Publications & Scientific Posters

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PUBLICATIONS

Versatility of Amantadine and Rimantadine for Detection of Cancer

Journal: Novel Approaches in Cancer Study; Published on April 21, 2020

Our Approach: We have developed a simple test that evaluates SSAT- 1 activity by measuring acetylated products in the urine. On this basis, we believe that SSAT-1 activity can predict the presence of cancer and possibly disease progression.

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A High-Performing Plasma Metabolite Panel for Early-Stage Lung Cancer Detection

Journal: Caners; Published on March 7, 2020

Abstract: The objective of this research is to use metabolomic techniques to discover and validate plasma metabolite biomarkers for the diagnosis of early-stage non-small cell lung cancer (NSCLC).The study included plasma samples from 156 patients with biopsy-confirmed NSCLC along with age and gender-matched plasma samples from 60 healthy controls. A fully quantitative targeted mass spectrometry (MS) analysis (targeting 138 metabolites) was performed on all samples. The sample set was split into a discovery set and validation set. Metabolite concentration data, clinical data, and smoking history were used to determine optimal sets of biomarkers and optimal regression models for identifying different stages of NSCLC using the discovery sets. The same biomarkers and regression models were used and assessed on the validation models. Univariate and multivariate statistical analysis identified β-hydroxybutyric acid, LysoPC 20:3, PC ae C40:6, citric acid, and fumaric acid as being significantly different between healthy controls and stage I/II NSCLC. Robust predictive models with areas under the curve (AUC) > 0.9 were developed and validated using these metabolites and other, easily measured clinical data for detecting different stages of NSCLC. This study successfully

identified and validated a simple, high-performing, metabolite-based test for detecting early stage (I/II) NSCLC patients in plasma. While promising, further validation on larger and more diverse cohorts is still required.

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Liquid Biopsy in Lung Cancer Screening: The Contribution of Metabolomics. Results of A Pilot Study

Journal: Cancers; Published on July 29, 2019

Abstract: Background: Lung cancer is the most common cause of cancer-related deaths worldwide. Early diagnosis is crucial to increase the curability chance of the patients. Low dose CT screening can reduce lung cancer mortality, but it is associated with several limitations. Metabolomics is a promising technique for cancer diagnosis due to its ability to provide chemical phenotyping data. The intent of our study was to explore metabolomic effects and profiles of lung cancer patients to determine if metabolic perturbations in the SSAT-1/polyamine pathway can distinguish between healthy participants and lung cancer patients as a diagnostic and treatment monitoring tool. Patients and Methods: Plasma samples were collected as part of the SSAT1 Amantadine Cancer Study. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify and quantify metabolite concentrations in lung cancer patient and control samples. Standard statistical analyses were performed to determine whether metabolite concentrations could differentiate between healthy subjects and lung cancer patients, as well as risk prediction modeling applied to determine whether metabolic profiles could provide an indication of cancer progression in later stage patients. Results: A panel consisting of 14 metabolites, which included 6 metabolites in the polyamine pathway, was identified that correctly discriminated lung cancer patients from controls with an area under the curve of 0.97 (95% CI: 0.875-1.0). Conclusion: When used in conjunction with the SSAT-1/polyamine pathway, these metabolites may provide the specificity required for diagnosing lung cancer from

other cancer types and could be used as a diagnostic and treatment monitoring tool.

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Predictive value and clinical significance of increased SSAT-1 activity in healthy adults

Journal: Future Science OA; Published on July 1, 2019

Abstract: This study describes the potential of a novel noninvasive urine test for screening of cancer using a safe and approved drug, amantadine. We have previously measured high urinary concentration of the acetylated form of amantadine in patients diagnosed with cancer. However, higher than expected acetylated amantadine concentration was also measured in some of the healthy adult volunteers. Subsequent clinical assessments revealed that these healthy individuals could have early clinical signs of cancer. This is a simple test, which may serve as a useful tool for routine screening in populations considered at high risk for cancer.

