This important milestone marks the first candidate drug from the collaboration to enter Phase I safety and tolerability studies. This drug candidate is on track to enter Phase II ‘proof-of-concept’ trials later this year.

The original agreement between the two companies was announced in January 2007. Scientists from the two companies are collaborating to identify long-acting muscarinic (M3) antagonist (LAMA) and dual-acting muscarinic antagonist-??2 agonist (MABA) candidate drugs. These compounds will be developed as once-daily, inhaled mono or combination therapies. AstraZeneca will be responsible for the development and worldwide commercialisation of products arising out of the collaboration. Dependent upon success, Argenta is eligible for further development, regulatory and sales milestone payments. Royalties will also be payable to Argenta.

Commenting on the progress, Dr. Christopher Ashton, Argenta Discovery’s CEO, said, “The programme continues to deliver beyond the expectations of both parties and we are firmly on track to achieve our joint strategic goals for the programme.”

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow obstruction that is progressive and current therapies, including inhaled corticosteroids, fail to treat disease progression. COPD is a leading cause of morbidity and mortality worldwide with an overall prevalence in adults over 40 years currently estimated at between 9 and 10%. Unlike many other major diseases, deaths due to COPD are increasing and the World Health Organisation (WHO) estimates by 2030 that COPD will be the third leading cause of mortality and fifth leading cause of morbidity in the world. Thus there is a high level of unmet medical need for this progressive and debilitating disease.

About Argenta Discovery

Argenta Discovery was founded in August 2000. Argenta has expertise in chronic respiratory diseases, including Chronic Obstructive Pulmonary Disease (COPD) and severe asthma. The company has generated a portfolio of pre-clinical bronchodilator and anti-inflammatory programmes with the goal of demonstrating clinical proof-of-concept. In 2009, Argenta completed its first Phase II clinical trial with ADC4022, an investigational medicine for the treatment of Chronic Obstructive Pulmonary Disease (COPD) and severe asthma.

Argenta also has a contract research division that provides integrated drug discovery services to a range of leading pharmaceutical and biotechnology companies worldwide. Argenta employs approximately 160 people and is based in Harlow, Welwyn Garden City and Slough, UK. For more information about Argenta Discovery, please visit argentadiscovery

Source
AstraZeneca

– bevacizumab in combination with paclitaxel for the first-line treatment of metastatic breast cancer

– bevacizumab in addition to platinum-based chemotherapy for the first-line treatment of patients with inoperable advanced, metastatic or recurrent non-small-cell lung cancer (other than predominantly squamous cell histology)

– carmustine implants as an adjunct to surgery in patients with recurrent glioblastoma multiforme (a type of brain cancer) for whom surgery is appropriate

– cetuximab for the treatment of colorectal cancer following failure of oxaliplatin-containing chemotherapy

Andrew Dillon, NICE Chief Executive said:

“NICE is committed to producing timely guidance to the NHS using our fast-track single technology appraisal process. This process relies on the manufacturer to submit evidence so that we can appraise the treatment. Occasionally, manufactures either fail to make a submission or the submission is inadequate. Where this happens we work with the company to try and resolve the problem. If the problem cannot be resolved we will have to bring an appraisal to a conclusion without undertaking a full evaluation.

“In these circumstances, we will issue advice to the NHS which will say that ‘NICE is unable to recommend the use of the technology’. The advice will explain why we have come to the conclusion to terminate the appraisal and will offer advice to the NHS on what to do next. Normally, this will be that the NHS should be cautious in considering use of the treatment. Of course, if sufficient evidence does become available in the future, we may take the opportunity to review and to revise our advice to the NHS.”

About NICE

The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.

NICE produces guidance in three areas of health:

– public health – guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector

– health technologies – guidance on the use of new and existing medicines, treatments and procedures within the NHS

– clinical practice – guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

NICE guidance is developed using the expertise of the NHS and the wider healthcare community including NHS staff, healthcare professionals, patients and carers, industry and the academic world.

nice

Cancer of the colon is the third most common kind of cancer in our society. And, in many cases, the first symptoms usually appear when the disease is already in quite an advanced state. Of those colon cancer patients who suffer metastasis, approximately 45 % will develop hepatic metastasis.

