A team of researchers from UCLA and Harvard University have demonstrated a technique that, by measuring the physical properties of individual cells in body fluids, can diagnose cancer with a high degree of accuracy.
The technique, which uses a deformability cytometer to analyse individual cells, could reduce the need for more cumbersome diagnostic procedures and the associated costs, while improving accuracy over current methods. The initial clinical study analysed pleural fluid samples from more than 100 patients.
Pleural fluid, a natural lubricant of the lungs as they expand and contract during breathing, is normally present in spaces surrounding the lungs. Medical conditions such as pneumonia, congestive heart failure and cancer can cause an abnormally large buildup of the fluid, which is called a pleural effusion.
When cytopathologists screen for cancer in pleural effusions, they perform a visual analysis of prepared cells extracted from the fluid. Preparing cells for this analysis can involve complicated and time-consuming dyeing or molecular labelling, and the tests often do not definitively determine the presence of tumour cells. As a result, additional costly tests often are required.
The method in the UCLA–Harvard study, developed previously by the UCLA researchers, requires little sample preparation, relying instead on the imaging of cells as they flow through in microscale fluid conduits.
Imagine squeezing two balloons, one filled with water and one filled with honey. The balloons would feel different and would deform differently in your grip. The researchers used this principle on the cellular level by using a fluid grip to ‘squeeze’ individual cells that are 10,000 times smaller than balloons—a technique called ‘deformability cytometry.’ The amount of a cell’s compression can provide insights about the cell’s makeup or structure, such as the elasticity of its membrane or the resistance to flow of the DNA or proteins inside it. Cancer cells have a different architecture and are softer than healthy cells and, as a result, ‘deform’ differently.
Using deformability cytometry, researchers can analyse more than 1,000 cells per second as they are suspended in a flowing fluid, providing significantly more detail on the variations within each patient’s sample than could be detected using previous physical analysis techniques.
The researchers also noted that the more detailed information they obtained improved the sensitivity of the test: Some patient samples that were not identified as cancerous via traditional methods were found to be so through deformability cytometry. These results were verified six months later.

‘Building off of these results, we are starting studies with many more patients to determine if this could be a cost-effective diagnostic tool and provide even more detailed information about cancer origin,’ said Dino Di Carlo, associate professor of bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science and a co-principal investigator on the research. ‘It could help to reduce laboratory workload and accelerate diagnosis, as well as offer doctors a new way to improve clinical decision-making.’ University of California – Los Angeles

For the first time, scientists at King’s College London have identified a gene linking the thickness of the grey matter in the brain to intelligence. The study may help scientists understand biological mechanisms behind some forms of intellectual impairment.
The researchers looked at the cerebral cortex, the outermost layer of the human brain. It is known as ‘grey matter’ and plays a key role in memory, attention, perceptual awareness, thought, language and consciousness. Previous studies have shown that the thickness of the cerebral cortex, or ‘cortical thickness’, closely correlates with intellectual ability, however no genes had yet been identified.
An international team of scientists, led by King’s, analysed DNA samples and MRI scans from 1,583 healthy 14 year old teenagers, part of the IMAGEN cohort. The teenagers also underwent a series of tests to determine their verbal and non-verbal intelligence.
Dr Sylvane Desrivières, from the MRC Social, Genetic and Developmental Psychiatry Centre at King’s College London’s Institute of Psychiatry and lead author of the study, said: ‘We wanted to find out how structural differences in the brain relate to differences in intellectual ability. The genetic variation we identified is linked to synaptic plasticity – how neurons communicate. This may help us understand what happens at a neuronal level in certain forms of intellectual impairments, where the ability of the neurons to communicate effectively is somehow compromised.’
She adds: ‘It’s important to point out that intelligence is influenced by many genetic and environmental factors. The gene we identified only explains a tiny proportion of the differences in intellectual ability, so it’s by no means a ‘gene for intelligence’.’
