Publications by authors named "Jordan Cheng"

11 Publications

  • Page 1 of 1

Methods and techniques for in vitro subcellular localization of radiopharmaceuticals and radionuclides.

Nucl Med Biol 2021 Apr 22;98-99:18-29. Epub 2021 Apr 22.

Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7EH, United Kingdom. Electronic address:

In oncology, the holy grail of radiotherapy is specific radiation dose deposition in tumours with minimal healthy tissue toxicity. If used appropriately, injectable, systemic radionuclide therapies could meet these criteria, even for treatment of micrometastases and single circulating tumour cells. The clinical use of α and β particle-emitting molecular radionuclide therapies is rising, however clinical translation of Auger electron-emitting radionuclides is hampered by uncertainty around their exact subcellular localisation, which in turn affects the accuracy of dosimetry. This review aims to discuss and compare the advantages and disadvantages of various subcellular localisation methods available to localise radiopharmaceuticals and radionuclides for in vitro investigations.
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http://dx.doi.org/10.1016/j.nucmedbio.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610823PMC
April 2021

Development and validation of a highly sensitive and specific electrochemical assay to quantify anti-SARS-CoV-2 IgG antibodies to facilitate pandemic surveillance and monitoring of vaccine response.

medRxiv 2020 Nov 16. Epub 2020 Nov 16.

Amperial™ is a novel assay platform that uses immobilized antigen in a conductive polymer gel followed by an electrochemical detection. A highly specific and sensitive assay was developed to quantify levels of IgG antibodies to SARS-CoV-2 in saliva. After establishing linearity and limit of detection we established a reference range of 5 standard deviations above the mean. There were no false positives in 667 consecutive saliva samples obtained prior to 2019. Saliva was obtained from 34 patients who had recovered from documented COVID-19 or had documented positive serologies. All of the patients with symptoms severe enough to seek medical attention had positive antibody tests and 88% overall had positive results. We obtained blinded paired saliva and plasma samples from 14 individuals. The plasma was analyzed using an EUA-FDA cleared ELISA kit and the saliva was analyzed by our Amperial™ assay. All 5 samples with negative plasma titers were negative in saliva testing. Eight of the 9 positive plasma samples were positive in saliva and 1 had borderline results. A CLIA validation was performed as a laboratory developed test in a high complexity laboratory. A quantitative non-invasive saliva based SARSCoV-2 antibody test was developed and validated with sufficient specificity to be useful for population-based monitoring and monitoring of individuals following vaccination.
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http://dx.doi.org/10.1101/2020.11.12.20230656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685352PMC
November 2020

Reviews on Current Liquid Biopsy for Detection and Management of Pancreatic Cancers.

Pancreas 2020 10;49(9):1141-1152

Center for Pancreatic Diseases, Yale University, New Haven, CT.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Pancreatic cancer presents dismal clinical outcomes in patients, and the incidence of pancreatic cancer has continuously increased to likely become the second most common cause of cancer-related deaths by as early as 2030. One of main reasons for the high mortality rate of pancreatic cancer is the lack of tools for early-stage detection. Current practice in detecting and monitoring therapeutic response in pancreatic cancer relies on imaging analysis and invasive endoscopic examination. Liquid biopsy-based analysis of genetic alterations in biofluids has become a fundamental component in the diagnosis and management of cancers. There is an urgent need for scientific and technological advancement to detect pancreatic cancer early and to develop effective therapies. The development of a highly sensitive and specific liquid biopsy tool will require extensive understanding on the characteristics of circulating tumor DNA in biofluids. Here, we have reviewed the current status of liquid biopsy in detecting and monitoring pancreatic cancers and our understanding of circulating tumor DNA that should be considered for the development of a liquid biopsy tool, which will greatly aid in the diagnosis and healthcare of people at risk.
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http://dx.doi.org/10.1097/MPA.0000000000001662DOI Listing
October 2020

Longitudinal Monitoring of and Mutations by Saliva-Based EFIRM in Advanced NSCLC Patients With Local Ablative Therapy and Osimertinib Treatment: Two Case Reports.

Front Oncol 2020 24;10:1240. Epub 2020 Jul 24.

School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States.

