The promise of viral therapies

11/30/2006 Toronto, Ontario, Canada Carolyn Abraham At any other moment in Brad Thompson's life it might have sounded too strange. But when University of Calgary researchers approached the entrepreneur in 1998 about the potential of using a common stomach bug to fight cancer, their timing was uncanny. Dr. Thompson had lost his mother to lung cancer that year, his uncle to esophageal cancer and he himself had been diagnosed with melanoma. "I was open to thinking about cancer, and thinking about it in a new way," said the microbiologist, who was working with a biotech firm on bowel diseases at the time. "I'm awfully glad they came to see me." Eight years later, Dr. Thompson, now CEO of Calgary-based Oncolytics Biotech, is in the vanguard of one of the more promising, if unconventional, approaches to treating cancer patients: deliberately infecting them with viruses. Cancer cells, it so happens, are particularly vulnerable to viral invasion and the century-old concept has cured laboratory mice, pushed some end-stage cancer patients into long-term remission and raised hopes for a new generation of cancer therapies. Hundreds of patients in clinical trials in Canada, the United States and Europe have volunteered to catch a cold, a stomach bug, a mutant form of herpes and even a chicken flu. Researchers have found cancer cells lack the defences that healthy cells have to protect themselves from infection. Flipped into overdrive, a cancer cell never shuts down the pathway that allows a viral intruder to waltz in, replicate [...]

2009-04-13T09:20:06-07:00November, 2006|Archive|

Focusing Radiation In The Affected Area Leads To Better Control Of Cranial-Base Tumor

11/30/2006 Boston, MA Pascal Pommier et al. Proton beam radiation therapy, a very precise type of radiation treatment, may be an effective treatment for advanced adenoid cystic carcinoma that has spread to the cranial base, according to a study from the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (MGH). In the November issue of Archives of Otolaryngology - Head and Neck Surgery, the research team describes results from 11 years of using proton therapy to treat this tumor, which can be dangerous when it spreads into the complex structures at the base of the skull. "We are very encouraged by our results, in which local tumor control of advanced adenoid cystic carcinoma of the cranial base compared very favorably with results reported from traditional radiation therapy," says Annie Chan, MD, MGH Radiation Oncology, who led the study. Frequently originating in the salivary glands, adenoid cystic carcinoma is an indolent but aggressive tumor that is usually treated surgically if diagnosed at an early stage. However, when it originates in or spreads into the cranial base - a complex area involving the cranial nerves, the eyes and critical brain structures - it is impossible to remove the tumor safely. Traditional radiation therapy has had limited success in controlling the tumors' growth, largely because the sensitive adjacent structures sharply limit the ability to deliver a strong enough dose. Proton therapy takes advantage of an inherent quality of the positively charged atomic particles. As they travel through tissues, protons release [...]

2009-04-13T09:19:30-07:00November, 2006|Archive|

Australia to Subsidize Merck Cervical Cancer Vaccine

11/29/2006 Canberra, Australia Vesna Poljak and Gemma Daley Australia's government agreed to add Merck & Co.'s Gardasil vaccine to its subsidized health program, reversing an earlier decision to exclude the shots which protect against viruses causing 70 percent of cervical cancer. Prime Minister John Howard said Australia will spend A$436 million ($342 million) making the vaccine free for women aged 12 to 26. The turnabout followed an agreement by its distributor CSL Ltd. to cut the price by 27 percent, and criticism from the Australian university where it was developed. "Gardasil will be available for a nationwide vaccination campaign commencing next year," Howard told reporters in Canberra today. "This remarkable Australian drug can be made cheaply available to women." Cervical cancer kills about 250,000 women annually, making it the second-biggest cause of death among female cancer patients globally, according to the World Health Organization. It is caused predominantly by human papillomavirus, or HPV, a virus carried by about 440 million people. Shots protecting against the sexually transmitted virus should be mandatory for preteen girls and available worldwide, researchers from Johns Hopkins University in Baltimore wrote in the scientific journal Nature Reviews Cancer in September. Gardasil is the first vaccine aimed at preventing cervical cancer. It is "an immense innovation," Didier Hoch, president of Sanofi Pasteur MSD, the vaccine joint venture between Merck & Co. and Sanofi-Aventis SA, said this week. European Union-member states should lead other governments by making the vaccinations mandatory for all girls aged 11-12 years, the [...]

