Monthly Archives: October 2007

Chewing tobacco: Not a risk-free alternative to cigarettes

  • 10/31/2007
  • Rochester, MN
  • staff

Get the facts about chewing tobacco. It’s more harmful and addictive than you might think.

You can call it what you want — smokeless tobacco, spit tobacco, snus, chew, snuff, pinch, plug or dip — but don’t call it harmless. If you’re considering making the switch from cigarettes to chewing tobacco because you think the smokeless version of tobacco won’t hurt you, be forewarned — chewing tobacco also causes serious health problems. Find out why chewing tobacco is not a healthy option.

Chewing tobacco: Just one form of smokeless tobacco
Smokeless tobacco products consist of tobacco or a tobacco blend that’s chewed, inhaled or sucked on rather than smoked. It’s available in three main forms:

– Chewing tobacco. This type of smokeless tobacco comes in loose leaf, plugs or twists. As the name suggests, it’s chewed.

– Snuff. This product is available dry or moist, in loose leaf or in pouches that look like small tea bags. A pinch of snuff may be placed between the cheek and the gum or inhaled into the nostrils.

– Betel quid. A product of India, Africa and Asia, betel quid is produced commercially or made at home. It consists of a dried paste that often includes tobacco, areca nuts, catechu, and scent or flavoring. Catechu is a plant-based product used to treat diarrhea and sometimes used for birth control in some parts of the world. Areca nuts are a plant-based product often used as a recreational drug. Betel is placed in the mouth, usually between the gum and cheek, and gently sucked and chewed.

Though the concept of chewing tobacco might conjure up images of spittoons and messy brown liquid, not all smokeless tobacco needs to be spit out during use. Tobacco companies have developed a friendlier version of chewing tobacco — a spitless tobacco — in an effort to convince more smokers to consider using smokeless products in places where smoking is prohibited.

Health risks of chewing tobacco and other forms of smokeless tobacco

Using chewing tobacco and other smokeless tobacco products can cause serious health problems, from gum irritation to oral cancer.

Chewing tobacco gets you hooked on nicotine, similar to the way cigarettes do. And once you’re addicted, it becomes difficult to stop using chewing tobacco. Just as with smoking, withdrawal from chewing tobacco causes signs and symptoms such as intense cravings, increased appetite, irritability and depressed mood.

People who use chewing tobacco eventually develop a tolerance for nicotine and need more tobacco to feel the desired effects of the nicotine. Some people switch to brands with higher nicotine content and tend to use chewing tobacco more frequently the longer they’ve been using smokeless products. More severely addicted users may leave the chew in their mouths overnight and swallow the tobacco juices.

Chewing tobacco and other forms of smokeless tobacco cause tooth decay. That’s because chewing tobacco contains high amounts of sugar, which contributes to cavities. Chewing tobacco also contains coarse particles that can irritate your gums and scratch away at the enamel on your teeth, making your teeth more vulnerable to cavities.

Gum disease
The sugar and irritants in chewing tobacco and other forms of smokeless tobacco can cause your gums to pull away from your teeth in the area of your mouth where you place the chew. Over time you can develop gum disease (gingivitis) and possibly tooth loss.

Heart problems and non-oral cancer
Smokeless tobacco increases your heart rate and blood pressure. Some evidence suggests that it may put you at an increased risk of heart attack. People who use smokeless tobacco also have higher cholesterol levels than those who don’t use tobacco. And a study published in June 2007 in the medical journal The Lancet showed a connection between the use of one form of smokeless tobacco (snus) and an increased risk of pancreatic cancer.

Precancerous mouth lesions
People who use smokeless tobacco are more likely to develop small white patches called leukoplakia (loo-ko-PLA-ke-uh) inside their mouths where the chew is most often placed. These mouth lesions are precancerous — meaning that the sores could one day develop into cancer. After stopping tobacco usage, the lesions usually go away in a few weeks or a few months.

Oral cancer
Your risk of oral cancer is increased if you use smokeless tobacco. Oral cancer includes cancers of the mouth, throat, cheek, gums, lips and tongue. Surgery to remove cancer from any of these areas can leave your jaw, chin, neck or face disfigured.

