New pathway could present an
intervention point for cancer treatment
A new cellular pathway leads to
destruction of a protein that promotes growth of breast, prostate and similar cancers and
could provide a new avenue through which to pursue treatment of such diseases, said a
researcher at Baylor College of Medicine.
"It is another intervention point
where one can now attack tumors. It's especially important for endocrine tumors such as
those of the breast, prostate, ovary and pituitary gland," said Dr. Bert O'Malley,
chair of the BCM department of molecular and cellular biology. O'Malley is senior author
of a report on the research that appears in the current issue of the journal Cell and a
faculty member in the College's Graduate School of Biomedical Sciences.
O'Malley and his colleagues concentrated
their efforts on a powerful oncogene or cancer-promoting gene called the steroid receptor
coactivator (SRC) 3 which is also a powerful promoter of tumor growth.
"In high concentrations, it drives
the cells to relentless replications," O'Malley said.
However, studies in the laboratory showed
that another molecule called REG-gamma takes SRC3 to the proteasome where it is destroyed.
"Because REG-gamma does this to
SRC3, it is a tumor suppressor," said O'Malley.
In breast cancer, when levels of
REG-gamma are low, SRC3 levels can be high, resulting in tumor growth, said O'Malley.
"This is an important pathway for
SRC3 degradation that has never been described," said O'Malley. Other modes of taking
proteins to the proteasome for destruction involve adding a molecule called ubiquitin and
using energy.
"This molecule does not require
ubiquitin or an energy source," he said. "It's a really strange and different
molecule for that reason.
He and members of his laboratory plan to
determine if the molecule controls similar proteins involved in tumor promotion as well.
Other members of the team that worked on
the project include: Drs. Xiaotao Li, David M. Lonard, Sun Yun Jung, Anna Malovannaya, Qin
Feng, Jun Qin, Sophia Y. Tsai and Ming-Jer Tsai.
Source: Baylor College of Medicine
Research improves hopes for
cancer vaccine
A special stretch of genetic material may
turn off the immune suppression that stymies attempts to fight cancer with a vaccine, said
researchers at Baylor College of Medicine at Houston.
In a report in today's issue of the
journal Science, Dr. Rong-Fu Wang, a professor in the BCM Center for Cell and Gene Therapy
and Department of Immunology, and his colleagues describe a new strategy to turn off the
function of a special group of T cells to suppress immune response to tumors and even
infectious diseases.
"Since 1995, many groups have tried
to develop a vaccine for the treatment of cancer," said Wang, also a member of the
faculty of the BCM Graduate School of Biomedical Sciences. "The only problem is that
after 10 years of clinical trials, the data suggest that you can induce (cancer)
antigen-specific immune responses, but such responses are too weak and transient to
eradicate tumor cells."
The answer lies in a group of cells
called CD4+ regulatory T cells (Treg for short). These cells have the ability to suppress
the body's natural immune response. If they are depleted, autoimmune diseases will result
because the immune system is unchecked and goes on to attack the body's own tissues.
His group previously reported the
existence of tumor-specific Treg cells at tumor sites. "Thus, the tumor cells use
these Treg cells to protect themselves," said Wang. "In fact, tumor cells can
actively recruit and activate them to turn on their immune suppressive function."
One way to stop this action is to simply
wipe out the cells with chemoagents or a specific antibody.
"But you may also deplete the good
cells needed for fighting cancer," said Wang.
He and his group identified particular
ligands (a special stretch of guanosine-containing DNA material) that can bind
specifically to a particular receptor called human Toll-like receptor 8 and then turn off
the suppressive function of Treg cells. Treatment of Treg cells with these ligands
converts suppressive Treg cells into non-suppressive T cells.
"In fact, in some cases, this
treatment actually enhanced anti-tumor immunity," he said.
He hopes that clinical trials with these
special ligands in patients with cancer can get underway quickly.
"It could have a huge impact on
cancer therapy or treatment of infectious disease," said Wang. "It could boost
response to cancer vaccine as well."
Others who participated in this research
include: Drs. Guangyong Peng, Yukiko Kiniwa, Kui shin Voo, Tihui Fu, and Yanchun Li; and
Zhong Guo, Weiyi Peng, Daniel Y. Wang, and Helen Y. Wang, all of BCM. This research was
supported by the National Institutes of Health and the Cancer Research Institute.
