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Taxotere®
and Genasense(TM) Active in Refractory Prostate Cancer-(ET-17/09/2003)
According
to results recently presented at the 39th annual meeting of the American
Society of Clinical Oncology, the treatment combination of Taxotere® and
Genasense(TM) appears to produce anti-cancer activity in hormone-refractory
prostate cancer. The prostate is a walnut-sized male sex gland that is
located between the bladder and rectum. The prostate is responsible for
secreting a substance that forms a component of semen. Treatment options
are varied for patients with prostate cancer, often depending upon the
stage, or extent, of the disease. Metastatic prostate cancer refers to
cancer that has spread outside the prostate to distant sites in the body,
often invading vital organs and bones. One component of therapy for prostate
cancer is called hormone therapy, in which levels of male hormones, which
have growth stimulatory effects on prostate cancer cells, are reduced
in the body. However, prostate cancer that ultimately stops responding
to hormone therapy is referred to as hormone refractory prostate cancer.Researchers
are evaluating novel therapeutic approaches for patients with this disease.
Response to treatment
is often measured by prostate specific antigen (PSA) levels in the blood.
Prostate specific antigens are small molecules normally shed from prostate
cells into the blood and when elevated, often indicate growth of prostate
cancer. An obstacle to achieving optimal therapeutic outcomes in patients
with cancer is that cancer cells become resistant to therapy. Genasense
(oblimersen sodium), a biologic agent still in clinical trials, targets
a protein called Bcl2 that is thought to play an important part in the
development of treatment resistance in cancer cells. Bcl2 is a protein
that exists in delicate balance with other related proteins and its function
is to prevent cells from apoptosis (death). Through several mechanisms
not entirely understood, Bcl2 proteins protect cancer cells from the lethal
effects of chemotherapy. Various types of cancer, including prostate cancer,
are associated with high levels of Bcl2 proteins.
Researchers from
the Cancer Treatment and Research Center in San Antonio TX, and the British
Columbia Cancer Center conducted a clinical trial evaluating the combination
of Taxotere and Genasense in the treatment of hormone-refractory prostate
cancer. Taxotere (docetaxel) is a chemotherapy agent that continues to
demonstrate promising activity in the treatment of prostate cancer This
trial included 29 patients who had received extensive prior treatment,
including hormone therapy, chemotherapy and/or radiation therapy. Following
treatment, nearly half (48%) of all patients had at least a 50% reduction
in their PSA levels. Of the patients who had cancer that was visible on
x-ray or could be measured on physical examination, 31% experienced an
anti-cancer response of these areas. Treatment was well tolerated.
The researchers concluded
that the combination of Taxotere and Genasense provides anti-cancer activity
in patients with prostate cancer that has stopped responding to standard
therapies. These results have prompted the initiation of a trial directly
comparing Taxotere alone to Taxotere plus Genasense in order to formally
assess the true clinical benefit of this treatment combination in men
with hormone-refractory prostate cancer. Patients with hormone-refractory
prostate cancer may wish to speak with their physician about the risks
and benefits of participating in a clinical trial further evaluating the
addition of Genasense to Taxotere or other promising therapeutic approaches.
[Top]
Prostate
Cancer Risk Highest with Affected Brother-(Reuters Health-15/09/2003)
To have a lower risk
of prostate cancer, it's better to have a father with the disease than
a brother, new research suggests. Of course, having no family members
with the disease carries the lowest risk. This finding is the opposite
of what is seen with breast cancer, in which a person's risk is lower
if they have a sister with the disease rather than a mother, lead author
Dr. Deborah Watkins Bruner said in a statement. "This may suggest that
the risk may be related to shared environmental factors such as dietary
exposures or age of onset of disease, which might reveal a stronger genetic
risk," Dr. Bruner, from the Fox Chase Cancer Center in Philadelphia, added.
The new findings
are based on a review of 24 studies that looked at a person's risk of
prostate cancer when different family members were affected. The report
is published in the International Journal of Cancer. Compared with having
no family members with prostate cancer, having any relative with the disease
raised the risk by 93 percent. If any first-degree relative such as a
father or brother was involved, a 120 percent increase in risk was seen,
whereas disease in a second-degree relative, such as an uncle, raised
the risk by 88 percent. Having a father with prostate cancer doubled a
person's risk of the disease, while having an affected brother nearly
tripled their risk. These findings could be used to better gauge prostate
cancer risk and could potentially reduce unnecessary screening tests and
diagnostic surgeries, Bruner noted.
[Top]
Test
Predicts Death After Prostate Cancer Therapy-(Reuters Health-16/09/2003)
After treatment for
prostate cancer, the amount of time it takes for a certain blood marker
to double predicts a person's risk of dying, new research suggests. The
prostate specific antigen, or PSA, is a commonly measured blood marker
in men with prostate cancer. In the new study, patients who had been treated
for prostate cancer were at increased risk for death if it took less than
three months for the PSA level to double.
Dr. Anthony V. D'Amico,
of Brigham and Women's Hospital in Boston, and colleagues followed more
than 8000 men treated for prostate cancer between 1998 and 2002. They
report in the Journal of the National Cancer Institute that 154 patients
died during a follow-up period of around 7 years; 110 of the deaths were
due to prostate cancer. During follow-up, 12 percent of patients treated
with surgery and 20 percent of those treated with radiation had a PSA
doubling time of less than 3 months. Such patients were nearly 20 times
more likely to die of prostate cancer than patients with longer doubling
times. Based on these findings, the authors propose that a doubling time
of less than 3 months could be used as a surrogate end point in prostate
cancer studies. In a related editorial, Dr. Howard M. Sandler and Dr.
Michelle L. DeSilvio note that by using doubling time of less than 3 months
as an end point instead of survival, clinical trials could be shortened
and trial results evaluated more rapidly. Both editorialists are radiologists,
Sandler at the University of Michigan in Ann Arbor, and DeSilvio at the
American College of Radiology in Philadelphia.
[Top]
Prostate
Cancer Therapy May Help Older Men-(Reuters Health-18/09/2003)
Although underused,
aggressive treatments, such as complete removal of the prostate gland,
can improve the survival of older men with early prostate cancer, new
research suggests. Men younger than 60 years with early prostate cancer
are 25 times more likely than men age 70 years or older to undergo "radical"
surgery, the authors explain, perhaps because of a perception that older
men are unlikely to benefit from such therapy. Dr. Shabbir M.H. Alibhai
from University Health Network, Toronto, Ontario, Canada and colleagues
used a special statistical model based on past data to compare radical
surgery, radiation, and regular observation in older men with prostate
cancer. The new findings are published in the Journal of Clinical Oncology.
For most men over
age 65 with really early disease, regular observation seemed to produce
the best balance between increasing survival and not impairing quality
of life. For men with slightly more advanced disease, the best treatment
was less clear. Surgery seemed to be the best choice for men younger than
65 years, but it was unclear whether observation became the best option
starting at 65 years or 75 years. For otherwise healthy men with the most
advanced disease, surgery and radiation were equally effective methods
of improving survival in men up to 85 years of age. Overall, the benefits
of these potentially curative treatments were restricted to men without
a lot of other coexisting diseases.
"Based on all of
the data accumulating," Alibhai told Reuters Health, "I believe there
is a survival advantage to treating patients with either surgery or (radiation),
although the gains may be huge or more modest...given the uncertainty
of the data." "Many men aged 70 to 80 who are generally well or have well-controlled,
stable diseases such as diabetes, asthma, or hypertension, will benefit
from aggressive therapy for (serious) disease," Alibhai concluded. "I
believe we need to be more aggressive in treating this group of patients."
