Autism diagnosis is slow and cumbersome, but new findings linking a hormone called vasopressin to social behaviour in monkeys and autism in people may change that. Low vasopressin in cerebrospinal fluid was related to less sociability in both species, indicating the hormone may be a biomarker for autism.
A paper describing the research, which was led by scientists at the Stanford University School of Medicine and the University of California-Davis, was recently published.
“Since autism affects the brain, it’s really hard to access the biology of the condition to know what might be altered,” said Karen Parker, PhD, associate professor of psychiatry and behavioural sciences at Stanford and the lead author of the new study. “Right now, the diagnosis is based on parents’ reports of their children’s symptoms, and on clinicians observing children in the clinic.”
The study’s senior author is John Capitanio, PhD, professor of psychology at UC-Davis.
Autism, a developmental disorder characterized by impaired social abilities, affects 1 in 68 U.S. children. Research has shown that early, intensive behavioural treatment is beneficial. Yet many children don’t receive a timely diagnosis. A biological test, with a specific lab measurement indicating autism, could make diagnosis faster.
Not only is the biology of autism difficult to study in people, but many research animals are unsuited to autism research, Parker said. For instance, mice often fail to show behavioural changes in response to gene mutations that cause autism in people.
So the researchers looked for autism biomarkers in rhesus monkeys, a species whose social capabilities are closer to those of humans. The monkeys had been raised by their mothers in social groups in a primate research colony at UC-Davis. From 222 male animals, the scientists selected 15 with naturally low sociability and compared them with 15 monkeys with naturally high sociability on several biological parameters.
The scientists measured levels of two hormones, oxytocin and vasopressin, in the monkeys’ blood and in their cerebrospinal fluid, which bathes the brain. Both hormones are peptides implicated in a variety of social roles, including parental care and bonds between mates. Some prior studies have hinted that these hormones may also be involved in autism.
Monkeys in the less social group had significantly less vasopressin in their cerebrospinal fluid than monkeys in the more social group. These vasopressin levels accurately predicted the frequency with which individual monkeys participated in social grooming, an important social activity for rhesus monkeys. Vasopressin levels in blood were not different between the two groups. In a second group of 10 monkeys, whose cerebrospinal fluid was sampled four times over four months, the scientists showed that vasopressin levels in the fluid were stable over time.
The researchers also compared vasopressin levels in 14 boys with autism and seven age-matched children without autism. (Vasopressin levels were tested in the children’s cerebrospinal fluid, which was collected via lumbar puncture for medical reasons; their families agreed to allow some fluid to be used for research.) Children with autism had lower vasopressin levels than children without autism, the study found.
“What we consider this to be at this point is a biomarker for low sociability,” Capitanio said.
The researchers now want to test a larger group of monkeys for vasopressin levels to determine whether the hormone levels can distinguish monkeys with low social abilities from others with a wide range of social ability. And they want to explore whether low vasopressin could be detected before symptoms of impaired social ability emerge.
“We don’t know if we see really low cerebrospinal fluid vasopressin before you see behavioral symptoms of autism,” Parker said. “Ideally, it would be a risk marker, but we haven’t studied that yet.”

Stanford School of Medicinemed.stanford.edu/news/all-news/2018/05/scientists-find-possible-autism-biomarker-in-cerebrospinal-fluid.html

