| Brain
cancer linked to nerve agent-(USA TODAY-25/07/2005)
For the first time, a study has found an increase in
brain cancer deaths among Gulf War veterans who might have been exposed to
the nerve agent sarin by the destruction of Iraqi weapons in 1991. About
100,000 of the 350,000 Army soldiers in the Persian Gulf could have been
exposed to sarin after soldiers blew up two large ammunition caches in
Khamisiyah, Iraq, in March 1991, according to a study commissioned by the
military and performed by the Institute of Medicine. The institute advises
the government on health policy.
According to the study, soldiers inside the "hazard
area" were about twice as likely as those outside it to die from brain
cancer. Because the actual number of brain cancer cases was small, the
overall mortality rate was the same for veterans in the hazard area and
outside the area, according to the study, published in the American
Journal of Public Health. Among unexposed soldiers, researchers found a brain
cancer death rate of 12 per 100,000 from 1991 to 2000, says William Page,
director of the study. Over the same period, researchers found 25 brain
cancer deaths per 100,000 veterans who were exposed. "It's a doubling of risk, but it's still a pretty
small risk," says Page, a senior program officer at the Institute of
Medicine.
The study did not address "Gulf War syndrome," as
some have called the collection of ailments experienced by returning
veterans. It examined whether soldiers possibly exposed to the destruction
of Iraqi weapons were more likely to die for any reason. They also singled
out specific diseases: breathing problems, infections, circulatory problems,
digestive ailments, accidents and suicides, as well as four types of cancer. The study's authors note that sarin has never been
shown to cause cancer. Page suggests that researchers follow veterans to see
whether the risk of brain cancer, which is believed to develop over 10 to 20
years, changes over time. Page also notes that the study doesn't prove that
being in the hazard area caused brain cancer.
Melissa Bondy, a professor of epidemiology at M.D.
Anderson Cancer Center in Houston, questions why only one or two days of
exposure would increase brain cancer mortality. Other experts note that the
study could shed light on the causes of brain tumors, about which doctors
know little.
[Top]
Study Says Brain Cancer Treatments Vary-(Yahoo
News-01/02/2005)
Brain cancer
in adults is a dreaded diagnosis with few established treatment guidelines,
resulting in wide variations in care that can make things even worse for
some patients, a study suggests. Nearly half of patients surveyed received
no chemotherapy despite evidence that it can boost survival. Anti-seizure
drugs were widely used even though most patients did not have seizures. And
while depression is common in people with brain cancer, more than 90 percent
said they never were given antidepressants. While there might have been valid reasons for the treatment choices, the
wide
variation suggests some patients are not getting appropriate care, said lead
author Dr. Susan Chang, a brain cancer specialist at the University of
California
at San Francisco. "We have a lot of work to do," she said.
The findings stem from a survey of 788 adult brain cancer patients at 52
centers
throughout the United States and Canada. The results appear in Journal of
the
American Medical Association. The survey serves as a report card on the care
of
newly diagnosed patients, and "unfortunately, the grades are sobering,"
according to a JAMA editorial. The study underscores a troubling, pervasive
problem in brain cancer: Patients get shortchanged, said Stanford University
brain tumor specialist Dr. Paul Fisher, co-author of the editorial. Many
view brain
cancer as a hopeless disease, and as a result, there is too little research
into
causes, risk factors and treatments, he said.
The study involved patients with advanced malignant gliomas, a type of
brain
cancer diagnosed in about 9,000 U.S. patients each year. Average survival
rates
range from less than a year for more advanced gliomas to about five years
for
less advanced forms. Most glioma patients are diagnosed when the tumor is
already large and root-like, infiltrating deeply into brain tissue and
making
complete surgical removal nearly impossible, Chang said. Treatment typically
involves a combination of surgery and radiation, but
high-grade gliomas generally
are considered incurable. Chemotherapy has shown
modest benefits, Chang said.
Kyla Nagel of Eugene, Ore., was diagnosed with an aggressive glioma three
years ago after a seizure. Doctors in Oregon told her there was nothing they
could do. "I went from being a healthy 23-year-old to all of a sudden you
have
cancer. I was given one year to live," said Nagel, who worried most about
her
then 1 1/2-year-old daughter. She underwent conventional treatment,
including
intravenous chemotherapy, but her cancer returned and she eventually
enrolled
in a UCSF research regimen using an experimental drug that was injected
through a catheter directly into her tumor. Nagel's outcome was not typical
three years later her brain scans show no signs of cancer.
Her case shows that brain cancer is not always hopeless, and it
underscores
the need for more research, Chang said. European research released last
year,
after Chang's study ended, showed improved survival rates for patients on a
newer pill, temozolomide, when used with radiation promising results that
might change treatment practices, the JAMA study authors said.
[Top]
YM BioSciences to Advance
Into Late-Stage Study for Brain Cancer Treatment-(ET-25/01/2005)
YM BioSciences Inc. reported that it expects to
complete a late-stage clinical trial for its brain cancer treatment by the
second quarter of 2006 after reaching a success milestone in mid-stage trials. The company said its European partner, Oncoscience AG, confirmed that a mid-stage trial testing the monoclonal
antibody h-R3 as a stand-alone brain cancer therapy reached a clinical
milestone allowing it to convert data for use in late-stage trials.
The trial enrolled 18 patients -- all children with brain cancer expected
to live 4 to 6 weeks -- and was halted because the treatment had reached
its predefined levels showing effectiveness in three or more patients.
The antibody will be tested as a front-line brain cancer treatment for
patients following surgery, in combination with radiation treatments versus
radiation alone. YM expects to enroll about 100 patients in the Phase
III trial.
[Top]
Breakthrough in treatment of brain
tumour-(Times of India-30/09/2004)
A simple genetic test can identify which patients with deadly brain tumours
will be helped by a treatment hailed as the first significant advance
against the disease in decades. A study by Swiss doctors found that 46%
of patients with the right genetic profile were still alive after two
years if they got the drug temozolomide as well as radiotherapy whereas
the chance of survival among patients with the wrong genetic signature
was only 14%-not much better than radiation alone.
Experts say the test could avoid the raising of false hopes in patients
with glioblastomas who would not benefit, freeing doctors to try other
approaches. The finding is another step in the quest for the individual
tailoring of cancer treatment.
[Top]
Arthritis
Drugs May Help Fight Cancer-Study-(Reuters-22/10/2004)
Arthritis drugs
like Celebrex and the recently withdrawn Vioxx may boost the immune
system's ability to attack brain tumors, and possibly other types of
cancer, researchers said on Friday. Doctors
at Cedars-Sinai Medical Center in Los Angeles have shown that the COX-2
enzyme is responsible for triggering a cellular process that disrupts the
body's immune response, allowing cancer cells to multiply. COX-2 blockers
-- a class that includes Pfizer Inc.'s Celebrex and Merck & Co Inc.'s
late Vioxx -- work to fight arthritis pain by blocking the
inflammation-causing COX-2 enzyme.
Results of the Cedars-Sinai study, which
appear in the Oct. 1 issue of the Journal of Immunology, support the idea
that medications attacking the enzyme may also boost the immune system's
ability to recognize and target cancer cells. "When secreted, COX-2
shuts down the immune system," said Dr. John Yu, the study's
principal investigator. "We would hope to incorporate use of COX-2
inhibitors in all patients with brain tumors."
Vioxx was withdrawn from the market last
month after twice as many patients taking it for at least 18 months
suffered heart attacks and strokes during a 2,600-patient trial of the
drug's ability to curb precancerous colon polyps. Merck also halted two
other cancer-related studies of the drug -- one in men at risk of prostate
cancer and another related to preventing colon cancer.
Using brain cancer cells, the Cedars-Sinai
researchers said laboratory tests showed that COX-2 set in motion a series
of interactions that altered messages sent to dendritic cells, which are
responsible for detecting foreign matter and instructing cancer-killing
cells to attack the tumor. But T-cells circulating in the bloodstream
showed a regulatory response against the patient's cancer cells, the study
found. "By using COX-2 inhibitors, these tumors may become more
detectable and therefore more vulnerable to destruction by the immune
system," Yu said. He said Cedars-Sinai plans to add drugs like
Celebrex to its clinical trials for brain tumors. "Studies need to be
done to see if there is relevance to other cancers," Yu added.
[Top]
Brain
Disease Rates Soaring, Pollution Link Cited-(Yahoo News- 18/08/2004)
Deaths from brain diseases such
as Alzheimer's, Parkinson's and motor neuron disease appear to have soared
in the past two decades in the world's most developed nations, and
researchers are blaming the increase on higher levels of pesticides,
industrial chemicals, car exhaust and other pollutants. A report on the
study by a Southampton University team, published in the journal Public
Health, finds that dementia rates have trebled in men and increased by 90
per cent among women, according to The Independent.
In the late 1970s, there were
about 3,000 deaths a year from brain diseases in England and Wales. At the
end of the last decade, that figure had risen to 10,000, researchers
found. The study examined rates of the diseases in Australia, Canada,
France, Germany, Italy, Japan, the Netherlands, Spain, the U.K. and the
United States between 1979 and 1997.
Meanwhile, from Spain came more
hopeful news: An ingredient in marijuana may be useful for treating brain
cancers, Spanish researchers reported Sunday. The chemicals called
cannabinoids could starve tumors to death by halting the growth of blood
vessels that feed them, according to a team from Complutense University in
Madrid. Their research, published in the Aug. 15 issue of Cancer Research,
showed that the cannabis extracts block a key chemical needed for tumors
to sprout blood vessels -- a process called angiogenesis.
And for the first time, the
team has shown the cannabinoids impede this chemical in people with the
most aggressive form of brain cancer, glioblastoma multiforme, which is
notoriously difficult to treat. They took samples from two patients with
glioblastoma multiforme who had not responded to surgery, chemotherapy and
radiotherapy treatment, BBC reported. Samples were taken before and after
the patients were treated with cannabinoid solution infused directly into
the tumor. In both patients, the tumor was reduced following treatment.
[Top]
Combo
Therapy Slows Incurable Brain Tumors- (HealthDayNews -16/08/2004)
A combination of immune therapy
and chemotherapy slows incurable brain tumors and extends patient
survival, says a study in the Aug. 15 issue of Clinical Cancer Research.
Researchers at Cedars-Sinai Medical Center found this approach slowed
tumor progression and lengthened survival of patients with aggressive and
incurable brain tumors called glioblastoma multiforme (GBM). This method
lengthened survival to about 26 months, compared to 18 months for patients
who received immune vaccine alone and 16 months for patients who received
chemotherapy alone.
Five of the 12 patients (41.7
percent) who received the combination treatment survived longer than two
years, compared with one of the 12 (8.3 percent) who received the vaccine
alone and one of 12 who received chemotherapy alone. Two patients in the
combined therapy lived longer than three years. No patients in the other
two groups lived that long. "We've very excited abut the results.
Obviously they need to be confirmed in a randomized trail, but assuming
these outcomes are reproducible, it would be extremely gratifying to see
this kind of increase in survival for such a devastating disease,"
researcher Dr. Keith L. Black, director of the Maxine Dunitz Neurosurgical
Institute at Cedars-Sinai, said in a prepared statement.
Although he and his colleagues
don't know exactly how this combination therapy works, they believe it's a
one-two punch. The anti-tumor vaccine delivers the initial blow against
the tumor cells, increasing their vulnerability to the chemotherapy drugs.