[Top]
Prostate
Cancer Treatment Gets Under the Skin-(Reuters Health-03/09/2003)
A new method of delivering
a prostate cancer drug under the skin is useful in maintaining low levels
of testosterone, a hormone that can cause frustrating symptoms and promote
the growth of cancer cells, new research shows. The drug, called leuprolide,
and others like it are used to ease the symptoms in men with advanced
prostate cancer, the authors note. Long-term delivery systems for leuprolide
can contribute greatly to patient compliance. Dr. Robert C. Tyler, from
Atrix Laboratories, Inc. in Fort Collins, Colorado, and associates studied
the safety and effectiveness of a new leuprolide delivery system in 90
men with prostate cancer. The LA-2575 system involves injection of leuprolide
mixed with a biodegradable polymer under the skin, where it forms a solid
depot. Over time, the depot gradually releases leuprolide into the patient's
bloodstream. Within 28 days of injection, nearly all of the men had testosterone
levels that were as low as those seen in men without testes-the glands
where testosterone is produced.
The most common side
effect related to treatment was hot flashes, the investigators report,
although the level of testosterone suppression did not influence the frequency
and severity of hot flashes. In contrast to treatments tested in the past,
the authors note, no patients treated with the LA-2574 system required
additional or alternate drugs to control their testosterone levels. LA-2575
injected at 112-day intervals during 8 months in men with prostate cancer
"was effective in producing and maintaining therapeutic suppression of
testosterone," the researchers conclude. "Additional research is needed
to determine whether the degree of testosterone suppression is linked"
to prostate cancer survival, they add.
[Top]
Vitamin
D Mimic May Improve Prostate Cancer Therapy-(Reuters Health-27/08/2003)
Treating prostate
cancer cells with a vitamin D-like compound appears to make them more
susceptible to the destructive effects of radiation, lab experiments show.
If this research holds up, pretreating prostate cancer patients with the
vitamin D "analog" could offer two benefits. It might allow the radiation
dose to be reduced, resulting in fewer side effects, or it could enhance
the effectiveness of standard dose radiation. However, "our findings first
need to be verified in animal studies followed by testing in humans,"
Dr. Constantinos Koumenis, from Wake Forest University in Winston-Salem,
North Carolina, told Reuters Health. The analog, which is produced by
Abbott Labs under the name Zemplar, is already approved by the FDA as
treatment for an overactive parathyroid gland "which should expedite testing
in prostate cancer patients," Dr. Koumenis noted. Optimistically, "testing
in humans could begin in a year," he added.
In the new study,
the researchers irradiated human prostate cancer cells that were exposed
to Zemplar, calcitriol (the active form of vitamin D), or were untreated.
The results are published in the online issue of the British Journal of
Cancer. The killing effect of radiation was stronger when the cells were
first exposed to Zemplar or calcitriol. In addition, the enhanced destruction
was fairly selective, leaving normal prostate cells relatively unscathed.
"The reason for the synergy between Zemplar and radiation is unclear,"
Dr. Koumenis noted. However, vitamin D by itself has been shown to slow
the growth of prostate cancer cells, he added. Although calcitriol was
effective in these experiments, it has one major drawback: it tends to
cause high calcium levels in the blood, which can lead to a number of
problems. Zemplar, by contrast, appears much less likely to produce this
metabolic disturbance.
[Top]
Standard
Prostate Cancer Test Is Inaccurate, Study Says-(ET-23/07/2003)
The standard PSA
blood test used to screen for prostate cancer is highly inaccurate, failing
to flag eight of every 10 men under 60 who are later diagnosed with the
disease, according to a new study that promises to amplify debate over
medical practices concerning the common male malignancy. The study, in
this week's New England Journal of Medicine, said the results of the blood
test could be dramatically improved by simply lowering the threshold for
what is considered a problematic result to 2.6 from four on the PSA scale,
which measures how many billionths of a gram of prostate-specific antigen
are present in a milliliter of blood. But if the lower level were to become
the accepted new threshold, it would likely lead to far more prostate
biopsies -- operations in which small pieces of the prostate are extracted
to determine definitively whether cancer is present. Although that could
have benefits in early warning in some cases, most men who undergo a biopsy
after a PSA test don't have cancer and there is no hard evidence that
early detection of prostate cancer decreases mortality. In fact, critics
say, early detection can lead to unnecessary treatment.
About three- quarters
of the men over 50 in the U.S. have been screened by a PSA. The authors
-- from research centers in Boston, Chicago and St. Louis -- report that
the current standard for recommending a biopsy using a PSA test misses
82% of the cancers in men under 60 and two-thirds of the cases in men
over 60. Lead author Rinaa Punglia, a radiation oncologist at Brigham
and Women's Hospital in Boston, said past studies have indicated the PSA
test is near perfect. But her study found the test suffers from verification
bias, which is the simple fact that not every man who undergoes a PSA
test then has a biopsy performed, which is the gold standard for identifying
prostate cancer. Without knowing whether men who were screened out by
the PSA might have cancer, it is difficult to determine the true accuracy
of the PSA test.
The researchers used
a mathematical model to adjust for verification bias. Those results indicate
that lowering the threshold for recommending a biopsy to 2.6 can double
the cancer detection rate in men under 60 to 36% from 18%. For older men,
the rate increases to 60% from 35%. Howard Parnes, chief of the prostate
and urologic research group at the National Cancer Institute, praised
the work of the researchers, but said lowering the PSA standard has risks,
including subjecting more men to biopsies that are likely to be negative.
In the study, which examined cases involving 6, 691 men enrolled in a
prior study done at the Washington University College of Medicine, about
7% of the men fell in the PSA range of 2.6 to 4. In addition, Dr. Parnes
said many men may have localized cases of prostate cancer that don't pose
a serious health risk. "This is not to say PSA screening is only picking
up indolent, unimportant disease," he said. "I'm making a point that there
is a lot of prostate cancer out there and to me that is one of the hidden
downsides. When you screen for this disease, some of the disease you pick
up doesn't need to be found. It is not destined to pose a threat."
As evidence of the
controversy surrounding PSA testing, the journal also published a companion
editorial that rebuffs the suggestion of the study authors that the PSA
standard be lowered. The editorial authors, from the Erasmus Medical Center
in Rotterdam, the Netherlands, warned that lowering the PSA threshold
for performing a biopsy will increase the rate of overdiagnosis and, potentially,
overtreatment. The editorial authors said any decision to lower the PSA
threshold should come from clinical trials designed to show whether men
who undergo screening are less likely to die of prostate cancer than those
who don't. Two such trials are under way -- one in the U.S. and another
in Europe -- but results aren't expected for several years. Many experts
say the screening decision should be made by the patient. Some men may
be happy not knowing if they have the disease, particularly if there is
no evidence early detection will reduce their risk of death. However,
many doctors believe early detection can save lives, and at the very least,
the condition can be monitored to make sure it isn't worsening. For men
considering whether to undergo screening, the cancer prevention and control
division of the Centers for Disease Control and Prevention has recently
published a prostate cancer screening decision guide. It is available
at the agency's Web site: www.cdc.gov/cancer/prostate/decisionguide/index.htm
[Top]
Flaxseed-Rich
Diet Blocks Prostate Cancer Growth and Development in Mice-(ET-15/07/2003)
A diet rich
in flaxseed seems to reduce the size, aggressiveness and severity of tumors
in mice that have been genetically engineered to develop prostate cancer,
according to new research from Duke University Medical Center. And in
3 percent of the mice, the flaxseed diet kept them from getting the disease
at all. "We are cautiously optimistic about these findings," said Wendy
Demark-Wahnefried, Ph.D., associate professor, division of urology and
senior author of the study that appears in the November 2002 issue of
the journal Urology. "The amount of flaxseed given to each mouse was 5
percent of its total food intake, which would be a very difficult amount
for humans to eat, but it does signal that we are on the right track and
need to continue research in this area." According to Demark-Wahnefried,
planned clinical trials must be completed before it can be concluded that
dietary flaxseed is a useful protective against prostate cancer in humans.
