Chemokine Therapeutics
Corp. (the “Company”) (TSX:CTI, OTCBB:CHKT), a biotechnology company
developing chemokine-based therapies to treat cancer, blood disorders, and
vascular diseases, is pleased to announce results of clinical trials of its
hematological drug candidate, CTCE-0214.

The Company has completed the first two stages of the three part phase
Ib clinical trials for CTCE-0214. A total of 57 normal healthy volunteers
were evaluated using various doses and comparing intravenous versus
subcutaneous routes of administration. The study demonstrated CTCE-0214 to
be safe and well tolerated when administered intravenously as a single or
after multiple doses were administered on a daily basis for five
consecutive days. There were no serious adverse events reported. Subjects
receiving subcutaneous administrations of CTCE-0214 did however experience
transient injection site reactions and local pain after single and repeated
administration of the drug. As demonstrated in an earlier study,
administration of CTCE-0214 subcutaneously resulted in a 300% increase in
neutrophil counts that peaked at approximately 12 hours and were sustained
above the baseline value for approximately 48 hours after each
administration. Administration using the intravenous route demonstrated a
modest pharmacological neutrophil response to each dose administered after
each consecutive day of administration with a noticeable increase in stem
cell numbers at 3 days using colony forming assay techniques.

“We are encouraged by the results of these clinical studies which will
serve as a foundation for future development of CTCE-0214″, said Dr. Hassan
Salari, President and CEO of Chemokine Therapeutics. “The third part of the
phase Ib trial should provide us with additional information on the
benefits of combining CTCE-0214 with G-CSF.”

The primary objective of the recently completed phase Ib study
conducted under a US-IND was to evaluate the safety of CTCE-0214 in normal
health volunteers as well as to evaluate the effects of intravenous versus
subcutaneous administration. The original protocol was amended to include a
subcutaneous cohort of subjects for comparison to the planned intravenous
route of administration. These trials are designed to test primarily the
safety and optimal route of administration of CTCE-0214 in preparation for
future clinical trials that will evaluate the mobilization and regeneration
of infection-fighting white blood cells and other cells of hematopoietic
(blood) origin in a patient setting.

CTCE-0214 has the potential to restore a cancer patient’s immune system
and blood cells between cycles of chemotherapy. In this clinical scenario,
patients might be able to receive aggressive chemotherapy without delay by
restoring infection-fighting white blood cells and increasing platelet
counts to protect patients from bleeding, and/or increase in blood stem
cells suitable for transplant.

About CTCE-0214

CTCE-0214 is a stable peptide agonist of stromal cell-derived factor-1
(SDF-1), a key signaling molecule in the proliferation, homing, engraftment
and expansion of hematopoietic stem cells and white blood cells. SDF-1 is
also believed to work as a traffic controller for infection-fighting white
blood cells and progenitor cell migration providing an essential function
to combat immunosuppression. CTCE-0214, based on Chemokine’s preclinical
research, mimics the activity of the natural chemokine SDF-1 by increasing
the level of white blood cells (neutrophils), bleeding prevention cells
(platelets) and stem cells (primitive blood forming cells) in the blood.
These findings have been confirmed through independent laboratories at
Memorial Sloan Kettering Cancer Center and Cornell Medical School in New
York and the Walther Cancer Institute in Indianapolis.

About Chemokine Therapeutics Corp. (TSX: CTI, OTCBB: CHKT)

Chemokine Therapeutics is a product-focused biotechnology company
developing drugs in the field of chemokines. Chemokines are a class of
signaling proteins which play a critical role in the growth,
differentiation, and maturation of cells necessary for fighting infection
as well as tissue repair and regeneration. Chemokines also have an
important role in cancer metastasis and growth. Chemokine Therapeutics is a
leader in research in the field of chemokines and has several products in
various stages of development.

Safe Harbor Statement under the U. S. Private Securities Litigation
Reform Act of 1995: Statements in this document regarding managements’
future expectations, beliefs, goals, plans or prospects constitute
forward-looking statements that involve risks and uncertainties, which may
cause actual results to differ materially from the statements made. For
this purpose, any statements that are contained herein that are not
statements of historical fact may be deemed to be forward-looking
statements. Without limiting the foregoing, the words “believes”,
“anticipates”, “plans”, “intends”, “will”, “should”, “expects”, “projects”,
and similar expressions are intended to identify forward-looking
statements. You are cautioned that such statements are subject to a
multitude of risks and uncertainties that could cause actual results,
future circumstances, or events to differ materially from those projected
in the forward-looking statements. These risks include, but are not limited
to, those associated with the success of research and development programs,
the regulatory approval process, competition, securing and maintaining
corporate alliances, market acceptance of the Company’s products, the
availability of government and insurance reimbursements for the Company’s
products, the strength of intellectual property, financing capability, the
potential dilutive effects of any financing, reliance on subcontractors and
key personnel and other risks detailed from time-to-time in the Company’s
public disclosure documents and other filings with the U.S. Securities and
Exchange Commission and Canadian securities regulatory authorities.
Forward-looking statements are made as of the date hereof, and the Company
disclaims any intention and has no obligation or responsibility, except as
required by law, to update or revise any forward-looking statements,
whether as a result of new information, future events, or otherwise.

