4/9/2008 web-based articvle staff ScientistsLive.com Researchers from the University of Pennsylvania School of Medicine and colleagues at Merck Serono Research in Germany have found that two drugs bind to receptor sites on some tumours in different places at the same time, suggesting the possibility of a new combination therapy for certain types of cancer. An increasing number of therapies targeting tumours that have proteins called epidermal growth factor receptors (EGFR) sitting on their surface are already being used in the clinic or are in late stages of development. For example, Herceptin is an established treatment for certain types of breast cancer and Erbitux and Vectibix are in use for other types of cancer. An additional drug called matuzumab is in phase II clinical trials. Three years ago, Kate Ferguson, PhD, Assistant Professor of Physiology, and colleagues determined the precise molecular details of how Erbitux, a colorectal and head and neck cancer drug, binds to its target on cancer cells. EGFR drugs halt cell proliferation by blocking EGFR's molecular doorway, keeping hormones from binding and signalling tumour growth. X-ray crystallography provided a snapshot of the interaction between Erbitux and the extracellular component of the cancer cell's receptors. As is characteristic of many epithelial cancers - such as cancers of the colon, head and neck, breast, ovary, lung, and pancreas - the surface of cancer cells possess abnormally high levels of EGFR. In a cancer cell, an extracellular hormone binds to the outer piece of EGFR, and causes the inside part to [...]

4/9/2008 Amsterdam, The Netherlands R de Bree et al. Curr Opin Otolaryngol Head Neck Surg, April 1, 2008; 16(2): 154-7 Purpose of Review: The aim of this article is to examine the need for screening of endocrine dysfunction following treatment of head and neck cancer. Recent Findings: The incidence of occult hypothyroidism following treatment of head and neck cancer is high. Patients who develop hypothyroidism after treatment may have an increased survival compared with patients who did not become hypothyroid. Because of the growing body of evidence that supports a permissive role for thyroid hormone in the growth of certain solid tumours thyroid hormone replacement therapy may not be indicated in patients with subclinical hypothyroidism and prior or current cancer. Although the incidence of hypoparathyroidism after treatment for head and neck cancer is low, testing of serum calcium is easily performed during thyroid function evaluation. The incidence of hypopituitarism after irradiation of the nasopharynx or skull base is very high warranting regular evaluation of endocrine functions. Summary: Owing to the high incidence of endocrine dysfunction, all head and neck cancer patients who undergo treatment of the lower neck, nasopharynx or base of skull need regular endocrine evaluation during long-term follow-up to determine the need to start hormone replacement therapy and maintain optimal quality of life. Authors: R de Bree, P Lips, and CR Leemans Authors' affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands

4/9/2008 web-based article staff TamilStar.com The results of a study in the International Journal of Cancer confirm an association between smoking and cancers of the stomach and esophagus, and suggest that moist snuff, a popular form of smokeless tobacco in Scandinavia known as "snus," raises the risk of these cancers as well. Dr. Kazem Zendehdel, of the Karolinska Institute, Stockholm, and colleagues examined the occurrence of esophageal and stomach cancers in a group of male Swedish construction workers who were followed for up to 33 years. A total of 336,381 subjects provided information on tobacco smoking and snus use between 1971 and 1993. Follow-up through 2004 was accomplished through linkage to various nationwide registers. Fifty-eight percent of the workers reported current or former smoking, and 28 percent reported snus use. Tobacco smoking raised the risk of stomach and esophagus cancers by as much fivefold. Although snus use appeared to be safer, it still increased the risk of stomach cancer slightly and raised the odds of esophagus cancer by more than threefold. Although there is still some uncertainty about the cause and strength of these associations, and if they can be extended to other populations, "we conclude that at present, Scandinavian snus cannot be considered to be without a (cancer) risk," Zendehdel and colleagues conclude.

4/9/2008 web-based article Maura L. Gillison et al. JNCI Journal of the National Cancer Institute 2008 100(6):407-420 Background: High-risk types of human papillomavirus (HPV), including HPV-16, cause a subgroup of head and neck squamous cell carcinomas (HNSCCs). We examined whether the risk factors for HPV-16–positive HNSCCs are similar to those for HPV-16–negative HNSCCs in a hospital-based case–control study. Methods: Case subjects (n = 240) diagnosed with HNSCC at the Johns Hopkins Hospital from 2000 through 2006 were stratified by tumor HPV-16 status as determined by in situ hybridization. Two control subjects (n = 322) without cancer were individually matched by age and sex to each HPV-16–positive and HPV-16–negative case subject. Data on risk behaviors were obtained by use of audio computer-assisted self-interview technology. Multivariable conditional logistic regression models were used to estimate the odds ratios (ORs) for HPV-16–positive HNSCC and HPV-16–negative HNSCC associated with risk factors. All statistical tests were two-sided. Results: HPV-16 was detected in 92 of 240 case subjects. HPV-16–positive HNSCC was independently associated with several measures of sexual behavior and exposure to marijuana but not with cumulative measures of tobacco smoking, alcohol drinking, or poor oral hygiene. Associations increased in strength with increasing number of oral sex partners (Ptrend = .01) and with increasing intensity (joints per month, Ptrend = .007), duration (in years, Ptrend = .01), and cumulative joint-years (Ptrend = .003) of marijuana use. By contrast, HPV-16–negative HNSCC was associated with measures of tobacco smoking, alcohol drinking, and poor oral hygiene but not with any [...]

