subject:(pathology)

UCLA

1. Wang, Jiexin. The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs.

Degree: Cellular & Molecular Pathology, 2016, UCLA

URL: http://www.escholarship.org/uc/item/52p3n3tq

► Adipocyte differentiation is accompanied by a robust program of cell-type specific gene expression. Although transcriptional regulators of this process are well defined, the contribution of… (more)

Subjects/Keywords: Pathology

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APA (6^th Edition):

Wang, J. (2016). The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/52p3n3tq

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Jiexin. “The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs.” 2016. Thesis, UCLA. Accessed March 01, 2021. http://www.escholarship.org/uc/item/52p3n3tq.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Jiexin. “The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs.” 2016. Web. 01 Mar 2021.

Vancouver:

Wang J. The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs. [Internet] [Thesis]. UCLA; 2016. [cited 2021 Mar 01]. Available from: http://www.escholarship.org/uc/item/52p3n3tq.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang J. The paraspeckle protein Pspc1 promotes adipogenesis through differentiation-dependent nuclear export of adipogenic RNAs. [Thesis]. UCLA; 2016. Available from: http://www.escholarship.org/uc/item/52p3n3tq

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Wayne State University

2. Bottrell, Alyssa. The Role Of Pdgf C And Its Splice Variant In Breast Cancer.

Degree: PhD, Pathology, 2014, Wayne State University

URL: https://digitalcommons.wayne.edu/oa_dissertations/1285

► The PDGF family consists of four members; while PDGF A and B are secreted as active dimers, PDGF C and D are secreted as… (more)

▼ The PDGF family consists of four members; while PDGF A and B are secreted as active dimers, PDGF C and D are secreted as latent dimers that undergo serine protease-mediated extracellular proteolytic activation. Gene expression analysis of breast cancer cell lines showed that PDGF C expression is associated with Basal B subtype breast cancer cells which have cancer stem cell-like characteristics. Furthermore, PDGF C expression is associated with triple-negative (estrogen receptor-, progesterone receptor- and HER2/neu-negative) breast cancer cells, a challenging type of breast cancer to treat. During the course of our study, we discovered a splice variant of PDGF C encoding the truncated PDGF C protein (t-PDGF C). Specific aims of this dissertation are to determine the role of full-length PDGF C (FL-PDGF C) and t-PDGF C in breast cancer and to characterize their subcellular localizations. This study found that although t-PDGF C presumably lacks the signal peptide, it is secreted as a heterodimer with FL-PDGF C which can undergo extracellular proteolytic activation. Furthermore, PDGF C was found in the nuclear fraction of breast cancer cells, suggesting an uncharacterized function in breast cancer. A putative nuclear localization sequence in PDGF C showed little effect on its nuclear localization as determined by the point mutagenesis assay. Interestingly, we found that the serine protease cleavage site in the hinge region plays a critical role for both extracellular proteolytic processing and nuclear accumulation of PDGF C, suggesting that the biochemical processing and the subcellular localization are co-regulated. For the functional study, we established in vitro cell models engineered to overexpress PDGF C isoforms or inhibit its expression. This study found that PDGF C expression correlates with cell proliferation, invasive phenotype and anchorage-independent growth in vitro. Importantly, t-PDGF C expression further promoted PDGF C-induced phenotypic transformation. PDGF C downregulation decreased tumor growth and metastatic potential in vivo. Taken together, this study identified PDGF C and its splice variant as key signaling molecules in breast cancer. In addition, once thought of as primarily an extracellular signaling molecule, nuclear localization marks a potentially important paradigm shift in PDGF C biology. Advisors/Committee Members: Hyeong-Reh C. Kim.

Subjects/Keywords: Pathology

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APA (6^th Edition):

Bottrell, A. (2014). The Role Of Pdgf C And Its Splice Variant In Breast Cancer. (Doctoral Dissertation). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_dissertations/1285

Chicago Manual of Style (16^th Edition):

Bottrell, Alyssa. “The Role Of Pdgf C And Its Splice Variant In Breast Cancer.” 2014. Doctoral Dissertation, Wayne State University. Accessed March 01, 2021. https://digitalcommons.wayne.edu/oa_dissertations/1285.

MLA Handbook (7^th Edition):

Bottrell, Alyssa. “The Role Of Pdgf C And Its Splice Variant In Breast Cancer.” 2014. Web. 01 Mar 2021.

