Aspartyl (asparaginyl) β-hydroxylase (AABH), a serum biomarker for lung cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 45-45
Author(s):  
Kiarash Moshiri
Keyword(s):  
Lung Cancer ◽  
Sandwich Elisa ◽  
Elevated Serum ◽  
Ct Scanning ◽  
The United States ◽  
Serum Biomarker ◽  
Detection Methods ◽  
Great Promise ◽  
Lower Sensitivity ◽  
Serological Screening

45 Background: There are no serum biomarkers currently approved for the detection of lung cancer, a leading cause of cancer associated mortality world wide. More than 180,000 cases of lung cancer will be diagnosed in the United States in 2020 by other means such as by X-ray and CT scanning methods, which have inherently lower sensitivity and higher cost when compared generally to serological methods. While the five year survival for lung cancer is 15%, a survival rate of 50% can be achieved when detection is made early in individuals with localized cancer. Current detection methods, however, enable such detection in only about 18% of cases overall. Methods: A prospective serum biomarker Aspartyl (Asparaginyl) ß Hydroxylase (AABH), has been previously found to be elevated by immunohistochemical staining (IHC) in a broad range of cancers, including lung cancer. AABH was detected in > 99% of tumor specimens tested (n > 1000) but absent in adjacent tissue. The present study introduces a double monoclonal sandwich ELISA which provides detection and comparative quantification of AABH in serum of lung cancer patients vs. normal, and high-risk controls such as cigarette smokers without cancer. This is relevant since 87% of lung cancers are attributable to cigarette smoking, and associative parallels can be seen with recent reductions in rates of smoking. Results: Increased levels of serum AABH were found in 99% of patients with lung cancer (n = 192). Serum AABH was found to be undetectable in individuals not known to have cancer (n = 129, specificity = 93%). In patients with lung cancer, AABH was detectable at all stages. In a population of 50 smokers not known to have cancer, the mean serum AABH level was 0 ng/ml with 90% specificity. Conclusions: The AABH serum ELISA therefore has great promise as an additional diagnostic tool for lung cancer having the practicality and cost effectiveness of conventional serological screening. Elevated serum AABH in conjunction with CT scanning may greatly facilitate earlier diagnosis of lung cancer at a stage in which cure rates are significantly higher and thus may contribute to increased patient survival.

AABH (aspartyl [asparaginyl] β-hydroxylase) as a serum biomarker for breast cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 2-2
Author(s):  
Kiarash Moshiri
Keyword(s):  
Breast Cancer ◽  
Sandwich Elisa ◽  
Survival Rates ◽  
Elevated Serum ◽  
Disease Recurrence ◽  
The United States ◽  
Develop Breast Cancer ◽  
Detection Methods ◽  
Great Promise ◽  
Primary Tumors

2 Background: Breast cancer accounts for 27% of female cancers. One in every eight women will develop breast cancer in their lifetime. More than 220,000 new cases of breast cancer will be diagnosed in the United States in 2020. Five-year survival rates for breast cancer are 98% for localized disease, 83% for regionally spread and 26% for distantly spread cancer. However, 25% of all metastases occur more than 5 years after the initial diagnosis and thus survival rates decrease as time goes out to 10 years due to disease recurrence. Current detection methods rely on imaging modalities, including mammography and MRI. No serum bio-markers have been approved for either breast cancer screening or monitoring for disease recurrence, yet. In asymptomatic women in remission from breast cancer the guidelines of the major oncologic organizations only suggest annual mammography for detection of new primary tumors. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a serum bio-marker for cancer. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including breast cancer. It has been detected by IHC in > 99% of tumor specimens tested (n > 2000) but is absent in adjacent non-affected tissue, and in tissue samples from non-affected individuals. This led to the development of a sandwich ELISA that reliably measures AABH in serum. Results: In the current study we have utilized the assay to quantify AABH levels in the sera of patients diagnosed with Breast Cancer compared to women free of disease. Increased levels of AABH were found in the serum of 99% of patients with breast cancer (n = 189). In women not known to have cancer, AABH was essentially undetectable in serum (n = 65, specificity = 96%). Serum from several women currently in remission subsequent to treatment for breast cancer were also analyzed and found to be negative for AABH. Conclusions: Thus, measurement of serum AABH levels has great promise as a diagnostic tool for breast cancer with potential application in monitoring for disease recurrence. Elevated serum AABH in conjunction with mammography and MRI may greatly facilitate earlier diagnosis of both primary and recurrent Breast Cancer.

scholarly journals NCCN Task Force Report: Positron Emission Tomography (PET)/Computed Tomography (CT) Scanning in Cancer

2007 ◽  
Vol 5 (S1) ◽  
pp. S-1-S-22 ◽  
Author(s):  
Donald A. Podoloff ◽  
Ranjana H. Advani ◽  
Craig Allred ◽  
Al B. Benson ◽  
Elizabeth Brown ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Positron Emission Tomography ◽  
Task Force ◽  
Ct Scanning ◽  
The United States ◽  
Emission Tomography ◽  
Task Force Report ◽  
General Internists ◽  
Positron Emission ◽  
Cancer Network

The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology. (JNCCN 2007;5(Suppl 1):S1–S22)

Hamas and Civil Society in Gaza

2013 ◽  
Author(s):  
Sara Roy
Keyword(s):  
United States ◽  
Political Violence ◽  
West Bank ◽  
Gaza Strip ◽  
Social Institutions ◽  
The United States ◽  
Great Promise ◽  
Religious Congregations ◽  
Regional Dynamics ◽  
Second Intifada

