2/9/2005 staff report Cancer Weekly Feb, 8, 2005 Tobacco smoke triggers the production of COX-2, a cellular protein linked to the development and progression of cancer, according to new 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 Cancer Research report stated. The report by Andrew J. Dannenberg, MD, 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 nonsmoking 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 activity or an antibody that prevented ligands from binding to and activating the EGFR. [...]

2/9/2005 staff report Oncology Business Week Reb. 6, 2005 Researchers from Sweden reported study data concluding that human papilloma virus positively impacts prognosis in base of tongue cancer patients. "The frequency of human papilloma virus (HPV) and its influence on clinical outcome was analyzed retrospectively in pre-treatment paraffin embedded biopsies from 110 patients with tongue cancer," wrote L. Dahlgren and colleagues in the International Journal of Cancer. "The presence of HPV DNA was examined in 85 mobile tongue tumors and 25 base of tongue tumors by a polymerase chain reaction (PCR) with 2 general primer pairs, GPS+/6+ and CPI/IIG. When HPV-DNA was found, HPV-type specific primers and direct sequencing were used for HPV sub-type verification. "Twelve of 110 (10.9%) samples were HPV-positive; 9 for HPV-16, 1 for HPV-33, 1 for HPV-35 and 1 could not be analyzed because of shortage of DNA. HPV was significantly more common in base of tongue tumors (10/25, 40.0%) compared to tumors of the mobile tongue (2/85, 2.3%)," the authors reported. Kahlgren and colleagues noted, "The influence of HPV on clinical outcome in mobile tongue cancer could not be studied, due to that HPV was present in too few cases. "Of the 19 patients with base of tongue cancer that were included in the survival analysis, however, 7 patients with HPV-positive base of tongue cancer had a significantly favorable 5-year survival rate compared to the 12 HPV-negative patients." "In conclusion, HPV is significantly more common in base of tongue cancer than in mobile tongue cancer, [...]

2/9/2005 Philadelphia, PA staff report Biotech Week, Feb. 2, 2005 Cancer researchers at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found that zinc treatment may help prevent esophageal and oral cancers in those individuals at high risk. Oral and esophageal cancers are associated with nutritional zinc deficiency, and a rise in the expression of the enzyme COX-2 is connected with these cancers. Louise Fong, PhD, assistant professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University, and her coworkers have found that zinc given orally to zinc-deficient rats reverses the development of precancerous conditions in the esophagus and tongue and reverses the high expression of COX-2 there as well. These findings suggest that zinc supplements may prevent the development of esophageal or oral cancers, particularly in developing countries where zinc deficiency is a problem. The researchers reported their findings January 5, 2005 in the Journal of the National Cancer Institute. Zinc in the diet comes mostly from red meat and seafood. Whereas up to 10% of Americans have a zinc-deficient diet, as many as 2 billion individuals in developing countries are zinc-deficient. Epidemiological evidence show the incidence of esophageal and oral cancers is rising in recent years. As many as 13,000 Americans die from esophageal cancer each year. Fong has been studying zinc deficiency and its connection to esophageal cancer for some 20 years, and has developed animal models of zinc deficiency and cancer susceptibility. Zinc deficiency, she said, [...]

2/9/2005 staff report Medical Letter on the CDC & FDA, Feb. 6, 2005 Cel-Sci Corp. has submitted a phase III clinical trial protocol to the U.S. Food and Drug Administration (FDA) for the use of its investigational immunotherapy drug Multikine in the treatment of advanced primary squamous cell carcinoma of the oral cavity. Additional information in support of and to provide the rationale for the phase III trial (final reports of clinical trials conducted with Multikine to date and manufacturing and testing information) was included with this submission. The protocol was designed in consultation with a group of recognized experts in the field of head & neck cancer therapy to develop the conclusive evidence of the safety and efficacy of Multikine in the treatment of advanced primary squamous cell carcinoma of the oral cavity that would be required to license the product. The company plans to meet with the FDA to discuss the proposed phase III clinical trial over the next several months and obtain the agency's approval to initiate the study. Geert Kersten, CEO of Cel-Sci said, "We believe that Multikine has the ability to improve the success rate of first line therapy in head & neck cancer and this protocol is designed to prove our belief." Head and neck cancer is an aggressive cancer that affects about 500,000 people per annum worldwide. Multikine is an immunotherapeutic agent consisting of a mixture of naturally occurring cytokines including interleukins, interferons, chemokines and colony-stimulating factors. Multikine has completed several phase II [...]

