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N-(3-Oxododecanoyl)-L-Homoserine Lactone in the Breast Tumor MicroenvironmentBalhouse, Brittany Nicole 12 June 2017 (has links)
The tumor microenvironment is a well-recognized contributor to cancer progression in solid tumors. Cancer cell interactions with abnormal extracellular matrix, tumor associated immune and stromal cells, and aberrant fluid flow all contribute to cancer progression. Breast tumors are often characterized by a dense collagenous stroma and a hypoxic core. A recently identified and little understood component of the breast tumor microenvironment is the breast microbiome. The work described here elaborates on the importance of the tumor microenvironment in cancer progression and demonstrates the importance of studying cancer-microbiome interactions in the context of tumor microenvironmental stimuli. / Master of Science
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The Diversity and Functions of Microglia/Macrophages in Neurological Disease and Glioma MicroenvironmentRajagopalan, Shanmuga Priya January 2022 (has links)
No description available.
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Characterizing the Impact of Specific Genetic Mutations on Chemotherapy Resistance and the Efficacy of Oncolytic Viruses for the Treatment of Ovarian CancerCudmore, Alison 17 November 2022 (has links)
Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and urgently requires new therapies. Oncolytic viruses (OV) are a strong contender. OVs interact with immune components of the TME, which can be altered due to specific genetic mutations. The present study evaluates the impact of specific tumour mutations on the response to carboplatin, the current standard of care, and VSV∆M51, a promising OV candidate. After a study of genetically diverse models, constitutive KRas activation enhanced VSV∆M51 replication in-vitro and sensitivity in syngeneic in-vivo models. VSV∆M51 prolonged survival in syngeneic tumour- bearing mice with KRas, Trp53 and Pten mutations, including one tumour model that did not respond to carboplatin. Response to VSV∆M51 in-vivo was associated with activation of CD4+ and CD8+ T lymphocytes in the peritoneal TME. In summary, VSV∆M51-based immunotherapy has shown promise in diverse murine models of EOC bearing clinically relevant mutations.
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Identification of Key Pyroptosis- Related Genes and Distinct Pyroptosis-Related Clusters in PeriodontitisNing, Wanchen, Acharya, Aneesha, Li, Simin, Schmalz, Gerhard, Huang, Shaohong 23 October 2023 (has links)
Aim: This study aims to identify pyroptosis-related genes (PRGs), their functional immune
characteristics, and distinct pyroptosis-related clusters in periodontitis.
Methods: Differentially expressed (DE)-PRGs were determined by merging the
expression profiles of GSE10334, GSE16134, and PRGs obtained from previous
literatures and Molecular Signatures Database (MSigDB). Least absolute shrinkage and
selection operator (LASSO) regression was applied to screen the prognostic PRGs and
develop a prognostic model. Consensus clustering was applied to determine the pyroptosisrelated
clusters. Functional analysis and single-sample gene set enrichment analysis (ssGSEA)
were performed to explore the biological characteristics and immune activities of the clusters.
The hub pyroptosis-related modules were defined using weighted correlation network
analysis (WGCNA).
Results: Of the 26 periodontitis-related DE-PRGs, the highest positive relevance was for
High-Mobility Group Box 1 (HMGB1) and SR-Related CTD Associated Factor 11
(SCAF11). A 14-PRG-based signature was developed through the LASSO model. In
addition, three pyroptosis-related clusters were obtained based on the 14 prognostic
PRGs. Caspase 3 (CASP3), Granzyme B (GZMB), Interleukin 1 Alpha (IL1A), IL1Beta (B),
IL6, Phospholipase C Gamma 1 (PLCG1) and PYD And CARD Domain Containing
(PYCARD) were dysregulated in the three clusters. Distinct biological functions and
immune activities, including human leukocyte antigen (HLA) gene expression, immune
cell infiltration, and immune pathway activities, were identified in the three pyroptosisrelated
clusters of periodontitis. Furthermore, the pink module associated with
endoplasmic stress-related functions was found to be correlated with cluster 2 and
was suggested as the hub pyroptosis-related module.