[Top]
Vaccine
targeting cancer-related antigens in brain tumors appears to prolong survival
-(Yahoo news-15/07/2004)
Researchers
seeking to direct cancer-killing immune cells against the deadliest brain
tumors have three new targets that show promise in laboratory studies and
in a Phase I patient trial, according to two articles in the July 15 issue
of the journal Cancer Research.
The
antigens, previously associated with several other types of cancer cells,
were recently found to be expressed in the most common and aggressive type
of malignant brain tumor, glioblastoma multiforme (GBM). Scientists at
Cedars-Sinai's Maxine Dunitz Neurosurgical Institute and the National
Cancer Institute have generated cytotoxic T lymphocyte clones
(cancer-killing immune cells) that recognize GBM cells expressing these
antigens.
"In a Phase I clinical trial of 14
patients, we found that our dendritic cell vaccine not only generated an
immune response against these antigens but it appeared to play a
significant role in prolonging survival in patients with glioblastoma,"
said Keith L. Black, MD, director of the Institute, the Division of
Neurosurgery and the Comprehensive Brain Tumor Program at Cedars-Sinai.
The median length of survival of patients
with recurrent glioblastoma whose treatment included the vaccine was 133
weeks about two and a half years. A similar group of patients
receiving the same level of care but not the vaccine had a median survival
of only 30 weeks seven and a half months.
John S. Yu, MD, senior author of the
articles and co-director of the Comprehensive Brain Tumor Program, said
these findings represent a significant advance in the field of brain tumor
immunotherapy.
"This is the first time that a specific
response to brain tumor antigens has been demonstrated as the result of an
immunotherapy strategy," he said. "These antigens give us
specific targets to aim for and they give us potent tools with which to
measure immune responses. Therefore, we have a better way of monitoring
the progress of patients who undergo vaccination and we have a means of
improving these therapies."
In recent years, scientists have identified
several tumor-specific antigens that appear to play a role in the
development of certain cancer cells. The body's natural defensive cells, T
lymphocytes, have the capacity to attack "foreign" proteins, but
cancer cells and the antigens they express typically evade recognition by
the immune system. Therefore, cancer researchers search for new antigens
that may serve as targets, devise new methods to make the targets
"visible" and vulnerable to immune cells, and seek new ways to
multiply the number of cancer-killing cells responding to the threat.
"These three antigens HER2, gp100,
and MAGE-1 have been described since the 1980s but we have only
recently found them to be expressed in glioblastoma cells," said Dr.
Black.
HER-2 is expressed in a variety of normal
tissues, but it is selectively overexpressed in a number of malignancies,
including breast and ovarian tumors. Glycoprotein 100 (gp100) is an
antigen linked to melanoma. MAGE-1, initially analyzed from melanomas and
found to be expressed in a variety of tumor types, became the first
identified tumor antigen recognized by the immune system's protective T
cells.
In earlier studies at other centers, a
cancer vaccine combining MAGE-1 cells with specially cultured immune
system cells was able to produce a tumor-specific immune response among
patients with melanoma. Clinical trials using gp100 as a target in
melanoma and HER-2 as a target in several types of cancers also
demonstrated that the antigens elicit a strong immune response that
continues even after the vaccinations have ended.
Since then, researchers have worked to
develop a number of therapies that may be used individually or in
combination to target malignant brain tumors. Dendritic cell immunotherapy
is intended to stimulate a patient's immune system to recognize and attack
glioblastoma cells. Tumor cells that have been removed during surgery are
cultured in the laboratory with dendritic cells, also called
"antigen-presenting" cells, taken from the patient's blood. The
resulting cells are injected back into the patient, where they are
designed to identify brain tumor cells as invaders and stimulate a strong
response from tumor-infiltrating T lymphocytes.
In an earlier Phase I trial, tumor cells
were grown in culture, and proteins from the cell surfaces were used in
preparing the vaccine. In the Phase I trial described in the Cancer
Research article, this process was refined.
"Now we take the proteins directly from
the surgical specimen, which ensures that we are getting the relevant
proteins and not antigens or proteins that are artifacts of the culturing
process. This also avoids the technical problems of trying to grow out
tumor cells that have been irradiated and undergone chemotherapy,"
Dr. Yu said. "In addition, instead of just drawing blood to obtain a
patient's dendritic cells, we're using a process that allows us to get
25-fold more dendritic cells. This may account for the dramatic
prolongation of survival that we see compared to our control
patients."
Dr. Black said a larger Phase II trial of
the dendritic cell vaccine is now being completed and the researchers are
preparing to apply for a randomized Phase III trial.
In the lab studies described in Cancer
Research, seven established GBM tumor cell lines and cells from 43 GBM
tumors removed from patients at Cedars-Sinai were analyzed and compared
with normal brain tissue. MAGE-1 was not detected in normal tissue.
Although HER-2 and gp100 were detected in normal tissue, this does not
preclude their potential usefulness. In previous studies with different
tumor types, HER-2 and gp100 were overexpressed in cancer cells, while in
normal cells they were expressed at levels below the "threshold"
for activation by the immune system.
Furthermore, because healthy neural cells
are of a histocompatibility type that does not interact with cytotoxic T
cells, the immune system will not launch an attack on normal tissue
expressing the antigens. In contrast, however, the surfaces of GBM tumor
cells were found to express Major Histocompatibility Complex (MHC) Class I
molecules, the type that makes them vulnerable to interaction with
cytotoxic T lymphocytes.
The researchers documented that HER-2, gp100
and MAGE-1 are frequently expressed in glioblastoma cells. They generated
cytotoxic T lymphocyte clones specific to each antigen and cultured them
with GBM cells. The brain tumor cells were able to naturally process the
antigens, and the lymphocytes were able to process the antigen-derived
peptides or proteins on the surfaces of the GBM cells.
[Top]
Early
Chemo Promising Vs. Brain Cancer-(ET-07/06/2004)
Early low-dose chemotherapy
appears to substantially improve short-term survival in patients with
the most aggressive and common form of brain cancer, offering the first
significant advance against the disease in decades. Whether the treatment
can help cure brain cancer remains to be seen, but the approach at least
seems to slow the often rapid progression of the disease for some. The
treatment, tested in a form of brain cancer called glioblastoma multiforme,
involves the drug Temodar. Until now, the medicine has typically been
used only after radiation to shrink the tumor. A major international study
shows that giving low doses of the capsule at the very start - for six
or seven weeks during and after radiation - doubles the chance of being
alive two years later. "This is the first trial that has been clearly
positive in brain cancer in 30 years," said Dr. M.J. van den Bent of the
Daniel den Hoed Oncology Center in Rotterdam, the Netherlands. "This is
a great day."
Radiation and surgery
are the first-line treatments for glioblastomas, but even with them the
disease usually kills within a year or less. Intravenous chemotherapy
available since the 1970s improves these odds only marginally and can
have serious side effects. Several doctors predicted that upfront Temodar
will quickly become the new standard of care, routinely offered to all
victims of this disease. "To be able to tell people they may have two
or three years of survival rather than nine months is pretty major," said
Dr. Adam Mamelak of City of Hope National Medical Center in Duarte, Calif.,
who was not involved in the study. The study was conducted and financed
by the European Organization for Research and Treatment of Cancer and
released in New Orleans at a meeting of the American Society of Clinical
Oncology. It was done at more than 80 hospitals in Europe, Canada and
Australia.
The study's director,
Dr. Roger Stupp of University Hospital in Lausanne, Switzerland, said
patients found the drug easy to take, and fatigue was the most common
ill effect. "We have started with the most malignant and devastating form"
of brain cancer, he said. The next step will be to try the drug against
less aggressive tumors and combine it with the newer, so-called targeted
drugs designed to block cancer's internal growth signals. Unlike most
cancer, which kills by spreading through the body, glioblastomas grow
quickly inside the head, destroying everything in their path. They are
the most aggressive of the 100 or so forms of cancer that originate in
the brain, and they account for half or more of all cases. Around the
world, 175,000 cases are diagnosed annually, killing 125,000.
In the new study,
573 patients were randomly given standard treatment with or without early
Temodar. After two years, 26 percent receiving Temodar were still alive,
compared with just 10 percent getting the usual care. Even with the treatment,
most patients died quickly. Nevertheless, doctors said doubling short-term
survival is an important milestone in such a grim disease. "Twenty-six
percent survival is not that great in the large scheme of things. But
it is still progress," said Dr. Frank Haluska of Massachusetts General
Hospital.
[Top]
Ecopia
Presents Preclinical Data to the AACR - on its Anticancer Agent- (BUSINESS
WIRE-29/03/2004)
Ecopia
BioSciences Inc. presented preclinical data to the 95th annual meeting
of the American Association for Cancer Research (AACR) in Orlando, Florida.
The data presented in a poster session unveiled the chemical structure
of ECO-04601 as well as data that further supports previously reported
results showing tumour growth inhibition in a mouse model of glioma. In
addition, the data revealed that the compound is well-tolerated following
oral and parenteral administration, even in chronic treatment regimens.
Ecopia's President and Chief Executive Officer, Dr. Pierre Falardeau,
stated: "The results presented at this meeting strengthen our decision
to continue preclinical development of this compound. Developing ECO-04601
as an anticancer agent for the treatment of glioblastomas represents an
exciting opportunity to reach the market rapidly and address an unmet
medical need."
ECO-04601
is a structurally novel compound discovered using Ecopia's DECIPHER(R)
technology. It has shown anti-proliferative activity against several human
cancer cell lines including leukemia and melanoma cells as well as cancer
cell lines derived from lung, colon, brain, ovary, kidney, prostate and
breast tissues. Ecopia has built a pipeline of new anticancer, antibacterial
and antifungal agents using its proprietary DECIPHER(R) technology. The
Company's pipeline includes two anticancer agents, ECO-04601 and ECO-02201,
an antibacterial agent, ECO-00501, and two antifungal agents, ECO-02301
and ECO-14401.
[Top]
Brain
Scans Used to Monitor Effect of Cancer Drug- (Reuters-17/02/2004)
British scientists
said they have used a brain-imaging technique to monitor the effectiveness
of a drug on tumors. Instead of studying the size of the brain tumor over
time, the researchers used nuclear magnetic resonance imaging to monitor
molecular changes in cancer cells to predict at an early stage whether
the drug was working. "The technique has been around for a while but it
has not been used in this context for looking at the metabolism in cancer
cells," Professor Martin Leach, of the charity Cancer Research UK, said
in an interview. "The conventional scan is an image and you can see the
extent of a tumor. What this (new application) does is look at the cells
and asks how they are working. It gives information on chemicals in the
cells rather than just the distribution of tissue," he added
The scientists identified
changes caused by the chemotherapy drug temozolomide on patients with
low-grade glioma brain tumors-one of the most difficult types of cancer
to treat. A low-grade glioma tends to be slow-growing but it can quickly
change into a much more aggressive and deadly tumor. In research reported
in The British Journal of Cancer, they measured levels of a molecule called
choline, which indicates that cells are dividing and that the tumor is
growing. They also measured the size of the tumor with magnetic resonance
imaging scans in 13 patients. The amount of choline gave an early indication
whether the drug was halting cell division and the growth of the tumor.
Leach said the results show that using nuclear magnetic resonance could
give doctors an early indication of whether temozolomide is working or
if a patient could benefit more by switching to another drug.