Chemokine Therapeutics Corp
chemokine/ Continue reading →

Cardiff University scientists, funded by cancer charity Leukaemia Research, are at the forefront of world research with new discoveries which they hope will lead to a new, targeted treatment for leukaemia patients who currently respond badly to conventional drugs.

Dr Chris Pepper and his multi-disciplinary team at the School of Medicine have discovered that some patients with chronic lymphocytic leukaemia (CLL) have high levels of a protein (called Rel A) and that these people develop a more aggressive form of the disease. This means they require more intensive therapy to treat CLL, which is the most common leukaemia in the UK.

The scientists have also discovered that the amount of this protein in the patient’s leukaemia cells accurately predicts how he or she will respond to treatment.

Dr Pepper, Research Scientist in the Department of Haematology, explained: ” This protein is providing new information about CLL patients which we believe will allow us to identify those who have more aggressive forms of this leukaemia. This is important because the timing and type of treatment can then be matched to the patients’ requirements. ”

Additionally, Dr Pepper’s team has shown that a new drug called LC-1 can block this Rel A protein, resulting in the targeted killing of the leukaemia cells. Encouragingly, tests in the laboratory show the new drug is equally effective in treating the cells of patients that respond poorly to the current treatment, fludarabine.

Dr Pepper explained: “We used our discoveries about the protein Rel A in CLL to predict that the drug LC-1 would have an effect on drug resistant cells. This turned out to be the case and the combination of LC-1 with fludarabine proved highly effective. We have now started a clinical trial here in Cardiff to test this new drug in patients and we will know later this year how effective it really is. ”

Dr David Grant, Head of Research Information at Leukaemia Research, says: ” This work is very exciting because it shows how research can help doctors individualise treatments for patients. Results so far suggest that the new drug LC-1 could be particularly useful in patients who have previously responded badly to conventional chemotherapy. ”

Leukaemia Research currently has over ??1.1 million invested in research into blood cancers at Cardiff University.

This new research has just been published in the highly respected journals Journal of Clinical Oncology and Clinical Cancer Research.

1. This research is published in the January edition of the Journal of Clinical Oncology under the title ‘Rel A is an Independent Biomarker of Clinical Outcome in Chronic Lymphocytic Leukemia’ and the December edition of Clinical Cancer Research, under the title ‘The Novel Nuclear Factor -KB Inhibitor LC-1 Is Equipotent in Poor Prognostic Subsets of Chronic Lymphocytic Leukemia and Shows Strong Synergy with Fludarabine’. The corresponding author for both papers, Dr Chris Pepper, is of the Department of Haematology, School of Medicine, Cardiff University.

2. Chronic lymphocytic leukaemia is a slowly progressing form of leukaemia, characterised by an increased number of white blood cells known as lymphocytes. With about 2,750 new cases occurring each year in the UK, it is the most common form of leukaemia in the UK and occurs predominantly in late middle age onwards. It has variable symptoms and course, but may be diagnosed by chance before the patient develops any clinical symptoms of the disease.

3. Over the next five years, Leukaemia Research urgently needs to raise over ??100 million to commit to new research. From basic laboratory research to clinical trials with patients, Leukaemia Research is committed to saving lives by funding high quality, carefully selected research throughout the UK.

4. Leukaemia Research is the only national charity devoted exclusively to improving treatments, finding cures and learning how to prevent leukaemia, Hodgkin’s and other lymphomas, myeloma and the related blood disorders, diagnosed in 24,500 people in the UK every year. Further information, including patient information booklets, is available from lrf or call 020 7405 0101

5. Cardiff University

Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research intensive universities. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, Professor Sir Martin Evans.

Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise in research and research-led teaching encompasses: the humanities; the natural, physical, health, life and social sciences; engineering and technology; preparation for a wide range of professions; and a longstanding commitment to lifelong learning.

Visit the University website at: cardiff.ac

Cardiff School of Medicine

Cardiff University’s School of Medicine is a significant contributor to healthcare in Wales, a major provider of professional staff for the National Health Service and an international centre of excellence for research delivering substantial health benefits locally and internationally. The school’s 800 staff include 500 research and academic staff who teach more than 2,000 students, including 1,110 postgraduate students. The School is an international leader in basic and clinically applied research activities and scored highly in the most recent Government Research Assessment Exercise. School of Medicine researchers annually win tens of millions of pounds in research awards to work with Government, the healthcare industries and the charitable sector on the most pressing issues of human health.

