Center's robust teaching and biomedical research programs.
Source: University of Rochester Medical Center
Richard P. Phipps, Ph.D., professor of Environmental Medicine, Microbiology and Immunology, and of Pediatrics, has been studying this issue for years and recently presented his latest findings to an international conference on inflammatory diseases.
"What we've been saying all along, and continue to stress, is that it's probably not a good idea to take common, over-the-counter pain relievers for minor discomfort associated with vaccination," Phipps said. "We have studied this question using virus particles, live virus, and different kinds of pain relievers, in human blood samples and in mice -- and all of our research shows that pain relievers interfere with the effect of the vaccine."
A study by researchers in the Czech Republic reported similar findings in the Oct. 17, 2009, edition of The Lancet. They found that giving acetaminophen, the active ingredient in Tylenol, to infants weakens the immune response to vaccines.
Phipps' research has tested whether production of antibodies using a cell culture system was blunted by over-the-counter pain relievers. He found that a variety of pain relievers -- even though Tylenol and Advil have different ingredients -- seemed to dilute the production of necessary antibodies to protect against illness.
Many of the pain relievers in question are classified as NSAIDs or nonsteroidal anti-inflammatory drugs, which act in part by blocking the cyclooxygenase-2 (cox-2) enzyme. Blocking the cox-2 enzyme is not a good idea in the context of vaccination, however, because the cox-2 enzyme is necessary for the optimal production of B-lymphocytes.
Therefore, when a person takes a medication to reduce pain and fever, he or she might also inadvertently reduce the ability of B cells to make antibodies.
Phipps and colleagues also demonstrated that timing of the administration of pain relievers is important as well, according to the study published earlier this year in the journal Cellular Immunology.
They exposed human cells and mice to ibuprofen, Tylenol, aspirin and naproxen (Aleve) in amounts comparable to doses commonly used by millions of Americans every day to prevent or treat pain and fever, or arthritis, or to prevent heart attack and stroke.
Treatment during the earliest stages of inflammation - or when the first signs of pain, swelling, redness or fever would occur - had the most detrimental effects on the immune system, the study noted.
The connection between NSAIDs and antibody production is still being actively pursued. Phipps said researchers believe ibuprofen, in particular, affects lymphocytes' ability to produce antibodies.
Meanwhile, until a full clinical trial provides a clearer picture, Phipps urges regular users of NSAIDs to be aware of the risks.
"NSAIDs are one of the most commonly used drugs; they are recommended for all age categories, are prescribed for relieving transient pain or in cases of serious inflammatory diseases," Phipps said. "By decreasing antibody synthesis, NSAIDs also have the ability to weaken the immune system which can have serious consequences for children, the elderly and the immune-compromised patients."
The U.S. Public Health Service has funded Phipps' studies. URMC co-investigators on the study in Cellular Immunology include: David Topham, Ph.D., an expert in the immune response to influenza and a principal investigator in the David H. Smith Center for Vaccine Biology and Immunology, and Simona Bancos and Matthew P. Bernard, of the Department of Environmental Medicine, Lung Biology and Disease Program.
One of the nation's top academic medical centers, the University of Rochester Medical Center forms the centerpiece of the University's health research, teaching, patient care, and community outreach missions. The Medical Center receives more than $230 million in external research funding per year and the University of Rochester School of Medicine and Dentistry ranks in the top one-quarter of U.S. medical centers in federal research funding. The University's health care delivery network is anchored by Strong Memorial Hospital - a 739-bed, University-owned teaching hospital. As upstate New York's premier health care delivery network, patients benefit from the Medical Center's robust teaching and biomedical research programs.
Source: University of Rochester Medical Center
Benign Or Malignant? MTOR Makes The Decision
Tuberous sclerosis complex (TSC) is a genetic disorder that results in sufferers developing benign tumors in many parts of their body. It is caused by genetic mutation of either of two genes, TSC1 or TSC2. The proteins encoded by these genes are negative regulators of a signaling pathway that is initiated at the cell surface by a ligand binding to PDGFR and that involves activation of PI3K, AKT, and mTOR. The fact that individuals with TSC develop only benign tumors is somewhat surprising because genetic mutations that cause increased PDGFR, PI3K, and AKT activity are associated with malignant cancer, as are inactivating genetic mutations of other negative regulators of this signaling pathways (including PTEN). In a study appearing online in advance of publication in the March print issue of the Journal of Clinical Investigation, researchers from the Chinese Academy of Medical Sciences and Peking Union Medical College, People's Republic of China, use mouse models of TSC to provide a potential explanation for the fact that individuals with TSC develop only benign tumors.
