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Targeted Therapy Combination Overcomes Treatment Resistance In Liver Cancer, Study
Suggests (ScienceDaily - 15/04/2008)
Researchers at the University of Pennsylvania School of Medicine and Abramson Cancer
Center reported April 13 at the annual meeting of the American Association for Cancer
Research that combining two targeted therapies overcomes treatment resistance in liver
cancer cell lines. The team is currently designing a trial to test the combination in patients.
Liver cancer is resistant to many chemotherapies and to cell-death inducing agents. Last
year, however, the U.S. Food and Drug Administration approved sorafenib (Nexavar®) as a
treatment for liver cancer after a clinical trial showed that the targeted agent prolonged
survival in some patients. Unfortunately not all patients respond to sorafenib and the drug does not cure the disease.Therefore, Wafik El-Deiry, MD, PhD, Professor of Medicine, Genetics, and Pharmacology, and
co-Program Leader of Radiation Biology in the Abramson Cancer Center, and colleagues have
tested other targeted agents in combination with sorafenib. They found that treating liver cancer cells with sorafenib and an antibody or the natural ligand
that stimulates programmed cell death via the TRAIL pathway, dramatically increases the rate
of cell death.
"Sorafenib by itself causes a little cell death, but not that much," Dr. El-Deiry said. "Now you
combine sorafenib and TRAIL, and all of the sudden you get massive cell death. It is a real
synergistic interaction. It is very profound killing."
The combination works regardless of whether the researchers use a monoclonal antibody that
stimulates the TRAIL receptor, which resides on the surface of the cancer cells, or the
receptor's natural ligand, a small protein called TRAIL. Both the antibody and the TRAIL ligand
are currently being tested as single agents in patients. Within the next several months, Dr. El-Deiry's team expects to announce the details for a trial
testing the combination in patients.In a healthy individual, the immune system uses the TRAIL pathway to rid the body of
unwanted cells, including precancerous ones. Once cancer develops, however, the cells often
become less responsive to TRAIL activation, in part because of an overabundance of a protein
called Mcl-1, according to Dr. El-Deiry. His team found that sorafenib reduces the amount of
Mcl-1 in the cancer cells, restoring their sensitivity to TRAIL-induced cell death.
Although the Penn investigators focused their current report on liver cancer, they discovered
that the sorafenib-TRAIL combination also kills colon cancer cell in vitro and in animal models.
The current work was supported by grants from the National Cancer Institute and the
American Association for Cancer Research.
[Top]
Combo therapy extends life for liver cancer patients: study ( AFP - 8/04/2008)
Patients with advanced liver cancer may live longer if they receive a combination of a certain
kind of chemotherapy and radiothermal treatment, according to a study released Tuesday.
The findings, published in the April 9 issue of Journal of the American Medical Association,
could offer a breakthrough for treating liver cancer, which lacks a standard treatment, is often
diagnosed in mid to late stages and is increasing worldwide.Chinese researchers at Shandong University tested the potential of long term benefits when
treating liver cancer tumors larger than three centimeters with a combination of a
transcatheter arterial chemoembolization (TACE) and radiofrequency thermal ablation
(RFA). The team, led by Bao-Quan Cheng, studied 291 patients in China from January 2001 to May
2004. Some were given one therapy only, while others received combined treatment.
The follow-up showed that 69 percent of those in the combined group had died, compared to
84 percent in each group that received only one of the therapies. "Survival rates were significantly better in the TACE-RFA group than in the TACE or RFA
group," the study said, adding that the "lower rate of death in the TACE-RFA group was the
result of fewer deaths due to tumor progression." The study said: "Median (midpoint) survival times were 24 months in the TACE group, 22
months in the RFA group, and 37 months in TACE-RFA group." The TACE type of chemotherapy combines "the effect of targeted chemotherapy with that of
blocking the blood supply to the tumor," it said, while RFA involves "advancing a specially
designed probe into the tumor and applying radiofrequency energy."
[Top]
Study: Liver cancer breakthrough found
-
(USA TODAY)
Top cancer researchers are gathered at the American Society of Clinical Oncology annual meeting in Chicago.
For the first time, doctors said Monday they have found a pill that improves survival for people with liver cancer, a notoriously hard to treat disease diagnosed in more than half a million people globally each year.
The results in a multinational study of 602 patients with advanced liver cancer are impressive and likely will change the way patients are treated, say cancer specialists, including the study authors.
Patients got either two tablets daily of a drug called sorafenib or dummy pills in the study, which started in March 2005. Some patients are still alive,
although on average, sorafenib patients survived 10.7 months versus almost 8 months for those on dummy pills.
That type of survival advantage "has never happened" with liver cancer "and is a major breakthrough in the management of the disease," said Dr. Josep Llovet, the lead author.
"That may not sound like a lot of time," but for liver cancer, "this is actually a quite impressive gain," said Dr. Nancy Davidson of Johns Hopkins' Bloomberg School of Public Health. "It is the first effective systemic treatment for liver cancer, which is such a huge problem internationally."
"We now have moved forward" in treating advanced liver cancer "when it was not really possible before," Dr. William Blackstock of Wake Forest University School of Medicine said at a press briefing about the study.
Sorafenib attacks cancer with a targeted double-barreled approach. It zeros in on malignant cells themselves and cuts off the blood supply feeding the tumor. It is believed to work on tumors within the liver and those that have spread elsewhere.
In the study, tumors didn't shrink or disappear but in many cases they also didn't grow.
"You are not curing the disease but you are delaying the progression of the disease significantly and strikingly," said Llovet, of Mount Sinai School of Medicine in New York and Hospital Clinic of Barcelona, Spain.
The study was halted early in February because of the good results, and patients on dummy pills were switched to
sorafenib. "This is a very good step forward in this disease," said Dr. Emily Chan of Vanderbilt-Ingram Cancer Center in Nashville.