2009-04-13T09:18:59-07:00November, 2006|Archive|

Chemoprevention of Head and Neck Cancer With Aspirin

11/28/2006 Buffalo, NY Vijayvel Jayaprakash, MBBS et al. Arch Otolaryngol Head Neck Surg. 2006;132:1231-1236 Objective: To evaluate the chemopreventive potential of aspirin against head and neck cancer. Design: Hospital-based case-control study. Setting: National Cancer Institute–designated comprehensive cancer center. Patients: Individuals who received medical services at the Roswell Park Cancer Institute, Buffalo, NY, between 1982 and 1998 and who completed a comprehensive epidemiologic questionnaire. Main Outcome Measure: Aspirin use among 529 patients with head and neck cancer and 529 hospital-based control subjects matched by age, sex, and smoking status. Results: Aspirin use was associated with a 25% reduction in the risk of head and neck cancer (adjusted odds ratio, 0.75; 95% confidence interval, 0.58-0.96). Consistent risk reductions were also noted in association with frequent and prolonged aspirin use. Further, a consistently decreasing trend in risk was noted with increasing duration of aspirin use (Ptrend = .005). Risk reduction was observed across all 5 primary tumor sites, with cancers of the oral cavity and oropharynx exhibiting greater risk reduction. When analyzed by smoking and alcohol exposure levels, participants moderately exposed to either showed a statistically significant 33% risk reduction (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.91), whereas participants exposed to both heavy smoking and alcohol use did not benefit from the protective effect of aspirin. The reduction in risk was relatively more significant in women. Conclusions: Aspirin use is associated with reduced risk of head and neck cancer. This effect is more pronounced in individuals with low to moderate exposure to [...]

2009-04-13T09:18:29-07:00November, 2006|Archive|

Stem Cells May Lead to Cancer Vaccine

11/26/2006 Louisville, KY Miranda Hitti Tests on Mice Suggest Vaccine for Lung Cancer Might Be Possible, but Long Way Off It might be possible to make a cancer vaccine using embryonic stem cells, University of Louisville scientists report. Their prediction is based on early lab tests on mice. No such vaccine exists for humans yet. But results from mouse tests suggest the "exciting possibility" that embryonic stem cell vaccines might prevent cancer, write researcher John Eaton, PhD, and colleagues. Their findings were presented yesterday in Prague, Czech Republic, at a joint symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI), and the American Association for Cancer Research (AACR). "At present, all I can say is that so far it looks good, and that, unless something unexpected happens, this strategy might someday be applied to humans at high risk for development of cancer," Eaton says in an EORTC news release. Eaton is a professor of medicine and pharmacology/toxicology and the Brown Chair of Cancer Biology at the University of Louisville's medical school. Eaton's team used embryonic stem cells taken from mouse embryos to make two experimental vaccines against mouse lung cancerlung cancer. One of the vaccines contained only embryonic stem cells. The other vaccine contained embryonic stem cells plus a growth factor to boost immune response. The scientists split the test mice into three groups. One group of mice got the vaccine containing only stem cells. A second group got the vaccine [...]

