Monthly Archives: March 2004

Sunlight Linked to Cervical Cancer Risk

  • 3/30/2004
  • By Jennifer Warner
  • See sources at end of article

The effects of sun exposure on women’s health may be more than skin deep. A new study suggests that a woman’s risk of cervical cancer may be much higher during sunny months. Researchers tracked nearly a million Pap smear results collected over 16 years in southern Holland and found that women were twice as likely to be infected with the human papilloma virus (HPV) during the sunny days of August than in the darker days of winter. HPV is the most common sexually transmitted disease. Pap smears that test for HPV infection are commonly used worldwide as a tool to screen for signs of cervical cancer. The vast majority of women with HPV infection will not develop cervical cancer, but cervical cancer is a rare complication of this common infection. About 20 of the more than 230 types of HPV are considered high risk because of their close association with the disease.

HPV Risks Rise During Sunny Months?

In the study, researchers looked at seasonal patterns of HPV infection among 920,359 consecutive Pap smears collected from 1983 to 1998 and compared it with differences in sunlight exposure. The results showed that the number of HPV infections was twice as high in August compared with the lowest month, and the rates of HPV infection were closely linked to available sunlight exposure. “The sunnier the year, the higher the HPV rate, and the sunnier the month, the higher the HPV rate,” says researcher William Hrushesky, MD, a professor at the University of South Carolina School of Medicine.

Surprisingly, researchers say the study showed that HPV rates were not linked to sexual activity. The study looked at three centuries of birth records in Holland and found conception rates (and presumably heterosexual activity) peaked in the spring, but HPV infection rates peaked four months later. That prompted researchers to suspect that there might be a relationship between sunlight and ultraviolet (UV) light exposure and susceptibility to HPV.

Hrushesky says previous studies have suggested that UV exposure can negatively affect the body’s immune system by interfering with the production of disease-fighting T cells and therefore lower the body’s natural defenses against infection. In this case, he says that seasonal changes in sunlight exposure may make the body more prone to HPV infection even though the cervical cells aren’t directly exposed to sunlight. “Sunlight exposure and solar immune changes associated with sunlight exposure may render cervical epithelium [cells within the cervix] more sensitive to HPV infection,” says Hrushesky. In addition, Hrushesky says viruses are activated by exposure to ultraviolet rays, which may also make HPV more potent.

Connection ‘Makes Sense’

Raymond DuBois, MD, PhD, who moderated a discussion of the study’s findings at the annual meeting of the American Association for Cancer Research in Orlando, Fla., says the sunlight-HPV connection makes sense and merits further study. “I think it’s a complex biological and behavioral situation,” says DuBois, who is associate director for cancer prevention, control, and population-based research at Vanderbilt-Ingram Cancer Center in Nashville.

“We know, for example, that the amount of sunlight exposure affects a person’s mood and behavior, and that could affect downstream what things they are exposed to,” says DuBois. “All things that we’re exposed to in the environment are important, I think, because they could modulate our risk for cancer.”

SOURCES: American Association for Cancer Research 95th annual meeting, Orlando, March 27-31, 2004. William Hrushesky, MD, professor, University of South Carolina School of Medicine. Raymond DuBois, MD, PhD, associate director for cancer prevention, control, and population-based research, Vanderbilt-Ingram Cancer Center, Nashville. News release, American Association for Cancer Research. WebMD Medical News: “Women Misinformed About HPV-Cancer Link.”

March, 2004|Archive|

Tumor treatment determined by genetic profile, not clinical appearance

  • 3/30/2004
  • Honolulu, Hawaii
  • International Association for Dental Research, Annual Meeting presentation

Detailed molecular analysis of tumors is now providing molecular portraits which show the genetic basis of the different clinical presentations of disease. This technology will help identify metastasis signatures and provide logical targets for drug discovery. This moves us closer to a time when we will treat patients based on the genetic profile of the tumor rather than the clinical presentation of the disease. Finding targets that are differentially expressed in cancer and normal tissue will also provide better tests for early diagnosis.

There is also increasing interest in utilizing knowledge about tumor biology to address the vexing question as to why tumors recur despite seemingly adequate treatment.

