9/6/2005 New York, NY editorial Nature Structural & Molecular Biology 12, 729 (2005) By now everyone ought to know that smoking is bad for you. Even the United States government is seeking to hold tobacco companies accountable for the health risks of their products. Why, then, do so many people continue to use tobacco? Simply put, nicotine can make a person feel happy and relaxed, and it is as addictive as heroine and cocaine. While over 30% of smokers say they want to quit, most relapse within a few days of avoiding their tobacco product of choice, right when nicotine withdrawal symptoms reach their peak. Help is available for unhappy smokers, from nicotine patches to behavioral therapy, but the road to a nicotine-free life is still difficult for many. Therefore, researchers are working to develop drugs to inhibit nicotine metabolism. Such compounds would, in theory, keep the level of nicotine high in the blood, thus reducing nicotine cravings. On page 822 of this issue, we see the results of some of this work—the structure of the nicotine-metabolizing enzyme cytochrome P450 2A6 in complex with an inhibitor called methoxsalen. While methoxsalen, a drug currently approved for treating psoriasis, is not being touted as the holy grail of antismoking drugs, the authors of the study believe that their structure could aid in the design of other, more suitable inhibitors. The cytochrome P450 family of proteins comprises over 50 enzymes involved in metabolism. Potentially toxic substances are often acted upon by these enzymes [...]

9/6/2005 England staff CancerConsultants.com According to a study published in the journal The Lancet Oncology, head and neck cancer patients with low oxygen levels in their cancer cells have a better response to radiation therapy if they also receive a radiosensitizer (a drug that makes cancer cells more sensitive to radiation). Approximately 40,000 people in the United States are diagnosed with head and neck cancer every year. Cancers of the head and neck include cancers of the nasal cavity and sinuses, mouth, and throat. According to the American Cancer Society, 11,000 people died from head and neck cancer in 2004. Standard treatment for head and neck cancer is largely determined by the stage (extent to which the cancer has spread) and by the specific locations within the head or neck area where the cancer has spread. Among head and neck cancer patients receiving radiation therapy, the oxygen level in cancer cells influences the success of treatment. Radiation therapy is less successful when cancer cells have low oxygen levels. Unfortunately, many cancers, including head and neck cancers, tend to be hypoxic (lacking in oxygen). In order to overcome this problem, researchers are evaluating drugs that mimic oxygen in cancer cells. At this time, the US Food and Drug Administration (FDA) has not approved the use of these drugs, but researchers in Denmark have reported that use of one such drug, nimorazole, improves response to radiation therapy in head and neck cancer patients. Given the apparent benefit of nimorazole among head and [...]

9/6/2005 New York, NY Amy Dockser Marcus Wall Street Journal Researchers are working to unravel a medical mystery that they hope will lead to new ways to fight cancer: They're trying to figure out why people with Down syndrome are less likely to get certain common cancers than the general population, and why they respond better to treatment in other cancers. Recent research shows that people with Down syndrome, a genetic condition with a range of physical and intellectual disabilities, have a significantly lower-than-expected rate of breast cancer, lung cancer, mouth cancer and other common solid tumors. They are at significantly greater risk of getting a rare type of leukemia, called acute myeloid leukemia (AML), when they are children -- but they have a substantially higher survival rate and lower relapse rate than children in the general population. Now, studies are being done at Children's Hospital Boston, Johns Hopkins University School of Medicine, the University of Chicago, the Barbara Ann Karmanos Cancer Institute in Detroit, and other centers around the country, to find out why this is. By understanding the various characteristics of Down syndrome that relate to cancer, researchers hope to develop new cancer drugs, and identify specific targets for cancer treatments, that will benefit all patients. "Individuals with Down syndrome, who are too often viewed as a burden on society, have in fact provided us with a major clue that is fundamental to the health of everyone," says Roger H. Reeves, professor at the Johns Hopkins University School [...]