4/9/2008 Atlanta, GA Désirée Lie, MD, MSEd Medscape Today (www.medscape.com) Quadrivalent human papillomavirus (HPV) vaccine (Gardasil; Merck & Co, Inc; Cervarix; GlaxoSmithKline) seems to be safe in a review of data involving more than 30,000 prelicensure and 12.4 million postlicensure doses of the vaccine, although vasovagal syncope may be a newly identified adverse event. Senior author John Iskander, MD, MPH, acting director of the Immunization Safety Office, Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues reported these findings here at the International Conference on Emerging Infectious Diseases 2008. The quadrivalent HPV vaccine, manufactured by Merck, was the first to be approved in the United States. The vaccine is active against HPV types 6, 11, 16, and 18 and is indicated in girls and women aged 9 to 26 years. The researchers reviewed safety data of the vaccine from clinical trials and the US Vaccine Adverse Event Reporting System (VAERS). In 7 clinical trials involving approximately 21,500 patients, injection site reactions were reported more frequently with vaccine vs placebo (82.9% vs 73.3%), although comparable rates of serious adverse events and deaths were noted. No deaths among prelicensure vaccine recipients were judged to be caused by the vaccine. Congenital anomalies were also similar among pregnant women who received either the placebo or vaccine. Among patients vaccinated within 30 days of conception, 5 abnormalities in the vaccine group and none in the placebo group were noted, "but no pattern existed," the authors write in their abstract. In the VAERS analysis, [...]

4/9/2008 Phoenix, AZ Angela Gonzales Phoenix Business Journals (www.bizjournals.com/phoenix) Zila Inc. is in danger of being delisted from The Nasdaq Stock Market. Zila announced Wednesday it received a letter from Nasdaq warning it has failed to comply with the minimum bid price requirement for continued listing on the exchange. For the last 30 consecutive business days, the bid price of its common stock closed below $1 a share. Zila has 180 days, or until Sept. 16, to regain compliance. The company's stock is trading around 23 cents a share, barely hovering over its 52-week low of 21 cents a share, and far from the 52-week high of $2.19 a share. Zila reported a net loss of $9.6 million for the six months ended Jan. 31, on revenue of $21.9 million. That compares with a net loss of $6.4 million on revenue of $7.5 million during the same period a year earlier. The company's only main product is ViziLite, being marketed to dentists as an oral cancer detection tool. Earlier this year, Zila pulled its clinical trials of another oral cancer tool called OraTest. In October 2006, the company sold its nutraceuticals business unit for $37.5 million to NBTY Inc., and in May 2007 sold its Peridex brand of prescription periodontal rinse for $9.5 million. Focusing on its ViziLite suite of products, Zila recently was authorized to sell in Canada and plans to expand into the United Kingdom in May, according to its 10-Q filed March 11 with the U.S. Securities [...]

4/9/2008 web-based article S.-F. Yang et al. J Dent Res 87(4):401-406, 2008 Oral squamous cell carcinoma is the most common malignancy of the oral cavity, and treatment approaches are inadequate. Luteolin, a natural flavonoid compound, has been shown to have anti-tumorigenic properties on various types of tumors. Therefore, we hypothesized that luteolin has anti-tumorigenic properties for oral squamous cell carcinoma, and may provide effective chemotherapy. Results revealed that luteolin reduced the viability of SCC-4 cells and induced apoptosis by decreasing the expression of cyclin-dependent kinase (CDKs), cyclins, and phosphor- retinoblastoma (p-Rb) anti-apoptotic protein, but increased the expression of pro-apoptotic proteins and activated caspase 9 and 3, with a concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP). Combination treatment of luteolin with paclitaxel enhanced the cytotoxic effect of paclitaxel in SCC-4 cells, and continuous administration of luteolin suppressed the growth of xenograft tumors in nude mice. These results suggest that luteolin could be an effective chemotherapeutic agent for the treatment of oral squamous cell carcinoma. Authors: S.-F. Yang1, W.-E. Yang2, H.-R. Chang3, S.-C. Chu4, and Y.-S. Hsieh2 Authors' affiliations: 1 Institute of Medicine, 2 Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan; 3 Division of Nephrology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan; and 4 Department of Food Science, Central Taiwan University of Science and Technology, Taichung 406, Taiwan