The research was
sponsored by the National Institute on Aging, the National Cancer Institute
and the Committee for Urologic Research Education and Development at Duke
University Medical Center. Clinical studies by other researchers have
suggested that dietary fiber reduces cancer risk, and omega-3 fatty acids
also have shown a protective benefit against cancer. Flaxseed is the richest
plant source of omega-3 fatty acids and is high in fiber. Also, flaxseed
is a source of lignan, a specific family of fiber-related compounds that
appear to play a role in influencing both estrogen and testosterone metabolism.
Since testosterone may be important in the progression of prostate cancer,
lignan could help inhibit the growth and development of the disease.
In the Duke study,
135 mice genetically engineered to develop prostate cancer were divided
into a control group and an experimental group. The experimental group
received a regular mouse diet, but 5 percent of the diet was in the form
of flaxseed. Half of the mice in both groups were fed their respective
diets for 20 weeks and the remainder for 30 weeks. At the 20- and 30-week
end points, the mice were autopsied to check for tumor growth and progression
of the disease to other organs. "Tumors in the untreated control group
were twice the size of tumors in the flaxseed group," said Xu Lin, M.D.,
research associate, division of urology and lead author of the study.
"The tumors were also less aggressive in the flaxseed group, and two of
the mice in the flaxseed group did not develop prostate cancer at all.
The rates of apoptosis (tumor cell death) were also higher in the flaxseed
group. And while it was not statistically significant, the flaxseed group
had fewer rates of the cancer spreading to other organs. " While the results
are promising, the researchers say they are not surprising.
The study is the
third in a series by the Duke Medical Center researchers to show the benefits
of flaxseed in reducing the growth and development of prostate cancer.
The first study, published in July 2001 in Urology, demonstrated that
a low-fat diet supplemented with flaxseed was associated with slower tumor
growth. In this pilot study, 25 men with prostate cancer began adding
ground flaxseed to their diets for 34 days. At the end of the study, the
men saw a drop in testosterone levels and a trend toward lower prostate
specific antigen (PSA) levels, a marker for prostate cancer. The diet
also was tolerated well and gave the authors hope for this dietary intervention.
The second study, published in the November-December 2001 issue of Anticancer
Research, examined the effect lignans have on prostate cancer cell lines.
This study showed that flaxseed-derived lignans inhibited the growth of
three distinct human prostate cancer cell lines through hormonally dependent
and independent mechanisms.
"So far we have observed
the suppression of prostate cancer in humans, mice and at the cellular
level," said Lin. "It's not a fluke or a coincidence. It's an encouraging
line of research." Demark-Wahnefried adds, "Our results are encouraging.
However, before we can truly state that flaxseed is beneficial in humans,
larger well-controlled trials are needed. The National Cancer Institute
has provided us with the support to conduct a randomized clinical trial
in 160 men with prostate cancer that will examine whether a low-fat diet,
flaxseed supplementation or a combination of low-fat diet and flaxseed
supplementation will be most effective in stopping prostate cancer cells
from dividing. That trial is currently under way."
[Top]
Eat
Your Whey: It May Protect against Prostate Cancer-(ET-15/07/2003)
New research
suggests that whey, a liquid byproduct from cheese production, may play
a role in helping prevent prostate cancer. When Ohio State University
food scientists treated human prostate cells in the lab with whey protein,
cellular levels of the antioxidant glutathione increased. Antioxidants
such as glutathione have been shown to control cancer-causing free radicals.
Cancer researchers suspect that the accumulation of free radicals plays
a role in the development of prostate cancer. In the current study, the
Ohio State scientists found that treating prostate cells with whey protein
elevated glutathione levels in the cells by up to 64 percent. "The buildup
of free radicals is associated with the onset of many chronic illnesses,
such as heart disease and cancer," said Joshua Bomser, a study co-author
and an assistant professor of food science and technology at Ohio State.
"And human prostate tissue is particularly susceptible to oxidative stress."
The study appears
in the journal Toxicology in Vitro. Bomser conducted the study with Kyle
Kent, a graduate student in the department of food science at Ohio State,
and W. James Harper, the J.T. "Stubby" Parker Chair in Food Science and
Technology, also at the university. The researchers treated human prostate
cells with two concentrations of whey protein for 48 hours and then measured
the levels of glutathione in the cells. Whey contains the amino acid cysteine
-- a key ingredient for making glutathione in the body. Surprisingly,
both treatments increased the levels of glutathione considerably. The
larger dose increased glutathione by 64 percent and the smaller dose,
which was half of the larger dose, increased levels by 60 percent. "The
small difference in glutathione levels between the two whey concentrations
suggests that it may not take much whey protein to get an effect in the
prostate cells," Bomser said. "In diseases like cancer, there's usually
a reduction in the body's overall capacity to deal with oxidative stress,"
he continued. "Keeping antioxidant levels elevated through diet and supplementation
may prevent the development of chronic disease."
The researchers treated
another batch of prostate cells with casein, the major protein found in
cheese. Casein doesn't contain the key ingredient for manufacturing glutathione,
and, as expected, glutathione levels in these cells did not increase.
"Unlike casein, whey proteins are rich in cysteine, an amino acid that
increases glutathione in the prostate," Kent said. "Cheese contains various
proteins that can influence the levels of different antioxidants in prostate
cells," Kent continued. "But cysteine is the amino acid that helps create
healthy glutathione levels in the prostate, and glutathione helps keep
free radicals under control." The researchers warn that simply eating
cheese won't ensure an increase in glutathione levels, because cysteine
is contained in the whey that's separated from cheese early in the cheese-making
process. But cysteine is also found in foods such as poultry, wheat, broccoli
and eggs. While whey protein supplements have become popular among body
builders, Bomser and his colleagues say that most people living in the
United States already get plenty of protein in their diet, so adding an
additional protein shake isn't necessary. They stress the importance of
a well balanced diet, adding that whey is a complete protein, one that
has the right amount of amino acids that are essential to our bodies.
[Top]
Bad
Gene Ups Prostate Cancer Risk in Black Men- (HealthDayNews-09/07/2003)
A gene called macrophage
scavenger receptor 1 (MSR1) plays an important role in the development
of prostate cancer in black American men. So says a study in the July
1 issue of Cancer Research. The finding comes from a larger project called
the Flint Men's Health Study, which is meant to identify prostate cancer
risk factors in black American men. "African-American men have the highest
incidence of prostate cancer in the world. The severity is higher and
they tend to die more quickly after diagnosis," study author Dr. Kathleen
Cooney, an associate professor of internal medicine at the University
of Michigan Comprehensive Cancer Center, says in a statement. "We don't
know why this is, but part of the difficulty is that African-American
men are underrepresented in most genetics studies," Cooney says.
This study included
black men, aged 40 to 79, living in Flint, Mich. DNA samples were collected
from 134 men diagnosed with prostate cancer and 340 men without the disease.
