Eleftherios P. Diamandis's research while affiliated with Mount Sinai Hospital, Toronto and other places
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Publications (998)
Background
Multiple sclerosis (MS) remains a highly unpredictable disease. Many hope that fluid biomarkers may contribute to better stratification of disease, aiding the personalisation of treatment decisions, ultimately improving patient outcomes.
Objective
The objective of this study was to evaluate the predictive value of CSF brain-specific pro...
There is increasing evidence that B cells play a significant role in the immunobiology of melanoma; however, reports of the pro- vs. antitumour roles of B cells are inconsistent. We hypothesized that advanced melanoma favours regulatory B-cell phenotypes and class switching to less effective antibody isotypes. We conducted an in-depth characterizat...
The most prevalent symptoms of post-COVID-19 condition are pulmonary dysfunction, fatigue and muscle weakness, anxiety, anosmia, dysgeusia, headaches, difficulty in concentrating, sexual dysfunction, and digestive disturbances. Hence, neurological dysfunction and autonomic impairments predominate in post-COVID-19 condition. Tachykinins including th...
B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells...
We aimed to study mRNA levels and prognostic impact of all 15 human kallikrein-related peptidases (KLKs) and their targets, proteinase-activated receptors (PARs), in surgically treated prostate cancer (PCa). Seventy-nine patients with localized grade group 2-4 PCas represented aggressive cases, based on metastatic progression during median follow-u...
The revolution in electronic publishing now allows for papers to be continuously critiqued through letters to the editor, online comments, tweets and other means. However, established top-ranked journals still pose serious barriers regarding cultivation, documentation and dissemination of post publication critiques (1). To improve on this situation...
Background:
Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the futur...
The amyloid hypothesis has so far been at the forefront of explaining the pathogenesis of Alzheimer's Disease (AD), a progressive neurodegenerative disorder that leads to cognitive decline and eventual death. Recent evidence, however, points to additional factors that contribute to the pathogenesis of this disease. These include the neurovascular h...
Prostate-specific antigen (PSA) is one of the best known and clinically useful cancer biomarkers. It is widely used for screening, diagnosis, and management of prostate cancer. PSA (also known as kallikrein-3, KLK3) belongs to a family of 15 genes called “tissue kallikreins “or “tissue kallikrein-related peptidases” and is a secreted serine proteas...
Objectives
Neurofilament light (NfL) chain is a marker of neuroaxonal damage in various neurological diseases. Here we quantitated NfL levels in the cerebrospinal fluid (CSF) and serum from patients with multiple sclerosis (MS) and controls, using the R-PLEX NfL assay, which employs advanced Meso Scale Discovery ® (MSD) electrochemiluminescence (EC...
Objectives
Allogeneic hematopoietic cell transplantation (HCT) is associated with acute graft-vs.-host disease (aGVHD). The presented study applied a novel multiplex antibody-based proximity extension assay (PEA) proteomic platform that can detect thousands of serum proteins simultaneously for the identification of potential biomarkers of aGVHD.
M...
Background
Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile [i.e., presence/absence of estrogen receptor (ER), progesterone receptor (PR)...
Background Gliomas are among the most malignant tumors, with a very poor prognosis. Early diagnosis is highly desirable since it can help implement more effective treatments for smaller tumors, which have not yet extensively metastasized. Improving early diagnosis may facilitate access of patients to clinical trials and prepare them for the future...
Objectives
Ovarian cancer is the most lethal gynecological malignancy in developed countries. One of the key associations with the high mortality rate is diagnosis at late stages. This clinical limitation is primarily due to a lack of distinct symptoms and detection at the early stages. The ovarian cancer biomarker, CA125, is mainly effective for i...
Objectives
Immune checkpoint inhibitors (ICIs) cause a variety of toxicities, including immune-related adverse events (irAEs), but there are no biomarkers to predict their development. Guidelines recommend measuring circulating cardiac troponin I (cTnI) during ICI therapy to detect related cardiotoxicities. Moreover, elevated cTnI has also been ass...
