Monthly Archives: December 2006

Identification of high-risk oral premalignant lesions

  • 12/17/2006
  • Vancouver, BC, Canada
  • Miriam P. Rosin et al.
  • Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006

The genomic era has fueled a rapid emergence of new technology, with the potential for developing innovative approaches to detection, risk assessment and management of premalignant disease. A key missing link in the development of novel screening and intervention strategies has been our limited understanding of the natural history of the disease.

Not all early disease will progress to cancer. To be effective in reducing cancer risk, molecular (and other) technologies need to target change in early lesions that is strongly associated with outcome – in other words, the likelihood of progression to cancer.

This presentation will describe early results of an on-going Oral Cancer Prediction Longitudinal (OCPL) study located in British Columbia, funded by NIDCR for 8 years (1999 – 2008). This study is evaluating a set of innovative technologies alone and in combination to best correlate with outcome for oral premalignant lesions (OPLs). The plan is to use these devices to guide key clinicopathological decisions on patient risk and treatment. The long-term goal is to create a province-wide screening network in which these devices would act as a series of overlapping sieves that will in a step-by-step fashion progressively filter out patients in the community with high-risk OPLs and triage them to dysplasia clinics where higher-cost molecular tools will guide intervention.

The design of the OCPL study is as follows. Approximately 500 patients are being followed over time (patients are continuing to accrue): half with an oral cancer history (at risk for recurrence) and the other half with low-grade dysplasia (no oral cancer history, at risk for progression to cancer). Patients are seen at 6-month intervals with a rigorous collection of clinical, pathological and demographic data at each visit and repeated sample collection from oral premalignant lesions (OPLs) and high-risk sites (a combination of exfoliated cell brushings and biopsies).

The devices/approaches chosen for assessment in the OCPL study are positioned at key decision points that represent major barriers to screening activities. The first revolves around the clinical assessment of the oral cavity and detection of an oral lesion that requires follow-up. OPLs vary considerably in clinical appearance and the ability to differentiate abnormalities requiring biopsy from reactive lesions, associated with other causes such as infection or trauma, can be difficult. Visualization devices that facilitate the decision to biopsy (the next step in patient evaluation) could have a profound affect on outcome. We are assessing 2 approaches: a hand-held visualization device which makes use of tissue autofluorescence to detect and delineate abnormal lesions and fields requiring follow-up and the use of optical contrast agents such as toluidine blue. Preliminary data using each of these approaches has been promising. We have recently shown that OPLs with retention of toluidine blue have a >6-fold elevation in cancer risk. Fluorescence visualization appears to detect clinically non-apparent disease that is histologically high-risk and may play a role in the identification of surgical margins in the future. A second barrier revolves around risk prediction for OPLs.

At present, the gold standard for prediction involves the determination of the presence and degree of dysplasia in a biopsy. Histology is a good predictor of risk for severe dysplasia or carcinoma in situ (CIS), grouped as high-grade premalignant lesions, which are characterized by persistence, recurrence, and high risk of eventual progression to invasive cancer. Unfortunately, the majority of OPLs have little (mild and moderate dysplasia) or no dysplasia and histology alone does not clearly differentiate between those that will progress and those that will not.

The OCPL study is confirming several retrospectively-observed loss of heterozygosity (LOH) risk patterns previously associated with progression for OPLs. Data from the first 100 oral dysplasia in follow-up (with a limited follow-up time of 44 months) is promising. However, LOH analysis is comparatively time-consuming and labor-intensive. We are currently evaluating a further two semi-automated computer microscopy systems as high throughput filters that could be used for population-based studies and serve as upstream sieves for risk assessment prior to LOH analysis. These computer imaging devices measure specific phenotypic characteristics that make up the appearance of dysplastic cells in a quantitative fashion, with ~120 such features being assessed for each nuclei in a sample.