Gliomas, one of the
most common types of brain tumors, can cause headaches, seizures, behavior
changes and dizziness. Treatments include surgery and chemotherapy depending
on the size and the location of the tumor. Leach and his colleagues believe
studying the behavior of cancer cells with nuclear magnetic resonance
could be useful for doctors in identifying different types of gliomas
and how various drugs affect them. "They could then predict which tumor
types are likely to respond to treatments before giving them to patients,"
Leach added
[Top]
Breast
Implants Do Not Raise Risk of Brain Cancer-(Reuters Health-26/01/2004)
Contrary to study
results published in 2001, women who get breast implants do not appear
to be at increased risk of brain cancer, according to new research. In
the latest study, U.S. investigators reviewed information on more than
10,000 women who received breast implants and were followed for up to
29 years. A total of 12 women developed brain cancer - a rate similar
to that seen in the general population, the researchers found. "There
is no increase in brain cancer in women with breast implants," study author
Dr. Loren Lipworth told Reuters Health.
In recent years,
researchers have conducted numerous studies to investigate whether breast
implants increase the risk of any type of cancer, Lipworth and her colleague
write in the Annals of Plastic Surgery. Although the great majority of
reports showed no relationship between the cosmetic surgery and cancer,
one 2001 study found that women with breast implants were more than twice
as likely to die from brain cancer. The findings were based on a review
of the medical records and death certificates of 13,488 women who had
received breast implants between 1960 and 1988. Half of the participants
received silicone-gel implants, roughly one third of the women had double-lumen
implants and 12 percent had saline-filled implants.
To explain the discrepancy
between the results from the previous and the latest reports, Lipworth
pointed out that brain cancer is often a result of cancer that originated
in other parts of the body and spread to the brain. So while a patient
may die from brain cancer, their disease may have begun in the lungs,
explained Lipworth, who is based at the International Epidemiology Institute
in Maryland and Vanderbilt University in Tennessee. In contrast, studies
that follow people over time and record new cases of cancer note where
the disease began, Lipworth said. Consequently, for participants in those
studies who received breast implants and developed brain cancer, "this
is their first cancer," she noted. Indeed, according to a review of four
studies conducted in Scandinavia and the U.S. that followed women with
breast implants over time, opting for the cosmetic surgery caused no increase
in a woman's risk of brain cancer. "Our results rule out any two-fold
excess of brain cancer in any woman with breast implants," Lipworth said
in an interview. She added that none of the studies included women who
received breast implants following a mastectomy for breast cancer.
[Top]
Trial
Drugs Offer Hope for Brain Cancer-(HealthDayNews-20/11/2003)
By targeting specific
small proteins in cancerous brain tumors, researchers hope to develop
potent new treatments. Initial results of these experimental drugs in
mice and human cancer cells appear dramatically successful, according
to a presentation made Nov. 19 at the Molecular Targets and Cancer Therapeutics
meeting in Boston. "We have targeted ways cancer cells stimulate tumor
growth, promote their survival and create new blood vessels," says lead
researcher Dr. Jeremy Rich, an assistant professor of medicine in the
Brain Tumor Center at Duke University.
In his presentation,
Rich discussed three approaches to treatments. "One is a drug called ZD6474,
which is directed at vascular endothelial growth factor (VEGF), which
promotes blood vessel growth," Rich says. However, this drug also blocks
epidermal growth factor (EGF), which is involved in new blood vessel growth,
he adds. What is unusual about this drug is that it blocks both VEGF and
EGF, whereas most drugs block only one or the other, Rich notes. "In clinical
trials, neither single blocker has worked great," he says. "But the combination
has worked fantastically well," Rich notes. "This combination has worked
against gliomas, the most common type of brain tumor, but also other types
of tumors. . . That's a pretty exciting finding."
SB431542, another
new compound, was tested in human malignant glioma cell lines. The drug
successfully blocked the receptor protein called transforming growth factor-beta
(TGF-beta). Blocking the activity of the TGF-beta receptor also blocked
the protein PAI-1. This protein, which normally communicates with TGF-beta
in cancer cells, is a predictor of poor prognosis in patients. Another
drug combination, AEE788 and RAD001, blocked the growth of glioblastomas.
AEE788 targets epidermal growth factor receptor (EGFR) and also VEGF.
RAD001 targets mTOR. This protein is needed to regulate cell metabolism.
Without it, cells cannot grow properly. Combining these drugs blocked
tumor growth more effectively than either drug alone."These
developments will enable us to develop a cocktail approach to treating
each patient," Rich says. "We can tailor for each patient the particular
needs the patient has, based on the type of tumor."Rich
sees future treatment of brain cancers, and other cancers, as using a
combination of these drugs, customized for each patient, plus chemotherapy
and radiation. Rich believes that eventually drug therapy alone may prove
effective, eliminating the serious side effects associated with chemotherapy
and radiation. "There is really hope for the future, because treatments
are changing rapidly. There are a lot of new treatments that are showing
promise and that we hope will lessen side effects and increase our ability
to control cancers," Rich says.
Dr. Mitchel Berger,
a professor of neurosurgery and chairman of the Department Neurological
Surgery at the University of California at San Francisco, comments, "At
the UCSF Brain Tumor Research Center, we are conducting very similar trials
with similar small molecule inhibitors that do basically the same thing,
that is block EGFR, VEGF, mTOR, etc." "We are all optimistic, but must
remain cautious, since it is a long reach from animal models to humans.
Notwithstanding, many of us committed to brain tumor research and new
treatment therapies believe that we are making significant progress with
these small molecule inhibitors," he adds.
[Top]
Folic
Acid May Help Prevent One Type of Childhood Cancer-(ET-11/11/2003)
The number of children
who developed neuroblastoma dropped 60% in Canada after that country started
adding the B vitamin folic acid to foods, according to researchers from
Toronto's Hospital for Sick Children and the University of Toronto. Their
study was published in the journal Clinical Pharmacology and Therapeutics
(Vol. 74, No. 3: 288-294). The finding could have important implications
for preventing this deadly form of cancer, said study co-author Gideon
Koren, MD, of the University of Toronto. "It may be the first example
of a pediatric cancer being prevented through nutrition, and that's very
exciting," said Koren, who is also the director of the Motherisk Program
at the Hospital for Sick Children. Other
experts are more cautious about the finding. "I think there need to be
a few more studies to really have confidence in that," said Vicky Stevens,
PhD, a research scientist with the American Cancer Society. However, the
evidence does favor a protective role for folic acid, she added.
Neuroblastoma is
the most common cancer in infants, and the most common cause of cancer-related
death in children between the ages of one and four. Very little is known
about what causes this disease. Many researchers believe it begins to
develop before a baby is even born, because the cancer forms when certain
nerve cells do not mature beyond the fetal stage. This may be why folic
acid appears to protect against neuroblastoma, Koren said. Folic acid
is already known to protect against serious birth defects that develop
in the earliest weeks of pregnancy, like spina bifida, in which parts
of the brain or spinal cord don't develop properly. For this reason, doctors
recommend that women who are pregnant or trying to get pregnant take a
vitamin supplement that includes folic acid. Folic acid is also found
in many foods, including leafy vegetables, beans, grains and meat. But
because most people don't get enough folic acid from their diets, the
United States and Canada add this nutrient to flour, breads and other
grains. This fortification has led to a significant drop in the number
of brain and spinal birth defects in North America.
Koren and his colleagues
determined that fortification also paralleled a drop in cases of neuroblastoma.
The researchers compared the number of neuroblastoma cases in Ontario
before Canadian food was fortified (1985-1997) and after (1998-2000).
The number of neuroblastomas dropped from 1.57 cases per 10,000 births,
to 0.62 cases per 10,000 births - a decline of 60%. Folic acid fortification
is the most likely reason for this drop, Koren said, because it's probably
the only change that was consistent across the entire population. The
rates of women taking folic acid supplements during pregnancy did not
change substantially during the periods studied. Stevens said the effect
of folic acid on neuroblastoma may become more apparent as more countries
start fortifying foods the way Canada and the US do. If neuroblastoma
rates drop in those countries, as well, it will add weight to the argument
that folic acid prevents this disease.
This isn't the first
study to examine the role of folic acid in cancer prevention. Some research
has suggested folic acid may protect against colon cancer, breast cancer,
and a form of childhood leukemia called acute lymphoblastic leukemia (ALL).
Last year, researchers from the University of North Carolina, Chapel Hill,
found that women who took multivitamins during pregnancy were less likely
to have a child with neuroblastoma. Although they couldn't determine which
nutrient was responsible for this effect, folic acid was considered a
likely candidate. Koren said more research needs to be done to determine
whether adding higher levels of folic acid to food would cut the rate
of neuroblastoma even more. Researchers should also study whether folic
acid can be used to treat existing neuroblastomas, he said.
[Top]
Mutated
Virus Obliterates Brain Cancer in Mice-(Reuters Health-06/05/2003)
By tweaking the structure
of a common virus, researchers have created a stealth weapon that can
destroy brain cancer in mice, a study shows. Engineered to latch onto
cancer cells while leaving normal ones alone, the new virus can spread
throughout a tumor and completely destroy the malignancy, according to
the study published in the Journal of the National Cancer Institute. Researchers
designed a mutated form of an adenovirus, called Delta-24-RGD, to attack
a particularly dangerous type of brain cancer known as glioblastoma. "Glioblastoma
is one of the worst cancers," Dr. Frederick F. Lang, an associate professor
in the department of neurosurgery at the University of Texas M.D. Anderson
Cancer Center, said in an interview. "Typically patients die within a
year. And despite all our advances, survival with this cancer is the same
as it was 30 years ago."
Lang and his colleagues
first tweaked the virus to target only cancer cells. In normal cells,
a substance called Rb protein can prevent viruses from taking over the
cell's machinery to reproduce, Lang explained. But adenoviruses get around
the problem with their own countermeasure -- a protein called E1A that
latches onto Rb and disables it. As it turns out, cancer cells don't have
functioning copies of Rb protein. And, by engineering an adenovirus that
had a non-functional version of E1A, the researches were able to create
a germ that could replicate in cancer cells but not normal ones. This
virus was named Delta-24. There was still one more problem -- Delta-24
didn't lock on to cancer cells all that well. Normally, to infect a cell,
an adenovirus latches on to a receptor, called a coxsackie adenovirus
receptor (CAR) on the cell's surface. But cancer cells don't have many
CARs, making it difficult for Delta-24 to latch onto a tumor. Lang and
his colleagues got around this issue by altering Delta-24 so that it could
latch onto other proteins -- called integrins -- that are abundantly scattered
across a cancer cell's surface.
The researchers next
used the new version of the virus -- Delta-24-RGD -- to treat mice that
had had been injected with human tumor cells. The modified virus was injected
directly into the tumors in the brains of the mice. A comparison group
of mice that received no treatment lived an average of only 19 days. Another
group that was treated with Delta-24 died within about 50 days. But the
ones that were treated with Delta-24-RGD survived an average of 131 days.
The success with the animal model is a good sign, according to the study's
lead author, Dr. Juan Fueyo, an assistant professor in the department
of neuro-oncology at M.D. Anderson. "We believe this therapy has a lot
of potential, but one that needs much more study," said Fueyo in a prepared
statement. "We've never seen this kind of response before with any other
treatment tested in animals or humans."
[Top]
Brain
Cancer Treatment Can Impair Mental Function-(Reuters Health-01/11/2002)
Treatments for a
certain type of brain tumor may have detrimental effects on patients'
long-term mental functioning, new study findings suggest. The researchers
discovered that patients who received antiepileptic drugs and high doses
of radiation therapy to treat their low-grade, or relatively less serious,
brain tumors appeared to have more trouble with memory and attention than
cancer patients who didn't receive those treatments. Patients who had
previously been diagnosed with brain tumors also showed greater mental
impairments than patients with non-brain tumors.