![Fig. 1. Log-transformed concentration [intensity units/mL (IU/mL)] of...](profile/Antigona-Ulndreaj/publication/364082519/figure/fig1/AS:11431281095003151@1667684156129/Log-transformed-concentration-intensity-units-mL-IU-mL-of-IgG-against-SARS-CoV-2_Q320.jpg)
Background:
There are numerous benefits to performing salivary serology measurements for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for coronavirus disease 2019 (COVID-19). Here, we used a sensitive multiplex serology assay to quantitate salivary IgG against 4 SARS-CoV-2 antigens: nucleocapsid, receptor-bi...
Babesia microti is an obligate intra-erythrocytic parasite transmitted by infected ticks. B. microti is a eukaryote much larger than prokaryotic microbes and more similar to human hosts in their biochemistry and metabolism. Moreover, Babesia spp. possess various immune evasion mechanisms leading to persistent and sometimes life-threatening diseases...
While coronavirus disease 2019 (COVID-19) begins as a respiratory infection, it progresses as a systemic disease involving multiorgan microthromboses that underly the pathology. SARS-CoV-2 enters host cells via attachment to the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is widely expressed in a multitude of tissues, including the lung (...
Cancer screening has been a major research front for decades. The classical circulating biomarkers for cancer (such as PSA, CEA, CA125, AFP, etc.) are neither sensitive nor specific and are not recommended for population screening. Recently, circulating tumor DNA (ctDNA) emerged as a new pan-cancer tumor marker, with much promise for clinical appli...
We recently published some concerns with new technologies which are based on circulating tumor DNA (ctDNA) for early cancer detection. Most of our published criticism, including a commentary in this journal, has focused on tests developed by the biotechnology company GRAIL (their commercial product is also known as The Galleri Test). Scientists fro...
Objectives
Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19) presents occasionally with an aberrant autoinflammatory response, including the presence of elevated circulating autoantibodies in some individuals. Whether the development of autoantibodies against sel...
As part of the efforts to contain the pandemic, researchers around the world have raced to develop testing platforms to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the Coronavirus disease 2019 (COVID-19). Within the different detection platforms studied, the field effect transistor (FET) is a promising devi...
Objectives
Widespread SARS-CoV-2 testing is invaluable for identifying asymptomatic/pre-symptomatic individuals. There remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests suitable for frequent mass testing. Compared to nasopharyngeal (NP) swab-based tests, saliva-based methods are attractive due to easier an...
Circulating tumor DNA (ctDNA) is a new pan-cancer tumor marker with important applications for patient prognosis, monitoring progression, and assessing the success of the therapeutic response. Another important goal is an early cancer diagnosis. There is currently a debate if ctDNA can be used for early cancer detection due to the small tumor burde...
Probing the human proteome in tissues and biofluids such as plasma is attractive for biomarker and drug target discovery. Recent breakthroughs in multiplex, antibody-based, proteomics technologies now enable the simultaneous quantification of thousands of proteins at as low as sub fg/mL concentrations with remarkable dynamic ranges of up to 10-log....
Introduction: Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (dflow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell gene expression, which regulates endothelial...
Background:
Azoospermia could be due to either obstruction (obstructive azoospermia: OA) or spermatogenic failure (non-obstructive azoospermia: NOA). Close to 50% of men with NOA have small pockets of sperm in the testis which could be retrieved surgically and then injected into oocytes in a program of intra-cytoplasmic sperm insertion. Presently,...
Neurofilament light (NfL) is a promising biomarker of neurodegeneration in Alzheimer's disease (AD). In this study, cerebrospinal fluid (CSF) NfL was measured in a 24-month longitudinal cohort consisting of control (n = 52), amnestic mild cognitive impairment (aMCI) (n = 55), and probable AD dementia (n = 28) individuals. The cohort was reevaluated...
Background: In this pilot study, we perform a preliminary comparison of two targeted multiplex
proteomics technologies for discerning serum protein concentration changes that may correlate to tumor burden in ovarian cancer (OC) patients.
Methods : Using the proximity extension assay (PEA) and Quantibody® Kiloplex Array (QKA), we measured >1,000 pro...
Objectives
Severe traumatic brain injury (sTBI) patients suffer high mortality. Accurate prognostic biomarkers have not been identified. In this exploratory study, we performed targeted proteomics on plasma obtained from sTBI patients to identify potential outcome biomarkers.
Methods
Blood sample was collected from patients admitted to the ICU suf...