It is this theme that the Gipuzkoan biologist, Ms Amaya del Villar, deals with in her PhD, recently defended at the Faculty of Medicine and Odontology at the University of the Basque Country (UPV/EHU). It is research work in which colon cancer generated hepatic metastasis is analysed, a disease which may be propitiated by genes that are regulated by the very microenvironment or environment of the liver.

The PhD entitled “Study of the genes involved in hepatic metastasis of colon cancer and which are regulated by microenvironmental factors of the liver” was led by Fernando Vidal-Vanaclocha of the Department of Cell Biology and Histology at the UPV/EHU and obtained excellent cum laude. Cooperating in drawing up the doctoral thesis was the Pharmakine company and the Hepatic Surgery Unit at the Cruces Hospital in Bilbao.

Ms Amaya del Villar ??lvarez is a graduate in Biological Sciences from the University of Navarra and currently works for the Pharmakine company, continuing her research into cancer and metastasis.

This study aimed, on the one hand, to create an in vitro culture model of human colon cancer that would enable reproducing the gene regulation expressed by colon cancer cells during their growth as metastasis in the liver of patients with hepatic metastasis. On the other, it was aimed at identifying the origin of the factors regulating the expression of those genes. An in vitro model based on crops in the presence of conditional media

The in vitro model developed in this PhD thesis differs from current models in which the cell line from the human colon cancer is cultured in the presence of conditioned media of primary cells from the liver after being stimulated with tumour cell conditioned media. With in vitro conditioned media, the aim is to imitate the environment of the tumour cell during its implantation in an organ at a distance. This would be the simplest form to see the changes and responses produced with this kind of metastasis, and subsequently being able to develop new pharmaceutical drugs or therapeutic targets to combat it.

To this end, liver cells – hepatocytes and myofibroblasts – are isolated, and both cultured separately in the presence of conditioned media of a cell line of colon cancer. In each case, the media are collected in such a way that all the segregated soluble factors of these liver cells, responding to the tumour, are in the media. On the other hand, tumoural cells from the human colon cancer cell line were cultured for 24 hours in the presence of this conditioned media, in order to see the response that these produce in each case and compare it with both the hepatocytes and myofibroblasts.
More than 44,000 genes

To check the responses of the colon cancer tumoural cells in the conditioned media, a study of the genes was carried out and the origin of the factors regulating this expression identified. Once the 24 hours in the presence of conditioned media had passed, the nucleic acid of these cells was extracted and this subsequently subjected to the microarrays technique enabling the study of more than 44,000 genes at the same time. It was observed that one group of genes is regulated in the same way by both hepatocytes and myofibroblasts, but there are other groups that are regulated in a specific manner way by either hepatocytes or myofibroblasts. That is to say, genes regulated in the presence of conditioned media are different, depending on the cells. The biologist also observed that the hepatocytes regulate a significantly greater amount of genes than do the myofibroblasts.

“This study is only at its beginnings” stated the researcher. “Although we have possibly identified certain genes, further studies have to be undertaken. And, undoubtedly this is a field which will widen. The results so far obtained have to be corroborated with much wider studies, with a much larger number of patients, and so on”, she added.

“But, basically, I think it important to demonstrate the influence of the microenvironment in the process of metastasis”, she argued. “When studying cancer, it is good to have a more global, overall perspective, not solely focusing on the tumour or malignant cells”.

“If we manage to find out the process of regulation in the tumour cell during metastasis, we will have achieved the possibility of developing therapeutic targets in order to try and avoid, as it were, the metastasis occurring”.

ELHUYAR FUNDAZIOA
Zelai Haundi 3, Osinalde industrialdea
20.170 Usurbil
Gipuzkoa
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“I am pleased to announce that Sacramento and UC Davis Cancer Center, with funding from the National Cancer Institute, will
lead the way in reducing the toll of this disease among all Asian Americans – from the newest Hmong immigrants, who are at
high risk of cancers caused by chronic infections, to fifth- and sixth-generation Chinese and Japanese Americans, who face
rapidly increasing rates of such cancers as breast and colon cancer,” Matsui said.

“This grant will help make great strides in using what we have learned as to the causes behind the fast-rising numbers and
work with the community to make progress against this disease and save lives.”