After analyzing the DNA samples, the researchers concluded that rare germ-line
MSR1 mutations were associated with an increased risk of prostate cancer.
Previous studies found the same association in white men. "This study
adds to an expanding body of evidence in support of germ-line MSR1 mutations
as risk factors for prostate cancer. Although our study was modest in
size, the public health burden of prostate cancer in the African-American
community warrants further attention to potential genetic risk factors,"
lead author Dr. David Miller, a urology resident at the University of
Michigan Medical School, says in a news release.
[Top]
First
Prostate Cancer Prevention Drug Found, but Not All Men Benefit- (NIH/National
Cancer Institute-02/07/2003)
Men who took finasteride,
a drug that affects male hormone levels, reduced their chances of getting
prostate cancer by nearly 25 percent compared to men who took a placebo,
according to results of a national study released today online by the
New England Journal of Medicine. These findings resulted in the early
closing of the study, called the Prostate Cancer Prevention Trial (PCPT),
which was coordinated by a network of researchers called the Southwest
Oncology Group (SWOG) and funded by the National Cancer Institute (NCI).
The 10-year trial, involving nearly 19,000 participants nationwide, was
originally scheduled to end in May 2004. "Finasteride is the first drug
found to reduce the risk of prostate cancer," said Ian Thompson, M.D.,
University of Texas Health Sciences Center, who led the study. "The drug
worked for men at low risk for prostate cancer, as well as those at high
risk." Age, PSA level at enrollment, family history of prostate cancer,
and race or ethnicity did not affect the drug's ability to prevent the
disease.
"There is a cautionary
note," said Thompson. "Men in the study who developed prostate cancer
while taking finasteride were more likely to have high-grade cancers,
which, when found in the general population, may spread quickly even if
the tumors are small. But, more than 97 percent of men who did develop
prostate cancer during this study had early-stage cancers, which are most
often curable." The reason men on finasteride had more high-grade tumors
is currently unknown, but the researchers are studying several possibilities.
The drug affects the appearance of prostate cancer cells, and this may
lead to a false estimate of tumor grade, which is determined visually
by a pathologist. Another possible explanation being examined is whether
finasteride truly causes more aggressive tumors to develop--either by
preventing only low-grade tumors, or by making the prostate gland more
favorable to aggressive tumors.
Prostate cancer is
the most common cancer in men, after skin cancer, and will affect nearly
221,000 men in the United States this year. About 29,000 men will die
of the disease. The disease--as well as its treatment, which sometimes
leads to impotence, urinary incontinence, and other problems--causes a
significant health burden for men.
Finasteride was approved
in 1992 at a 5 milligram (mg) dose for treating benign prostatic hyperplasia
(BPH), a noncancerous enlargement of the prostate that can cause problems
with urine flow. A few years later, the drug was approved at a 1 mg dose
to treat male pattern baldness. In PCPT, healthy men ages 55 and older
were randomly assigned to take either 5 mg finasteride or placebo daily
for seven years. Neither the participants nor their doctors knew which
men were assigned to take which pills. This type of study, called a double-blind,
placebo-controlled trial, is considered the scientific gold standard for
determining if an intervention works. Men chosen for PCPT showed no evidence
of prostate cancer at the start of the trial. To enter the study, men
needed to have a normal digital rectal exam (DRE) and a prostate specific
antigen (PSA) level of 3 nanograms/milliliter (ng/ml) or less. These tests
were repeated annually. The participants also agreed to have a prostate
biopsy after they had participated for seven years. At the time the trial
ended, about 9,000 men had undergone biopsies.
PCPT researchers
will continue to monitor the men who participated in the trial at the
more than 200 sites around the country. "What these men have already given
us is priceless," said Thompson. "But, we will continue to learn much
more. The participants provided us with blood and biopsy samples, and
this repository of biological materials will prove invaluable in learning
more about the molecular changes that happen as prostate cancer develops."
On March 3, 2003, the Data and Safety Monitoring Committee, an independent
body that periodically examined the study, advised that the trial be closed
early. The recommendation came because data already collected were sound,
and the conclusions were extremely unlikely to change with the addition
of more data.
By the close of the
study, prostate cancer had been found in about 18 percent of the men who
took finasteride, or 803 men out of 4,368. About 24 percent of men who
took placebo, or 1,147 men out of 4,692, also had been diagnosed with
prostate cancer. Many of the men with cancer had normal DREs and PSA levels,
and the disease was found only because the trial required an end-of-study
biopsy. Despite the fact that men taking finasteride had fewer prostate
cancers overall, they had a greater proportion of high-grade prostate
cancers. Overall, 6.4 percent of men on finasteride (280 men out of 4,368)
had high-grade tumors. For men on placebo, 5.1 percent (237 men out of
4,692) had high-grade cancers.
Having a low PSA
level did not correlate with the development of aggressive tumors--some
of the men in both groups of the trial had high-grade disease despite
PSA levels that would not have been a concern if the participants had
received routine screening outside of the trial. "Although a larger percentage
of men taking finasteride had tumors that appeared to be more aggressive
to a pathologist, we do not know if those tumors will act biologically
aggressive," said Ford. "We will follow these men long term to determine
whether a cancer that looks high grade in a man taking finasteride correlates
medically with aggressive disease."
The researchers regularly
monitored participants for side effects. Compared to men on placebo, more
men taking finasteride experienced sexual side effects at some point during
the study. On the other hand, urinary symptoms were reported by more men
taking placebo. "PCPT and its findings mark a milestone for the field
of cancer prevention, and we will continue to learn more in the years
to come," Ford said. "Finasteride's ability to prevent prostate cancer
has the potential to reduce the health care burden for this very common
disease. The next time men see their doctors, they may want to talk to
them about these findings."
Finasteride is just
one agent the NCI has been studying to prevent prostate cancer. Another
large prevention study currently underway, the Selenium and Vitamin E
Cancer Prevention Trial, or SELECT, is determining if these two dietary
supplements can protect against prostate cancer. SWOG, the same group
that coordinated PCPT, is conducting the SELECT study for NCI. "Men can
take finasteride and still participate in SELECT," said Charles A. Coltman
Jr., M.D., chairman of SWOG and director of the San Antonio Cancer Institute
in Texas.
[Top]
Too
Much Zinc Ups Prostate Cancer-(HealthDayNews-02/07/2003)
Men who overdose
on zinc supplements more than double their risk of prostate cancer, a
government study finds. The researchers looked at 46,974 men who were
involved in the Health Professionals Follow-Up study, and the increased
risk was seen in those who took more than 100 milligrams a day of zinc
supplements or used zinc supplements for more than 10 years. The report
appears in the July 2 issue of the Journal of the National Cancer Institute.
It's an important finding because prostate cancer is the second leading
cancer killer for American men, taking 30,000 lives a year. And 30 percent
to 40 percent of all men take one supplement or another, says study author
Dr. Michael F. Leitzmann, an epidemiological investigator at the National
Cancer Institute.
Zinc has long been
a target of prostate cancer research because it is found in high concentrations
in the prostate, but studies of its effects on malignancy have gotten
mixed results. One study released four years ago found an association
between daily doses of zinc and a reduced risk of the cancer. There isn't
necessarily a conflict between the two trials, says Dr. Janet Stanford,
a research professor of epidemiology at the Fred Hutchinson Cancer Research
Center in Seattle and a leader of the earlier study. "Our study was not
designed to assess supplement use," Stanford says. The new study is "intriguing,"
she says, and "does raise a question about the role of zinc in prostate
cancer. But it is not the basis for making decisions."