We have recently completed a pilot study in which a small set of tissue biopsies of OPLs with known outcome (N = 44) were assessed for algorithm-derived nuclear phenotype scores. Strikingly, there was a 9-fold increase in relative risk of progression to cancer for cases with high versus low scores. In a separate study, we used a parallel system, this time with exfoliated cell samples, to generate some equally interesting data. The sample set included a total of 196 cytological samples from areas collected just prior to biopsy, 108 normals and 60 abnormals (patients with squamous cell carcinoma, carcinoma in situ and severe dysplasia). Using a crude algorithm with just 2 features, the system was able to correctly identify 86% of the abnormal cases and 86% of the normal cases. Of equal importance was the fact that the system also correctly identified 92% of samples from sites with inflammation/infection (N = 28) as non-OPLs, supporting a potential use of the system to assist clinicians in differentiating reactive lesions from OPLs requiring biopsy.

In summary, early data from the OCPL study suggests that positioning devices at critical decision points in patient evaluation might greatly facilitate screens for high-risk lesions. It is important to note that this approach of stepwise “sieving” for risk carries with it an additional equally important benefit: the creation of a cohort of patients with OPLs of known outcome upon which genomic studies can be conducted. The OCPL study has such a strategy in place. We are currently using a whole genome bacterial artificial chromosome tiling set (BAC) array (~32,000 clones) to create a database of high-resolution genomic profiles of tumors and early OPLs, with known outcome, to ultimately identify a novel set of predictive markers of progression that may guide intervention strategies.

Finally, we are beginning the process of knowledge transfer to community clinics. A screening clinic has been established in the Downtown Eastside of Vancouver, one of the poorest neighborhoods in Canada with a population characterized by multiple risk factors including heavy tobacco/alcohol usage, poverty, poor nutrition and chronic infections/inflammations. We have already identified a very high risk of disease in this community using our screen: of 250 residents, 2 had cancers and 9 had precancerous lesions. We have also begun the process of knowledge transfer to community health practitioners, beginning with 10 dental offices in the Vancouver mainland. The plan is to begin the process of seeding the use of the various devices into the 2900 dentists of British Columbia, thus creating a broad network that will identify cases for triage to clinics for assessment and intervention.

Authors:
Miriam P. Rosin, Catherine F. Poh, Martial Guillard, Michele Williams, Wan Lam, Calum MacAulay and Lewei Zhang

Authors’ affiliation:
BC Cancer Agency, Vancouver, BC, Canada

December, 2006|Archive|

Introgen Announces New Clinical Data Confirming Advexin Survival Benefit

  • 12/17/2006
  • web-based article
  • press release
  • Biotechtalk.net

Biomarkers to Play Key Role in Phase 3 Analyses

Introgen Therapeutics, Inc. announced important new Advexin clinical data and regulatory updates. Advexin delivers the tumor suppressor p53 that targets a fundamental molecular cancer defect and selectively kills cancer cells. Expanded p53 biomarker studies confirmed with high statistical significance the survival benefit of Advexin therapy in patients with abnormal p53 function. The new results demonstrated that patients with the abnormal p53 biomarker in recurrent squamous cell carcinoma of the head and neck were most likely to have a survival benefit from their use of Advexin therapy. The data was announced as Introgen prepares to initiate the analyses of Phase 3 clinical trial data in support of its registration of Advexin. The U.S. Food and Drug Administration (FDA) has agreed to Introgen’s plans for incorporating p53 and other biomarker analyses in the evaluation of its Advexin Phase 3 clinical trials in recurrent head and neck cancer.

Introgen has now analyzed additional head and neck cancer patients for the abnormal p53 molecular biomarker predictive of Advexin activity. The prognostic p53 biomarker is detected in tumor tissues by a routine laboratory test. Tumor samples were evaluated for the abnormal p53 biomarker by an independent laboratory in 28 patients with recurrent head and neck cancer who were treated with Advexin during Phase 2 clinical trials. The results confirm and extend previous Advexin biomarker studies. The abnormal p53 biomarker was associated with statistically significant increases in tumor response and median survival following Advexin treatment. Median survival of patients with tumors abnormally expressing p53 was 11.6 months compared to only 3.5 months in patients whose tumors had a normal p53 biomarker (p=0.0007). Tumor disease control was observed in 75 percent of patients with the abnormal p53 biomarker compared to 18 percent of patients with normal p53 (p=0.0063).