A new generation of ultra-sensitive diagnostics has highlighted the problem of subcutaneous foci of residual tumors that may remain at the operative site, or be disseminated throughout the body. These approaches have also revealed that the extent of spread of a precancerous patch is often much greater than previously realized.

Long-term follow-up of cases screened by these molecular diagnostics suggests that detecting these troublesome foci of disease can help to identify individuals at risk of developing local and distant recurrence.

In a Keynote Address during the 82nd General Session of the International Association for Dental Research, Dr. Maxine Partridge (King’s College Hospital, London, UK) reports that a host of novel therapeutic strategies is now on the horizon for management of these problems. These include gene-mediated strategies to replace defective sequences, blocking signal transduction, and anti-angiogenic agents. Early clinical trials show promise. However, targeting residual tumor and precancerous lesions is not straightforward, and strategies to improve delivery of these novel therapeutics to the sites of active disease will be presented.

This is a summary of a Keynote Address entitled ‘Molecular Diagnostics for Oral Cancer’, to be presented by M. Partridge (King’s College Hospital, London, UK), at 8 a.m. on Friday, March 12, in Room 316-C of the Hawaii Convention Center, during the 82nd General Session of the International Association for Dental Research.

OCF Note: OCF founder Brian Hill was part of the oral cancer lecture presentations at this meeting as a guest speaker invited by the National Institutes of Health.

March, 2004|Archive|

Environmental and dietary influences on cancer risk

  • 3/29/2004
  • Orlando, FL
  • By Aimee Frank
  • American Association for Cancer Research

Studies show how exposure to environmental carcinogens causes dna damage in smokers, women and their unborn children.

Genetic damage triggered by environmental carcinogens, including smoking, is being further defined with the aid of new technology, including microarrays, polymorphisms and DNA adducts, one of the first steps in the carcinogen pathway that ultimately leads to tumor formation. In this press briefing at the 95th Annual Meeting of the American Association for Cancer Research, scientists report their findings of specific DNA damage resulting from combustion and smoking-related carcinogens, and in the case of two studies, the impact of prenatal exposures on unborn children.

Levels of Polycyclic Aromatic Hydrocarbons in Amniotic Fluid Samples from Smokers and Nonsmokers: Abstract No. 3189

The amniotic fluid of smoking women in their first trimester of pregnancy contains about 10 times the amount of a known tobacco carcinogen — polynuclear aromatic hydrocarbons (PAHs) – than nonsmokers. Similar results were found for another established cancer-causing agent, known as benzo(a)pyrenes. “This is the first study to show the presence of carcinogens in the fetus at this early stage of development,” said Steven R. Myers, Ph.D., Director of the Center for Environmental and Occupational Health Sciences at the University of Louisville School of Medicine and lead author of the study.

In all, more than 500 women participated in the study, which involved routine amniocentesis performed between 16 to 20 weeks of pregnancy. The first trimester is a particularly critical period for the developing fetus, during which rapid cell division and growth takes place. Amniotic fluid not only helps protect and cushion the fetus, it also plays an important role in the development of many fetal organs, including the lungs, kidneys and gastrointestinal tract.

“There is a great potential at this time for severe DNA damage and potential alterations in genes that may predispose the child to later cancers,” said Myers. “Any compounds that have potential to disrupt these processes such as chemical carcinogens found in tobacco are detrimental.”

Scientists analyzed fluid extracted from nonsmokers and smokers, ranging from a half-pack to more than two packs per day. Levels of PAHs were detected in virtually all amniotic samples. However, there was a clear correlation between smoking and high concentrations of PAHs and benzo(a)pyrenes that passed from the mother’s circulatory system across the placenta and into the amniotic fluid. Levels range from about 1.5 micrograms per liter in nonsmokers to about 11.7 in women who smoked more than two packs per day, about a 10-fold increase. Myers added that his group is now following the growth curves of these children, in addition to other short-term outcomes, including respiratory and cognitive function.

