Tumour cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer — even though most free-floating cancer cells will not go on to establish a new tumour.
But if these cast-offs could be accurately counted, they could provide an additional way to track treatment or screen for the disease.
New research by University of Wisconsin–Madison School of Pharmacy Professor Seungpyo Hong and his collaborators builds on several years of work in isolating these circulating tumour cells, or CTCs, by demonstrating improved methods for their capture on clinical samples for the first time. By forcing cancer cells to slow down and developing stronger molecular traps specific to CTCs, researchers were able to identify large numbers of the cells in cancer patients undergoing radiation therapy.
The number of CTCs dropped during therapy and subsequently rebounded in those patients that ended up requiring additional treatment — suggesting that this technology could supplement other techniques for tracking the progress of treatment.
Scientists have recognized CTCs as potentially useful metrics for tracking a patient’s disease for some time. But the cells are the proverbial needle-in-a-haystack, drowned out by billions of ordinary red blood cells and other cells found in the blood. Developing ways to specifically concentrate and trap CTCs has been technically challenging, with existing technologies only identifying a handful of cells from certain patients.
Hong’s team was inspired by the behaviour of CTCs in the blood, which attach themselves to blood vessel walls and begin tumbling along looking for suitable places to invade. This behaviour separates them from the oxygen-carrying cells floating by and is mimicked in the CapioCyte technology using an array of sticky proteins that force the CTCs to begin rolling, which slows them down.
The cells are then trapped using a series of three cancer-specific antibodies, proteins that tightly bind and hold onto the CTCs. To make the connection even stronger, the researchers developed a nanoscale structure shaped a little like a tree, with each branch tipped with an antibody. As a cancer cell passes nearby, many individual branches can latch on, increasing the strength of the attachment.
The cell rolling and multi-tipped branches helped the researchers capture an average of 200 CTCs from each millilitre of a patient’s blood, many times the number of cells captured with previous technology. They identified cancer cells in each of 24 patients undergoing treatment for head-and-neck, prostate, rectal or cervical cancer that enrolled in the study.
“The absolute numbers of CTCs don’t represent too much because there’s too much variation individually, but the more important thing we found was the trend — how the CTC numbers change over time upon treatment. So, for example, we’ve shown that the CTCs go down when the patients are responding really well to the radiotherapy,” says Hong.
Although the number of cells did not correlate with the stage, and thus severity, of the cancer, the reduction in cells was correlated with successful radiation therapy. In two of the three patients that had recurring or persistent disease, CTC numbers came back up.
“Our data suggest that we have a good chance of making CTCs a predictive biomarker or biomarker for surveillance for at least a few cancers, and that’s always exciting,” says Wang.
University of Wisconsin – Madisonnews.wisc.edu/improved-capture-of-cancer-cells-in-blood-could-help-track-disease/

After becoming the first to definitively discover genetic markers for major depression, researchers at Virginia Commonwealth University and collaborators have found more genetic clues to the disease.
A study details the discovery of three additional genetic risk markers for depression, which builds on the ground breaking discovery of two genetic risk factors in 2015. Lead authors include Roseann Peterson, Ph.D., an assistant professor of psychiatry at the VCU Virginia Institute for Psychiatric and Behavioral Genetics, and Na Cai of the European Bioinformatics Institute and the Wellcome Sanger Institute in the United Kingdom.
Initially, the researchers were able to isolate changes in DNA that increase risk for major depression. The most recent findings take this a step further by determining that the additional genetic markers are relevant to the disease in a subset of people who have not experienced extreme adversity.
Kendler, M.D., professor of psychiatry and human molecular genetics in the Department of Psychiatry in the School of Medicine, and one of five VCU faculty authors, said the work could shed more light on subtypes of depression and their treatment.
 “We have struggled for years using twin and family studies to try to understand how genes and environment interrelate in causing depression,” Kendler said. “This is the first study where we have been able to do this using molecular variants. This is an important advance in our understanding of this important, severe and common psychiatric disorder.”
The researchers collected information on environmental adversity measures from their subjects. Environmental adversity includes experiences of extreme stressful life events such as childhood sexual and physical abuse. Observing groups who were adversity exposed and non-adversity exposed allowed researchers to account for diverse causes of depression, or the disease’s etiological heterogeneity, in determining genetic causes, Peterson said.
“Identifying genetic risk variants for major depressive disorder has been difficult, likely due to associated clinical and etiological heterogeneity,” Peterson said. “Here, we highlight individual differences in clinical presentation and the importance of collecting symptom level data to tackle clinical and etiological heterogeneity in complex psychiatric traits.”