Introgen’s research demonstrates that the key biomarker that defines the target patient population benefiting most from Advexin also identifies the patients who respond very poorly to standard therapies and need new treatment approaches. This research also shows that abnormal p53 function is a common and fundamental molecular defect that is a predictive marker for Advexin efficacy, which is consistent with Advexin’s mechanism of action — restoration of p53 function — and is an example of targeted molecular therapy. Introgen believes that the correlation of abnormal p53 protein levels with increased survival of patients treated with Advexin provides compelling data to support its U.S. and European regulatory applications for treatment of head and neck cancer and reinforces its Exceptional Circumstances Approval application in Europe for treatment of Li-Fraumeni Syndrome. Introgen believes the Advexin biomarker results will support its efforts to bring Advexin to the market as a personalized medicine.

The identification of prognostic indicators of Advexin activity complies with recent FDA biomarker initiatives to accelerate the approval of oncology products by predicting the patient populations most likely to benefit from a specific cancer therapy. The FDA, the National Cancer Institute, and the Centers for Medicare & Medicaid Services previously announced the Oncology Biomarker Qualification Initiative to expedite the development of novel cancer treatments.

About Biomarkers

Biomarkers are tests or measurements that predict response to treatment. Molecular biomarkers include measurements of genetic markers or molecular pathways while clinical biomarkers refer to clinical history or clinical measurements. Introgen’s biomarkers include the identification of aberrant p53 function by detecting abnormally elevated levels of p53 protein in tumor tissue, a more inclusive indicator of p53 defects than the analysis of p53 mutations. Introgen believes that application of molecular and clinical biomarkers can predict the patients who are most likely to respond to Advexin treatment.

About Advexin

Advexin p53 therapy is a targeted molecular therapy with broad applicability in a wide range of tumor types and clinical settings because it targets one of the most fundamental and common molecular defects, abnormal p53 tumor suppressor function, associated with cancer initiation, progression and treatment resistance. Advexin has demonstrated increased survival and durable tumor growth control in recurrent head and neck cancer patients. Advexin has demonstrated clinical activity in a number of solid tumor types in multiple phase 1, 2 and 3 clinical trials conducted worldwide. A request for accelerated approval for Advexin is now pending at the FDA. The FDA has selected Advexin for its fast track program to fill an unmet medical need and has designated Advexin for orphan drug use for recurrent head and neck cancer.

Gendux AB, Introgen’s European subsidiary has been advised by the European Medicines Agency (EMEA) to file for Advexin therapy marketing approval under the EMEA’s Exceptional Circumstances Approval provisions. The application will be for the use of Advexin p53 therapy for the treatment of Li-Fraumeni Syndrome (LFS). LFS is a genetic disorder characterized by inherited mutations in the p53 tumor suppressor gene. Due to these mutations, LFS patients suffer from numerous cancers often presenting with tumors at an early age. The EMEA has granted orphan status to Advexin for use in LFS. Exceptional Circumstances Approval provisions are designed to facilitate access to needed treatments for certain Orphan Medicinal Products. The EMEA has also invited a Marketing Authorization Application for the use of Advexin in the treatment of head and neck cancer.

December, 2006|Archive|

Health Canada Endorsed Important Safety Information on Iressa (Gefitinib)

  • 12/17/2006
  • Ottawa, Ontario, Canada
  • staff
  • www.docguide.com

Subject: Lack of Survival Benefit and Increased Incidence of Tumour Haemorrhage in Association with Iressa® in Patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN)

OTTAWA, CANADA — December 12, 2006 — AstraZeneca, following discussions with Health Canada, is informing health care professionals of new safety information regarding Iressa (gefitinib).

Iressa is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Although Iressa is indicated for the treatment of locally advanced non-small cell lung cancer in patients who have failed two prior chemotherapy regimens, its use has been restricted by Health Canada to patients who are currently benefiting from Iressa and whose tumours are EGFR expression status positive or unknown.

For continued supply of the drug, patients have had to be registered by a pharmacist into the Iressa Patient Registry (IPR) program. Head and neck cancer is not an approved indication for Iressa, but patients with this diagnosis could have been registered if benefiting from therapy.

This letter is to inform health care professional involved in the IPR, of the top-line results from an Iressa study in patients with squamous cell carcinoma of the head and neck (SCCHN) entitled: A phase 3 randomized, stratified, parallel-group, multi-centre, comparative study of Iressa 250 mg and 500 mg versus methotrexate for previously treated patients with squamous cell carcinoma of the head and neck (1839IL/0704, IMEX).