2/7/2005 Rustburg, VA Cynthia T. Pegram The Lynchburg News and Advance Stephen L. Thompson, M.D., looked relaxed and healthy sitting in his office this week. The husky timbre of his voice might have been the aftermath of a cold. But it was throat cancer, not a seasonal microbe, that added the bit of hoarseness to his voice and kept him away from the office from October to January. On Jan. 5, Thompson began working a half-a-day a week in his family practice group, on his way back to full time. Nowadays patients will see him sip a glass of water he keeps nearby to combat the dry mouth after-effects of radiation treatment. Although not seen as frequently as other cancers, cancers of the head and neck are not rare. The most recent data from the Virginia Cancer Registry reported 715 patients in 1999. During 2005 nationwide, nearly 10,000 new cancers in and around the vocal cords are likely to occur, according to the American Cancer Society. Tobacco use is a factor in about 80 percent of head and neck cancers. Thompson, like most doctors, is part health educator - he wants people to be aware of throat cancer potential, so he gave permission for his doctors to talk about his treatment. Thompson, who has practiced in Campbell County for more than 30 years, was lucky. The cancer was found early, in part because of the odd way it turned up last spring. It was Mother’s Day, he recalled. “I had [...]

2/6/2005 Carlo La Vecchia et al. Journal of Thrombosis and Haemostasis as reported by www.medicalnewstoday.com Consumption of alcohol, including wine, increases the risk of several common cancers, even though many studies confirm a reduced risk of cardiovascular disease from alcohol intake. An article appearing in the Journal of Thrombosis and Haemostasis presents definite evidence of these findings amongst other papers as part of an open forum discussion on wine, alcohol, and cardiovascular risk. "Moderate alcohol drinking, less than 25 grams per day, has a favorable role on cardiovascular disease risk," states Professor , co-author of the article. "[However] it is associated with increased risk of cancers of the upper digestive tract and larynx, and also of the intestines, liver, and breast." The article lists primary liver cancer, cancers of the female breast and of the large bowel in both sexes, as being associated with alcohol drinking. Further death from diseases including cirrhosis, chronic pancreatitis, hypertension and stroke are strongly related to alcohol drinking. The analysis was based on a quantitative review, or meta-analysis, of 156 different studies, and heavy alcohol drinking was strongly linked to the diseases noted. The risks are shown to increase with the amount of alcohol consumed yet the overall evidence does not determine "whether there is any threshold, below which no effect is evident." About the Author Carlo La Vecchia, MD, MSc, is Head of the Laboratory of Epidemiology at the Mario Negri Institute for Pharmacological Research in Milan, Italy. His main fields of interest include [...]

2/5/2005 Kunihiro Nakada et al. Journal of Nuclear Medicine Vol. 46 No. 2 261-266 Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon candy decreases salivary gland injury after radioiodine therapy. Methods: The incidence of the side effects of radioiodine therapy on the salivary glands was prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000, 116 consecutive patients were asked to suck 1 or 2 lemon candies every 2–3 h in the daytime of the first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders, diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels of serum free thyroxine (L-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean dose of 131I administered [...]

