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 →

Hospital-at-home care may be a practical alternative to traditional hospital inpatient care for patients with acutely decompensated (suddenly worsening) chronic heart failure, according to a report in the September 28 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Nearly 7 million Europeans and 5 million North Americans are affected by chronic heart failure, a progressive and disabling syndrome, according to background information in the article. Hospitalization for chronic heart failure for older patients has increased and occurs in 2 percent to 3 percent of patients over age 85 every year. In the United States, decompensation (worsening) of chronic heart failure leads to more than 1 million hospital admissions per year and a 50 percent risk of subsequent hospitalization within six months of discharge. “Although the hospital is the standard venue for providing acute medical care, it may be hazardous for older persons, who commonly experience iatrogenic illness [complications due to treatment], functional decline and other adverse events.”

Vittoria Tibaldi, M.D., Ph.D., and colleagues at the University of Torino, San Giovanni Battista Hospital, Torino, Italy, compared the effectiveness of a physician-led hospital-at-home service for elderly patients with acute decompensation of chronic heart failure with traditional hospital inpatient care. Patients age 75 or older with decompensation of chronic heart failure were randomly assigned to either a general medical ward (53 patients) or to the Geriatric Home Hospitalization Service (48 patients) between April 2004 and April 2005. The Geriatric Home Hospitalization Service provided diagnostic and therapeutic treatments by hospital health care professionals in the home of the patient.

At six months, 15 percent of all patients had died, with no significant differences between the two groups. “The number of subsequent hospital admissions was not statistically different in the two groups, but the mean [average] time to first additional admission was longer for the Geriatric Home Hospitalization Service patients (84.3 days vs. 69.8 days). Only the Geriatric Home Hospitalization Service patients experienced improvements in depression, nutritional status and quality-of-life scores,” the authors write.

“Recent trends in health care favor alternatives to traditional acute care in hospitals. These trends include advancement in telehealth technologies and increased demand for treatment at home,” the authors conclude. “Further development of hospital-at-home care will require additional research and dedicated resources to support dissemination.”

Arch Intern Med. 2009;169[17]:1569-1575.

Source
Archives of Internal Medicine Continue reading →

Researchers at Johns Hopkins have discovered that cancers arising from epigenetic changes – in this case the inappropriate activation of a normally silent gene – develop by becoming addicted to certain growth factors. Reporting online in next week’s Early Edition of the Proceedings of the National Academies of Sciences, the team shows that blocking this “addiction” can greatly prevent cancer growth.

“If this is translatable to people, it could be really exciting,” says Andrew Feinberg, M.D., professor of medicine, oncology and molecular biology and genetics and director of the Epigenetics Center at Hopkins. “It means we might be able to do something about at-risk cells before cancer develops, and treat these cells biochemically and specifically, rather than using current drugs that are nonspecific and kill everything in their path.”

The gene for growth factor IGF-II (insulin-like growth factor two) is one of several in the human genome that is controlled by imprinting – where one of the two copies of the gene is turned off, depending on which parent it came from. Normally, the IGF-II gene from your father is turned on and the one from your mother is turned off. Loss of this imprinting causes the activation of the maternal copy, leading to activation of both copies of the IGF-II gene, which has been associated with a fivefold increased frequency of intestinal tumors in people.

The Hopkins team tested mouse cells with imprinting intact, which have only one copy of IGF-II activated, and compared them to cells that had lost imprinting and have both copies of IGF-II activated. They found that normally imprinted cells respond to normal doses of growth factor and recover within 90 minutes. However, cells that had lost imprinting were activated by the smallest doses and continued to stay activated for more than 120 minutes.

“It’s like they were on a hair trigger, which was totally counterintuitive to what we might have predicted,” says Andre Levchenko, Ph.D., an assistant professor of biomedical engineering at Hopkins and co-director of the study. “You would expect in cells that have lost imprinting, and therefore have twice the amount of gene product, that it would take higher doses to activate the cell. In fact, the cell becomes hypersensitized while having too much IGF-II around.”

The researchers then wondered if blocking the cells’ response to IGF-II could block cancer growth in animals. Mice that develop colon cancer were given a drug that specifically blocks a cell’s ability to respond to IGF-II. These mice developed 70 percent fewer precancerous lesions than mice without treatment.

“Finding the molecular mechanism behind cancer development allowed us to use a specific drug to actually take care of these risky cells before the animal developed cancer,” says Feinberg. “It’s making us think about cancer prevention in a whole new way.”

The research was funded by the National Institutes of Health and the Swedish Cancer Research Foundation.

Authors on the paper are Atsushi Kaneda, Chiaochun Wang, Raymond Cheong, Winston Timp, Patrick Onyango, Bo Wen, Christine Iacobuzio-Donahue, Andre Levchenko and Feinberg of Hopkins; Rolf Ohlsson of Uppsala University in Uppsala, Sweden; Rita Andraos and Mark Pearson of Novartis Institute of Biomedical Research in Basel, Switzerland; and Alexei Sharov, Dan Longo and Minoru Ko of the National Institute on Aging in Baltimore, Md.

Johns Hopkins Medicine
901 S. Bond St., Ste 550
Baltimore, MD 21231
United States
hopkinsmedicine Continue reading →

A comparison of breast milk samples from Denmark and Finland revealed a significant difference in environmental chemicals which have previously been implicated in testicular cancer or in adversely affecting development of the fetal testis in humans and animals. This finding is published in the International Journal of Andrology.

In recent years a worldwide increase in testicular cancer has been noticed, but the cause remains unknown. In some countries, such as Denmark the prevalence of this disease and other male reproductive disorders, including poor semen quality and congenital genital abnormalities is conspicuously high; while in Finland, a similarly industrialized Nordic country, the incidences of these disorders are markedly lower. In the UK, almost 2,000 men are diagnosed with testicular cancer every year, and in the US this number is over 8,000. There is a wide variation in incidence rates of testicular cancer around the globe, and the reasons behind the observed trends are unexplained.