The current study
indicates that the majority of mental decline stems from the tumor, and
not the treatment, according to Dr. Martin Klein of Vrije Universiteit
Medical Center in Amsterdam, the Netherlands, and his colleagues. However,
Klein's team notes, patients diagnosed and treated for low-grade brain
tumors called gliomas have a strong chance of surviving many years, and
the long-term effects of the treatments they are given should be investigated.
"Our findings suggest that the tumor itself has the most deleterious effect
on cognitive function and that radiotherapy mainly results in additional
long-term cognitive disability when high fraction doses are used," Klein
and colleagues write in the The Lancet. "Additionally, the effects of
other medical factors, especially antiepileptic drug use, on cognitive
function in glioma patients deserve attention."
The investigators
obtained their findings from tests of mental functioning in 195 patients
with a low-grade glioma, of whom more than half had been given radiotherapy
up to 22 years earlier. To compare their results to others, the research
team also tested 100 patients diagnosed with low-grade blood cancers,
and 195 people who had no history of cancer. All glioma patients--whether
they had received radiation or not--performed worse on the tests than
other cancer patients, and the discrepancy increased when glioma patients
were compared with those who had never had cancer.
However, glioma patients
who had never received radiation therapy outperformed those who had, the
report indicates--especially those patients who were given relatively
high doses. Patients who received antiepileptic drugs to control their
seizures also fared less well in the mental functioning tests than those
who did not receive the drugs. Based on these findings, the authors recommend
that doctors avoid giving radiotherapy to younger patients in the early
stages of glioma, since, at this point, the benefits of the treatment
remain unclear. And if radiotherapy is needed, Klein and his team suggest
that doctors stick with a relatively low dose.
[Top]
New
study shows A-Bomb survivors at increased risk of nervous system tumors
(ET-15/10/2002)
Survivors of the
atomic bomb attacks on Hiroshima and Nagasaki have a 40 percent increased
risk of developing a rare brain tumor and a slightly raised lifetime risk
of other types of nervous system tumors, new research shows. In a study
appearing in the Journal of the National Cancer Institute, researchers
checked the medical histories of 80,160 Japanese survivors of the attacks.
The researchers found the survivors had a 6 percent greater chance than
other people of developing tumors of the brain or spinal cord over a lifetime.
For schwannomas,
a rare type of nonmalignant, but dangerous tumor, the risk soared to 40
percent, said Dr. Dale Preston, first author of the study. Of survivors
checked, Preston said they found 55 cases of schwannomas. He said this
is about 20 more cases than would be expected to occur among a typical
population not linked to radiation exposures. Preston noted that even
with the increased occurrence of the tumors, schwannomas are still rare
among the survivors.
Preston is a researcher
with the Radiation Effects Research Foundation in Hiroshima, a joint U.S.-Japanese
agency that studies the health effects of the nuclear attacks on the Japanese
survivors. The U.S. military dropped atomic bombs on Hiroshima and Nagasaki
in August, 1945. The attack was swiftly followed by the unconditional
surrender of Japan and the end of World War II.
Schwannomas are tumors
of the nerve covering and usually occur along nerves of the spine and
along the auditory nerve in the brain. "These are dangerous because of
their location," said Preston. Preston said the conclusion does not suggest
that current allowed exposures in routine medical procedures, such as
X-ray, pose a significantly increased risk of cancer because the atomic
bomb survivors were exposed to higher doses.
[Top]
Smelly
Plant Could Offer Brain Cancer Treatment-(Reuters Health-01/10/2002)
A protein from a
highly poisonous, foul-smelling plant known as jimson weed could one day
be used to help fight a type of brain cancer called glioma, Japanese researchers
reported. The protein, Datura stramonium agglutinin, or DSA, caused glioma
cells with cancerous characteristics to begin developing normally, or
differentiating, in lab studies, they report in the British Journal of
Cancer. The differentiation DSA induced was irreversible, being sustained
once the protein was removed, the researchers report. "DSA controls glioma
cells as a result of glial differentiation rather than actually killing
cells," said lead researcher Dr. Tasuku Sasaki, from the Tokyo Metropolitan
Institute of Gerontology. "Any drug based on this concept would help patients
suffering with tumors that are difficult to remove such as gliomas."
Glioma cells were
also inhibited from growing and dividing out of control, or proliferating,
by the presence of DSA, Sasaki's team reports. "Taken together, these
observations suggest that Datura stramonium agglutinin may be useful as
a new therapy for treating glioma without side effects," they write.
Professor John Double,
head of the Cancer Research UK Unit at Bradford University, said the discovery
was exciting, but extremely preliminary. "More needs to be done before
we have enough evidence to commit to trials. Potential treatment, based
on DSA, for this form of brain cancer is still a long way off."
Cancer Research UK's
chief executive, Sir Paul Nurse, agreed, noting "there is much work to
be done on the journey from the laboratory bench to the patient's bedside."
[Top]
Study
Links Measles, Flu to Childhood Cancer Risk (Reuters-17/09/2002)
British scientists
suspect there could be a link between childhood brain cancer and exposure
to the measles or influenza virus around the time of birth. In the first
study suggesting that particular infections could be associated with brain
cancer, Cancer Research UK found children had twice the normal risk of
developing the disease if they had been born when measles was common in
their area. Early exposure to the influenza virus more than tripled the
normal risk of brain cancer, according to the British research charity.
"There's increasing
interest in the possibility that exposure to infections very early on
in life might contribute to the incidence of children's brain cancer and
our study is certainly consistent with that possibility," said Professor
Louise Parker, the lead researcher from the University of Newcastle.
The scientists stressed
that the findings are preliminary but they support the theory that cancer
is caused by a complex mix of factors including genetics and environment.
Viruses are also known to play a part in some cancers. "It is difficult
to produce strong evidence on the causes of childhood brain cancer because
the disease is rare and even when you look at large numbers of children,
in our case 100,000, the number of cancers will be quite small," Parker
said. "But our results do suggest that measles and flu could be associated
with increased risk of the disease, and therefore that avoiding these
infections might be one way of reducing cancer rates," she added in a
statement.
Childhood cancers
are comparatively rare and affect about one in 600 children before the
age of 15. Leukemia makes up about one third of the cancer cases and brain
tumors account for about a quarter. In Britain, brain tumors affect an
estimated 290 children each year and cause about 100 deaths. Treatment
usually involves surgery followed by radiotherapy.
Parker and her colleagues
examined all birth records in the county of Cumbria, in northern England,
from 1975 to 1992. Their research is published in the British Journal
of Cancer. The scientists assessed the levels of infections around the
time of the birth of the children who developed brain cancer. They estimated
exposure levels before birth, in the three months around and after birth
and in the following three months. "This is the first study to pinpoint
measles and influenza as being possible culprits," Sara Hiom, a scientific
adviser at Cancer Research UK, said in an interview.
Exposure to other
kinds of infection, apart from measles and flu, did not seem to have any
effect on brain cancer rates. Although the number of brain cancers found
in the study were small, Hiom said the scientists felt there was enough
evidence and clustering to show they were not just chance. "It is yet
another piece to the puzzle," Hiom added. Further studies will be needed
to confirm the findings but scientists believe that recognizing the link
between viruses and cancers could pave the way to prevention through the
use of vaccines.
[Top]
Plant
Compound Seen as Possible Brain Tumor Therapy (Reuters Health-29/08/2002)
Blocking a molecular
pathway that goes awry in the most common form of childhood brain cancer
may hold promise as a therapy for the disease, new research suggests.
The approach, aimed at tumors called medullablastomas, has not been tested
in children yet. But the new study shows that a plant-derived compound
that interferes with abnormal growth signals can slow tumor growth in
mice and kill medulloblastoma cells taken from human patients.
Depending on the
stage of the cancer at diagnosis, 50% to 70% of children survive medulloblastoma,
according to the study's lead author, Dr. Philip A. Beachy of Johns Hopkins
University and the Howard Hughes Medical Institute in Baltimore, Maryland.
But the radiation used to destroy cancer cells that might linger afterward
"can cause fairly significant brain damage," he told Reuters Health in
an interview. "An agent that would specifically target the tumor would
be great to have," he said.
In previous research,
Beachy and his colleagues discovered that the molecular pathway involving
a protein called Hedgehog behaves abnormally in children with medulloblastoma.
As an embryo forms, the Hedgehog pathway is activated to send signals
that guide the appropriate development of other cells. But if the pathway
is activated inappropriately later in life, certain cancers may develop,
Beachy explained. Both medulloblastoma and basal cell carcinoma, a common
form of skin cancer, have been linked to abnormal activation of the Hedgehog
pathway, according to the Johns Hopkins researcher.
In the mid-1990s,
Beachy and his colleagues found that cyclopamine, a chemical derived from
corn lilies that grow in mountain meadows in the western US, blocks the
Hedgehog pathway. So they decided to test it as a treatment for medulloblastoma.
In experiments with a mouse model of medulloblastoma, cyclopamine reduced
the growth of cancer cells in the laboratory and shrank tumors implanted
in mice. What's more, treatment with the plant chemical killed up to 99.9%
of cancer cells in medulloblastoma tumors that had been surgically removed
from human patients.
A report on the findings
is published in the August 30th issue of Science. The study "shows the
potential for cyclopamine and other drugs that could block the pathway,"
according to Beachy. The chemical did not cause any side effects in the
mice, but it has never been tested in humans, he said. Still, Beachy said
that there is enough evidence of the beneficial effects of cyclopamine
to justify developing the chemical so that its safety and effectiveness
can be tested in human trials. It is still uncertain, though, he noted,
how much of the chemical can be collected by harvesting corn lilies. Due
to the complexity of the chemical, it would be very difficult to make
synthetically, according to Beachy.
[Top]
Allergies
May Protect Against Brain Cancer: Study -(Reuters Health-13/05/2002)
Allergies and autoimmune
conditions such as lupus and multiple sclerosis may reduce the risk of
a particular type of brain tumor, according to the results of a new study.
Researchers are not sure why allergies and autoimmune diseases may protect
against brain tumors, but the results suggest that immunological factors
may be involved, since both allergies and autoimmune diseases occur when
immune system function goes awry. In most cases, the cause of brain cancer
is a mystery. A few hereditary syndromes increase the risk, but they only
account for about 5% of all brain tumors. The only proven environmental
risk factor is exposure to ionizing radiation.
Recently, several
studies have raised the possibility that people with overstimulated immune
systems may have a reduced risk of brain cancer. Both allergies and autoimmune
diseases result from inappropriate immune reactions. In the case of allergies,
the immune system responds to harmless outside substances, while in autoimmune
diseases, it launches an attack against the body's own tissue. To see
whether autoimmune disease and allergies offer any protection against
brain cancer, a team led by Dr. Alina V. Brenner of the National Cancer
Institute in Bethesda, Maryland, compared 782 people hospitalized with
a brain tumor with a "control" group of 799 patients hospitalized for
other causes. Having allergies or an autoimmune illness reduced the risk
of some, but not all, brain tumors, Brenner and her colleagues report
in the International Journal of Cancer.
The risk of a type
of brain tumor called glioma was reduced 33% in people with a history
of allergies and 51% in those with an autoimmune disease. The risk was
lowest in people who had both allergies and autoimmune disease. The risk
of another type of brain cancer, meningioma, was lower in people with
an autoimmune disease, but not in those with allergies, the report indicates.
