6/26/2005 Jacques Bernier Nature Clinical Practice Oncology (2005) 2, 305-314 Summary Despite recent advances in multimodality management of patients with stage III−IV head and neck squamous cell carcinoma, the prognosis in these patients remains disappointing. In an attempt to improve treatment outcome, several teams recently investigated the role of altered fractionation radiotherapy in conjunction with systemic chemotherapy. The controlled trials that investigated this combined approach indicate that, although the magnitude of its effect was less marked for survival indices than for local-regional control, the addition of chemotherapy to altered fractionation regimens results in a clear improvement for these endpoints compared with hyperfractionated or accelerated regimens alone. The key challenge now is to optimize the synergism of these regimens in order to increase their therapeutic ratio in terms of both local-regional and systemic outcomes. This review is a critical appraisal of the real opportunities offered by the application of treatments aimed at increasing the dose intensity of radiotherapy delivered concurrently with cytotoxic drugs. Introduction Head and neck squamous cell carcinomas (HNSCC) represent 4−5% of all solid malignancies, with almost half a million cases diagnosed annually worldwide.1 Until the late 1970s radiation therapy was the treatment of choice for locally advanced HNSCC but, despite significant technologic improvements in radiation therapy, the high incidence of local-regional recurrences continued to pose the greatest threat.2 Tumor hypoxia, repopulation of tumor cells during treatment, and intrinsic resistance to radiotherapy, have all been implicated as causes of treatment failure.3, 4 From the late 1970s, altered fractionation radiation [...]

6/26/2005 New York City, NY press release Genetic Engineering News (www.genengnews.com) ImClone Systems Incorporated announced today that, following discussions with the FDA, the Company intends to submit a supplemental Biologics License Application (sBLA) to seek approval for use of Erbitux(R) (Cetuximab) in combination with radiation and as a single agent in Squamous Cell Carcinoma of the Head and Neck (SCCHN) in the third quarter of 2005. The following clinical trials would serve as the basis of the sBLA, together with other supportive data: 1. a randomized, international phase III trial (IMCL-9815), conducted by ImClone Systems and Merck KGaA, presented at the 2004 American Society of Clinical Oncology (ASCO) annual meeting examining the impact of combining Erbitux with radiation on locoregional control and overall survival in 424 patients with locally advanced SCCHN. and 2. a multicenter phase II trial (EMR-016) conducted by Merck KGaA presented at the 2004 ASCO annual meeting evaluating the response rate of Erbitux as a single agent in 103 patients with advanced recurrent and/or metastatic SCCHN not suitable for further local therapy and who have failed platinum-based chemotherapy. About Head and Neck Cancer According to the American Cancer Society, approximately 40,000 Americans will be diagnosed with oral, head and neck cancer this year, including cancers of the tongue, mouth, pharynx, and larynx. More than 11,000 will die from the disease in 2005. About Erbitux (Cetuximab) On February 12, 2004, the FDA approved Erbitux for use in the United States in combination with irinotecan in the treatment of [...]

6/26/2005 Austin, TX press release Austin Business Journal Austin biopharmaceutical company Introgen Therapeutics Inc. received a patent that covers many of the features of its Advexin molecular therapy for cancer patients. The patent is one of a family of patents that cover Advexin issued to the Board of Regents of The University of Texas System and exclusively licensed to Introgen. "This important patent further expands Introgen's formidable adenoviral p53 patent portfolio. This particular patent was specifically crafted to directly cover many of the special features of Introgen's ADVEXIN product candidate, as well as to the host cells that are employed to produce the product," says David Parker, Introgen's vice president of Intellectual Property. To date, Introgen has 30 issued patents and a number of pending patent applications in the U.S. and in foreign countries relating to its Advexin. In 2003, Introgen's investigational drug, Advexin, was granted "fast track" designation by the U.S. Food and Drug Administration as a treatment for head and neck cancer. Introgen develops biopharmaceutical products for the treatment of cancer and other diseases. The company conducts research, development, manufacturing, clinical and regulatory activities at its Austin headquarters.