9/5/2005 London, England Jenny Bangham [email protected] The administration of chemotherapy together with anti-angiogenic drugs seems to be a particularly effective way of slowing tumour growth. However, this combination also poses some practical problems — cutting off the tumour blood supply makes it difficult to achieve a high drug concentration, and hypoxia can trigger the expression of chemotherapy-resistance genes. Now, a group led by Ram Sasisekharan has designed a sophisticated delivery system that gets around these complications — a 'nanocell' that localizes to tumours and then shuts down the tumour vasculature before delivering a cytotoxic agent to tumour cells. Their nanocell consists of a phosopholipid envelope and, inside it, a nanoparticle made of a biodegradable polymer. The researchers incorporated an anti-angiogenic agent — in this case combretastatin — into the liposome, and attached the chemotherapeutic agent doxorubicin to the nanoparticle. They found that combretastatin escapes rapidly from the lipid envelope, while the conjugated doxorubicin is freed more slowly, degrading into smaller, inactive fragments before breaking down further into free, active doxorubicin. These release kinetics correlate well with the effect of the nanocell combination on the tumour endothelium in vitro — the system caused the vasculature to collapse as early as 12 hours post-administration, and tumours to be completely ablated by 30 hours. The authors tested the therapeutic efficacy of this system in vivo using mice with B16:F10 melanomas and mice with Lewis lung carcinoma. They compared the effects of sequential drug delivery using nanocells with several other treatments —one or both [...]

9/5/2005 Phillipines Michael Hopkin [email protected] Oil may help stave off cancer, as long as you stick to the good stuff. Good news for lovers of extra-virgin olive oil: besides being delicious on salads, it also contains a compound that mimics the effects of ibuprofen. So a Mediterranean-style diet might give you the supposed long-term benefits of that drug, such as a reduced cancer risk. A daily dose of 50 g or 4 tablespoons of olive oil confers the equivalent of around 10% of the recommended ibuprofen dose for adult pain relief, say researchers led by Paul Breslin of the Monell Chemical Senses Center in Philadelphia, who discovered the effect. So although it won't cure a headache, it may give you some of the long-term benefits of repeated ibuprofen use, including helping to ward off Alzheimer's. The compound, called oleocanthal, acts in the same way as ibuprofen to stifle components of a pain pathway called the prostaglandin system. This is in spite of the two chemicals' very different structures, the team reports in Nature 1. The compound should be present in any extra-virgin oil, Breslin says. But concentrations will vary depending on a range of factors, such as the variety of olive, and the age of the olives at pressing. So how do you know which olive oil will give you the biggest dose? Simple, just go for the authentic Mediterranean taste, says Breslin. "Most supermarket-style extra-virgin olive oils will be relatively low in this compound," he explains. "But there are [...]

9/4/2005 Steven Reinberg DrKoop.com BRCA2 mutations up risks for other malignancies, study finds. A mutation in the BRCA2 gene that increases the risk of breast and ovarian cancer in women may also increase the odds of pancreatic, prostate, bone and throat cancer in men, new research suggests. Compared with the general population, those with the BRCA2 mutation were almost seven times more likely to have pharyngeal cancer and eight times as likely to have pancreatic cancer, Dutch researchers report. In addition, the investigators found that men with the mutation were more than twice as likely to have prostate cancer. The report appears in the September issue of the Journal of Medical Genetics. In the study, Dutch researchers led by Flora E. van Leeuwen, the head of the department of epidemiology at the Netherlands Cancer Institute, examined 139 families with 66 different mutations of the BRCA2 gene between them. The families were all part of a national register of families with a strong history of breast and/or ovarian cancers. Of the 441 people tested for BRCA2, 69 percent had the mutation, the researchers reported. Overall, among 303 carriers of the mutation, there were 158 cases of cancer compared with 18 cases among 138 who did not carry the mutation. Among those with the mutations, van Leeuwen's team found that the cases of prostate, pancreatic, pharyngeal and bone cancers were substantially higher than is expected in the general population. Individuals with the mutation were 15 times more likely to have bone cancer, [...]

9/2/2005 Besthesda, MD Jeffrey Schlom Blood, 15 September 2005, Vol. 106, No. 6, pp. 1897-1898 An innovative approach to the use of cancer vaccines targets the vascular endothelial growth factor receptor-2 (FLK-1), suppresses tumor-associated angiogenesis, and results in antitumor activity. In a highly innovative approach to the suppression of tumor growth, Zhou and colleagues (a) have developed an anticancer vaccine that targets the vascular endothelial growth factor receptor-2 (VEGF-R2, FLK-1), an important molecule expressed on tumor-associated endothelial cells.(1) Angiogenesis is a rate-limiting step in the development of tumors of any appreciable size.(2) Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases have been shown to play important roles in angiogenesis. VEGF-R2, also known as FLK-1, demonstrates expression restricted to endothelial cells and is up-regulated once these cells proliferate during angiogenesis in the tumor vasculature. Numerous approaches by many groups have been used to block FLK-1, including the use of monoclonal antibodies against VEGF and the use of synthetic receptor kinase inhibitors. In this issue of Blood, Zhou and colleagues demonstrate the broad depth to which vaccines can be used to attack tumors. Previous studies by this group have demonstrated that vaccines containing the entire FLK1 gene can suppress tumor growth.(3) In the study reported here, however, they used an oral DNA minigene vaccine, using a Salmonella-based vector containing only a single cytotoxic T lymphocyte (CTL) epitope of FLK-1. The oral carrier system, consisting of a double attenuated strain of Salmonella typhimurium, delivers the DNA to secondary lymphoid organs for [...]