The researchers looked at over 54,000 genetic variants possibly involved in brain development. They found that, on average, teenagers carrying a particular gene variant had a thinner cortex in the left cerebral hemisphere, particularly in the frontal and temporal lobes, and performed less well on tests for intellectual ability. The genetic variation affects the expression of the NPTN gene, which encodes a protein acting at neuronal synapses and therefore affects how brain cells communicate.
To confirm their findings, the researchers studied the NPTN gene in mouse and human brain cells. The researchers found that the NPTN gene had a different activity in the left and right hemispheres of the brain, which may cause the left hemisphere to be more sensitive to the effects of NPTN mutations. Their findings suggest that some differences in intellectual abilities can result from the decreased function of the NPTN gene in particular regions of the left brain hemisphere.
The genetic variation identified in this study only accounts for an estimated 0.5% of the total variation in intelligence. However, the findings may have important implications for the understanding of biological mechanisms underlying several psychiatric disorders, such as schizophrenia, autism, where impaired cognitive ability is a key feature of the disorder.
Paper reference: Desrivières, S. et al. ‘Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents’ published in Molecular Psychiatry King’s College London

Johns Hopkins Kimmel Cancer Center investigators report they have designed a blood test that accurately detects the presence of advanced breast cancer and also holds promise for precisely monitoring response to cancer treatment.
The test, called the cMethDNA assay, accurately detected the presence of cancer DNA in the blood of patients with metastatic breast cancers up to 95 percent of the time in laboratory studies.
Currently, there is no useful laboratory test to monitor patients with early stage breast cancer who are doing well, but could have an asymptomatic recurrence, says Saraswati Sukumar, Ph.D., who is the Barbara B. Rubenstein Professor of Oncology and co-director of the Breast Cancer Program at the Johns Hopkins Kimmel Cancer Center. Generally, radiologic scans and standard blood tests are indicated only if a woman complains of symptoms, such as bone aches, shortness of breath, pain, or worrisome clinical exam findings. Otherwise, routine blood tests or scans in asymptomatic patients often produce false positives, leading to additional unnecessary tests and biopsies, and have not been shown to improve survival outcomes in patients with early stage breast cancer who develop a recurrence.
Sukumar, also a professor of pathology at Johns Hopkins, says that the current approach to monitoring for recurrence is not ideal, and that ‘the goal is to develop a test that could be administered routinely to alert the physician and patient as soon as possible of a return of the original cancer in a distant spot. With the development of cMethDNA, we’ve taken a first big step toward achieving this goal.’
To design the test, Sukumar and her team scanned the genomes of primary breast cancer patients, as well as DNA from the blood of metastatic cancer patients. They selected 10 genes specifically altered in breast cancers, including newly identified genetic markers AKR1B1, COL6A2, GPX7, HIST1H3C, HOX B4, RASGRF2, as well as TM6SF1, RASSF1, ARHGEF7, and TMEFF2, which Sukumar’s team had previously linked to primary breast cancer.
The test, developed by Sukumar, collaborator Mary Jo Fackler, Ph.D., and other scientists, detects so-called hypermethyation, a type of chemical tag in one or more of the breast cancer-specific genes present in tumour DNA and detectable in cancer patients’ blood samples. Hypermethylation often silences genes that keep runaway cell growth in check, and its appearance in the DNA of breast cancer-related genes shed into the blood indicates that cancer has returned or spread.
In one set of experiments, the researchers tested the assay’s ability to detect methylated tumor DNA in 52 blood samples – 24 from patients with recurrent stage IV breast cancer and 28 from healthy women without breast cancer, and again in blood samples from 60 individuals – 33 from women with all stages of breast cancer and 27 from healthy women. In each case, the blood test was up to 95 percent accurate in distinguishing patients with metastatic breast cancer from healthy women.
The investigators also studied the assay’s potential to monitor response to chemotherapy. They evaluated 58 blood samples from 29 patients with metastatic breast cancer, some taken before the initiation of therapy and some taken 18 to 49 days after starting a new chemotherapy regimen. In as little as two weeks, they report, the test detected a significant decrease in DNA methylation in patients with stable disease or in those who responded to treatment; this decrease was not found in patients whose disease progressed or who did not respond to treatment.