The finding of a reduced risk of glioma in people with a history of allergies
or autoimmune diseases is in agreement with several previous studies,
according to Brenner. "Given that so little is known about factors that
influence the risk of glioma, this finding is particularly exciting,"
she told Reuters Health. She cautioned, however, "At this point, it is
premature to draw definite conclusions about the underlying basis of the
association." There are several possible explanations for the apparent
reduction in risk, according to Brenner. Immune factors that are involved
in or predispose people to autoimmunity or allergies might play a role,
she said. It is also possible that medications used to treat these conditions
could offer some protection. Other factors including some that are not
involved with the immune system may also affect the risk, she noted. "Clearly,
this is a promising area of research that warrants further investigation,"
Brenner said.
[Top]
Doctor:
Cell Phones May Cause Cancer-(Yahoo News-20/03/2002)
A prominent researcher,
once employed by the cell phone industry, has launched a new effort to
track the potential dangers of cell phone use, 10News reported. Epidemiologist
Dr. George Carlo ran a seven-year study of the phones' safety, and claims
radiation from the phone can penetrate four inches inside a person's head.
"Medical science now shows us that cell phone users are at an increased
risk of tumors -- an increased risk of cancer; brain cancer and eye cancer,
that we know of so far," Carlo said.
Gibb Brower has undergone
surgery three times over the last two years to remove a fatal brain tumor,
which he said came from talking on a cell phone 1,200 minutes a month.
"This is pretty much a fatal outlook that the doctors gave me. They told
me I was going to live maybe 10 months or a year," Bower said. "(The tumor)
happens to be where I held my cell phone. If there is any possibility
that you can get cancer from these things, do anything you can to keep
them away from your body, away from your head," he added. Brower has filed
a lawsuit against the wireless industry, and said more studies are crucial,
especially given that within three years, the number of cell phone users
is expected to grow to more than 1 billion people worldwide, according
to 10News. Bower said he no longer uses a cell phone, but 110 million
Americans rely on the wireless devices, 10News reported.
To track health risks,
Carlo has launched a Web site, which provides information about cell phones
and registers people with symptoms. "Consumers have the right to know
what the problems are and what the solutions are," Carlo said. Carlo said
the registry is the first step toward independent studies. Most research
to date, showing low risks, has been funded by the wireless industry.
Carlo said that if you have any concerns at all about health risks associated
with your cell phone, you should use a hands-free headset, and keep the
phone as far away from your body possible. He said the headset eliminates
radiation penetration. Children are perhaps at the greatest risk, because
radiation penetrates their bodies more easily.
Cellular trade groups
counter his findings, stating that there is no proof that cell phones
pose a health risk.
[Top]
Infections
May Cause Childhood Brain Cancers-Study (Reuters-02/04/2002)
British scientists
have found what they believe is further evidence that viral or bacterial
infections cause childhood brain tumors. In research reported in the British
Journal of Cancer, Professor Jillian Birch and colleagues at the University
of Manchester said they discovered that childhood brain tumors occur in
clusters over short periods of time, suggesting they may be influenced
by infections.
"Our results indicate
that environmental factors are involved in causing brain tumors in children
and the most likely explanation for the pattern we have seen is that one
or more types of infections are responsible," Birch said.
A so-called double
whammy, combining biological and genetic causes, is thought necessary
for some cancers to develop. Birch and his team analyzed brain cancer
in children from northwest England between 1954 and 1998, finding those
born in the autumn and winter had a higher risk of developing two types
of brain tumors, called astrocytoma and ependymoma. They also discovered
that in certain years children living near each other were more likely
to be diagnosed with a brain tumor, a pattern scientists call space-time
clustering. Diseases linked to more constant environmental causes usually
produce clusters over longer periods of time than those linked to space-time
clustering.
"The fact that the
space-time clusters and the seasonal pattern in births are restricted
to particular types of childhood brain tumors adds weight to our findings
and will allow us to focus our future research on these cases," Birch
added in a statement.
Sir Paul Nurse, a
director general of the charity Cancer Research UK, which funded the study,
said the results back the theory that infections play a role in a number
of cancers. "These initial findings aren't conclusive and we need more
evidence to support them, but if an infection is playing a role, this
might lead to new ideas for preventing and treating this important disease."
Childhood cancers
are rare and survival rates have improved. About 1,500 children in Britain
and 8,400 in the United States develop cancer each year. Leukemia is the
most common type of childhood cancer, followed by brain and spinal tumors.
[Top]
Chemo
Slightly Extends Brain Cancer Survival (Reuters Health-22/03/2002)
Adding chemotherapy
to the treatment of some patients with aggressive brain tumors may make
a modest difference in their survival, UK researchers report. In a review
of 12 studies, the investigators found that overall, adding chemotherapy
to radiation treatment prolonged survival slightly among adults with high-grade
glioma. Glioma refers to cancers that arise from support cells in the
brain, and high-grade gliomas contain highly abnormal cells that grow
quickly. Just 5% to 10% of patients with high-grade gliomas survive for
2 years.
Whether adding chemotherapy
to the standard treatment of surgery and radiation makes a dent in this
dismal rate has been unclear. Individual studies have yielded conflicting
results, according to the authors of the report. But in their analysis
of a dozen of these studies, radiation plus chemotherapy was associated
with an overall 15% decrease in death risk compared with radiation alone.
While 40% of radiation-only patients lived one year, 46% of chemotherapy
patients did. Overall, chemotherapy patients lived about 2 months longer
than patients given radiation alone, the researchers note.
Dr. Lesley A. Stewart
and colleagues at the Medical Research Council Clinical Trials Unit in
London report the findings in The Lancet. "This small but clear improvement
in survival from chemotherapy encourages further study of drug treatment
of these tumours," the researchers write.
But for now, they
stress, the benefit of chemotherapy for any one patient must be weighed
against downsides including the toxic effects of the drug treatment and
the impact on their quality of life. "In decisions about treatment," they
write, "the interpretation of such information is likely to be affected
by many personal beliefs and preferences."
[Top]
Researcher:
Report of Prozac Link to Cancer is Wrong (HealthScoutNews-26/03/2002)
An American scientist
involved in an international research project expressed outrage today
at London media reports that said his study potentially linked common
antidepressants to brain cancer. Randy Blakely, director of the Center
for Molecular Neuroscience at Vanderbilt University in Nashville, Tenn.,
told HealthScout News, "There is no link to cancer for these medications."
"As one of the scientists
associated with the study, let me just make an emphatic statement that
the study has no bearing, as far as we know, on brain cancer, nor does
it have any bearing at all on the safety of SSRI medications, which are
in fact extremely valuable to people suffering from depression," Blakely
said.
At issue were the
antidepressants known as selective serotonin reuptake inhibitors (SSRIs),
which include well-known drugs like Prozac, Paxil and Celexa, and a study
published in the online edition of Blood, the journal of the American
Society of Hematology.
The controversy arose
earlier today, after at least one London newspaper, The Independent, misinterpreted
the research results in its report on the findings. The story claimed
the study potentially linked drugs like Prozac to brain cancer. However,
the actual research, which Blakely conducted in concert with a group of
respected British scientists, including Prof. John Gordon of the University
of Birmingham, made no such connections. Instead, it involved laboratory
experiments on a line of cells contained in a disease known as Burkitt's
lymphoma, an extremely rare type of cancer.
The study, said Blakely,
found that "a special class of lymphoid cells in culture respond to serotonin
through apoptosis [cell death] and that the serotonin transporter that
is the target of Prozac will block that action." More simply put, the
research said serotonin may play a role in helping to destroy cancer cells
involved in Burkitt's lymphoma and that antidepressant medications like
Prozac, may, in fact, block that action from occurring.
However, Blakely
said, "There is no indication that this behavior is found anywhere in
the nervous system or in the brain... So there is absolutely no reason
to extend from the data on the antidepressants [these findings] to brain
diseases, particularly brain cancer, which is a very different kind of
disorder."
Burkitt's lymphoma
is an extremely rare cancer that afflicts mostly children living in central
Africa. It often begins with a lesion in the jaw that quickly progresses
to the bony cavity that encloses the eye, and occasionally to other parts
of the head. Sometimes, the disease may encompass the bone marrow and
central nervous system, which could then worsen the outcome of the disease.
In the research conducted
by Gordon and Blakely, cells containing Burkitt's lymphoma were combined,
in a test tube, with the mood-elevating brain chemical serotonin. The
researchers noted that the serotonin was able to get inside the cells,
and cause them to die. Medications like Prozac, Paxil and Celexa, which
work to keep serotonin levels from being reabsorbed by brain cells, might
hamper that process.
This, however, said
Blakely, is a far cry from any notion that the drugs could play any role
in instigating or encouraging the growth of a brain tumor, which, in fact,
is not in any way even related to Burkitt's lymphoma.
[Top]
Virus
linked to brain cancer in children-(Times of India Online-24/02/2002)
A protein produced
by a common virus in human brain has been found to be responsible for
the most common brain cancer in children. The virus, a human neurotropic
polyomavirus called JCV, is present in at least 65 per cent of humans
by the time they reach the age of 14. Though JVC has been shown to cause
tumors in animals, this is the first time it has been seen in human tumors.
Usually, the virus
remains dormant. In certain cases, though it can cause progressive multifocal
leukoencephalopathy (PML), a fatal neurological disease similar to multiple
sclerosis and often seen in AIDS patients. Research suggests JCV may also
stimulate the growth of cancerous tumors, says a report in Health Scout.
Scientists aren't sure how JCV is transmitted, but believe parents may
pass it to children. Researchers also don't know how the viral protein,
lodged in a child, is triggered.
"I think some transient
immune suppressive condition might activate the viral genome," says Kamel
Khalili, lead author of the paper and director of the Center for Neurovirology
and Cancer Biology at Temple University College of Science and Technology
in Philadelphia. "There also may be some genetic component that makes
them susceptible, and maybe a combination of genetic and environmental
factors can induce the tumor in these patients."
Medulloblastomas are
the second most common brain tumors in children -- and the most common
malignant tumors -- and they are difficult to treat. Typically, surgery
and chemotherapy are used depending on the age of the child. Currently,
about half of the children who develop this malignant tumor die from it.
Although some subsets of the tumour are easier to treat than others, even
curable tumors carry the risk of serious long-term side effects, says
Ira Dunkel, assistant attending pediatrician at Memorial Sloan-Kettering
Cancer Center in New York City.
"Our understanding
of the mechanisms of the tumor is still pretty primitive, and studies
like this -- that give clues about how medulloblastomas are developing
or progressing -- will hopefully lead us towards better and less toxic
therapies," Dunkel says.
[Top]
How
dangerous is you mobile?-(Times of India Online-24/01/2002)
The United Kingdom
government is to spend 7 million pounds to establish the health risks
of mobile phone usage. The research programme, backed jointly by government
and the mobile phone manufacturing industry, is being launched amid confusion
about the safety of mobile phones and aerial masts. An initial 4.5 million
pounds will be provided to fifteen science projects for a wide-range of
studies examining the biological effects of mobile phone radiation. Out
of these, four studies will investigate whether the use of mobile phones
increases the risk of brain cancer or leukaemia.
Others will look
at the effect of mobile phone signals on brain function, and exposed cells
in the laboratory, and examine how energy is absorbed by the body. One
study will see how mobile phones affect the performance of drivers.
Two years ago, the
Stewart Inquiry reported there was no evidence that mobile phones were
a health hazard and could cause brain or nervous system cancers. Nevertheless,
the report concluded that radiation from handsets and base station masts
could cause "subtle biological changes".