Smokeless doesn’t mean harmless
If you aren’t convinced that chewing tobacco, spit tobacco and other forms of smokeless tobacco aren’t risk-free, consider the words of someone who’s seen the damage tobacco can do. Joe Garagiola, a former spit tobacco user, played major league baseball and later worked in broadcasting. After retiring from baseball he became a crusader against spit tobacco — the term he prefers since “smokeless” makes tobacco sound harmless.

“I chewed tobacco because it seemed to be the thing to do if you were playing baseball,” says Garagiola. “Everybody chewed when I was playing, and nobody knew the dangers of it.” But he’s seen the dangers since, losing three close friends to oral cancer and seeing the harmful effects of spit tobacco on other people.

“You won’t die of gum disease or yellow teeth, but develop oral cancer and it’s a terrible way to go,” Garagiola says. “Here you are with oral cancer from using spit tobacco, your jaw has been removed and you have to eat through a tube. You die one piece at a time. Spit tobacco is a horrible, horrible thing. I just wish I could get this message across to everyone.”

It’s never too late to quit
If you’re using smokeless tobacco, quit. Now that you know the dangers associated with it, you have extra motivation to give it up. Here’s what to do:

– Set a quit date. Mark your quit day on your calendar and commit to it. Select a day at least one week away so that you have time to prepare for your life as a former tobacco user.

– Talk to your doctor. Tell your doctor about your goal to quit using smokeless tobacco and ask for advice. Smokeless tobacco users have more success with quitting if they talk to a doctor or dentist about strategies for quitting.

– Consider medications. Ask your doctor about medications that can help you quit, such as over-the-counter nicotine replacement products, including patches, gum, inhalers and lozenges. There are also non-nicotine prescription medications such as bupropion (Zyban) and varenicline (Chantix) that can ease nicotine withdrawal symptoms when you quit.

– Get support. Join a support group in your area. Go online. Get help and support from people who understand what you’re going through. Free resources are available, so don’t worry about a financial cost.

Devise a plan to deal with cravings and know that cravings typically last only a few minutes. Eating licorice, chewing gum, going for a walk or calling a friend can help you get through them. And the interval between cravings increases the longer you’ve stopped using tobacco and eventually the cravings will go away.

October, 2007|Archive|

Improving Head and Neck Cancer Survival

  • 10/31/2007
  • Orlando, FL
  • Kate McHugh, Ivanhoe Health Correspondent

Head and neck cancers affect more than 40,000 people in the United States every year and more than 500,000 worldwide. When caught early, the prognosis is promising, but survival rates decrease as the disease advances. Now, two treatment therapies are making a big difference in the survival of patients suffering from advanced head and neck cancers.

Standard initial treatment for advanced head and neck cancers is chemotherapy. Two new studies show promising results with treatments following chemo.

“I think that patients get very scared when they get this diagnosis, frightened and anxious. I think they should recognize that we are now clearly above the 50-percent [survival] level — quite a bit above it,” Marshall Posner, M.D., medical director of the Head and Neck Oncology Center at the Dana-Farber Cancer Institute in Boston, told Ivanhoe.

In a recent study out of Europe, researchers found a combination therapy treatment, known as TPF — adding docetaxel to the standard PF therapy (cisplatin and fluorouracil) — improved survival outcomes by 27 percent in patients with an unresectable cancer — tumors that cannot be removed.

“What the European trial demonstrates is that TPF is a reasonable therapy for patients with an unresectable disease and promotes an improvement in survival,” said Dr. Posner, the lead author of another new study, which reveals using the TPF therapy after chemotherapy and following with chemoradiotherapy — a combination of chemotherapy with radiation therapy — gives patients a 30-percent reduction in mortality and may even eliminate the cancer.

“What our trial shows is that induction chemotherapy with TPF followed by chemoradiotherapy improves survival across all subtypes and groups of patients with head and neck cancer, and that it represents a reasonable treatment for patients with locally advanced disease,” Dr.Posner said.

According to Dr. Posner, these drugs are already FDA approved and available for treatment. “It would just be a matter of discussing it and deciding what is best for them in terms of the treatment,” Dr. Posner said.

“Both of these trials demonstrate one of the same things, which is that the three drug regimen … is significantly better in terms of survival for patients with advanced head and neck cancer compared to the prior standard care, which is PF,” Dr. Posner said.