Source: Baylor College of Medicine
Research breakthrough
pinpoints aim of ion beams fired at cancer tumors
Nonsurgical cancer therapy that destroys
tumors but leaves healthy surrounding tissue intact could be available at every hospital
if research reported this week in the journal Nature eventually comes to fruition.
The Los Alamos National Laboratory
Trident laser team, in collaboration with researchers from the University of Nevada, Reno
and elsewhere, has succeeded in concentrating the intensity of a laser-driven carbon ion
beam into a narrow range.
This work builds upon past research led
by the University of Nevada that discovered much higher quality laser proton beams from
laser acceleration as opposed to conventional particle acceleration.
Producing carbon ion beams and limiting
their spread removes the major impediment to improving such applications as tumor
irradiation therapy.
Many technological challenges still have
to be met to develop a compact particle generator that could be used in a hospital
setting. No clinical trials are imminent.
This research also opens up opportunities
for advances in nuclear fusion applications.
The article, "Laser acceleration of
monenergetic MeV ion beams," will be published Jan. 26. This research was supported
by the Los Alamos National Laboratory Directed Research and Development program. The
University of Nevada was also supported by the Department of Energy's National Nuclear
Security Administration through the University of Nevada.
Source: University of Nevada
2/3 of cancer deaths related to
tobacco use and diet
Chemical Carcinogenesis Program - Karam
El-Bayoumy, PhD, Program Leader
In the United States, nearly two-thirds
of cancer deaths can be linked to tobacco use and diet. Tobacco consumption is directly
related to cancer of the lung, mouth, larynx, esophagus, bladder, kidney, pancreas,
leukemia, and cervix. More recent studies are now providing new information linking
tobacco smoking with breast and colon cancer, and suggest that tobacco smoking also
enhances metastasis of the prostate. Excess or deficiencies of certain dietary components
can account for cancer of the colon, breast, prostate, and stomach. The predominance of
environment over genes in cancer causation has been suggested. The overall research
direction in this program is to uncover, by using a step-wise approach, exactly how cancer
develops, and then provide the means for cancer prevention.
To reduce the incidence and mortality of
major cancers, observations from studies involving people (epidemiological studies) direct
our basic research in this Program to the following:
a) Understanding the mechanisms by which
chemicals found in our environment induce cancer. We focus on chemicals that have been
detected and fully characterized in tobacco smoke, diet and urban air pollution.
Carcinogenesis (cancer development) is a multi-step process that takes 20-30 years in
people, and in this program, we focus on understanding the molecular pathways by which
normal cells progress to the first definable stage of cancer;
b) Identifying sensitive and selective
markers in preclinical investigations (laboratory animals) as useful tools for the
assessment of human exposure and risk assessment to cancer causing agents; and
c) Developing mechanism-based
chemopreventive agents and dietary components that can inhibit specific molecular targets
involved in the carcinogenic process. Chemoprevention is defined as the use of naturally
occurring or synthetic agents that can inhibit, delay, and/or reverse the carcinogenic
process.
More
(n-3) Fatty Acids and Cancer
Therapy
W. Elaine Hardman
Pennington Biomedical Research Center,
Louisiana State University, Baton Rouge, LA 70808
Supplementing the diet of tumor-bearing mice or rats with oils containing (n-3) (omega-3)
or with purified (n-3) fatty acids has slowed the growth of various types of cancers,
including lung, colon, mammary, and prostate. The efficacy of cancer chemotherapy drugs
such as doxorubicin, epirubicin, CPT-11, 5-fluorouracil, and tamoxifen, and of radiation
therapy has been improved when the diet included (n-3) fatty acids. Some potential
mechanisms for the activity of (n-3) fatty acids against cancer include modulation of
eicosanoid production and inflammation, angiogenesis, proliferation, susceptibility for
apoptosis, and estrogen signaling.
In humans, (n-3) fatty acids have also
been used to suppress cancer-associated cachexia and to improve the quality of life. In
one study, the response to chemotherapy therapy was better in breast cancer patients with
higher levels of (n-3) fatty acids in adipose tissue [indicating past consumption of (n-3)
fatty acids] than in patients with lower levels of (n-3) fatty acids. Thus, in
combination with standard treatments, supplementing the diet with (n-3) fatty acids may be
a nontoxic means to improve cancer treatment outcomes and may slow or prevent recurrence
of cancer. Used alone, an (n-3) supplement may be a useful alternative therapy
for patients who are not candidates for standard toxic cancer therapies.
