Raman spectroscopy poised to make thyroid cancer diagnosis less invasive

Researchers have demonstrated that an optical technique known as Raman spectroscopy can be used to differentiate between benign and cancerous thyroid cells. The new study shows Raman spectroscopy’s potential as a tool to improve the diagnosis of thyroid cancer, which is the ninth most common cancer with more than 50,000 new cases diagnosed in the United States each year.
“Our encouraging results show that Raman spectroscopy could be developed into a new optical modality that can help avoid invasive procedures used to diagnose thyroid cancer by providing biochemical information that isn’t currently accessible,” said James W. Chan from the University of California, Davis, U.S.A. “This could have a major impact in the field of pathology and could lead to new ways to diagnose other diseases.”
A lump — or nodule — in the neck is a common symptom of thyroid cancer. However, most thyroid nodules aren’t cancerous. Ultrasound-guided fine needle aspiration biopsies are typically used to check for cancer by inserting a thin needle into the nodule to obtain cells that are prepared on a microscope slide, stained and analysed by a pathologist. For about 15 to 30 percent of cases, the pathologist cannot determine whether cells acquired from the biopsy are benign or malignant. For these cases, a surgical procedure known as a thyroidectomy is required to remove tissue, which provides more information for a more accurate diagnosis. The researchers turned to Raman spectroscopy as a possible solution because it is a non-invasive technique that requires no sample preparation or staining to determine subtle differences in the molecular composition of complex samples such as cells.
“We would like to use Raman spectroscopy to improve the pathologist’s analysis of the cells obtained with fine needle aspiration to reduce the number of thyroidectomies necessary,” said Chan. “This would both minimize surgical complications and reduce healthcare costs.”
For the new study, the researchers used a line-scan Raman microscope that allowed them to rapidly acquire Raman signals from an entire cell volume. This allowed them to more accurately capture the chemical composition of entire cells compared to other approaches that acquire a Raman spectrum from only part of a cell’s volume. Multivariate statistical methods and classification methods were then used to analyse the Raman data and classify the cells in an objective, unbiased manner.
The researchers applied this Raman spectroscopy approach to individual cells isolated from 10 patient thyroid nodules diagnosed as benign or cancerous. The data analysis identified unique spectral differences that could distinguish cancerous cells from benign with 97 percent diagnostic accuracy. They also showed that other subtypes could be identified by their spectral differences.
“These preliminary results are exciting because they involve single cells from human clinical samples, but more work will need to be done to take this from a research project to final clinical use,” said Chan.
The Optical Society (OSA) https://tinyurl.com/y6hw35z8

Reconstructing histological slices into 3D images

Japanese scientists report a new method to construct 3D models from 2D images. The approach, which involves non-rigid registration with a blending of rigid transforms, overcomes several of the limitations in current methods. The researchers validate their method by applying it to the Kyoto Collection of Human Embryos and Fetuses, the largest collection of human embryos in the world, with over 45,000 specimens.
MRI and CT scans are standard techniques for acquiring 3D images of the body. These modalities can trace with unprecedented precision the location of an injury or stroke. They can even reveal the microscopic protein deposits seen in brain pathologies like Alzheimer’s disease. However, for the best resolution, scientists still depend on slices of the specimen, which is why cancer and other biopsies are taken. Once the information desired is acquired, scientists use algorithms that can put together the 2D slices to recreate a simulated 3D image. In this way, they can reconstruct an entire organ or even organism.
Stacking slices together to create a 3D image is akin to putting a cake together after it has been cut. Yes, the general shape is there, but the knife will cause certain slices to break so that the reconstructed cake never looks as beautiful as the original. While this might not upset the party of five-year olds who want to indulge, the party of surgeons looking for the precise location of a tumour are harder to appease.
“The sectioning process stretches, bends and tears the tissue. The staining process varies between samples. And the fixation process causes tissue destruction,” explains Nara Institute of Science and Technology (NAIST), Nara, Japan, Associate Professor Takuya Funatomi, who led the project.
Fundamentally, there are three challenges that emerge with the 3D reconstruction. First is non-rigid deformation, in which the position and orientation of various points in the original specimen have changed. Second is tissue discontinuity, where gaps may appear in the reconstruction if the registration fails. Finally, there is a scale change, where portions of the reconstruction are disproportional to their real size due to non-rigid registration.
For each of these problems, Associate Professor Takuya Funatomi and his research team proposed a solution that when combined resulted in a reconstruction that minimizes all three factors using less computational cost than standard methods.
“First, we represent non-rigid deformation using a small number of control points by blending rigid transforms,” says Funatomi. The small number of control points can be estimated robustly against the staining variation.
“Then we select the target images according to the non-rigid registration results and apply scale adjustment,” he continues.
The new method mainly focuses on a number of serial section images of human embryos from the Kyoto Collection of Human Embryos and Fetuses and could reconstruct 3D embryos with extraordinary success.
Notably, there are no MRI or CT scans of the samples, meaning no 3D models could be used as a reference for the 3D reconstruction. Further, wide variability in tissue damage and staining complicated the reconstruction.
Nara Institute of Science and Technology https://tinyurl.com/y4ealgow