Background
Cancer immunotherapy with monoclonal antibodies and chimeric antigen receptor (CAR) T cell therapies can benefit from selection of new targets with high levels of tumor specificity and from early assessments of efficacy and safety to derisk potential therapies.
Methods
Employing mass spectrometry, bioinformatics, immuno-mass spectrometr...
A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA...
The detection of cancer at an early stage while it is curable by surgical resection is widely believed to be one of the most effective strategies for reducing cancer mortality. Hence, the intense interests in the development of a simple pan-cancer screening test. Lack of sensitivity and specificity when combined with the low prevalence of most type...
Since its initial outbreak in late 2019, the COVID-19 pandemic has profoundly affected the global community. In addition to the negative health consequences of contracting COVID-19, the implementation of strict quarantine and lockdown measures has also disrupted social networks and devastated the global economy. As a result, there is rising concern...
Immune checkpoint inhibitors (ICIs) have significantly improved advanced cancer outcomes. Although ICIs unleash anti-tumor immune responses, negating natural immune inhibitory mechanisms can result in the development of self-reactive immune cells and an array of immune-related adverse events (irAEs). Although reports of serious myocarditis have eme...
Widespread SARS-CoV-2 testing is highly valuable for identifying asymptomatic/pre-symptomatic individuals to slow community disease transmission. However, there remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests that are suitable for frequent mass testing. Compared to the conventional nasopharyngeal (NP) sw...
Background
In addition to deposits of amyloid β (Aβ) plaques and neurofibrillary tangles, growing evidence demonstrates that complex and multifaceted biological processes can arise during Alzheimer disease (AD) pathogenesis. The recent failures of clinical trials based on the amyloid hypothesis and the presence of Aβ plaques in cognitively healthy...
Early detection of cancer has been a major research focus for almost a century. Current methods for early cancer detection suffer from suboptimal sensitivity and specificity, especially when used for population screening. For most major cancers, including breast, prostate, lung, ovarian, and pancreatic cancer, population screening is still controve...
Background
It has long been known that mutations are at the core of many diseases, most notably cancer. Mutational analysis of tissues and fluids is useful for cancer and other disease diagnosis and management.
Main body
The prevailing cancer development hypothesis posits that cancer originates from mutations in cancer-driving genes that accumulat...
In-depth analysis of the human genome sequence has led to the annotation of approximately 20,000 human protein-coding genes. Although mass spectrometry (MS)-based workflows have made a great headway in achieving near genome-wide coverage, an equivalent complete map of the human proteome remains elusive. Delineating the spatial distribution of all h...
Background
High-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer. A growing body of evidence suggests tumor-supporting roles of several members of the kallikrein-related peptidase (KLK) family, including KLK5 and KLK7, in this cancer subtype. In normal physiology, KLK5 and KLK7 are the major proteases invo...
Objectives:
To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant PCa (CRPC), and cancer-specific survival (CSS), following therapy for localized disease.
Methods:
A single-center retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR...
Background
We investigated an ultrasensitive prostate-specific antigen (uPSA) immunoassay (MesoScale; lower limit of detection (LLD) of 0.0035 pg/mL) to monitor patients with prostate cancer (PCa) following radical prostatectomy (RP) and to examine whether changes in PSA in the conventionally undetectable range (<1 pg/mL) can predict biochemical re...
Objectives:
Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic...
There is an ongoing scientific debate regarding the merits and shortcomings of P4 Medicine (predictive, preventive, personalized, and participatory) and O4 Medicine (overtesting, overdiagnosis, overtreatment, and overcharging). P4 Medicine promises to revolutionize scientific wellness through longitudinal big data collection, denoted as "dense phen...
Objective: Owing to tumor heterogeneity, we hypothesize that each tumor secretes a unique mixture of tumor-related proteins into the bloodstream, which when quantified can serve as personalized markers of tumor load. We previously introduced the concept of "personalized tumor markers", which are highly sensitive for monitoring tumor load in a small...
Background: To account for cancer heterogeneity, we previously introduced the concept of “personalized” tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual p...
The skin is a vital organ of the human body, serving numerous protective and functional roles that are essential for survival. Residing in the epidermis are various epidermal proteases responsible for the establishment and regulation of barrier function. The human tissue kallikrein-related peptidase family conserves homeostasis of the skin barrier...