2/4/2005 Toronto, Ontario, Canada pharmalive.com Viventia Biotech Inc. announced today that its lead drug candidate Proxinium(tm) has been granted orphan drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of advanced, recurrent head and neck cancer. The US Orphan Drug Act provides financial, regulatory and marketing incentives to companies to help facilitate the development and marketing of drugs for the treatment of rare diseases or conditions that affect fewer than 200,000 patients in the United States. Orphan drug designation entitles Viventia to various incentives, including seven years of exclusive marketing rights if Proxinium(tm) receives marketing approval by the FDA. Historically, many orphan drugs have received expedited regulatory review because they have been developed to treat serious or life-threatening illnesses, leading to more rapid approval times. About head and neck cancer: Head and neck cancer, comprising cancers of the larynx, tongue, mouth, oral cavity, and pharynx, is the sixth most common form of cancer globally. In the United States alone over 50,000 new cases of head and neck cancer are diagnosed annually. Despite aggressive measures, such as radical surgery, radiation and/or chemotherapy, as well as concerted efforts from clinicians to eradicate these tumors, long-term survival rates have not improved in the last 30 years and the five year survival rate remains less than 40%. As more than two-thirds of patients will present with advanced disease, curative treatments are often not possible. Compounding the poor prognosis for survival are the often devastating effects these tumors and their treatment [...]

2/4/2005 John McKenzie New England Journal of Medicine as reported by abcnews.go.com A study published in today's New England Journal of Medicine offers encouraging news about a novel way to fight cancer. It finds that injecting a type of liquid radiation, called Bexxar, into patients with lymphoma — a cancer of the immune system — can fight the disease more quickly and with fewer side effects that existing treatments. The approach might eventually be used on a variety of cancers. "This is the first time we're using injectable radiation to treat cancer," said Dr. Andrew Zelenetz, a hematologic oncologist at Memorial Sloan-Kettering Cancer Center in New York. The radioactive drug is delivered intravenously and works like a guided missile. It travels throughout the body, homing in on a specific protein found on the cancer cells. "And when it latches on to it, it now has radiation attached to it and the radiation is essentially there at the site where you want it, radiating the tumor and not radiating other tissues," said Dr. Mark Kaminski, director of the Multidisciplinary Lymphoma Clinic at the University of Michigan Cancer Center. When Bexxar was used to combat non-Hodgkin's lymphoma, 59 percent of patients remained cancer-free during the five years of study. "These results are very similar to the results we're getting with state-of-the-art chemotherapy," said Zelenetz. "However, the distinct advantage here is that it is much more user-friendly for the patient." Few Side Effects The liquid radiation treatment is completed in just one week, [...]

3/2/2005 Syed S.A. Qadri et al. Ann Thorac Surg 2005;79:990-995 Background: Even after apparently curative resection, lung cancer recurrence continues to lead to high mortality levels. The aim of this study was to assess the effects of cyclooxygenase-2 (COX-2) inhibitor on local and systemic recurrent tumor growth. Methods: C57BL/6 mice underwent mammary fat pad inoculation with 3LL cells. After two weeks growth, flank tumors were resected completely and followed for recurrent tumor growth. Postresection mice were randomized to receive placebo alone (group 1) or the selective COX-2 inhibitor, rofecoxib (group 2), daily for two weeks by tube feeding. Recurrent tumor growth kinetics were compared for both groups. Two weeks following primary tumor excision animals were sacrificed, after which lungs were resected and pulmonary metastatic burden was assessed using the lung-body weight ratio. Apoptotic and mitotic indices were established for recurrent tumors and lungs, using hematoxylin and eosin histology. Results: Two weeks postexcision of the primary tumor, recurrent tumors in the placebo group were significantly greater than the treatment group (p = 0.002). While primary tumors were typically encapsulated and not adherent, recurrent tumors in the placebo group were invasive, adherent to the chest wall and the overlying wound. In contrast, recurrent tumors in the treatment group were nonadherent to the chest wall. Moreover, postoperative pulmonary metastatic burden was significantly reduced in treated animals. Histologic examination revealed increased apoptosis as well as an increase in the apoptosis-mitosis ratio in treated animals. Conclusions: Primary tumor excision was associated with accelerated local and [...]