Many in the United States and Israel believe that Hamas is nothing but a terrorist organization, and that its social sector serves merely to recruit new supporters for its violent agenda. Based on extensive fieldwork in the Gaza Strip and West Bank during the critical period of the Oslo peace process, this book shows how the social service activities sponsored by the Islamist group emphasized not political violence but rather community development and civic restoration. The book demonstrates how Islamic social institutions in Gaza and the West Bank advocated a moderate approach to change that valued order and stability, not disorder and instability; were less dogmatically Islamic than is often assumed; and served people who had a range of political outlooks and no history of acting collectively in support of radical Islam. These institutions attempted to create civic communities, not religious congregations. They reflected a deep commitment to stimulate a social, cultural, and moral renewal of the Muslim community, one couched not only—or even primarily—in religious terms. Vividly illustrating Hamas's unrecognized potential for moderation, accommodation, and change, the book also traces critical developments in Hamas' social and political sectors through the Second Intifada to today, and offers an assessment of the current, more adverse situation in the occupied territories. The Oslo period held great promise that has since been squandered. This book argues for more enlightened policies by the United States and Israel, ones that reflect Hamas' proven record of nonviolent community building. A new afterword discusses how Hamas has been affected by changing regional dynamics and by recent economic and political events in Gaza, including failed attempts at reconciliation with Fatah.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis

2021 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

Detection by real-time quaking-induced conversion (RT-QuIC), ELISA, and IHC of chronic wasting disease prion in lymph nodes from Pennsylvania white-tailed deer with specific PRNP genotypes

2021 ◽  
pp. 104063872110214
Author(s):  
Deepanker Tewari ◽  
David Steward ◽  
Melinda Fasnacht ◽  
Julia Livengood
Keyword(s):  
Real Time ◽  
Disease Susceptibility ◽  
Chronic Wasting Disease ◽  
Low Frequency ◽  
The United States ◽  
Detection Methods ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Diagnostic Laboratory ◽  
Highly Sensitive

Chronic wasting disease (CWD) is a prion-mediated, transmissible disease of cervids, including deer ( Odocoileus spp.), which is characterized by spongiform encephalopathy and death of the prion-infected animals. Official surveillance in the United States using immunohistochemistry (IHC) and ELISA entails the laborious collection of lymphoid and/or brainstem tissue after death. New, highly sensitive prion detection methods, such as real-time quaking-induced conversion (RT-QuIC), have shown promise in detecting abnormal prions from both antemortem and postmortem specimens. We compared RT-QuIC with ELISA and IHC for CWD detection utilizing deer retropharyngeal lymph node (RLN) tissues in a diagnostic laboratory setting. The RLNs were collected postmortem from hunter-harvested animals. RT-QuIC showed 100% sensitivity and specificity for 50 deer RLN (35 positive by both IHC and ELISA, 15 negative) included in our study. All deer were also genotyped for PRNP polymorphism. Most deer were homozygous at codons 95, 96, 116, and 226 (QQ/GG/AA/QQ genotype, with frequency 0.86), which are the codons implicated in disease susceptibility. Heterozygosity was noticed in Pennsylvania deer, albeit at a very low frequency, for codons 95GS (0.06) and 96QH (0.08), but deer with these genotypes were still found to be CWD prion-infected.

scholarly journals The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 563
Author(s):  
Jon Vincze ◽  
Brian W. Skinner ◽  
Katherine A. Tucker ◽  
Kory A. Conaway ◽  
Jonathan W. Lowery ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biological Effects ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Fractional Excretion ◽  
The United States ◽  
Vitamin D Supplementation ◽  
Loss Of Function ◽  
Case Presentation ◽  
Serum Inorganic Phosphate

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

scholarly journals A Synthetic Biology Approach Using Engineered Bacteria to Detect Perfluoroalkyl Substance (PFAS) Contamination in Water

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 801-807
Author(s):  
Nathaniel A Young ◽  
Ryan L Lambert ◽  
Angela M Buch ◽  
Christen L Dahl ◽  
Jackson D Harris ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Dna Sequences ◽  
Detection System ◽  
The United States ◽  
Detection Methods ◽  
Health Concern ◽  
Contaminated Water ◽  
Engineered Bacteria ◽  
Synthetic Biology Approach ◽  
Rhodococcus Jostii

ABSTRACT Introduction Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds used industrially for a wide variety of applications. These PFAS compounds are very stable and persist in the environment. The PFAS contamination is a growing health issue as these compounds have been reported to impact human health and have been detected in both domestic and global water sources. Contaminated water found on military bases poses a potentially serious health concern for active duty military, their families, and the surrounding communities. Previous detection methods for PFAS in contaminated water samples require expensive and time-consuming testing protocols that limit the ability to detect this important global pollutant. The main objective of this work was to develop a novel detection system that utilizes a biological reporter and engineered bacteria as a way to rapidly and efficiently detect PFAS contamination. Materials and Methods The United States Air Force Academy International Genetically Engineered Machine team is genetically engineering Rhodococcus jostii strain RHA1 to contain novel DNA sequences composed of a propane 2-monooxygenase alpha (prmA) promoter and monomeric red fluorescent protein (mRFP). The prmA promoter is activated in the presence of PFAS and transcribes the mRFP reporter. Results The recombinant R. jostii containing the prmA promoter and mRFP reporter respond to exposure of PFAS by activating gene expression of the mRFP. At 100 µM of perfluorooctanoic acid, the mRFP expression was increased 3-fold (qRT-PCR). Rhodococcus jostii without exposure to PFAS compounds had no mRFP expression. Conclusions This novel detection system represents a synthetic biology approach to more efficiently detect PFAS in contaminated samples. With further refinement and modifications, a similar system could be readily deployed in the field around the world to detect this critical pollutant.

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