1/19/2005 Robert Cooke Newsday.com - Health/Science The experiment was daring - squared. Two brave little Ohio girls underwent the world's first authorized gene therapy experiment - an attempt to give them functioning immune systems for the rest of their lives. The procedure delivered new, corrective genes into their white blood cells, using a virus as the delivery vehicle. That was 15 years ago. Today, both are college students. Without those new genes, it was unlikely they could have survived in a world of germs - even if sheltered inside huge plastic bubbles. Their survival signaled the advent of a promising frontier, one designed to repair genetic flaws behind life-threatening disorders. But after 5,000 patients had participated in 350 trials, things began to go wrong. First, in 1999, a young man being treated by the University of Pennsylvania died of a massive immune reaction to the gene treatment for a rare metabolic disorder. Three years later, a French baby was successfully treated for the same disorder the Ohio girls had, but developed leukemia as a byproduct of the treatment. The next year, a second French child did likewise. Researchers called a timeout. Today, a leading researcher says those downturns have provided a reason for optimism: They taught valuable lessons and, as a result, gene therapy is poised for a renaissance. The expert, Dr. Savio Woo, said that today researchers not only understand what triggered leukemia in the two children, but also are emboldened because the therapy itself has proven a success. [...]

1/19/2005 William M. Mendenhall Journal of Clinical Oncology, Vol 22, No 24 (December 15), 2004: pp. 4867-4868 The presentation of osteoradionecrosis (ORN) after radiotherapy (RT) for head and neck cancer varies from small, asymptomatic bone exposures that may remain stable for months to years or heal with conservative management, to severe necroses necessitating surgical intervention and reconstruction. The risk of developing ORN depends on a number of factors, including primary site, T stage, proximity of the tumor to bone, dentition, type of treatment (external beam RT, brachytherapy, surgery, and chemotherapy), and RT dose. Other factors that probably influence the likelihood of developing ORN include the nutritional status of the patient and continued tobacco or alcohol abuse. The mandible is the most common site of ORN, probably because it is often necessary to deliver a high RT dose to tumors near the mandible and possibly also because the blood supply may be less abundant than that of the maxilla. The incidence of severe ORN, defined as necessitating either surgical intervention, hyperbaric oxygen (HBO) treatments, or both (1) in a series of 1,495 patients treated with definitive RT for head and neck squamous cell carcinomas at the University of Florida (Gainesville, FL) is depicted in Table 1. Minimum follow-up was 2 years; all but two patients (0.13%) had follow-up until death or within 1 year of data analysis. Twenty-seven patients (2%) experienced severe ORN, which occurred most often in those patients treated for oral cavity cancers. Although patients treated with definitive RT [...]

1/19/2005 Cheyenne, Wyoming Curtis B. Wackerle Casper Star-Tribune (www.casperstartribune.net) After years of swallowing chew spit so she could hide her addiction from her fellow nurses, Kevin Dager decided that she no longer wanted to be one of the 5 percent of Wyoming women who chew tobacco. ''I quit when I was tired of the deceit in my life,'' Dager said Wednesday at a news conference to rally support for Wyoming's statewide campaign to end smokeless tobacco addiction. Wyoming has more chewing tobacco users per capita than any other state besides West Virginia, speakers said. One of five adult males uses snuff here, putting a significant portion of the population at risk of mouth cancer and other nasty oral afflictions. The reason chew is so prevalent in Wyoming is a mixture of cowboy culture and marketing, said Niki Sue Mueller, program coordinator for Wyoming's Through With Chew Week, which takes place Feb. 13-19. ''How long has this been Marlboro Country?'' she said. People live in Wyoming because they love the wide-open country and Wild West lifestyle that encourages people to do as they please, Mueller said. Unfortunately, a bond was formed between that lifestyle and tobacco use with the Marlboro Man campaign, Mueller said. And it continues today with chew, which is heavily marketed to the rodeo, rancher and outdoorsman set, Mueller said. Wyoming's chewing tobacco problem is not unique in the region. Montana and South Dakota have comparable rates of addiction. The Wyoming Department of Health launched the campaign as [...]