Vancouver:

Bottrell A. The Role Of Pdgf C And Its Splice Variant In Breast Cancer. [Internet] [Doctoral dissertation]. Wayne State University; 2014. [cited 2021 Mar 01]. Available from: https://digitalcommons.wayne.edu/oa_dissertations/1285.

Council of Science Editors:

Bottrell A. The Role Of Pdgf C And Its Splice Variant In Breast Cancer. [Doctoral Dissertation]. Wayne State University; 2014. Available from: https://digitalcommons.wayne.edu/oa_dissertations/1285

3. Birbrair, Alexander. PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY.

Degree: 2014, Wake Forest University

URL: http://hdl.handle.net/10339/39384

► Normal tissue homeostasis as well as tissue regeneration and repair after damage rely on resident stem cells. Incomplete regeneration in mammals has been attributed to… (more)

Subjects/Keywords: pathology

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APA (6^th Edition):

Birbrair, A. (2014). PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/39384

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Birbrair, Alexander. “PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY.” 2014. Thesis, Wake Forest University. Accessed March 01, 2021. http://hdl.handle.net/10339/39384.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Birbrair, Alexander. “PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY.” 2014. Web. 01 Mar 2021.

Vancouver:

Birbrair A. PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY. [Internet] [Thesis]. Wake Forest University; 2014. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10339/39384.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Birbrair A. PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY. [Thesis]. Wake Forest University; 2014. Available from: http://hdl.handle.net/10339/39384

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cape Town

4. Chambuso, Ramadhani Salum. Human Immunodeficiency Virus/Human Papillomavirus co-infection and host molecular genetics of cervical carcinoma.

Degree: PhD, Pathology, 2019, University of Cape Town

URL: http://hdl.handle.net/11427/31668

► A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV1) and human papillomavirus (HPV) progress relatively rapidly to cervical disease regardless… (more)

▼ A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV1) and human papillomavirus (HPV) progress relatively rapidly to cervical disease regardless of the number of absolute CD4 count. During infection, viral peptides are recognized by the host immune system. It is reasonable to propose that the development of viral-associated cancers, like cervical cancer, requires interference with specific immune-response genes. This thesis investigates this proposition with consideration of host molecular genetic alterations and variations of the human leukocyte antigen class II (HLA II) genes as one of the groups of immune-response genes that are involved in directing CD4 T-cell responses during infection, in the instance of cervical cancer progression in HIV-1/HPV co-infected women. Study I, reviewed the available literature on host molecular genetics and HIV-1/HPV coinfection on cervical cancer progression. This study suggests that the dual pro-oncogenic effects of HPV oncoproteins E6/E7 and the HIV-1 oncoprotein Tat, may exacerbate and accelerate the rate of cervical disease progression in a subgroup of HIV-1-positive women. Additionally, HIV-1-positive cervical cancer has three important carcinogenesis steps: firstly, HPV integration into the host genome, secondly, dual pro-oncogenic effects of HPV oncoproteins E6/E7, and the HIV-1 Tat oncoprotein in the host genome and, thirdly, the accumulation of repeated, unrepaired genetic mutations and genetic alterations within the host chromosomal DNA. Genetic variations or mutations that affect the following host gene categories were suggested to be responsible for cervical cancer susceptibility and disease progression; (i) genes for the immune-response against oncogenic HPV infection, (ii) oncogenes, (iii) tumour-suppressor genes, (iv) apoptosis-related genes, (v) DNA damagerepair genes, and (vi) cell cycle-regulatory genes. However, studies II, III and IV are linked together and listed according to the specific objectives of this thesis. Study II, characterized the distribution of HPV genotypes within cervical tumour biopsies from a cohort of 181 HPV-unvaccinated South African women and studied the relationships with HIV-1 infection, age of patients, absolute CD4 count, CD4 percentage and the stage of cervical disease, and identified the predictive power of these variables for cervical disease stage. Distribution of HPV genotypes was related to the stage of cervical disease in HIV-1-positive women. Older age was a significant predictor for invasive cervical cancer (ICC) in both HIV-1-seronegative (p<0.0001) ) and HIV1-positive women (p=0.0003, q=0.0003). Sixty-eight percent (59/87) of HIV-1-positive women with different stages of cervical disease presented with CD4 percentage below or equal to 28 and a median absolute CD4 count of 400 cells/µl (IQR 300-500 cells/µl). Of the HIV-1-positive women, 75% (30/40) with ICC, possessed ≤28% CD4 cells versus 25% (10/40) who possessed >28% CD4 cells (both p< 0.001, q<0.001). Furthermore, 70% (28/40) of women… Advisors/Committee Members: Ramesar, Raj (advisor), Gray, Clive (advisor), Williamson, Anna-Lise (advisor).