· IMEX trial results demonstrate lack of survival advantage for Iressa 250 mg and 500 mg versus methotrexate in patients with squamous cell carcinoma of the head and neck.

· IMEX trial results identify a potential new safety finding of tumour haemorrhage in patients treated with Iressa 250 mg and 500 mg compared to methotrexate.

· Patients with head and neck cancer who are taking Iressa should be informed of the IMEX trial results by their physicians; and, where appropriate, alternative treatment options should be discussed.

The objectives of the IMEX trial were to examine the efficacy and safety/tolerability of Iressa 250 mg and 500 mg versus methotrexate in a refractory, unselected population of patients with recurrent SCCHN. A total of 486 patients were recruited from approximately 100 centres worldwide; 483 patients were evaluable for safety. The trial was designed to demonstrate superiority for Iressa versus methotrexate for the primary endpoint of overall survival (OS).

The trial results did not demonstrate an improvement in survival for Iressa 250 mg or 500 mg compared to methotrexate, although there was some evidence of anti-tumour activity as measured by response rate. There was a numerical advantage for patients randomized to methotrexate, which did not reach statistical significance. The median survival times were consistent with published data for active monotherapy treatments in the recurrent disease setting and are presented below:

· Iressa 250 mg versus methotrexate OS: Median OS 5.6 vs. 6.7 months (HR 1.22; 95% CI 0.95 to 1.57; p= 0.1205)

· Iressa 500 mg versus methotrexate OS: Median OS 6.0 vs. 6.7 months (HR 1.12; 95% CI 0.87 to 1.43; p= 0.3899)

Analysis of the safety data from the IMEX trial identified a potential new safety finding of “tumour haemorrhage” in patients treated with Iressa 250 mg and 500 mg. The incidence of tumour haemorrhage seen in the Iressa 250 mg & 500 mg treated patients was; 8.9% (n=14/158) and 11.4% (n=19/166) respectively, compared to 1.9% (n=3/159) seen in the methotrexate treated patients. The majority of these tumour haemorrhages were considered by the reporting physician to be mild to moderate in nature (CTC grades 1 or 2), and resolved whilst study treatment continued.

Of the 36 patients with tumour haemorrhage, 3 died as a result of their tumour haemorrhage; 2 of these 3 patients were receiving Iressa 250 mg and the third was receiving Iressa 500 mg. These 3 cases were not considered by the reporting physician to be causally related to Iressa therapy.

AstraZeneca is undertaking a comprehensive review of the IMEX study data to fully understand the significance of these findings. As a Health Care Professional involved in the Iressa Patient Registry program, Health Canada, in collaboration with AstraZeneca, has requested that you be made aware of the IMEX trial results and that you communicate these results to any patient currently receiving Iressa for the treatment of SCCHN.

Source:
Health Canada

December, 2006|Archive|

New chew made from tea leaves

  • 12/17/2006
  • Minneapolis, MN
  • Mike Enright
  • Minnesota Daily (www.mndaily.com)

Bill Whalen said his chewing tobacco days began as a football player at the University of Pennsylvania.

Whalen regularly chewed a tin a day, which contains the same amount of nicotine as 60 cigarettes. It wasn’t until getting married and having kids that he realized he had to stop.

“I think every dipper, at some point in their life, realizes it’s time to quit,” Whalen said.

But, when push came to shove, Whalen couldn’t beat his addiction.

“So I decided to come up with something that was going to be much better,” he said. “Something that would allow me to dip … but take away all the carcinogens.”

Seven years later, Whalen is the CEO and founder of Blue Whale, LLC, and creator of what he calls a smokeless tobacco alternative, made from a blend of more than 20 different kinds of tea leaves.

The product, Blue Whale Smokeless, which has been available in Texas since the end of September, is now on its way to Minnesota and should be available in select stores over the next several weeks, said Chris Giannini, the company’s director of strategic marketing.

And although Blue Whale is not the first smokeless tobacco alternative – others include Smokey Mountain, Bacc-Off and Golden Eagle – it is the only brand that contains nicotine.

“The other ones are about as helpful as chewing gum,” Whalen said.