A handful of scientists
continue to insist that mobiles are potentially dangerous. They claim
that even ignoring serious hazards such as cancer, users may suffer noises
in the head, migraine, headaches and other symptoms. Sir William Stewart,
who chaired the inquiry, has recommended a "precaution already been adopted
by the government.
[Top]
WHO:
Cell-phone cancer risk needs study-(Cancer Info-14/09/2001)
A link between mobile-phone
usage and cancer cannot be dismissed without further research, an official
at a World Health Organization agency said. "More research is needed,"
Elisabeth Cardis, chief of radiation and cancer at the WHO's International
Agency for Research in Cancer, told a conference in Helsinki.
The explosive growth
in mobile-phone usage, particularly in Europe and the United States, has
increased the public debate over possible health risks linked to mobile
phones. While a few studies claim there is a connection, most authoritative
studies have not been able to conclude that regular mobile-phone usage
could damage a person's brain.
"Based on current
epidemiological evidence, there is no evidence of a strong association
between RF (radio frequency) exposure and cancer," said Cardis, referring
to radio waves emitted from devices like mobile phones. "One can't rule
out that there is a risk, but if there is a risk to mobile-phone users
it would be very small."
Mobile phones are
tiny radio stations that send and receive. Last year, a UK government-sponsored
scientific inquiry, chaired by Sir William Steward, concluded that while
there was no evidence of danger to health, it would be wise to discourage
children from using mobile phones excessively. It concluded that the radio
frequency signals emitted by phones generated heat in the brain, but said
it was not clear whether this could have other biological effects, such
as triggering cancer.
European and U.S.
authorities have now asked mobile-phone manufacturers, such as Nokia,
Motorola and Ericsson, to label their phones with the level of radiation,
or Specific Absorption Rate (SAR)--the best way of measuring radiation--they
emit, partly in response to consumer demands. The SAR safety limit agreed
on in Europe is 2.0, while most phones on the market are now showing values
between 0.5 and 1.0.
There are more than
800 million mobile-phone users worldwide, and about 400 million handsets
are expected to be sold this year. By early next year as many as 1 billion
people are expected to own a handset.
New four-year study
Cardis, in Helsinki attending an international conference on the biological
effects of exposure to electromagnetic radiation, said research by the
Interphone study group would focus on a link between cancer and phones.
She said this would be more thorough than previous studies, such as the
Cohort study into cellular phone users in the United States, because it
would span a period of three years and would go into more detail, such
as research into lower-frequency electromagnetic fields to and from phones.
Cardis said one reason
previous studies, particularly on the link between brain tumors and phones,
had proved inconclusive was because brain tumor cases often had not used
phones much. Widespread mobile-phone usage is relatively new. The Interphone
study should be ready in 2004. "At present, possible effects on cancer
initiation cannot be studied due to the short follow-up times," concluded
a recent Finnish study into phone use and the risk of brain cancer.
Nokia, the world's
largest mobile-phone maker, addresses the issue of mobile-phone safety
on its Web site. "Scientific research conducted all over the world over
many years demonstrates that radio signals within established safety levels
emitted from mobile telephones and their base stations present no adverse
effects to human health," Nokia said.
U.S. neurologist Christopher
Newman last year filed a lawsuit against leading U.S. phone companies,
including Motorola, saying that the use of his mobile phone had caused
a malignant brain tumor.
[Top]
Duke
Researchers Identify 10 Genes Believed To Protect Oxygen-Starved Cancer
Cells-(Cancer Info-12/09/2001)
Cancer researchers
at Duke University Medical Center have identified 10 genes believed to
have significant roles in allowing cancerous tumors to thrive under oxygen-deficient
conditions. The discovery is the first step in what could eventually lead
to new treatments for some of the deadliest forms of cancer. Led by Dr.
Gregory J. Riggins, an assistant professor of pathology and genetics at
Duke, the team sifted through 24,504 genes expressed in the oxygen-deprived
(hypoxic) cells in Glioblastoma multiforme, which is a form of brain cancer.
The researchers identified
10 genes, some of which can lead to the creation of new blood vessels
that will connect to oxygen-starved tumors. "This is a crucial first step
in understanding the complex interactions driving hypoxia response in
tumors," Riggins said. "The potential for exploiting these genes is tremendous
in terms of turning off the angiogenesis (the formation of new blood cells)
of cancer and it may have significant use in other types of diseases as
well, such as stroke and heart disease. This is a very early, very preliminary
discovery. The gene discovery is the very first step in a very long road
that will lead to something that has clinical use."
Previously, scientists
thought angiogenesis was primarily influenced by a small set of genes
including the vascular endothelial growth factor protein (VEGF), but Riggins
suspects that the number of genes involved is significantly greater. "All
of these genes are turned on to a higher level than what has classically
been studied as a potent inducer of angiogenesis -- VEGF. If any one of
these genes turns out to be as potent or more potent than VEGF, then this
is a fairly significant find. There is significant investment from the
pharmaceutical industry to try and inhibit the function of this one particular
gene," he said.
Other scientists had
previously identified 10 genes that respond to hypoxia. The new Duke discovery
adds another 10 to the mix of which three had never previously been identified,
Riggins said. "These are completely novel genes that no one knows anything
about," he said. "We are working now to determine what their functions
are beyond being induced by hypoxia. What specifically are they trying
to do? Blood vessel growth? Are they trying to maintain pH in the tumor
or are they trying to protect the cell in some other way?"
One of the10 genes
is similar to a gene protein called angiopoietin-1, Riggins said. It has
a structure that suggests it could be an angiogenesis promoting gene.
And another of the genes, carbonic anhydrase IX (CA9), is believed to
be a useful marker to predict survival in some breast cancer patients.
In addition to Glioblastoma
multiforme, the same genes were expressed in, and could have implications
for, treating squamous cell carcinomas, breast, colon and lung cancers,
the researchers said. "If we can disrupt the function of some of these
protective genes, then maybe we can find ways to kill off the part of
the part of the tumor that's traditionally has been very difficult to
treat," Riggins said.
Tumors need a blood
supply to grow, but when this blood supply and the oxygen it carries is
cut, producing the oxygen-deficient known as hypoxia, the tumor shrinks.
Most solid tumors develop hard-to-reach hypoxic regions as they grow,
but some tumors, particularly Glioblastoma multiforme, continue to thrive
under hypoxic conditions. The cells in the tumors can alter gene expression
to produce new blood vessels (a process known as angiogenesis) with VEGF
and other proteins. Radiation and chemotherapy are often ineffective in
fighting hypoxic regions of tumors.
Because cancers are
so complex, Riggins said targeting one gene isn't enough. Instead, the
entire pattern of gene expression should be examined, and treatments formulated
based on more than one gene.
"Cancers can adapt
rapidly to environmental challenges, which partially explains why single
modality cancer therapy had not been successful as a multi-agent therapy.
This work documents a more complete set of genes whose function may be
to allow the tumor to adopt to hypoxia. More importantly, the products
from such genes may be tumor-specific targets for therapy. Based on the
observation that many angiogenesis-related genes are hypoxia-induced,
it is possible that successful targeting of the right combination of hypoxia
over-expressed genes (HOGs) could result in the disruption of growth of
blood vessels in tumors," the authors wrote in the article. "The next
step is to gather more documentation as to precisely what the molecular
function of these genes are in the tumor. We are currently synthesizing
(replicating) the proteins of these genes and testing to see if alterations
of these genes cause tumors to grow differently in mouse experimental
models," Riggins said.
Riggins is the director
of the Duke Brain Cancer Genomics Laboratory. The laboratory specializes
in locating genes useful for the diagnosis and treatment of brain cancer,
as well as understanding how these cancers develop.
[Top]
Stem
cells give hope for brain disease treatment (Times of India Online-12/08/2001)
With research in stem
cells - undifferentiated cells that can evolve into blood, liver, muscle
and other cells - picking up, scientists world over are hoping to come
out with treatments for head injuries, stroke, and progressive neurological
diseases like multiple sclerosis and brain cancer, according to a report
in a science journal. Stem cells obtained from embryos have been successfully
used in many experiments. However, due to ethical issues involved in their
use, researchers are now trying to use non-embryonal stem cells, which
reside in every tissue in the body and replace old cells when they die,
a report in New Scientist said. But, without the knowledge that
might be gained from studying embryonic stem cells, many of these efforts
might be wasted, the report warns.
Embryonic stem cells
have also led to advances in treating the animal equivalent of motor neuron
disease, which leaves humans unable to move. Jeffrey Rothstein at Johns
Hopkins University in Baltimore, found that paralysed rats, injected with
embryonal stem cells into the spinal fluid, dramatically regained partial
leg movement.
Evan Snyder of Harvard Medical School in Boston has reported progress
in using stem cells to kill cancerous brain cells. He is also working
with non-embryonal stem cells and has claimed success in treating strokes
in mice.
[Top]
Cancer
treatment shows promise-(Cancer Info-03/07/2001)
A genetically altered
virus kills cancer cells in tests in the laboratory. A research group
at Keio University School of Medicine is investigating a new cancer treatment
using a genetically altered virus to destroy cancer cells. The group will
seek approval this week from the university's ethics committee to test
the procedure on human patients with malignant brain tumors. It is hoped
the procedure will offer the possibility of treatment to patients for
whom surgery is difficult or impossible. Takahito Yazaki, an assistant
professor of the universitys Department of Neurosurgery, leads the research.
In the treatment,
a herpes simplex virus is used. In ordinary circumstances, a person infected
with the virus would develop encephalitis or inflammation of the brain.
The group, however, has manipulated the genes of the virus so that it
will only attack cancer cells. Though the modified virus multiplies using
enzymes produced by cancer cells, it will not do so in normal cells. Also,
the neurotoxicity of the virus has been removed, making it harmless to
patients. To increase its effectiveness, the virus is injected with a
gene that checks the production of enzymes that promotes the spread of
cancer cells.
In an experiment using
cultivated cancer cells of a human brain tumor, the viral therapy killed
50 percent of the cancer cells after two days and by the fifth day, destroyed
all the cancer cells. In another experiment the same type of cancer cells
were implanted in the brain of a laboratory mouse. Researchers were successful
in confirming a greatly increased survival rate for the mouse.
The team views the
research as a form of gene therapy. If they get the approval of their
university's ethics committee, they say the next step would be to seek
government approval. ``We hope to apply this to the treatment of cancer
of the bladder, liver cancer and prostate cancer in the future,'' one
of the researchers said.
[Top]
Common
virus may fight brain tumours (Times of India Online-21/06/2001)
In research that may
offer new hope for treating an aggressive and lethal cancer, doctors say
an injection of a common virus into the brains of mice caused tumours
to shrink without causing other disease. Although the study was conducted
in laboratory mice, the virus injection therapy may be ready for human
clinical trials in about six months. The study extends earlier work that
proved the concept of treating cancer using what is called a reovirus.
This is a virus that is common in the lungs and gut of humans, but which
is thought to be harmless except to cancer cells.
Normal cells have
a block to infection and death from reovirus so the virus can get into
the normal cell but cannot infect it further. But the reovirus can invade
cancer cells and go wild. The cancer cell become a bloated bag of viral
particles, explodes, and the viruses are released to go on and infect
and kill other cancer cells.
In the study, laboratory
cells of glioblastoma, a highly aggressive form of brain cancer, were
implanted into the brains of two dozen mice. Once the cancer cells were
established and growing, half of the mice received injections of live
reovirus and half got injections dead reovirus. The mice with the inactive
virus died within a short time from their tumours, while at 90 days eight
of the 12 mice that received live virus were still living.
