Impedance-Based Miniaturized Biosensor for Ultrasensitive and Fast Prostate-Specific Antigen Detection

This paper reports the successful fabrication of an impedance-based miniaturized biosensor and its application for ultrasensitive Prostate-Specific Antigen (PSA) detection in standard and real human plasma solution, spiked with different PSA concentrations. The sensor was fabricated using photolithographic techniques, while monoclonal antibodies specific to human PSA were used as primary capture antibodies. Electrochemical impedance spectroscopy (EIS) was employed as a detection technique. The sensor exhibited a detection limit of 1 pg/ml for PSA with minimal nonspecific binding (NSB). This detection limit is an order of magnitude lower than commercial PSA ELISA assays available on the market. The sensor can be easily modified into an array for the detection of other biomolecules of interest, enabling accurate, ultrasensitive, and inexpensive point-of-care sensing technologies

miRNAs associated with prostate cancer risk and progression

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate cancer. The discussion highlights key findings from previous studies, which reported the role of miRNAs in risk and progression of prostate cancer, providing an understanding of the influence of miRNA on prostate cancer. Our review indicates that somewhat consistent results exist between these studies and reports on several prostate cancer related miRNAs. Present promising candidates are miR-1, −21, 106b, 141, −145, −205, −221, and −375, which are the most frequently studied and seem to be the most promising for diagnosis and prognosis for prostate cancer. Nevertheless, the findings from previous studies suggest miRNAs may play an important role in the risk and progression of prostate cancer as promising biomarkers

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q Results The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p Conclusion These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.Peer reviewe

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68–0.90, p = 5.59 × 10−4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways

Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.Other Research Uni

Photoluminescence Spectroscopy Of Bioconjugated Quantum Dots And Their Application For Early Cancer Detection

Most of the bio-applications of semiconductor quantum dots (QDs) show and utilize their superior optical properties over organic fluorophores. An estimated 3-35% of all cancer deaths could be avoided through early detection, therefore, there is a critical need to develop sensitive probes. The objectives of this work are: Research the phenomena of blue photoluminescence (PL) spectral shift on the dried bioconjugated QDs and develop the relevant mechanism; Develop a methodology that will allow successful confirmation of the bioconjugation reaction between biomolecules and QDs; Propose a modification of an existent method or approach to employ the blue spectral shift of bioconjugated QDs for early cancer detection. Results indicated that the blue spectral shift, observed for dried on the silicon substrates bioconjugated QDs, is increased with the time of storage and reaches 30-40nm in 14 days. It is accelerated at elevated temperatures and slowed down at lower temperatures. Larger size QDs generate spectral shifts of larger magnitudes, and the spectral shift is positively correlated with the biomolecule\u27s size/weight. This phenomenon is explained by elastic and compression stress due to nonhomogenious drying of the QD droplet and the reaction with the solid surface. Agarose gel electrophoresis technique, optimized with organic dye fluorescamine, is suitable for bioconjugation verification. The optimal running parameters were found to be 2% agarose gel, 1.5V working voltage, 0.5X TBE as a running buffer, and about 120 mins running time. The spectral shift was implemented for improving the sensitivity of Prostate Specific Antigen (PSA) Enzyme-Linked ImmunoSorbent Assay (ELISA). It was found that QD ELISA could be as much, as 100 times more sensitive than the regular commercial ELISA, based on the enzymatic detection. The results of this work show that QDs may be very useful for early detection of several types of cancers, including prostate cancer in men and breast/ovarian/uterine cancers in women

Photoluminescence Spectroscopy Of Bioconjugated Quantum Dots And Their Application For Early Cancer Detection

Most of the bio-applications of semiconductor quantum dots (QDs) show and utilize their superior optical properties over organic fluorophores. An estimated 3-35% of all cancer deaths could be avoided through early detection, therefore, there is a critical need to develop sensitive probes. The objectives of this work are: Research the phenomena of blue photoluminescence (PL) spectral shift on the dried bioconjugated QDs and develop the relevant mechanism; Develop a methodology that will allow successful confirmation of the bioconjugation reaction between biomolecules and QDs; Propose a modification of an existent method or approach to employ the blue spectral shift of bioconjugated QDs for early cancer detection. Results indicated that the blue spectral shift, observed for dried on the silicon substrates bioconjugated QDs, is increased with the time of storage and reaches 30-40nm in 14 days. It is accelerated at elevated temperatures and slowed down at lower temperatures. Larger size QDs generate spectral shifts of larger magnitudes, and the spectral shift is positively correlated with the biomolecule\u27s size/weight. This phenomenon is explained by elastic and compression stress due to nonhomogenious drying of the QD droplet and the reaction with the solid surface. Agarose gel electrophoresis technique, optimized with organic dye fluorescamine, is suitable for bioconjugation verification. The optimal running parameters were found to be 2% agarose gel, 1.5V working voltage, 0.5X TBE as a running buffer, and about 120 mins running time. The spectral shift was implemented for improving the sensitivity of Prostate Specific Antigen (PSA) Enzyme-Linked ImmunoSorbent Assay (ELISA). It was found that QD ELISA could be as much, as 100 times more sensitive than the regular commercial ELISA, based on the enzymatic detection. The results of this work show that QDs may be very useful for early detection of several types of cancers, including prostate cancer in men and breast/ovarian/uterine cancers in women