The drug, sold under the brand name Nexavar, is approved in the United States and dozens of other countries to treat advanced kidney cancer. It is marketed by Bayer Pharmaceuticals Corp. and Onyx Pharmaceuticals Inc., which funded the liver cancer study. They hope to receive approval for liver cancer use from U.S. and foreign regulators.
Llovet has done consulting for the sponsors. Liver cancer is diagnosed in about 19,000 Americans annually but is much more common elsewhere and is the fifth most common cancer globally. Risk factors include chronic liver infections and some forms of hepatitis. The disease is common in China and countries without widespread use of the hepatitis B vaccine, which is routinely given to U.S. infants.
Liver cancer doesn't respond well to conventional chemotherapy and is often diagnosed too late for surgery to be an option. Many patients die within a year of diagnosis.
Robert Throckmorton, a 73-year-old attorney in Orange County, Calif., said his doctor told him "You better get your affairs in order" after he was diagnosed with inoperable liver cancer last August.
But then the doctor offered sorafenib off-label, and Throckmorton readily agreed. He did not take part in the study.
After nine months on the drug, Throckmorton said his cancer shows no sign of progression and he has no significant side effects. He said he walks three miles six days a week to stay active and feels fine.
Instead of thinking about wills and funerals, Throckmorton is looking forward to get-togethers with his eight children and 18 grandchildren, and even a possible church trip to Uruguay with his wife.
"I have good energy," Throckmorton said. "We are optimistic."
[Top]
Coffee May Curb Liver Cancer Researchers Say Disease Appears To Be Rarer In Coffee Drinkers Than In Non-Drinkers-
(Yahoo News- 2/08/2007)
Could a cup of coffee cut your risk of developing liver cancer? Maybe, but don't bet your next latte on it just yet.
A new report, published in the August edition of the journal Hepatology, boils down the findings from 10 studies on coffee and liver cancer.
The studies were reviewed by researchers including Francesca Bravi, ScD of the Istituto di Ricerche Farmacologiche "Mario
Negri" in Milan, Italy.
Together, the studies included 2,260 people with liver cancer and nearly 240,000 people without liver cancer. Participants lived in Greece, Italy, or Japan.
Participants reported their coffee-drinking habits. The data show that coffee drinkers were 41 percent less likely to have been diagnosed with liver cancer than people who don't drink coffee. For every daily cup of coffee people drank, their odds of having been diagnosed with liver cancer dropped by 23 percent, compared with people who never drink coffee.
People who drank a lot of coffee were 55 percent less likely to have been diagnosed with liver cancer than those who didn't drink any coffee.
What's a lot of coffee? That depends on which of the 10 studies you look at. Some of the studies defined high coffee consumption as three or more daily cups. Others set the bar lower, at more than one daily cup.
The fact that liver cancer was rarer among coffee drinkers a world apart — in Greece, Italy, and Japan — suggests that the coffee findings weren't a fluke or a local phenomenon, note Bravi and colleagues.
They speculate that coffee perks up liver enzymes and may cut cirrhosis and liver cancer.
But Bravi's team doesn't promise that drinking coffee will prevent liver cancer. They note that people with various digestive and liver diseases might choose not to drink coffee for reasons that aren't reflected in the data.
Whether or not coffee prevents liver cancer "remains open to discussion," write Bravi and colleagues.
[Top]
Nexavar Approved for Liver Cancer-
(Yahoo News- 19/11/2007)
The Bayer anticancer drug Nexavar (sorafenib) has been approved by the U.S. Food and Drug Administration to treat the most common form of liver cancer that can't be surgically removed, medically called unresectable hepatocellular carcinoma (HCC), the drug maker said Monday.In 2005, Nexavar was approved to treat advanced kidney cancer. It's among a newer class of drugs called kinase inhibitors, which target enzymes that spur tumor cell growth.
HCC is responsible for about 90 percent of malignant liver tumors, Bayer said in a statement. Liver cancer is the world's sixth most common form of cancer, with roughly 600,000 cases diagnosed globally each year, including 19,000 annually in the United States.
In clinical testing, Nexavar improved overall survival by 44 percent among people with HCC. Median overall survival was 10.7 months among those treated with the drug, versus 7.9 months among those who took a placebo, Bayer said.
[Top]
Natural Protein Could Help Spot, Treat Liver Cancer-
(Yahoo News- 19/09/2007)
A natural protein called nerve growth factor (NGF) may prove an effective target for the treatment of liver cancer, Italian researchers say.
NGF is an essential component in the growth and differentiation of neuronal cells, explained the team, who reported their findings in the Oct. 7 issue of the World Journal of Gastroenterology.
This study found that NGF also appears to be a factor in liver cancer, one of the leading causes of cancer death worldwide.
A team at the National Research Council of Italy and elsewhere found that NGF and its receptor trk/ANGF were expressed in the livers of patients with liver cirrhosis and/or hepatocellular carcinoma (HCC). The two molecules were not detected in the livers of healthy people.
The findings indicate that NGF plays an important role in the development of liver cirrhosis and its progression to HCC, the researchers said. By targeting NGF, it may be possible to prevent or suppress the development of cirrhosis and HCC.
NGF may also prove a useful marker for early diagnosis of liver cirrhosis and HCC, the team noted.
[Top]
Cell
death mark liver cancer clue-(BBC News-24/07/2005)
Scientists say they have
discovered how a protein causes liver cancer - it tags cancer preventing
cell machinery for destruction.
The Japanese and UK team first
linked gankyrin to liver or hepatocellular cancer, which affects some 250
million people worldwide, five years ago. Then they discovered that it
appeared to encourage DNA synthesis so cells grew unchecked and became
cancerous. Now they say, in Cancer Cell,
gankyrin promotes cancer by another pathway too. It puts a death mark on cell
machinery tasked with deciding which cells in the liver should continue to
divide and replicate their DNA and which should die.