9/1/2005 London, England C Scully, L Newman, and JV Bagan Dent Update, July 1, 2005; 32(6): 326-8, 331-2, 335-7 Oral cancer is among the ten most common cancers world-wide, and is especially seen in disadvantaged elderly males. Members of the dental profession have a duty to detect both potentially malignant and malignant oral lesions. Early detection and prompt treatment offer the best hope to the patient with oral cancer, providing the best chance of a cure. As patient awareness regarding the danger of oral cancer increases, the demand for oral cancer 'screening' is also expected to increase significantly. The signs and symptoms of cancer often resemble less serious conditions more commonly found in the mouth and similarly presenting as a lump, red or white patch or ulcer. If any such lesion does not heal normally within 3 weeks, a malignancy or some other serious disorder must be excluded. A biopsy is indicated. Prompt referral to an appropriate specialist usually allows for the best management but, if this is not feasible, the dental practitioner should take the biopsy which should be sent to a specialist oral pathologist for histological evaluation. Clinical Relevance: Early detection and prompt treatment offer the best hope to the patient with oral cancer, providing the best chance of a cure. As patient awareness regarding the danger of oral cancer increases, the demand for oral cancer'screening' is expected to increase significantly as well. Authors affiliation: Eastman Dental Institute for Oral Health Care Sciences, 256 Gray's Inn Road, University [...]

9/1/2005 Linda Geddes NewScientist.com Men carrying a genetic mutation that significantly increases the risk of breast cancer in women are at a greater risk of prostate and pancreatic cancers than men without the mutation. Dutch researchers have confirmed that men carrying a mutated BRCA2 gene are twice as likely to develop prostate cancer and six times more likely to develop pancreatic cancer than those free of the mutation. The altered gene may also put them at increased risk of developing bone and throat cancer. A previous study suggested that carriers of mutant BRCA2 genes are at increased risk of cancer of the prostate, pancreas, gallbladder, bile duct and stomach, as well as malignant melanoma, breast cancer and ovarian cancers (Journal of the National Cancer Institute, vol 91 p 1310). But this study only looked at known mutated-BRCA2 carriers with a strong family history of breast or ovarian cancer. Christi van Asperen and her colleagues at the Centre for Human and Clinical Genetics at Leiden University in The Netherlands speculated that estimates of cancer risk at other sites in the body may differ in mutated-BRCA2 carriers with less striking , though still present, family histories of cancer. Retrospective incidence They investigated 139 families with 66 different mutations of the BRCA2 mutation between them. Using information from known mutated-BRCA2 carriers in these families, the researchers studied the retrospective incidence of cancers among both male and female family members with a 50% chance of being a carrier – amounting to 1811 people. Among [...]

9/1/2005 New York, NY staff www.cancerpage.com The plasma level of osteopontin, a marker for tissue hypoxia, can predict whether the radiosensitizing agent nimorazole will be useful in patients with head and neck cancer, new research indicates. Adequate tissue oxygen levels are needed for radiotherapy to be most effective. Nimorazole works by modifying hypoxic environments, making the tissues more sensitive to radiotherapy. "Our study suggests that high plasma concentrations of osteopontin predict the need for hypoxia modification" with an agent like nimorazole, lead author Dr. Jens Overgaard and colleagues, from Aarhus University Hospital in Denmark, note. Still, further studies are needed to determine the exact plasma levels that are important. The present findings, which appear in the August 30th online issue of The Lancet Oncology, are based on a study of 320 patients enrolled in the Danish Head and Neck Cancer Study Group (DAHANCA) 5 trial, which compared the effects of radiotherapy combined with nimorazole or placebo. Stored samples from the subjects were analyzed to determine osteopontin levels, which were then correlated with outcomes. Patients treated with nimorazole had about half the risk of locoregional tumor failure and disease-specific mortality compared with control subjects. On further analysis, the benefits of nimorazole therapy on locoregional tumor failure and disease-specific mortality were confined to subjects with high osteopontin levels. By contrast, among patients with low or intermediate osteopontin levels, treatment with nimorazole seemed to offer no benefit over placebo. "We have shown that high plasma concentrations of osteopontin in patients with squamous-cell carcinoma [...]