Sequenom Inc. has reported positive results from screening studies using their noninvasive circulating cell-free fetal nucleic acid SEQureDx™ Technology. This technology can detect fetal aneuploidy, including Down syndrome, from maternal blood. The announcement was made at the International Society of Prenatal Diagnostics (ISPD) conference in Vancouver, Canada.
Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or in part (e.g., due to translocations). Current tests for Down syndrome rely on ‘surrogate’ epigenetic markers, those associated with the phenotype, rather than markers directly related to the extra number 21 chromosome itself. Another approach is to measure different combinations of markers at different times in the pregnancy. The SEQureDx test uses a maternal blood sample taken as early as the first trimester and identifies the extra number 21 chromosome directly. The technology enables fetal nucleic acid to be extracted from maternal blood. This may mean an end to tests that disturb the amniotic fluid, which are associated with risks.
The company performed blinded studies involving approximately 200 clinical samples collected both prospectively and retrospectively in both normal and high-risk patients. Their test for Down syndrome correctly identified 100% of Down syndrome samples without any false-positive outcomes, indicating the test to be both highly sensitive and specific. Currently used methods of serum-testing have detection rates of between 70 and 90% and false positive rates as high as 5%. This results in unnecessary confirmatory diagnostic tests, often meaning increased anxiety and complications associated with invasive procedures.
“We are very pleased to be reporting substantial progress toward commercializing an important test to screen for Down syndrome that can be administered as early as late in the first trimester through a simple blood draw from the mother,” said Harry Stylli, Sequenom’s President and Chief Executive Officer. “Data from our blinded screening study for the detection of fetal aneuploidy indicate that the current version of our test has identified all Down syndrome samples without any false-positive outcomes. Also our coverage has improved to at least 93% of the US population. Although these results require further validation in larger studies, such results using SEQureDx™ Technology can potentially transform current clinical practice for Down syndrome-risk assessment.”
Source: www.sequenom.com
MRI to track cells magnetically labeled by bacterial gene
Scientists from Emory University (GA, USA) have been investigating the full potential of the MRI scanner. The group believe that, in addition to generating anatomical images, MRI can be used to provide functional, physiological and molecular information to greatly improve biomedical research and clinical healthcare. The study indicates that a gene expression marker for MRI can be achieved using bacterial magnetosomes. Magnetosomes are magnets produced by naturally occurring magnetotactic bacteria and consist of 15–20 magnetite crystals, with each crystal approximately 35–120 nm long.
The gene magA, found in magneto, tactic bacteria and known to be involved with iron transport is expressed in the commonly used human cell line 293FT. Expression of this gene results in the production of magnetic, iron-oxide nanoparticles by these cells and leads to increased transverse relaxivity. The production of these magnetite crystals in human cells allow them to show up in an MRI scan, with the potential for this technology to allow scientists to track the movement of cells through the body.
This study has demonstrated that these nanoparticles can be formed in vivo utilizing endogenous iron and can be used to visualize cells positive for magA. The authors conclude that, “These results demonstrate that magA alone is sufficient to produce magnetic nanoparticles and that it is an appropriate candidate for an MRI reporter gene.”
Xiaoping Hu, professor of biomedical engineering at Emory University and the Georgia Institute of Technology believe MagA to be nontoxic, “MagA can be thought of as the equivalent of green fluorescent protein, but for magnetic resonance imaging.”
Source: Zurkiya O, Chan AW, Hu X. MagA is sufficient for producing magnetic nanoparticle in mammalian cells, making it an MRI reporter. Magn. Reson. Med. 59, 1225–1231 (2008).
Superparamagnetic particles in new prolactin assay
Olympus America Inc. launches test for plasma serum that utilizes chemiluminescent immunoassay technology.
A new test for the hormone prolactin has become available in the USA by Olympus America Inc. DynaBeads® form the basis of this chemiluminescent immuno-assay. Dynabeads are superparamagnetic, meaning that they only exhibit magnetic properties in the presence of a magnetic field. The test is standardized against the 3rd WHO Ref. Standard 84/500 for human prolactin. The assay is intended to be used with the automated Olympus AU300i® immunoassay system.