Blue Whale combines the best of both worlds, he said, because it has everything chewing tobacco users want without sharing any of the negative health consequences.

“It’s genuinely a better product,” said Whalen, who has been using it exclusively for two years now.

Giannini said Whalen’s creation also breaks the stigma of most smokeless tobacco alternatives, which often don’t live up to users’ expectations.

“He’s really come up with the first real-world solution to finding an alternative to smokeless tobacco,” he said.

“It provides all of the benefits, without the cancer-causing carcinogens.”

Others are less sure of Blue Whale’s superiority.

Dorothy Hatsukami, director of the University’s Transdisciplinary Tobacco Use Research Center, was quick to point out that no independent research has yet been done to confirm the company’s findings.

“I’m hesitant to recommend it as an alternative to chewing tobacco until there is sufficient evidence to show what the toxicity of this product is, the levels of nicotine it delivers,” she said.

Compared with regular chewing tobacco, which is known to increase users’ risk for cancer, diabetes and a host of other health problems, Blue Whale might be less harmful, but by how much remains uncertain, Hatsukami said.

“Certainly, it is far less toxic than many of the tobacco products that are out there,” she said.

“But you are still being exposed to nicotine, which is addictive and has some risk factors in its own right.”

Economics junior and chewing tobacco user Shea McAdaragh might not be sure whether Blue Whale is safer than chewing tobacco, but he does know the risks associated with dipping.

“You can get lip cancer, tongue cancer, throat cancer or stomach cancer if you swallow, which I don’t do,” he said. “It’s like going to the casino and putting $500,000 down; you know you could walk away fine or you could walk away losing your entire life savings. You don’t know.”

McAdaragh, who has been chewing for seven years and usually goes through two tins in a week, said he began dipping as a teenager working construction.

“All the guys I worked with were all chewers, every single one of them, even my boss,” he said. “They didn’t have any qualms about giving it to a 15-year-old.”

Calling it his “favorite vice, by far,” McAdaragh said he chews because it accentuates everything he does, whether it’s playing video games or taking a shower.

December, 2006|Archive|

New Nutrition and Exercise Guidelines for Cancer Survivors

  • 12/10/2006
  • Washington, DC
  • Laurie Barclay, MD
  • Mescape (www.medscape.com)

The American Cancer Society (ACS) has issued nutrition and physical activity guidelines for cancer survivors during phases of treatment and recovery and for others living with advanced cancer. The new recommendations appear in the November/December issue of CA: A Cancer Journal for Clinicians.

“Cancer survivors are often highly motivated to seek information about food choices, physical activity, and dietary supplement use to improve their treatment outcomes, quality of life, and survival,” write Ted Gansler, MD, MBA, of the 2006 Nutrition, Physical Activity and Cancer Survivorship Advisory Committee, and colleagues. “To address these concerns, the ACS convened a group of experts in nutrition, physical activity, and cancer to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer. This report summarizes their findings and is intended to present health care providers with the best possible information from which to help cancer survivors and their families make informed choices related to nutrition and physical activity.”

More than 10 million Americans are cancer survivors, defined as anyone who has been diagnosed as having cancer, from the time of diagnosis through the rest of life. Topics covered in the new guidelines include nutrition and physical activity issues during the phases of cancer treatment and recovery, living after recovery from treatment, and living with advanced cancer; nutrition and physical activity issues including body weight, food choices, and food safety; issues related to specific cancer sites (breast, colorectal, hematologic, lung, prostate, head and neck, and upper gastrointestinal); and common questions about diet, physical activity, and surviving cancer.

These guidelines, intended for healthcare providers caring for cancer survivors as well as for direct use by survivors and their families, update the most recent recommendations published in 2003.

“It is important for both health care providers and cancer survivors to consider the nutritional and physical activity issues discussed in this report within the context of the individual survivor’s overall medical and health situation,” the authors write. “This report is not intended to imply that nutrition and physical activity are more important than other clinical or self-care approaches…. In writing these suggestions, we have assumed that survivors are receiving appropriate medical and supportive care and are seeking information on self-care strategies to provide further relief of symptoms and to enhance health and improve the quality of their lives.”