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Follow-up evaluation of outliers with elevated spermine-spermidine acetyltransferase-1 activity

The 2019 American Society of Clinical Oncology (ASCO) Annual Meeting

Released on May 15, 2019

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Use of amantadine as substrate for SSAT-1 activity as a reliable clinical diagnostic assay for breast and lung cancer

Journal: Future Science OA; Published on December 11, 2018

Abstract: This study describes a novel noninvasive urine test for detecting and screening of breast and lung cancer using a safe and approved drug called amantadine. Higher concentration of the acetylated form of amantadine in the urine are detectable in the urine of both breast and lung cancer patients as compared with healthy adult volunteers. This test is simple and may serve as a useful tool for determining the presence of breast and lung cancer.

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Spermidine/spermine N1-acetyltransferase-1 as a diagnostic biomarker in human cancer

Journal: Future Science OA; Published on September 10, 2018

Abstract: In response to cancer, cells tend to overproduce specific enzymes as a self-defense mechanism. By using a safe and reliable method to capture and measure the excess enzyme spermidine/spermine N1-acetyltransferase-1, the presence of cancer can be established. This study describes a novel approach of detecting and screening cancer noninvasively in the urine of cancer patients using a safe and approved drug called amantadine that acts as a smart-tracking agent. Higher levels of the acetylated form of amantadine are detectable in the urine of cancer patients, which may serve as a detection tool. In addition, increases in the amount of spermidine/spermine N1-acetyltransferase-1 in tumor tissue may provide a tool for determining the presence of cancer during pathology assessment.

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SCIENTIFIC POSTERS

Liquid Biopsy in Lung Cancer Screening

Abstract: Lung cancer is the most common cause of cancer-related deaths worldwide. Early diagnosis is crucial to increase the curability chance of the patients. Low dose CT screening can reduce lung cancer mortality, but it is associated with several limitations. Metabolomics is a promising technique for cancer diagnosis due to its ability to provide chemical phenotyping data. The intent of our study was to explore metabolomic effects and profiles of lung cancer patients to determine if metabolic perturbations in the SSAT-1/polyamine pathway can distinguish between healthy participants and lung cancer patients as a diagnostic and treatment monitoring tool.

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Follow-up Evaluation of Outliers with Elevated SSAT-1 Activity

Abstract: In the evolving role of biomarkers, proteinomic signatures related to up-regulation of polyamine synthesis including spermine/spermidine acetyltransferase-1 (SSAT-1) appear to be promising markers of malignancy. Acetylamantadine (AA) excretion, a measure of SSAT-1 up-regulation, has been shown to be a marker for malignant proliferation. In preliminary analyses of ostensibly normal individuals from Canada (Winnipeg) and Bangladesh (Dhaka), a proportion were identified to have evidence of SSAT-1 up-regulation above the expected non-malignant range (outliers). These outliers were assessed and followed for development of identifiable medical conditions.

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Physiologically-based Pharmacokinetic Modeling of  Amantadine and Acetylamantadine Metabolites for Potential Applications as Cancer Biomarker

Abstract: Cancer is the second leading cause of death globally. Despite advances in treatment, there is a need for faster and economical screening tests for early diagnosis of cancer. Spermidine/spermine N1 -acetyltransferase (SSAT-1), an enzyme involved in the homeostasis of the polycationic aliphatic amines, spermine and spermidine, is overexpressed in many types of cancer cells. Amantadine is an FDA and Health Canada approved drug that is acetylated by SSAT-1 producing acetylamantadine, a terminal and stable end product excreted in urine. Recent studies suggest that that SSAT-1 based acetylation of amantadine could serve as a biomarker for lung cancer. However the SSAT-1 expression and activity within tumor compartments required to produce the reported levels of acetylamantadine as well as the potential use of amantadine for detection of tumor in other tissues is unclear.

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