Cardiff School of Medicine Continue reading →

Most of the experts who tell us to take cholesterol lowering drugs have made money from pharmaceutical companies that produce them, say consumer groups.

Cholesterol lowering drugs sell well – a whopping $26 billion around the world in 2003. This year the figure is expected to be much higher. They are the best selling drugs on the market today.

Nine of the USA’s top cholesterol experts wrote the new guidelines which were issued by the American Heart Association and the US government.

The guidelines focus in reducing the number of heart attacks in the USA.

Of those nine experts, six have received money from producers of cholesterol lowering drugs. They received money for consultations, making speeches and carrying out research.

Experts say that 7 million more Americans will probably be taking pills to lower their cholesterol levels as a result of the new guidelines. There are already 36 million.

James Cleeman, National Cholesterol Education Program Coordinator, said that advising high risk heart patients to lower their LDL is good advice, regardless of connections to the drug industry by the people who wrote the guidelines.

Some people have responded to the accusations by saying that any top expert in any field of medicine will have connections with many organisations, some of which will be pharmaceutical companies that carry out research – they would not be top experts otherwise. Continue reading →

GE Healthcare announced that the U.S. Food and Drug Administration has granted clearance for the company’s newest model of Positron Emission Tomography/ Computed Tomography (PET/CT) scanner. This new addition to GE’s Discovery family of scanners continues GE’s commitment to help enable the earlier detection and monitoring of disease with advanced molecular imaging technology, in both hardware and software.

The new system will be optimized for use in oncology, which represents more than 90% of clinical PET/CT exams. The system continues using the highest-sensitivity crystals in the industry, along with GE’s exclusive VUE Point HD, High Definition imaging to help clinicians advance towards the goal of Motion Free PET/CT imaging.

Motion generated by the patient’s respiration can blur small lesions affecting resolution and quantitative accuracy. VUE Point HD, combined with other GE-exclusive motion-management techniques help improve lesion detectability, treatment planning and quantitative accuracy, improved contrast-to-noise of moving lesions up to 60% vs static acquisition for overall better clinical confidence.

“We anticipate shipping the first new scanners to customers in the fourth quarter of this year,” said Henry Hummel general manager of the PET/CT business at GE Healthcare. “The newest members of the Discovery line represent an outstanding evolution to GE PET/CT technology, from clinical to research applications.”

“As a market leader, GE has continued to focus on developing technologies that provide clinical excellence in PET/CT imaging,” said Hummel, “We believe our newest PET/CT scanners are an important step toward further reducing the effects of motion and improving the physician’s ability to help patients through better clinical images.”

About GE Healthcare

GE Healthcare provides transformational medical technologies and services that are shaping a new age of patient care. Our expertise in medical imaging and information technologies, medical diagnostics, patient monitoring systems, performance improvement, drug discovery, and biopharmaceutical manufacturing technologies is helping clinicians around the world re-imagine new ways to predict, diagnose, inform, treat and monitor disease, so patients can live their lives to the fullest.

GE Healthcare’s broad range of products and services enable healthcare providers to better diagnose and treat cancer, heart disease, neurological diseases and other conditions earlier. Our vision for the future is to enable a new “early health” model of care focused on earlier diagnosis, pre-symptomatic disease detection and disease prevention. Headquartered in the United Kingdom, GE Healthcare is a $17 billion unit of General Electric Company (NYSE: GE). Worldwide, GE Healthcare employs more than 46,000 people committed to serving healthcare professionals and their patients in more than 100 countries.

GE Healthcare Continue reading →

Nearly 150 basic and clinical scientists will assemble in Boston this week to better understand the role of the central nervous system in conditions such as postpartum depression and female anxiety at the Parental Brain Conference at Boston’s Back Bay Hilton. The event begins at 7 p.m. on Thursday, June 7.

The four-day event, hosted by Cummings School of Veterinary Medicine at Tufts University faculty member Robert S. Bridges, Ph.D., will bring together some of the leading minds on maladaptive parental response to share state-of-the-art methods and compare findings on several species, including humans. Leading gender biologist David R. Rubinow, M.D., Chair of Psychiatry at the University of North Carolina at Chapel Hill, will deliver the conference’s keynote lecture, “Postpartum depression: Context-Dependent Effects of Reproductive Steroids.”

“Most mammals, including humans, experience postpartum changes in behavior and emotional state, as well as similar maladaptive responses – and yet so little is known about the underlying mechanisms that cause them,” said Robert S. Bridges, Ph.D., professor and head of the Section of Reproductive Biology at the Cummings School and host of the conference. “It is our hope in gathering these top minds that we might come closer to understanding parenting.”