For example, if a cell is
infected with a virus the protein p53 - sometimes called the "guardian of
the genome" - will send out a signal so the cell commits suicide. In hepatocellular cancer, this
process is disrupted. Instead, gankyrin binds to an enzyme called mdm2,
which gives p53 a molecular label that tags it for death. The marked p53 is then sent to
the cell's waste disposer, called the proteasome, where it is broken down
and destroyed. This means damaged cells can
continue dividing unchecked in the liver and grow into tumours.
Researcher Professor John
Mayer, from Nottingham University, said: "It's amazing that gankyrin
controls the two major cancer-controlling mechanisms. The cells go on and on
dividing and become cancer cells." He said that although around
half of all tumours in the body involved p53 defects, gankyrin only appears
to be linked to liver cancer, which might be down to certain properties of
this organ. "The liver is really
interesting because the cells divide very slowly, but the cells can
regenerate. They are in a division limbo,
so to speak. We think this is why overexpression of gankyrin leads to liver cancer."
Professor Mayer and co-worker
Professor Jun Fujita from Kyoto University are now trying to work out the
structure of gankyrin in the hope that it will lead to a way to make
anti-cancer drugs that block its action. Currently there are few drugs
for liver cancer and no cure. Dr Julie Sharp, senior science
information officer at Cancer Research UK, said: "Identifying some of the
molecular events that may contribute to the development of liver cancer
provides an important step towards finding better ways of treating this
disease. "This could help improve
survival rates in the future."
[Top]
NCI
Begins Validation Study Of New Test To Detect Early–Stage Liver Cancer
A
two-year study to validate a test to detect early-stage liver cancer has
been initiated by the National Cancer Institute (NCI), part of the National
Institutes of Health, at six centers across the United States. This test,
conceived with the assistance of NCI’s Early Detection Research Network (EDRN),
looks at whether a substance called des-gamma carboxyprothrombin (DCP) can
identify those at risk for liver cancer.
Validation-proving that the measurement of a substance accurately
signifies the risk for or presence of cancer-is the critical step to create
a truly useful test. “It’s the first study testing a marker for liver
cancer, and the first Phase II EDRN-supported study,” said Sudhir Srivastava,
Ph.D., who heads EDRN as chief of the Cancer Biomarkers Research Group in
NCI’s Division of Cancer Prevention.
Liver cancer, or hepatocellular carcinoma, with over 20,000 estimated new
cases this year in the United States, is both one of the more common cancers
worldwide and one of the few cancers in the United States in which the
number of new cases is rising, and expected to continue to rise over the
next two decades. Frequent surveillance of patients with liver cirrhosis is
recommended, but current procedures have shortcomings. Alpha-fetoprotein, a
blood test currently used for surveillance of liver cancer, suffers from
poor sensitivity and specificity (ability to determine if someone actually
has, or does not have, liver cancer). Liver ultrasound is dependent on the
skills and knowledge of the technician and can lead to false-negative
results. This EDRN-supported study looks to improve upon these negatives.
DCP is a protein precursor of prothrombin, one of the factors produced by
the liver to help the blood clot. In patients with liver cancer, this
protein seems to be elevated compared to those without liver cancer. Early
studies have shown that DCP is better than alpha-fetoprotein for the
diagnosis of liver cancer and has close to 90 percent accuracy.
The investigators conducting the validation study, headed by Jorge A.
Marrero, M.D., of the University of Michigan, and Paul Wagner, Ph.D.,
program director in NCI’s Cancer Biomarkers Research Group, plan to enroll
450 patients diagnosed with liver cancer, of which at least 170 will be
early stage. Four hundred fifty patients with cirrhosis and no cancer will
serve as controls. The participating institutions will collect samples from
patients in this study, and the samples will be analyzed for DCP using an
assay manufactured by Eisai Company, Teaneck, N.J. The primary goal of the
study is to determine whether DCP can lead to improved accuracy in the
detection of early-stage hepatocellular carcinoma.
This trial will run for two years and final results are expected in early
2007. If successful, this study will provide a much-needed tool for the
early detection of liver cancer. Additionally, EDRN’s gastrointestinal
collaborative group is working on two other early novel detection tests for
liver cancer for future validation.
EDRN, established by NCI in early 2000, is a broad, interdisciplinary
consortium whose work is aimed at both identifying and validating cancer
biomarkers for use in early cancer detection, and is divided among
collaborative groups studying specific tumors. Numerous proteins and genes
have been linked with a variety of cancers, which can make them targets for
therapy, as well as targets for identifying the risk of cancer onset,
progression, or recurrence.
[Top]
Liver
Cancer Fastest Growing Cancer in U.S. - Report-(Reuters
Health-01/11/2004)
A preliminary
report from the Liver Cancer Network shows that liver cancer is increasing
at the fastest rate of any other cancer in the US. Hepatitis C infection
is involved in more than half of liver cancer cases, researchers said here
Monday at the annual meeting of the American Association for the Study of
Liver Diseases. In presenting the early data, Dr. Alex S. Befeler of St.
Louis University, Missouri, noted that the Network was established because
of a dearth of information about the extent of liver cancer.
The Network has
currently enrolled approximately 250 patients to date from 6 centers to
study demographics, risk factors for liver cancer, liver disease, tumor
characteristics and different treatments. The average age of the patients
was 59 years and 75 percent are male. Eighty percent Caucasian, 10 percent
African American, 4 percent Hispanic and 4 percent East Asian. Most liver
cancer patients (87 percent) had underlying liver disease and more than
half (52 percent) of those enrolled had hepatitis C infection. A history
of alcohol abuse was involved in 20 percent of those cases.
Liver cancer "in the US is almost
always associated with chronic liver disease," the Network data show.
