Myron Szewczuk

Queen's University | QueensU · Department of Biomedical and Molecular Sciences

Folate receptor alpha (FRα) is a glycosylphosphatidylinositol (GPI) membrane-anchored protein containing three N-glycosylated residues at the N47, N139, and N179 termini. These glycosylation sites have been reported to be crucial for the receptor’s structural integrity and its ability to bind and internalize FA. Here, we investigated the role of FR...

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the i...

Simple Summary Non-nutritive sweeteners (NNS) are widely used by individuals to lower their caloric intake, lose weight, and sustain a healthy diet. The specific mechanistic details of the effects of NNS consumption by individuals on host metabolism and energy homeostasis are unknown. This topic is highly relevant as NNS has been promoted as an opt...

Understanding the role of biased G protein-coupled receptor (GPCR) agonism in receptor signaling may provide novel insights into the opposing effects mediated by cannabinoids, particularly in cancer and cancer metastasis. GPCRs can have more than one active state, a phenomenon called either ‘biased agonism’, ‘functional selectivity’, or ‘ligand-dir...

Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgica...

Mutations and the glycosylation of epitopes can convert immunogenic epitopes into non-immunogenic ones via natural selection or evolutionary pressure, thereby decreasing their sensitivity to neutralizing antibodies. Based on Thomas Francis’s theory, memory B and T cells induced during primary infections or vaccination will freeze the new mutated ep...

Our understanding of angiogenesis has significantly expanded over the past five decades. More recently, research has focused on this process at a more molecular level, looking at it through the signaling pathways that activate it and its non-direct downstream effects. This review discusses current findings in molecular angiogenesis, focusing on its...

Simple Summary YAP/TAZ are the central effectors of the Hippo pathway and orchestrate their oncogenic program by binding to TEAD transcriptional factors. Here, we document a comprehensive understanding of how YAP/TAZ dependent tumors could be exploited for improving cancer therapies. Aside from providing the recent updates to the YAP/TAZ oncogenic...

Since the discovery of insulin over 100 years ago, our understanding of the insulin signaling pathway has greatly expanded [...]

We discovered a novel therapeutic target critical for SARS-CoV-2, cellular infectivity and the induction of the cytokine release syndrome. Here, we show that the mammalian enzyme neuraminidase-1 (Neu-1) is part of a highly conserved signaling platform that regulates the dimerization and activation of the ACE2 receptors and the TOLL-like receptors (...

Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing tissues. It also plays a vital role in the development of neoplastic disorders. Pentoxifylline (PTX) is a vasoactive synthetic methyl xanthine derivative used for decades to manage ch...

Epigenetic reprogramming predicts the long-term functional health effects of health-related metabolic disease. This epigenetic reprogramming is activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The epigenetic and environmental changes involve a roadmap of epigenetic networking, such as dietary co...

The concept of epigenetic reprogramming predicts long-term functional health effects. This reprogramming can be activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The exogenous or endogenous changes that involve developing a roadmap of epigenetic networking, such as drug components on epigenetic i...

[This corrects the article DOI: 10.18632/oncotarget.28011.].

Metastatic pancreatic cancer has an invariably fatal outcome, with an estimated median progression-free survival of approximately six months employing our best combination chemotherapeutic regimens. Once drug resistance develops, manifested by increased primary tumor size and new and growing metastases, patients often die rapidly from their disease...

Resistance to chemotherapeutics and high metastatic rates contribute to the abysmal survival rate in patients with pancreatic cancer. An alternate approach for treating human pancreatic cancer involves repurposing the anti-inflammatory drug, aspirin (ASA), with oseltamivir phosphate (OP) in combination with the standard chemotherapeutic agent, gemc...

Thymoquinone has anti-cancer properties. However, its application for clinical use is limited due to its volatile characteristics. The current study aims to develop a polymeric nanoformulation with PLGA-PEG and Pluronics F68 as encapsulants to conserve thymoquinone’s (TQ) biological activity before reaching the target sites. Synthesis of nanopartic...

Objective: Aberrations in the PI3K/AKT/mTOR survival pathway in many cancers are the most common genomic abnormalities. The phytochemical and bioactive agent sulforaphane (SFN) has nutrigenomic potential in activating the expression of several cellular protective genes via the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2)...

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpresse...

Therapeutic targeting of stem cells needs to be strategically developed to control tumor growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes present, including cancer stem cells (CSCs). The development of 3D stem-like properties of human breast tumor spheroi...

We have previously reported on a functionalized folic acid (FA) conjugated poly(styrene-alt-maleic anhydride) (SMA) via biological linker 2,4-diaminobutyric acid (DABA) (FA-DABA-SMA) copolymer. This biocompatible nanocopolymer self-assembles in a pH-dependent manner, providing stimuli responsiveness, active targeting, and extended release of hydrop...

Advancements in our understanding of the complex process of tumorigenesis have uncovered the many challenges faced by current systemic therapeutic options for the treatment of cancer. Drug delivery systems (DDS), particularly in the context of nanomedicine, have demonstrated a remarkable ability to overcome many of the physiological challenges asso...