‘Our assay shows great potential for development as a clinical laboratory test for monitoring therapy and disease progression and recurrence,’ Sukumar says. If it’s determined early that a treatment is not working, clinicians can save time and switch to a different therapy, she says.
In addition, the researchers tested the gene panel used in the cMethDNA assay against samples from The Cancer Genome Atlas, a catalog of genes in various cancer types, finding that the gene panel may also be useful in detecting recurrent lung or colorectal cancers but not as accurate in detecting recurrent ovarian, kidney or stomach cancers. Johns Hopkins Kimmel Cancer Center

For the first time, large-scale information on the biochemical makeup of small interfering RNA (siRNA) molecules is available publicly. These molecules are used in research to help scientists better understand how genes function in disease. Making these data accessible to researchers worldwide increases the potential of finding new treatments for patients.
NIH’s National Center for Advancing Translational Sciences (NCATS) collaborated with Life Technologies Corporation of Carlsbad, Calif., which owns the siRNA information, to make it available to all researchers.
RNA interference(RNAi), a cellular process that can stop specific proteins from being coded by silencing the genes that produce them.
The siRNA molecules, which can selectively inhibit the activity of genes, are used in RNA interference (RNAi) research. RNAi is a natural process that cells use to control the activity of specific genes. Its discovery led to the 2006 Nobel Prize in Physiology or Medicine.
Last month, a team of NIH scientists, led by Richard Youle, Ph.D., at the National Institute of Neurological Disorders and Stroke (NINDS), and Scott Martin, Ph.D., at NCATS, used RNAi to find genes that linked to Parkinson’s disease, a devastating movement disorder. The new genes may represent new starting points for developing treatments.
Scientists have harnessed the power of RNAi to study the function of many individual genes by reducing their activity levels, or silencing them. This process enables researchers to identify genes and molecules that are linked to particular diseases. To do this, researchers use siRNAs, which are RNA molecules that have a complementary chemical makeup, or sequence, to that of a targeted gene. While the gene is silenced, researchers look for changes in cell functions to gain insights about what it normally does. By silencing genes in the cell one at a time, scientists can explore and understand their complex relation to other genes in the context of disease.
Until now, a major limitation in the scientific community’s use of RNAi data has been the lack of a publicly available dataset, along with siRNA sequences directed against every human gene. Historically, providers have not allowed publishing of proprietary siRNA sequence information. To address this problem, NCATS and Life Technologies are providing all researchers with access to siRNA data from Life Technologies’ Silencer Select siRNA library, which includes 65,000 siRNA sequences targeting more than 20,000 human genes. Simultaneously, NCATS is releasing complementary data on the effects of each siRNA molecule on biological functions. All of this information is available to the public free-of-charge through NIH’s public database PubChem.
‘Producing and releasing these data demonstrate NCATS’ commitment to speeding the translational process for all diseases,’ said NCATS Director Christopher P. Austin, M.D. ‘The Human Genome Project showed that public data release is critical to scientific progress. Similarly, I believe that making RNAi data publicly available will revolutionise the study of biology and medicine.’
Experts from the NIH RNAi initiative, administered by NCATS’ Division of Pre-Clinical Innovation, conduct screens for NIH investigators. They will add new RNAi data into PubChem on an ongoing basis, making the database a growing resource for gene function studies.
‘By releasing all our siRNA sequences, we are enabling novel strategies to advance fundamental understanding of biology and discovery of new potential drug targets,’ said Mark Stevenson, president and chief operating officer of Life Technologies.
NIH invites other companies that sell siRNA libraries and researchers who conduct genome-wide RNAi screens with the Life Technologies library to deposit sequence data and biological activity information into PubChem. For assistance with submitting data to PubChem, researchers may contact info@ncbi.nlm.nih.gov.
‘Translation of siRNA library screening results into impactful downstream experiments is the ultimate goal of scientists using our library,’ said Alan Sachs, M.D., Ph.D., head of global research and development for Life Technologies. ‘The availability of these sequence data should greatly facilitate this effort because scientists no longer will be blinded to the actual sequence they are targeting.’ National Institutes of Health