Randox RX series gains NGSP certification for direct HbA1c

Randox Laboratories recently announced its achievement in being awarded the Manufacturer Certification by the National Glycohemoglobin Standardization Program (NGSP) for direct HbA1c testing on three of its clinical chemistry analysers: the RX modena, RX imola and RX daytona+.

NGSP is recommended for laboratories conducting diabetes-related clinical trials and is only granted on the basis of 98% accuracy. With the global prevalence of diabetes mellitus increasing rapidly, affecting roughly 8% of the total population, the achievement of this certification emphasizes that the Randox RX series clinical chemistry analysers correlate with global standards and deliver accurate, reliable and precise results for direct HbA1c testing, helping clinicians make informed decisions for patients with diabetes.

The Randox automated immunoturbidmetric HbA1c test exhibits high accuracy and reproducibility with the added advantages of using liquid reagents with good stability, and on-board pre-treatment of samples; therefore, offering an improved method for the rapid direct measurement of HbA1c in human blood.

Randox Direct HbA1c assay features
· Sample type – suitable for use with whole blood samples
· Latex enhanced immunoassay method – the Randox assay utilizes an immunoassay method making it simple and quick to perform
· Liquid ready to use reagents – for ease of use and convenience
· Excellent stability – all reagents are stable to expiry date when stored at +2-8ºC or 28 days on board the analyser at approximately 10°C

Advantages of the RX series direct HbA1c testing

· Fully automated on-board hemolysis function for HbA1c testing
· Continuous loading and STAT sample functionality to enhance productivity in the laboratory (analyser dependent)
· Low sample volumes required
· 1200 tests per hour including ISE (RX modena)

www.randox.com

Greiner Bio-One supports the Swiss Red Cross in Lebanon

Greiner Bio-One is supporting a Swiss Red Cross (SRK) project to modernize the blood donor service and the provision of safe blood supplies for Syrian refugees and the wider public in Lebanon.
Greiner Bio-One has been a project partner of the Swiss Red Cross since May 2019. Due to its extensive and long-term experience, SRK is in a strong position to provide support to several countries in establishing a professional blood donor service. One of these countries is Lebanon.
In addition to promoting quality assurance in the blood donor service, the goal of the Swiss Red Cross is to increase the stock of blood through regular donations. Because safe blood saves lives!
Giving blood is not (yet) necessarily the norm everywhere
In some regions of the world, people often only donate blood for family members so there is therefore not enough available or it needs to be paid for. There is a need to raise awareness here and encourage people to donate blood for others outside their own families. “If somebody needs my blood, I’m there for them,” says Said Mrad, a voluntary Lebanese blood donor. The 26-year-old is giving blood for the fourth time. Thanks to the work of the SRK in cooperation with the Lebanese Red Cross, he now sees it as completely natural to give his blood for other people.
Blood supplies need to be safe
A professional blood donor service not only needs donors but it also needs suitable products and expert knowledge to ensure high quality standards, maximum safety and wide coverage for this vital service. The SRK’s international experience helps the Lebanese Red Cross a great deal as it establishes this valuable service. Greiner Bio-One is supporting this project through its financial contribution, its products and its expertise. www.gbo.com

Continuing medical education course at the Leiden University Medical Center

On 14th November 2019 a “continuing medical education course” is organized at the Leiden University Medical Center (LUMC) entitled “Prime time for precision diagnostics driven by unmet clinical needs”. During this symposium (inter)national experts will discuss health and disease at a molecular level on the basis of Clinical Proteomics. Case studies are presented to exemplify the potential for precision diagnostics. Furthermore, it will be emphasized that clinical needs need to be defined to contribute to patient care in an efficient and effective way. www.boerhaavecontinuingmedicaleducation.com