The new grant builds on a previous NCI-funded project, known as the Asian American Network for Cancer Awareness, Research and
Training (AANCART). Also headquartered at UC Davis, AANCART was funded through the NCI’s Special Populations Network and
included investigators from seven other universities. The new project, which will also be called AANCART, is funded through
the NCI’s Community Networks Program. As such, the new project will take a much more community-based, participatory approach
to addressing health disparities.

The new project unites cancer-control experts from the California Department of Health Services, UCSF, UCLA, the University
of Hawaii in Honolulu, the Fred Hutchinson Cancer Research Center/University of Washington in Seattle, and Dana-Farber Cancer
Institute/Harvard University in Boston with two community groups, the Sacramento-based Hmong Women’s Heritage Association and
the San Francisco Medical Society Foundation/Chinese Community Health Plan.

In addition to the $4.48 million in NCI funding, UC Davis and other project participants are contributing another $400,000 in
new or in-kind support for the effort.

“Asian Americans have long been overlooked in cancer-prevention efforts,” said U.S. Rep. Mike Thompson, whose district
includes UC Davis. “Winning this major grant, in today’s highly competitive federal grants climate, is a credit to UC Davis
and the other participating institutions. This is an important step toward one of our most important public health goals –
eliminating ethnic disparities in cancer and other diseases.”

Over the next five years, the project will focus on:

– reducing the unequal and preventable burden of hepatitis B-induced liver cancer in Asian Americans by increasing hepatitis
B immunization rates in children and screening rates in adults.

– improving breast and cervical cancer screening rates among Asian American women, who are among the least likely to get Pap
tests and mammograms.

– encouraging Asian Americans to retain the traditionally low-fat, vegetable-based diets common in Asian countries and
resist pressures to adopt the higher-fat American diet.

– increasing the rates of colorectal cancer screening among Asian Americans.

Cambodian, Chinese, Filipino, Hmong, Korean and Vietnamese communities in
Seattle, San Francisco, Honolulu, Los Angeles and Sacramento will be the populations of special emphasis. Investigators will
focus on building relationships with grassroots organizations, arming them with information and strategies that can reduce
cancer risks and rates in their communities.

“This new grant is a godsend,” said K.W. Lee, 77, a survivor of liver and stomach cancer who lost both his parents and every
one of his six siblings to hepatitis B-induced liver disease. “Since my liver transplant in 1992, I have encountered so many
wretched fellow immigrants who have lost their lives, when they should be enjoying the fruits of their lifelong hard work in
their golden years. This grant means new hope for high-risk newcomers from Asia, and it will empower grassroots neighborhood
groups, churches and service agencies to save many thousands of lives from preventable and unnecessary disease.” Lee, an
award-winning Korean American journalist, lives in Sacramento.

Recent data suggest that while Asian Americans have a relatively low risk of cancer overall, their cancer death rate is
climbing faster than that of any other racial group. In addition, they suffer disproportionately from several forms of the
disease. Asian Americans are more than five times as likely as whites to die of liver cancer, for example, and on an
aggregate basis, Asian Pacific Islander women over age 40 have the lowest mammogram screening rates in the country. In some
Asian groups, the incidence of cervical cancer is as much as five times that of whites.

“With our first project, we were able to document that with respect to cancer awareness and cancer control, Asian Americans
are not ‘hard-to-reach’ – they are hardly reached,” said Moon Chen, Jr., professor of Public Health Sciences at UC Davis and
principal investigator of the new grant and is one of the nation’s foremost investigators into the cancer burden of ethnic
minority groups. “In this project, we will tailor interventions specifically to Asian Americans through linguistically
appropriate and culturally competent means, and apply what we have learned to reduce the unique, unusual and Americans
unnecessary cancer burden affecting Asian Americans.”

Asian American community leaders greeted the new grant as good news. Jerry Chong, chief legal counsel for the
Sacramento-based organization CAPITAL (Council of Asian Pacific Islanders for Advocacy and Leadership), says the grant and
its predecessor unite the Asian community against a common foe, cancer.

“Dr. Chen and his fellow investigators are to be commended for their visionary leadership and innovative approach in
connecting with the entire API community,” Chong said. “The new grant is a medical treasure to the Asian American community.”

UC Davis Cancer Center is the nation’s 61st National Cancer Institute-designated cancer center. It is ranked by U.S. News &
World Report as one of the nation’s top 50 cancer treatment centers.

