C achexia — the wasting of skeletal muscle, with or without fat loss — is often considered inevitable in patients with advanced cancer. But for more than a decade, basic biologists have been saying that cancer cachexia deserves a closer look. Two recent studies in mice suggest that the biologists are right and raise the possibility that the condition will someday be preventable or even reversible. Amgen researchers led by HQ Han, M.D., Ph.D. , reported in Cell in August that a new compound that inhibits the action of myostatin and activin, two proteins that block muscle development, not only reversed muscle wasting in mice with several types of advanced cancer but also increased their lifespan. University of Miami researchers reported similar results on muscle-wasting reversal earlier in the year. The Amgen and Miami scientists are just two of the groups working on cachexia. Many in the fi eld are focusing on diseases other than cancer, such as sarcopenia (severe muscle depletion) and muscular dystrophy. But cachexia affects a large number of patients with advanced cancers — up to 80% by some estimates--and has been estimated to be the immediate cause of death in 20-40% of patients. Exact fi gures are unknown, partly because there is no agreement on the defi nition of cachexia (see statbite). Clinicians do agree, though, that the condition limits the ability to treat cancer. Vickie E. Baracos, Ph.D. , at the University of Alberta in

Priscilla A. Furth, M.D., can imagine a day when breast cancer risk assessment is as simple and accurate as testing for heart disease risk. Like a blood test to check cholesterol levels, fi ne-needle aspiration could remove a few cells from the breast to look at genetic markers in young women. “You wouldn’t even need a piece of tissue, just some cells,” said the professor of oncology and medicine at Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C. “It’s a little dreamy, but it’s feasible.” Furth and many others are working hard to improve breast cancer risk assessment. But so far, the only well-tested way to gauge breast cancer risk is through models that use a few self-reported factors, including age, reproductive history (age at onset of menstruation, fi rst live birth), whether a mother or sister had breast cancer, and previous history of breast cancer. The Breast Cancer Risk Assessment Tool (BCRAT), also known as the Gail model, is one example. Unfortunately, existing models are more helpful in looking at populations than at specifi c women. “Our ability to assess risk at an individual level is somewhat lacking,” said Eitan Amir, M.D., who recently evaluated six assessment tools with his colleagues from the Division of Medical Oncology and Hematology at Princess Margaret Hospital in Toronto. “We need to improve those models.” Genomewide association studies linked several genetic variations, single-nucleotide polymorphisms (SNPs), to breast cancer. Adding those to the assessments makes sense. But the known genetic variations, except for the clearly infl uential BRCA1 and BRCA2 mutations, don’t yet give enough information to make them worth using, according to a National Cancer Institute study published in March in the New England Journal of Medicine. Meanwhile, the pressure is mounting; several companies are selling their versions of genetic tests to physicians or directly to the public ( see sidebar). The mammography debate (whether screening should begin at age 40 or 50 years) is moving this fi eld along as well. “Risk assessment is sexy again because of the issues related to the U.S. Preventive Services Task Force routine mammography recommendations,” said Susan M. Domchek, M.D. , associate professor of medicine at the Abramson Cancer Center

When researchers realized a decade ago that genes inhabit a specific space within a cell’s nucleus and that they sometimes change location during differentiation and in certain diseases, they began to contemplate why. Tom Misteli, Ph.D., and his group at the National Cancer Institute are now asking whether they can exploit evidence of gene movement as a diagnostic tool. In a preliminary study comparing 14 invasive breast cancer tissue samples with 11 healthy breast tissue samples, the researchers found that several genes have a different physical position in the nucleus in invasive breast cancer. One gene, HES5, known to affect pathways involved in cancer, allowed identifi cation of invasive breast cancer in more than 90% of cases. The fi ndings were published in the December 14, 2009, Journal of Cell Biology . Today pathologists look through a microscope in search of distinctive changes in shape and size of the cell nucleus as signs of cancer. But the Misteli group’s approach is different because it’s quantitative and spatial. They use fl uorescence in situ hybridization to label specifi c genes in an intact nucleus. Using little tissue, just 100 – 200 cells, they can compare gene position in biopsy tissue against a standardized normal. “To the best of my knowledge, we are the only group trying to utilize the position of genes for diagnostic purposes,” said Karen Meaburn, Ph.D., in Misteli’s lab in NCI’s Center for Cancer Research. The approach makes sense to Mark T. Groudine, M.D., Ph.D., who studies gene positioning during differentiation of hematopoietic stem cells, which shifts as the precursor cells become red blood cells or white blood cells. “This may be a simple way of trying to determine if cells are normal or cancerous based on the positioning of chromosomes or genes,” says Groudine, deputy director of the Fred Hutchinson Cancer Research Center in Seattle. “It’s a very nice model.” “What’s so exciting about Karen’s paper is it’s a large number of genes and she did it in tumor biopsies,” says Joanna M. Bridger, Ph.D., deputy director of the Centre for Cell and Chromosome Biology at Brunel University in West London. “The data are so nice that she can make that correlation with diagnosis.” Meaburn did her doctoral studies in Bridger’s lab.

Vitamin D is getting its moment in the sun, and news of its potential health benefits has some scientists wondering if warning people away from solar rays is doing more harm than good. Are we inviting some diseases—including common cancers—to avoid skin cancers? The list of maladies linked with vitamin D insufficiency is growing far beyond rickets and other bone diseases. Epidemiologic studies suggest that higher intake of vitamin D protects against multiple sclerosis and rheumatoid arthritis. A study from Finland showed that vitamin D supplementation in infancy is associated with a reduced risk for type 1 diabetes. Clinical studies have linked low serum vitamin D levels with hypertension. “There’s more to this vitamin D story,” said Ronald Lieberman, M.D., program director of the Prostate and Urologic Cancer Research Group in the National Cancer Institute’s Division of Cancer Prevention. “It is fascinating as a molecule. It’s been shown to be antiproliferative, proapoptotic, antiangiogenic. In prostate cancer, its effects appear to be on the cell cycle, stopping growth by upregulating [the tumor suppressor] p21.” He is quick to add, “Yet we don’t have a bit of data that I could show you to say it will work as a preventative.” Most of the evidence is from ecologic, epidemiologic, and laboratory studies of cancers of the prostate, breast, colon, and pancreas. For now, the available studies in patients are treatment trials suggesting that vitamin D may heighten the effects of chemotherapy or radiation. There have been few studies of vitamin D as a cancer chemopreventive.

evidence for an infectious origin, demonstrating space-time clustering of ALL associated with movement from rural areas into cities in response to increasing political stability.Alexander has proposed a hypothesis focused on a specific pathogen -the mycoplasma pneumonia bacteria.She notes that M. pneumonia "has the appropriate socioeconomic correlates and clinical symptoms," and provides evidence from U.K. public health records in support of her prediction that children whose first year of life corresponded to high incidence of reported M. pneumonia infections should be at low risk of ALL, and vice versa.