6/26/2005 Los Angeles, CA ABC Channel 7 News (abc7.com) Oral cancer is often associated with smoking, but an increasing number of young non-smokers are being diagnosed with the disease. It's a killer that could be hiding right under your nose. Oral cancer strikes 30,000 Americans a year. Of those, only half survive. Brian Hill, the Founder of the Oral Cancer Foundation, a 501(c)3 non-profit, did not smoke, or fall into the "historical" stereotype of an oral cancer patient. But that stereotypical patient model is changing. He was diagnosed with stage four oral cancer, and in his case a viral association was likely the precursor trigger. Oral cancer it seems is not just for smokers. Brian tested positive for the HPV virus, as did his wife. Researchers believe HPV interferes with proteins that inhibit tumor growth. This is a very common virus that as many as 40% of all Americans have. However, only some forms of it may cause malignancy. Two versions of it - 16 and 18, are the same virus that causes approximately 98% of all cervical cancer, and now are documented to be involved in oral cancers as well. HPV is usually spread through sexual activity. It is possible to transmit the virus from one individual to another. Doctors say it is highly unlikely that the virus can be transmitted through casual contact. Brian endured 7 weeks of radiation followed by surgery to remove a portion of the floor of his mouth, and the right side of his [...]

6/25/2005 New York, NY Randy Dotinga Forbes Magazine (www.forbes.com) Besides raising the risk of oral cancer, smokeless tobacco -- also known as snuff, dip or chewing tobacco -- appears to boost the odds male users will die from heart disease, according to the largest study of its kind ever conducted. The findings contradict earlier research, finding instead that people who chew or "dip" tobacco are 20 percent more likely to be killed by a heart attack or stroke than nonusers. It isn't clear why smokeless tobacco might contribute to cardiovascular problems, and the study isn't the final word on the issue, said co-author Jane Henley, an epidemiologist with the American Cancer Society. Even so, the research, released this month in the journal Cancer Causes and Control, should give users another reason to kick their habit, she said. Some chew users are ex-smokers who turn to smokeless tobacco to "tide them over" as they try to kick the smoking habit. But "any form of tobacco is harmful to your health," Henley said. "We should be encouraging smokers who want to quit to use nicotine-replacement and other safe therapies." In their study, Henley and her colleagues examined two U.S. surveys of American adults, one spanning the years 1959-1972 and another from 1982-2000. Together, nearly 1 million men filled out questionnaires, including almost 10,000 smokeless tobacco users. The studies encompassed both chewing tobacco, found in pouches and kept between the cheek and gums, and "dip," also known as "snuff," which comes in small [...]

6/19/2005 Ann Arbor, MI press release University of MIchigan Health System (www.med.umich.edu) University of Michigan scientists have created the nanotechnology equivalent of a Trojan horse to smuggle a powerful chemotherapeutic drug inside tumor cells – increasing the drug's cancer-killing activity and reducing its toxic side effects. Previous studies in cell cultures have suggested that attaching anticancer drugs to nanoparticles for targeted delivery to tumor cells could increase the therapeutic response. Now, U-M scientists have shown that this nanotechnology-based treatment is effective in living animals. “This is the first study to demonstrate a nanoparticle-targeted drug actually leaving the bloodstream, being concentrated in cancer cells, and having a biological effect on the animal's tumor,” says James R. Baker Jr., M.D., the Ruth Dow Doan Professor of Biologic Nanotechnology at the University of Michigan, who directed the study. “We're very optimistic that nanotechnology can markedly improve cancer therapy,” says Baker, who directs the Michigan Nanotechnology Institute for Medicine and the Biological Sciences. “Targeting drugs directly to cancer cells reduces the amount that gets to normal cells, increases the drug's anti-cancer effect and reduces its toxicity. By improving the therapeutic index of cancer drugs, we hope to turn cancer into a chronic, manageable disease.” Results of the study will be published in the June 15, 2005, issue of Cancer Research. The drug delivery vehicle used by U-M scientists is a manmade polymer molecule called a dendrimer. Less than five nanometers in diameter, these dendrimers are small enough to slip through tiny openings in cell [...]