Peterson said the ultimate goal is to identify high-risk individuals for early intervention and personalized medicine. Cai said the discovery could lead to additional findings on potential links between metabolism and depression. 
“Some of the genes implicated by variants we found to be associated with depression are involved in mitochondrial function and metabolism,” Cai said. “So, one potential direction for future research is to try to understand the link between depression and metabolism.”
Virginia Commonwealth Universitynews.vcu.edu/article/Three_new_genetic_markers_associated_with_risk_for_depression

More than 100 industry experts to highlight the latest medical laboratory and diagnostics trends and innovation
The 5^th edition of MEDLAB Asia Pacific Exhibition & Congress, leading B2B business and educational platform in the field of laboratory and diagnostics for the Asia Pacific region, will offer visitors the opportunity to attend a series of scientific conferences that will cover advancement in science, technology and application of various laboratory techniques to strengthen cooperation between lab and clinic interface.
Supported by The Academy of Medicine, Singapore and accredited by Singapore Medical Council, the 15 CME-certified conferences will empower delegates with the knowledge and skills to guarantee the fastest, safest and most accurate laboratory results in improving patient service and care.
During the three-day congress, which takes place from 2 – 4 April 2018 at Suntec Singapore Convention & Exhibition Centre in Singapore, a variety of carefully-designed sessions, panel discussions, demonstrations and interactive activities will enable delegates to network and share best practices with more than 100 regional and international experts who are champions of laboratory medicine in the Asia Pacific.
The congress will host 11 dedicated laboratory tracks: Laboratory Management, ­Clinical Chemistry, Haematology & Blood Transfusion, Infectious Diseases, Point of Care Testing, Cytology, Molecular Diagnostics, Laboratory Informatics, Cardiac Markers, ­ Lab Testing: Obs Gyne & Women’s Health and Lab Testing & Management: Diabetes.
During these sessions, delegates will able schooled in a wide variety of key topics including the role of the laboratory director, 4^th generation sequencing, updates in assays to improve skills in test accuracy, digital pathology, and the evaluation of current and future biomarkers, to name a few.
Due to the expanding role of laboratory medicine, the meeting is combined with other clinical specialties that will underscore the overarching influence of the laboratory in medical decision-making and treatment. New conferences in the MEDLAB Asia Pacific Congress portfolio are: Obs Gyne & Women’s Health, Gynae-Oncology, Diabetes Management and Antimicrobial Resistance.
“The advent of groundbreaking diagnostic solutions is gaining pace across the region. By introducing new medical tracks from key specialties that interact with the laboratory, the 2018 MEDLAB Asia Pacific Congress will provide the latest evidence-based research into diagnosis and treatment as well as enhance cooperation between laboratory professionals and clinicians to enable the best possible patient outcomes.” said Rejoy Penacerrada, Senior Conference Producer, MEDLAB Asia.
MEDLAB Asia Pacific 2018  is supported by a large number of key healthcare federations and associations across the region including The Royal College of Pathologists of Australasia, Singapore Society of Pathology, College of Pathologists, Academy of Medicine of Malaysia, Indonesian Association of Clinical Pathologist and Laboratory Medicine, Singapore Society of Haematology, College of American Pathologists, Philippine Society of Pathologists, Inc., Philippine Society of Biochemistry and Molecular Biology, Philippine Society of Microbiology, Indonesian Association of Clinical Chemistry, Society of Infectious Disease Singapore, and Society of Cytology Singapore and Diabetes Singapore.
Held alongside the congress is the MEDLAB Asia Pacific exhibition – a platform for leading companies from across the globe to showcase current technologies and innovations in the field of laboratory and diagnostics to an expected 4,000 visitors.
MEDLAB Asia Pacific is also co-located with Asia Health, a trade exhibition for medical equipment, products, services and technologies hosting more than 250 international companies and bringing together the world of medical laboratory and healthcare under one roof.
Registration for the MEDLAB Asia Pacific Congress is now open via www.medlabasia.com.

Researchers at The Johns Hopkins Kimmel Cancer Center have developed a test for urine, gathered during a routine procedure, to detect DNA mutations identified with urothelial cancers.
UroSEEK uses urine samples to seek out mutations in 11 genes or the presence of abnormal numbers of chromosomes that would indicate the presence of DNA associated with bladder cancer or upper tract urothelial cancer (UTUC).