UC Davis Health System
4900 Broadway, Suite 1200
Sacramento, CA 95820
Phone: (916) 734-9040
FAX: (916) 734-9066
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ucdmc.ucdavis/newsroom

QI is currently sponsoring and conducting an FDA-authorized Phase I/II clinical trial testing the safety and efficacy of its immunotherapy on 27 Stage IV breast cancer patients who have failed conventional therapy. According to Mr. Chuck Broes, CEO of QI, “This achievement marks a significant milestone in the life cycle of our company, and we look forward with great hope and commitment as we aspire to a successful trial outcome.”

The clinical trials involve the use of dendritic cell therapy using the oncofetal antigen (“OFA”), or iLRP — immature Laminin Receptor Protein, as a cancer antigen (a protein found on cancer cells that can be targeted by the body’s own immune system) found in many tumor cell lines or fetal tissue, but absent on normal, healthy tissue. QI believes that the OFA antigen can serve as a unique, valuable and promising antigen for individualized breast cancer immunotherapy.

Centered in Mobile, AL, QI’s clinical trial is designed around the use of QI’s proprietary dendritic cell therapy, which employs OFA to recruit the patient’s own immune system to target and attack the cancer cells with the intent to improve patient survivability and quality of life. Each patient will receive three monthly injections of the patient’s own dendritic cells that have been sensitized to OFA. It is anticipated that once the sensitized cells are injected back into the patient, the patient’s T-cells will locate the OFA found on the patient’s cancer cells, thereby generating an immune response with the goal of killing the cancer cells and preventing further spread of the disease.

About Quantum Immunologics

Quantum Immunologics, Inc. (“QI”) is a research-driven biotechnology company that is pioneering discoveries in immunotherapy science. QI is dedicated to the research, development and production of technologies that focus on the treatments and diagnoses of cancer and other diseases related to the immune system. Leveraging an expansive pipeline of biopharmaceutical innovations, QI remains committed to advancing medicine with the ultimate goal of dramatically improving lives.

In the study, which was led by Eiki Takimoto and David Kass, when mice lacking the protein RGS2 were manipulated such that they had persistent high blood pressure they developed hypertrophy of the muscle wall of the heart more rapidly than normal mice manipulated in the same way. Further, these mice went on to exhibit heart failure and died at a young age. Additional analysis indicated that a drug that prevents hypertrophy by targeting the protein PDE5 was less effective at preventing hypertrophy caused by high blood pressure in RGS2-deficient mice than in normal mice. These data have clinical implications, as they provide insight into the mechanism by which PDE5 inhibitors, which have recently entered clinical trials to treat a form of heart failure, work.

TITLE: Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice
Journal of Clinical Investigation

AUTHOR CONTACT:

Eiki Takimoto
Johns Hopkins University, Baltimore, Maryland, USA.

David A. Kass

Johns Hopkins University, Baltimore, Maryland, USA.

View the PDF of this article at: https://the-jci/article.php?id=35620

Since April, Neurochem has provided regular updates on the program,
including preliminary data and reports on the model. Certain of the
confounding factors identified by the statisticians and included so far in
adjustments to the model are the use of concomitant drugs, including change
in memantine use and dose, change in vitamin E use and dose, change in
anti-depressant use, and change in acetylcholinesterase inhibitor dose.

To date, Neurochem has invested significant human and financial
resources in this program. The Company is committed to continuing its
efforts to adjust the model in order to evaluate the significance of the
data and remains hopeful that the results will prove valuable in the
development of the first potential disease-modifying treatment for this
terrible disease. Given the magnitude and duration of this trial, the size
of the patient population, and the challenge of testing a first-in-class
product candidate, which is hypothesized to target the underlying pathology
of AD, Neurochem will need more time to work with experts in the field,
including the trial’s investigators and the regulatory authorities.

The Company has been also advised by its statistical team that
refinement of the statistical model needs further adjustments. In view of
the continuing complexities of the trial, which involves the first attempt
to employ these particular primary outcome measures across multiple
clinical sites for a potential disease modification effect over 18 months,
the next steps are expected to require the guidance of the U.S. Food and
Drug Administration (FDA). Consequently, the Company has contacted the
agency to request a meeting with the objective of seeking its advice and
explore alternative approaches acceptable to the agency.