Other researchers
noted that although the reovirus does not produce any recognised disease
in humans, there are many unknowns about the effect the virus might have
if it were injected into the brain of a human.
[Top]
Tobacco
Litigator Targets Mobile Phone Industry in Safety Suits-(Yahoo News-13/06/2001)
Having had success
suing the tobacco industry, Peter G. Angelos now has his sights set on
wireless phone manufacturers. The Baltimore, Maryland, attorney is filing
class-action suits in four states, claiming phone makers are selling products
that have been linked to brain cancer and other health-related problems,
according to published reports. The Washington Post and other media outlets
have reported that Angelos, who won a US$4 billion class-action settlement
from tobacco companies, has filed suits in Maryland, Pennsylvania, New
Jersey and New York alleging conspiracy, fraud and negligence by major
phone manufacturers. Angelos reportedly is seeking a judgment that includes
requiring all manufacturers to supply headsets at no cost to all purchasers
or lessees, or to reimburse any consumer who has purchased a headset.
The suits also ask for punitive damages and costs, the reports said.
Among the 25 defendants
are wireless industry leaders Motorola, Sprint, Audiovox, Nextel, Matsushita,
Philips, Qualcomm, Samsung, Sanyo, Sony, AT&T, Verizon, Cingular,
SBC, Cellular One and Voicestream, published reports said. The suits are
the latest in a series of legal actions taken on behalf of consumers,
despite industry claims, backed by research reports, that there is no
definitive link between cell phone use and brain cancer or other illnesses.
Health concerns have been raised regarding the radiation from handheld
cellular phones based on the close proximity of the antenna to the head
of the user.
[Top]
Mobile
Phone Makers Patent 'Radiation Shields' To Combat Cancer Risk-(Yahoo News-13/06/2001)
Mobile phone manufacturers
have patented "radiation shields" to reduce the risk of brain tumors among
consumers, despite their claims that phone use presents no serious health
hazards. Although the companies dismissed the report, it could be used
as ammunition in lawsuits recently filed by consumers against manufacturers.
According to The Times
of London, leading phone makers Nokia, Ericsson and Motorola have created
components to protect users from the radio frequency radiation emitted
by handsets. Manufacturers have been developing such components for at
least eight years, the newspaper said, citing an application filed by
Nokia with the U.S. Patent Office in Washington, D.C., that states "it
has been suggested that" extended exposure to radio frequency radiation
could lead "to a development of malignant tumor." The U.S.-based Wireless
Consumer Alliance discovered 25 such patents, the Times said.
Phone makers rejected
the claim that the patents indicate that they accept the existence of
health hazards. "Patenting new innovations is a standard practice," Nokia
spokesperson Keith Nowak told Wireless NewsFactor. "Patents are often
filed before inventions are ready for commercial use, and others turn
out not to be technically viable at all. Therefore, Nokia, like many large
technology companies, has an extensive patent portfolio which includes
designs and devices which are not currently used in production models."
Nowak added that Nokia's
products meet emissions safety standards set by government and administrative
agencies, so "the fact that Nokia may have alternative means of meeting
these standards which have not been incorporated into current complying
products is not relevant."
Ericsson spokesperson
Robert Elston said that all Ericsson phones are designed and tested to
comply with existing safety standards for radio frequency exposure, which
leave wide margins of safety. Elston cited the World Health Organization
(WHO), which said, "Scientific evidence does not indicate any need for
RF absorbing covers or other shields on mobile phones."
"Extensive research
over the course of many years has not established any conclusive evidence
of a link between adverse health effects and the use of mobile phones
meeting those standards and regulations," Elston said.
Ericsson spokesperson
Michael Westmark told Reuters that the patents were designed to improve
the performance of mobile phones by reducing the radio waves they use,
not specifically to prevent brain tumors, and denied the inventions were
an admission that using the company's phones presented a health hazard.
Although studies by
the Journal of the American Medical Association and the New England Journal
of Medicine, as well as the National Cancer Institute and a number of
international health authorities that have studied the issue, have found
no definitive link between cell phone use and health problems such as
cancer, scientists acknowledge that more research is needed. Others are
not convinced and have taken legal action against phone manufacturers,
stating the companies knowingly are selling hazardous devices. The report
that phone makers have developed radiation-shield technology could be
a powerful tool for high-profile attorney Peter G. Angelos, who has filed
class-action suits in four states, claiming phone makers are selling products
that have been linked to brain cancer and other health-related problems.
Angelos is seeking
a judgment that includes requiring all manufacturers to supply headsets
at no cost to all purchasers or lessees, or to reimburse any consumer
who has purchased a headset, as well as punitive damages. His is one of
several lawsuits filed against phone manufacturers in the United States.
[Top]
A
re-engineered polio virus is used as a weapon against deadly brain tumours-(Cancer
Info-23/05/2001)
While health workers
race to eradicate poliomyelitis, a re-engineered poliovirus has been used
as a weapon against deadly brain tumours by researchers in North Carolina.
They have found by chance a genetic trick that makes the wild poliovirus
attack and destroy tumour cells instead of the neurons that are its normal
target.
Matthis Gromeier,
a microbiologist now at Duke University in Durham, North Carolina, and
his colleagues were working to understand the poliovirus better by examining
the effect of swapping an instruction on its RNA for an analogous snippet
from a rhinovirus. The latter is responsible for the common cold. Normal
polio viral cells attach to neurons at a receptor protein known as cd155
and destroy them. Glial cells form the support structure for neurons and
can mutate to form glioma brain tumours. They also have cd155 but polio
does not normally affect them. But with the rhinovirus RNA instruction,
the team found that the poliovirus killed glial cells instead of neurons.
The effect is not
fully understood yet, but the team has now exploited it to create a potential
treatment for gliomas. These are the most common brain tumours and are
nearly always fatal as no effective treatment is currently available.
They have found that injecting the re-engineered poliovirus into gliomas
in mice causes them to shrink dramatically within a week and almost disappear
within two. Equally important, all their results have shown the altered
virus to be incapable of causing poliomyelitis, though Gromeier says that
possibility can never be completely eliminated.
The Duke team is currently
working toward human trials of the technique with the National Cancer
Institute in Bethesda, Maryland, though Glomeier says they are probably
a few years off.
[Top]
Pharmacyclics
pins hopes on cancer-treatment drug (Cancer Info-08/05/2001)
While a graduate student
in chemistry at Stanford, Jonathan Sessler suffered a relapse of Hodgkin's
disease-a cancer of the lymph nodes-and was treated by a young university
oncologist, Dr. Richard Miller. "I'd do chemotherapy in the day,
go home and vomit a bit, and go back and do lab work at night,'' recalls
Sessler, who recovered and remains healthy two decades later. He also
remembers that Miller issued him a challenge: to use his knowledge of
chemistry to develop new compounds for fighting cancer.
And that's just what
Sessler has been doing as a professor of chemistry at the University of
Texas. There he and his colleagues invented a family of chemicals dubbed
"texaphyrins" that accumulate in tumors but not in healthy tissue.
They are Texas-size versions of natural compounds called porphyrins, a
class that includes a key component of the hemoglobin in red blood cells
and the chlorophyll in green plants.
In 1991, Sessler and
Miller launched Pharmacyclics in Sunnyvale to apply these colorful compounds
to the treatment of cancer and other diseases. In March, medical researchers
treated the last of 428 patients in a test of one of these compounds,
Xcytrin. Half the patients were given radiation plus Xcytrin for tumors
that had spread to their brains; the other half got radiation alone.
Sessler and Miller,
a co-founder of Idec Pharmaceuticals in San Diego, are optimistic that
the study conducted at 60 medical centers will show that Xcytrin improves
the effectiveness of radiation, extending lives and reducing the debilitating
impact of multiple tumors in the brain. They should know if they're right
when the data is fully analyzed by the end of the year.
That would be good
for the patients with brain metastases, whose life spans are typically
measured not in years but in months. And it will be good for a company
that sees a possible billion-dollar-a-year market for a drug that can
enhance the benefit of radiation in cancer treatment without contributing
much in the way of ill effects of its own.
In the case of Xcytrin,
there is a side effect that sets it apart, one that lasts only a few days:
It turns patients slightly green. "It has no clinical consequence,
is the way I'd describe it," Miller said. "But you do tell patients
about it."
"In the clinic,
it's a source of humorous conversation," said Dr. Minesh Mehta, the
University of Wisconsin radiation oncologist who heads the large-scale
clinical trial of the drug now in its final stages. It comes up a lot
around St. Patrick's Day, he said.
While not all patients
pay much attention to the color, their doctors can see it, making it impossible
to do what is called a blinded trial, where neither patients nor doctors
know whether an individual patient is getting an injection of the drug
or an inert salt solution.
There's a reason for
the tint. Porphyrins are by nature colorful compounds -- the word comes
from the Greek word for purple. The porphyrin in blood cells gives them
a red or bluish hue. And as they break down in a bruise, they change from
purple to green to yellow. Xcytrin just happened to be a dark-green.
Sessler said he began
looking at these compounds because it has long been known that they accumulate
in tumors. Moreover, an expanded version of a porphyrin could carry a
sizable metal atom. The metal in Xcytrin is gadolinium, which can be detected
in an MRI, providing a sharp image and an easy way to measure any changes
in tumor size. Other compounds in the family can be equipped with radioactive
metals that could carry destruction to the cancer cells. "I realized
that the texaphyrins target tumors better than antibodies," Miller
said.
Other texaphyrins
being developed by Pharmacyclics can be energized by light from lasers
for the treatment of cancer, hardening of the arteries and macular degeneration,
an overgrowth of small blood vessels in the eye. But Xcytrin remains the
Sunnyvale company's lead product. It could win relatively speedy approval
by the Food and Drug Administration if the current tests of the drug are
a success, in part because the plight of patients whose cancer has spread
to the brain is so grim.
An estimated 170,000
patients are treated each year for cancer that has spread to the brain.
The median survival is only four months, even with radiation treatments.
"I cannot imagine anything worse happening to a patient," Miller
said. "Multiple tumors in the brain have unpredictable effects on
the ability to speak and to think."
Earlier results in
a small, preliminary trial in 22 patients were promising: 72 percent of
those treated with Xcytrin plus radiation showed a marked reduction in
their tumors. But that study did not directly compare these patients with
those getting radiation alone. Those are the results expected later this
year. Still, said Mehta, "I have been working with radiosensitizers
for quite a long time and I have not seen responses as dramatic as those
with this agent."
There are other drugs
that sensitize cancer cells to radiation, including some standard chemotherapy
agents. But most have significant side effects. Other promising drugs
are in development, including one called RSR13 from Allos Therapeutics
in Denver. But Thomas J. Dietz, an analyst with Pacific Growth Equities,
gives the edge to Pharmacyclics' Xcytrin.
He notes the National
Cancer Institute is sponsoring several different trials of the drug in
tumors that originate in the brain, as well as lung and pancreatic cancer.
"The drug takes the standard practice of radiation therapy to a new
level," Dietz said.
The path to FDA approval,
however, is not always a smooth one for any drug. And there was at least
one worrisome moment for Pharmacyclics a year ago, when researchers from
several major centers reported they saw no evidence that Xcytrin increased
the effects of radiation in killing tumor cells in petri dishes or in
mice. Last summer, when an article in Barron's picked up on those findings,
Pharmacyclics shares took a beating- losing almost of third of their value
over the next several days. Company officials point to several recent
studies that support the effectiveness of Xcytrin in animals and in people.
