Mouse ‘avatars’ could aid pancreatic cancer therapy

Mouse ‘avatars’ could in future allow physicians to find the most effective cocktail of cancer drugs to combat a particular tumour before giving them to a patient, according to researchers at the annual meeting of the Human Genome Organisation (HUGO) in Australia last week.

“Using a personalized cancer avatar makes it possible to try out different combinations and make some mistakes before going into the clinic,” says Edison Liu, president of HUGO and head of the Jackson Laboratory at Bar Harbor in Maine. “It’s the direction in which a lot of research groups are going.”

An ‘avatar’ is a term informally used by cancer researchers to describe a mouse or other animal onto which tissue from a human tumour is grafted to create a personalized model of one patient’s cancer. In one example of this approach, cancer researcher Sean Grimmond of the University of Queensland in Brisbane, with his colleagues from the Australian Pancreatic Cancer Genome Initiative, analysed a patient’s pancreatic tumour to identify mutations that make the cancer susceptible to particular drugs. The researchers then created a personalized mouse model of that specific pancreatic cancer by xenografting a piece of the patient’s tumour onto immunodeficient mice. This allowed them to test the tumour’s response to the drug mitomycin C, which their initial analysis had shown might be an effective treatment for the patient’s cancer. Reporting their preliminary results at the meeting in Sydney, the researchers found that the tumours shrank after the mouse was administered the drug; however, the patient died before he could be treated with it.

via Mouse ‘avatars’ could aid pancreatic cancer therapy : Nature News & Comment.

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Lapses in oversight compromise omics results

apses in oversight that prevented a US university from identifying the flawed research behind a series of clinical trials are symptomatic of a larger problem says a report by the US Institute of Medicine (IOM), released today. The case in question, which revolves around papers relating to cancer treatment published by researcher Anil Potti, indicates a need for higher standards in the development of tests based on genomics, proteomics and similar large-scale studies, the report says.

Loosely dubbed ‘omics’, such large-scale studies of genes, proteins and other molecular characteristics of whole organisms have been lauded as a way potentially to detect disease and evaluate how people respond to drugs. In theory, the approach could pave the way to personalized treatments. But the development of reliable clinical tests based on omics findings has taken longer than expected.

via Lapses in oversight compromise omics results : Nature News & Comment.

Getting the dirt on immunity

revious human studies have suggested that early life exposure to microbes (i.e., germs) is an important determinant of adulthood sensitivity to allergic and autoimmune diseases such as hay fever, asthma and inflammatory bowel disease.

This concept of exposing people to germs at an early age (i.e., childhood) to build immunity is known as the hygiene hypothesis.

Medical professionals have suggested that the hygiene hypothesis explains the global increase of allergic and autoimmune diseases in urban settings. It has also been suggested that the hypothesis explains the changes that have occurred in society and environmental exposures, such as giving antibiotics early in life.

However, neither biologic support nor a mechanistic basis for the hypothesis has been directly demonstrated. Until now. Continue reading “Getting the dirt on immunity”

Opioid receptors revealed

On a small table in his office at the Scripps Research Institute in La Jolla, California, Ray Stevens spreads out a sheet of paper covered with colourful branched lines, each sprouting and thinning before terminating in an esoteric code. “This is the dream,” he declares.

The intricate diagram represents the largest family of receptor proteins encoded in the genome — the G-protein-coupled receptors (GPCRs), ubiquitous cell-surface molecules that are activated by light, odours, hormones and neurotransmitters. Stevens wants to determine the atomic structures of receptors on all branches of the tree. This week, that goal moved two receptors closer: Stevens’s group has solved the atomic structure of the κ-opioid receptor (κ-OR)1, and a team led by Brian Kobilka at Stanford University in California has solved the medically crucial μ-opioid receptor (μ-OR)2. The structures, published in Nature, bring the tally of GPCR structures solved this year alone up to five.

via Opioid receptors revealed : Nature News & Comment.

Researchers show that memories reside in specific brain cells

Our fond or fearful memories — that first kiss or a bump in the night — leave memory traces that we may conjure up in the remembrance of things past, complete with time, place and all the sensations of the experience. Neuroscientists call these traces memory engrams.

But are engrams conceptual, or are they a physical network of neurons in the brain? In a new MIT study, researchers used optogenetics to show that memories really do reside in very specific brain cells, and that simply activating a tiny fraction of brain cells can recall an entire memory — explaining, for example, how Marcel Proust could recapitulate his childhood from the aroma of a once-beloved madeleine cookie.

“We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells, in this case by light,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT and lead author of the study reported online today in the journal Nature. “This is the rigorously designed 21st-century test of Canadian neurosurgeon Wilder Penfield’s early-1900s accidental observation suggesting that mind is based on matterResearchers show that memories reside in specific brain cells

via Researchers show that memories reside in specific brain cells – MIT News Office.

Clues to the cause of male pattern baldness

Researchers have identified a biological pathway previously unknown to have a role in male pattern hair loss.

Published today in Science Translational Medicine1, the study finds that a lipid compound called prostaglandin D2 (PGD2) has a role in inhibiting hair growth.

The study “is likely to lead to new hair growth products based on prostaglandin biology,” says Anthony Oro, an epithelial biologist at Stanford University in California, who was not involved in the study.

Male pattern baldness, or androgenetic alopecia (AGA), affects around 80% of men at some point in their lives. Only one predisposing factor — a mutation in a testosterone receptor — has been identified, and it is found in only a minority of men with AGA. Other causes are largely unknown, and present treatments were discovered serendipitously — finasteride (Propecia) was originally prescribed for prostate enlargement, and minoxidil (Rogaine) for hypertension. Their molecular mechanisms are unclear.

To look for other factors involved in AGA, researchers led by George Cotsarelis, a dermatologist at the University of Pennsylvania in Philadelphia, examined gene expression in balding and non-balding scalp tissue from five men with AGA. They found that PGD2 was more abundant in the balding scalp tissue, as was prostaglandin D2 synthase, which catalyses PGD2.

The authors also found that, in mice, PGD2 expression peaks during the hair-growth cycle stage in which the follicle begins regressing. Cultured human follicles and mice treated with PGD2 also had hair growth inhibited

via Clues to the cause of male pattern baldness : Nature News & Comment.

Potential Breakthrough in Pancreas Cancer Treatment Reported

Scientists in Seattle are reporting a potential breakthrough in the treatment of pancreas cancer, a disease which stubbornly resists most therapies.

Pancreas cancer tumors are resistent to chemotherapy partly because they form a biological barrier around themselves.

Researchers at the Fred Hutchinson Cancer Research Center believe they’ve found a way to break that barrier down.

“Pancreas cancer actually has the highest one-year and five-year mortalities of any cancer,” says Sunil Hingorani, senior author of the study published in Cancer Cell.

Scientists at Fred Hutchinson Cancer Research Center report  they've found a way to break through the unique biological barrier a pancreas cancer tumor builds around itself.

via Potential Breakthrough in Pancreas Cancer Treatment Reported | Health | English.