2/25/2006 Taiwan P.N. Chen et al. This Article Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Here, we provide molecular evidence associated with the anti-metastatic effect of silibinin by showing a marked inhibition of the invasion and motility of SCC-4 tongue cancer cells, with 89% and 66.4% of inhibition, respectively, by 100 µM of silibinin. This effect was associated with a reduced expression of MMP-2 and u-PA, together with an enhanced expression of TIMP-2 and PAI-1. Silibinin also exerted an inhibitory effect on the phosphorylation of ERK1/2. Additionally, pre-treatment of SCC-4 cancer cells with 10 and 20 µM of U0126, a specific MEK inhibitor, resulted in a reduced expression of MMP-2 (18.7 and 51.4%) and u-PA (19.2 and 48.9%) concomitantly with a marked inhibition of cell invasion (13.7 and 45.7%). Finally, silibinin was evidenced by its inhibition of the metastasis of Lewis lung carcinoma (LLC) cells in vivo. These results suggested that silibinin can reduce the invasion and metastasis of tumor cells, and such a characteristic may be of great value in the development of a potential cancer therapy. Authors: P.-N. Chen1,2, Y.-S. Hsieh1,a, C.-L. Chiang2, H.-L. Chiou3, S.-F. Yang1, and S.-C. Chu2,a Authors' affiliations: 1 Institute of Biochemistry, 2 Department of Food Science, Central Taiwan University of Science and Technology, No. 11 Pu-tzu Lane, Pu-tzu Road, Taichung 406, Taiwan 3 School of Medical Technology, Chung Shan Medical University, No. 110, Section 1, Chien Kuo N. Road, Taichung 402, Taiwan; and

2/23/2006 Larchmont, NY press release Genetic Engineering News (www.genengnews.com) ImClone Systems Incorporated today issued the following statement regarding the announcement that Merck KGaA, Darmstadt, Germany, has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the EMEA (European Medicines Agency), for its application to extend the use of ERBITUX(Cetuximab), an IgG1 monoclonal antibody, to the treatment of squamous cell carcinoma of the head and neck (SCCHN): "We are pleased that our partners, Merck KGaA, may soon be able to offer ERBITUX to head and neck cancer patients in the European Union. This is the first new modality of treatment for this disease state since chemoradiation began use over thirty years ago," stated Eric K. Rowinsky, M.D., Chief Medical Officer of ImClone Systems. The CHMP opinion recommends marketing authorization by the European Commission for the use ERBITUX in combination with radiation in patients with locoregionally advanced SCCHN. The license application is based on the results from a randomized, international phase III trial (IMCL-9815), conducted by ImClone Systems and Merck KGaA, which examined the impact of combining ERBITUX with radiation on locoregional control and overall survival in 424 patients with locally or regionally advanced SCCHN. About Head and Neck Cancer In Europe alone, around 100,800 people are diagnosed with head and neck cancer and almost 40,000 die from the disease every year.(1) Head and neck cancer is the sixth most frequently occurring cancer worldwide.(2) Head and neck cancer includes cancers of the tongue, [...]

2/23/2006 Tampa Bay, FL Christine R. Vaughn Largo Leader (www.thnweekly.com) For the estimated 15 million people in the U.S. diagnosed with dysphagia, the act of swallowing is a tremendous challenge. Taking a bite of a juicy steak or savoring the taste of a warm chocolate chip cookie is an unattainable pleasure of the past for such patients. It was a tedious recovery for Phyllis Hamel, a former patient at East Bay Nursing Center. After respiratory failure, Hamel required a tracheotomy, which affected her ability to swallow. She could not eat or drink without choking. Most of her nutrition was given through a feeding tube inserted in her stomach. At the nursing center, Hamel was treated with VitalStim Therapy, which is used in the treatment of swallowing disorders. Her muscles were re-educated to help her swallow properly. “I noticed a difference after just a few sessions,” she said. At the end of 15 sessions, Hamel was able to return home, where she is eating all her favorite foods again and has a nearly complete return of her muscle function. The treatment was developed by Marcy Freed, a speech-language pathologist. The procedure utilizes electrodes placed on the neck, similar to those used during an EKG. The device sends a low-current electrical impulse that stimulates the nerve supply to the oropharyngeal muscles. Patients receive up to one hour of therapy each day until their swallowing function is restored to an acceptable level. It is the only such method cleared by the FDA to [...]