Crucially, since prolactin levels vary greatly among individuals according to reproductive status, the assay is sensitive to a wide range of prolactin concentrations of approximately 0.05–300 µg/l. Following a 28 min processing time, the two-step immunometric assay quantitively measures concentrations of pro-lactin in either 50 µl of serum or lithium–heparin plasma samples.
The prolactin test complements the other reproductive function tests available from Olympus, as Lorraine Damico, Director of Immunoassay Marketing for Olympus explains, “The addition of the prolactin assay to the already available Olympus fertility assays LH and FSH is an important step in the development of a panel of tests comprising from 7 to 10% of the test volume in a routine clinical laboratory”.
Prolactin levels can indicate to physicians what is likely to be the problem in a patient with symptoms of a reproductive disorder, and as such is the most commonly undertaken hormonal investigation in these patients. Diagnosis of pituitary tumors, breast cancer and hypothalamic–pituitary disorders can also be aided by the determination of prolactin levels. Elevated levels of prolactin are linked with infertility, impotence, primary hypothyroidism and pituitary tumors.
Source: www.olympusamerica.com/au3000i
Antibody analysis system receives approval by the US FDA
Invitrogen Corp. announces that their DynaChip™ system may now be used for organ transplant donor–recipient matching.
Invitrogen’s DynaChip system has received clearance from the FDA. The DynaChip system detects and identifies HLA antibodies and is the only automated chip-based system of its kind, to be currently available.
Kip Miller, Senior Vice President of BioDiscovery comments, “We’re very pleased to have received this FDA approval, which validates the accuracy of DynaChip data and demonstrates Invitrogen’s commitment to providing clinicians with accurate and more efficient solutions.”
Perhaps the system’s most significant application is in the identification of compatible organ transplant donors and recipients, since it is HLA cells which are involved in the signaling pathway which notifies the immune system of foreign particles such as viruses or bacteria.
The DynaChip system consists of three parts: a processor, a protein array and interpretation software. The processor makes the assay system automated by controlling aspects such as dispensing, incubation and washing, image detection and results analysis. The protein array enables multiple antibodies to be tested at the same time. The interpretation software provides rapid, efficient and automated analysis.
“The high capacity of the DynaChip allows us to add a larger number of proteins than competitive products, reducing the amount of testing and overall turn-around time,” added Jim Janicki, Vice President and General Manager of Invitrogen’s Applied Markets business unit. “With organ donations, time is of the essence and this analysis system will help physicians make fast, reliable clinical decisions.”
Source: www.invitrogen.com/dynachip
Confocal laser endomicroscopy used to diagnose digestive disorders
Scientists from the John Hopkins University School of Medicine (MD, USA) have investigated a technique which may speed up the diagnosis of digestive disorders.
Confocal laser endomicroscopy enables clinicians to view highly magnified images of a patient’s gastrointestinal tract through the attachment of a microscope to an endoscope.
The main benefit of this technology is that it has the potential to reduce the time it takes to diagnose diseases such as inflammatory bowel disease. Kerry Dunbar, from John Hopkins, explains, “Previously, it took a few days or a week to find out a diagnosis because we’d have to take photos and then do a mucosal biopsy. But with confocal laser endo-microscopy, we can see what’s going on at the time of the endoscopy and then diagnose and treat patients immediately, instead of waiting a week or more.” Gastro-intestinal cancers often progress rapidly, therefore prompt detection and treatment is particularly paramount.
The research group from John Hopkins performed a confocal laser endo-micro-scopy examination on 1771 patients with suspected gastrointestinal problems. Traditional diagnostic tests were also carried out on these patients. They found confocal laser endo-micro-scopy to be 91% accurate at identifying problems in the upper gastrointestinal tract and 93% accurate at identifying problems in the lower gastrointestinal tract. In the study, presented at Digestive Disease Week 2008 in San Diego (CA, USA), 422 patients were correctly diagnosed with gastro–esophageal reflux disease, 84 with esophageal cancer, 99 with colon cancer, 75 with gastritis, 22 with stomach cancer, 39 with celiac disease and 893 with inflammatory bowel disease.