Nutrition and cancer: A review of
the evidence for an anti-cancer diet
It has been estimated that 30–40
percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity,
nutrient sparse foods such as concentrated sugars and refined flour products that
contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake,
consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to
excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant
portions of fruits and vegetables will lower cancer risk. Allium and cruciferous
vegetables are especially beneficial, with broccoli sprouts being the densest source of
sulforophane. Protective elements in a cancer prevention diet include selenium, folic
acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids
(a-carotene, ß-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited
benefits orally, but could be very beneficial intravenously. Supplementary use of oral
digestive enzymes and probiotics also has merit as anticancer dietary measures. When a
diet is compiled according to the guidelines here it is likely that there would be at
least a 60–70 percent decrease in breast, colorectal, and prostate cancers, and even
a 40–50 percent decrease in lung cancer, along with similar reductions in cancers at
other sites. Such a diet would be conducive to preventing cancer and would favor recovery
from cancer as well.
Full article here
Vitamin C and cancer
Pharmacologic ascorbic acid
concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen
peroxide to tissues
Qi Chen *, , Michael Graham Espey ,
Murali C. Krishna , James B. Mitchell , Christopher P. Corpe *, Garry R. Buettner , Emily
Shacter and Mark Levine *, ¶
*Molecular and Clinical Nutrition
Section, National Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, MD 20892; Radiation Biology Branch, National Cancer
Institute, National Institutes of Health, Bethesda, MD 20892; Free Radical and Radiation
Biology Program, University of Iowa, Iowa City, IA 52242-1101; and Laboratory of
Biochemistry, Center for Drug Evaluation and Research, Food and Drug Administration,
Bethesda, MD 20892
Human pharmacokinetics data
indicate that i.v. ascorbic acid (ascorbate) in pharmacologic concentrations could have an
unanticipated role in cancer treatment.
Our goals here were to test whether
ascorbate killed cancer cells selectively, and if so, to determine mechanisms, using
clinically relevant conditions. Cell death in 10 cancer and 4 normal cell types was
measured by using 1-h exposures. Normal cells were unaffected by 20 mM ascorbate, whereas
5 cancer lines had EC50 values of <4 mM, a concentration easily achievable i.v. Human
lymphoma cells were studied in detail because of their sensitivity to ascorbate (EC50 of
0.5 mM) and suitability for addressing mechanisms.
Extracellular but not intracellular
ascorbate mediated cell death, which occurred by apoptosis and pyknosis/necrosis. Cell
death was independent of metal chelators and absolutely dependent on H2O2 formation. Cell
death from H2O2 added to cells was identical to that found when H2O2 was generated by
ascorbate treatment. H2O2 generation was dependent on ascorbate concentration, incubation
time, and the presence of 0.5-10% serum, and displayed a linear relationship with
ascorbate radical formation. Although ascorbate addition to medium generated H2O2,
ascorbate addition to blood generated no detectable H2O2 and only trace detectable
ascorbate radical.
Taken together, these data indicate that
ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for
formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues.
These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have
unexpected implications for treatment of infections where H2O2 may be beneficial.
Beer and cancer prevention
A compound found only in hops and the
main product they are used in - beer - has rapidly gained interest as a micronutrient that
might help prevent many types of cancer.
Researchers at Oregon State University
first discovered the cancer-related properties of this flavonoid compound called
xanthohumol about 10 years ago. A recent publication by an OSU researcher in the journal
Phytochemistry outlines the range of findings made since then. And many other scientists
in programs around the world are also beginning to look at the value of these hops
flavonoids for everything from preventing prostate or colon cancer to hormone replacement
therapy for women.
"Xanthohumol is one of the more
significant compounds for cancer chemoprevention that we have studied," said Fred
Stevens, a researcher with OSU's Linus Pauling Institute and an assistant professor of
medicinal chemistry in the College of Pharmacy. "The published literature and
research on its properties are just exploding at this point, and there's a great deal of
interest."
Quite a bit is now known about the
biological mechanism of action of this compound and the ways it may help prevent cancer or
have other metabolic value. But even before most of those studies have been completed,
efforts are under way to isolate and market it as a food supplement. A "health
beer" with enhanced levels of the compound is already being developed.