Background Aspirin (acetylsalicylic acid) and celecoxib have been used as potential anti-cancer therapies. Aspirin exerts its therapeutic effect in both cyclooxygenase (COX)-dependent and -independent pathways to reduce tumor growth and disable tumorigenesis. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduces factors that cause infl...

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selectiv...

Introduction Targeted multimodal approaches need to be strategically developed to control tumour growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes that arise. The tumour stage and cellular subtypes often dictate the appropriate clinical treatment regimen....

Introduction Core fucosylation of N-glycans on the integrin β1 subunit is essential for the functional activity of the integrin. The binding of α5β1 integrin with the tripeptide Arg-Gly-Asp (RGD) motif within the extracellular matrix protein fibronectin may be influenced by the α-1,6-fucose core or α-1,2-fucose and α-1,3/4-fucose peripheral N-glyca...

Nanomedicine as a multimodality treatment of cancer utilizes the advantages of nanodelivery systems of drugs. They are superior to the clinical administration of different therapeutic agents in several aspects, including simultaneous delivery of drugs to the active site, precise ratio control of the loading drugs and overcoming multidrug resistance...

Metastatic breast cancer is the most common cancer in women after skin cancer, with a 5-year survival rate of 26%. Due to its high prevalence, it is important to develop therapies that go beyond those that just provide palliation of symptoms. Currently, there are several types of therapies available to help treat breast cancer including: hormone th...

Recent advancements in cancer research have led to a deeper understanding of tumor biology and uncovered the crucial role of the tumor microenvironment (TME) in promoting multistage tumorigenesis. As such, it is widely accepted that the tumor microenvironment is plastic and can shape a tumor’s response to therapy and subsequently contribute to the...

The complex process of cancer development and tumorigenesis involves several critical events that take place concurrently or build upon each other, ultimately manifesting as a malignancy with therapeutically targetable components. Given the broad and unspecific cytotoxic effects of chemotherapy, supplementing conventional therapeutic options with t...

Purpose The potential physical or psychosocial factors that play a role in the progression of childhood cancer survivors into adulthood are essential in the identification of an effective patient-centred approach to therapy. Despite the presence of guidelines published by the Children’s Oncology Group, knowledge of the long-term health sequelae for...

Individuals widely use non-nutritive sweeteners (NNS) in attempts to lower their overall daily caloric intake, lose weight, and sustain a healthy diet. There are insufficient scientific data that support the safety of consuming NNS. However, recent studies have suggested that NNS consumption can induce gut microbiota dysbiosis and promote glucose i...

Cancer immunotherapy is a promising innovative treatment for many forms of cancer, particularly melanoma. Although immunotherapy has been shown to be efficacious, patient response rates vary and, more often than not, only a small subset of the patients within a large cohort respond favourably to the treatment. This issue is particularly concerning...

Bessi Qorri,1 William Harless,2 Myron R Szewczuk1 1Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada; 2ENCYT Technologies Inc., Membertou, Nova Scotia, CanadaCorrespondence: Myron R SzewczukDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, CanadaTel +1 613 533...

Targeted therapies were initially developed to exploit the upregulation and dependence on key oncogenic pathways critical to cancer progression. Additionally, they also presented as a method to overcome chemoresistance by supplementing conventional therapeutic regimens with targeted therapies. However, the development of resistance to these combina...

The extracellular matrix (ECM) is a highly dynamic noncellular structure that is crucial for maintaining tissue architecture and homeostasis. The dynamic nature of the ECM undergoes constant remodeling in response to stressors, tissue needs, and biochemical signals that is are mediated primarily by matrix metalloproteinases (MMPs), which work to de...

Advances in nanomedicine have become indispensable for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. Nanoparticle-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy administration, such as reduced drug solubility, chemoresistance, syst...

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treat...

With the proposed Canadian July 2018 legalization of marijuana through the Cannabis Act, a thorough critical analysis of the current trials on the efficacy of medicinal marijuana (MM) as a treatment option is necessary. This review is particularly important for primary care physicians whose patients may be interested in using MM as an alternative t...

Insulin signaling, as mediated through the insulin receptor (IR), plays a critical role in metabolism. Aberrations in this signaling cascade lead to several pathologies, the majority of which are classified under the umbrella term "metabolic syndrome". Although many of these pathologies are associated with insulin resistance, the exact mechanisms a...

Pickering emulsions are colloidal dispersions stabilized by particles that either migrate to, or are formed at, the oil-water interface during emulsification. Here, we fabricated and characterized Pickering water-in-oil emulsions where molten glycerol monostearate crystallized at the surface of micron-sized water droplets and formed protective soli...

G protein-coupled receptors (GPCR) can participate in a number of signaling pathways, and this property led to the concept of biased GPCR agonism. Agonists, antagonists and allosteric modulators can bind to GPCRs in different ways, creating unique conformations that differentially modulate signaling through one or more G proteins. A novel neuromedi...