At the meeting, the Company expects to discuss some of the alternatives
it is considering to further adjust the model. These include suggestions
for a more detailed review of individual patient files to try to identify
other confounding factors.

About the Two Phase III Clinical Trials in North America and Europe

The North American study was a multicenter, randomized, double-blind,
placebo-controlled, three-armed and parallel-designed, 18-month Phase III
clinical trial. The study included 1,052 patients with mild-to-moderate AD
recruited across 67 sites in Canada and the United States randomized to
receive either placebo or one of two doses (100mg or 150mg twice daily) of
tramiprosate (ALZHEMED(TM)). All patients were required to be treated with
conventional symptomatic AD therapies during the clinical trial and were
required to be on a stable dose of such therapies for at least four months
prior to the initial screening visit of the trial. At study entry, patients
in this trial had been administered standard therapies for an average of
approximately 20 months.

All patients who completed the clinical trial were eligible to receive
tramiprosate (ALZHEMED(TM)) in an open-label extension study initiated in
May 2006. Approximately 90% of the patients who completed the Phase III
double-blind study for tramiprosate (ALZHEMED(TM)) elected to enroll in the
ongoing extension study and receive 150mg twice daily of tramiprosate
(ALZHEMED(TM)).

Neurochem is also currently conducting a European Phase III clinical
trial for tramiprosate (ALZHEMED(TM)) for the treatment of AD. The European
study is of a similar design to the North American double-blind trial and
over 950 mild-to-moderate AD patients are already enrolled at about 70
clinical centers across 10 European countries. To date, the European Data
Safety Monitoring Board has met three times and recommended on each
occasion that the study should continue as planned. The Company expects to
continue patient enrolment and is presently considering modifications that
would need to be made to the design of the European trial to take best
advantage of the experience gained from the North American Phase III
clinical trial.

About Tramiprosate (ALZHEMED(TM))

Tramiprosate (ALZHEMED(TM)) is a small, orally-administered molecule
known as an amyloid Beta antagonist. Tramiprosate (ALZHEMED(TM)) crosses
the blood-brain-barrier, binds to soluble ABeta peptide and interferes with
the amyloid cascade that is associated with amyloid deposition and the
toxic effects of ABeta peptide in the brain. The presence of amyloid in the
brain is one of the major histopathological characteristics of AD. The
amyloid cascade hypothesis proposes that certain forms of the ABeta peptide
are toxic and causally related to the severity of AD. The ABeta peptide is
one of the most promising targets for the development of AD therapies.

About Alzheimer’s Disease

AD is a leading cause of death in older people. The disease is
characterized by the progressive death of nerve cells in the brain, making
it difficult for the brain’s signals to be transmitted properly. A person
with AD experiences problems with memory, judgment, thinking, and
eventually with motor functions, all of which make it difficult for the
person to participate in daily activities.

According to the U.S. Alzheimer Association (2007), there are now more
than five million people in the United States living with Alzheimer’s
disease. This number includes 4.9 million people aged 65 and older. It also
includes at least 200,000 individuals younger than 65 with early-onset
Alzheimer’s disease. It is estimated that by 2010, there will be 454,000
new cases of AD a year, 615,000 new cases by 2030 and 959,000 new cases by
2050. In the United States, the direct and indirect costs of AD and other
dementias amount to more than US$148 billion annually.

About Neurochem

Neurochem Inc. is focused on the development and commercialization of
innovative therapeutics to address critical unmet medical needs. Eprodisate
(KIACTA(TM)) is currently being developed for the treatment of Amyloid A
(AA) amyloidosis, and is under regulatory review for marketing approval by
the U.S. Food and Drug Administration, the European Medicines Agency and
Swissmedic. Tramiprosate (ALZHEMED(TM)), for the treatment of Alzheimer’s
disease, has completed a Phase III clinical trial in North America and is
currently in a Phase III clinical trial in Europe, while tramiprosate
(CEREBRIL(TM)), for the prevention of Hemorrhagic Stroke caused by Cerebral
Amyloid Angiopathy, has completed a Phase IIa clinical trial.

(1) Alzheimer’s Disease Assessment Scale, cognitive subpart (ADAS-cog).
The ADAS-cog is a 70- point scale designed to measure, with the use
of questionnaires, the progression and the severity of cognitive
decline as seen in AD.