Leitzmann agrees,
noting his results might not conflict with those from the earlier study,
in part because the two trials used entirely different methods. The older
study asked men with prostate cancer if they had taken zinc supplements
and compared their answers with cancer-free men. The new study followed
men who started out cancer-free for 14 years, asking about their zinc
intake. The important point is that the risk was concentrated in men who
took the largest amounts of zinc for the longest time, Leitzmann says.
No increased risk was found in men who took up to 100 milligrams a day.
But those who took more than that amount daily were 2.29 times more likely
to develop the cancer than those who took less. And the risk was 2.37
times greater for men who took zinc supplements for 10 or more years.
Zinc is known to increase blood levels of insulin-like growth factor and
testosterone, both of which are directly related to prostate cancer, Leitzmann
says. It's possible malignancy occurs because high levels of zinc increase
the growth rate of slow-growing prostate cancers, he says. Not much is
known about modifiable risk factors for prostate cancer, Leitzmann says.
The best known risk factors are increasing age, a family history, and
race, with blacks at higher risk. Even with the latest findings, the evidence
that avoiding zinc supplementation might reduce prostate cancer risk "overall
is not very compelling," Leitzmann says. "This one study cannot conclusively
answer that question." But one obvious implication is that men "should
avoid supplements that contain multiple amounts of the recommended dietary
amounts," Leitzmann says.
[Top]
New
MRI Able to Pinpoint Smaller Tumors-(AP-18/06/2003)
An enhanced type
of MRI can detect much smaller tumors than ever before - some tinier than
a pea - in an advance that could open a new age in diagnosing cancer without
surgery, researchers say. The experimental technique examines the lymph
nodes for signs of spreading cancer. Doctors already routinely use MRIs
to check the lymph nodes to see whether cancer that originated somewhere
else in the body - say, in the breast or the prostate gland - is spreading.
But the enhanced technique proved superior to conventional MRIs when tested
with cancer that had spread from the prostate. And the leader of the research,
Dr. Mukesh Harisinghani, said his team has also had preliminary success
using the approach to detect the spread of breast, testicular, bladder
and kidney cancer.
In the prostate study,
the technique found 63 cancerous lymph nodes in 33 patients. Conventional
magnetic resonance imaging, or MRI, would have missed 71 percent of the
nodes, and the spreading cancer would have gone undetected in nine patients.
"Even if it only works this well for prostate cancer, it's a significant
advance," said Dr. Jeffrey Brown, a radiologist at Washington University
in St. Louis. Earlier detection of spreading prostate cancer would allow
more aggressive treatment sooner, help doctors track the response, and
spare some patients unnecessary removal of the prostate gland or lymph
nodes.
About 200,000 prostate
cancer cases are diagnosed each year, and 32,000 people die from it. The
Food and Drug Administration is considering whether to approve the new
technique. It is unclear when the FDA might decide. Dr. Samuel Wickline,
who studies imaging at Washington University, said this method and others
like it will eventually "allow us to diagnose things that you can't even
see with any imaging" now in use. The study, funded partly by the National
Cancer Institute, was carried out by Massachusetts General Hospital in
Boston and University Medical Center in Nijmegen, the Netherlands. The
findings appear in New England Journal of Medicine.
The method relies
on minuscule magnetic particles, known as nanoparticles, to enhance an
MRI. Acting like a television's contrast dial, the injected particles
collect in the immune system's lymph nodes and create a clearer separation
between dark and light areas in the image. Imaging systems have never
reliably shown tumors this small before anywhere in the body. Up to now,
the smallest tumors detectable by MRI have been about four-tenths of an
inch - the size of a fingernail. Conventional MRI uses a magnetic field,
which allows doctors to see enough only to gauge the size of lymph nodes.
Nodes bigger than four-tenths of an inch are generally considered cancerous;
however, they are not always cancerous, while some smaller nodes are.
The new technique shows detail within the nodes that reveals cancer's
presence.
The researchers gave
patients an imaging agent known as lymphotropic superparamagnetic nanoparticles,
which are specks of iron oxide less than a billionth of an inch across.
Normally, the liver sucks up imaging agents before they reach the lymph
nodes, but these particles are so small, they seep into the lymph system.
The technique appeared to work in cancerous lymph nodes from two-tenths
to four-tenths of an inch, which would normally go unnoticed with regular
MRI. It detected 96 percent of cancerous nodes that size, compared with
a detection rate of 29 percent for regular MRI, and it found 41 percent
of cancerous nodes smaller than two-tenths of an inch, which are invisible
to conventional MRI. When spreading cancer has already reached the lymph
nodes, doctors typically order radiation or hormonal treatments. The researchers
did not report any major side effects from the imaging agent. "I would
anticipate that it's going to get approved, and I would anticipate that
it's going to be a big seller," said Dr. Otis Brawley, a cancer specialist
at Emory University in Atlanta.
[Top]
Protein
Found Key in Prostate Cancer Spread-(Reuters Health-17/06/2003)
A protein
found in normal cells and some tumor cells may help block prostate cancers
from spreading, according to early study findings. In work with human
tissue samples, researchers had previously found that the protein, dubbed
RKIP, existed in average to high levels in normal prostate cells and in
prostate tumors that had not spread -- or metastasized -- to other parts
of the body. In contrast, RKIP was nearly absent in tumor cells that had
spread. Now, in work published in the Journal of the National Cancer Institute,
the same researchers found that adding RKIP back to metastatic prostate
cancer cells rendered them less adept at spreading. Dr. Zheng Fu and her
colleagues focused on RKIP after earlier work had shown the protein appeared
to be under-expressed in prostate tumor cells that had broken off and
spread.
"We found RKIP at
normal to high levels in normal prostate cells and in cells from the primary
tumor," study co-author Dr. Evan T. Keller of the University of Michigan
said in an interview with Reuters Health. "But it was virtually absent
in all the metastatic cells." To discover what role RKIP might play in
cancer's spread, the researchers genetically engineered metastatic prostate
cancer cells to again produce RKIP. These genetically engineered cells
were then injected into one group of mice. Unaltered cells were injected
into another group of mice for comparison. "By putting RKIP back, we ended
up with (an) over 70 percent reduction in metastasis," Keller said. "It
didn't affect the growth rate of the tumor itself. Instead, it somehow
inhibits the cells' ability to invade blood vessels."
For cancer cells
to spread to a new site, they must first be able to commandeer blood vessels
so that they will have fuel to grow, Keller explained. The new research
could lead to therapies to block tumors from metastasizing, according
to Keller. "Perhaps with gene therapy we could restore RKIP to these cells,"
he said. "Or if we understand the signaling pathways that this gene turns
on or off, we could inhibit those pathways." An editorial published with
the report notes: "The molecular understanding of cancer metastasis has
taken yet another step forward with findings published in this issue of
the Journal." The results signal "a major step toward controlling the
most deadly attribute of cancer cells," write Drs. Danny R. Welch, of
the University of Alabama at Birmingham, and Kent W. Hunter, of the National
Cancer Institute.
[Top]
Eat
Your Whey: It May Protect against Prostate Cancer-(ET-28/05/2003)
New research
suggests that whey, a liquid byproduct from cheese production, may play
a role in helping prevent prostate cancer. When Ohio State University
food scientists treated human prostate cells in the lab with whey protein,
cellular levels of the antioxidant glutathione increased. Antioxidants
such as glutathione have been shown to control cancer-causing free radicals.
