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Electronic Theses and Dissertations (ETD) Repository This section preserves Master's theses and doctoral dissertations accepted at Laurentian University and is a mechanism for making this form of scholarly work widely accessible.

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Recent Submissions

Access status: Open Access ,
Investigating the role of prostaglandin system dysregulation in radiation resistance of triple negative breast cancer cells
(Laurentian University Library & Archives, 2024-12-13) Dickinson, Noah A.; Dr. Sujeenthar Tharmalingam, Dr. Tom Kovala
The overall goal of this research program was to elucidate the molecular mechanisms underlying radiation resistance in breast cancer. Prostaglandin (PG) signaling dysregulation has been implicated in various aspects of cancer progression, including tumor growth, metastasis, and inflammation, but its potential role in promoting radiation resistance remains underexplored. Among the key components of the PG system, prostaglandin-endoperoxide synthase 2 (PTGS2) emerged as a critical mediator potentially driving this resistance mechanism. Therefore, the primary aim of this study was to investigate the role of PTGS2 dysregulation in the development of radiation resistance in triple-negative breast cancer cells. To address this gap, radiation resistant variants of MDA-MB-231 cells were generated by repeated exposures to x-ray radiation (57 Gy total dose) followed by clonal cell selection. RT-qPCR and Western blot analysis revealed robust upregulation of PTGS2 mRNA and protein expression in radiation resistant cells compared to the parental MDA-MB-231Control cells. Whole-transcriptome analysis further corroborated these results, whereby radiation resistant variants demonstrated a 16.7-fold (p<0.05) increase in PTGS2 mRNA expression. In addition, 6 Gy radiation challenge further increased PTGS2 expression 48 hours post radiation exposure (76% increase; p<0.05) in radiation resistant variants, whereas the MDA-MB-231Control cells showed lack of PTGS2 expression changes. The next goal was to determine whether the upregulation of PTGS2 expression in MDA-MB-231 cells promoted the development of radiation resistance. Here, PTGS2 was overexpressed using the CRISPR/dCas9 system, and expression was verified using RT-qPCR and Western blotting. Surprisingly, PTGS2 overexpression led to decreased survival following radiation exposure. This suggests that although PTGS2 is upregulated in radiation-resistant cells, its overexpression alone makes the cells more susceptible to radiation-induced damage. In addition, PTGS2 overexpression reduced adhesion to fibronectin and increased anchorage independent growth. These changes suggest that PTGS2 promotes a more aggressive cancer phenotype by enhancing cell detachment and survival in non-anchorage conditions. Taken together, this study highlights the role of PTGS2 in the development of radioresistance, suggesting that PTGS2 and its downstream effectors within the prostaglandin signaling pathway may serve as promising therapeutic targets for therapy resistant cancers.
Access status: Open Access ,
Biodegradation of polyethylene terephthalate (PET) : a critical review
(Laurentian University Library & Archives, 2025-08-26) Patel, Kishankumar Bharatbhai; Dr. Sujeenthar Tharmalingham
Polyethylene terephthalate (PET) is a highly persistent plastic pollutant that undergoes minimal natural degradation, prompting increasing interest in biological strategies as alternatives to conventional recycling methods. This critical review systematically analyzed 152 peer-reviewed studies, categorized into four methodological groups: enzyme-only, microbial-only, combined, and unconventional approaches to PET biodegradation. Studies were identified through structured searches and selected based on relevance, methodological quality, and availability of degradation data. Enzymatic systems - particularly engineered variants of PETase and cutinase - demonstrated high depolymerization efficiencies under optimized laboratory conditions. Microbial approaches effectively metabolized PET breakdown products across diverse environments but generally exhibited slower performance. Hybrid systems integrating enzymes, microorganisms, or pretreatments showed enhanced overall conversion, while unconventional strategies offered proof-of-concept insights with limited validation. Despite these advances, key challenges remain, including the lack of standardized degradation metrics, difficulties in scaling processes, and inconsistent substrate characterization. This review consolidates existing findings into systematic pathways, highlights recurring limitations, and outlines application contexts. The future of PET biodegradation will depend on continued innovations in enzyme engineering, microbial design, and integrated systems, with emphasis on improving efficiency and scalability to enable practical, real-world implementation within sustainable plastic waste management frameworks.