2009-04-13T09:17:57-07:00November, 2006|Archive|

Low dose vitamin A derivative does not prevent head and neck tumors

11/24/2006 Italy staff Xagena Medicine ( Taking a vitamin A derivative called Isotretinoin (Accutane/Roaccutane) did not reduce the risk of second primary tumors or improve survival in patients with stage I or II head and neck squamous cell cancers (HNSCC). In addition, current smokers had an increased risk of second primary cancers and death. HNSCCs are the fifth most common cancers and sixth leading cause of cancer related death today. In 2002, there were 600,000 new cases diagnosed worldwide. Some studies have suggested that vitamin A derivatives called retinoids may halt or even reverse growth of head and neck tumors. A clinical trial of high doses of a retinoid called isotretinoin, widely used to treat cystic acne, in patients with HNSCC found that those receiving isotretinoin developed fewer second primary tumors, particularly smoking-related tumors. However, there were substantial side effects among those who received the high-dose isotretinoin, and subsequent studies of the compound have shown mixed results. To assess the effect of lower, more tolerable doses of isotretinoin on the development of second primary tumors and survival among patients with early-stage HNSCC, Fadlo R. Khuri, of the Emory University School of Medicine in Atlanta, and colleagues conducted a randomized clinical trial of 1190 patients diagnosed with stage I or II HNSCC. Patients were randomly assigned to receive low-dose Isotretinoin (30 mg/day) or a placebo for 3 years. Researchers continued to monitor the patients for 4 or more years after treatment. This clinical trial is the largest chemoprevention study to date [...]

2009-04-13T09:17:25-07:00November, 2006|Archive|

Fluorescence Visualization Detection of Field Alterations in Tumor Margins of Oral Cancer Patients

11/24/2006 Vancouver, British Columbia, Canada Catherine F. Poh et al. Clinical Cancer Research Vol. 12, 6716-6722, November 15, 2006 Purpose: Genetically altered cells could become widespread across the epithelium of patients with oral cancer, often in clinically and histologically normal tissue, and contribute to recurrent disease. Molecular approaches have begun to yield information on cancer/risk fields; tissue optics could further extend our understanding of alteration to phenotype as a result of molecular change. Experimental Design: We used a simple hand-held device in the operating room to directly visualize subclinical field changes around oral cancers, documenting alteration to fluorescence. A total of 122 oral mucosa biopsies were obtained from 20 surgical specimens with each biopsy being assessed for location, fluorescence visualization (FV) status, histology, and loss of heterozygosity (LOH; 10 markers on three regions: 3p14, 9p21, and 17p13). Results: All tumors showed FV loss (FVL). For 19 of the 20 tumors, the loss extended in at least one direction beyond the clinically visible tumor, with the extension varying from 4 to 25 mm. Thirty-two of 36 FVL biopsies showed histologic change (including 7 squamous cell carcinoma/carcinomas in situ, 10 severe dysplasias, and 15 mild/moderate dysplasias) compared with 1 of the 66 FV retained (FVR) biopsies. Molecular analysis on margins with low-grade or no dysplasia showed a significant association of LOH in FVL biopsies, with LOH at 3p and/or 9p (previously associated with local tumor recurrence) present in 12 of 19 FVL biopsies compared with 3 of 13 FVR biopsies (P = [...]

2009-04-13T09:16:32-07:00November, 2006|Archive|

Cyclooxygenase-2 Inhibition Suppresses {alpha}v{beta}6 Integrin-Dependent Oral Squamous Carcinoma Invasion

11/22/2006 United Kingdom Staff Cancer Res., November 15, 2006; 66(22): 10833-42 Worldwide oral squamous cell carcinoma (OSCC) represents about 5.5% of all malignancies, with approximately 30,000 new cases each year in the United States. The integrin alpha(v)beta(6) and the enzyme cyclooxygenase-2 (COX-2) are implicated in OSCC progression and have been suggested as possible therapeutic targets. Each protein also is reported to identify dysplasias at high risk of malignant transformation, and current clinical trials are testing the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) at preventing OSCC development. Given the probable increased expression of alpha(v)beta(6) and COX-2 in OSCC and the inhibition of several integrins by NSAIDs, we investigated whether NSAIDs affected alpha(v)beta(6)-dependent cell functions. We found that expression of both alpha(v)beta(6) and COX-2 was significantly higher in OSCC compared with oral epithelial dysplasias. Neither protein preferentially identified those dysplastic lesions that became malignant. Using OSCC cell lines, modified to express varying levels of alpha(v)beta(6), we assessed the effect of COX-2 inhibition on cell invasion. We found that the COX-2 inhibitor NS398 inhibited specifically alpha(v)beta(6)-dependent, but not alpha(v)beta(6)-independent, OSCC invasion in vitro and in vivo, and this effect was modulated through prostaglandin E(2) (PGE(2))-dependent activation of Rac-1. Transient expression of constitutively active Rac-1, or addition of the COX-2 metabolite PGE(2), prevented the anti-invasive effect of NS398. Conversely, RNA interference down-regulation of Rac-1 inhibited alpha(v)beta(6)-dependent invasion. These findings suggest that COX-2 and alpha(v)beta(6) interact in promoting OSCC invasion. This is a novel mechanism that, given the ubiquity of alpha(v)beta(6) expression by head and [...]