(2) Dementia Rating – sum of boxes rating scale (CDR-SB), a measure of
global performance.

This news release contains forward-looking statements regarding
tramiprosate (ALZHEMED(TM)) as well as regarding continuing and further
development efforts. These statements are based on the current analysis and
expectations of management. Drug development necessarily involves numerous
risks and uncertainties, which could cause actual results to differ
materially from this current analysis and these expectations. Analysis
regarding the results of clinical trials may not provide definitive results
regarding safety, tolerability or therapeutic benefits. Even if all the
endpoints sought in the clinical trials were met (which is not certain),
there is no certainty that regulators would ultimately approve tramiprosate
(ALZHEMED(TM)) for sale to the public. Risks and uncertainties may include:
failure to demonstrate the safety, tolerability and efficacy of our
product, that actual results may vary once the final and quality-controlled
verification of data and analyses has been completed, the expense and
uncertainty of obtaining regulatory approval, including from the FDA, and
the possibility of having to conduct additional clinical trials. Further,
even if regulatory approval is obtained, therapeutic products are generally
subject to: stringent on-going governmental regulation, challenges in
gaining market acceptance, and competition. Neurochem does not undertake
any obligation to publicly update its forward-looking statements, whether
as a result of new information, future events, or otherwise. Please see the
Annual Information Form for further risk factors that might affect the
Company and its business.

NEUROCHEM INC.
neurochem

The Specialized Program of Research Excellence (SPORE) grant for brain tumor research is the 11th such grant received by M. D. Anderson under the NCI’s program, which is designed to move basic science findings into early stage clinical trials.

M. D. Anderson already holds SPORE grants in leukemia and melanoma as well as cancers of the breast, bladder, pancreas, ovaries, uterus, head and neck, prostate and lung, with the last shared with The University of Texas Southwestern Medical Center in Dallas. The 11 grants out of 60-plus SPOREs awarded by the NCI are the most held by a single institution.

“This award marks a very significant event for M. D. Anderson and indicates the important role that the institution plays in the field of translational research,” said Raymond DuBois, M.D., Ph.D, M. D. Anderson provost and executive vice president. “We are essentially leading the way in developing multidisciplinary research teams to accelerate the transition of basic knowledge into the clinic. I am extremely proud of our neuro-oncology team and all of the people involved who will use this brain tumor SPORE to ultimately make a difference for patients.”

The five-year, $12.5 million brain tumor SPORE builds on existing institutional expertise in multiple departments, said W. K. Alfred Yung, M.D., chair of M. D. Anderson’s Department of Neuro-Oncology and co-principal investigator of the brain tumor SPORE with Oliver Bogler, Ph.D., associate professor in M. D. Anderson’s Department of Neurosurgery.

“All four of the projects funded by this grant apply molecular and genetic approaches to develop new targeted therapies and biomarkers that will improve treatment by personalizing therapy,” Yung said.

The NCI estimates that 21,810 new cases of brain or central nervous system tumors will be diagnosed in 2008, and about 13,000 people will die from brain malignancies. Tumors range in severity from benign to the highly malignant glioblastoma multiforme, which will be the focus of M. D. Anderson’s SPORE.

Project 1: Deploying a tumor-killing virus

The engineered adenovirus Delta-24-RGD, developed at M. D. Anderson, will advance to clinical trial and a second-generation version will be developed as a single therapy and in combination with other drugs. Delta-24 will be injected directly into tumors during a phase I clinical trial that is under review at the U.S. Food and Drug Administration. The virus is genetically altered to prevent it from entering normal cells but attacks glioblastoma cells, which lack a specific anti-viral protein. Principal investigators are Juan Fueyo, M.D., associate professor of neuro-oncology, and Frederick Lang, M.D., professor of neurosurgery.

Project 2: Blocking a malignant pathway

Drugs that block a molecular signaling cascade known to fuel brain tumors – the PI3K pathway – will be developed and tested in phase I trials. Both individual targeted molecules and rational drug combinations will be studied for their potential to inhibit PI3K. One candidate inhibitor has been developed by Garth Powis, Ph.D., professor and chair of M. D. Anderson’s Department of Experimental Therapeutics, who is co-PI with Yung and Bogler on the project.