To test the efficacy of novel antitumor drugs and delivery systems, in vitro models that mimic solid tumors are necessary. Three-dimensional (3D) models such as multicellular tumor spheroids (MTS) have been deemed superior to two-dimensional (2D) cell cultures due to their ability to mimic the 3D nature of solid tumors. Although several methods exi...

Despite the controversies surrounding the therapeutic use of cannabis in the treatment of several medical conditions, the fact remains that there is a scientific rationale for its use, particularly in the treatment of colorectal cancer (CRC). Constituents of cannabis such as CBD have demonstrated anti-cancer effects via endocannabinoid signaling. H...

Colorectal cancer (CRC) is the third most commonly diagnosed cancer [1]. Although the advent of metastasis is only observed in 20% of patients who present with this malignancy [2], metastatic disease remains the leading cause of death in patients with CRC [3]. Aberrant patterns of glycosylation have emerged as a fundamental characteristic of cancer...

The gastrointestinal (GI) tract is colonized by trillions of microorganisms that play a vital role in maintaining homeostasis, contributing to several local and systemic processes including digestion, and have been shown to influence the immune response. Although the crucial contributions of the gut microbiota have been studied in great detail in r...

Combination therapies against multiple targets are currently being developed to prevent resistance to a single chemotherapeutic agent and to extirpate pre-existing resistance in heterogeneous cancer cells in tumors due to selective pressure from the single agent. Gemcitabine (GEM), a chemotherapeutic agent, is the current standard of care for patie...

The therapeutic potential of polymeric nanoparticles has garnered attention due to the multiple applications for which this technology can be used. This is particularly important for cancer as many of the cytotoxic drugs that are used to treat patients have negative side effects on healthy cells. Polymeric nanoparticle technology can reduce these n...

Today, emerging therapies must effectively shut down multiple enabling characteristics that drive pancreatic cancer invasion and progression. These therapies include the concomitant suppression of growth factor signaling and anti-apoptotic pathways, immune-derived promoters of tumorigenesis, mechanisms of acquired drug resistance, as well as pro-me...

Background Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell–cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking i...

Gastrointestinal (GI) cancer is an all-encompassing term that refers to the forms of cancers of the digestive system including the esophagus, liver, gallbladder, stomach, small intestine, colon, rectum, anus and pancreas. Of the cancers mentioned, pancreatic ductal adenocarcinoma (PDAC) is the most deadly form of GI cancer owing partially to the la...

One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse...

Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA...

KRAS mutations: efficacy and sensitivity of early predictive screening of cancer progression require other gene mutations in addition to KRAS

Multicellular tumor spheroids (MTS) have been at the forefront of cancer research, designed to mimic tumor-like developmental patterns in vitro. Tumor growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS formation are not well defined. Matrix...

Pancreatic cancer, the fourth leading cause of cancer-related death worldwide, is highly aggressive and associated with a poor prognosis. Resistance to drug therapy, along with high rates of metastasis, contributes to the low survival rates in patients diagnosed with pancreatic cancer. Gemcitabine, a chemotherapeutic agent, is the current standard...

Targeted drug delivery using polymeric nanostructures has been at the forefront of cancer research, engineered for safer, more efficient and effective use of chemotherapy. Here, we designed a new polymeric micelle delivery system for active tumor targeting followed by micelle-drug internalization via receptor-induced endocytosis. We recently report...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Patients with triple-negative breast cancers (TNBCs) lacking the estrogen, progesterone, and epidermal growth factor (EGF) receptor-2 (HER2/neu) receptors have typical high grading, frequent relapses, and exhibit poorer outcomes or prognosis compared with the other su...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Snail is a transcriptional factor and repressor of E-cadherin. It is well known for its role in cellular invasion, epithelial to mesenchymal transition (EMT), tumor progression and metastases. shRNA lentiviral knockdown (KD) of Snail and its associated member Slug in...

Several of the growth factors and their receptor tyrosine kinases (RTK) such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and insulin are promising candidate targets for cancer therapy. Indeed, tyrosine kinase inhibitors...

Poly (lactic co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Her...

Background Triple-negative breast cancers (TNBCs) lack the estrogen, progesterone, and epidermal growth factor (EGF) receptor-2 (HER2/neu) receptors. Patients with TNBC have typical high grading, more frequent relapses, and exhibit poorer outcomes or prognosis compared with the other subtypes of breast cancers. Currently, there are no targeted ther...

Insulin receptor (IR) signaling plays a key role in the regulation of glucose homeostasis. A dysfunctional and/or unregulated IR activation has been shown to cause a range of clinical manifestations including insulin resistance, type 2 diabetes, obesity, cancer, hypertension, and cardiovascular disorders. The molecular mechanisms mediating IR activ...

Snail, a transcriptional factor and repressor of E-cadherin is well known for its role in cellular invasion. It can regulate epithelial to mesenchymal transition (EMT) during embryonic development and in epithelial cells. Snail also mediates tumor progression and metastases. Silencing of Snail and its associate member Slug in human A2780 ovarian ep...