Subjects/Keywords: Pathology

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APA (6^th Edition):

Chambuso, R. S. (2019). Human Immunodeficiency Virus/Human Papillomavirus co-infection and host molecular genetics of cervical carcinoma. (Doctoral Dissertation). University of Cape Town. Retrieved from http://hdl.handle.net/11427/31668

Chicago Manual of Style (16^th Edition):

Chambuso, Ramadhani Salum. “Human Immunodeficiency Virus/Human Papillomavirus co-infection and host molecular genetics of cervical carcinoma.” 2019. Doctoral Dissertation, University of Cape Town. Accessed March 01, 2021. http://hdl.handle.net/11427/31668.

MLA Handbook (7^th Edition):

Chambuso, Ramadhani Salum. “Human Immunodeficiency Virus/Human Papillomavirus co-infection and host molecular genetics of cervical carcinoma.” 2019. Web. 01 Mar 2021.

Vancouver:

Chambuso RS. Human Immunodeficiency Virus/Human Papillomavirus co-infection and host molecular genetics of cervical carcinoma. [Internet] [Doctoral dissertation]. University of Cape Town; 2019. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/11427/31668.

Council of Science Editors:

Chambuso RS. Human Immunodeficiency Virus/Human Papillomavirus co-infection and host molecular genetics of cervical carcinoma. [Doctoral Dissertation]. University of Cape Town; 2019. Available from: http://hdl.handle.net/11427/31668

5. Reiche, Michael Anton. Visualising the Mycobacterial Mutasome.

Degree: Image, Pathology, 2018, University of Cape Town

URL: http://hdl.handle.net/11427/28381

► An SOS-inducible DNA repair system has been linked to transient hyper-mutation and the development of drug resistance in Mycobacterium tuberculosis. Previous work has established that… (more)

▼ An SOS-inducible DNA repair system has been linked to transient hyper-mutation and the development of drug resistance in Mycobacterium tuberculosis. Previous work has established that this “mycobacterial mutasome” comprises the specialist DNA polymerase, DnaE2, and accessory factors of unknown function, ImuA′ and ImuB. However, the molecular interactions and sub-cellular recruitment dynamics enabling mutasome function remain poorly understood. Here, a panel of fluorescent strains of M. smegmatis was developed to investigate expression and subcellular localization of ImuA′ and ImuB in live mycobacteria exposed to genotoxic agents. Using fluorescence microscopy, it was observed that, during prolonged genotoxic stress, single M. smegmatis cells exhibited an elongated cell phenotype and apparent aneuploidy – potentially providing an environment for recombination between differentially mutated chromosomes. Furthermore, ImuB was seen to associate with the dnaNencoded β clamp in discrete foci during mutagenic DNA repair. In contrast, ImuA′ did not exhibit similar localization and instead appeared to diffuse throughout the bacillus. A mutant ImuB protein deficient in the β clamp-binding motif failed to colocalize with the β clamp, reinforcing the inferred essentiality of the ImuB-β clamp protein-protein interaction for mutasome recruitment and induced mutagenesis. Additionally, exposure of M. smegmatis to griselimycin, a novel β clamp-targeting natural product antibiotic, prevented ImuB-β clamp co-localization during SOS induced mutagenesis, an observation confirmed by superresolution, threedimensional interferometric photo-activated light microscopy. These results establish the capacity of griselimycin to inhibit DNA replication as well as prevent DNA damage-induced mutagenesis by disrupting mutasome assembly and activity. Notably, this differentiates griselimycin from other inhibitors of DNA metabolic function which carry the often-unavoidable liability of accelerating drug-resistance by inducing mutagenic DNA repair. In turn, it suggests the potential application of griselimycin as an anti-evolution agent in novel therapeutic regimens designed to protect existing tuberculosis drugs. Advisors/Committee Members: Warner, Digby (advisor).

Subjects/Keywords: pathology

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APA (6^th Edition):

Reiche, M. A. (2018). Visualising the Mycobacterial Mutasome. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/28381

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Reiche, Michael Anton. “Visualising the Mycobacterial Mutasome.” 2018. Thesis, University of Cape Town. Accessed March 01, 2021. http://hdl.handle.net/11427/28381.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Reiche, Michael Anton. “Visualising the Mycobacterial Mutasome.” 2018. Web. 01 Mar 2021.