Comparison of Polycyclic Aromatic Hydrocarbon (PAH)-DNA Adducts in Four Populations of Mothers and Newborns in the U.S., Poland and China: Abstract No. 1975

Prenatal exposure to combustion-related pollutants found in the urban air in the United States, Poland and China results in genetic damage that has been linked to increased cancer risk. The research provides molecular evidence that the fetus is more susceptible to DNA damage than the mother.

According to a new study of mothers and their newborns, even low levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs) are damaging the DNA of fetuses in the womb. The type of DNA damage measured here (termed “carcinogen-DNA adducts”) has been shown to increase the risk of cancer in humans.

Four population groups were selected for the study, including mothers and their newborns from two sites in New York City (Northern Manhattan and the World Trade Center area); Krakow, Poland; and Tongliang, China. In all, carcinogen-DNA adducts were analyzed in cord blood from 822 newborns and blood samples collected at delivery from 867 women.

“This study suggests that even small exposures to the pollutants pose some risk to the fetus and supports preventive policies to limit exposures of pregnant women and children,” said Frederica P. Perera, Dr.P.H., professor of public health and director of the Columbia Center for Children’s Environmental Health at the Mailman School, Columbia University. “The evidence that the fetus is more susceptible than the mother to DNA damage underscores the need for prevention.”

The populations were selected to represent the range of environmental exposure to air pollutants worldwide and, in the case of the World Trade Center study, to learn about possible risks from that unprecedented event. Available air monitoring data from the three cities indicate that the average levels of benzo[a]pyrene, a representative PAH, ranged from a low of 0.5 nanograms per cubic meter in New York City to greater than 15 nanograms per cubic centimeter in Tongliang, about a 30-fold range. Mean adduct concentrations in cord blood increased across the populations, consistent with the trend in ambient exposure to PAHs.

Levels of DNA damage, or adducts, seen among newborns from Northern Manhattan and the World Trade Center population were significantly lower than in either the Polish or Chinese newborns. The study suggested that the fetus may be as much as 10 times more susceptible to DNA damage than the mother. Despite the estimated 10-fold lower PAH dose to the fetus, the adduct levels in the newborns were similar to or higher than in the mother.

The alcohol dehydrogenase 3 polymorphism is associated with an increased alcohol/tobacco-associated risk of oral and pharyngeal carcinomas: Abstract No. 3975

Scientists have identified a genetic variant that places heavy drinkers who smoke at a much higher risk of oral cancer than their counterparts.

According to a Boston-based study, heavy alcohol consumption accompanied by smoking resulted in a 12-fold higher risk of head and neck squamous cell cancer among this population group. “These findings provide clear evidence that, at least in this case, consideration of the interaction between smoking and drinking can be critical for assessing and accurately estimating the magnitude of genetic susceptibility to HNSCC,” said Edward S. Peters, D.M.D., Sc.D., at the Harvard School of Public Health and Brigham and Women’s Hospital in Boston, and lead author of the study.

The scientists analyzed the genetic makeup of 520 individuals in the Boston area with confirmed cases of HNSCC, along with 597 controls. Specifically, the team homed in on variants of a gene known as ADH3. Alcohol is eliminated through oxidation, first to acetaldehyde — a suspected oral carcinogen — with the aid of a catalyst known as alcohol dehydrogenase, or ADH. The ADH3 gene, which helps encode ADH, comes in several forms, or is polymorphic. The ADH3*1 form is capable of metabolizing ethanol to acetaldehyde at a higher rate than its sibling, the ADH3*2 allele.

In a preliminary analysis, the scientists found that approximately 40 percent of those individuals with head and neck cancer carried the homozygous ADH3*1 genotype, while one-third of the controls shared this genetic characteristic. For the remaining part of the group, 46 percent and 47 percent were heterozygous, while 14 percent and 15 percent were ADH3*2.

Examination revealed that heavy drinking increased the risk of oral cancer by a factor of 5 among individuals who inherited both copies of the ADH3*2 gene, compared to a 3-fold higher risk among ADH3*1 polymorphism. However, since the interaction of smoking and drinking has been linked in previous studies to increased risk of HNSCC, the scientists sought to determine how this interaction would influence the ADH3 polymorphism.