The Parental Brain Conference will include 11 symposia on topics ranging from maternal stress, anxiety and depression to bi-parental care. Conference supporters include National Institutes of Health, Cummings School Dean’s Fund, Mother-Infant Conference at Montreal’s Douglas Hospital, Tufts University Office of the Vice Provost for Research, University of Richmond, British Society for Neuroendocrinology, Boston College, and The Heinz Family Philanthropies.

Cummings School of Veterinary Medicine at Tufts University

Founded in 1978 in North Grafton, Mass., Cummings School of Veterinary Medicine at Tufts University is internationally esteemed for academic programs that impact society and the practice of veterinary medicine; three hospitals that treat more than 28,000 animals each year; and groundbreaking research that benefits animal, public, and environmental health.

Contact: Thomas Keppeler

Tufts University, Health Sciences Continue reading →

Kikkoman Corporation, in collaboration with Tohoku University, has discovered that the extract of tomato plays a role in healing atopic dermatitis.

The joint research compared two groups of mice: one that had been given tomato extract and the other, naringenin chalcone (NGC), a kind of polyphenol found in tomato peels. Both groups showed favorable results, and symptoms of atopic dermatitis improved. In particular, the administration of NGC inhibited the rise of serum IgE, an indicator of allergy.

Details of the research will be presented at the Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry 2006, to be held in Kyoto from March 25.

By Aki Tsukioka, JCN Staff Writer

Copyright © 2006 JCN. All rights reserved. A division of Japan Corporate News Network KK.

Company Profile Continue reading →

Keryx Biopharmaceuticals
(Nasdaq: KERX) announced that the Independent Data Safety Monitoring
Committee (DSMC) responsible for monitoring Sulonex(TM) (sulodexide oral
gelcaps), the Company’s lead drug candidate under development as a
treatment for diabetic nephropathy, recently met to evaluate the data from
the ongoing Phase 3 trial. Following a complete review of all available
safety and efficacy data, the DSMC found no cogent reason to recommend
alteration or termination of the Phase 3 trial. The DSMC raised no safety
concerns regarding Sulonex or the trial. As planned, no review was
conducted of the safety and efficacy data from the Phase 4 trial during
this meeting.

Prior to this most recent meeting, the DSMC had previously convened in
November 2006, in March 2007 and in August 2007 to review data from the
Phase 3 and Phase 4 studies. At each of these meetings the DSMC raised no
safety concerns.

On June 18, 2007, the Company announced the completion of patient
randomizations into the Phase 3 portion of the clinical registration
program. The Company anticipates that the last patient will complete the
active treatment period in mid-December 2007 and the two month
off-treatment period in mid-February 2008.

ABOUT THE SULONEX(TM) PHASE 3 and PHASE 4 CLINICAL PROGRAM

Sulonex is in a pivotal Phase 3 and Phase 4 clinical program under a
Special Protocol Assessment with the Food & Drug Administration. These
trials are being conducted by the Collaborative Study Group, the world’s
largest standing renal clinical trials group.

The clinical plan to support an NDA approval for Sulonex(TM) under
Subpart H (accelerated approval), as agreed upon with the FDA under an SPA,
consists of: (i) a single Phase 3 trial in patients with microalbuminuria
based on the surrogate marker of regression of microalbuminuria as the
primary endpoint; (ii) supportive data from previously conducted clinical
studies; and (iii) substantial recruitment into our Phase 4 confirmatory
study that will measure clinical outcomes in patients with overt
nephropathy, or macroalbuminuria.

The Phase 3 clinical program is a multi-center, randomized,
double-blind, placebo-controlled study, comparing 200 mg daily of
Sulonex(TM) versus placebo, with a 1:1 randomization between the two arms.
The objective of this study is to determine the safety and efficacy of
sulodexide in the treatment of patients with type 2 diabetes and persistent
microalbuminuria, or diabetic nephropathy, despite being treated with a
maximum approved or tolerated dose of an angiotensin II receptor blocker
(ARB) or angiotensin-converting enzyme inhibitor (ACEi). The study is
designed for patients to be on treatment for six months, followed by two
months of evaluation off-treatment.

During the treatment and off-treatment evaluation period, all patients
in the study population are expected to continue to receive maximum
approved or tolerated doses of ACEis or ARBs. Patients who were not already
on maximum approved or tolerated doses of ACEis or ARBs for 120 days were
required to go into a run-in period prior to randomization of up to 120
days. This run-in period was designed to stabilize blood pressure and to
confirm persistent microalbuminuria while the patients are treated with
maximum approved or tolerated doses of ACEis or ARBs.

The primary endpoint for the Phase 3 clinical trial is “therapeutic
success” at 6 months, where therapeutic success is defined as (i)
conversion from microalbuminuria to normoalbuminuria, as measured by
albumin/creatinine ratio (ACR), with at least a 25% reduction in ACR
relative to baseline ACR, or (ii) a 50% reduction in ACR relative to
baseline ACR.