Survival is "significantly better for those who were asymptomatic at
presentation or who were candidates for liver transplantation,"
Befeler said. The bottom line is that "chemotherapy is generally
ineffective for liver cancer. Liver transplantation is the best
approach...Most patients also have advanced cirrhosis, so drug metabolism
is poor," Befeler added.
[Top]
FDA
Clears Celsion to Initiate Clinical Trials for the Use of ThermoDox with
RFA in the Treatment of Liver Cancer-(Yahoo News-31/08/2004)
Celsion Corporation today
announced that the Food and Drug Administration (FDA) will allow the human
clinical trial for its investigational therapy for the treatment of liver
cancer to proceed. The Phase I study will investigate the use of Celsion's
proprietary product, ThermoDox(TM), in combination with Radiofrequency
Ablation (RFA). ThermoDox, Celsion's temperature-sensitive liposomal
encapsulation of doxorubicin, a common cancer drug, allows focused,
concentrated delivery of the drug to the tumor target. The trial will be
conducted at the National Institutes of Health (NIH) Clinical Center in
Bethesda, Maryland and will be funded under a Collaborative Research and
Development Agreement between Celsion and NIH. Under the agreement,
Celsion will supply ThermoDox and provide regulatory and clinical support
and NIH will enroll and treat the patients.
The trial is designed to
determine the maximum safely tolerated dose and pharmacokinetic profile of
ThermoDox when used in combination with RFA in the treatment of liver
cancer. The study approach will utilize RFA (80 degrees celsius or above)
to ablate (destroy) the center of the tumor and the lower temperature zone
(greater than 40 degrees celsius) in the tumor margins to activate and
release the doxorubicin to kill any remaining viable cancer cells. Celsion
hopes to commence the study before the end of the year. The clinical plans
for liver cancer rely, in part, on the preclinical results of the work
conducted in large animals by the FDA in conjunction with NIH. These
results were presented by Dr. Bradford J. Wood, Senior Clinical
Investigator, Diagnostic Radiology Department, Imaging Sciences Program,
NIH Clinical Center; Surgery Branch, National Cancer Institute, at the
National Institutes of Health at the 89th Annual Radiological Society of
North America (RSNA) in December 2003. These results demonstrated that
ThermoDox, used in this manner, deposited fifteen times more drug at the
tumor site than conventional, intravenous delivery of doxorubicin.
Dr. Augustine Cheung, Celsion's
President and Chief Executive Officer said, "Initiating this study is
a major step in the evolution of Celsion from a medical device company to
a company focused on targeted drug delivery using combination therapies.
We believe that the mechanism of action of RFA in conjunction with
ThermoDox, using heat-sensitive nanoparticles to target ThermoDox, could
result in high deposits of the encapsulated drug, doxorubicin, in the
tumor, thus ablating the tumor as well as viable cancer cells in the tumor
margin. This may lead to a significant reduction of local tumor
recurrence, which is currently the major limitation in using RFA alone to
treat liver cancer."
Tony Deasey, Celsion's Chief
Operating Officer, added, "Clearance to initiate this study enables
us to attempt to address a significant unmet medical need by treating
liver cancer. This trial increases our cancer treatment portfolio,
building upon our ongoing Phase I trial using ThermoDox to treat prostate
cancer in conjunction with Celsion's proprietary microwave heating
technology (Prolieve(TM))."
[Top]
Vitamin
K Might Prevent Liver Cancer-(HealthDay-20/07/2004)
Researchers trying
to prevent bone loss in women with cirrhosis of the liver have made an
unexpected yet welcome discovery -- that vitamin K may help prevent liver
cancer in those most at risk of the disease. The study, which appears
in the Journal of the American Medical Association, was originally designed
to assess the effects of vitamin K supplementation on bone loss in women
with viral cirrhosis of the liver. However, at the end of the study, the
researchers realized the women who took the vitamin K had significantly
lower rates of liver cancer. "The results suggest a possible role for
vitamin K2 in the prevention of liver cancer in women with viral cirrhosis,"
said study co-author Dr. Susumu Shiomi, a professor of nuclear medicine
at the Graduate School of Medicine at Osaka City University in Japan.
Shiomi added that "vitamin K2 is cheap and safe to use."
Dr. Jay Brooks, chief
of hematology/oncology at Ochsner Clinic Foundation Hospital in New Orleans,
explained that people with viral cirrhosis from diseases such as hepatitis
C are at an increased risk of developing liver cancer. While researchers
still don't know why, Brooks said, "we do know that they run an incredibly
increased risk." And, he said, the problem will likely only increase because
hepatitis C is being diagnosed in more people.
Between 1996 and
1998, 40 women with viral cirrhosis were recruited for a study in preventing
bone loss. The women were randomly assigned to either the treatment group
or the placebo group. The treatment group took a pill containing 45 milligrams
of vitamin K2 daily. Vitamin K is a fat-soluble vitamin that is produced
in the intestines. It can also be found in leafy green vegetables such
as broccoli and spinach, vegetable oils, cereals and some meats and cheeses.
Excess amounts of this vitamin are stored in the liver. The recommended
daily allowance of vitamin K in the United States is 75 micrograms to
90 micrograms (a thousandth of a milligram) per day for women and 75 micrograms
to 120 micrograms for men. Most of the women enrolled in the study had
hepatitis C. The average age of the study participants was around 60.
Two of 21 women in the treatment group developed liver cancer, while nine
out of 19 women in the placebo group did. After adjusting for age, severity
of disease and treatment, the researchers found the women receiving vitamin
K supplementation were nearly 90 percent less likely to develop liver
cancer.
The researchers said
it wasn't clear how vitamin K could prevent liver cancer, but theorized
that it may dampen cancer cell growth. "A number of findings indicate
that vitamin K2 may play a role in controlling cell growth. But the mechanisms
responsible for the vitamin K-mediated inhibition of cell growth remains
unexplained," Shiomi said. "It's an interesting early observation, but
it's a very small study," Brooks said. Both the authors of the study and
Brooks said these results need to be confirmed with a much larger group
of people. And, Brooks added, "it would be extremely premature for anyone
with hepatitis C to start taking vitamin K."