2009-04-13T09:16:04-07:00November, 2006|Archive|

BC Cancer Agency study sheds new light on controlling oral cancer

11/22/2006 Vancouver, Canada BC Cancer Agency Vancouver, B.C. - A study recently published in Clinical Cancer Research takes BC Cancer Agency researchers into the operating room to shed new light on oral cancer. Using a hand-held blue light device that could chance clinical practices, pioneered at the BC Cancer Agency, researchers examined oral cancer patients for pre-cancerous and cancerous lesions that are not visible to the naked eye. The light device makes cancerous lesions that look like normal tissue under regular white light appear as dark patches. "This light device could revolutionize surgical practice, allowing us to see previously hidden changes at the edge of cancers during surgery," says Dr. Scott Durham, surgeon, Vancouver General Hospital. The light device detected dark patches that extended beyond the tumour and its surgical boundary in 19 of the 20 patients involved in the study. Biopsies taken from the tissue outside the surgical boundary confirmed the existence of both cancerous and abnormal cells. Recognizing the tissue surrounding oral cancers is at high-risk for developing cancer, surgeons generally remove an arbitrary width of 10 millimeter or more of normal-looking tissue surrounding the tumour, if anatomically possible. However, the study has shown that this approach still fails to completely remove the high-risk tissues in many patients. "By using the light device, we were able to see that cancerous and pre-cancerous lesions are not evenly distributed around the tumour," says Dr. Catherine Poh, Oral Pathology Specialist at the BC Cancer Agency and Principal Investigator of the study. [...]

2009-04-13T09:15:32-07:00November, 2006|Archive|

High HPV Concentrations, Cigarette Smoking Significantly Raise Risks of Later Cervical Cancer

11/21/2006 Philadelphia, PA staff PharmaLive ( Cigarette smoking and concurrent infection with high levels of the virus associated with cervical cancer can increase cancer risk by as much as 27 times, according to a study published in the November 2006 issue of Cancer Epidemiology, Biomarkers & Prevention. Anthony Gunnell, a medical biostatistician and epidemiologist and colleagues at the Karolinska Institutet in Stockholm reviewed the medical exams of women with non-invasive cervical cancer in situ (the most common type) and cancer-free women in one of the largest studies to date to examine the relationships between smoking and the human papilloma virus (HPV). The virus and smoking behavior have long been associated with the disease, but not enough evidence has come forth to determine how either may cause the disease. Gunnell’s study, in fact, suggests that both may create a biochemical synergy that propels the disease. The researchers looked at “Pap” smear examination data from 105,760 Swedish women and identified 499 women with cervical cancer in situ, along with 499 cancer-free women as controls. For these women, they compared their smoking behavior with concentrations (known as viral load) of HPV-16, the viral strain most associated with cervical cancer. The researchers found that a combination of high viral loads and smoking during the time they were initially examined resulted in very high risk of later cervical cancer. “We were surprised to see this dramatically increased risk among women with high viral loads who smoked,” Gunnell said. Among their findings: - Women who smoked [...]

2009-04-13T09:14:34-07:00November, 2006|Archive|
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