Concurrently with the Phase 3 clinical trial, the Company is continuing
enrollment into its Phase 4 clinical trial, which is a randomized, double-
blind, placebo-controlled study, also comparing 200 mg daily of Sulonex(TM)
versus placebo, with a 1:1 randomization between the two arms. The
objective of this Phase 4 study is to determine the efficacy of Sulonex(TM)
in reducing the rate of progression to End-stage renal disease and adverse
clinical sequelae in patients with type 2 diabetes and macroalbuminuria or
overt diabetic nephropathy, despite being treated with a maximum approved
or tolerated dose of an ARB. All patients in the Phase 4 study population
are expected to continue to receive maximum approved or tolerated doses of
ARBs during the course of the study. The Phase 4 study is designed to
enroll approximately 2,200 patients.

The Company has committed to the FDA, as a condition to the approval of
Sulonex(TM) based on the Phase 3 clinical trial under the guidelines of
accelerated approval, that the Phase 4 study would be substantially
enrolled at the time of the filing of the NDA for Sulonex.

ABOUT SULONEX(TM)

Sulonex (sulodexide oral gelcap) belongs to a proposed new class of
nephroprotective, or kidney protecting, drugs, known as the
glycosaminoglycans. A variety of members of this chemical family have been
shown to decrease pathological albumin excretion in diabetic nephropathy in
humans. Some of the members of this chemical family include the following
approved drugs: standard heparin, low molecular weight heparin and
danaparoid. These agents all require therapy by injection and are all
potent anticoagulants, which are blood thinners capable of inducing
bleeding. Sulonex, on the other hand, is given orally and, in this form,
has demonstrated little, if any, anticoagulant effects to date.

Keryx owns the exclusive rights to use Sulonex(TM) for the treatment of
diabetic nephropathy in North America, Japan and certain other markets
outside of Europe. Diabetic nephropathy is a long-term complication of
diabetes in which the kidneys are progressively damaged. Sulonex is a
glycosaminoglycan compound with structural similarities to the broad family
of marketed heparins and low molecular weight heparins. This drug has been
marketed in a number of European, Asian and South American countries for
many years by our licensor for certain cardiovascular conditions and has an
established safety profile at the doses used for such indications.
Additionally, it has been demonstrated in multiple clinical trials
conducted in Europe and the U.S., including two randomized, double-blind,
placebo-controlled Phase II studies, that Sulonex can reduce urinary
protein excretion in patients with diabetic nephropathy.

Sulonex is in a pivotal Phase 3 and Phase 4 clinical program under a
Special Protocol Assessment, or SPA, with the Food & Drug Administration,
or FDA. These trials are being conducted by the Collaborative Study Group,
or the CSG, the world’s largest standing renal clinical trials group.

ABOUT KERYX BIOPHARMACEUTICALS, INC.

Keryx Biopharmaceuticals, Inc. is focused on the acquisition,
development and commercialization of medically important, novel
pharmaceutical products for the treatment of life-threatening diseases,
including diabetes and cancer. Keryx’s lead compound under development is
Sulonex(TM) (sulodexide oral gelcap), previously referred to as KRX-101, a
first-in-class, oral heparinoid compound for the treatment of diabetic
nephropathy, a life-threatening kidney disease caused by diabetes. Sulonex
is in a pivotal Phase 3 and Phase 4 clinical program under a Special
Protocol Assessment with the Food & Drug Administration. Additionally,
Keryx is developing Zerenex(TM), an oral, iron- based compound that has the
capacity to bind phosphorous and form non- absorbable complexes. Zerenex is
currently in Phase 2 clinical development for the treatment of
hyperphosphatemia (elevated serum phosphorous levels) in patients with
end-stage renal disease. Keryx is also developing clinical- stage oncology
compounds, including KRX-0401 (perifosine), a novel, first-in- class, oral
modulator of Akt, a pathway associated with tumor survival and growth, and
other important signal transduction pathways. KRX-0401 is currently in
Phase 2 clinical development for multiple tumor types. Keryx also has an
active in-licensing and acquisition program designed to identify and
acquire additional drug candidates. Keryx is headquartered in New York
City.

Cautionary Statement

Some of the statements included in this press release, particularly
those anticipating future performance, future results from the Phase 3 and
Phase 4 clinical trials, timelines for the completion of the Sulonex(TM)
pivotal clinical trial program, including the Phase 3 and the Phase 4
clinical trials, the number of patients and clinical sites included in the
Phase 3 and Phase 4 clinical trials, expectations regarding FDA approval
and commercial launch of Sulonex(TM), market size estimates for
Sulonex(TM), growth and operating strategies, safety and/or efficacy of
Sulonex(TM), and similar matters, are forward-looking statements that
involve a number of risks and uncertainties. For those statements, we claim
the protection of the safe harbor for forward- looking statements contained
in the Private Securities Litigation Reform Act of 1995. Important factors
may cause our actual results to differ materially, including: our ability
to successfully complete the Sulonex(TM) pivotal clinical program on a
cost- effective basis; failure to meet the endpoints of the Phase 3 or
Phase 4 studies; and other risk factors identified from time to time in our
SEC reports, including, but not limited to, the report on Form 10- K for
the year ended December 31, 2006, and our quarterly report on Form 10-Q for
the quarter ended September 30, 2007. Any forward-looking statements set
forth in this news release speak only as of the date of this news release.
We do not intend to update any of these forward-looking statements to
reflect events or circumstances that occur after the date hereof. This
press release and prior releases are available at keryx.
The information in Keryx’s website is not incorporated by reference into
this press release and is included as an inactive textual reference only.