Project 3: Identifying treatment guideposts

Researchers are developing and validating a set of genes that predict survival and sensitivity to treatment for glioblastoma patients. This biomarker approach to sorting out personalized treatment is being conducted in collaboration with existing clinical trials testing a variety of therapies and combinations for glioblastoma. Co-principal investigators are Kenneth Aldape, M.D., professor in the Department of Pathology, and Howard Colman, M.D., Ph.D., assistant professor of neuro-oncology.

Project 4: Pinpointing genetic role in brain impairment

By analyzing the genetic makeup of glioblastoma patients and relating it to the type and degree of cognitive impairment they experience after radiation treatment, researchers aim to identify and understand genes that affect cognitive outcomes. Co-principal investigators are Melissa Bondy, Ph.D., professor in the Department of Epidemiology, and Christina Meyers, Ph.D., professor of neuro-oncology.

The four research projects are supported by five cores: administrative (Yung and Bogler); pathology (Aldape and colleague Craig Fuller, M.D., Ph.D., professor of pathology); clinical (Mark Gilbert, M.D. professor of neuro-oncology); biostatistics (Kenneth Hess, Ph.D., associate professor in the Department of Biostatistics); and animal models (Charles Conrad, M.D., associate professor of neuro-oncology).

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 39 Comprehensive Cancer Centers designated by the National Cancer Institute. For five of the past eight years, M. D. Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News and World Report.

“Finding out that your child has a heart murmur causes a great deal of anxiety,” said Dr. Louis Bezold, associate professor of pediatrics and chief of the division of pediatric cardiology, University of Kentucky College of Medicine, and co-director of the Kentucky Children’s Heart Center. “It is a common misconception that all murmurs are serious, but this is not the case.

Murmurs are actually extremely common findings in infants and children. In fact, most children will have a murmur at some point during childhood.

According to Bezold, a murmur is simply an extra noise in addition to the normal heart sounds (so-called “lub-dub”) heard using a stethoscope. When your doctor listens to your child’s heart they will note the location, intensity and other characteristics of the extra sound. Based on the examination, murmurs can be classified in two broad categories: innocent or pathologic.

Innocent murmurs (also known as benign, functional or flow murmurs) are the most common. As their name implies, they are not considered abnormal and have no effect on a child’s health. Most innocent murmurs disappear at some point during infancy or childhood. Children with innocent murmurs require no medications or restrictions on activity or diet. In fact, regular physical activity and a healthy diet are very important for heart health. An innocent murmur is not a heart condition.

On the other hand, a pathologic murmur indicates a heart abnormality, including congenital heart defects (present at birth) or heart muscle functional problems. Pathologic murmurs are less common; for example, only about one to two percent of babies are born with a structural heart defect.

Some infants will exhibit signs of a problem early in life. However, some heart defects are detected only because a murmur is noted during childhood. Symptoms that can indicate a heart problem in infancy include feeding problems, fast breathing, poor weight gain and blueness of the tongue or inside of the mouth. Older children may have excessive fatigue or chest pain with physical exertion.

Some pathologic murmurs are due to relatively minor problems that may resolve spontaneously. Treatment for more significant defects may involve medications, antibiotics for dental work, activity restrictions and/or more definitive treatment via surgery or heart catheterization. Fortunately, highly successful potential therapies now exist for most pediatric heart problems.

It is fairly common for a “new” murmur to be noted during a check-up.

Innocent murmurs tend to be louder in certain situations such as with fever or after crying. Very quiet murmurs can go undetected until the child is old enough to be cooperative enough for your doctor to hear. However, some pathologic murmurs initially may not be audible, but will become louder if the condition worsens over time. Also, although some loud murmurs suggest more serious problems, loud doesn’t necessarily mean bad: the tiniest holes in the heart cause the loudest murmurs, but are generally of little consequence with respect to a child’s health and often spontaneously close.
Evaluation of heart murmurs by a pediatric cardiologist will include a thorough physical examination and may include other tests such as a chest x-ray, electrocardiogram (ECG) and/or an echocardiogram. Some murmurs can be classified as innocent by examination alone. An echocardiogram is an ultrasound examination which provides moving images of the structure and function of the heart, allowing detection of congenital defects and other heart problems. After the evaluation is complete the doctor will go over the findings and explain in detail what your child’s murmur means.