1/19/2005 Yang Li et al. Clinical Cancer Research Vol. 10, 8442-8450, December 15, 2004 Purpose: Oral fluid (saliva) meets the demand for noninvasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease. Experimental Design: Unstimulated saliva was collected from patients (n = 32) with primary T1/T2 OSCC and normal subjects (n = 32) with matched age, gender, and smoking history. RNA isolation was done from the saliva supernatant, followed by two-round linear amplification with T7 RNA polymerase. Human Genome U133A microarrays were applied for profiling human salivary transcriptome. The different gene expression patterns were analyzed by combining a t test comparison and a fold-change analysis on 10 matched cancer patients and controls. Quantitative polymerase chain reaction (qPCR) was used to validate the selected genes that showed significant difference (P < 0.01) by microarray. The predictive power of these salivary mRNA biomarkers was analyzed by receiver operating characteristic curve and classification models. Results: Microarray analysis showed there are 1,679 genes exhibited significantly different expression level in saliva between cancer patients and controls (P < 0.05). Seven cancer-related mRNA biomarkers that exhibited at least a 3.5-fold elevation in OSCC saliva (P < 0.01) were consistently validated by qPCR on saliva samples from OSCC patients [...]

1/19/2005 Health Section ExpressNewsline.com Larynx helps in the production of sound. When air is forced through the larynx, it causes vibration of the true vocal cords and the sound is produced. Laryngectomy is the removal of larynx. When a person is diagnosed with throat cancer, often the remedy is removal of the larynx. Unfortunately, once the decision to perform the laryngectomy is made, the surgery is done within days. This does not give the patient or his family much time to consider the life-altering implications of living without one's voice. As the patient suffers a lot because of the operation so, the need is to give him complete assurance and support. After the patient is released from the hospital, it is important that you locate a local support group. The incidence of laryngectomy is reasonably high; therefore, many support groups are in existence, and you should be able to find one in your area. The support group will help on many levels. Without your voice, you tend to feel isolated, and there is generally a feeling of self pity. Being in a group of people who have gone through the same surgery will give you a sense of community. Also, many of these people had their laryngectomy many years prior. They tend to have a wealth of information on products that can make your life easier. Once you have begun to heal physically, it will now be the time to think about an artificial voice. These instruments are called "electronic [...]

1/18/2005 Avraham Eisbruch Nature Clinical Practice Oncology (2005) 2, 34-39 Article Summary: Intensity-modulated radiation therapy (IMRT) is a new technical improvement of radiotherapy, in which computer-controlled treatment machines produce multiple beams of radiotherapy whose intensity is optimized to deliver a high dose of radiation to specified volumes, while reducing the dose to adjacent non-target organs. The potential benefits include the ability to deliver higher doses to the target with an improved safety than has previously been possible, and to reduce side effects and complications. Using IMRT to treat some head and neck cancers is especially attractive due to the close vicinity of the targets and many critical, dose-limiting and non-involved structures, and because of the lack of breathing-related motion. The main clinical uncertainties in the use of IMRT for head and neck cancer relate to uncertainties in the extent of radiation to the target areas. In addition, large volumes of adjacent, non-target tissue receive moderate to low radiation doses, raising concerns of increased risk of radiation-related carcinogenesis in young patients. Initial promising clinical data have emerged from IMRT treatment of several head and neck tumor sites. Full text article available at http://www.nature.com/ncponc/journal/v2/n1/full/ncponc0058.html About the Author: Avraham Eisbruch is Associate Professor and Director of Clinical Research at the Department of Radiation Oncology at the University of Michigan in Ann Arbor. He completed training in Medical Oncology at MD Anderson Hospital in Houston and in Radiation Oncology at Washington University in St. Louis. His clinical research focuses on improving the therapy of [...]

1/17/2005 Michael Day Journal of the National Cancer Institute (vol 95, p 1772) as reported by www.newscientist.com Oral sex can lead to oral tumours. That is the conclusion of researchers who have proved what has long been suspected, that the human papilloma virus can cause oral cancers. The risk, thankfully, is tiny. Only around 1 in 10,000 people develop oral tumours each year, and most cases are probably caused by two other popular recreational pursuits: smoking and drinking. The researchers are not recommending any changes in behaviour. The human papilloma virus (HPV), an extremely common sexually transmitted infection, has long been known to cause cervical cancers. Several small studies have suggested it also plays a role in other cancers, including oral and anal cancers. "There has been tremendous interest for years on whether it has a role in other cancers. Many people were sceptical," says Raphael Viscidi, a virologist at Johns Hopkins University School of Medicine in Baltimore, Maryland, a member of the team that did the latest work. The researchers, working for the International Agency for Research on Cancer in Lyon, France, compared 1670 patients who had oral cancer with 1732 healthy volunteers. The participants lived in Europe, Canada, Australia, Cuba and Sudan. HPV16, the strain seen most commonly in cervical cancer, was found in most of the oral cancers too. Antibodies against HPV The people with oral cancers containing the HPV16 strain were three times as likely to report having had oral sex as those whose tumour did [...]