But Martin Brown, a Stanford professor and one of the authors of the critical
scientific paper, sticks by the findings, adding, "The bottom line,
however, is that we will have to see what happens in the clinical trial."
[Top]
Therapy
on horizon for rare brain tumor in young (Times of India Online)
Researchers have discovered
that a rare pediatric brain cancer is actually not one, but two types
of tumor. One of the tumor types appears to be caused by two different
genetic mutations, and the discovery should help pave the way for a targeted
drug therapy to eradicate that type.
By analyzing both
recently removed and stored tissue from brain tumors, the scientists found
that medulloblastoma, a brain cancer that affects 400 to 500 American
children each year, has two different subtypes. A quarter of medulloblastomas,
which they called desmoplastic, seem to be caused by mutations in two
genes that are important to normal development and the brain and other
organs. The mutations likely cause the genes to be overactive, which could
lead to uncontrolled growth of cancer cells.
At the same time other
researchers found a substance that seems to block the uncontrolled cell
growth from the mutations. The discovery could lead to a drug targeted
to stop this over-activation. The genetic mutations were not found in
so-called ``classic'' medulloblastomas, which account for 75 per cent
of cases.
[Top]
Study
Shows No Connection Between Cell Phone Usage And Brain Cancer-(Cancer
Info-21/12/2000)
With
more than 86 million American cellular phone users reported in 1999 and
the number still increasing, there has been growing concern about the
risk of developing brain cancer from radiofrequency signals given off
by handheld cellular phones. A case-control study of 891 people who regularly
used a cellular phone showed no statistical association between the amount
of cell phone usage and the likelihood of developing brain cancer. Researchers
from the American Health Foundation and Memorial Sloan-Kettering Cancer
Center and four United States medical centers reported their findings
in the December 20 issue of the Journal of the American Medical Association.
In a
retrospective, case-control study, 469 men and women diagnosed with primary
brain cancer and 422 people without brain cancer were interviewed between
1994 and 1998 using a structured questionnaire. They were asked which
type of cell phone (manufacturer) they used, the usage per month in minutes
and hours, the year of first use, and the number of years of usage. In
addition, an estimated monthly phone bill was ascertained. The patients,
aged 18 to 80, were scrupulously matched to the control group by age,
sex, race, years of education, and occupation.
The usage
reported for cancer patients and the control group was not statistically
significant. The median monthly use was 2.5 hours for cases with cancer
and 2.2 hours for the control. The mean duration of use was 2.8 years
for brain cancer patients and 2.7 years for the controls. Because 85 percent
of people in the study reported extending the antenna during calls, a
disproportionate cluster of tumors might have been expected behind the
eye and the ear on the side the cell phone was used since radiation emission
is highest at the antenna. In fact no link was found between cell phone
usage and temporal lobe tumors, nor was there any association between
handedness and tumor location.
Based
on all available data including studies by other groups, the researchers
believe that extended use of cellular phones does not appear to cause
brain cancer. However, further research is indicated as this study covers
people who have mostly used analog cellular phones for a relatively short
period of time (two to three years). As people continue to use cell phones
for extended durations, the long-term health effects, if any, need to
be monitored.
[Top]
Neuroblastoma
Imaging Compound Now Used To Kill It-(Cancer Info-6/12/2000)
A radioactive
compound used for the past two decades to find certain types of cancer
is now showing surprising promise in helping to kill those tumors too.
All 11 children treated for neuroblastoma in the drug's first clinical
test initially had a positive response with no significant side effects.
The compound,
called MIBG, was originally developed and patented in the 1970s and is
now used around the world in medical imaging to find and classify certain
forms of cancer -- including neuroblastoma, the second most common solid
childhood cancer. New results indicate that higher doses of MIBG can also
help shrink the same tumors. MIBG acts as a tumor bullet, specifically
targeting the neuroblastoma itself, sparing other parts of the body from
complications or side effects. MIBG was incorporated into a neuroblastoma
treatment regimen, combining it with chemotherapy and a transplant of
the child's own bone marrow.
In the
Phase I trial, the therapy produced partial remission in three children
and complete remission in eight others. All were aged 2 to 14 years and
had a history of advanced, or persistent, neuroblastoma. The MIBG regimen
caused many of the patients' tumors to shrink or disappear entirely for
at least 100 days, and up to one year, with few side effects. However,
some have since relapsed and died, while others continue to be stable.
More
than 60 percent of all neuroblastoma patients have an advanced stage,
high-risk form of the disease that is often resistant to treatment. Advanced-stage
patients usually have a life expectancy of one to two years; many of the
patients in the trial had a worse prognosis because they had failed prior
treatment. Advanced neuroblastoma patients often undergo surgery along
with radiation therapy and chemotherapy, and may even have a transplant
of their own bone marrow. Despite all the modern advances in medical science,
still only 25 to 30 percent of children with advanced neuroblastoma are
able to be cured at this point in time. One thought is optimal delivery
of the therapy to the tumor itself is not being achieved. That is why
the idea of using MIBG is so promising. The compound combines a substance
called meta-iodobenzylguanadine -similar to norepinephrine -with a radioactive
form of iodine called iodine-131. It was originally developed to treat
high blood pressure, but researchers discovered another effect: the MIBG
was found to bind to tumor cells that produced chemicals called catecholamines,
like neuroblastomas.
MIBG
will go through the body looking for neuroblastomas and once it finds
it, it will bind to it. That finding led the U-M to pioneer the use of
MIBG in the 1970s and 80s to diagnose neuroblastomas. The MIBG is given
as an infusion into a patient's IV, and attaches to any neuroblastoma
that's in the body so that we can see it on an X-ray type image. Ninety
percent of neuroblastomas will take up the MIBG. If, however, the MIBG
can't successfully attach to a patient's tumor, it can't be used to find
or treat it.
Prior
trials attempted to use MIBG alone. Through the present study, it was
determined that if bone marrow transplant was combined with MIBG therapy
as two knock-out punches back to back, there was better chance of success
in treating patients with extensive neuroblastomas.
The protocol
used to produce the new results was developed through cooperation among
nuclear medicine specialists, oncologists, radiologists and bone marrow
transplant specialists. The MIBG is made at the Phoenix Memorial Laboratory.
The regimen starts with a regular low-dose MIBG imaging scan, to make
sure the patient's tumors will take up the compound and to pinpoint where
the tumors are found. Then, the patient's bone marrow is harvested and
frozen, before starting a 21-day attack.
The assault
on the cancer starts with an infusion of the MIBG solution in the patient's
IV. The MIBG is administered over 90 minutes to the patient in a special
lead-lined hospital room. The shielding around the patient keeps parents
and other healthy people from exposure to radiation. During the three
to five days in the special room, the children can watch TV and play with
video games or toys while the radioactivity in the MIBG does its silent
work attacking the tumors. Though the dose is high, the only side effects
reported during administration of the MIBG were mild nausea and vomiting.
Three
to four days after receiving the MIBG, patients are discharged from the
hospital. They are then re-admitted in two weeks for four days of high-dose
chemotherapy followed by an infusion of their stored bone marrow. The
patients are then required to stay in the hospital for several weeks to
recover from the transplant.
The promising
results from the initial trial have led to the research being performed
in several other pediatric transplant centers in the U.S. The University
of Michigan has joined forces with several other medical centers, including
the University of California at San Francisco, Children's Hospital of
Los Angeles, and the Children's Hospital of Philadelphia, to treat patients
with MIBG using a common protocol.
Meanwhile,
research designed to help predict which patients may benefit most from
MIBG earlier in their treatment course, rather than waiting until they
have failed conventional treatment continues.
[Top]
Cell
transplants safe for stroke patients-(Times of India-23/08/2000)
Cells taken from a
deadly tumour and retrained to become brain cells have been safely used
to treat stroke patients. While only half the patients improved, the study
shows that the method is safe and strengthens the idea that brain cell
transplants can be used to help stroke patients recover.
The cells came from
a 22-year-old cancer patient who died of a tumour called teratocarcinoma.
These cells have properties similar to tem cells, the master cell from
which all other cells are produced. The cells were kept alive in a laboratory
and a way was found to coax them into becoming what appear to be normal
neurons.
The stroke patients
got injections of the cells and in just under 6 months, six of the 12
patients had improved scores on standard measures of stroke effects. They
showed a better ability to use arms, legs, walked without braces, had
improved strength in terms of being able to hold something better.
Positron Emission
Tomography scans showed the cells seemed to be functioning in about half
the patients.
[Top]
Gene
therapy for brain tumours, leukemia-(Times of India-17/08/2000)
Researchers have succeeded
in cloning genes that result in brain tumours, paving the way for possible
gene therapy against the disease. Called the low oxygen-inducing factor,
the gene was recently cloned from a galotinous tumour sample from a human
brain. Existing inside the human body, the gene could induce various diseases
and cause nerve system damage and brain tumours.
A whole set of genes
which play a key role in treating an acute form of leukaemia has also
been discovered. The 169 genes can be adjusted by Atra, a chemical element
derived from Vitamin A, to form a genetic system which controls the division
of WBCs and helps cure Acute Promyelocytic Leukaemia.
[Top]
Institute
To Create New Therapies For Brain Cancer-(Cancer Info-26/05/2000)
Continuing its leading-edge
research into treatments for malignant diseases, the Dana-Farber Cancer
Institute is launching a new, comprehensive neuro-oncology center to focus
on the genetics of brain development-with the goal of creating new clinical
therapies for brain cancers and other neurological malignancies.
The Charles A. Dana
Foundation, whose support of the Institute spans nearly four decades,
has awarded it $7.4 million for the establishment of the David Mahoney
Center for Neuro-Oncology. The center will enable Dana-Farber and other
Harvard Medical School-affiliated researchers to gain valuable insight
into the process of both normal and abnormal brain development.
[Top]
Neural
stem cells and brain cancer: a mission to seek and destroy-(Nature Medicine
April, 2000)
A study in the April, 2000 issue of Nature Medicine offers hope for treating
malignant tumors of the central nervous system by making use of the ability
of genetically modified neural stem cells to engraft into the brain and
produce cancer-fighting molecules. Human brain tumors such as glioblastomas
are among the most difficult cancers to treat. Their tendency to spread
throughout the central nervous system often makes surgical removal impossible,
and chemotherapy cannot usually penetrate the blood-brain-barrier effectively.
As for many cancers, there has long been hope that harnessing the power
of the immune system would enable the effective treatment of these tumors.
The difficulty is delivering the therapeutic agents to the right locations
within the brain for extended periods of time. Now, Gaetano Finocchiaro
and his colleagues at the Instituto Nazionale Neurologico Besta in Milan,
Italy describe immunotherapy of glioblastoma using stem cells of the central
nervous system as vehicles for the delivery of the immunomodulator, interleukin
(IL)-4.
[Top]
Medical revolution is
under way on the net (TOI-17/12/99)
The singer Carnie Wilson was not alone during
her gastrointestinal bypass operation. As well as half a dozen doctors
and nurses, there were 52,000 people watching the two-hour procedure live
on the net. Cybersurgery is the latest health craze on the net and its
promoters are predicting eventual audiences of more than a million.
Other health sites are already offering virtual
check-ups, heart monitoring and cancer risk assessments.
The net is spearheading a technological revolution
in the delivery of health care and a survey by the Royal College of Surgeons
of Edinburgh shows health surfers, including doctors, to be the biggest
measurable group of net users.
[Top]
|