Olympus launches the first Global Image of the Year Award

Olympus’ Image of the Year Award recognizes the best in life science imaging worldwide. Participants can win a CX43 microscope with a DP27 digital camera, X Line objectives, or an OM-D E-M5 Mark II camera. Those interested in participating can enter until 31 January 2020 by uploading images at www.olympus-lifescience.com/ioty. Winners will be selected by a jury panel and announced in March 2020.
The jury consists of global representatives from both science and the arts, including photo-
grapher Ron Caplain; Geoff Williams, a bioimaging facility manager at Brown University; Urs Ziegler, the head of a microscopy imaging facility at the University of Zurich; Stefan Terjung, the operational manager of an advanced light microscopy facility at EMBL Heidelberg; Hiroaki Misono, a graduate school professor of brain science at Doshisha University; Zhu Xueliang, a professor at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; Yalin Wang, Director of Biomedical Research Core Facilities at Westlake University, Hangzhou, China; and Wendy Salmon, a light microscopy specialist of a bioimaging facility at MIT.
All entries will be evaluated based on artistic and visual aspects, scientific impact, and microscope proficiency. Regional prizes in Asia, Europe, and the Americas will be awarded in addition to the global prize.
The Image of the Year European Life Science Light Microscopy Award began in 2017 to celebrate both the artistic and scientific value of microscopy images. Now on a global scale, the competition aims to encourage people to look at scientific images in a new way, appreciate their beauty, and share images with others.
Participants may upload up to three microscopy images when submitting the online form. Images, accompanied by a brief explanation that notes the equipment used, can be uploaded until 31 January 2020. The jury will select and notify the winners in March 2020.

www.olympus-lifescience.com/ioty

Aesku has completed acquisition of MBL Bion

AESKU.GROUP recently announced completed acquisition of immunofluorescence assay (IFA) specialist MBL BION from MBL Intl., securing their position as the leading provider of IFA solutions to clinical laboratories. The acquisition increases AESKU.GROUP’s addressable market and strengthens its market position.
AESKU.GROUP has a track record of developing, producing, and marketing innovative diagnostic assays and automated systems, and has a global network of proven distribution partners. A significant factor in their success is complete solutions for clinical laboratories, including all-in-one testing and reading automation with the SQII for enzyme immunoassay (ELISA), HELIA® for line immunoassay (LIA), and HELIOS®, which was the first all-in-one system on the market for IFA. This innovation, along with the confirmation of IFA as the gold-standard for autoimmunity screening in clinical guidelines, has led to over 400 HELIOS placements worldwide and in-creased demand for AESKU IFA reagents.
MBL Bion has over 40 years’ experience manufacturing IFA products of the highest quality and is a leading provider of autoimmunity and infectious disease testing slides. They have a strong market presence in the Americas, and a centre of manufacturing excellence in Des Plaines, IL, USA. Adding MBL Bion’s manufacturing capacity and broad range of reagents lets AESKU.GROUP help laboratories expand their IFA testing with the most extensive range of IFA products available on all-in-one automation combined with a unique quality control portfolio for the diagnosis of autoimmune and infectious diseases.
AESKU.GROUP CEO Dr. Torsten Matthias was delighted with the acquisition, saying, “We have found true synergy. MBL BION’s operations and product portfolio fit perfectly with the AESKU.GROUP. Between the expansion of our IFA manufacturing in Buffalo, NY, and MBL BION’s Des Plaines operations, AESKU can speed order processing and delivery times. Furthermore, the high quality of their HEp-2 cells and extensive infectious disease testing slides add incredible value to our new HELIOS ‘HTC’ humidity and temperature control module. For the first time, clinical laboratories can access the highest level of automation and environmental control for both auto-
immunity and infectious serology testing.”