1/17/2005 Robert D. Hart, MD et al. Arch Otolaryngol Head Neck Surg. 2005;131:34-38 Objectives: To ascertain the feasibility of sentinel lymph node (SLN) localization by preoperative lymphoscintigraphy and intraoperative gamma probe radiolocalization and to determine the predictive value of the SLN for occult metastasis of the neck in N0 squamous cell carcinoma of the oral cavity and oropharynx. Design: A prospective study of 20 consecutive patients with N0 squamous cell carcinoma of the head and neck who underwent lymphoscintigraphy and SLN biopsy. Interventions: On the day before surgery, each patient who completed the study underwent a submucosal peritumoral injection of unfiltered technetium 99m sulfur colloid followed by lymphoscintigraphy. Focal areas of radioactivity were marked on the overlying skin. The following day, the patients underwent resection of the primary tumor, elevation of subplatysmal flaps, identification and removal of the SLNs as identified by gamma probe, and complete neck dissections. Results: Lymphoscintigraphy and gamma probe radiolocalization accurately identified 1 or more SLNs in all 20 patients. In 4 (20%) of the 20 patients, the SLN correctly identified metastatic disease. In no instance was the SLN negative when the lymphadenectomy specimen was positive. Conclusions: In this study, the SLN had a negative predictive value of 100%. Sentinel lymph node biopsy is feasible and appears to accurately predict the presence of occult metastatic disease. Although further study is warranted, SLN biopsy could potentially guide head and neck oncologists to the patient with N0 disease who would benefit most from selective neck dissection and prevent [...]

1/17/2005 Vancouver, British Columbia Canadian Cancer Society as reported by newswire.ca The Canadian Cancer Society believes that the British Columbia government must make curbing tobacco a priority. Tobacco use is the number one cause of preventable disease, disability, and death in Canada. More than 47,000 Canadians, including 5,600 British Columbians, die each year from tobacco related illness, including lung cancer, throat and oral cancer, heart disease, stroke, and emphysema. Further, each year more than 500 British Columbians die from exposure to second-hand smoke. Cigarette smoking is responsible for 30% of all cancer deaths and more than 85% of lung cancers. "Given these sobering statistics, it is startling that British Columbia's existing second-hand smoke regulation allows smoking in enclosed rooms in restaurants and bars," said Barbara Kaminsky, CEO of the Canadian Cancer Society, BC and Yukon Division. The regulation, which states that rooms must be separately ventilated and workers can not spend more than 20% of their shift in these rooms, is more cosmetic than real. There is little enforcement of the law and businesses are not held accountable. Research has shown that the designated smoking rooms do not protect workers and patrons to the dangerous effects of second-hand smoke. Something must be done about this. The Canadian Cancer Society, BC and Yukon Division, believes that the government of British Columbia must enact legislation that would restrict smoking in all public places and workplaces, including restaurants and bars. In Canada, British Columbia was once a leader in tobacco control. Today, six [...]

1/16/2005 Philadelphia, PA Andrew J. Dannenberg, M.D. et al. Cancer Research Journal, Jan. 2005 Tobacco smoke triggers the production of COX-2, a cellular protein linked to the development and progression of cancer, according to research published in the January 15 issue of the journal Cancer Research. Tobacco smoke also promoted rapid cellular production of two proteins that initiate an epidermal growth factor receptor (EGFR) driven cascade leading to the production of COX-2, the report stated. The report by Andrew J. Dannenberg, M.D., director of cancer prevention, Weill Medical College of Cornell University, and colleagues, indicates that smokers produce as much as four times the amount of COX-2 in oral mucosal cells lining their mouths than their non-smoking counterparts. After observing the increased amount of COX-2 in the oral mucosa of smokers, Dannenberg and his team of collaborating scientists exposed cells in culture to tobacco smoke to define the mechanism underlying smoke-induced elevation of COX-2. The researchers determined that COX-2 levels were increased due to tobacco smoke induced activation of EGFR, a cell membrane protein also associated with various types of cancer. Tobacco smoke stimulated the oral mucosal cells to rapidly release two proteins that activate the EGFR, initiating a cascade resulting in COX-2 protein production. "In an oral mucosal cell line, tobacco smoke clearly activated the epidermal growth factor receptor. Tobacco smoke caused increased EGFR phosphorylation leading to increased COX-2 production," Dannenberg reported. "We were able to block the induction of COX-2 with either a small molecule that inhibited EGFR [...]