The longitudinal monitoring of actionable oncogenes in circulating tumor DNA (ctDNA) of non-small cell lung cancer (NSCLC) is crucial for clinicians to evaluate current therapeutic response and adjust therapeutic strategies. Saliva-based electric field-induced release and measurement (EFIRM) is liquid biopsy platform to that can directly detect mutation genes with a small volume of samples. Herein, we compared the effectiveness of longitudinal monitoring for the combination of epidermal growth factor receptor ( and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha ( mutations between saliva-based EFIRM and plasma-based platforms (ddPCR and NGS) in two advanced NSCLC patients undergoing the treatment with osimertinib before and after local ablative therapy (LAT). Two patients with unresectable advanced NSCLC were enrolled into the National Institutes of Health Clinical Center (NIHCC) Study (ClinicalTrials.gov: 16-C-0092; local ablative therapy for the treatment of oligoprogressive, -mutated, non-small cell lung cancer after treatment with osimertinib). Serial collections of saliva, plasma, and metastatic tumor volume measurement by computed tomography (CT) were performed. Longitudinal paired saliva and plasma samples were analyzed for p.L858R , and p.E545K ctDNA using EFIRM (saliva) and ddPCR and NGS (plasma). In Case 1, the saliva ctDNA curve of by EFIRM demonstrated a strong similarity to those of tumor volume ( = 0.78, = 0.00) and in ddPCR ( = 0.53, = 0.01). Moreover, the curve of p.E545K in EFIRM showed similarity to those of tumor volume ( = 0.70, = 0.00) and p.E545K in NGS ( = 0.72, = 0.00). In Case 2, the curve of p.E545K in EFIRM revealed a reverse relationship to that of tumor volume ( = -0.65, = 0.01). In these two case reports, saliva-based EFIRM platform demonstrates a high level of concordance to plasma-based platforms (ddPCR and NGS) for longitudinally monitoring the combination of and ctDNA and can be a useful platform to monitor tumor progression and response to targeted therapy in NSCLC patients.
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http://dx.doi.org/10.3389/fonc.2020.01240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393232PMC
July 2020

Electric Field-Induced Release and Measurement (EFIRM): Characterization and Technical Validation of a Novel Liquid Biopsy Platform in Plasma and Saliva.

J Mol Diagn 2020 08 1;22(8):1050-1062. Epub 2020 Jun 1.

UCLA School of Dentistry, University of California, Los Angeles, Los Angeles, California; Liquid Diagnostics LLC, San Clemente, California. Electronic address:

Electric field-induced release and measurement (EFIRM) is a novel, plate-based, liquid biopsy platform capable of detecting circulating tumor DNA containing EGFR mutations directly from saliva and plasma in both early- and late-stage patients with non-small-cell lung cancer. We investigated the properties of the target molecule for EFIRM and determined that the platform preferentially detects single-stranded DNA molecules. We then investigated the properties of the EFIRM assay and determined the linearity, linear range, precision, and limit of detection for six different EGFR variants (the four most common g.Exon19del variants), p.T790M, and p.L858R). The limit of detection was in single-digit copy number for the latter two mutations, and the limit of detection for Exon19del was 5000 copies. Following these investigations, technical validations were performed for four separate EFIRM liquid biopsy assays, qualitative and quantitative assays for both saliva and plasma. We conclude that EFIRM liquid biopsy is an assay platform that interrogates a biomarker not targeted by any other extant platform (namely, circulating single-stranded DNA molecules). The assay has acceptable performance characteristics in both quantitative and qualitative assays on both saliva and plasma.
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http://dx.doi.org/10.1016/j.jmoldx.2020.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416077PMC
August 2020

Acoustofluidic Salivary Exosome Isolation: A Liquid Biopsy Compatible Approach for Human Papillomavirus-Associated Oropharyngeal Cancer Detection.