"We can't say that drinking beer
will help prevent cancer," Stevens said. "Most beer has low levels of this
compound, and its absorption in the body is also limited. But if ways can be developed to
significantly increase the levels of xanthohumol or use it as a nutritional supplement -
that might be different. It clearly has some interesting cancer chemopreventive
properties, and the only way people are getting any of it right now is through beer
consumption."
Xanthohumol was actually first discovered
in 1913, isolated as a yellow substance found in hops. Researchers started studying its
molecular structure in the 1950s, but for decades the only people who showed any real
interest in it were brewers, who were trying to learn more about how hops help impart
flavor to beer.
In the 1990s, researchers at OSU,
including Stevens and toxicologist Don Buhler, began to look at the compound from another
perspective - its anti-cancer properties. It showed toxicity to human breast, colon and
ovarian cancer cells, and most recently has shown some activity against prostate cancer in
OSU studies.
Xanthohumol appears to have several
mechanisms of action that relate to its cancer preventive properties, scientists say. It,
and other related flavonoid compounds found in hops, inhibit a family of enzymes, commonly
called cytochromes P450 that can activate the cancer process. It also induces activity in
a "quinone reductase" process that helps the body detoxify carcinogens. And it
inhibits tumor growth at an early stage.
In recent years, it has also been shown
that some prenylflavonoids found in hops are potent phytoestrogens, and could ultimately
have value in prevention or treatment of post-menopausal "hot flashes" and
osteoporosis - but no proper clinical trials have been done to study this.
Information about these compounds appears
to be spreading. Hop-containing herbal preparations are already being marketed for breast
enlargement in women, the OSU research report said, without waiting for tests to verify
their safety or efficacy. And a supposed "health" beer is being developed in
Germany with higher levels of xanthohumol.
It's possible, scientists say, that hops
might be produced or genetically engineered to have higher levels of xanthohumol,
specifically to take advantage of its anti-cancer properties. Some beers already have
higher levels of these compounds than others. The lager and pilsner beers commonly sold in
domestic U.S. brews have fairly low levels of these compounds, but some porter, stout and
ale brews have much higher levels.
Ideally, researchers say, cancer
chemoprevention is targeted at the early stages of cancer development and prevented by
long-term exposure to non-toxic nutrients, food supplements or drugs that prevent the
formation of cancers. With its broad spectrum activity, presence in food products, and
ability to inhibit cancer at low concentrations, xanthohumol might be a good candidate for
that list, experts say.
Xanthohumol also appears to have a role
as a fairly powerful antioxidant - even more than vitamin E. And it has shown the ability
to reduce the oxidation of LDL, or bad cholesterol.
Source: Oregon State University
Vitamin E in plant seeds could
halt prostate, lung cancer, says Purdue scientist
The form of vitamin E found in many plant
seeds – but not in most manufactured nutritional supplements – might halt the
growth of prostate and lung cancer cells, according to a Purdue University study.
A team led by Qing Jiang (pronounced
"ching zhang") has found that gamma-tocopherol, which occurs naturally in
walnuts, pecans, sesame seeds, and in corn and sesame oils, inhibits the proliferation of
lab-cultured human prostate and lung cancer cells. The vitamin's presence interrupts the
synthesis of certain fatty molecules called sphingolipids, important components of cell
membranes. However, the gamma-tocopherol leaves healthy human prostate cells unaffected,
which could give it value as an anticancer agent.
"This is the first time
gamma-tocopherol has been shown to induce death in lab-grown human cancer cells while
leaving healthy cells alone," said Jiang, who is an assistant professor of foods and
nutrition in the College of Consumer and Family Sciences. "This could be wonderful
news for cancer patients if the effect can be reproduced in animal models. But because
most nutritional supplements contain only alpha-tocopherol, a different form of vitamin E
that alone does not have these anticancer properties, it may be better to supplement the
diet with mixed forms of vitamin E. The study shows that the anticancer effect is enhanced
when mixed forms are used."
Jiang's research appears in the current
(week of Dec. 13) online edition of the scientific journal Proceedings of the National
Academy of Sciences. She co-authored the paper with Jeffrey Wong, Henrik Fyrst, Julie D.
Saba and Bruce N. Ames of the Children's Hospital Oakland Research Institute in Oakland,
Calif.
Scientists have been studying vitamin E
for more than three-quarters of a century, but most efforts have focused largely on
alpha-tocopherol, one of eight known forms in the vitamin's family. Alpha-tocopherol was
found early on to have the most beneficial effects on laboratory animals fed diets
deficient in vitamin E, and also is the major form found in body tissues. For these
reasons, it has been nearly the only form of the vitamin to be included in most
manufactured nutritional supplements.
