5/25/2006 Durham, NC Lee W.T. Alkureishi et al. The Oncologist, Vol. 11, No. 5, 469-480, May 2006 Head and neck cancer frequently presents at a late stage, leading to a poor prognosis despite optimal treatment with surgery and/or radiotherapy. Chemotherapy for advanced disease has shown little benefit as a single-modality treatment, and the use of concurrent chemoradiation is limited by problems with severe toxicity at higher doses. RADPLAT is the acronym used to describe a new technique, combining intra-arterial delivery of cisplatin with systemic neutralization by i.v. sodium thiosulphate, and concurrent radiotherapy. This allows very high cisplatin dose intensities to be used while potentially minimizing adverse systemic effects. Initial results suggest that excellent locoregional control rates are achievable in patients with unresectable disease, with a favorable side-effect profile when compared with conventional chemoradiation protocols. In addition, RADPLAT may potentially be of benefit in selected patients with resectable disease, allowing for preservation of organ function and quality of life without compromising locoregional control or survival. While current phase II data are encouraging, phase III randomized controlled trials are required in order to directly compare RADPLAT with i.v. chemoradiation therapy, the current standard of care. This article reviews the evolution of the RADPLAT concept, from initial clinical trials to its current application in the treatment of patients with advanced head and neck cancer. Note: The full text of the article is available here Authors: Lee W.T. Alkureishi(a), Remco de Bree(b), Gary L. Ross(c) Authors' affiliations: a Department of Plastic Surgery, Canniesburn Hospital, [...]

5/25/2006 Helsinki, Finland staff Medical News Today (www.medicalnewstoday) It has been estimated that in developed countries up to 80 % of the cancers of mouth, pharynx and oesophagus are caused by smoking and alcohol drinking. According to Finnish researchers these epidemiological findings can at least in part be explained by the fact that alcohol drinking and smoking result in a strong local exposure of the upper digestive tract to acetaldehyde, and they have proved that acetaldehyde exposure can be markedly prevented by a tablet that releases amino acid, l-cysteine. The research group of professor Mikko Salaspuro, University of Helsinki and Helsinki University Hospital, Finland, published already in 1990s a hypothesis, that microbes representing normal human digestive tract flora produce locally acetaldehyde from ethanol and that this may expose them for an increased risk of digestive tract cancers. The hypothesis was strongly supported by Japanese studies showing that digestive tract cancer risk is markedly increased in Japanese drinkers, who have a decreased ability to remove acetaldehyde because of a gene mutation. The cause and effect relationship was subsequently strongly supported by a novel finding of the Finnish research group showing that after a small dose of alcohol Asians with the above mentioned gene mutation have 2-3 times higher concentrations of acetaldehyde in their saliva than those with the normal acetaldehyde removing enzyme. Most recently, a research group from NIH reported a mechanism that induces DNA-damage in those acetaldehyde concentrations that are found in the saliva after drinking of alcohol. It has [...]

5/24/2006 Rochester, MN staff Mayo Clinic (www.mayoclinic.com) Researchers hope that stopping angiogenesis could make cancer a more manageable disease. As with all living things, even cancer needs oxygen and nutrients to help it grow and thrive. To get the fuel they need, tumors develop a network of new blood vessels in a process called angiogenesis. Angiogenesis is an area of intense focus by cancer researchers who hope that stopping angiogenesis could mean stopping cancer from growing and spreading. Numerous drugs that may one day help prevent, stop or reverse angiogenesis are under investigation. These drugs are referred to as angiogenesis inhibitors or anti-angiogenic drugs. Only one drug that acts solely as an angiogenesis inhibitor is currently approved for use, but researchers are finding that many cancer drugs intended to attack cancer cells in other ways may also act as angiogenesis inhibitors. Researchers hope that stopping or reversing angiogenesis could leave tumors small and manageable. What is angiogenesis? Angiogenesis describes the formation of new blood vessels within your body. For instance, an embryo uses angiogenesis to develop inside the womb, a woman experiences angiogenesis as a normal part of menstruation, and body tissues use angiogenesis to help heal wounds. Angiogenesis also refers to the process by which a tumor develops a blood supply. Small tumors can survive without a network of blood vessels to deliver oxygen and nutrients. These small tumors rely on nearby tissue to deliver small amounts of energy. In order to grow larger and spread (metastasize), a tumor [...]