Cancer drops sparse chemical hints of its presence early on, but unfortunately, many of them are in a class of biochemicals that could not be detected thoroughly, until now.
Researchers at the Georgia Institute of Technology have engineered a chemical trap that exhaustively catches what are called glycoproteins, including minuscule traces that have previously escaped detection.
Glycoproteins are protein molecules bonded with sugar molecules, and they’re very common in all living things. Glycoproteins come in myriad varieties and sizes and make up important cell structures like cell receptors. They also wander around our bodies in secretions like mucus or hormones.
But some glycoproteins are very, very rare and can serve as an early signal, or biomarker, indicating there’s something wrong in the body – like cancer. Existing methods to reel in glycoproteins for laboratory examination are relatively new and have had big holes in their nets, so many of these molecules, especially those very rare ones produced by cancer, have tended to slip by.
 “These tiny traces are critically important for early disease detection,” said principal investigator Ronghu Wu, a professor in Georgia Tech’s School of Chemistry and Biochemistry. “When cancer is just getting started, aberrant glycoproteins are produced and secreted into body fluids such as blood and urine. Often their abundances are extremely low, but catching them is urgent.”
This new chemical trap, which took Georgia Tech chemists several years to develop and is based on a boronic acid, has proven extremely effective in lab tests including on cultured human cells and mouse tissue samples.
“This method is very universal,” said first author Haopeng Xiao, a graduate research assistant. “We get over 1,000 glycoproteins in a really small lab sample.”
In comparison tests with existing methods, the chemical trap, a complex molecular construction reminiscent of an octopus, captured exponentially more glycoproteins, especially more of those trace glycoproteins.
Wu, Xiao and Weixuan Chen, a former Georgia Tech postdoctoral researcher, who was also first author of the study alongside Xiao.
For chemistry whizzes, here’s a short summary of how the researchers made the octopus. They took a good thing and doubled then tripled down on it.
Those who recall high school chemistry class may still know what boric acid is, as do people who use it to kill roaches. Its chemical structure is an atom of boron bonded with three hydroxyl groups (H3BO3).
Boronic acids are a family of organic compounds that build on boric acid. There are many members of the boronic acid family, and they tend to bond well with glycoproteins, but their bonds can be less reliable than needed.
“Most boronic acids let too many low-abundance glycoproteins get away,” Wu said. “They can catch glycoproteins that are in high abundance but not those in low abundance, the ones that tell us more valuable things about cell development or about human disease.”
But the Georgia Tech chemists were able to leverage the strengths of boronic acids to develop a glycoprotein capturing method that works exceptionally well.
First, they tested several boronic acid derivatives and found that one called benzoboroxole strongly bound with each sugar component on the glycopeptide. (“Peptide” refers to the basic chemical composition of a protein.) 
Then they stitched many benzoboroxole molecules together with other components to form a "dendrimer," which refers to the resulting branch- or tentacle-like structure. The finished large molecule resembled an octopus ready to go after those sugar components.
In its middle, similarly positioned to an octopus’s head, was a magnetic bead, which acted as a kind of handle. Once the dendrimer caught a glycoprotein, the researchers used a magnet to grab the bead and pull out their chemical octopus along with its ensnared glycopeptides (e.g. glycoproteins).
“Then we washed the dendrimer off with a low pH solution, and we had the glycoproteins analysed with things like mass spectrometry,” Wu said.
The researchers have some ideas about how medical laboratory researchers could make practical use of the new Georgia Tech method to detect odd biomolecules emitted by cancer, such as antigens. For example, the chemical octopus could improve detection of prostate-specific antigens (PSA) in prostate cancer screenings.
“PSA is a glycoprotein. Right now, if the level is very high, we know that the patient may have cancer, and if it’s very low, we know cancer is not likely,” Wu said. “But there is a gray area in between, and this method could lead to much more detailed information in that gray area.”
The researchers also believe that developers could leverage the chemical invention to produce targeted cancer treatments. Immune cells could be trained to recognize the aberrant glycoproteins, track down their source cancer cells in the body and kill them.

Georgia Institute of Technologywww.news.gatech.edu/2018/05/04/chemical-octopus-catches-sneaky-cancer-clues-trace-glycoproteins