Ivanhoe interview with Marshall Posner, M.D., The New England Journal of Medicine, 2007;357:1695-1704,1705-171

October, 2007|Archive|

Vaccine Treatment Takes Aim At Oral Cancer

  • 10/29/2007
  • web-based article
  • Hilary Waldman

Promising New Drug Was Originally Designed To Fight Cervical Cancer

A new cervical cancer vaccine headed for FDA approval this month could also put a dent in new cases of oral cancer – one of the deadliest cancers in the United States.

At least one-quarter of oral cancer cases may be linked to human papillomavirus, the same sexually transmitted bug that causes cervical cancer.

“Because of this vaccine, in 10 to 15 years, we’re going to find many fewer head and neck cancers, it will have a positive collateral benefit not related to its primary cervical cancer use.” said Brian Hill, founder and executive director of the Oral Cancer Foundation.

Researchers started looking for new possible causes of oral cancer when tobacco use dropped precipitously in the United States but the incidence of oral cancer did not.

About 34,000 people will be diagnosed with oral cancer in the United States this year, and only half of them will be alive in five years. The death rate for oral cancer is higher than that for cancer of the cervix, testicles, skin (melanoma), Hodgkins disease, a type of blood cancer and other we commonly hear about.

Six years ago, researchers at Johns Hopkins School of Medicine looked at 253 patients with head and neck tumors and found HPV-16 – the tumor-causing strain of the virus – in 25 percent of those patients.

HPV-positive tumors are most likely to occur in the throat, base of the tongue, and tonsils and appear to be more responsive to treatment than tumors that are not associated with the virus.

Although the presence of HPV in head and neck tumors has not yet been convincingly linked to sexual practices, such as kissing and oral sex, several studies suggest that there may be a connection. (OCF disagrees with this statement, the connection to oral sex is well established in peer reviewed publications.)

Thus, said Hill and others, the vaccine called Gardisil will not help people who are already sexually active. But advocates recommend that 11- and 12-year-old children be vaccinated, a move that could drastically reduce deaths from cervical and oral cancer.

For people who are already sexually active, there is no substitute for a thorough annual examination by a dentist or a physician.

Caught in its earliest stages, oral cancer can be cured in 80 percent to 90 percent of cases. Once it has spread beyond the mouth, however, the survivla rate drops – only 50 percent percent of patients survive for five years when all stage are considered.

“Sixty percent of the American population sees a dentist every year,” Hill said. “When exit surveys are done, only 7-to-15 percent of patients said they had had an oral cancer exam while they were there.”

Hill recommends that patients ask their dentists for an oral cancer screening during every routine check-up.

A proper exam includes lifting the tongue with a gauze pad to examine the underside and the floor of the mouth ( OCF added note after publication:also pulling the tongue forward to siualize the base of it where HPV lesions often appear). The doctor or dentist should then put one finger under the tongue and one under the chin to feel for unusual bumps.

Some precancerous spots appear as white or red patches in the mouth that linger for more than two weeks. Cancer is most likely to appear on the sides of the tongue, the floor of the mouth, the soft palate or the tonsils. It is very rare in the hard palate, cheeks or the top of the tongue.

“There is no substitute for a good oral exam in the hands and eyes of a knowledgeable clinician,” said Dr. Ellen Eisenberg, a professor of oral health and diagnostic sciences at the University of Connecticut Health Center.

Some new technologies are emerging to help dentists detect and test for oral cancer. One product uses an acid rinse and an ultraviolet light stick to help dentists see suspicious spots in the mouth.

The product, called ViziLite, adds about $50 to $100 to the price of a routine dental exam and is not covered by most insurance.

Another product called the oral brush biopsy allows dentists or doctors to look at suspicious spots without sending the patient for an immediate surgical biopsy.

The brush biopsy has been compared to a Pap test for the mouth. Using a small tool, the doctor or dentist can remove a tiny sample of cells from a suspicious spot. With the help of computer analysis, the test can identify cancer cells in their earliest stages.

The brush biopsy is considered useful because it is not painful and is simple to perform. Experts hope the availability of the test will persuade doctors and dentists to test suspicious lesions quickly, instead of waiting to see if they go away.

Dr. Sol Silverman, a professor of oral medicine at the University of California, San Francisco, and a spokesman for the American Dental Association, said dentists who find suspicious lesions might recommend that the patient come back in a few weeks for a second look.

But, if the patient does not return, an opportunity for early diagnosis could be missed, Silverman said. “What these technologies do is accelerate the biopsy.”