5/23/2006 Davis, CA staff Life Science News (news.biocompare.com) Doctors have long been encouraging Americans to add more fruits and vegetables to their daily diets. Now, UC Davis researchers have discovered one way in which flavonoid-rich apples inhibit the kinds of cellular activity that leads to the development of chronic diseases, including heart disease and age-related cancers. "We've known for a long time that it's the flavonoids in fruits that are protecting the body. We just haven't known exactly how. Now, at least in the case of apples, we have a good idea about what's going on," said Eric Gershwin, professor of allergy, rheumatology and immunology at the UC Davis School of Medicine. Gershwin and his colleagues found that apple extract was able to protect cells from damage and death by interfering with communication between cells. The current findings appear in the latest issue of Experimental Biology and Medicine. Earlier studies have shown that flavonoids--which are found in chocolate and green tea, as well as other fruits and vegetables--behave as anti-oxidants, taking up free oxygen radicals that can damage precious DNA. The UC Davis study takes that research further by looking beyond the antioxidant effects of apple flavonoids. In the current study, Gershwin and his colleagues exposed human endothelial cells to an extract of an apple mash made from different apple varieties. The researchers then challenged these cells by exposing them to tumor necrosis factor (TNF), a compound that usually triggers cell death and promotes inflammation via a mechanism called the [...]

5/18/2006 Augusta, GA press release Biocompare Life Science News (www.biocompare.com) The blood of patients with head and neck cancer appears to have unique patterns of protein expression that one day could serve as a screening test for the highly aggressive cancer that is often diagnosed too late, researchers say. Studies comparing protein expression in 78 patients with head and neck cancer to 68 healthy controls revealed numerous differences in protein expression, Medical College of Georgia researchers say. “We found scores and scores of proteins that were differentially expressed,” says Dr. Christine Gourin, MCG otolaryngologist specializing in head and neck cancer and the study’s lead author. “We found there are at least eight proteins whose expression significantly differs between controls and people with cancer.” This protein fingerprint correctly classified study participants as cancer patients with a high degree of sensitivity and specificity – 82 percent and 76 percent, respectively, according to research published in the current issue of Archives of Otolaryngology. “If these results hold up over time, they would suggest that this would be a good screening test for at-risk people,” Dr. Gourin says. “Right now there is no good, effective screening test for head and neck cancer short of physical examination. Unfortunately it takes the development of symptoms to warrant a visit to the doctor, such as a sore throat; ear, tongue or mouth pain; painful eating or swallowing; or a change in the voice. Sometimes the first sign is a lump in the neck which is already a [...]

5/18/2006 Chicago, IL Laura A. Goguen, MD et al. Arch Otolaryngol Head Neck Surg. 2006;132:526-531 Objectives: To (1) determine clinical factors that predict pathologic complete response (pCR) on neck dissection after sequential chemoradiotherapy (SCRT) for advanced head and neck cancer and (2) compare survival parameters between those who underwent neck dissection and those who did not among those patients with a clinical complete response (cCR) in the neck after SCRT, thus assessing the benefit of neck dissection in patients with a cCR in the neck. Design: Retrospective review with a mean follow-up of 3.5 years. Setting: Regional cancer center. Patients: The study population comprised 55 patients undergoing SCRT for advanced head and neck cancer with N2 or N3 neck disease. Three patients developed progressive disease and were excluded, and 28 patients underwent neck dissection. Interventions: Patients were assessed by physical examination and radiographically after SCRT. Main Outcome Measures: Physical examination and radiographic assessments of residual neck disease were compared with pathologic findings in those patients who underwent neck dissection. Survival comparisons were made between patients with a cCR in the neck who underwent neck dissection and those who did not. Results: Of 28 patients who underwent neck dissection, 8 had persistent pathologically positive nodal disease: 5 (45%) of 11 had N3 and 3 (18%) of 17 had N2 disease. Individual clinical neck assessments after SCRT were fairly predictive of a negative pathologic finding at neck dissection. The negative predictive values were physical examination (75%), computed tomography or magnetic resonance imaging [...]