J Mol Diagn 2020 01;22(1):50-59

Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina. Electronic address:

Previous efforts to evaluate the detection of human papilloma viral (HPV) DNA in whole saliva as a diagnostic measure for HPV-associated oropharyngeal cancer (HPV-OPC) have not shown sufficient clinical performance. We hypothesize that salivary exosomes are packaged with HPV-associated biomarkers, and efficient enrichment of salivary exosomes through isolation can enhance diagnostic and prognostic performance for HPV-OPC. In this study, an acoustofluidic (the fusion of acoustics and microfluidics) platform was developed to perform size-based isolation of salivary exosomes. These data showed that this platform is capable of consistently isolating exosomes from saliva samples, regardless of viscosity variation and collection method. Compared with the current gold standard, differential centrifugation, droplet digital RT-PCR analysis showed that the average yield of salivary exosomal small RNA from the acoustofluidic platform is 15 times higher. With this high-yield exosome isolation platform, we show that HPV16 DNA could be detected in isolated exosomes from the saliva of HPV-associated OPC patients at 80% concordance with tissues/biopsies positive for HPV16. Overall, these data demonstrated that the acoustofluidic platform can achieve high-purity and high-yield salivary exosome isolation for downstream salivary exosome-based liquid biopsy applications. Additionally, HPV16 DNA sequences in HPV-OPC patients are packaged in salivary exosomes and their isolation will enhance the detection of HPV16 DNA.
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http://dx.doi.org/10.1016/j.jmoldx.2019.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943372PMC
January 2020

Clinical validity of saliva and novel technology for cancer detection.

Biochim Biophys Acta Rev Cancer 2019 08 30;1872(1):49-59. Epub 2019 May 30.

Center for Oral and Head/Neck Oncology Research, School of Dentistry, University of California at Los Angeles, United States of America; UCLA's Jonsson Comprehensive Cancer Center, United States of America. Electronic address:

Cancer, a local disease at an early stage, systemically evolves as it progresses by triggering alterations in surrounding microenvironment, disturbing immune surveillance and further disseminating its molecular contents into circulation. This pathogenic characteristic of cancer makes the use of biofluids such as blood/serum/plasma, urine, tear and cerebrospinal fluids credible surrogates harboring tumor tissue-derived molecular alterations for the detection of cancer. Most importantly, a number of recent reports have credentialed the clinical validity of saliva for the detection of systemic diseases including cancers. In this review, we discussed the validity of saliva as credible biofluid and clinical sample type for the detection of cancers. We have presented the molecular constituents of saliva that could mirror the systemic status of our body and recent findings of salivaomics associated with cancers. Recently, liquid biopsy to detect cancer-derived circulating tumor DNA has emerged as a credible cancer-detection tool with potential benefits in screening, diagnosis and also risk management of cancers. We have further presented the clinical validity of saliva for liquid biopsy of cancers and a new technology platform based on electrochemical detection of cancer-derived ctDNA in saliva with superior sensitivity and point-of-care potential. The clinical utilities of saliva for the detection of cancers have been evidenced, but biological underpinning on the existence of molecular signatures of cancer-origin in saliva, such as via exosomal distribution, should be addressed in detail.
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http://dx.doi.org/10.1016/j.bbcan.2019.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692231PMC
August 2019

Salivary Exosomes as Nanocarriers for Cancer Biomarker Delivery.

Materials (Basel) 2019 Feb 21;12(4). Epub 2019 Feb 21.

Center for Oral/Head and Neck Oncology Research, School of Dentistry, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 73-017, Los Angeles, CA 90095, USA.

Human saliva is an ideal body fluid for developing non-invasive diagnostics. Saliva contains naturally-occurring nanoparticles with unique structural and biochemical characteristics. The salivary exosome, a nanoscale extracellular vesicle, has been identified as a highly informative nanovesicle with clinically-relevant information. Salivary exosomes have brought forth a pathway and mechanism by which cancer-derived biomarkers can be shuttled through the systemic circulation into the oral cavity. Despite such clinical potential, routine and reliable analyses of exosomes remain challenging due to their small sizes. Characterization of individual exosome nanostructures provides critical data for understanding their pathophysiological condition and diagnostic potential. In this review, we summarize a current array of discovered salivary biomarkers and nanostructural properties of salivary exosomes associated with specific cancers. In addition, we describe a novel electrochemical sensing technology, EFIRM (electric field-induced release and measurement), that advances saliva liquid biopsy, covering the current landscape of point-of-care saliva testing.
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http://dx.doi.org/10.3390/ma12040654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416587PMC
February 2019

Surveillance of HPV-Positive Head and Neck Squamous Cell Carcinoma with Circulating and Salivary DNA Biomarkers.