www.aesku.com

Biological markers that could guide treatment for prostate cancer

Genetic alterations in low-risk prostate cancer diagnosed by needle biopsy can identify men that harbour higher-risk cancer in their prostate glands, Mayo Clinic has discovered. The research found for the first time that genetic alterations associated with intermediate- and high-risk prostate cancer also may be present in some cases of low-risk prostate cancers.
The study found the needle biopsy procedure may miss higher-risk cancer that increases the risk of disease progression. Researchers say that men diagnosed with low-risk cancer may benefit from additional testing for these chromosomal alterations.
“We have discovered new molecular markers that can help guide men in their decisions about the course of their prostate cancer care,” says George Vasmatzis, Ph.D., co-director of the Center for Individualized Medicine Biomarker Discovery Program and lead author on the study. “Overtreatment has been issue for the group of men that our study targets. We found that the presence of genetic alterations in low-risk cancer can help men decide whether treatment or active surveillance is right for them.”
Prostate cancer is assessed by Gleason patterns and score that indicate grade. The Gleason patterns are strongly associated with risk of disease progression. Gleason pattern 3 prostate cancer is considered to be low-risk. Gleason patterns 4 and 5 cancer carry a higher risk of aggressive behaviour.
Men whose tumour is composed entirely of Gleason pattern 3 may choose active surveillance. They are monitored closely with blood tests and needle biopsies, as necessary. Or they may be referred to treatment, such as surgery and radiation, particularly if they have Gleason pattern 4 or 5.
Men with a low-risk cancer sometimes choose surgery because they don’t want to risk disease progression. The study found that men who do not have these alterations in their cancers have a low risk of harbouring aggressive disease. These men may feel more comfortable choosing active surveillance. Alternatively, if a man’s low-risk tumour shows these alterations, they have a higher risk that their cancer may progress. They may consider treatment, including surgery.
Researchers performed DNA sequencing with a high-tech genomic tool known as mate-pair sequencing. This research was performed on specific Gleason patterns from frozen cancer specimens from 126 men who had their prostate glands removed. They found five genes are more frequently altered in Gleason patterns 4 and 5. These alterations were found more commonly in Gleason pattern 3 associated with higher Gleason patterns and not when Gleason pattern 3 was found alone.
“The needle biopsy procedure samples only a small portion of the tumour. It is not uncommon that a man with a Gleason pattern 3 on needle biopsy specimen harbours a higher-grade cancer next to the pattern 3 that was missed by the procedure,” says John Cheville, M.D., co-director of the Center for Individualized Medicine Biomarker Discovery Program and co-author of the study. “Therefore, if we identify these alterations in a Gleason pattern 3, there is a higher likelihood that Gleason pattern 4 is nearby.”

Mayo Clinic https://tinyurl.com/yxcg3wzk

Fluorescent marker can guide surgeons to remove dangerous brain tumour cells more accurately

A chemical that highlights tumour cells has been used by surgeons to help spot and safely remove brain cancer in a trial presented at the 2018 NCRI Cancer Conference. The research was carried out with patients who had suspected glioma, the most common form of brain cancer. Treatment usually involves surgery to remove as much of the cancer as possible, but it can be challenging for surgeons to identify all of the cancer cells while avoiding healthy brain tissue.

Researchers say that using the fluorescent marker helps surgeons to distinguish the most aggressive cancer cells from other brain tissue and they hope this will ultimately improve patient survival. The research was presented by Dr Kathreena Kurian, a Reader/Associate Professor in brain tumour research at the University of Bristol and consultant neuropathologist at North Bristol NHS Trust, UK. The study was led by Colin Watts, Professor of Neurosurgery and chair of the Birmingham brain cancer programme at the University of Birmingham, UK. Dr Kurian explained: “Gliomas are difficult to treat with survival times often measured in months rather than years. Many patients are treated with surgery and the aim is to safely remove as much of the cancer as possible. Once a tumour is removed, it is passed on to a pathologist who examines the cells under a microscope to see if they are ‘high-grade’, fast growing cells, or ‘low-grade’ slower growing cells. And we can plan further treatment, such as radiotherapy or chemotherapy, based on that diagnosis. “We wanted to see if using a fluorescent marker could help surgeons objectively identify high-grade tumour cells during surgery, allowing them to remove as much cancer as possible while leaving normal brain tissue intact.”

The researchers used a compound called 5-aminolevulinic acid or 5-ALA, which glows pink when a light is shone on it. Previous research shows that, when consumed, 5-ALA accumulates in fast growing cancer cells and this means it can act as a fluorescent marker of high-grade cells.