Keryx Biopharmaceuticals
keryx Continue reading →

Certain types of brain cancer cells, called cancer stem cells, help brain tumors to buffer themselves against radiation treatment by activating a “repair switch” that enables them to continue to grow unchecked, researchers at Duke University Medical Center have found.

The researchers also identified a method that appears to block the cells’ ability to activate the repair switch following radiation treatment. This finding may lead to the development of therapies for overcoming radiation resistance in brain cancer as well as other types of cancer, the researchers said.

Working with animal and cell culture models, the researchers found that a specific cellular process called the “DNA damage checkpoint response” appears to enable cancer stem cells to survive exposure to radiation and to switch on a signal to automatically repair any damage caused to their DNA.

“In recent years, people have hypothesized that cancer stem cells are responsible for the resistance of malignant tumors to radiation treatment,” said Jeremy Rich, M.D., senior investigator of the study and an associate professor of neurology at Duke. “We have shown, for the first time, that this is indeed the case.”

The findings appear Oct. 18, 2006, in the advance online edition of the journal Nature. The research was supported by the National Institutes of Health and a number of philanthropic organizations [complete list below].

The type of cancer that the researchers studied, glioblastoma, is highly resistant to radiation and other forms of treatment and is the most deadly form of brain cancer worldwide. Although aggressive treatments can destroy the majority of the cancerous cells, a small fraction of them remain and often regenerate into even larger masses of tumor cells.

Until recently, scientists knew little about what made these resistant cells different from those that succumb to radiation treatment. It was clear, however, that the cells shared characteristics similar to those of normally functioning nerve stem cells, Rich said.

In the current study, the researchers used glioblastoma tissue removed from patients during neurosurgery and created two separate models. For one model, the researchers extracted cells from the tissue and grew them in cultures in the laboratory. For the second model, they transplanted the glioblastoma tissue into the frontal lobes of the brains of mice.

The researchers first measured the number of glioma stem cells present in the original tissue and then administered set doses of ionizing radiation to the cell cultures and to the mice. In both cases, the researchers observed a roughly fourfold jump in the number of glioma stem cells present in the tumor tissue following radiation treatment.

Because ionizing radiation works primarily by causing permanent damage to the key genetic material of cells, DNA, the researchers hypothesized that the glioma stem cells survive and multiply by somehow fixing radiation-induced DNA damage better than the other cancer cells.

To test this, the researchers searched the tissue samples for specific proteins that are responsible for detecting DNA damage. Using cell samples taken from both study models, the team examined the DNA damage checkpoint response both before and after use of ionizing radiation treatments by testing for activation of the key proteins that detect DNA damage. The researchers wanted to know whether the cells, following exposure to radiation treatment, would repair the DNA damage by activating the checkpoint response or whether they would instead die.

The team found that after ionizing radiation, the DNA damage checkpoint proteins in glioma stem cells were more highly activated than in other cancer cells. This heightened activation, the researchers said, leads cancer stem cells to more effectively repair DNA damage and thus render the cells less likely to die as a result of the treatment.

In another set of experiments, the researchers treated both the test animals and the cell cultures with a drug, called debromohymenialdisine, which is known to inhibit the proteins involved in the activation process. They added the drug before and after radiation treatment and measured the number of surviving cancer stem cells.

They found that administering the drug before radiation did little to change the number of cancer stem cells, but giving the drug in conjunction with radiation appeared to halt the resistance of cancer stem cells to radiation. This finding, the researchers said, suggests that use of a checkpoint inhibitor during radiation ruins the cells’ potential to repair themselves and increases the likelihood that the cells will die.

“Our findings show one pathway in cancer stem cells that promotes the radiation resistance of glioblastomas,” said Rich. “Treatments that target DNA damage checkpoint response in cancer stem cells may overcome the radiation resistance and eventually allow us to help even greater numbers of cancer patients.”

Other researchers involved in the study were Shideng Bao, Qiulian Wu, Roger McLendon, Yueling Hao, Qing Shi, Anita Hjelmeland, Mark Dewhirst and Darell Bigner.

