Digital innovation for cancer risk assessment allows large-scale service redevelopment of regional cancer genetics service delivery.

Family-history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention and Early Detection (SPED). The online patient-facing cancer Family History Questionnaire Service (cFHQS) is a digitalised, resource efficient tool for family history data capture to facilitate this. The capturing of digital data from cFHQS allows for data interrogation of patients referred to Clinical Genetics for the purposes of service improvement.

Proactive familial cancer risk assessment: a service development study in UK primary care.

Background: Family history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention, and Early Detection (SPED). Family History Questionnaire Service (FHQS) is a resource-efficient patient-facing online tool to facilitate this. In the UK, cancer risk assessment is usually only offered to concerned individuals proactively self-presenting to their GP, leading to inequity in accessing SPED in the community.

Characterisation of a Novel Cell Line (ICR-SS-1) Established from a Patient-Derived Xenograft of Synovial Sarcoma.

Synovial sarcoma is a rare translocation-driven cancer with poor survival outcomes, particularly in the advanced setting. Previous synovial sarcoma preclinical studies have relied on a small panel of cell lines which suffer from the limitation of genomic and phenotypic drift as a result of being grown in culture for decades. Patient-derived xenografts (PDX) are a valuable tool for preclinical research as they retain many histopathological features of their originating human tumour; however, this approach is expensive, slow, and resource intensive, which hinders their utility in large-scale functional genomic and drug screens.

A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts.

SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS.

The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.

: Tyrosine kinases are key mediators of intracellular signaling cascades and aberrations in these proteins have been implicated in driving oncogenesis through the dysregulation of fundamental cellular processes including proliferation, migration, and apoptosis. As such, targeting these proteins with small molecule tyrosine kinase inhibitors (TKI) has led to significant advances in the treatment of a number of cancer types.: Soft tissue sarcomas (STS) are a heterogeneous and challenging group of rare cancers to treat, but the approval of the TKI pazopanib for the treatment of advanced STS demonstrates that this class of drugs may have broad utility against a range of different sarcoma histological subtypes.

A rapid test for endotoxin in whole blood.

A rapid whole blood agglutination test has been developed for the detection of endotoxin. The test reagent consists of polymyxin B (PmB) conjugated to the Fab fragment of the anti-glycophorin antibody 1C3/86. After addition of reagent to whole blood, red cell agglutination occurs within two minutes in samples from endotoxaemic patients or with the addition of either whole Gram negative bacteria, supernatants from Gram negative bacterial cultures or purified endotoxin.

The detection of D-dimer in plasma by enzyme immunoassay: improved discrimination is obtained with a more specific signal antibody.

Most commercial D-dimer enzyme immunoassays employ two antibodies, a fibrin specific capture monoclonal and a less specific antibody cross-reacting with epitopes present on fibrinogen. Two different ELISA systems were compared to test whether this cross-reaction can lead to overestimation of the true levels of cross-linked fibrin derivatives. Both assays used the same D-dimer specific antibody for capture, DD-3B6/22, but utilized signalling antibodies which differed in fibrinogen reactivity.

Automated determination of cross-linked fibrin derivatives in plasma.

Automated assays for the measurement of cross-linked fibrin derivatives in plasma (XL-FbDP) have been developed utilizing latex beads coated with anti-D dimer monoclonal antibody (DD-3B6/22) for both the Cobas Fara Chemistry Centrifugal and the Cobas Mira analysers (Roche, Basle, Switzerland). The analysers were programmed to mix plasma and latex reagent simultaneously and analyse absorbance changes over a 10-15 min period. Results were interpolated by the analyser from a standard curve derived from a polymer of D-dimer.

Plasma cross linked fibrin degradation products in pulmonary embolism.

Plasma concentrations of cross linked fibrin degradation products, a marker of intravascular thrombosis and fibrinolysis, were measured in 495 patients with suspected pulmonary embolism referred for ventilation-perfusion lung scanning to determine whether concentrations are increased in pulmonary embolism and their potential use in diagnosis. Lung scans were described as normal (n = 66) or as showing a low (n = 292), indeterminate (n = 58), or high probability (n = 79) of pulmonary embolism. There was a difference between the mean levels of cross linked fibrin degradation products in each scan category: normal scans, 142 ng/ml; low probability scans, 295 ng/ml; indeterminate probability scans, 510 ng/ml; high probability scans, 952 ng/ml (p less than 0.

The simpliRED D dimer test: a novel assay for the detection of crosslinked fibrin degradation products in whole blood.