Smoking and drinking together conferred a 12-fold increase in risk for oral cancer among the ADH3*2 homozygous variant population, compared to a 6-fold increase among the ADH3*1 homozygous wildtype or heterozygous ADH3 individuals. “These findings suggest that the ADH3 variant allele is associated with susceptibility to smoking/drinking-related HNSCC,” said Peters.

Founded in 1907, the American Association for Cancer Research is a professional society of more than 22,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR’s mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR’s Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.

March, 2004|Archive|

Teen mouth cancer

  • 3/24/2004
  • San Antonio, TX
  • News 9, San Antonio

Salivary Gland Tumors
There are three main pairs of salivary glands. The first and largest are the parotid glands in front and just below the ears. The second largest are the submandibular glands at the back of the mouth under the side of the jaw. The third pair is the sublingual glands. They are found in the floor of the mouth under the tongue. There are several other minor salivary glands scattered below the lining of the mouth and throat. The salivary glands secrete saliva into the mouth through ducts. Saliva moistens food, makes it easier for us to chew food and swallow, and aids in breaking down food for digestion. Saliva also washes away bacteria and food particles and keeps the mouth moist.

Salivary tumors are rare, especially in children. The tumors can be benign or malignant and most commonly are located in the parotid glands. Signs of a possible tumor include: development of a painless lump or growth, swelling or gradual increase in the size of a gland, or, in rare cases, facial paralysis.

Diagnosing and treating salivary tumors
Sometimes salivary tumors are detected during a routine dental exam. A fine needle may be used to withdraw some cells for laboratory examination. From this information, doctors will determine if the tumor is benign or malignant and what steps need to be taken for treatment.

If a tumor is malignant, surgeons need to remove the tumor and a small margin of healthy tissue. Patients may lose part of the jaw, and several teeth. As with many types of oral cancer, the surgery can be extremely extensive and disfiguring. Traditionally, doctors make the incision through the skin over the face and cut down to the bone to get at the tumor and surrounding tissue.

Some doctors are using a less visible approach called midface degloving. Instead of working from the outside of the face, an incision is made inside – along the upper lip and gum line. Next, the skin is lifted from the face to expose the facial skeleton. Doctors remove the tissue and replace the overlying skin. Since all the incisions are made inside the mouth, there are no visible scars or bruising.

When a tumor is located on the roof of the mouth, the patient is left with a large hole in the hard palate, creating both cosmetic and functional problems. With no separation between the mouth and nasal passages, air, food, and liquids can pass from the mouth and out the nose. Speech and swallowing become difficult.

Doctors also have a way to deal with this problem. Prior to surgery, impressions are taken of the patient’s mouth. These impressions are used to create a special appliance, called an obturator prosthesis that fills in the gap at the roof of the mouth. A temporary obturator is inserted just after surgery while the patient is still asleep. When he/she wakes, the hole is covered. The obturator also protects the surgical site and helps the surrounding tissue to heal. The patient is able to talk and take oral fluids soon after surgery. As the area heals, the device is adjusted to ensure a tight seal and prevent leakage of air, fluids, and food into the nasal cavity. Once doctors have determined healing is complete, a permanent device is constructed. The obturator can also be designed to replace teeth and gums that need to be removed during surgery.

March, 2004|Archive|

HPV Test Catching On as the More Definitive Cervical Cancer Screening

  • 4/23/2004
  • Associated Press

A more definitive cervical cancer screening test that helps reduce uncertainty in diagnosing the disease is gaining support from doctors and health insurers. Aetna, the nation’s largest health insurer, on Wednesday became the latest plan to cover the new DNA test that checks for the presence of a virus that studies show causes more than 99 percent of cervical cancers. The test is used when a Pap smear proves inconclusive, which happens about 5 percent of the time. Kaiser Permanente, United Healthcare and most Blue Cross and Blue Shield plans already cover the test for human papillomavirus, or HPV, according to the test’s maker, Digene Corp. of Gaithersburg, Maryland. About 400,000 U.S. women had the HPV test in the past year, a Digene spokeswoman said. If the test shows no sign of HPV, a woman is assured she doesn’t have cancer. If the HPV virus present, there is a greater likelihood the woman has cancer and she is sent for additional testing which most likely include a biopsy. “Aetna is a bellwether for the adoption of HPV testing as a standard of care in cervical cancer screening,” said Evan Jones, Chairman and CEO of Digene Corporation.