5/18/2006 Toxicological Sciences 2006 91(2):476-483; doi:10.1093/toxsci/kfj153 Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death. Authors: Jun Cao1, Li Jia2, Hui-Min Zhou3, Yong Liu4 and Lai-Fu Zhong1 Authors' affiliations: 1 Department of Toxicology, 2 College of Laboratory Medicine, and 3 Department of Microbiology, Dalian Medical University, Dalian 116027, China; and 4 Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, the Chinese Academy of Sciences, Dalian 116023, China

5/16/2006 Los Angeles, CA Dorothy J. Wiley et al. Cancer Epidemiology Biomarkers & Prevention Vol. 15, 915-920, May 2006 Objective: To determine the association between tobacco smoking and serologic evidence of human papillomavirus type 16 (HPV16)–specific antibodies among HPV16 DNA–positive women. Design, Setting, and Participants: Baseline health history, physical examination, and laboratory data for 205 HPV16 DNA–positive women with no prior cytologic evidence of squamous intraepithelial lesions who were enrolled subsequently in a randomized clinical trial. Main Outcome Measure: HPV16-L1 antibody (anti-HPV16 antibody) detected from serum using RIA or ELISA. Results: Eighty-seven percent (179 of 205) of women tested positive for HPV16 DNA using cervicovaginal swabs or lavage specimens, and 26 women showed similar results using swab specimens of external genitalia alone. HPV16-infected women who reported increasingly greater levels of daily cigarette smoking were less likely to test positive for anti-HPV16 antibodies than nonsmoking women (P = 0.02). Smokers were twice as likely as nonsmokers to test negative for anti-HPV16 antibodies, even after controlling for the effects of other covariates in the analyses (adjusted odds ratio, 0.5; 95% confidence limits, 0.2-0.9). Although Papanicolaou test findings and smoking characteristics were poorly correlated (r2 = 0.01), women who showed atypical cells of unknown significance or squamous intraepithelial lesion were twice as likely to test anti-HPV16 antibody positive as women who showed normal Papanicolaou tests (adjusted odds ratio, 2.0; 95% confidence limits, 1.1-3.7). Conclusion: These data suggest that smoking may influence the long-term risk for cancer by perturbing early immune responses to the [...]

5/15/2006 Evergreen, VA staff Physorg.com We may look different on the outside, but inside we are all the same -so much has been scientifically proven. Research at the University of Bergen has shown that the pathways that lead to cancer are similar, no matter where you come from. At any rate, there are remarkable genetic similarities among cancer tumours from Norway, Sudan, Sri Lanka, India, the UK and Sweden. "We had actually expected to find a greater range of variation," says post-doctoral fellow Salah Osman Ibrahim of the University's Department of Biomedicine. He is first author of an article that has been published in the prestigious American journal "Clinical Cancer Research". The article is the product of collaboration among several departments and units at the University of Bergen, Western Norway Regional Health Trust and a number of national and international scientists. The researchers compared patients in Norway and Sudan with head and neck squamous cell carcinomas (HNSCC). There are wide variations in the global incidence of HNSCC, which is a form of cancer that seems to be more common in developing countries than in our art of the world. The aim of the study, therefore, was to find out whether differences in life-style, diet or ethnic background could explains these variations. The scientists used cDNA micro-matrix studies to compare patterns of gene expression in cancerous cells and cells from healthy tissue, in order to determine which genes had been switched on or off in the tumours. "We looked at a [...]

5/15/2006 Los Angeles, CA press release UCLA News (www.newsroom.ucla.edu) UCLA School of Dentistry researchers studying a basic human protein essential in processing and metabolizing RNA have discovered it works as a natural tumor suppressor effective against head and neck cancer. These findings are reported in the May 15 issue of Clinical Cancer Research, one of the leading peer‑reviewed journals of the American Association for Cancer Research. The protein, heterogeneous nuclear ribonucleoprotein G (hnRNP G), was until now perhaps the least investigated of a class of 30 ribonucleic acid-binding proteins with diverse biological functions. While the researchers readily detect hnRNP G in healthy skin tissue, they report they do not find the protein in the vast majority of precancerous and cancerous tissues. Moreover, the UCLA scientists present evidence that hnRNP G injected into human oral squamous cell carcinoma (HOSCC) cells is effective in inhibiting the proliferation and tumor-forming capacity of HOSCC in test tubes and in an animal model. While the scientists acknowledge that hnRNP G's particular mechanisms of action require further investigation, these findings suggest the protein's value in the development of new ways to diagnose and treat HOSCC. According to the National Cancer Institute, most head and neck cancers can be attributed to this type of cancer, which begins in the squamous cells that line the mucosal surfaces in the head and neck. It is estimated that nearly 40,000 people will develop a form of head and neck cancer this year. "If we know that hnRNP G is present [...]