The study involved patients with suspected high-grade gliomas treated at the Royal Liverpool Hospital, Kings College Hospital in London or Addenbrooke’s Hospital in Cambridge, UK. They were aged between 23 and 77 years, with an average (median) age of 59 years. Before surgery to remove their brain tumours, each patient was given a drink containing 5-ALA.

Surgeons then used operating microscopes to help them look for fluorescent tissue while removing tumours from the patients’ brains. The tissue they removed was sent to the pathology lab where scientists could confirm the accuracy of the surgeons’ work.

A total of 99 patients received the 5-ALA marker and could be assessed for signs of fluorescence. During their operations, surgeons re-ported seeing fluorescence in 85 patients and 81 of these were subsequently confirmed by pathologists to have high-grade disease, one was found to have low-grade disease and three could not be assessed.

In the 14 patients where surgeons did not see any fluorescence, only seven tumours could be subsequently evaluated by pathology but in all these cases, low-grade disease was confirmed. Professor Watts said: “Neurosurgeons need to be able to distinguish tumour tissue from other brain tissue, especially when the tumour contains fastgrowing, high-grade cancer cells. This is the first prospective trial to show the benefits of using 5-ALA to improve the accuracy of diagnosing high-grade glioma during surgery. These results show that the marker is very good at indicating the presence and location of high-grade cancer cells.
National Cancer Research Institute www.ncri.org.uk/wp-content/uploads/2018/11/Kurian-Glioma-for-online.pdf

Improved understanding of the pathology of dwarfism may lead to new treatment targets

Pseudoachondroplasia (PSACH) is a severe inherited dwarfing condition characterised by disproportionate short stature, joint laxity, pain, and early onset osteoarthritis. In PSACH, a genetic mutation leads to abnormal retention of cartilage oligomeric matrix protein (COMP) within the endoplasmic reticulum (ER) of cartilage-producing cells (chondrocytes), which interferes with function and cell viability. In a report, investigators describe how this protein accumulation results in “ER stress” and initiates a host of pathologic changes. These findings may open up new ways to treat PSACH and other ER-stress-related conditions.

“This is the first study linking ER stress to midline 1 protein (MID1), a microtubule stabilizer that increases mammalian target of rapamycin complex 1 (mTORC1) signalling in chondrocytes and other cell types. This finding has significant implications for cellular functions including autophagy, protein synthesis, and potentially cellular viability. These results identify new therapeutic targets for this pathologic process in a wide spectrum of ER-stress disorders such as type 2 diabetes, Alzheimer disease, and tuberculosis,” explained Karen L. Posey, PhD, Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.

PSACH symptoms generally are recognized beginning at two years of age. Patients with PSACH have normal intelligence and cranio-facial features. PSACH is caused by mutations in the gene encoding the cartilage oligomeric matrix protein (COMP). ER stress occurs when abnormal (unfolded or misfolded) COMP (MT-COMP) accumulates in the rough endoplasmic reticulum of chondrocytes. Rough ER, the portion of ER displaying ribosomes, is the network of membranous tubules within cells associated with protein and lipid synthesis and export.

In previous studies, Dr. Posey and her colleagues have investigated chondrocyte pathology in the growth plates of dwarf mice that express MT-COMP, in cultured rat chondrosarcoma (RCS) cells that express human MT-COMP, as well as in cultured cartilage nodules from PSACH patients. The mice replicate many of the clinical features and chondrocyte pathology reported in patients with PSACH.

In the current study, the researchers showed increased levels of MID1 protein in chondrocytes from the mutant dwarf mice as well as in cells from human PSACH patients. They also found that ER-stress-inducing drugs increased MID1 signalling, although oxidative stress did not.

The up-regulation of MID1 was associated with increased mTORC1 signalling in the growth plates of the dwarf mice. Rapamycin decreased intracellular retention of MT-COMP and decreased mTORC1 signaling. The mTOR pathway is activated during various cellular processes (eg, tumor formation and angiogenesis, insulin resistance, adipogenesis, and T-lymphocyte activation) and is dysregulated in diseases such as cancer and type 2 diabetes.

The results of this work show that MID1, mTORC1 signalling, the microtubule network, protein synthesis, inflammation, and autophagy form a complex multifaceted response to protein accumulation in the ER when clearance efforts fail and MID1 may act as a pro-survival factor.
EurekAlertwww.eurekalert.org/pub_releases/2018-12/e-iuo121018.php