The lack of malignant tumors in mice expressing decreased levels of TSC1 or TSC2 is associated with decreased PDGFR expression and decreased PI3K and AKT activity, despite increased mTOR activity. Hongbing Zhang and colleagues now show that in mouse cell lines, activation of PI3K or AKT, as well as inhibition of PTEN, results in decreased PDGFR expression and negative feedback to dampen AKT activity, despite increased mTOR activity. Furthermore, inhibiting mTOR restored PDGFR expression levels and AKT activity in mouse cell lines expressing decreased levels of TSC1 or TSC2, and overexpression of active AKT or PDGFR in such cells rendered them able to induce malignant tumors when transplanted into immunocompromised mice. This study therefore demonstrates that increased mTOR activity decreases PDGFR expression and AKT activity in mouse cells expressing decreased levels of TSC1 or TSC2. More importantly, it offers a potential explanation for the observation that humans expressing mutant forms of TSC1 or TSC2 develop only benign tumors.
TITLE: PDGFRs are critical for PI3/Akt activation and negatively regulated by mTOR
AUTHOR CONTACT:
Hongbing Zhang
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
JCI table of contents -- February 8, 2006
Contact: Karen Honey
Journal of Clinical Investigation
The lack of malignant tumors in mice expressing decreased levels of TSC1 or TSC2 is associated with decreased PDGFR expression and decreased PI3K and AKT activity, despite increased mTOR activity. Hongbing Zhang and colleagues now show that in mouse cell lines, activation of PI3K or AKT, as well as inhibition of PTEN, results in decreased PDGFR expression and negative feedback to dampen AKT activity, despite increased mTOR activity. Furthermore, inhibiting mTOR restored PDGFR expression levels and AKT activity in mouse cell lines expressing decreased levels of TSC1 or TSC2, and overexpression of active AKT or PDGFR in such cells rendered them able to induce malignant tumors when transplanted into immunocompromised mice. This study therefore demonstrates that increased mTOR activity decreases PDGFR expression and AKT activity in mouse cells expressing decreased levels of TSC1 or TSC2. More importantly, it offers a potential explanation for the observation that humans expressing mutant forms of TSC1 or TSC2 develop only benign tumors.
TITLE: PDGFRs are critical for PI3/Akt activation and negatively regulated by mTOR
AUTHOR CONTACT:
Hongbing Zhang
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
JCI table of contents -- February 8, 2006
Contact: Karen Honey
Journal of Clinical Investigation
Scientists Identify Genes That Both Extend Life And Protect Against Cancer
A person is 100 times more likely to get cancer at age 65 than at age 35. But new research reported in the journal Nature Genetics identifies naturally occurring processes that allow many genes to both slow aging and protect against cancer in the much-studied C. elegans roundworm.
Many of the worm genes have counterparts in humans, suggesting that new drugs may some day ensure a long, cancer-free life. The new research and a related study the scientists reported in Science last year indicate that cellular changes leading to longevity antagonize tumor cell growth.
The studies are by scientists at the University of California, San Francisco, who say the research also underscores the deep evolutionary connection between lifespan and cancer.
The worms, known formally as Caenorhabditis elegans, were the stars of a startling 1993 discovery by UCSF biologist Cynthia Kenyon, PhD. She found then that a change in just one gene, called daf-2, doubled the worms' lifespan. This finding led to the understanding that lifespan is regulated by genes and is therefore changeable, rather than the inevitable result of the body's breakdown. The discovery in worms has been confirmed in other animals including mice.
The new research by Kenyon and graduate student Julie Pinkston is reported in the advanced online edition of the journal.
Kenyon is the American Cancer Society Professor and director of the Hillblom Center for the Biology of Aging at UCSF.
"This is very exciting," Kenyon said. "There is a widely held view that any mechanism that slows aging would probably stimulate tumor growth. But we found many genes that increase lifespan, but slow tumor growth. Humans have versions of many of these genes, so this work may lead to treatments that keep us youthful and cancer-free much longer than normal."