About 50 million Pap smears are performed annually in the United States. Before the HPV test was approved by the Food and Drug Administration in 1999, women who had an inconclusive Pap test would have to get another Pap test or an outpatient procedure that would likely include a biopsy. The results of a biopsy could take two weeks, a period in which the woman would not know if she had cancer. An HPV test can be done typically in a lab the same day as a Pap test, and it is done using the same Pap smear. Aetna is working with its clinical labs for them to automatically do the HPV test when the Pap test proves inconclusive, or mildly abnormal. “For the patient this is a tremendous value, because the anxiety of being told you have an abnormal Pap is taken away,” said Dr. Arnold Cohen, Aetna’s medical director for women’s health. Cohen estimated that about 60 percent of HPV tests done after an inconclusive Pap test will show no signs of the virus that causes cervical cancer. Thus, for Aetna and other health insurers, the HPV test eliminates the cost of paying for further office visits and a biopsy. According to the American Cancer Society, an estimated 12,800 cases of cervical cancer will be diagnosed this year and 4,600 women will die of the disease. Some experts say the HPV test can help make sure women are diagnosed earlier when the disease is more easily treated. “This is a real breakthough, a great advance in cervical cancer screening,” said Dr. Mark Schiffman, who is studying the impact of HPV testing at the National Cancer Institute But how widely the screening is used will depend on whether Digene makes the price affordable, especially for public health clinics, he said. The cost for the HPV test to check for cancer is about $50. In comparison, the conventional Pap test costs about $10. Another type of cervical cancer screening test, which was approved in the mid 1990s, is the ThinPrep or Prep Pap test. In those tests, which cost about $30, a computer rather than a laboratory technician scans the Pap smear slide for abnormalities. Studies show this test typically can better identify abnormal cells than the conventional Pap test.

March, 2004|Archive|

Widow awarded $1.8M in lawsuit

  • 3/20/2004
  • SHEILA BURKE
  • The Tennessean

When Melvin Wilson went to the doctor three years ago complaining of neck pain, he told his doctor he was concerned because his family had a history of cancer.

Doctors performed a CT scan and assured him he was fine. But Wilson wasn’t. He died last June at age 63.

A Davidson County Circuit Court jury in Judge Walter Kurtz’s court awarded his widow $1.8 million for Wilson’s wrongful death.

The jury’s award last week will be challenged, defense attorneys said.

His widow, Patricia Wilson, of Gallatin sued radiologist Dr. Gregory Weaver and his company, Radiology Alliance, claiming her husband wouldn’t have died had the cancer been diagnosed earlier.

The doctor’s attorneys fiercely disputed that allegation.

They claimed Wilson still would have had less than a 50% chance of survival.

Melvin Wilson was diagnosed with tongue cancer a year after he had the CT scan.

His widow’s attorney said Melvin Wilson had two cancerous nodes when the CT scan was taken and said that Weaver had misread the results.

There was no indication that the tongue cancer had spread past two nodes on his neck when he was given the CT scan in February 2001, said Daniel Clayton, the widow’s attorney.

Each side had its own set of medical experts.

Two professors at Vanderbilt University Medical Center said the man would have had less than a 50% chance of survival with an earlier diagnosis, Weaver’s attorney, Phillip North, said.

Other expert testimony contended that Wilson probably would have survived if the disease had not reached his chest.

March, 2004|Archive|

University Of Pittsburgh Researchers Find Pet/Ct Imaging Better At Localizing And Monitoring Head And Neck Cancer

  • 3/19/2004
  • Toronto
  • University of Pittsburgh

University of Pittsburgh researchers have found the combined PET/CT scanner is the most powerful imaging tool available for localizing, evaluating and therapeutic monitoring of head and neck cancer and may be equally useful for other cancers that are difficult to pinpoint.