Rates of inherited mutations in genes other than BRCA1/2 are twice as high in breast cancer patients who have had a second primary cancer – including, in some cases, different types of breast cancer – compared to patients who have only had a single breast cancer. But the rates of these mutations were still found to be low overall, meaning it’s difficult to assess whether and how these individual mutations may drive the development of cancer. The study from the Basser Center for BRCA in the Abramson Cancer Center of the University of Pennsylvania also investigated the use of polygenic risk scores – which have recently been added to some commercial clinical multiplex genetic testing panels. Kara N. Maxwell, MD, PhD, an instructor of Hematology-Oncology and the study’s lead author, presented the findings at the 2018 American Society of Clinical Oncology Annual.
Genetic testing can help identify patients have a genetic predisposition that puts them at risk for developing cancer. Recently, new therapies called PARP inhibitors have been FDA approved to specifically target cancers caused by certain mutations – such as BRCA1/2, which carry a lifetime breast cancer risk of as much as 85 percent and 50 percent for ovarian cancer, as well as higher risks of pancreatic, prostate and other cancers.
“We need to gain a better understanding of why patients who have multiple cancers may be susceptible to them, and that work needs to go beyond the common genes we’re already been looking at,” Maxwell said.
The team – led by Susan M. Domchek, MD, executive director of the Basser Center for BRCA, and Katherine L. Nathanson, MD, deputy director of the Abramson Cancer Center, specifically looked at patients who did not have a BRCA1/2 mutation and tested them for a panel of 15 different genetic mutations. They evaluated 891 patients who had a second primary cancer – breast or otherwise – after initial breast cancer and compared them to 1,928 who only had a single breast cancer. About eight percent of patients who had second primary cancers had mutations, compared to just four percent of patients from the single cancer cohort. The current threshold for whether or not genetic testing is recommended is five percent.
“Our data show that patients who have had multiple primary cancers should undergo genetic testing, and likely this holds true for a number of other types of second cancer,” Maxwell said. “However, the overall numbers are still low, which shows the level of uncertainty that still exists and highlights the need for further research.”
The research also evaluated polygenic risk scores, a somewhat controversial metric recently added to some commercial clinical multiplex genetic testing panels. Polygenic risk scores are determined by how many single nucleotide polymorphisms (SNPs) a person has. SNPs are common variants with smaller effect sizes, and if a patient has multiple of certain SNPs, they may be at a similar increased for cancer a as patients with a single rare mutation.
“Our study does not provide strong evidence of higher polygenic risk scores in patients with more than one breast cancer,” but many more patients will need to be studied to confirm this,” Maxwell said.

Penn Medicinewww.pennmedicine.org/news/news-releases/2018/june/beyond-brca-examining-links-between-breast-cancer-second-primary-cancer-inherited-genetic-mutations
 

Patient-derived organoids, hollow spheres of cells cultured from tumours, can quickly and accurately predict how patients with pancreatic cancer respond to a variety of treatments, facilitating a precision-medicine approach to the deadly disease. The ability to use organoids as a treatment tool was investigated by an international team of researchers led by Dr. David Tuveson, M.D., Ph.D., Cold Spring Harbor Laboratory (CSHL) Professor and Chief Scientist for The Lustgarten Foundation.
“We’ve identified an approach to prioritize treatment strategies for pancreas cancer patients, with the goal of giving them the best shot at survival and the best shot at a good quality of life,” says Dr. Hervé Tiriac, a researcher in Tuveson’s lab and first author of the paper published today in Cancer Discovery.
With only 8 percent of patients surviving 5 years beyond their diagnosis, pancreatic cancer is one of the deadliest cancer types. Currently, surgical removal of the cancerous tissue is the only effective treatment, but because the disease progresses so quickly, only 15 percent of patients are eligible for the procedure. Surgery-ineligible patients can be treated with drugs or chemotherapy, but patient response is highly varied and there is no good method to determine which treatment is best for any given patient.
For several years, Tuveson has been honing organoid technology to improve research into the disease. Aside from taking only as little as six weeks to grow, a major advantage of organoids is that they can be derived from patients with even very advanced pancreatic cancer, using tiny biopsies.
In this latest development, the Tuveson team generated a library of 66 organoids derived from pancreatic ductal adenocarcinoma (PDAC) tumor specimens at various stages of the disease. The researchers demonstrated that the organoids provide an effective precision-medicine “pharmacotyping,” or drug-testing, pipeline. To do this, “we culture the organoid from the patient’s cancer and then test all possible standard-of-care drugs as well as experimental drugs,” Tiriac explains.
The team assessed RNA levels in individual organoids—a way to measure gene activity—to predict the sensitivity of an organoid to the five chemotherapies currently administered to pancreatic cancer patients. They found that three so-called “signatures” of gene activity in the organoids correctly identified patients who had responded well to these drugs. “The signatures should enable physicians to choose the best initial chemotherapy treatment for pancreatic cancer,” Tuveson says.
Tuveson and his team plan to further refine the gene signatures through additional experiments, and to test in clinical trials the ability of signatures found in organoids to predict the responses of pancreatic cancer patients.

Cold Spring Harbour Laboratory
www.cshl.edu/organoid-profiling-personalizes-treatments-for-pancreatic-cancer/