The researchers said the test, when combined with cytology, the gold standard non-invasive test currently used for detection, significantly enhanced early detection for patients who are considered at risk for bladder cancer and surveillance of patients who had already been treated for bladder cancer.
“There were nearly 80,000 new cases of bladder cancer and more than 18,000 deaths in 2017,” said George Netto, M.D., a senior author on the UroSEEK paper, formerly at The Johns Hopkins University and currently chair of pathology at the University of Alabama-Birmingham. “This is about using the urine to detect the cancer. UroSEEK is a method of detection that many people have tried to find that is non-invasive.”
Most cancers are curable if they are detected early, and the researchers are exploring ways to use cancer gene discoveries to develop cancer screening tests to improve cancer survival. They announced the development of CancerSEEK, a single blood test that screens for eight cancer types, and PapSEEK, a test that uses cervical fluid samples to screen for endometrial and ovarian cancers.
UroSEEK is aimed toward early detection of bladder cancer in at-risk patients, those who may have blood in their urine or people who smoke, as well as patients who have already gone through a procedure to treat bladder cancer and need to be monitored for any recurrence of the disease.
“In almost one-third of patients, bladder cancer detection is late. The cancer has already gotten into the surrounding muscle,” Netto said. “Even in those detected at an earlier stage, the tumours frequently recur. Patients are committed to a lifelong surveillance that requires invasive cystoscopy procedures and biopsies and is costly.”
Saying current non-invasive approaches for detection of urothelial cancer are suboptimal, researchers wanted to develop a test for bladder and UTUC cancer that would allow it to be found sooner and cheaper than current methods using cytology, which is not particularly sensitive and does not do well in detecting low-grade bladder cancer or UTUC.
Researchers studied 570 patients who were considered at risk for bladder cancer and found UroSEEK was 83 percent positive in those who developed cancer. When combined with cytology, the sensitivity increased to 95 percent of patients who developed the disease.
“When you combine them, you get better results,” said Nickolas Papadopoulos, Ph.D., a senior author and an investigator at the Ludwig Center at Johns Hopkins. “Side by side, UroSEEK has better sensitivity. There are some cases when cytology detects when UroSEEK doesn’t. Combining them produces the best results.”
John Hopkins Kimmel Cancer Centerwww.hopkinsmedicine.org/news/media/releases/gene_based_test_for_urine_detects_monitors_bladder_cancer

Until very recently, Parkinson’s had been thought a disease that starts in the brain, destroying motion centres and resulting in the tremors and loss of movement. New research shows the most common Parkinson’s gene mutation may change how immune cells react to generic infections like colds, which in turn trigger the inflammatory reaction in the brain that causes Parkinson’s. The research offers a new understanding of Parkinson’s disease.                                                     
“We know that brain cells called microglia cause the inflammation that ultimately destroys the area of the brain responsible for movement in Parkinson’s,” said Richard Smeyne, PhD, Director of the Jefferson Comprehensive Parkinson’s Disease and Movement Disorder Center at the Vickie and Jack Farber Institute for Neuroscience. “But it wasn’t clear how a common inherited mutation was involved in that process, and whether the mutation altered microglia.”
Together with Dr. Smeyne, first author Elena Kozina, PhD, looked at the mutant version of the LRRK2 gene (pronounced ‘lark’). Mutations in the LRRK2 gene are the most common cause of inherited Parkinson’s disease and are found in 40 percent of people of North African Arab descent and 18 percent of people of Ashkenazi Jewish descent with Parkinson’s. However there’s been controversy around the exact function of the LRRK2 gene in the brain.
“We know that gene mutation is not enough to cause the disease,” said Dr. Kozina, Post-Doctoral student at Jefferson.“We know that twins who both carry the mutation, won’t both necessarily develop Parkinson’s. A second ‘hit’ or initiating event is needed.”
Based on his earlier work showing that the flu might increase risk of Parkinson’s disease, Dr. Smeyne decided to investigate whether that second hit came from an infection. Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent — the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.
When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a “cytokine storm,” with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.
Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.
“Although more tests are needed to prove the link, as well as testing whether the same is true in humans, these findings give us a new way to think about how these mutations could cause Parkinson’s,” said Dr. Smeyne. “Although we can’t treat people with immunosuppressants their whole lives to prevent the disease, if this mechanism is confirmed, it’s possible that other interventions could be effective at reducing the chance of developing the disease.”
Thomas Jefferson Universitywww.jefferson.edu/university/news/2018/03/21/Parkinsons_gene_triggers_the_disease_from_outside_brain.html