He said that in the
past there have been studies on vitamins that initially looked promising
in the prevention of cancer, but then with further study, were found to
be ineffective or, worse, harmful.
[Top]
Genetic
Link to Liver Cancer Found-(HealthDayNews-14/04/2004)
A gene that causes
liver cancer in mice has been identified by researchers at the University
of Illinois at Chicago. When the researchers deleted the gene, called
Foxm1b, from liver cells in lab mice, the animals didn't develop tumors.
The mice with the deleted gene remained cancer-free even when the researchers
tried to use artificial means to induce tumors. "To my knowledge, this
is the first time a gene has been directly linked to the growth of cancer
cells in live animals," lead investigator Robert Costa, a professor of
biochemistry and molecular genetics, said in a prepared statement. The
research appeared in a recent issue of Genes and Development. "Foxm1b
is expressed in many different kinds of cancer cells, which leads us to
believe it plays a key role in promoting the growth of tumors other than
liver cancer," Costa added. He and his colleagues have created a prototype
for a drug to block Foxm1b activity and starve tumor cells of the protein
manufactured by Foxm1b. Depriving tumors of this protein prevents them
from multiplying.
[Top]
Diabetes
Raises Risk of Serious Liver Problems-(Reuters Health-25/02/2004)
Men with diabetes
have about a two-fold greater risk of developing liver cancer and other
chronic liver diseases compared with nondiabetic men, new research suggests.
The same may hold true in women, but the study did not have enough women
to reach firm conclusions. "Our study provides evidence that diabetes
is an important risk factor for chronic liver disease including (liver
cancer)," Dr. Hashem B. El-Serag from the Houston VA Medical Center in
Texas told Reuters Health. The study is also the first to show that diabetes
precedes, rather than follows, the development of these diseases, he added.
Using the computerized
records of the Department of Veterans Affairs, investigators studied all
patients with a hospital diagnosis of diabetes between 1985 and 1990.
They matched each diabetic patient to three nondiabetic patients and tracked
them through 2000. Nearly all of the subjects were men and most had type
2 diabetes. None of the subjects had liver disease when first diagnosed
with diabetes. As reported in the medical journal Gastroenterology, the
rates of chronic non-alcohol related liver disease and liver cancer were
significantly higher in diabetic than in the nondiabetic patients.
The increased risk
"seems to be independent of age, gender, ethnicity, or (other) illnesses,"
El-Serag noted, and is higher in patients with diabetes for 10 years or
more. This study, Dr. Adrian M. Di Bisceglie from Saint Louis University
School of Medicine points out in an editorial, "provides evidence that
long-standing diabetes is followed by the development of liver disease
and (liver cancer), suggesting a causative role for diabetes mellitus."
The current study supports the team's earlier findings from the same group
of patients in which diabetes raised the risk of acute liver failure by
44 percent. In light of the present findings, El-Serag and colleagues
recommend regular liver blood tests in diabetic patients. Further studies
are needed to examine the association between diabetes and liver disease
in women and to clarify the mechanisms behind the link, the authors note
[Top]
Combo
Treatment Helps Liver Cancer Patients-(HealthDayNews-28/10/2003)
New research supports
radiologists who are trying to treat liver cancer by using a "smart bomb"
treatment that first shrinks the tumor and then tries to burn it away.
The one-two punch extended the lives of patients, claims a German study
that appears in the journal, Radiology. The combination therapy also greatly
reduces recovery time when compared to the standard surgery treatment,
says Dr. Jonathan Susman, an assistant professor of radiology at Columbia
University in New York City. Liver cancer remains one of the most deadly
cancers, however, and even cutting-edge treatments don't prevent recurrence
in many patients with the most advanced forms of the disease. "Traditionally,
patients have been plagued by poor survival," says Dr. J.F. Geschwind,
director of cardiovascular and interventional radiology at The Johns Hopkins
Hospital in Baltimore.
Even after doctors
remove the liver tumors through surgery, they return within five years
in 75 percent of cases, he says. Liver cancer is especially difficult
to treat because it's often the result of existing liver disease, such
as cirrhosis or hepatitis. "You can even consider it a side effect," Geschwind
says. In other cases, liver cancer develops when tumors migrate from other
parts of the body, especially the colon or breast. An estimated 17,300
cases of primary liver cancer -- which do not spread from elsewhere in
the body -- are diagnosed in the United States each year, according to
the American Cancer Society. Most patients are men. An estimated 14,300
Americans will die of the disease this year.Doctors
can try to burn up the tumors with lasers and high-frequency radio waves.
However, tumors with diameters of more than 3 or 4 centimeters are often
too large to be treated effectively. "You never know how much of the tumor
you burned," Geschwind says. "If you leave a little bit of the tumor behind,
it returns with a vengeance."
In the new study,
the researchers from University Hospital in Frankfurt recruited 162 liver
cancer patients whose tumors were large and the result of cancer that
had spread from elsewhere in the body. The doctors tried to shrink the
tumors and then, if possible, destroy them with lasers. All the patients
had a treatment called chemoembolization to shrink the tumors. "We inject
the chemotherapy right into the tumor cells, and then cut off the oxygen
supply by blocking the blood flow," says Susman, who uses that approach
to treat his patients. In the new study, the tumors shrunk in more than
half of the patients. Doctors went on to treat their tumors by burning
them with lasers. Susman uses a similar approach, utilizing radio-frequency
waves instead of lasers. "I treat [the tumor] from the inside first to
hamper its defenses and shrink it down, so that I can use a device to
burn it away and completely eradicate it. It is the medical equivalent
of a smart bomb," he says.