2/22/2006 Vienna, VA press release PRNewswire (prnewswire.com) CEL-SCI Corporation announces positive results from a long-term follow-up study of head & neck cancer patients treated with its drug Multikine(R) in a Phase II clinical trial. The follow-up study indicated that Multikine treatment resulted in a substantial increase in the survival of patients. In addition, Multikine treatment also improved local regional control of the patients' tumors. Improved local regional control of the tumor is considered by many surgeons and oncologists to be an important measurement of the success of a head & neck cancer drug. Both survival and local regional control of the tumor are stated endpoints in CEL-SCI's planned Phase III clinical trial. The Phase II study, which used the same Multikine treatment protocol as proposed for the Phase III trial, included advanced primary head & neck cancer patients who were scheduled for their first cancer treatment. The Multikine treatment was administered for 3 weeks prior to the standard treatment for head & neck cancer, surgery or surgery plus radiation/chemotherapy. Results from this study were published in a leading cancer publication, the Journal of Clinical Oncology (Timar et al, JCO, 23(15): May 2005) The median follow-up period for the patients was 3.2 years. The results of the Phase II trial follow-up study showed that the Multikine-treated patients had substantially increased survival rates and achieved a higher rate of 2-year local regional control as compared to the survival and the 2-year local regional control rates published in the scientific literature (39 clinical [...]

2/21/2006 Poland D Mielcarek-Kuchta et al. Otolaryngol Pol, January 1, 2005; 59(5): 683-8 Aim of the Study: The evaluation of the importance of the prognostic of sentinel node biopsy in head and neck cancer with N0 neck. Material and Methods: Prospective study included 19 patients with squamous cell carcinoma of the oral cavity, pharynx and larynx without enlarged lymph nodes in ultrasound examination (N0). The study was carried out in ENT Department of Medical University in Pozna between 2001-2004. Each patient underwent lymphoscintigraphy after administration of radionuclide Technetium 99m (Nanocol). In case of detection of sentinel node, blue dye was injected into the tumour bed and dyed lymph nodes were removed. The specimens were evaluated histologically and immunohistochemically. The patients are still followed up. Results: So far 19 patients were included in our study. The tumours were classified from T1 to T4. In each case sentinel nodes were located. Metastases in removed lymphnodes were found in 5 patients. In one of them regional recidive was observed after 5 month. In the other patients no changes were found in follow up examination. In 14 cases in histological examination no metastases were found in sentinel nodes. In this group in one case local recurrence was observed and in another two lymph nodes metastases were confirmed. In patients with positive sentinel node elective neck dissection was performed. So far immunohistochemical examination has not provided us with any vital information. In no case with negative sentinel node we found micrometastases with the use of [...]

2/19/2006 St. Louis, MO Dan Ferber ScienceNow Daily News (sciencenow.sciencemag.org) Human saliva contains telltale markers of breast cancer, diabetes, and an autoimmune disease, according to new results presented here today at annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW). If the findings are validated in clinical trials, spit tests could make up a new non-invasive way to quickly diagnose these diseases. To form saliva, the salivary gland uses the soluble component of blood, known as serum, as its starting material. Physicians have dreamed for years of using saliva-based tests instead of blood tests. Among other conveniences, such a shift would remove the need for needles. Last year, oral biologist David Wong of the University of California, Los Angeles, and his colleagues reported progress toward one saliva test, showing that levels of four of the 3000 messenger RNA molecules typically found in human saliva were consistently elevated in oral cancer patients, but not in healthy patients. Recently, the UCLA team had an accuracy of 94% when attempting to diagnose oral cancer in 320 patients using these 4 RNAs as markers. But oral cancer was just the beginning. At the meeting yesterday, Wong reported that his team has also examined the saliva from groups of 10 people with either type II diabetes, breast cancer, or Sjogren's syndrome, an autoimmune disease that afflicts mostly women and destroys the salivary gland and pancreas. By using a gene chip to compare the salivary RNA of people in each disease [...]

2/19/2006 Thousand Oaks, CA Ralph W. Moss, PhD Integrative Cancer Therapies, Vol. 5, No. 1, 63-82 (2006) In September 2005, CA: A Cancer Journal for Clinicians published a warning by Gabriella D’Andrea, MD, against the concurrent use of antioxidants with radiotherapy and chemotherapy. However, several deficiencies of the CA article soon became apparent, not least the selective omission of prominent studies that contradicted the author’s conclusions. While acknowledging that only large-scale, randomized trials could provide a valid basis for therapeutic recommendations, the author sometimes relied on laboratory rather than clinical data to support her claim that harm resulted from the concurrent use of antioxidants and chemotherapy. She also sometimes extrapolated from chemoprevention studies rather than those on the concurrent use of antioxidants per se. The article overstated the degree to which the laboratory data diverged in regard to the safety and efficacy of antioxidant therapy: in fact, the preponderance of data suggests a synergistic or at least harmless effect with most high-dose dietary antioxidants and chemotherapy. The practical recommendations made in the article to avoid the general class of antioxidants during chemotherapy are inconsistent, in that if antioxidants were truly a threat to the efficacy of standard therapy, antioxidant-rich foods, especially fruits and vegetables, ought also be proscribed during treatment. Yet no such recommendation is made. Furthermore, the wide-scale use by both medical and radiation oncologists of synthetic antioxidants (eg, amifostine) to control the adverse effects of cytotoxic treatments is similarly overlooked. In sum, this CA article is incomplete: there [...]