4/7/2008 Buffalo, NY staff ScienceDaily.com Persons with periodontitis who also are infected with human papillomavirus (HPV) are at increased risk of developing tongue cancer, new research conducted at the University at Buffalo School of Dental Medicine has shown. Periodontitis is a chronic inflammatory disease that destroys connective tissue and bone supporting the teeth. It has been associated with various systemic diseases, including diabetes and heart disease. Researchers from UB and Roswell Park Cancer Institute published the first study showing an association between long-standing periodontitis and risk of tongue cancer in the May 2007 issue of Archives of Otolaryngology - Head and Neck Surgery. Studies conducted elsewhere have found that HPV is an independent risk factor for a subset of head and neck cancers. The UB researchers now have shown that the two infections appear to work in tandem to boost the chances of developing tongue cancer. Mine Tezal, D.D.S., Ph.D., assistant professor in the Department of Oral Diagnostic Sciences, UB dental school, and research scientist at Roswell Park Cancer Institute, presented results of this research today (April 4, 2008) at the 2008 American Association of Dental research meeting in Dallas, Texas. Evidence of periodontitis-HPV synergy has important practical implications," said Tezal, "because there is a safe treatment for periodontitis, but no treatment for HPV infection. If these results are confirmed by other studies, this has a tremendous relevance in predicting and intervening in the initiation and prognosis of HPV-related diseases, including head and neck cancers." The study involved 30 patients [...]

4/6/2008 web-based article press release EurekAlert.com Accuracy, convenience, and non-invasiveness are the most critical characteristics for any diagnostic tool. A new concept, Salivaomics Knowledge Base (SKB), an in silico (i.e., performed on computer or via computer simulation) saliva diagnostic atlas, is launching today during the 37th Annual Meeting of the American Association for Dental Research in Dallas, Texas. With people increasingly adopting a ‘digital life’, the SKB will serve as a catalyst for future development and expansion of salivary diagnostics. For over three years, saliva has shown genuine promise as a diagnostic tool for oral cancer detection. As a result, the scientific community and general public have developed a keen interest in its value. Central to the SKB is the recent creation of two diagnostic alphabets in saliva, the proteome and the transcriptome. In the SKB, the salivary proteome and transcriptome are mapped to 23 human chromosomes, totaling1166 distinct proteins and 851 unique mRNA transcripts in saliva. The available information presently includes profiles from healthy males and females, as well as oral cancer patients. These profiles can be used to determine distinct differences between groups of interest. For example, if one wants to know the differences in the salivary protein or transcriptome profiles of males and females, the user-friendly interface can be utilized to retrieve information from the database. First, an overview of the biomarker distribution on the 23 human chromosomes can be determined. Then, one can zoom in on specific gene segments to extract more detailed information, all done [...]

4/3/2008 Houston, TX Ajaikumar B. Kunnumakkara et al. linical Cancer Research 14, 2128-2136, April 1, 2008 Curcumin Sensitizes Human Colorectal Cancer Xenografts in Nude Mice to {gamma}-Radiation by Targeting Nuclear Factor-{kappa}B–Regulated Gene Products Purpose: How colorectal cancer develops resistance to {gamma}-radiation is not fully understood, but the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) and NF-{kappa}B–regulated gene products have been proposed as mediators. Because curcumin, a component of turmeric (Curcuma longa), has been shown to suppress NF-{kappa}B activation, whether it can sensitize the colorectal cancer to {gamma}-radiation was investigated in colorectal cancer xenografts in nude mice. Experimental Design: We established HCT 116 xenograft in nude mice, randomized into four groups, and treated with vehicle (corn oil), curcumin, {gamma}-radiation, and curcumin in combination with {gamma}-radiation. NF-{kappa}B modulation was ascertained using electrophoretic mobility shift assay and immunohistochemistry. Markers of proliferation, angiogenesis, and invasion were monitored by immunohistochemistry and Western blot analysis. Results: Curcumin significantly enhanced the efficacy of fractionated radiation therapy by prolonging the time to tumor regrowth (P = 0.02) and by reducing the Ki-67 proliferation index (P < 0. 001). Moreover, curcumin suppressed NF-{kappa}B activity and the expression of NF-{kappa}B–regulated gene products (cyclin D1, c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1, cyclooxygenase-2, matrix metalloproteinase-9, and vascular endothelial growth factor), many of which were induced by radiation therapy and mediate radioresistance. The combination of curcumin and radiation therapy also suppressed angiogenesis, as indicated by a decrease in vascular endothelial growth factor and microvessel density (P = 0.002 versus radiation alone). Conclusion: Collectively, [...]