Blocking blood flow
to the tumor helps in the burning process, Susman adds. "The blood supply
works like the radiator in your car, pulling heat away. When we block
the blood supply you no longer have the radiator circulating. You heat
the tumor more easily because the heat doesn't go away." The patients
who underwent the combination treatment lived for a median of 26.2 months,
while the other patients who only received the chemoembolization lived
a median of 12.8 months. Those survival rates may seem low, Susman says,
but they'd be higher in patients with smaller tumors. Also, the treatment
lets patients avoid surgical removal of tumors, which requires months
of recovery time and poses great risks, he adds. The German researchers
say the dual treatment has applications for lung, bone and lymph node
tumors as well.
[Top]
Transplants
For Liver Cancer Becoming More Successful-(ET-12/10/2003)
Researchers from
Johns Hopkins University School of Medicine have found that patients with
liver cancer treated with a liver transplant are living longer than in
past years. They compared transplant results from three eras, 1987-91,
1992-95, and 1996-2001. The study was published online by the Journal
of Clinical Oncology in October, and will appear in the December 1 print
edition (Vol. 21, No. 23). Worldwide, cancer starting in the liver, called
hepatocellular cancer, is a leading cause of cancer-related deaths. The
major cause of this cancer is infection with hepatitis viruses. In the
United States, where alcoholism is another cause, liver cancer is expected
to kill around 14,400 people in 2003.
The only successful
treatment for this cancer is surgery. Usually doctors remove the tumor
along with part of the liver. But because the liver is damaged, many patients
can't withstand losing part of their liver. Beginning in the 1980s, removing
the entire liver and replacing it with a transplanted one became another
option. The researchers from Johns Hopkins used data from the United Network
for Organ Sharing (UNOS), the nation's only organ procurement and transplantation
network, to compare survival rates among liver cancer patients who received
a liver transplant. In the early years, only about 30% percent of patients
were surviving five years. Now, though, around 60% are surviving that
long. "These findings are particularly reassuring for patients with tumors
that cannot be surgically removed," said senior author Paul M. Thuluvath,
MD. More than 80% of liver cancer patients fall into that category, he
added.
Thuluvath and his
colleagues say that careful selection of patients is the most likely reason
transplants for liver cancer have become more successful in recent years.
In general, people with small tumors, and no more than three tumors, are
offered this treatment. Most treatment centers use this standard, they
said, even though it is not an official guideline. Their study couldn't
prove that better patient selection was the reason for the improvement
in survival, because the UNOS database does not have information about
the size of the tumors or how many a patient had. But two other experts,
who wrote an editorial accompanying the study, also believe patient selection
is a likely cause. Jean-Nicolas Vauthey and Jaffer A. Ajani, of the M.D.
Anderson Cancer Center, say survival after transplant could be improved
even more if doctors used additional factors like whether the tumor has
penetrated blood vessels - to decide which patients should have transplants.
The Johns Hopkins
researchers say that liver transplants may be the "optimal treatment"
for patients with liver cancer, as long as patients are selected carefully.
But this treatment option isn't always readily available to cancer patients.
Donor livers, which usually come from people who have died, are a very
scarce resource. It can take months for a suitable organ to become available
- time that many cancer patients don't have. The Johns Hopkins researchers
found that waiting periods for donor livers increased dramatically --
from about one month to seven months or even more than a year -- between
1987 and 2001. To overcome this problem, the Hopkins researchers and the
editorialists both suggest trying surgery first on those patients who
are eligible. Then, if the cancer comes back, a liver transplant can be
performed. Unfortunately, only about 20% of patients have liver cancer
that can be treated with surgery. Another option is transplanting liver
tissue from a living donor. UNOS data suggest that growing numbers of
liver cancer patients are receiving transplants in this way, the researchers
write. However, these strategies have not been well-studied, and more
research will have to be done to determine their long-term effects on
patients with liver cancer.
[Top]
Liver
Cancer Treated Outside Body-(HealthScoutNews-20/12/02)
Italian scientists
have treated liver cancer by removing the entire organ, zapping it with
radiation, then implanting it back into the body. The surgery is expected
to have minimal impact on other organs, which is not the case with traditional
radiation therapy. The surgery, performed a year ago on a 48-year-old
man with multiple tumors on his liver, appears to be a success, reports
the magazine New Scientist. The liver now seems functionally normal and
there are no signs of any tumors. Doctors from the San Matteo Hospital
in Pavia plan to treat six more patients with the same technique. The
physicians say the procedure is still in its infancy and can only be used
on the most serious of cases until it is better refined and proven safe.
[Top]
Go
Easy on the Booze During the Holidays-(HealthScoutNews-15/12/2002)
It's fine to hoist
a glass of rum and eggnog or champagne to toast the festive season, but
don't get carried away with your celebratory drinking over the holidays.
University of Michigan emergency physicians remind you that even moderate
drinking may impair your judgment and result in serious safety and health
problems. Alcohol affects the brain and central nervous system, and impairs
your ability to function. At the same time, alcohol can give you a feeling
of self-confidence or denial that you're being seriously affected by the
alcohol.
There's more. Alcohol
kills brain cells and can cause memory loss, emotional disturbances, loss
of coordination and brain damage. Long-term alcohol abuse can lead to
liver cirrhosis and throat, mouth, esophagus, stomach and liver cancers.
Then there's the obvious danger of impaired driving. Research shows that
people's driving abilities are actually impaired even when they're still
below the legal limit for intoxication. The best way to protect yourself
from alcohol-related health and safety risks is to avoid drinking or drink
in moderation.