"Since then, alpha-tocopherol has
justifiably earned a good reputation as an antioxidant, which helps to fight against
damage caused by unwanted free radicals," Jiang said. "But its familiarity has
perhaps attracted research away from the other seven forms of vitamin E, and since
gamma-tocopherol is the vitamin's most commonly occurring natural form in the American
diet, I grew interested in it a few years ago."
In 2000 another study by Jiang and
colleagues found that gamma-tocopherol inhibits inflammation, which had already been
implicated in cancer development. They theorized that it might retard the progress of
cancer and cardiovascular disease, and to test their hypothesis they exposed cultures of
cancerous prostate and lung cells to the vitamin. Normal prostate epithelial cells were
used as a control group.
"We discovered that as we increased
the quantity of gamma-tocopherol, the cancer cells grew more slowly," Jiang said.
"But the normal prostate cells were not affected and grew normally. This could
indicate that the vitamin could be used to target lung and prostate cancer cells without
the damaging side effects of chemotherapy."
The study also revealed that
gamma-tocopherol caused cell death by interrupting sphingolipid synthesis.
"This is also a novel
discovery," Jiang said. "Although there have been prior indications that some
form of vitamin E may cause cell death in some mouse cell lines, we are the first to
provide a mechanism for such an effect."
Gamma-tocopherol, though rarely available
in vitamin pills, is nevertheless found in abundance in the typical American diet. Many
nuts are rich in it, including walnuts and pecans, as are cooking oils such as corn and
sesame oil.
Though Jiang said she would be cautious
about using food sources to slow prostate or lung cancer's progress in humans, she said
that high-risk groups such as older men could benefit from supplementation – if
carried out with prudence.
"Foods rich in gamma-tocopherol are
also rich in fats, and some products bring other hazards as well," she said.
"Corn oil, for example, is rich in linolic acid, which has been shown to promote
certain types of cancer in some studies. But sesame seeds and pecans seem to be good
all-around choices."
Jiang said the next step for her research
team would be testing the effect of gamma-tocopherol and mixed forms of vitamin E on
animal cancers.
"Although this discovery is
promising, we do not yet know whether gamma-tocopherol has any effect on cancer in living
creatures," she said. "We hope that future research not only will clarify
whether gamma-tocopherol could have applications in human cancer treatment, but also will
show how we might supplement the body with the vitamin to prevent cancer from developing
in the first place. These questions will continue to direct our work."
This research was funded in part by the
National Institutes of Health.
Writer: Chad Boutin, (765) 494-2081,
cboutin@purdue.edu
Source: Qing Jiang, (765) 494-2483 or
496-6407, qjiang@purdue.edu
Source: Purdue University
Intensity Modulated Radiation
Therapy
IMRT is the one of the most
technologically advanced treatment methods available in external beam radiation therapy.
Cancer Treatment Centers of America at Tulsa is treating patients with the Peacock system
for Intensity Modulated Radiotherapy, also known as IMRT. IMRT allows very precise
external beam radiotherapy treatments. Rather than having a single large radiation beam
pass through the body, with IMRT the radiation is effectively broken up into thousands of
tiny pencil-thin radiation beams. With millimeter accuracy, these beams enter the body
from many angles and intersect on the cancer. This results in a high dosage to the
tumor and a lower dose to the surrounding healthy tissues.
Intensity modulation radiotherapy can
allow us to treat tumors to a higher dose, retreat cancers which have previously been
irradiated, and safely treat tumors which are located very close to delicate organs like
the eye, spinal cord, or rectum. Simply put, this can translate into a higher cancer
control rate and a lower rate of side effects. Cancers being treated with IMRT
We are using IMRT to treat the following
tumors:
- Prostate cancer
- Metastatic brain tumors
- Primary brain tumors (glioblastomas,
gliomas, etc)
- Pancreatic tumors
- Liver tumors (metastases, hepatocellular
carcinoma)
- Head & neck cancer (larynx, tongue,
sinus, base of skull, mouth, etc)
- Lung cancer
More info
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onmogelijk alles alleen kunnen doen dus mocht je willen helpen bij een bepaald thema,
vertaalwerk, links bezoeken etc dan is alle hulp welkom.
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Ron Fonteine
Email adres: ugamedia@wirehub.nl