Crit Rev Oncog 2018 ;23(3-4):235-245

School of Dentistry, University of California Los Angeles, Los Angeles, California, United States of America.

Head and neck squamous cell carcinoma (HNSCC) manifests in the mucosal epithelial lining of the oral cavity, oropharynx, hypopharynx, nasopharynx or larynx and has a tremendous disease burden worldwide. Smoking and alcohol consumption were once major risk factors, but HPV-associated infection has emerged as the major contributor to HNSCC occurrence in developed countries. Circulating biomarker evaluations in biofluids, also known as liquid biopsy, are an attractive alternative for cancer screening as they are minimally invasive, potentially low cost, and easily repeatable on a serial basis. This review summarizes the current knowledge and potential of assessing circulating blood and salivary HPV DNA and HPV antibodies for the surveillance of HPV-positive HNSCC. Additionally, the biological underpinnings of the presence and relevance of circulating HPV DNA is discussed.
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http://dx.doi.org/10.1615/CritRevOncog.2018027689DOI Listing
July 2019

Electric Field-Induced Release and Measurement Liquid Biopsy for Noninvasive Early Lung Cancer Assessment.

J Mol Diagn 2018 11 8;20(6):738-742. Epub 2018 Oct 8.

School of Dentistry, University of California, Los Angeles, Los Angeles, California.

Previously, we detected circulating tumor DNA that contained two EGFR mutations (p.L858R and exon19 del) in plasma of patients with late-stage non-small-cell lung carcinoma (NSCLC) using the electric field-induced release and measurement (EFIRM) platform. Our aim was to determine whether EFIRM technology can detect these mutations in patients with early-stage NSCLC. Prospectively, 248 patients with radiographically determined pulmonary nodules were recruited. Plasma was collected before biopsy and histologic examination of the nodule. Inclusion criteria were histologic diagnosis of benign nodule (control) and stage I or II adenocarcinoma harboring either p.L858R or exon19 delEGFR mutations. Plasma samples were available from 44 patients: 23 with biopsy-proven benign pulmonary nodules and 21 with stage I or II adenocarcinoma (12 p.L858R and 9 exon19 delEGFR variants). Samples were analyzed for the EGFR mutations using the EFIRM platform. Assay sensitivity was 92% for p.L858R (11 of 12 samples positive) and 77% for exon19 del (7 of 9 samples positive). Specificity was 91% with two false-positive results in 23 patients with EGFR-positive nodules and 95% for the entire 44-patient series. Concordance was 100% with identical mutations discovered in plasma and nodule biopsy. The EFIRM platform is able to noninvasively detect two EGFR mutations in individuals with early-stage NSCLC.
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http://dx.doi.org/10.1016/j.jmoldx.2018.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198245PMC
November 2018

Caries and dental erosion: are Soroti children and adolescents at risk from increased soft-drink availability in Uganda?

Afr Health Sci 2016 Dec;16(4):943-946

Faculty of Dentistry, University of British Columbia, Canada.

Objective: An initial field study to investigate dental caries and dental erosion in children and adolescents in the community of Soroti, Uganda.

Methods: A stratified two-stage cluster sample of 84 children (ages 8-10) and adolescents (ages 16-19) were recruited. A survey was undertaken to assess the state of determinants of oral health, oral hygiene practices, and soft-drink and sweetened-tea consumption. Intra-oral photographs were taken and reviewed to measure Decayed, Missing, and Filled Teeth (DMFT) and dental erosion.

Results: A significant difference was observed in DMFT between children and adolescents (3.7 ± 2.7 versus 2.1 ± 2.4 p=.02). A trend of lower erosion scores was seen in children compared to adolescents. Greater frequency of sweetened-tea consumption over soft-drinks was noted in both groups.

Conclusion: This study did not reveal any relationship between different levels of cariogenic beverage consumption and DMFT or dental erosion in this sample group.
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http://dx.doi.org/10.4314/ahs.v16i4.9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398439PMC
December 2016