Cancer researchers suspect that the accumulation of free radicals plays
a role in the development of prostate cancer. In the current study, the
Ohio State scientists found that treating prostate cells with whey protein
elevated glutathione levels in the cells by up to 64 percent. "The buildup
of free radicals is associated with the onset of many chronic illnesses,
such as heart disease and cancer," said Joshua Bomser, a study co-author
and an assistant professor of food science and technology at Ohio State.
"And human prostate tissue is particularly susceptible to oxidative stress."
The study appears in the journal Toxicology in Vitro.
Bomser conducted
the study with Kyle Kent, a graduate student in the department of food
science at Ohio State, and W. James Harper, the J.T. "Stubby" Parker Chair
in Food Science and Technology, also at the university. The researchers
treated human prostate cells with two concentrations of whey protein for
48 hours and then measured the levels of glutathione in the cells. Whey
contains the amino acid cysteine -- a key ingredient for making glutathione
in the body. Surprisingly, both treatments increased the levels of glutathione
considerably. The larger dose increased glutathione by 64 percent and
the smaller dose, which was half of the larger dose, increased levels
by 60 percent. "The small difference in glutathione levels between the
two whey concentrations suggests that it may not take much whey protein
to get an effect in the prostate cells," Bomser said. "In diseases like
cancer, there's usually a reduction in the body's overall capacity to
deal with oxidative stress," he continued. "Keeping antioxidant levels
elevated through diet and supplementation may prevent the development
of chronic disease."
The researchers treated
another batch of prostate cells with casein, the major protein found in
cheese. Casein doesn't contain the key ingredient for manufacturing glutathione,
and, as expected, glutathione levels in these cells did not increase.
"Unlike casein, whey proteins are rich in cysteine, an amino acid that
increases glutathione in the prostate," Kent said. "Cheese contains various
proteins that can influence the levels of different antioxidants in prostate
cells," Kent continued. "But cysteine is the amino acid that helps create
healthy glutathione levels in the prostate, and glutathione helps keep
free radicals under control." The researchers warn that simply eating
cheese won't ensure an increase in glutathione levels, because cysteine
is contained in the whey that's separated from cheese early in the cheese-making
process. But cysteine is also found in foods such as poultry, wheat, broccoli
and eggs. While whey protein supplements have become popular among body
builders, Bomser and his colleagues say that most people living in the
United States already get plenty of protein in their diet, so adding an
additional protein shake isn't necessary. They stress the importance of
a well balanced diet, adding that whey is a complete protein, one that
has the right amount of amino acids that are essential to our bodies.
[Top]
Families
Sought in Hunt for Male Cancer Genes-(Reuters-27/05/2003)
British scientists
launched a national hunt for families with a history of testicular or
prostate cancer to help in the search for genes related to the diseases.
They are looking for men who have three or more relatives who developed
prostate cancer before the age of 70 or who have two or more family members
with testicular cancer. By examining the genetic profiles of men with
the disease, they hope to identify genes that increase a man's risk of
developing the cancers. "Fifteen percent of prostate cancer and up to
30 percent of testicular cancer may be due to an inherited predisposition,"
Professor Colin Cooper of the Institute of Cancer Research, told a news
conference. "Genes are important because they provide targets for new
drugs and they help to determine the course of the disease," he added.
Scientists have discovered
genes involved in breast cancer, but the search for male cancer genes
has lagged behind. Six possible sites for prostate cancer genes and one
for testicular cancer have been identified, and researchers are hoping
the genetic studies will help them pinpoint the culprits. Cooper said
testicular is the most genetic of all cancers. A man with a brother who
has testicular cancer has an eight to 10-fold increase in the chances
of getting it himself. Men with a family history of either testicular
or prostate cancer can contact their family doctor or a specialist at
the Institute for Cancer Research (www.icr.ac.uk) if they want to take
part in the study.
[Top]
Broccoli
Could Be Prostate Cancer Fighter-(HealthScoutNews-14/05/2003)
It's no secret that
men who eat lots of vegetables seem more likely to avoid prostate cancer,
but researchers now think a chemical in broccoli and cauliflower could
help doctors treat the disease, too. No one has tested the chemical on
humans yet, however, and it may take years to turn it into a usable drug.
"It's interesting early work, but it's a long way from something going
on in a test tube to exactly what goes on in humans," says Dr. Durado
Brooks, director of prostate and colorectal cancers for the American Cancer
Society. Prostate cancer is the most commonly diagnosed cancer among men
in the United States and kills about 30,000 each year, according to the
National Prostate Cancer Coalition.
A number of treatments
are available, but side effects commonly include incontinence and impotence.
Prostate cancer rates are lower in countries where people eat plenty of
fruits and vegetables, although the exact link between diet and the disease
isn't clear, Brooks says. Researchers at the University of California
at Berkeley decided to investigate the cancer-fighting effects of chemicals
in cruciferous vegetables such as broccoli, cauliflower, kale, Brussels
sprouts and cabbage. "We realized that what was missing was a comprehensive
study of how these natural compounds affect the growth and function of
reproductive cancer cells," says study co-author Gary Firestone, a professor
of molecular and cell biology at the University of California at Berkeley.
The researchers found
that a chemical known as 3,3'-diindolylmethane (DIM), a byproduct of eating
cruciferous vegetables, appeared to prevent the growth of breast cancer
cells. They next turned to prostate cancer cells. The researchers found
that prostate cancer cells treated with DIM grew 70 percent slower than
untreated cells. Their research will appear in the June 6 issue of the
Journal of Biological Chemistry. The chemical appears to prevent cancer
cells from receiving signals from the hormone testosterone, Firestone
says. That, in turn, prevents the cells from growing. By contrast, traditional
hormone therapy for prostate cancer patients is designed to prevent testosterone
from getting to the cells in the first place. "You cut off the signal
that makes the prostate cancer cells grow," Firestone says. It's possible
that the chemical could be used in combination with hormone therapy, Firestone
says, letting doctors dampen the side effects of lowering testosterone
levels. Producing drugs from the vegetables may be easy and inexpensive,
he adds: "There's a lot of broccoli and cabbage, and you should be able
to obtain a lot of this chemical at a very cheap price."
However, Brooks says
hormone treatment is much less common than other prostate cancer treatments.
Surgery and radiation are the usual treatments. Research into chemicals
derived from vegetables may be more important in terms of prevention,
says Satya Narayan, an associate professor of anatomy and cell biology
at the University of Florida. "These compounds may be of greater importance
for prostate cancer prevention at the early stages of the prostate cancer
development, instead of at the later stages when the cancer is advanced."
But it's still not clear how many vegetables men would need to eat to
protect themselves from getting prostate cancer in the first place.
[Top]
Research
Helps Prostate Cancer Victims-(ET-07/05/2003)
Scientists
at Baylor College of Medicine are quickly catching up with a killer. They
have discovered a gene that could help destroy prostate cancer before
it strikes 30,000 men this year -- men like Tony Masraff. "I'm tired,
in a way, of doctors and people talking about, 'Oh it's a slow-growing
cancer. You don't need to worry about it as much,'" Masraff said. There
has not been a wealth of research for prostate cancer, so its victims
have few options -- surgery or chemotherapy -- and they often cause impotence.
"They belittle sexual dysfunction, the incontinence," Masraff said. So
Masraff, a restaurateur in the Galleria area, launched his own battle
to raise money. "To me, my quality of life was much more important than
how long I'm going to live," Masraff said. Since research relies on money,
Masraff wanted to make a difference, one step at a time. "I'll run the
marathon. Well, I've never run in my life," Masraff said. With overwhelming
support, he finished the race, and raised $100,000 for prostate cancer
research. It helped Dr. Timothy Thompson and his team at Baylor.