PET imaging for diagnosis of early head and neck cancer
A study published in the Journal of the National Cancer Institute has investigated the accuracy of PET using the radio-active tracer 18F-fluorodeoxyglucose (18F-FDG PET) in detecting lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). This imaging technique has been proposed to enhance the preoperative assessment of cervical lymph node status in this type of carcinoma.
Establishing the presence or absence of spread of the carcinoma to nearby lymph nodes is important in determining the prognosis. There is currently controversy over the use of 18F-FDG PET on patients with a clinically negative (cN0) neck. Such patients appear to be clinically free of metastases in the lymph nodes, but MRI scans, CT scans and FDG-PET are used to confirm this. However, no evidence has conclusively supported the use of 18F-FDG PET in such patients.
A total of 32 studies involving 1236 patients were included in the meta-analysis of all available studies of the diagnostic performance of 18F-FDG PET in patients with head and neck squamous cell carcinoma. The sensitivity and specificity across studies was calculated and a summary receiver operating characteristic curves using hierarchical regression models. Where possible, the performance of 18F-FDG PET was compared with that of conventional diagnostic methods such as computed tomography, magnetic resonance imaging and ultrasound with fine-needle aspiration.
The sensitivity and specificity of 18F-FDG PET was found to be 79% (95% confidence interval [CI]: 72–85%) and 86% (95% CI: 83–89%), respectively. For cN0 patients, the sensitivity of 18F-FDG PET was only 50% (95% CI: 37–63%), whereas specificity was 87% (95% CI = 76–93%).
The authors of the study, from the University of Ioannina School of Medicine (Greece), concluded that, “18F-FDG PET has good diagnostic performance in the overall pretreatment evaluation of patients with HNSCC but still does not detect disease in half of the patients with metastasis and cN0.”
Source: Kyzas PA, Evangelou E, Denaxa-Kyza D, Ioannidis JP. 18F-fluorodeoxyglucose positron emission tomography to evaluate cervical node metastases in patients with head and neck squamous cell carcinoma: a meta-analysis. J. Natl Cancer Inst. 100(10), 712–720 (2008).
Efficacy of breast cancer treatment may be determined early by blood test
Circulating tumor cells have been associated with disease progression.
Scientists at Georgetown University Medical Center (DC, USA) have completed research which suggests that a blood test could enable doctors to assess the efficacy of treatment for patients with metastatic breast cancer. In the study, the number of circulating tumor cells (CTC) in patients with metastatic breast cancer was measured by the US FDA-approved CellSearch™ technology. This procedure was carried out with 1 tablespoon of blood every 3–4 weeks. Concurrently, standard radiology studies were performed every 9–12 weeks to monitor disease response or progression. The women participating in the study received various treatments including chemotherapy, endocrine therapy and combination therapy with a biologic agent. The study used a threshold CTC count of five, based on previous studies. A CTC higher than five was significantly associated with disease progression; 75% of patients with a CTC greater than or equal to five had disease progression, while 66% of patients with a CTC count of less than five did not.
Minetta Liu, from Georgetown’s Lombardi Comprehensive Cancer Center explains the present situation in the assessment of cancer treatment, “It can take several weeks and sometimes months to determine if a particular cancer treatment is working because it can take that long to observe any significant radiographic changes in tumor size or appearance.” Currently, disease progression is assessed by radiologic methods such as CT scans and ultrasound.
Liu is keen to find further evidence to strengthen the case for testing for CTC routinely in patients with metastatic breast cancer, “We have a follow-up study underway that evaluates CTC results within the framework of a randomized clinical trial to eliminate potential variability from the treatment administered.”
Source: http://lombardi.georgetown.edu