With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician ...in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments—DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.
Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC ...technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed “fresh” via Epic CTC Platform or from “frozen” PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples.
Canine positioner Landers, James L
General dentistry,
2006 Sep-Oct, Letnik:
54, Številka:
5
Journal Article
Recenzirano
This article describes a method for general dentists to treat impacted maxillary canines that are in a lingual position to achieve predictable results and minimize the number of office visits for the ...patient.
A high prevalence of metabolic bone disease and osteonecrosis among HIV+ patients on highly active antiretroviral therapy (HAART) has been reported in predominantly white cohorts. We examined bone ...health in an ethnically diverse cohort of 23 African-Americans and 21 non-African-Americans who were mean (standard deviation) age 45 (7) years old, 66% male, and on HAART for 34 (28) months. Non-African-Americans were more likely to have osteopenia or osteoporosis (59%) compared to African-Americans (26%) (p = 0.09). The prevalence of vitamin D insufficiency (< 34 ng/ml) and elevated i-PTH (>65 pg/ml) was 79% and 20%, respectively. Higher mean urinary N-telopeptide levels were found in non-African-Americans 58 (34) nmol BCE/mmol compared to African-Americans 41 (18) nmol BCE/mmol (p = 0.09). Magnetic resonance imaging identified one African-American subject (3%) with bilateral asymptomatic hip osteonecrosis. Our findings suggest that the burden of metabolic bone disease in HIV+ patients with HAART-associated lipodystrophy may be greater in whites than in African-Americans. Studies to examine ethnic variations in bone metabolism are necessary to devise optimal interventions.
DNA and silica-coated magnetic particles entangle and form visible aggregates under chaotropic conditions with a rotating magnetic field, in a manner that enables quantification of DNA by image ...analysis. As a means of exploring the mechanism of this DNA quantitation assay, nanoscale SiO2-coated Fe304 （Fe3O4@SiO2） particles are synthesized via a solvothermal method. Characterization of the particles defines them to be -200 nm in diameter with a large surface area （141.89 m2/g）, possessing superparamagnetic properties and exhibiting high saturation magnetization （38 emu/g）. The synthesized Fe3O4@SiO2 nanoparticles are exploited in the DNA quantification assay and, as predicted, the nanoparticles provide better sensitivity than commercial microscale Dynabeads for quantifying DNA, with a detection limit of 4 kilobase-pair fragments of human DNA. Their utility is proven using nanoparticle DNA quantification to guide efficient polymerase chain reaction （PCR） amplification of short tandem repeat loci for human identification.
We describe a microfluidic genetic analysis system that represents a previously undescribed integrated microfluidic device capable of accepting whole blood as a crude biological sample with the ...endpoint generation of a genetic profile. Upon loading the sample, the glass microfluidic genetic analysis system device carries out on-chip DNA purification and PCR-based amplification, followed by separation and detection in a manner that allows for microliter samples to be screened for infectious pathogens with sample-inanswer-out results in <30 min. A single syringe pump delivers sample/reagents to the chip for nucleic acid purification from a biological sample. Elastomeric membrane valving isolates each distinct functional region of the device and, together with resistive flow, directs purified DNA and PCR reagents from the extraction domain into a 550-nl chamber for rapid target sequence PCR amplification. Repeated pressure-based injections of nanoliter aliquots of amplicon (along with the DNA sizing standard) allow electrophoretic separation and detection to provide DNA fragment size information. The presence of Bacillus anthracis (anthrax) in 750 nl of whole blood from living asymptomatic infected mice and of Bordetella pertussis in 1 μl of nasal aspirate from a patient suspected of having whooping cough are confirmed by the resultant genetic profile.
Abstract Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance ...spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk.
Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused ...exon resequencing in 218 prostate cancer tumors identified the nuclear receptor coactivator
NCOA2 as an oncogene in ∼11% of tumors. Additionally, the androgen-driven
TMPRSS2-ERG fusion was associated with a previously unrecognized, prostate-specific deletion at chromosome 3p14 that implicates
FOXP1,
RYBP, and
SHQ1 as potential cooperative tumor suppressors. DNA copy-number data from primary tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. The genomic and clinical outcome data from these patients are now made available as a public resource.
► Integrated genomic profiling of 218 prostate tumors provides a unique public resource ► Androgen receptor coactivator
NCOA2 is amplified in primary and metastatic disease ►
TMPRSS2-ERG
+
tumors associate with 3p14 loss and candidates
FOXP1,
RYBP, and
SHQ1 ► Degree and pattern of CNAs in primary tumors is associated with risk of relapse
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