They said that they
have discovered a gene with a protein that kills cancer and tells the
body to keep killing it. "It's almost like calling in armed forces. This
gene recruits other troops if you will, other immune cells, to come in
and use the body's own response mechanisms to eliminate cancer," Thompson
said. Thompson's research is so promising that clinical trials will begin
next year. Anyone interested in becoming a part of the trials should contact
Baylor College of Medicine at (713) 799-8718 to get on the list for phase
one. Masraff has posted information online about prostate cancer and research.
For more information, visit www.masraffs.com/prostatecancer.htm
[Top]
Viagra
May Restore Erections After Prostate Surgery-(Reuters Health-28/04/2003)
Men who undergo
surgery for prostate cancer may ward off problems with erections by taking
Viagra every night for nine months after surgery, researchers said. According
to the report, men who took nightly Viagra (sildenafil) for nine months
after having their prostate removed in a surgery known as radical prostatectomy
were more than seven times as likely to regain their normal, pre-operative
erectile functioning as men who received a placebo, or inactive, drug.
These findings suggest that along with treating erectile dysfunction,
Viagra can also prevent the condition in the first place, study author
Dr. Harin Padma-Nathan of the University of Southern California in Los
Angeles told Reuters Health. "The results of this study are so dramatic
that every man undergoing (radical) prostatectomy should consider this
if he is interested in preserving erections," Padma-Nathan said. Although
newer forms of the surgery do not involve cutting the nerves leading to
and from the penis, which are crucial to erections, even this "nerve-sparing"
radical prostatectomy can injure these nerves, causing problems.
During the procedure,
the researchers asked 23 and 28 men to take 50 milligrams and 100 milligrams
of Viagra, respectively, every night for nine months staring four weeks
after surgery. Another 25 men took a placebo during the same time period.
None of the men knew whether they were taking Viagra or placebo. All of
the men had normal erectile function before surgery. After nine months
of treatment, study participants then spent another eight weeks without
taking any medication. Padma-Nathan and his colleagues discovered that
27 percent of men who had received Viagra -- regardless of dose -- had
regained full erectile functioning, equal to what they reported before
undergoing surgery, a finding seen in only 4 percent of men given placebo.
These findings, presented during the annual scientific meeting of the
American Urological Association in Chicago, suggest that Viagra "prevents
the degeneration of erection function following the surgery," Padma-Nathan
said in an interview. And the difference between using and not using Viagra
was "dramatic," he added. "If you don't do anything, it's not very good,"
he said. "Intervention certainly made it a whole lot better."
Typically, men take
either 50 or 100 milligrams of Viagra to treat erectile dysfunction, and
the current findings suggest that the lower dose is just as effective
at preventing the problem, he added. Previous research in animals suggests
that Viagra, along with increasing blood flow to the penis, may actually
help repair nerves that have been damaged during surgery, Padma-Nathan
noted. None of the men taking Viagra reported any serious side effects
from the medication, and only two dropped out of the study, citing headache
and fatigue, the researcher said. Although taking Viagra every night for
nine months could be a significant expense for some patients, Padma-Nathan
noted that men who typically undergo radical prostatectomy start taking
Viagra after surgery and use it to treat erectile problems for the rest
of their lives. Given that the men included in this study were in their
mid-50s, that represents a long time to take the drug, he said. "It's
actually cheaper to use it continuously for nine months and stopping it
altogether than using it intermittently for a couple times a week for
the rest of their lives," Padma-Nathan said. The study was funded by Pfizer
Inc., maker of Viagra.
[Top]
Study
Suggests Western Diet Tied to Prostate Cancer-(Reuters Health-28/04/2003)
Prostate
cancer is 10 times more common in the United States than Japan and preliminary
research suggests that differences in diet may be a reason why. There
has been much speculation that the Western diet is a factor because when
Japanese men move to the U.S. and start eating plenty of high-fat burgers
and pizza and less soy, their risk of prostate cancer increases. "Within
one generation, the prostate cancer incidence begins skyrocketing," said
study author Dr. Leonard S. Marks, a clinical associate professor of urology
at the University of California at Los Angeles. In a new study at a meeting
of the American Urological Association in Chicago, Marks and colleagues
examined blood and prostate cancer tissue samples and compared health
data from 50 men who had undergone surgery to remove a cancerous prostate
gland. Half of the men lived in Japan, while the other half were Los Angeles
residents born in the U.S. to Japanese parents. As such, both groups had
similar genetic roots. But there were marked differences in what they
ate. The Japanese-American men reported eating a diet substantially higher
in animal fat. Not surprisingly, they also had a greater percentage of
body fat and higher triglyceride levels in their blood. The native Japanese
men ate more soy than the Japanese-American men. Soy has been thought
to possibly offer protection against prostate cancer. "Soy didn't protect
these men," Marks said, "but soy may be protecting many other men who
don't get prostate cancer in Japan."
While the prostate
cancer samples from the two groups appeared similar, detailed analysis
of the tumor cells' genetic material told another story. "Since the DNA
was arranged differently, there may be a gene-nutrient interaction responsible
for the differences," Marks said. "The cancers look the same but their
genesis appears to be different, and that may be a result of diet," he
told Reuters Health. Still, much more research is needed to explain why
prostate cancer rates vary widely around the world. "Does this study prove
why the differences are there? It doesn't," Marks said. "It's a first
step."
[Top]
Research
Sheds New Light On Why Some Prostate Cancers Become Untreatable-(Yahoo
News-28/04/2003)
Three new studies
by researchers at UC Davis Cancer Center provide new pieces to the puzzle
of why some prostate cancers become resistant to androgen suppression
therapy. The studies were presented Sunday afternoon at the 2003 annual
meeting of the American Urological Association. Of the nearly 190,000
men in the United States who develop prostate cancer every year, a substantial
proportion will require androgen suppression therapy to reduce levels
of male hormones-a treatment that can shrink prostate cancers or slow
their growth. Hormone suppression therapy eventually fails, however, as
prostate cancer cells adapt to an androgen-depleted environment, a state
known as androgen independence. When this happens, few treatment options
remain. Determining how androgen independence develops, and how the process
can be derailed, is a chief focus of prostate cancer research at UC Davis.
"If we could prevent androgen independence from happening, it would have
a dramatic impact on treatment and outcomes for prostate cancer," says
Ralph deVere White, chair of urology at UC Davis School of Medicine and
Medical Center and director of the UC Davis Cancer Center.
Two of the studies
presented report new information about p53's role in androgen independence.
Mutations in p53 are seen in two out of three prostate cancers that have
developed androgen independence. In one of the studies, deVere White and
his colleagues demonstrated that four particular p53 mutations -- G245S,
R248W, R273C and R273H -- facilitate androgen-independent growth in human
prostate cells. The researchers were able to grow the four mutant cell
lines in androgen-free conditions both in cell culture and in female laboratory
mice. In addition, the researchers successfully used siRNA technology
to target an siRNA molecule to the R273H mutation and down-regulate (suppress)
its activity -- suggesting that siRNA technology may have therapeutic
value in the treatment of hormone-independent prostate cancer. In a second
study, Clifford G. Tepper and his colleagues used microarray technology
to hunt for specific genes that contribute to androgen independence.