For survivors at risk for unintentional weight loss, including those who are already malnourished or those who receive directed treatment to the gastrointestinal tract, it is crucial to maintain energy balance or prevent weight loss. Most cancer therapies, including surgery, radiation, and chemotherapy, can significantly affect nutritional needs, eating habits, and digestion.

Individualized nutritional therapies may include:

– For survivors with decreased appetite, consuming smaller, more frequent meals without liquids can help increase food intake.

– For survivors who cannot meet nutritional requirements through food alone, fortified and commercially prepared or homemade nutrient-dense beverages or foods may improve the energy and nutrient intake.

– For survivors who are unable to meet their nutritional needs with these means, other means of short-term nutritional support may include pharmacotherapy, enteral nutrition via tube feeding, or intravenous parenteral nutrition. However, using dietary supplements, such as vitamins, minerals, and herbal preparations, during cancer treatment is still controversial. Folate may interfere with the efficacy of methotrexate, and antioxidants may prevent the cellular oxidative damage to cancer cells that are required for efficacy of radiotherapy and chemotherapy.

“Despite methodologic limitations and small sample sizes, existing evidence strongly suggests that exercise is not only safe and feasible during cancer treatment, but that it can also improve physical functioning and some aspects of quality of life,” the authors write. “It is unknown if exercise has any effects on cancer treatment completion rates or on the efficacy of cancer treatments…. Persons receiving chemotherapy and radiation therapy who are already on an exercise program may need temporarily to exercise at a lower intensity and progress at a slower pace, but the principal goal should be to maintain activity as much as possible.”

After completion of therapy, survivors require ongoing nutritional assessment and guidance. Although the ACS has established nutrition and physical activity guidelines for cancer prevention, there are insufficient data at present to support the reasonable assumption that following these guidelines would also decrease cancer recurrence or improve survival.

These guidelines include maintaining a healthy weight throughout life, balancing caloric intake with physical activity, avoiding excessive weight gain, adopting a physically active lifestyle, consuming a healthy diet emphasizing plant sources, limiting consumption of processed and red meats, and limiting consumption of alcoholic beverages to no more than one drink per day for women or 2 per day for men. The recommended amounts and type of fat, protein, and carbohydrate to reduce cardiovascular disease risk are also appropriate for cancer survivors.

Omega-3 fatty acids may have specific benefits for cancer survivors, including reducing cachexia, improving quality of life, and perhaps enhancing the effects of some forms of treatment. Adequate protein intake is essential during all stages of cancer treatment, recovery, and long-term survival. Whole grains and whole-grain food products are preferred to refined grains. Higher vegetables and fruit intake have been specifically associated with a reduced incidence of cancer at several sites, including the colorectum, stomach, lung, oral cavity, and esophagus.

The guidelines recommend following specific recommendations regarding food safety. Except in specific situations, use of supplements containing more than the recommended daily amounts is not recommended.

Resistance exercise may improve bone strength and decrease risk for osteoporosis, and stretching exercise may improve range of motion in cancer survivors with lymphedema. In general, exercise programs may reduce anxiety and depression, improve mood, boost self-esteem, and reduce fatigue.

“The benefits of eating a variety of vegetables and fruits probably exceed the health promoting effects of any individual constituents in these foods because the various vitamins, minerals, and other phytochemicals in these whole foods act in synergy,” the authors conclude. “It is reasonable to recommend that cancer survivors adopt the general recommendations issued by the ACS for cancer prevention to eat at least five servings of a variety of vegetables and fruit each day. … Colorful choices such as dark green and orange vegetables are typically good sources of nutrients and healthful phytochemicals.”

Source:
CA Cancer J Clin. 2006;56:323-353.

December, 2006|Archive|

Study Finds No Link Between Cellphones and Cancer

  • 12/10/2006
  • Bethesda, MD
  • Katherine Hobson
  • US News (www.usnews.com)

A big, new comprehensive study should provide some comfort to those still worried about a connection between cancer and cellphones: It finds no link and provides more evidence that electromagnetic fields from the phones do not cause tumors of the head and neck.

The study, published in the current Journal of the National Cancer Institute (an independent publication no longer associated with the NCI), looked at cellphone records from more than 420,000 people in Denmark who began using the phones between 1982 and 1995. Relying on the country’s national cancer registry, researchers looked at cancer cases through 2002 among the cellphone users and the overall population.