Original article can be found here .

October, 2007|OCF In The News|

A New Job for Bill Clinton

  • 10/29/2007
  • web-based article
  • Cliff Kincaid
  • Accuracy in Media (

My commentary on the need for Bill Clinton to take the lead in warning teenagers about the dangers of oral sex caught the eye of Brian R. Hill, the founder/ Executive Director of the Oral Cancer Foundation, Inc. He is a stage IV oral cancer survivor.

On the matter of a link between HPV 16, a sexually transmitted virus, and cancer, especially oral cancer, he writes:

“The real data about this has been mostly published by Maura Gillison at Johns Hopkins, and the correlation between HPV 16 in particular and oropharangeal and tonsillar cancers is without doubt, ditto the oral sex /oral cancer issue. There is no doubt that the HPV’s forms which have cancer causing capabilities are on the rise, and the number of young, non-smoking, oral cancer patients has risen dramatically in recent years. While the primary cause, tobacco, has had its use steadily decline for more than 10 years in the U.S., the incidence rate of oral cancer has stayed the same. This would indicate that a new etiology is replacing the old stereotypical mechanism of getting this very deadly disease.

“While you mention a Swedish study, the U.S. is way ahead of others in the peer-reviewed research that shows all this to be a major issue…Though the issue of awareness is critical, and Dr. Gillison even uses the word epidemic when she discusses HPV in the U.S., it is hard to get people of celebrity and power to discuss anything sexual…I wish I could identify someone to come forward and talk about it beside myself. While I have been on numerous TV news stories about it, and lecture on it extensively in many arenas, I am a virtual nobody. The disease and the issues need a celebrity or corporate powerhouse to champion a very deadly disease that kills someone in the U.S. every hour of every day. Our efforts to raise public awareness have not gone unnoticed, and our website (below) gets 15 million hits a month.”

The website of the oral cancer foundation is

Hill says a celebrity is needed to discuss the link between oral sex and cancer. Will Bill Clinton step forward? He should do so. He did more than anyone else to make oral sex into a household topic for young people and adults alike. And he told the nation under oath that it really wasn’t sex, making it seem attractive or harmless. The disgraced former president can be contacted through his Clinton Foundation at If he won’t step forward to take on this campaign, perhaps he can ask Monica Lewinsky to fill in for him.

I agree that it is a risk for Clinton. It’s much easier for him to step forward as a former junk food junkie who ate too many hamburgers. We can all laugh about that, even though he did have to get a heart bypass operation. It’s much tougher for him to step forward and admit that he exploited a young girl for oral sex and is sorry about it. But that’s why the media, if they had any integrity, would challenge him. They can ask him about giving up junk food. Why not ask him about immoral, unhealthy and compulsive sexual behavior?

It’s a matter of life and death.

The original article can be found here .

October, 2007|OCF In The News|

Dentistry: Checking for Oral Cancer

  • 10/29/2007
  • Washington, D.C.
  • Sherri Dalphonse
  • Washingtonian (

While the number of oral-cancer cases diagnosed annually—about 30,000 in this country—has remained steady, the victims have changed. There’s been a fivefold increase in oral cancer in people under age 40, particularly women.

And while smoking and drinking are still the biggest risk factors, one-quarter of all patients are not smokers.

A study by Johns Hopkins University found human papillomavirus in one-fourth of oral-cancer patients. The rise in HPV and oral sex has been linked to oral cancer in young women.

“One problem,” says Brian Hill, director of the Oral Cancer Foundation and an oral-cancer survivor, “is that dentists are still looking for the stereotypical smoker” when screening for cancer.

How do you know if your dentist does a thorough check for oral cancer? In an exam, Hill says, a dentist should pull out the tongue for a good look—many cancers occur at the base of the tongue qwhich can more easily be seen when pulled forward—and run a finger along the edges to feel for lumps. He or she should feel the floor of the mouth and the sides of the neck.

When oral cancer is caught early, there’s an 80-percent survival rate. Because it is usually caught late, half of such patients die within five years.

According to the Oral Cancer Foundation (, symptoms include

• a sore or lesion in the mouth that does not heal within two weeks.

• a lump or thickening in the cheek.

• a white or red patch on the gums, tongue, tonsil, or lining of the mouth.

• a sore throat or feeling that something is caught in the throat.

• difficulty chewing or swallowing.