The philanthropic organizations that supported the research include the Childhood Brain Tumor Foundation, the Pediatric Brain Tumor Foundation of the United States, the Damon Runyon Cancer Research Foundation, the Sidney Kimmel Foundation for Cancer Research, Accelerate Brain Cancer Cure, and the Duke Comprehensive Cancer Center Stem Cell Initiative.

Contact: Tracey Koepke

Duke University Medical Center Continue reading →

Patients with diabetic nephropathy (kidney disease caused by diabetes) who received high dose B-vitamin therapy experienced a more rapid decline in kidney function and had a higher rate of heart attack and stroke than patients who received placebo, according to a study in the April 28 issue of JAMA.

Diabetic nephropathy typically affects the network of tiny blood vessels in the glomerulus, a key structure in the kidney composed of capillary blood vessels, which is necessary for the filtration of the blood. “In addition to the personal burden, the societal burden of diabetic nephropathy is enormous, exceeding U.S. $10 billion in annual medical expenditures. Despite effective therapies to slow disease progression, approximately 40 percent of the estimated 21 million patients with diabetes in the United States develop overt nephropathy. New treatment approaches to this problem are needed,” the authors write.

According to background information in the article, several observational studies have shown a significant association between high concentrations of plasma total homocysteine and the risk of developing diabetic nephropathy, retinopathy, and vascular diseases, including myocardial infarction (MI; heart attack) and stroke. B-vitamin therapy (folic acid, vitamin B6, and vitamin B12) has been shown to lower the plasma concentration of homocysteine.

Andrew A. House, M.D., of the University of Western Ontario, and J. David Spence, M.D., of the Robarts Research Institute, London, Ontario, and colleagues conducted a study to examine whether B-vitamin therapy would slow the progression of diabetic nephropathy and prevent vascular events in 238 patients with type 1 or 2 diabetes. The randomized, placebo-controlled trial was conducted at five university medical centers in Canada between May 2001 and July 2007. Patients received single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d), or matching placebo. The primary outcome was change in radionuclide glomerular filtration rate (GFR; a measure of kidney function) between baseline and 36 months. Other outcomes included dialysis and a composite of heart attack, stroke, revascularization and all-cause death. Plasma total homocysteine was measured. Participants were followed-up for an average of 31.9 months.

Among the results, the researchers found that participants assigned to the B-vitamin group had a greater decrease in radionuclide GFR (and subsequently poorer kidney function) compared with the placebo group. Also, participants randomized to receive B vitamins had a significantly greater number of cardiovascular and cerebrovascular events, with the 36-month risk of a composite outcome, including heart attack, stroke, revascularization, and all-cause mortality that was double in the B-vitamin group, compared to the placebo group. There was no difference in requirement of dialysis.

Regarding plasma total homocysteine levels, at 36 months, participants in the B-vitamin group had an average decrease while participants in the placebo group had an average increase.

“Given the recent large-scale clinical trials showing no treatment benefit, and our trial demonstrating harm, it would be prudent to discourage the use of high-dose B vitamins as a homocysteine-lowering strategy outside the framework of properly conducted clinical research,” the authors conclude.

JAMA. 2010;303[16]:1603-1609.

Source
Journal Of the American Medical Association Continue reading →

Forest
Laboratories (NYSE: FRX) announced that single doses of inhaled
aclidinium produced a significant bronchodilatory response in 17 patients
with COPD according to results of a phase IIa trial presented today at the
European Respiratory Society (ERS) Annual Congress in Stockholm.(1)

Results of the study showed that mean FEV1 and FVC values – important
measures of lung function – were significantly increased with all studied
doses of aclidinium over a 24-hour time period, as compared to placebo.
Onset of significant bronchodilation was observed as early as 15 minutes
after aclidinium treatment and this effect was sustained for at least 24
hours. Forest licensed aclidinium, currently in phase III clinical trials
in COPD, from Spanish pharmaceutical company, Almirall.

Aclidinium was well-tolerated during the phase IIa trial and no
patients withdrew from the study because of adverse events. The majority of
adverse events reported were mild to moderate in intensity. The most
frequent drug- related adverse event observed was headache, which occurred
after both placebo and aclidinium treatment and was not dose-related.
Single doses of aclidinium did not result in any clinically significant
adverse effect on vital signs, heart function (as assessed by 12-lead ECG)
or laboratory data.

“Given the increasing disease burden of COPD in the US, there is a need
for new treatment options for patients suffering from this debilitating
disease,” said Lawrence S. Olanoff, M.D., Ph.D., President and Chief
Operating Officer. “These phase II data reinforce our belief that
aclidinium has the potential to be a significant addition to the existing
armamentarium of COPD treatments.”