The results? There was no increased risk of tumors in the brain, salivary glands, eyes, or inner ear. Nor was there a heightened risk of leukemia. In fact, the risk of cancer was slightly less in cellphone users, something lead author Joachim Schuz, head of biostatistics and epidemiology at the Institute of Cancer Epidemiology at the Danish Cancer Center, can’t explain but says might be because of chance alone. Early cellphone users might also differ socioeconomically from nonusers in a way that might affect cancer risk, he says. (For example, professional males with high incomes–typical for early adopters of new technology–might have healthier lifestyles.)

“We think it’s a very strong study,” he says. The findings build on the researchers’ earlier study looking at the same group, which also found no link but only tracked cellphone users until 1996. Since cancer can take years to develop, it’s important to keep monitoring the health of the earliest users to see if any association to cancer emerges later. In addition to that follow-up, Schuz and his fellow researchers are also studying children and young adults–an important population to research, given that so many kids start using cellphones at such a young age.

Because cellphones emit electromagnetic fields that can penetrate the human brain, there’s been concern that users might be at risk of cancer or other diseases. “If everyone is using a mobile phone, even a small increase in risk could have a big effect,” says Schuz. But according to the American Cancer Society, of 16 earlier studies looking at cancer and cellphone use, just two have found some kind of link. Those studies were not as well designed as the ones showing no link, the ACS said.

The new study is large, covers a lot of people over a long period of time, and uses phone records rather than relying on people to recall past cellphone use–all pluses–but has a few limitations. People whose cellphones were in their companies’ or employers’ names were excluded; that might be significant because business users might have also been the heaviest users. Also, anyone who started using a cellphone after 1995 was not included, whereas the general population comparison group included people who started using cellphones after that year. Researchers said this shouldn’t skew the study, since brain tumors take a long time to develop.

This study received no funding from the cellphone industry.

December, 2006|Archive|

‘Erectile dysfunction’ drugs heighten natural anti-cancer activity

  • 12/10/2006
  • Baltimore, MD
  • staff
  • Eurekalert.org

Sildenafil and other “impotence drugs” that boost the production of a gassy chemical messenger to dilate blood vessels and produce an erection now also show promise in unmasking cancer cells so that the immune system can recognize and attack them, say scientists at the Johns Hopkins Kimmel Cancer Center.

Tests at Hopkins on mice with implanted colon and breast tumors showed that tumor size decreased two- and threefold in sildenafil-treated animals, compared to mice that did not get the drug. In mice engineered to lack an immune system, tumors were unaffected, proof of principle, the scientists say, that the drug is abetting the immune system’s own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of Experimental Medicine, the Hopkins team says boosted levels of the chemical messenger nitric oxide appear to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.

Lab-grown cancer cells treated with sildenafil showed similar results, as did tissue samples taken from 14 head and neck cancer and multiple myeloma patients.

Sildenafil, marketed under the trade name Viagra, is one of a class of drugs used to treat erectile dysfunction in millions of men, and in recent years, its ability to stimulate the production of NO has been investigated by experts in diseases linked to the activity of blood vessels and blood components.

The new Hopkins study homes in on a tactic used by cancers to avoid detection by the immune system by turning elements of that system to its own advantage, says Ivan Borrello, M.D., assistant professor at the Johns Hopkins Kimmel Cancer Center.

Borrello and his colleagues found that tumors exploit nitric oxide-producing immune cells to create a sort of “fog” that keeps them hidden from white blood cells (T-cells) that mount attacks on tumors.

These NO-producing cells, a.k.a. myeloid-derived suppressor cells (MDSCs), normally use nitric oxide to help bring the immune system back down to surveillance levels after an “attack mode” response to foreign material.

The impotence drugs seem to reverse this process, stopping the production of nitric oxide by MDSCs thereby allowing other immune cells to “see” the cancer and attack it, says Paolo Serafini, Ph.D., a research fellow in Borrello’s laboratory and lead author on the paper.

Nitric oxide is infamous among city dwellers as a component of air-polluting smog, but is gaining importance in medical research for its cell-signaling duties and its ability to divert soldiering T-cells that patrol and protect.