Since her early finding that the gene daf-2 and another gene known as daf-16 regulate lifespan, Kenyon's research team has hoped to identify the genes that they in turn affect -- those that more directly affect aging and tumor growth.
"Now we are really getting there," Kenyon said.
The gene daf-2 codes for a receptor for insulin and also for an insulin-like protein that promotes growth. It influences daf-16, which makes a so-called transcription factor -- a protein that determines when and where hundreds of other genes are turned on. The focus of the new study was to identify specific genes regulated by daf-16 which affect cancer and/or lifespan.
The scientists used an established tumor model in the worms. Then, starting with a list of 734 genes known to be targets of daf-16, they identified 29 genes that either promote or suppress tumor cell growth. They did this using several techniques, including RNA interference or RNAi, a powerful tool that allows scientists to control the expression of just one kind of gene at a time.
About half of the genes stimulated tumor growth and half suppressed it, they found. Strikingly, about half of these genes also affect lifespan in animals that do not have tumors, further strengthening the model Kenyon and others have conceived in which the insulin receptor, daf-2, works in concert with the transcription factor daf-16 to link longevity and tumor resistance. The "downstream" genes appear to act in a cumulative way, they found.
The genes that stimulated tumor growth also accelerated aging itself, and the genes that prevented tumor growth slowed down the aging process and extended lifespan. These findings greatly strengthen the view that the controls of lifespan and cancer have deep, common roots, Kenyon and Pinkston conclude.
The research was funded by the National Institutes of Health.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Source: Wallace Ravven
University of California - San Francisco
Many of the worm genes have counterparts in humans, suggesting that new drugs may some day ensure a long, cancer-free life. The new research and a related study the scientists reported in Science last year indicate that cellular changes leading to longevity antagonize tumor cell growth.
The studies are by scientists at the University of California, San Francisco, who say the research also underscores the deep evolutionary connection between lifespan and cancer.
The worms, known formally as Caenorhabditis elegans, were the stars of a startling 1993 discovery by UCSF biologist Cynthia Kenyon, PhD. She found then that a change in just one gene, called daf-2, doubled the worms' lifespan. This finding led to the understanding that lifespan is regulated by genes and is therefore changeable, rather than the inevitable result of the body's breakdown. The discovery in worms has been confirmed in other animals including mice.
The new research by Kenyon and graduate student Julie Pinkston is reported in the advanced online edition of the journal.
Kenyon is the American Cancer Society Professor and director of the Hillblom Center for the Biology of Aging at UCSF.
"This is very exciting," Kenyon said. "There is a widely held view that any mechanism that slows aging would probably stimulate tumor growth. But we found many genes that increase lifespan, but slow tumor growth. Humans have versions of many of these genes, so this work may lead to treatments that keep us youthful and cancer-free much longer than normal."
Since her early finding that the gene daf-2 and another gene known as daf-16 regulate lifespan, Kenyon's research team has hoped to identify the genes that they in turn affect -- those that more directly affect aging and tumor growth.
"Now we are really getting there," Kenyon said.
The gene daf-2 codes for a receptor for insulin and also for an insulin-like protein that promotes growth. It influences daf-16, which makes a so-called transcription factor -- a protein that determines when and where hundreds of other genes are turned on. The focus of the new study was to identify specific genes regulated by daf-16 which affect cancer and/or lifespan.
The scientists used an established tumor model in the worms. Then, starting with a list of 734 genes known to be targets of daf-16, they identified 29 genes that either promote or suppress tumor cell growth. They did this using several techniques, including RNA interference or RNAi, a powerful tool that allows scientists to control the expression of just one kind of gene at a time.
About half of the genes stimulated tumor growth and half suppressed it, they found. Strikingly, about half of these genes also affect lifespan in animals that do not have tumors, further strengthening the model Kenyon and others have conceived in which the insulin receptor, daf-2, works in concert with the transcription factor daf-16 to link longevity and tumor resistance. The "downstream" genes appear to act in a cumulative way, they found.
The genes that stimulated tumor growth also accelerated aging itself, and the genes that prevented tumor growth slowed down the aging process and extended lifespan. These findings greatly strengthen the view that the controls of lifespan and cancer have deep, common roots, Kenyon and Pinkston conclude.
The research was funded by the National Institutes of Health.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Source: Wallace Ravven
University of California - San Francisco
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