Vancouver:

Reiche MA. Visualising the Mycobacterial Mutasome. [Internet] [Thesis]. University of Cape Town; 2018. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/11427/28381.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Reiche MA. Visualising the Mycobacterial Mutasome. [Thesis]. University of Cape Town; 2018. Available from: http://hdl.handle.net/11427/28381

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cape Town

6. Logan, Erin. Early-life immunity and susceptibility to Mycobacteria.

Degree: PhD, Pathology, 2018, University of Cape Town

URL: http://hdl.handle.net/11427/29195

► The naïve and not-yet developed infant immune system exhibits heightened susceptibility to external factors (e.g pathogens), and is shaped by these and others, such as… (more)

▼ The naïve and not-yet developed infant immune system exhibits heightened susceptibility to external factors (e.g pathogens), and is shaped by these and others, such as maternal immunity. However, we do not yet fully understand their impact on development of infant immunity. A better understanding of these effects would benefit children world-wide, but especially those in low-middle income countries (LMIC), where increased exposure to pathogens due to poorer living conditions highlights the necessity of robust early-life immunity. Mycobacterium tuberculosis (Mtb) and helminths are pathogens co-endemic in many LMIC and cause significant morbidity and mortality in children. Infant immune responses to these pathogens, whether during standalone infection, co-infection or resulting from maternal infection are not fully understood. To contribute to this knowledge gap, we investigated early-life immune responses, how they relate to childhood Mtb/helminth infection and how they are affected by maternal infectious history and immunity. Analysis of clinical humoral responses revealed total IgG that increased significantly between baseline and tuberculosis (TB) investigation in infants who did not acquire Mtb infection; these infants also exhibited raised levels of measles-specific IgG and BCG-specific IgG2. No active helminth infections were detected, but the presence of Ascaris lumbricoides- and Trichuris trichiura-specific class-switched antibodies indicated prior exposure. No association was found between helminth-specific humoral responses and risk of Mtb infection, nor with maternal helminth-specific humoral responses. Conversely, data from murine experiments revealed a protective effect of maternal helminth infection (Nippostrongylus brasiliensis) on BCG infection in offspring, with reduced lung bacterial burden and increased numbers of activated CD4+ T cells and B cells. Maternal Nb infection may have a synergistic effect on BCG vaccination, as BCGvaccinated/infected pups from Nb-infected mothers had reduced lung bacterial burdens, increased CD4+ T cell and B cell responses and increased IFNγ-producing CD4+ T cells. Findings from this study suggest that childhood vaccines could provide heterologous protection against unrelated pathogens such as Mtb. The murine data suggest a protective effect of maternal helminth infection against BCG infection in offspring, but no similar finding was observed with the clinical data. The clear protective effect of maternal Nb infection during offspring BCG infection warrants a more in-depth clinical study addressing the functional effects of maternal helminth infection on Mtb infection outcome in infants. Advisors/Committee Members: Horsnell, William (advisor), Hatherill, Mark (advisor), Cunningham, Adam F (advisor).

Subjects/Keywords: pathology

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APA (6^th Edition):

Logan, E. (2018). Early-life immunity and susceptibility to Mycobacteria. (Doctoral Dissertation). University of Cape Town. Retrieved from http://hdl.handle.net/11427/29195

Chicago Manual of Style (16^th Edition):

Logan, Erin. “Early-life immunity and susceptibility to Mycobacteria.” 2018. Doctoral Dissertation, University of Cape Town. Accessed March 01, 2021. http://hdl.handle.net/11427/29195.

MLA Handbook (7^th Edition):

Logan, Erin. “Early-life immunity and susceptibility to Mycobacteria.” 2018. Web. 01 Mar 2021.

Vancouver:

Logan E. Early-life immunity and susceptibility to Mycobacteria. [Internet] [Doctoral dissertation]. University of Cape Town; 2018. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/11427/29195.