A new system for the detection of fibrin degradation products in whole blood has been developed. The test provides a clearly visible agglutination of the patient's red blood cells in the presence of elevated levels of the crosslinked fibrin derivative, D dimer. The test, which uses a bispecific reagent prepared from Fab' fragments of monoclonal antibodies, gives a positive result in 1-2 minutes.

Automation of routine coagulation testing using a random access centrifugal analyzer.

The results are reported of a clinical and laboratory evaluation of the use of a random-access centrifugal analyzer linked to a personal computer in the management of the routine workload of a hemostasis laboratory. Over a three-month period, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), and derived fibrinogen (Fib) were performed on a total of 929 samples. Included in the study were 448 samples from patients receiving anticoagulants (oral anticoagulants, 228; heparin, 166; heparin and warfarin, 130) and 351 samples from patients requiring coagulation screens (PT, APTT, TCT, Fib).

A latex agglutination assay for D dimer: evaluation and application to the diagnosis of thrombotic disease.

Although latex agglutination assays have been used for some years to diagnose thrombotic disorders, only recently has it been possible to measure specifically the products of fibrin breakdown in the presence of fibrinogen degradation products, by using monoclonal antibodies. We have evaluated a preparation of latex particles coupled to the monoclonal antibody DD-3B6/22, which is specific for cross-linked fibrin degradation products (XDP) and allows accurate discrimination between normal and pathological conditions. Of samples from 515 apparently healthy volunteers, 97.

Measurement of crosslinked fibrin derivatives--use in the diagnosis of venous thrombosis.

The measurement of crosslinked fibrin derivatives in plasma has received evaluation as a screening test in the diagnosis of venous thrombosis. Plasma samples were taken from 104 patients undergoing venography because of clinical suspicion of lower limb venous thrombosis. The samples were assayed using a monoclonal antibody identifying an epitope on D dimer and larger crosslinked fibrin derivatives in an enzyme immunoassay.

Rapid detection of cross-linked fibrin degradation products in plasma using monoclonal antibody-coated latex particles.

Conformational and structural changes on conversion of fibrinogen to fibrin and its cross-linking by Factor XIIIa lead to the development of new antigenic determinants that permit differentiation between their plasminolytic cleavage products. A monoclonal antibody (DD-3B6/22) that is specific for cross-linked fibrin derivatives containing the D dimer configuration has been used in developing a latex agglutination procedure that can detect fibrin degradation products in either plasma or serum. Fibrinogen or its degradation products do not cross-react with this antibody.

Measurement of cross linked fibrin derivatives in plasma: an immunoassay using monoclonal antibodies.

Fibrinogen degradation, fibrin polymerisation, and the insertion of cross links into fibrin by fibrin stabilising factor lead to the appearance of new antigenic determinants. Antibodies against these antigenic sites may react specifically with the derivatives but not with the parent molecules. We have utilised a monoclonal antibody, which interacts with the cross linked fragment D dimer and related high molecular weight fibrin derivatives, to develop an enzyme immunoassay which measures cross linked fibrin derivatives in plasma and serum using D dimer as standard.

An immunoassay for human D dimer using monoclonal antibodies.

Monoclonal antibodies (MAb) were raised against human D dimer. The hybridomas were screened with a solid phase enzyme immunoassay against D dimer and fibrinogen degradation products. Among the panel of MAb identified, two distinct patterns emerged; the majority belonging to a panspecific class reacting against epitopes present on both D dimer and fibrinogen degradation product Dcate and a monospecific class reacting with determinants apparently present only on D dimer.

Measurement of crosslinked fibrin degradation products - an immunoassay using monoclonal antibodies.

We have prepared a monoclonal antibody which recognises an antigenic determinant on D dimer, a specific fragment resulting from the degradation of crosslinked fibrin. This antibody has been used in the development of an enzyme-linked immunoassay for D dimer and related degradation products containing crosslinked gamma-gamma chains, to provide a simple assay of circulating crosslinked fibrin degradation products suitable for clinical use. Since these crosslinked fibrin degradation products are characteristic of fibrinolysis, as distinct from fibrinogenolysis, their measurement should aid in the diagnosis, evaluation and monitoring of thrombotic and thrombolytic states.

Plasma levels of aspirin following effervescent and enteric coated tablets, and their effect on platelet function.

Single doses of effervescent tablets (1200 mg) and enteric coated (EC) tablets (1300 mg and 650 mg) of acetylsalicylic acid (aspirin, ASA) were given to healthy volunteers in random order. Plasma ASA and salicylic acid (SA) levels were measured and concurrent in vitro measurements of the volunteers' platelet aggregation were carried out. The effervescent preparation resulted in peak ASA concentrations of 17-40 mg/l, achieved 20 to 30 min after a 1200 mg dose, whereas peak ASA levels of 0.