Results of a study showing PET/CT has a distinct advantage over PET or CT alone were presented today at the annual meeting of the Society of Nuclear Medicine. According to the researchers, the prototype of the combined PET/CT machine at the University of Pittsburgh Medical Center is able to effectively localize cancerous activity in the head and neck, an area of the body that presents substantial challenges to other imaging methods because of densely packed tissue structures and the frequent involvement of lymph nodes.

Separately, computed tomography (CT) and positron emission tomography (PET) do not provide images with the necessary combination of clear structural definition and metabolic activity that is achieved with the PET/CT. “The PET/CT tells us the exact size, shape and location of the cancer and provides a specific target for surgery or other treatment,” said Carolyn Cidis Meltzer, M.D., associate professor of radiology and psychiatry and medical director of the UPMC PET Facility. “The PET/CT can also be used to help us develop the best course of treatment for an individual, then monitor that individual’s progress during treatment.”

Head and neck cancers often have already involved lymph nodes when first discovered and can spread rapidly if they are not found and treated quickly. Images from the combined PET/CT scanner are particularly useful in allowing a radiologist to see cancerous activity at a metabolic level and pinpoint its exact location in the tissue so a biopsy can be performed and proper treatment begun. Tumors among the skeletal muscle, salivary glands and lymphoid tissue in the head and neck area are difficult to separate from healthy tissue in standard PET images, which look like blotches of color amidst fuzzy structures. With CT, unless they are clearly swollen, cancerous lymph nodes may look normal.

Size matters when radiologists evaluate lymph nodes for signs of cancer. Seen by CT, lymph nodes under one centimeter are considered normal and not biopsied. The PET/CT, developed in part by David Townsend, Ph.D., senior PET physicist, professor of radiology at the University of Pittsburgh School of Medicine, and a co-director of the University of Pittsburgh PET facility, works by combining PET technology, in which the scanner reads cellular metabolism of glucose, and CT, which builds a clear cross section of tissue structures using x-rays. “Because head and neck cancer starts small and spreads rapidly, the PET/CT will provide doctors with a means for earlier diagnosis and treatment to potentially save lives,” said Dr. Townsend. “With PET/CT an accurate diagnosis of cancer could be provided months earlier than with any other imaging method.”

The groundbreaking research done by Drs. Townsend and Meltzer in Pittsburgh led the FDA to approve the PET/CT, known commercially as the Biograph, earlier this year for use as a diagnostic and therapeutic tool for cancer treatment. Other authors that contributed to the research are Carl H. Snyderman, Melanie B. Fukui, Daphne A. Bascom, Subash Chander, Jonas T. Johnson, Eugene N. Myers, Marsha A. Martinelli and Paul E. Kinahan.

March, 2004|Archive|

Trying to stop cancer’s start

  • 3/18/2004
  • Irvine, Ca.
  • Linda Marsa
  • LA Times

Because the early signs of oral cancer — white spots or red areas in the mouth —are painless and difficult to detect, diagnosis usually occurs only after the disease has spread to the lymph nodes in the neck. Consequently, patients often need aggressive, disfiguring surgical treatments. Half of those diagnosed will die of the disease. “Mortality rates haven’t changed in 40 years because we don’t have any good treatments beyond surgery, and no way of preventing cancers from returning,” says Dr. Frank L. Meyskens Jr., an oncologist at the Chao Family Comprehensive Cancer Center at the UC Irvine Medical Center.

But Meyskens and other scientists are testing a soy-derived experimental treatment that could reduce this deadly toll — by stopping oral cancers from developing in the first place. If the drug proves effective, it may be used routinely to protect against oral cancer in people who are at increased risk.
“Survival rates haven’t improved much over the years, so a preventive agent would be very useful,” says Sol Silverman, a professor of oral medicine at UC San Francisco Medical School and spokesman for the American Dental Assn. in Chicago. “This approach seems promising.” About 30,000 Americans are diagnosed with oral cancer each year, and only 57% survive more than five years.