• difficulty moving the jaw or tongue.

• numbness of the tongue or other area of the mouth.

These symptoms can be caused by other, less serious problems.

While suspicious spots may have to be biopsied, some dentists use tools such as the Oral CDx brush or the ViziLite to first rule out cancer and the need for a biopsy.

Some dentists may suggest keeping an eye on a lesion. Oral surgeon Steven Guttenberg warns against watching too long: “This cancer doubles every six weeks. If you wait, it could be too late.”

Original article can be found here.

October, 2007|OCF In The News|

Gene Chip Enables Personalized Cancer Treatment

  • 10/29/2007
  • Jerusalem, Israel
  • staff
  • The Future of Things (

An oncologist from Michigan has devised a new approach to clinical medicine. Using DNA micro-array chips, Dr. Eric Lester analyzed gene expression profiles of tumors in patients with advanced incurable cancer. For each patient, he first identified certain genes associated with a favorable response to anti-cancer drugs, and then determined an individualized treatment plan according to these findings.

New, targeted cancer therapies focus on specific genetic mutations in the patient’s body in order to fight the disease. These therapies usually also have fewer side-effects than conventional chemotherapy. However, cancer is a complex, dynamic and unpredictable disease with a wide array of embodiments at the molecular level. For this reason, no single treatment is effective against every type of tumor. In order to effectively treat cancer we need to understand the biological mechanisms behind it. Since every cancer tumor is unique, doctors struggle to find the most suitable personalized treatment plan for each patient. Currently, they rely mostly on their instincts and personal experience to choose the appropriate treatment methods.

Dr. Eric Lester, of the Oncology Care Associates in St. Joseph, Michigan, devised an experiment that illustrates the promise of personalized medicine. He had six patients with advanced, incurable cancer. In order to determine which anti-cancer drugs would benefit each patient, Lester analyzed his patients’ tumors, seeking the expression of genes associated with responsiveness to various anti-cancer drugs. He then based his drug treatment plans on the experiment’s findings.

To analyze gene expression in the tumors Dr. Lester used Affymetrix’s DNA micro-arrays, which are small chips used to measure genetic information on a large scale. Affymetrix’s gene chips can be tagged with hundreds of thousands of gene sequences that will either attract or repel pieces of DNA or RNA from a certain sample. The attraction or repulsion of the DNA and RNA indicate gene mutations (genotype testing) or gene activity patterns (expression testing) in the sample.

Dr. Lester and Craig Webb, Ph.D., Director of Translational Medicine at the Van Andel Research Institute in Grand Rapids, Michigan, surveyed the scientific literature and compiled a list of genes whose expression levels may predict responsiveness to certain drugs against a type of tumors. Webb and Lester compared the tested patients’ personal micro-array results to the pharmaceutical and genomic data bases and determined an individualized treatment plan for each patient. In some cases, after analyzing the information derived from the chips, the doctors suggested completely different treatment strategies for patients with the same type of cancer.

Out of six patients with advanced cancer that participated in this limited study, four responded better than was expected. This may suggest that a personalized molecular oncology approach, basing chemotherapy on relative gene expression in the tumors, holds a promise even for patients with incurable cancer. However, is it too early to draw unequivocal conclusions regarding the benefits and effectiveness of the new approach. In order to establish the results of this experiment, studies should be held on a large scale and over a long period, in a manner that will enable monitoring the therapy’s comprehensive influence on the patients’ health and life span.

Lester and Webb’s experiment is unusual because oncologists don’t tend to be enthusiastic about basing their treatment decisions on gene profiling, especially when it might involve pairing drugs together in a novel combination or using varied doses, Dr. Lester said. He added that to truly help patients the most, all potentially effective drugs and combinations must be matched up against the unique genetic profile of a patient’s tumor. According to Dr. Lester, this kind of polypharmacy will become more common in cancer treatment and at the moment, the best way to deal with issues of effectiveness and toxicity of drug doses is to build a database of gene expression data and match it with patient treatment results.

TFOT recently covered a couple of other research projects dealing with chips for detection of cancer biomarkers. These chips include the “lab on a chip” device enabling detection of oral cancer cells, developed at the Texas University, and the Nanocytometer, which locates cancer cells or other specific cells in the blood,developed at the University of California, Berkeley.