Access status: Open Access ,
Mineralogical, textural, and chemical thermodynamic constraints of the Crawford Ni-Co-(PGE) deposit, Abitibi greenstone belt, Superior Province, Ontario, Canada
(Laurentian University Library & Archives, 2025-04-17) Carter, Nathan; Dr. Pedro Jugo
The 2704 ± 0.88 Ma Crawford Ni-Co-(PGE) deposit, located 50 km north of Timmins, is hosted in a mafic-ultramafic intrusion emplaced within volcanic rocks of the Stoughton-Roquemaure assemblage in the Abitibi greenstone belt. The intrusion shows progressive stages of serpentinization, and nickel mineralization occurs dominantly in the dunitic section of the intrusion as disseminated to patchy net-textured assemblages containing pentlandite, heazlewoodite, and awaruite. The deposit is dissected into two bodies (the western body and the eastern body) by a Proterozoic N-NW sinistral strike-slip fault. An assumed Archean fault cuts the eastern body parallel its dunitic-peridotitic core. The main goal of the project was to document the effects of serpentinization and extract mineralogical and geochemical parameters from present mineral assemblages to better understand mineralization processes and assist in locating and evaluating similar deposits elsewhere. Ninety-one samples were collected from eight drill holes based on core-logging and preliminary petrography. The suite of samples collected includes dunite, peridotite, pyroxenite, and gabbro. However, the focus of the work was on the dunitic samples since those are the intervals hosting the Ni mineralization. The mineralogy and textures were characterized using optical microscopy and SEM-EDS. A subset of samples was analyzed by EPMA. The results show that the dunites were almost monomineralic adcumulates consisting of subhedral olivine, typically containing less than 5% pyroxene, chromium spinel, and primary sulfides. Samples from the East zone are completely serpentinized, whereas samples from the Main-West zone range from completely serpentinized near a fault to approximately 20% towards the western margin of the intrusion and away from a fault. Serpentinization also affected accessory minerals. Samples from the Main-West zones record the progressive destruction of primary olivine and pentlandite during serpentinization and the appearance of secondary heazlewoodite and awaruite. Completely serpentinized samples contain heazlewoodite, awaruite, and secondary magnetite, but only minor relict pentlandite. Native copper was observed in some samples and was used to assess changes in sulfur and oxygen fugacity during serpentinization. Olivine composition could be extracted from samples where primary olivine was preserved. On average, olivine grains are Fo88 ± 1 and have 2,800 ± 350 ppm Ni (average range: 2,200 to 3,380 ppm). Nickel-bearing mineral composition yields Fe4.6Ni4.1S8 for pentlandite (i.e., with an Fe:Ni ratio close to 1:1), stoichiometric heazlewoodite (Ni3S2), and Ni2.5Fe for awaruite. Rare primary Cr-spinel (Mg# 0.53 ± 0.08; Cr# 0.67 ± 0.02) is mostly preserved but secondary magnetite is also present. The mineralogical changes indicate loss of sulfur during serpentinization, mobilization of Fe, Ni, and Cu, and the release of Ni previously locked in the olivine structure. The relatively high Ni content in olivine and nearly monomineralic nature of the dunite layers indicate that the Ni liberated from olivine during serpentinization could become part of the Ni in secondary Ni-bearing minerals. However, as expected, the original (magmatic) pentlandite content largely controls the bulk nickel content in the system. Desulfurization of primary pentlandite, linked to the effects of serpentinization, results in formation of secondary Ni-bearing minerals and increasing in the Ni:S values in the target rocks.
Access status: Open Access ,
Circulating tumor DNA as a biomarker to detect minimal residual disease for colorectal and breast cancer
(Laurentian University Library & Archives, 2025) Madhu, Mitul Jayeshkumar; Dr. Sujeenthar Tharmalingham
Minimal residual disease (MRD) is a key contributor to cancer recurrence, often escaping detection by conventional imaging and biomarker techniques. Circulating tumor DNA (ctDNA), a component of cell-free DNA shed by tumor cells into the bloodstream, has emerged as a promising biomarker for the non-invasive detection and monitoring of MRD in solid tumors. This review critically examines current evidence on the application of ctDNA for MRD detection in colorectal cancer (CRC) and breast cancer, two of the most common malignancies worldwide. It compares ctDNA detection platforms, including digital droplet PCR (ddPCR) and next-generation sequencing (NGS), emphasizing differences in sensitivity, specificity, and clinical relevance. The review also discusses the use of tumor-informed versus untargeted ctDNA assays and highlights key biomarkers such as KRAS, BRAF, TP53, and PIK3CA. Although ctDNA holds substantial potential to enhance surveillance strategies, challenges such as assay variability and tumor heterogeneity must be addressed to enable broader clinical implementation.
Access status: Open Access ,
Targeting long non-coding RNAs in glioblastoma : a new frontier in cancer therapy
(Laurentian University Library & Archives, 2025-08-12) Limbachiya, Vishva V.; Sujeenthar Tharmalingham
Glioblastoma (GBM) is the most aggressive primary brain tumor observed in adults. It progresses quickly, it has a poor prognosis and is resistant to common treatments like temozolomide (TMZ). This study critically examines the function that long non-coding RNAs (lncRNAs) play in the pathological processes of GBM, highlighting their roles in tumor heterogeneity, therapeutic resistance, and dysregulated signaling. A systematic search of 679 papers using PRISMA guidelines resulted 389 studies that were chosen for a comprehensive review. The review addresses at how lncRNAs regulate important pathways like PI3K/AKT, p53, NF-κB, Wnt/β-catenin, and JAK/STAT. It also categorizes lncRNAs according to their genetic origin, subcellular location, and functional roles. The article also emphasizes how lncRNAs affect glioma stemness and immune evasion, as well as their dual oncogenic and tumor-suppressive roles. Overall, this work identifies lncRNAs as promising biomarkers and therapeutic targets, supporting their potential integration into precision medicine for GBM.