They reported that
over-expression of one gene, known as Id-1, is a feature of androgen-independent
tumors with p53 mutations. In order to identify Id-1, the researchers
profiled more than 12,000 genes. They found 21 that are over-expressed
in cells harboring G245S, R248W, R273C or R273H. Further analysis singled
out one, the Id-1 gene, which produces a protein known to suppress cell
aging and promote tumor aggressiveness. In the third study, Christopher
Evans and his colleagues report development of the first in vivo neuroendocrine
model to study the progression of prostate cancer cells from androgen
dependence to androgen independence. Using the model, the researchers
demonstrated that neuroendocrine differentiation contributes to androgen-independent
prostate cancer growth, proliferation and migration in an androgren-free
environment.
[Top]
Drug
Study Could Boost Prostate Cancer Survivability-(Yahoo News-25/04/2003)
This year in the
United States, nearly 221,000 men will be told they have prostate cancer.
About 30 percent of those cancers will have already spread outside the
prostate. Now, doctors have discovered a way to keep it from spreading
even further. Robert Miller is a force in front of his congregation. Preaching
is his life's work. His life's battle started 11 years ago when he was
diagnosed with prostate cancer. "All I heard was the word cancer and I'm
thinking cancer, death, cancer, death," Miller tells Ivanhoe. PSA levels,
the markers for prostate cancer, are considered high at four. At diagnosis,
Miller's levels were nearly 80. His prostate was removed, but the cancer
stayed behind. He soon found oncologist Michael Carducci, M.D.
When prostate cancer
spreads, it first goes to the bones. Dr. Carducci is studying the drug
atrasentan to keep the cancer from getting there. "This may not necessarily
kill cancer cells per se, it may slow prostate cancer down to a trickle,"
says Dr. Carducci, of the Kimmel Cancer Center at Johns Hopkins University
in Baltimore. It does that by targeting endothelin -- a protein overproduced
in men with prostate cancer that has spread. Dr. Carducci says, "We get
to the lock before endothelin does and therefore, the cancer cells never
see this growth factor, this protein that really stimulates further growth."
Studies show there was a 52-percent delay in the time it took for the
cancer to progress. Miller still has cancer, but it hasn't reached his
bones. He says, "Eleven years ago, I never thought I would see 59. I am
satisfied that God allowed me to live this long."
[Top]
Can
Lifestyle Changes Stop Prostate Cancer?- (HealthScoutNews - 28/04/2003)
Changes in lifestyle
can reverse the progress of prostate cancer, a leading proponent of alternative
medicine says in a claim met with interested skepticism by medical experts.
The claim was made in a presentation Monday by Dr. Dean Ornish, founder
and director of the Preventive Medicine Research Institute in Sausalito,
Calif., at the annual meeting of the American Urological Association in
Chicago. Ornish has been preaching lifestyle change as a way to reverse
heart disease for years, in medical journals and five best-selling books.
His prescription calls for a low-fat vegan diet supplemented with soy
and oxidants, moderate aerobic exercise, stress management and psychosocial
group support. Now he says the same regimen lowered levels of prostate-specific
antigen (PSA), a marker of the cancer, in a one-year study. The study
included 87 men with diagnosed prostate cancer at an early stage, when
doctors often choose to do nothing while they check on the progress of
the tumor -- "watchful waiting," in medical terms.
In the study, 41
of the men were assigned to observe the Ornish regimen carefully, under
supervision. The others were allowed to follow the regimen if they chose,
with no supervision. At the end of three months, PSA levels dropped by
5 percent in the group following the regimen but rose by 1 percent in
the control group, Ornish says. The difference in PSA levels was greater
after one year: down by 3 percent in the regimen group, up 7 percent in
the control group. The regimen must be followed precisely to achieve its
full results, Ornish stresses. Most of the men in the control group tried
to follow the regimen, with middling success; their PSA levels rose --
but not as much as would have happened if they had not adopted some of
the measures, he maintains.
The study's reliance
on PSA levels, however, is seen as a major problem by Andrew Vickers,
an assistant attending research methodologist at Memorial Sloan-Kettering
Cancer Center in New York. "When you get down to it, no one should care
about the PSA level," he says. "It is widely used, but one has to be cautious
in interpreting it. It is a marker of cancer growth, but not necessarily
a one-to-one marker." What Vickers would like to see are measurements
of how the cancer is affecting the patients' quality of life. "The results
they show are highly provocative, but they are not measuring anything
that makes a difference in someone's life," he says. Dr. B. Jay Brooks,
chief of hematology/oncology at the Ochsner Clinic in Baton Rouge, La.,
also looks at the study with a skeptical eye. "This was an extremely small
study, and the endpoint was a rise in PSA, which is not necessarily related
to the progress of the cancer," Brooks says. "The difference between the
experimental group and the control group was extremely small and barely
reached statistical significance." It is "an interesting concept," Brooks
adds, "but this needs to be expanded to a larger group of patients and
followed for a long period of time, perhaps five years." "If it were me
or any of my patients, I would certainly not rely on a change in lifestyle
to affect a proven diagnosis," Brooks sums up.
[Top]
Prostate
Cancer Patients Appear Not to Experience Genetic Damage from Soy Isoflavones-(Cancer.com-21/04/2003)
According to an article
recently published in the American Journal of Clinical Nutrition, soy
isoflavones appear not to damage DNA of cancer patients or healthy volunteers.
The prostate is a male sex gland that is located between the bladder and
the rectum and is responsible for creating a component of semen. Several
treatment options exist for patients with prostate cancer, including watchful
waiting, surgical removal of the prostate (radical prostatectomy), radiation
therapy, cryosurgery, and/or hormone therapy. Researchers are also investigating
complementary and alternative medicine (CAM) therapies. CAM consists of
various therapies, such as acupuncture, massage therapy, and vitamin supplementation.
Clinical research into the efficacy of specific CAM therapies on treating
cancer, managing symptoms, and/or promoting wellness provides evidence
for cancer patients and their physicians seeking to make informed decisions.
Soy is sometimes utilized as a type of CAM and categorized as a biologic/orthomolecular
therapy. Soy comes from soybeans, a plant indigenous to east Asia.
Laboratory research
has isolated components of soy, known as isoflavones, that are believed
to be its active ingredients. Isoflavone is the general name for a class
of compounds that include genistein, daidzein and glycitein. These substances
appear to act as phytoestrogens (plant estrogens), exerting weak estrogen
effects in the body. Several studies have suggested that isoflavones may
help prevent cancer, although clinical trials are needed to confirm these
findings. In addition, soy has been promoted as a potential therapy for
breast and prostate cancer patients. However, in vitro research has indicated
that soy may cause DNA damage to human cells. In the current study, 20
prostate cancer patients received daily doses of 300 mg genistein for
28 days. Over the following 56 days, each patient consumed 600 mg of genistein
each day. At the start of the study, researchers conducted laboratory
tests on peripheral lymphocytes (a type of white blood cell) to determine
baseline DNA damage in each patient. Throughout the study, these tests
were repeated to monitor changes in frequency of broken DNA strands and
rearrangement of genes on DNA.
Six healthy volunteers
also underwent testing. Concurrently, an in vitro study was conducted
to determine the effects of this specific genistein on cultured human
cells. The study reported no changes in the group average or individual
levels of DNA damage. Surprisingly, one test of DNA damage exhibited a
significant decrease within the first 28 days of the trial. As suggested
by previous research, however, genistein did produce genetic damage in
cultured human cells. These researchers concluded that while in vitro
research suggests that genistein can impair DNA, it appears not to induce
such damage in human subjects. Additional resea |