October, 2007|Archive|

Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer

  • 10/29/2007
  • web-based article
  • Jan B. Vermorken et al
  • New England Journal of Medicine (

Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.

We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival.

A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007).

Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group.

As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck.

Jan B. Vermorken, M.D., Ph.D., Eva Remenar, M.D., Carla van Herpen, M.D., Ph.D., Thierry Gorlia, M.Sc., Ricard Mesia, M.D., Marian Degardin, M.D., John S. Stewart, M.D., Svetislav Jelic, M.D., Jan Betka, M.D., Joachim H. Preiss, M.D., Ph.D., Danielle van den Weyngaert, M.D., Ahmad Awada, M.D., Ph.D., Didier Cupissol, M.D., Heinz R. Kienzer, M.D., Augustin Rey, M.D., Isabelle Desaunois, M.Sc., Jacques Bernier, M.D., Ph.D., Jean-Louis Lefebvre, M.D.

Authors’ affiliations:
From Universitair Ziekenhuis Antwerpen, Edegem, Belgium (J.B.V.); the National Institute of Oncology, Budapest, Hungary (E.R.); Universitair Medisch Centrum Nijmegen, Nijmegen, the Netherlands (C.H.); EORTC Data Center, Brussels (T.G., I.D.); Institut Catala d’Oncologia, Barcelona (R.M.); Centre Oscar Lambret, Lille, France (M.D., J.-L.L.); Charing Cross Hospital, London (J.S.S.); the Institute of Oncology and Radiology, Belgrade, Serbia (S.J.); University Hospital Motol, Prague, Czech Republic (J. Betka); Caritasklinik St. Theresia, Saarbrucken, Germany (J.H.P.); Ziekenhuis Netwerk Antwerpen Middelheim, Antwerp, Belgium (D.W.); Institut Jules Bordet, Brussels (A.A.); Centre Régional de Lutte contre le Cancer Val d’Aurelle, Montpellier, France (D.C.); Kaiser Franz Josef Spital, Vienna (H.R.K.); Sanofi-Aventis Global Oncology, Paris (A.R.); and Clinique de Genolier, Genolier, Switzerland (J. Bernier)

October, 2007|Archive|

Gold Nanorods Shed Light On New Approach To Fighting Cancer

  • 10/29/2007
  • West Lafayette, IN
  • staff
  • Biocompare Life Science News (

Researchers have shown how tiny “nanorods” of gold can be triggered by a laser beam to blast holes in the membranes of tumor cells, setting in motion a complex biochemical mechanism that leads to a tumor cell’s self-destruction.

Tumor cell membranes often have an abnormally high number of receptor sites to capture molecules of folic acid, or folate, a form of vitamin B that many tumor cells crave. The Purdue researchers attached folate to the gold nanorods, enabling them to target the receptors and attach to the tumor cell membranes.

“The cells are then illuminated with light in the near-infrared range,” said Ji-Xin Cheng (pronounced Gee-Shin), an assistant professor in Purdue’s Weldon School of Biomedical Engineering. “This light can easily pass through tissue but is absorbed by the nanorods and converted rapidly into heat, leading to miniature explosions on the cell surface.”

Scientists have recently determined that gold nanorods and other nanostructures can be used to target and destroy tumor cells, but it was generally assumed that cell death was due to the high heat produced by the light-absorbing nanoparticles. The Purdue team discovered, however, that a more complex biochemical scenario is responsible for killing the cells.

“We have found that rather than cooking the cells to death, the nanorods first punch holes in the membrane, and cell death is then chemically induced, in this case by an influx of calcium,” said Alexander Wei, an associate professor of chemistry at Purdue.

Findings are detailed in a research paper appearing Oct. 19 in the journal Advanced Materials. The paper, which appeared online last week, was written by doctoral students Ling Tong, Yan Zhao, Terry B. Huff and Matthew N. Hansen, along with Wei and Cheng.

The gold rods are less than 15 nanometers wide and 50 nanometers long, or roughly 200 times smaller than a red blood cell. Their small size is critical for the technology’s potential medical applications: the human immune system quickly clears away particles larger than 100 nanometers, whereas smaller nanoparticles can remain in the bloodstream far longer.

Shining light on the gold nanorods causes them to become extremely hot, ionizing the molecules around them.