[Top]
Experimental
Drug Destroys Liver Cancer (HealthScoutNews-15/07/2002)
An experimental
drug with a taste for energy-thirsty cells appears to kill off liver tumors
in rabbits. Johns Hopkins University scientists found the chemical, known
as 3-bromopyruvate, destroys liver cancer and also shrinks tumors that
have spread into the lungs. The substance, which is related to a molecule
that occurs naturally in the breakdown of sugar, starves cancerous cells
of energy, but appears to leave healthy tissue alone. The researchers
say they must confirm the drug's lack of toxicity to normal tissue before
they test it in people. However, they add, if it does prove benign, it
might offer doctors a promising new therapy for other forms of tumors.
Liver cancer, which
has been linked to the hepatitis B virus, strikes about 16,600 Americans
a year and accounts for roughly 1 percent of tumor deaths in the United
States. However, it's much more common in Asia and Africa, where it makes
up half of all cancer fatalities. About 50 percent of patients can be
cured of the disease. However, for those with inoperable liver cancer,
especially tumors that spread from the colon, surviving a year is a feat.
A unique feature of liver tumors is that while they draw their nutrients
from an artery, the organ itself is fed separately by the portal vein.
In theory, it's possible to target cancerous cells by injecting drugs
directly into arterial blood, yet do minimal damage to the surrounding
organ. The latest study, published in Cancer Research, attempts such a
strategy.
Led by radiologist
Dr. Jean-Francois Geschwind, the scientists gave injections of 3-bromopyruvate
to rabbits with liver cancer. The potent chemical drains cells of their
energy in two ways: by greatly suppressing their ability to use glucose
for fuel; and by hindering the ability of internal power plants called
mitochondria to make the energy molecule adenosine triphosphate, or ATP.
Because cancer cells are lusty for glucose, needing it to support their
frenetic growth, a drug that selectively kills tissues that demand sugar
will turn this thirst against them. Indeed, a single injection of the
drug into the artery supplying the tumors led to "dramatic" shrinkage
of the masses, Geschwind says. "By being able to thread a catheter and
get close to the tumor, we can deliver agents in much higher concentrations
directly to the tumor. You can really kill the tumor that way," he adds.
Surprisingly, the healthy cells were spared. "We would have expected some
collateral damage, but in this case the specificity of the drug and the
method of administering it made a perfect marriage," Geschwind says. The
treatment was gentler on normal cells than a current therapy for liver
cancer called chemoembolization, in which doctors inject drugs into the
tumors while using an oil solution to block off the artery that feeds
them.
Some of the rabbits
developed liver cancer nodules in their lungs. So the researchers then
injected 3-bromopyruvate directly into their bloodstream through a vessel
in their ears. Again, the tumors shrank markedly, but the animals appeared
otherwise unscathed, says Peter Pedersen, a Johns Hopkins biochemist and
a co-author of the study. "We didn't find problems with toxicity, but
we don't know what the long-term [outlook] is," Pedersen says. If 3-bromopyruvate
ultimately passes the safety tests, Geschwind says it could be useful
against a wide range of tumors, because all have the common feature of
requiring heaps of energy. However, finding as finely tuned a way to deliver
the drug as is possible with the liver will be trickier, he adds.
[Top]
Hepatitis
B Virus Linked to Liver Cancer (HealthScoutNews-17/07/2002)
People with active
hepatitis B infections are 60 times more likely to develop liver cancer
than those without evidence of the virus, new research has found. The
study, reported in New England Journal of Medicine, followed almost 11,900
Taiwanese men who had no initial signs of liver tumors. When hepatitis
B enters the body, fragments of the virus, called antigens, can be detected.
If a person's blood has HBsAg antigens, they've been infected in the past
with hepatitis B. If they have HBeAg fragments, the virus is still infecting
their cells. When the liver is infected with hepatitis, its cells undergo
rapid turnover, dividing 100 to 1,000 times the normal rate to replace
damaged tissue. This process may pave the way for cancerous gene mutations
in the organ. It generally takes 20 to 30 years before the toll of hepatitis
infection becomes cancer, says Dr. Bruce Bacon, a liver expert at St.
Louis University.
Among the Taiwanese
men, 111 developed hepatocellular carcinoma, the most common form of liver
cancer, within about a decade. In those with no hepatitis, there were
39 cases of liver cancer for every 100,000 person years. For those with
HBsAg alone, that rose to 324 cases per 100,000 person years. However,
for men with both HBsAg and HBeAg, the number jumped to 1,169 per 100,000
person years. After accounting for other factors that increase the risk
of liver cancer, including smoking, alcohol consumption and infection
with hepatitis C, a history of hepatitis B infection upped the odds of
cancer 9.6-fold and an active hepatitis B infection upped it 60-fold.
The researchers also conducted a smaller study in 130 men, and found hepatitis
DNA was a strong predictor of liver cancer in men with HBsAG, but not
HBeAg. However, they add, since DNA testing for the virus is expensive
and requires special lab equipment, screening for HBeAg "may be a more
practical way" of trying to estimate the risk of liver cancer.
Marc Ghany, of the
National Institute of Diabetes and Digestive and Kidney Diseases, says
the findings aren't surprising, since scientists have long known that
hepatitis virus triggers liver cancer. However, the Taiwanese study is
a smoking gun. "Intuitively, we knew it, but there was not this sort of
proof," says Ghany, co-author of an editorial accompanying the journal
article. Between 65 percent and 70 percent of people who contract hepatitis
B have a form of the virus that spurs the production of HBeAg. The rest
are infected with mutant strains that don't have that protein. Yet, Ghany
says, those people are still vulnerable to liver cancer if they have the
mutant strains, which have become more prevalent and appear harder to
treat. An estimated 16,600 people in the United States will be diagnosed
with liver cancer this year, and 14,100 will die of the disease, according
to the American Cancer Society. Although relatively uncommon in the United
States, liver cancer is one of the world's most prolific tumor killers.