Conclusion: The study identified 14 key pyroptosis-related genes, three distinct
pyroptosis-related clusters, and one pyroptosis-related gene module describing several
molecular aspects of pyroptosis in the pathogenesis and immune micro-environment
regulation of periodontitis and also highlighted functional heterogeneity in pyroptosisrelated
mechanisms.
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Differential membrane-type matrix metalloproteinase expression in phenotypically defined breast cancer cell lines: Comparison of MT-MMP expression in environmentally-challenged 2D monolayer cultures and 3D multicellular tumour spheroidsKashtl, Ghasaq J. January 2018 (has links)
Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases capable of digesting the extracellular matrix (ECM), which is essential for tissue structure and transmitting messages between cells. MMPs play an important role in cancer, controlling cell migration, proliferation, apoptosis, regulation of tumour expansion, angiogenesis and invasion. Previous research has indicated high expression of MT1-MMP in breast cancers suggesting a potential role in tumour progression. Our results confirm that 3D multicellular tumour spheroids (MCTS) using phenotype-specific breast cancer cell lines are a valuable experimental model of the tumour microenvironment.
Optimisation of MCTS culture growth conditions using different breast cancer cell lines (MCF-7, T47D, MDA-MB-468 and MDA-MB-231) was performed. Unexpected detection of MT1-MMP in MCF-7 MCTS warranted further investigation. MT1-MMP expression in different micro-environmental conditions, including hypoxia and nutrient deprivation (serum-free induced autophagy) were measured in MCF-7 monolayer cultures and MCTS models using immunofluorescence (IF), immunohistochemistry (IHC) and western blot (WB).
MT1-MMP expression was rapidly and irreversibly up-regulated in MCF-7 breast cancer cells under conditions of stress (hypoxia and autophagy) compared to normal conditions suggesting an important role of the culture environment on cells behaviour and protein expression.
We employed isobaric tags for relative and absolute quantitation (iTRAQ) technology to correlate MT1-MMP increase with proteomic profiles in MCF-7 breast cancer cell grown under hypoxic, serum-free and 3D MCTS conditions. More than 3500 proteins were identified, which were clustered into groups based on response to unique or shared microenvironment changes. Hypoxic monolayer and spheroid cells exhibited changes in anaerobic metabolism and lipid synthesis, respectively, whereas autophagy resulted in up-regulation of cellular component disassembly. The result indicated multiple drivers of MT1-MMP expression in MCF-7 cells. / Al-Mstansiriya University, Iraq
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The role of a sickled microenvironment in cardiac dysfunctionHealey, Allison Nicole 06 August 2021 (has links)
This study helps to fill a remaining knowledge gap surrounding the mechanisms and pathways that contribute to cardiomyopathies in SCD. A better understanding of the pathophysiological mechanisms could lead to more accurate therapeutic targets to improve quality of life as well as life expectancy. In this study I recapitulate cardiac dysfunction in vitro by exposing engineered mouse cardiac tissues to ANG II or the sickled microenvironment. Experimental results include gene expression profiles and oxidative stress generation. Gene expression profiles in the ANG II treated tissues indicated a pathological state with upregulation in biomarkers for inflammation, cell adhesion, wall stress and ECM related genes. Further research is being conducted using insights gained from this study which will lead to a broader understanding of the biological processes involved and potentially identify novel therapeutic targets that may ultimately improve patient outcomes.
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Miniaturized 3D culture of stem cells with biomaterials derived from alginateDumbleton, Jenna K. 01 September 2015 (has links)
No description available.
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Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug ResistanceWang, Xuan January 2017 (has links)
No description available.
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Targeting Cancer-Associated Fibroblasts: New Opportunity for Therapeutic Intervention in Cutaneous MelanomaYang, Kun 04 September 2018 (has links)
No description available.
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Capability of the Tumor Microenvironment to Attract a Precursor of B-cells and Dendritic Cells from Bone MarrowNandigam, Harika 26 July 2011 (has links)
No description available.
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