“This generates a plasma bubble that lasts for about a microsecond, in a process known as cavitation,” Wei said. “Every cavitation event is like a tiny bomb. Then suddenly, you have a gaping hole where the nanorod was.”

The gold nanorods also are ideal for a type of optical imaging known as two-photon luminescence, used by Cheng and his research group to monitor the position of nanorods in real time during tumor-cell targeting. The imaging technique provides higher contrast and brighter images than conventional fluorescent imaging methods.

In experiments with tumor cells in laboratory cultures, the nanorods attached to the cell membranes and were eventually taken up into the cells. The researchers found that it could take far less power to injure cells by exposing the nanorods to near-infrared light while they are still on the membrane surface instead of waiting until the nanorods are internalized.

“This means that if you wait until the nanorods are inside the cell, then you really have to pump up the laser power, so localizing the nanorods on the cell membrane strongly influences their ability to inflict cell damage,” Cheng said.

The findings suggest an optimal window of opportunity for applying near-infrared light to the nanorods for cancer treatment.

“We like to believe this opens the possibility of using nanorods for biomedical imaging as well as for therapeutic purposes,” Cheng said.

The Purdue researchers observed that light-absorbing nanorods cause the formation of membrane “blebs, ” similar to severe blistering. These blisters, however, are not produced directly by the high heat generated by the nanorods.

“The blebbing is triggered by the nanorods, but it’s really caused through a complex biochemical pathway – a chemically induced process,” Cheng said. “Extra calcium gets into the cell and triggers enzyme activity, which causes the infrastructure inside the cell to become loose, and that gives rise to the membrane blebs.”

Researchers used a calcium-sensitive fluorescent dye to back up their argument that calcium influx caused the tumor cell death. When the nanorod-bearing tumor cells were maintained in a calcium-free nutrient medium, no blisters were formed if the nanorods were exposed to near-infrared light. But when the researchers added calcium to the medium, the blebbing took place immediately.

Although the technique offers promise for a new cancer treatment, it is too early to determine when it could be in clinical use, said Wei, who is collaborating with the National Cancer Institute to determine the suitability of the functionalized gold nanorods for future clinical studies.

Source: Purdue University

October, 2007|Archive|

Three Chemo Drugs Better Than Two for Advanced Head-Neck Cancers

  • 10/29/2007
  • Serena Gordon

The addition of the chemotherapy drug, docetaxel, to the standard two-drug regimen used for head and neck cancers improved the efficacy of the treatment while reducing the toxicity, two new studies report.

The triple drug chemotherapy regimen was so effective that it increased survival in both studies and more than doubled the average overall survival in one of the studies.

“This is a study that demonstrates that a three-drug regimen is better by a substantial amount in terms of survival for head and neck cancer. There was a 30 percent reduction in mortality with less toxicity,” said Dr. Marshall R. Posner, lead author of the first study and medical director of the head and neck oncology program at the Dana-Farber Cancer Institute in Boston. “This is a wonderful step forward for patients.”

Results from both clinical trials are published in the Oct. 25 issue of the New England Journal of Medicine. Both studies were funded, at least partially, by Sanofi-Aventis, the manufacturer of docetaxel.

About 3 percent to 5 percent of all cancers in the United States are head and neck cancers, according to the National Cancer Institute. That means almost 40,000 Americans are diagnosed with these cancers each year. They most commonly occur in people over 50, and the biggest risk factor for head and neck cancers is tobacco use.

Treatment for these cancers can be difficult, because surgical removal of tumors can affect the way a person chews, talks and swallows. In some cases, it’s impossible to surgically remove some of these cancers, because the risk of harm outweighs the potential benefit. The cancer is then referred to as unresectable.

The study done by Posner and his colleagues included 501 people with advanced — stage III or IV — head and neck cancers. None of the volunteers had any signs of cancer in areas far from the original tumor site. Posner said his study included people who had both unresectable and resectable tumors.

The study participants were randomly assigned to receive the standard two-drug regimen (cisplatin and fluorouracil) or the new three-drug treatment which included cisplatin, fluorouracil and docetaxel. People in both groups then received seven weeks of weekly chemoradiotherapy (chemotherapy and radiation combined) with carboplatin, and radiotherapy (radiation treatment) for five days a week. Those who became eligible for surgery were able to have surgery six to 12 weeks after completing chemoradiotherapy.