2/19/2006 The Netherlands Paul Roepman et al. Cancer Research 66, 2361-2366, February 15, 2006 Genome-wide mRNA expression measurements can identify molecular signatures of cancer and are anticipated to improve patient management. Such expression profiles are currently being critically evaluated based on an apparent instability in gene composition and the limited overlap between signatures from different studies. We have recently identified a primary tumor signature for detection of lymph node metastasis in head and neck squamous cell carcinomas. Before starting a large multicenter prospective validation, we have thoroughly evaluated the composition of this signature. A multiple training approach was used for validating the original set of predictive genes. Based on different combinations of training samples, multiple signatures were assessed for predictive accuracy and gene composition. The initial set of predictive genes is a subset of a larger group of 825 genes with predictive power. Many of the predictive genes are interchangeable because of a similar expression pattern across the tumor samples. The head and neck metastasis signature has a more stable gene composition than previous predictors. Exclusion of the strongest predictive genes could be compensated by raising the number of genes included in the signature. Multiple accurate predictive signatures can be designed using various subsets of predictive genes. The absence of genes with strong predictive power can be compensated by including more genes with lower predictive power. Lack of overlap between predictive signatures from different studies with the same goal may be explained by the fact that there are more predictive [...]

2/19/2006 Manchester, UK Stephen Mangar et al. Radiother Oncol, February 5, 2006 Background and Purpose: To identify objective pre-treatment clinical parameters that could be used to predict for patients at high risk of requiring enteral tube feeding prior to head and neck radiotherapy. Pa;tients and Methods: A retrospective study was conducted on 160 consecutive patients attending for radiotherapy assessment. Regression analysis was used to determine various pre-treatment nutritional and tumour specific parameters associated with the use of enteral nutrition either before (prophylactic) or during (reactive) radiotherapy (RT). The significant parameters identified were then selected into categorical variables and compared between those who needed reactive enteral nutrition and the remainder of the group who did not. These results were used to generate predictive factors that could be used to identify those at high risk of malnutrition during RT for whom early or prophylactic enteral nutrition should be considered. Results: Fifty patients required enteral feeding of which 60% required this prior to radiotherapy. Multivariate analysis identified the following factors to be significant-body mass index, performance status (PS), advanced stage, pre-treatment weight loss, low serum albumin and protein, age, and smoking. The most significant categorical predictive parameters for reactive enteral feeding were stage 3-4 disease, PS 2-3, and smoking (3)20/day. The combination of these factors predicted a 75% chance of needing enteral nutrition. Conclusion: Nutritional assessment is important prior to radiotherapy and is multifactorial. Using a combination of relatively simple and objective parameters, (performance status, smoking and disease stage) it is possible to [...]

2/19/2006 Martinsreid, Germany staff Medical News Today (www.medicalnewstoday.com) Cancer researcher Professor Axel Ullrich, a director at the Max Planck Institute of Biochemistry in Martinsried, Germany, already showed at the beginning of the 1990s that blocking blood vessel development in a tumour slows down its growth, and shrinks its tissue. This fundamental principle led to the development of SUTENTÂ, whose active ingredient is Sunitinib. SUTENTÂ was recently approved for clinical use in the United States, and it is expected to be brought onto the German market this year. When particular growth factors are bound to specific receptors on the surface of a cell, this can cause the cell to propagate itself and build certain tissue similar to blood vessels. Worldwide, research into receptors has focused on a special class of proteins, called tyrosine kinases. They are responsible for causing the received signal to be transduced through a long signalling cascade into the nucleus, triggering cell division and multiplication. Signalling cascades are absolutely necessary, if various tissues - like blood vessels, nerve tissue, and connective tissue - are to be built up during the development of an organism and in the process of tissue regeneration. Research has focussed on these tumour cell signalling cascades, because in cancers they are often disturbed. If there were a way to block growth factors, or the receptors on the cellular surface from tumour cells, that could lead to targeted therapies against cancers. Already in the 1980s, cancer researcher Axel Ullrich, then a scientist at Genentech (USA), [...]