Diabetes is the leading cause of end-stage renal disease worldwide. Our understanding of the early kidney response to chronic hyperglycemia remains incomplete. To address this, we first investigated the urinary proteomes of otherwise healthy youths with and without type 1 diabetes and subsequently examined the enriched pathways that might be dysreg...
https://doi.org/10.1016/j.neulet.2020.135078
Multifactorial pathological processes of Alzheimer’s disease (AD) begin decades prior to clinical onset. Early identification of patients at risk of developing AD using biomarkers reflecting various aspects of pathogenesis is necessary for prevention and early intervention. Cortical β-amyloid (Aβ) burde...
Background: Validated biomarkers are needed to identify patients at increased risk of immune-related adverse events (irAEs) to immune checkpoint blockade (ICB). Antibodies directed against endogenous antigens can change after exposure to ICB.
Methods: Patients with different solid tumors stratified into cohorts received pembrolizumab every 3 weeks...
Cerebrospinal fluid (CSF) is a circulatory fluid of the central nervous system (CNS) and it can reflect the biochemical changes occurring in the brain. Although CSF retrieval through lumbar puncture is invasive, it remains the most commonly used fluid in exploring brain pathology as it is less complex and contains a higher concentration of brain de...
Despite significant investment of funds and resources, few new cancer biomarkers have been introduced to the clinic in the last few decades. Although many candidates produce promising results in the laboratory, deficiencies in sensitivity, specificity, and predictive value make them less than desirable in a patient setting. This review will analyze...
Immune checkpoint blockade (ICB) is a breakthrough form of cancer immunotherapy that employs antibody targeting of specific inhibitory receptors and ligands, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The major limitations of ICB are high cost, li...
The important conclusion that ctDNA is a mediocre proxy for liquid biopsies of tumor tissues for early detection was reached after new data were published recently in Nature Genetics . These data have shown that most mutations found in ctDNA are not related to tumor tissues but rather to the precancerous condition clonal hematopoiesis. Previously,...
We teach and practice ethical behavior with all clinical and research activities. Notably, we are well educated to treat the subjects participating in research studies with high ethical standards. However, the ethics of interacting with colleagues, or with junior faculty members, are neither well defined nor taught. Dealing with junior faculty has...
Chronic hyperglycemia is known to disrupt the proteolytic milieu, initiating compensatory and maladaptive pathways in the diabetic kidney. Such changes in intrarenal proteolysis are captured by the urinary peptidome. To elucidate the early kidney response to chronic hyperglycemia, we conducted a peptidomic investigation into urines from otherwise h...
![Abbreviations [ 11 C]PiB: Pittsburgh Compound B; [ 18 F]FDG-PET: [ 18...](publication/335436446/figure/fig5/AS:796673412452352@1566953151901/Abbreviations-11-CPiB-Pittsburgh-Compound-B-18-FFDG-PET-18-FFluoro-D-glucose_Q320.jpg)
Background:
Alterations in the expression of human kallikrein-related peptidases (KLKs) have been described in patients with Alzheimer's disease (AD). We elucidated the suitability of KLK6, KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers.
Methods:
KLK levels in cerebrospinal fluid (CSF), as deter...
Background:
Inflammatory arthritis (IA) is an immunological disorder in which loss of immune tolerance to endogenous self-antigens perpetuates synovitis and eventual destruction of the underlying cartilage and bone. Pathological changes in the joint are expected to be represented by synovial fluid (SF) proteins and peptides. In the present study,...
Where should I submit my paper? This is a question that young scientists and trainees frequently ask. In this Commentary, we advise on how to make such a decision whilst balancing the risks and benefits. We argue that trying to publish in top tier journals may not always be the best option and that publishing in indexed, open access journals may ex...
[This corrects the article DOI: 10.1186/s12014-019-9246-0.].
Renal cell carcinoma (RCC) is often diagnosed incidentally as a small renal mass (SRM; pT1a, ≤4 cm). Increasing concerns surrounding the overtreatment of patients with benign or clinically silent SRMs has resulted in a recent shift in treatment recommendations, especially in elderly and infirm patients. There are currently no biomarkers that can pr...