Environmental endocrine disrupting chemicals (EDCs) are commonly found in fatty foods, paints, plasticizers, pesticides, and the byproducts of industrial processes, and in recent studies an association has been shown between some of these agents and male reproductive problems. To investigate whether EDCs could be related to such great differences in reproductive disorders between closely related countries, Konrad Krysiak-Baltyn and colleagues from Denmark, Finland, and Germany measured levels of 121 chemicals in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to EDCs.

With so many chemicals, they used sophisticated, bioinformatics tools to interpret the complex data, and the results showed a clear distinction between the countries.

“We were very surprised to find that some EDC levels, including some dioxins, PCBs and some pesticides, were significantly higher in Denmark than in Finland,” said Professor Niels Skakkebaek, a senior member of the research team, based at the University Department of Growth and Reproduction, Rigshospitalet, Denmark. “Our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.”

“In spite of the findings, I would strongly urge women, including Danish mothers, to continue with breast feeding, which has many beneficial effects for the child,” added Skakkebaek.

Continue reading →

Consuming foods high in animal protein, saturated fat, eggs and dairy leads to an increased risk of developing non-Hodgkin’s lymphoma (NHL), a cancer that attacks the lymphatic system, part of the body’s immune system, Yale researchers have found.

Published in the American Journal of Epidemiology, the study also showed that diets high in dietary fiber — tomatoes, broccoli, mixed lettuce salad with vegetables, cauliflower, etc.– were associated with a reduced risk of NHL.

‘An association between dietary intake and NHL is biologically plausible because diets high in protein and fat may lead to altered immunity, resulting in increased risk of NHL,’ said principal investigator Tongzhang Zheng, M.D., associate professor of epidemiology and environmental health at Yale School of Medicine. ‘The antioxidants found in vegetables and fruits may result in reduced risk of about 40 percent.’

The study was conducted between 1995 and 2001 on 601 Connecticut women between the ages of 21 and 84 diagnosed with varying subtypes of NHL. Using a Food Frequency Questionnaire (FFQ) developed by the Fred Hutchinson Cancer Research Center, each participant was asked to characterize her usual diet in the year prior to being interviewed. The FFQ collects consumption frequency and portion size data for approximately 120 foods and beverages and is periodically updated to reflect U.S. food consumption patterns and major market changes.

After completion, the FFQ was sent to the Fred Hutchinson Cancer Research Center for calculating average daily nutrient intakes. The study included a control group of 717 women.

‘So far, risk of NHL associated with animal protein and fat intakes has only been investigated in American women, in three studies,’ said Zheng. ‘If the association could also be demonstrated in American men, it would provide important information towards understanding the cause of NHL.’

Other authors on the study included Theodore R. Holford, Yawei Zhang, M.D., Brian Leaderer, Stuart Flynn, M.D., Geovanni Tallini, M.D. and Patricia Owens of Yale; Sheila Hoar Zahm of the National Cancer Institute; and Peter Boyle of Europe Institute of Oncology, Milan, Italy and Qing Lan, M.D. and Nathaniel Rothman, M.D., of the National Cancer Institute.

The National Cancer Institute funded the study. Citation: American Journal of Epidemiology, March 1, 2004; Volume 159, Issue 5 454-466

Contact: Karen N. Peart
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203-432-1326
Yale University Continue reading →

University of Manchester scientists have discovered for the first time an important new way in which the human papilloma virus (HPV) triggers cancer in what could lead to new treatments for cervical and mouth cancer.

HPV infection is known to increase the risk of developing cancers of the cervix and mouth with the two high-risk forms of the virus accounting for approximately 70% of all cervical cancer cases.

Vaccinations against these high-risk forms of HPV should reduce the incidence of cervical cancer but the frequency of mouth cancer actually increased in the UK by about 50% between 1989 and 2007, a trend that seems to be accelerating.

If the current vaccines prove effective at preventing oral HPV infection, the authors claim their findings provide additional justification for the current programme of vaccinating young girls and may also lend support to extending the programme to young boys too.

“Scientists have known for some years about the link between HPV and certain cancers but the biological processes involved are not fully understood,” said Dr Ian Hampson, who with wife Dr Lynne Hampson headed the research. “Our latest results shed new light on this.

“Our study has shown that a protein in cells called Cdc42, which is already known to be implicated in a number of cancers as well as in tumour spread, is inappropriately activated by the human papilloma virus.

“The findings are important since it is essential to increase our understanding of how the virus causes the disease if we are to design new approaches for the prevention or treatment of HPV-related cancers. Mouth cancer, in particular, is notoriously difficult to treat and often leads to long-term disability.

“If the vaccination programme is shown to reduce the incidence of oral HPV infection then this study would appear to support its continued use as a way to prevent HPV-related mouth cancer and perhaps consideration should be given to extending the programme to boys.”

The research, published in the British Journal of Cancer, was carried out in the Gynaecological Oncology Laboratories at St Mary’s Hospital, Manchester, by one of the Hampsons’ PhD students, Dr Anthony Oliver.

Dr Oliver said: “There are literally hundreds of publications describing the potential role of Cdc42 in malignant disease but our work is the first to show that HPV can activate this protein.

“There is already a drive towards developing drugs that target activated Cdc42 and our findings now indicate that these agents may be useful for the treatment of HPV-related cancers too.”

The study was funded by the Humane Research Trust with additional funding also provided by The Association for International Cancer Research, The Caring Cancer Trust and the Cancer Prevention Research Trust.

Sources: Manchester University, AlphaGalileo Foundation. Continue reading →