The Hopkins team also analyzed gene expression patterns of the myeloid-derived suppressor cells and found that sildenafil blocked two genes regulating enzymes — arginase and nitric oxide synthase — which are key to triggering immune suppression via MDSCs. Borrello’s team found that the arginase enzyme, which metabolizes a dietary supplement called L-arginine, also contributes to dampening the immune system through MDSCs much like nitric oxide, and its production can be reversed by sildenafil.

“Impotence drugs won’t cure cancer,” Borello cautioned, “but could be used in addition to standard chemotherapy or immunotherapy treatments.”

The investigators are planning human studies to begin in the next year.

Funding for the study was provided by the Italian Association for Cancer Research.

Coauthors:
Kristin Meckel, Michael Kelso, Kimberly Noonan, Joseph Califano, and Wayne Koch from Johns Hopkins; and Luigi Dolcetti and Vincenzo Bronte from the Istituto Oncologico Veneto in Padua, Italy.

December, 2006|Archive|

Tea extracts repair radiotherapy skin damage

  • 12/10/2006
  • New York, NY
  • Anthony J. Brown, MD
  • today.reuters.co.uk

Findings from a new study confirm that tea extracts applied to the skin promote the repair of damage from radiotherapy, and shed light on the mechanisms involved in the injury. The beneficial effects of the extracts are mostly from their ability to attenuate the body signals that trigger inflammation.

Radiotherapy interruption because of toxic effects to the skin may compromise the outcome of cancer treatment, lead author Dr. Frank Pajonk, from the David Geffen School of Medicine at UCLA, told Reuters Health. “So, it is important to have an effective treatment for this problem.”

According to Pajonk, “tea extracts have been used as a folk remedy for sunburns, which led to their use as a treatment for radiation-induced skin toxicity. They have proven quite successful in this regard, but there were no scientific data” to clarify their effects.

In a study reported in the journal BMC Medicine, the researchers analyzed the effects of green or black tea extracts given to 60 patients with skin damage related to radiotherapy for head and neck cancers and cancer in the pelvic region.

Treatment with the tea extracts enhanced skin repair, the report indicates. For radiation damage in the head and neck region, the green and black tea extracts were comparable in promoting repair, whereas in the pelvic region, green tea extract was superior, Pajonk said.

The tea extracts inhibit a key proteasome, which “is at the center of the inflammatory machinery,” explained Pajonk. This effect is associated with a reduction in several cells that lead to inflammation.

The researchers also found that the anti-inflammatory effects of the tea extracts did not stem solely from epigallocatechin-gallate, considered the most active component found in green tea.

Pajonk said that there is now a need for additional studies to compare tea extract therapy with standard treatments for radiation-induced skin toxicity.

Source:
BMC Medicine, December 1, 2006.

December, 2006|Archive|

Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial

  • 12/8/2006
  • Hong Kong
  • EH Pow et al.
  • Int J Radiat Oncol Biol Phys, November 15, 2006; 66(4): 981-91

Purpose:
To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC).

Methods and Materials:
Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H&N35) were completed at baseline and 2, 6, and 12 months after radiotherapy.

Results:
Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy.

Conclusions:
IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.

Authors:
EH Pow, DL Kwong, AS McMillan, MC Wong, JS Sham, LH Leung, and WK Leung

Authors’ affilation:
Oral Rehabilitation, Faculty of Dentistry, University of Hong Kong, Hong Kong SAR

December, 2006|Archive|

Molecular biology in head and neck cancer

  • 12/8/2006
  • Madrid, Spain
  • R Hitt and MJ Echarri
  • Clin Transl Oncol, November 1, 2006; 8(11): 776-9

Major changes in the treatment of head and neck cancer are possible today because of the knowledge that we have on the molecular biology of these tumors. Different pathways are active in the development of this cancer and field cancerization is a major problem for the cure in early stage disease. Epidermal growth factor signal transduction pathway is now the principal target for this disease. New therapeutic strategies such as monoclonal antibodies and small molecules have appeared, however no more than 20% of the patients have objective responses with these therapies. Consequently, new alternatives of treatment in the basis of the understanding of molecular biology are necessary to increase the number of patients that can be cured in the future.

Authors’ affiliation:
Division of Medical Oncology. Hospital Universitario 12 de Octubre. Madrid. Spain

December, 2006|Archive|