Overall survival after three years was estimated to be 62 percent for the three-drug group compared to 48 percent for the two-drug group. Median overall survival was 71 months for the newer treatment versus just 30 months for the older regimen, according to the study.

The second study, conducted by European researchers, randomly assigned 358 people with unresectable stage III or IV head and neck cancer to receive either the two-drug regimen or the newer three-drug treatment. If there was no progression of disease after the study participants completed chemotherapy, they were given radiotherapy.

Overall survival increased from 14.5 months for the two-drug group to 18.8 months for the three-drug group in this study.

In both studies, the three-drug regimen had a similar, though slightly reduced, side-effect profile than the two-drug therapy. Posner said that’s because they were able to use less fluorouracil in the three-drug regimen.

“We maximized efficacy and reduced toxicity. With the inclusion of the [three-drug induction chemotherapy] followed by chemoradiotherapy, we saw unprecedented survival,” said Posner.

Of the new research, Dr. David Pfister, chief of the head and neck medical oncology service at Memorial Sloan-Kettering Cancer Center in New York City, said that the “triple-drug regimen is more effective than the standard regimen alone when given prior to radiation-based treatment and not at a cost of side effects. There was no increase in overall toxicity.”

But, what he said oncologists want to know is whether induction chemotherapy (as was done in these studies) plus chemoradiotherapy is more effective than chemoradiotherapy alone. The addition of induction therapy, said Pfister, adds about three months to the treatment process.

He said studies are currently under way to determine which treatment is best, and, in the meantime, said that chemoradiotherapy alone is the current standard of care.

Marshall R. Posner, M.D., associate professor, medicine, and medical director, head and neck oncology program, Dana-Farber Cancer Institute, Boston; David Pfister, M.D., chief, head and neck medical oncology service, Memorial Sloan-Kettering Cancer Center, New York City; Oct. 25, 2007, New England Journal of Medicine

October, 2007|Archive|

Integrated approach to IMRT provides quality care for head and neck cancer patients

  • 10/29/2007
  • Los Angeles, CA
  • press release
  • EurekAlert! (

Results from a University of Pittsburgh study demonstrate that intensity-modulated radiation therapy (IMRT) for head and neck cancer can be uniformly delivered in a large health care system of academic and community cancer centers through a centralized planning and treatment process. The findings were presented today at the 49th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Los Angeles.

“Our study demonstrates that it is feasible for head and neck cancer patients to receive IMRT in their own communities without sacrificing high-quality care,” said Dwight Heron, M.D., associate professor of radiation oncology, University of Pittsburgh School of Medicine and director of radiation oncology, University of Pittsburgh Medical Center (UPMC). “This is possible through an integrated network in which treatment is standardized across all cancer centers.”

According to study results, there were no significant differences in toxicity profiles and treatment outcomes in 604 head and neck cancer patients treated with IMRT at 12 community cancer centers and one academic flagship facility. Two hundred and forty-eight patients (41 percent) were treated at the flagship facility, and 356 patients (59 percent) received IMRT at one of the community centers. All 13 centers, connected through a telemedicine network, followed the same clinical pathway guidelines for the radiotherapy management of head and neck cancer, which included specific details on volumes for radiation treatment planning and recommended doses of IMRT. When the investigators compared outcomes between the academic center and the community centers, they found that there were no significant differences between survival or recurrence rates.

“By standardizing planning and treatment for IMRT, patients who live in remote locations can benefit from the same quality of care available at a large National Cancer Institute-designated comprehensive cancer center,” said Dr. Heron. “Bringing advanced radiation therapy to community locations can have a very positive effect on a patient’s quality of life by relieving the anxiety and stress of traveling for treatment.”

IMRT treatment planning for the centers was performed at one central location, D3 Radiation Planning, located in Pittsburgh. Through telemedicine capabilities, medical physicists based at D3 collaborated with radiation oncologists at community locations to develop individualized treatment plans for the patients.

Co-authors of the study include Ajay Bhatnagar, M.D., Ryan Smith, M.D., Sushil Beriwal, M.D., Saiful Huq, Ph.D., Sanjeev Bahri, M.D., Jonas Johnson, M.D., Susan Rakfal, M.D., with the University of Pittsburgh School of Medicine; and Y. Wang, Ph.D., and Marc Sontag, Ph.D., with D3 Radiation Planning. UPMC is an investor in D3 Radiation Planning.

October, 2007|Archive|