Tobacco use is the culprit behind about 75% of oral cancer cases, and alcohol also is a major contributing factor. Oral cancer is the leading cancer among men in India, and incidence rates can be as high as 40% in Southeast Asia, where people chew betel nuts, which contain lye, or tobacco laced with lime, both of which irritate mouth tissue. The soy derivative, known as the Bowman-Birk inhibitor, seems to work by blocking the production of certain enzymes that can prompt cells to turn cancerous. (Scientists had noticed that people whose diets were rich in soybean products had a lower incidence of cancer, which prompted studies of soy’s chemical constituents.)
A 1999 study of 32 patients with leukoplakia, a potentially precancerous disease of the mouth in which white patches form on the tongue and inside the mouth, was promising.

Volunteers took a twice-daily dose of the soy derivative in a mouth rinse, which they swished around their mouths and then swallowed. After a month, there was an overall 24.2% decrease in lesion size. “In a couple of patients the lesions were completely gone, which we found very encouraging for such a short study,” Meyskens says.

Researchers are now in the midst of a longer study of 130 patients. Half receive a placebo, while the remainder take the drug for as long as two years to determine whether it can completely eradicate lesions and protect against recurrences of the precancerous condition. If it works, the next step is to test it on people with head and neck cancers, which have high rates of recurrence. “Right now, these patients have no preventive options,” Meyskens says.

About the chemical

The Bowman-Birk inhibitor is a very versatile chemical, says Ann R. Kennedy, a radiation oncologist who has studied the soy derivative for more than 30 years. In addition to potentially guarding against cancer, this component of soy also may reduce inflammation and prevent muscles from weakening from disuse.
The compound already has shown promise in clinical trials for reducing colon inflammation in people with ulcerative colitis and easing swelling in patients with enlarged prostates, which is a common condition in older men. In the near future, scientists plan tests of the chemical’s ability to prevent muscle atrophy in multiple sclerosis sufferers and in people with spinal cord injuries who are bedridden.

“When we first studied the Bowman-Birk inhibitor, we observed that it stopped the malignant transformation of cells,” says Kennedy, a professor of research oncology at the University of Pennsylvania School of Medicine. “But now we’ve discovered that it can be useful in many other areas.”

March, 2004|Archive|

In Saliva Veritas

  • 3/17/2004
  • Eugene Russo
  • thescientist.com

Spit’s potential diagnostic value has funding agencies putting money where the mouth is

Human Saliva magnified 100x

A trip to the doctor’s office generally entails a deposit of blood or urine from which some diagnoses can be produced after a laborious process. Now, groups of biologists and engineers are working to make disease diagnoses quicker and more efficient by giving credit to a less conventional humor–the Rodney Dangerfield of bodily fluids–spit.

In the past year and a half, the National Institutes of Health’s National Institute of Dental and Craniofacial Research (NIDCR) has used a set of seven grants totaling $27 million (US) through 2006 to form a Salivary Diagnostics Group for technology development. Once disparate disciplines, oral salivary biology and engineering are melding in order to give saliva its due respect as a diagnostic fluid.

Scientists and healthcare workers have long known the power of saliva to indicate HIV exposure or drug abuse. Indeed, certain informative molecules or analytes in saliva, such as DNA, RNA, peptides, or fatty acids, could indicate a variety of conditions including cancer, Alzheimer, and heart disease. “It turns out that almost anything you can measure in blood, you can measure in saliva,” says NIDCR director Lawrence Tabak. But often, informative saliva analytes are present in hard-to-detect levels–one hundredth to one thousandth of what’s found in blood. Qualitative measures are feasible, for example, when someone tests positive for HIV antibodies. But quantitative measures, such as a precise glucose level, are not.

Nanoscale sensors may break down the barrier, says David Wong, chair of the Division of Oral Biology and Medicine at the University of California, Los Angeles. Such sensors could eventually detect “virtually anything that one wishes to detect at single-molecule level,” says Wong.

Wong and his engineer colleagues are designing nanosensors to detect trace analytes. In a recent paper, he and his group report the first comprehensive detection of mRNA in saliva.1 Wong uses oral cancer as a salivary diagnostic test case, and he is starting to look at breast cancer and diabetes.