Methodology

The phase IIa study of aclidinium was a two-center, double-blind,
randomized, ascending single-dose, placebo-controlled, cross-over trial
which enrolled 17 patients with moderate to severe COPD. Treatment was with
one of three doses of aclidinium (100 micrograms, 300 micrograms or 900
micrograms) or placebo-administered via dry-powder inhaler. The study’s
primary outcome measure was area under the normalized curve (AUC) of FEV1
over a 24-hour time period.

Findings of a phase I single-dose study, also presented at ERS 2007,
demonstrate the bronchodilatory effects of aclidinium.(2) In the phase I
study, in 12 healthy volunteers, bronchoconstriction was induced with
methacholine challenge and then treated with one of three doses of
aclidinium. Aclidinium proved superior to placebo in improving specific
airway conductance. Aclidinium also provided statistically significant and
sustained protection against methacholine-induced airway constriction over
24 hours. Aclidinium was well-tolerated throughout the trial. Headache was
reported by two subjects and one subject experienced a serious adverse
event which was not considered to be related to study drug.

Results of preclinical studies also presented at the congress show
aclidinium’s selectivity, long duration of action and rapid clearance from
the plasma.(3,4) When compared to other bronchodilatory agents in vitro,
aclidinium demonstrated potent anticholinergic activity comparable to both
tiotropium and ipratropium, but with a faster onset of action than
tiotropium and a significantly longer duration of action versus
ipratropium, allowing for 24- hour duration of action.(4)

About COPD

COPD is a preventable and treatable lung disease characterized by
chronic airflow limitation that is not fully reversible.(5) COPD is a
leading cause of death, illness, and disability in the United States, with
an estimated 10 million to 24 million adults in the US living with COPD.(6)

About Aclidinium Bromide

Aclidinium bromide is a novel inhaled anticholinergic bronchodilator
that is currently in phase III clinical development as a once-daily
maintenance treatment for COPD.

About Forest Laboratories and Its Products

Forest Laboratories (frx) is a US-based pharmaceutical company
dedicated to identifying, developing and delivering products that make a
positive difference in peoples’ lives. Forest Laboratories’ growing product
line includes Lexapro(R) (escitalopram oxalate), an SSRI indicated for
adults for the initial and maintenance treatment of major depressive
disorder and generalized anxiety disorder; Namenda(R) (memantine HCl), an
N-methyl D- aspartate (NMDA)-receptor antagonist indicated for the
treatment of moderate to severe Alzheimer’s disease; Benicar(R)
(olmesartan medoxomil), an angiotensin receptor blocker, and Benicar
HCT(R) (olmesartan medoxomil – hydrochlorothiazide), an angiotensin
receptor blocker and diuretic combination product, each indicated for the
treatment of hypertension; and Campral(R) (acamprosate calcium), indicated
in combination with psychosocial support for the maintenance of abstinence
from alcohol in patients with alcohol dependence who are abstinent at
treatment initiation.

Benicar is a registered trademark of Daiichi Sankyo, Inc., and Campral
is a registered trademark of Merck Sante s.a.s., subsidiary of Merck KGaA,
Darmstadt, Germany.

Except for the historical information contained herein, this release
contains “forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements involve a number
of risks and uncertainties, including the difficulty of predicting FDA
approvals, the acceptance and demand for new pharmaceutical products, the
impact of competitive products and pricing, the timely development and
launch of new products, and the risk factors listed from time to time in
the Forest Laboratories’ SEC reports, including the Company’s Annual Report
on Form 10-K for the fiscal year ended March 31, 2007 and quarterly report
on form 10-Q for the period ended June 30, 2007.

References

1. Joos GF, Schelfhout VJ, Kanniess F et al. Bronchodilator effects of
aclidinium bromide, a novel long-acting anticholinergic, in COPD
patients: a phase II study. European Respiratory Society (ERS) Annual
Congress, September 2007. Poster.

2. Schelfhout VJ, Joos GF, Gil EG et al. Bronchodilator/bronchoprotective
effects of aclidinium bromide, a novel long-acting anticholinergic: a
phase I study. European Respiratory Society (ERS) Annual Congress,
September 2007. Poster.

3. Gavalda A, Miralpeix M, Ramos I et al. Aclidinium bromide, a novel
muscarinic receptor antagonist combining long residence at M3 receptors
and rapid plasma clearance. European Respiratory Society (ERS) Annual
Congress, September 2007. Poster.

4. Miralpeix M, Gavalda A, Morcillo E et al. Assessment of the potency and
duration of action of aclidinium bromide in guinea pig isolated trachea
in vitro. European Respiratory Society (ERS) Annual Congress, September
2007. Poster.

5. Global Initiative for Chronic Obstructive Lung Disease. Global strategy
for the diagnosis, management, and prevention of chronic obstructive
pulmonary disease; MCR Vision, Inc.; 2006

6. CDC, cdc/nceh/airpollution/copd/copdfaq.htm, accessed
September 11, 2007.

Forest Laboratories
frx

View drug information on Benicar; Campral. Continue reading →