“In many cases, this will be good news, but even if the murmur is pathologic your pediatric cardiologist can still provide good treatment options for your child,” Bezold said.

The recommendation is the result of findings from one of the world’s largest population-based studies on psychological
distress in heart disease patients. It has established that men and women with heart disease in the USA suffer from higher
than normal levels of distress – yet only a third have been seen by mental health professionals.

The research published in EHJ – an official journal of the European Society of Cardiology – is by Dr Amy Ferketich, Assistant
Professor in the Division of Epidemiology and Biostatistics at the Ohio State University School of Public Health in Columbus,
USA and Dr Philip Binkley, Professor of Medicine at The Ohio State University Department of Internal Medicine and Division of
Cardiovascular Medicine.

The researchers took data from the 2002 National Health Interview Survey (NHIS) as their starting point. This survey –
conducted annually by the National Center for Health Statistics and the Centers for Disease Control and Prevention – is the
primary source of information on health and illness in the USA and is representative of all US households.

They analysed data on 17,541 men and women over 40 in the survey who had self-reported different forms of heart disease,
including coronary heart disease (CHD), myocardial infarction (MI) and congestive heart failure (CHF). A questionnaire called
K6[2] assessed the presence and level of psychological distress to establish whether a higher proportion of the study group
experienced distress compared with the estimated prevalence among the healthy population, and if so, whether having more than
one cardiovascular condition added to the levels of distress. Of the total, 644 patients scored high enough to be classified
as suffering from psychological distress.

Dr Ferketich said: “The level of psychological distress among the healthy population is estimated to be 2.8%. But, we found
that in our study over 4.1% with coronary heart disease and 6.4% with MI had psychological distress. And for those with
congestive heart failure the figure was as high as one in 10.”

She said that the increased level among those with CHD was not statistically significant, but for those who had MI it was
double that of the healthy population and triple for those with heart failure. In each disease category the level of distress
was higher if the illness had been diagnosed within the last 12 months.

“Because of the way the NHIS conducts its survey we know that our study group is representative of the general population in
the USA with heart disease,” she said. “This means there are over one million in the USA with a history of CHD, MI or CHF
experiencing psychological distress.”

There was a higher proportion of females, individuals with less than a high school education, Hispanics and non-Hispanic
black people, the obese, non-drinkers, current smokers, the sedentary and individuals with hypertension or diabetes among
heart disease patients with elevated distress levels.

“It’s hard to know why, but we typically see this in research,” said Dr Ferketich. “It may be that there are additional
sources of stress in individuals in these groups.”

The findings suggested that psychological distress was a significant co-morbidity (associated condition) of cardiovascular
disease, according to co-author Dr Binkley.

“All the symptoms of psychological distress measured on the K6 – sadness, nervousness, restlessness, hopelessness,
worthlessness and the feeling that everything is an effort – are more prevalent among respondents with one or more of the
heart diseases. So, we are not talking here about an unequal distribution of one or two particular symptoms.

“What is perhaps most alarming, is the low prevalence of visits to a mental health professional. All heart disease patients
with a diagnosis of serious mental illness should receive such services and these data indicate that only 31% to 35% have
seen a mental health professional, although it is possible some may have been treated for distress by another type of
practitioner.”

The authors said there were some limitations to the study, but its main strength was that it involved a large
population-based sample and a method of evaluating distress developed by experts in the field of psychological measurement.

“Our findings imply that psychological distress must be taken into consideration in the management of cardiovascular disease.
Other studies have demonstrated a link between psychological distress and morbidity and mortality. All these findings provide
the impetus for future investigations that assess the role that a medical and mental health care professional may have in
altering these outcomes if they target distress.”

Dr Binkley concluded: “Further investigation may indicate that screening is warranted, and certainly clinicians should be
alert to this problem.”

[1] Psychological distress and cardiovascular disease: results from the 2002 National Health Interview Survey. European
Heart Journal. doi:10.1093/eurheartj/ehi329.

[2] K6: A measurement of psychological distress that rates responses on a scale from 0-24, with 13 as a cut-point for
classifying individuals as having a serious mental illness.

The European Heart Journal is an official journal of the European Society of Cardiology. Please acknowledge the journal as a
source in any articles.

Contact: Margaret Willson
m.willsonmwcommunications
44-153-677-2181
European Society of Cardiology
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