6/17/2005 England Thea Jourdan The Telegraph (www.telegraph.co.uk) English strawberries are now in peak season - just in time for Wimbledon, where about three tonnes will be consumed. Overindulgence, however, could be a good thing: as well as being delicious, the world's most popular berry is said to do wonders for your health. Traditionally, strawberries, which contain more vitamin C than the equivalent weight of oranges, have been used to cleanse the digestive system. They also contain a range of phytonutrients, with many health-boosting effects. "Strawberries can legitimately claim to be heart protective, anti-cancer and anti-inflammatory, all rolled into one," says dietician Nigel Denby. "They rank as one of the world's healthiest foods." Why are they good for you? Anti-cancer Strawberries are a rich source of phenols - including anthocyanins and ellagic acid - which are potent, cancer-busting antioxidants. Anthocyanins give the berries their distinctive red colour, and mop up free radicals in the blood, which can cause cancerous changes in cells. In laboratory studies, ellagic acid has been shown to halt the growth of tumours in the lungs, oesophagus, breast, cervix and tongue. Anti-inflammatory Some phenols found in strawberries reduce the activity of cyclooxygenase (COX) enzymes. In people with rheumatoid and osteo-arthritis and asthma, their overactivity contributes to inflammation. Drugs with a similar effect can cause intestinal bleeding. Anti-ageing Researchers have found that rats fed a strawberry-rich diet showed less of an age-related decline in brain function. Their learning capacity and motor skills were also improved. This could be because [...]

6/15/2005 Chicago, IL Medical News staff Medical News Today (www.medicalnewstoday.com) The emergence of acupuncture is allowing some patients to relieve or significantly reduce dry mouth's debilitating effects, according to a report in the May/June 2005 issue of General Dentistry, the Academy of General Dentistry's (AGD) clinical, peer-reviewed journal. Dry mouth (also known as xerostomia) is a painful condition caused by a decrease in the amount of saliva in the mouth when salivary glands do not work properly. Saliva is a natural defense for teeth and plays a major role in preventing tooth decay by rinsing away food particles and neutralizing harmful acids. A decrease in saliva puts patients at risk for cavities, gum disease and discomfort since foods that are consumed adhere to the teeth longer. Dry mouth can be caused by medications like antihistamines, decongestants, antidepressants and diuretics and can often be treated by the dentist. The quality of life of patients suffering from dry mouth is often profoundly impaired. Symptoms include extensive dental decay, infections of the tissues of the mouth, difficulty in speaking, eating and swallowing, ulceration or soreness of the mouth, an altered sense of taste and difficulty in wearing dentures. However, "typical treatment options for dry mouth have been short-term at best," according to Warren M. Morganstein, DDS, MPH, and associate dean at the Baltimore College of Dental Surgery, University of Maryland Dental School. "Studies have found that acupuncture was a viable option to successfully treat dry mouth pain in patients and provide long-term relief." [...]

6/15/2005 New Milford, CT Jamboor K. Vishwanatha et al. Mol Cancer Ther. 2005;4:865-875 An early interventional effort in oral premalignancy requires novel molecular targets and diagnostic biomarkers to delay or reverse incidences of malignant progression. Microarray-based transcriptional profiling in disease states provides global insight into the causal biomolecular processes and novel pathways involved. In this study, we investigated transcript profiles in precancerous oral lesions to identify nearly 1,700 genes as significantly overexpressed or underexpressed and a primarily affected metabolic pathway that may be responsible for irreversible transition to progressive stages of oral cancer. For the first time, we show a convergence of several genes and pathways known for their oncogenic capabilities, in progression of premalignant oral epithelial tissues. This study consequently provides a molecular basis for persistent proinflammatory conditions in oral premalignant tissues. We found that lipocalin-type prostaglandin D2 synthase (PTGDS), a key enzyme in the arachidonic acid metabolism pathway, as repressed in premalignant stages. We show the protective role of these enzyme-derived metabolites in inhibiting cell proliferation using an in vitro oral cancer progression model. We have also confirmed the overexpression of two invasion-related biomarkers, psoriasin (PSOR1) and versican (CSPG2), in oral premalignant and malignant archival tissues. Our results clearly indicate that pharmacologic intervention with anti-inflammatory prostaglandin D2–like analogues may help prevent or delay oral epithelial carcinogenesis because of metabolic restoration of a negative feedback regulatory loop through its several cognate receptors or target molecules. Further studies directed toward a multitude of possible protective mechanisms of this lipocalin-type enzyme [...]