He envisions that within a few years, researchers will be using high-throughput nanosensors to test for 10 different ailments simultaneously. The tests would be quick, noninvasive, and could be done onsite in remote areas of the world, perhaps in cultures where blood collection is considered taboo.

Other investigators are studying the feasibility of detecting salivary cancer analytes such as p53, or potential heart disease indicators such as C-reactive protein, a sign of inflammation.2

University of Pennsylvania professor of biochemistry, Daniel Malamud, is working on a platform he hopes will improve HIV diagnosis by closing the so-called window, the highly infectious four to 12 weeks between infection and measurable antibody load. His group is seeking to reliably measure the virus according to multiple analyte signatures using a $3,000 toaster oven-sized detector that analyzes cassettes containing saliva samples. A single sample is separated into a series of channels: In one the instrument detects bacterial or viral antigens, and in another it detects human antibodies to the pathogen. From yet another channel the researcher can obtain the RNA or DNA fingerprint by PCR.

The group is also seeking ways to detect the seven or so viruses and bacteria that cause all childhood respiratory diseases. By diagnosing these ailments within a half-hour rather than a few days, Malamud hopes to stem antibiotic overuse, a major cause of rampant antibiotic resistance. For now, Malamud’s efforts are focused on one virus, HIV, and one bacterium, Bacillus cereus, a close relative of Bacillus anthracis.

Salivary diagnostic approaches have many potential limitations, however. Before the FDA approves any product, scientists and engineers must account for practically every eventuality, for example, how recent meals or mouthwash use might affect test results. Furthermore, only some diseases present diagnostic biomarkers in saliva, and of those, only a portion may be reliably detectable.

To discover reliable analytes, Wong suggests controlled studies in which researchers attempt to accurately distinguish known diseased individuals from normal individuals based on a suspected reliable analyte. Disease-specific biomarker searches could be greatly enhanced with the planned completion of the “human salivary proteome,” a research project for which NIDCR will soon award grants.

References
1. Y. Li et al., “RNA profiling of cell-free saliva using microarray technology,” J Dent Res, 83:199-203, 2004.
2. C. Streckfus et al., “A preliminary study of CA15-3, c-erbB-2, epidermal growth factor receptor, cathepsin-D, and p53 in saliva among women with breast carcinoma,” Cancer Invest, 18:101-9, 2000.

March, 2004|Archive|

HPV in Oral Exfoliated Cells Associated With Head and Neck Cancer

  • 3/16/2004
  • New York
  • Rueters

Infection of oral epithelial cells with oncogenic types of human papillomavirus (HPV) is an independent risk factor for the development of head and neck cancer, investigators report in the March 17th issue of The Journal of the National Cancer Institute.

In a case-control study, Dr. Elaine M. Smith of the University of Iowa and colleagues detected oncogenic HPV types in oral exfoliated cells from 22.9% of 201 patients with head and neck cancer and 10.8% of 333 cancer-free control subjects.

HPV 16 was the most frequently detected type, present in 19% of cases and 10% of controls. In analyses adjusting for age, tobacco use, and alcohol intake, the risk of head and neck cancer was statistically significantly greater in subjects infected with high-risk HPV types, with an adjusted odds ratio of 2.6, but not in those infected with non-oncogenic HPV types (adjusted OR = 0.8)compared with HPV-negative individuals.

There was also a significant synergistic effect between detection of high-risk HPV types and heavy alcohol use (OR=18.8) and an additive effect between detection of high-risk HPV and tobacco use (OR = 5.5). “Any biologic interaction effect with HPV is associated primarily with alcohol consumption and not with tobacco use,” the researchers note. The team also found a significant association between detection of high-risk HPV in oral cells and detection of high-risk HPV in tumor tissue.

Head and neck cancers cause “clinically significant morbidity and disfiguration,” Dr. Smith and colleagues remind readers, making “early detection of disease and biomarkers to identify individuals at high risk of great importance.” With further study, “HPV testing of an oral rinse may be predictive of an HPV-related head and neck cancer,” they conclude.

March, 2004|Archive|