[Top]
Popular
liver cancer drug harmful: Study –(Times of India Online-20/11/2001)
Tamoxifen,
a popular drug used to treat liver cancer in the developing world, has
been found to be harmful to patients in a new Asia-Pacific study. "The
study showed conclusively that not only is tamoxifen not benefitting the
patient at all ... you are making them worse," Pierce Chow, who headed
the nine-country study group said. "Doctors should be discouraged from
using tamoxifen" in liver cancer treatment," said Chow, a consultant
at Singapore General Hospital.
Liver
cancer, which claims 1.25 million lives a year, is endemic among men in
the Asia Pacific, he said. Surgery offers the only significant chance
of prolonged survival, but only 10 percent of patients discover the disease
early enough to be operated on. Most other victims discover the disease
in its final stages and are treated with tamoxifen, which has a proven
record with breast cancer.
Tamoxifen
pills were cheap, costing about 22 Singapore cents (12 US cents) a day,
and doctors dispensed it hoping it would work on the liver as well, said
Chow. "If you have no proven treatment, you either treat them based on
anecdotal evidence or use drugs that have been trialed," he said. "The
doctors hoped that if it doesn't do you good, it doesn't do you bad either.
That is no longer true."
The
findings were drawn from a three-year study of 324 patients in Singapore,
Malaysia, Mynamar, South Korea, Indonesia, Thailand, Hong Kong, Australia,
New Zealand. A third of the patients were given a placebo and survived
an average 2.7 months, another third consumed 60 milligrams of tamoxifen
a day and died 2.1 months later, while the remainder took 120 milligrams
a day and died after 2.2 months. "It shows that not only does tamoxifen
not benefit the patient, it can actually harm them," Chow said, adding
the study found there was "no appreciable difference" in the patients'
quality of life. Seven previous trials conducted in Western countries
had been conflicting and inconclusive, he said.
Chow
is to begin a new study on liver cancer patients in January using megace,
an alternative drug for breast cancer patients who do not respond to tamoxifen.
[Top]
Clinical
trials to find option for treating liver cancer-(Cancer Info-06/10/2001)
Cancer is the fourth
biggest killer in Singapore, and it is men who suffer most. The problem
confronting doctors and patients alike is that when it is diagnosed, it
is already too late. Cancer specialists from 9 countries in the region
have come together to decide on the best strategy to tackle this silent
killer. Dr Pierce Chow, Consultant (Department of Surgery), Singapore
General Hospital, said, "The only proven way of treating this disease
is actually surgery, but liver cancer or primary liver cancer being such,
most patients are in a stage of the disease where surgery is no longer
possible at the moment they are diagnosed by the doctor."
In fact, in most parts
of Asia, only 10 to 15 percent of patients can undergo surgery. That leaves
the vast majority of sufferers without any options. To try to turn the
tide, the first of 3 trials was started 4 years ago with 329 patients
from 9 different countries. Associate Professor Lucien Ooi, Chief, (Hepatobiliary
Surgery), National Cancer Centre, said, "One of the beauties of doing
a study like this is involving many countries, so it's multi-national,
multi-centre, and therefore people like from Myanmar for example, from
Indonesia, from Australia, from Taiwan who are keen to participate." Strict
rules were set to ensure there was consistency. The first 2 studies also
looks at Tamoxifen, a drug that has been used for 30 years to treat breast
cancer, but now may offer some hope for those people with inoperable liver
cancer.
Associate Professor
Ooi said, "What we are trying to do in the third study is to try and administer
a particular nuclear material, and this would reduce the chance of long
term recurrence, hopefully therefore curing the patient of liver cancer."
Doctors are expecting the first results in 2 years.
[Top]
New
drug for Hepatitis C –(Times of India Online-07/08/2001)
A new drug developed
by Swiss pharmaceutical giant Roche for treating Hepatitis C has been
granted marketing approval by the Swiss regulatory authorities, the company
said.
It was the first approval for the treatment "Pegasys" in the world. The
treatment had been shown in research and trials to be "up to four times
more effective" than previous treatments with interferon, or systems for
triggering a response from the immune system.
It also had fewer side effects than conventional combination therapy.
Hepatitis C is a viral infection that can lead to liver inflammation,
liver disease, cirrhosis or liver cancer. It is transmitted primarily
through infected blood. About 170 million people are infected with the
hepatitis C virus, the company said.
[Top]
Liquor
combats liver diseases, say researchers-(Cancer Info-07/06/2001)
A four-year research
project in China has shown that Maotai, the most famous brand of Chinese
liquor can effectively combat hepatic fibrosis and hepatocirrhosis. The
liquor causes the liver to produce 22 times more metallothioneine than
normal, which is believed to prevent the formation of hepatic fibrosis.
Metallothioneine and superoxide dismutase, another element in Maotai,
can remove free radicals in human body and combat tumours.
Medical examinations
conducted on 99 workers at the Maotai liquor plant in southwest China's
Guizhou province, who drink an average of 250 grams of Maotai per day,
found no cases of hepatic fibrosis or hepatocirrhosis. Maotai is rich
in proteins, vitamins and aminophenols.
Research results also
showed a low rate of gastric ulcers and digestive system diseases among
Maotai drinkers. Maotai made its reputation at an international exposition
in 1915, and has become a popular alcoholic drink for important occasions.
[Top]
Treating
Liver Cancer With Glass Beads Approved-(Cancer Info 06/06/2000)
A method for treating
liver cancer with tiny radioactive glass beads, developed by researchers
at the University of Missouri-Rolla and the University of Missouri-Columbia,
has been approved for use in the United States. The first patients to
be treated with radioactive glass beads, now marketed under the name TheraSphere
by MDS Nordion, will be treated later this year at the Mayo Clinic in
Rochester, Minn., and at the University of Pittsburgh School of Medicine.
The treatment consists
of injecting millions of tiny, radioactive glass beads into the main artery
supplying blood to the liver. The blood carries the beads into the liver,
where they deliver localized radiation to malignant cells in liver tumors.
[Top]
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