Council of Science Editors:

Logan E. Early-life immunity and susceptibility to Mycobacteria. [Doctoral Dissertation]. University of Cape Town; 2018. Available from: http://hdl.handle.net/11427/29195

University of Cape Town

7. Katsandegwaza, Brunette. Determining the impact of Heligmosomoides polygyrus infection on the development of colitis.

Degree: PhD, Pathology, 2019, University of Cape Town

URL: http://hdl.handle.net/11427/31778

► The ability of helminths to regulate inflammatory disorders and the mechanisms by which they carry this out are of great scientific interest. Currently, established literature… (more)

▼ The ability of helminths to regulate inflammatory disorders and the mechanisms by which they carry this out are of great scientific interest. Currently, established literature emphasises the protective role of helminth infection in mouse models of inflammatory bowel disease (IBD). Utilising two well-established murine models of human disease, the oxazolone and dextran sulfate sodium (DSS) models, I found that induction of murine IBD is highly sensitive to diet change and mouse gender. Using the gastrointestinal helminth Heligmosomoides polygyrus (H.polygyrus), I demonstrate that helminth infection exacerbates IBD in both the oxazolone and DSS models of colitis. Underlying helminth infection results in increased inflammation locally in the colon and systemically in the spleen in both models of IBD, as measured by histology and flow cytometry. Exacerbation of DSS colitis is dependent on the dose of H.polygyrus but is independent of the phase of H.polygyrus infection, with both acute and chronic infections resulting in the same phenotype. Helminth exacerbated DSS colitis is characterised by significant bacterial translocation to the spleen, which is concluded to be due to loss of intestinal epithelial integrity. Helminth infection also resulted in a microbial shift of translocating bacteria following DSS administration, as evidenced by gram staining and bacterial sequencing. Administration of an 8- strain probiotic during acute helminth infection ameliorated helminth exacerbation of DSS colitis, restored epithelial integrity and abrogated splenomegaly. This work uncovers an unexpected and novel role for live helminth infection in exacerbating IBD and suggests that helminth-induced dysbiosis of the microbiota may drive disease. These studies reveal restoration of the microbiota through probiotics or helminth eradication as potential therapies for the treatment of gastrointestinal inflammatory disorders. Advisors/Committee Members: Smith, Katherine (advisor), Horsnell, Bill (advisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Katsandegwaza, B. (2019). Determining the impact of Heligmosomoides polygyrus infection on the development of colitis. (Doctoral Dissertation). University of Cape Town. Retrieved from http://hdl.handle.net/11427/31778

Chicago Manual of Style (16^th Edition):

Katsandegwaza, Brunette. “Determining the impact of Heligmosomoides polygyrus infection on the development of colitis.” 2019. Doctoral Dissertation, University of Cape Town. Accessed March 01, 2021. http://hdl.handle.net/11427/31778.

MLA Handbook (7^th Edition):

Katsandegwaza, Brunette. “Determining the impact of Heligmosomoides polygyrus infection on the development of colitis.” 2019. Web. 01 Mar 2021.

Vancouver:

Katsandegwaza B. Determining the impact of Heligmosomoides polygyrus infection on the development of colitis. [Internet] [Doctoral dissertation]. University of Cape Town; 2019. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/11427/31778.

Council of Science Editors:

Katsandegwaza B. Determining the impact of Heligmosomoides polygyrus infection on the development of colitis. [Doctoral Dissertation]. University of Cape Town; 2019. Available from: http://hdl.handle.net/11427/31778

University of Cape Town

8. Khumalo, Jermaine. The temporal requirement of IL-4Rα signalling in allergic asthma and the role of IL-4Rα-responsive Regulatory T cells in restraining allergic airway inflammation.

Degree: PhD, Pathology, 2019, University of Cape Town

URL: http://hdl.handle.net/11427/31728

► Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. The asthma pathology is predominantly elicited by… (more)

▼ Allergic asthma is a chronic inflammatory airway disease driven predominantly by a TH2 immune response to environmental allergens. The asthma pathology is predominantly elicited by IL-4 and IL-13 signalling via IL-4Rα-signalling which is essential for driving TH2-type immunity to allergens. Interestingly, the failure by regulatory T cells to maintain tolerance during allergic asthma, suggested to be driven by TH2 inflammatory signals, still remains elusive and anti-TH2 therapies with the potential to effectively reduce airway obstruction and inflammation in allergic asthma, have had limited success. Therefore, we aimed to investigate the function of IL-4/IL-13 responsive regulatory T cells in a TH2 rich environment and the temporal requirement of IL-4Rα-signalling in asymptomatic and acute airway disease. Objective 1: We investigated potential therapeutic effects of selective inhibition of this pathway in mice with established allergic airway disease and systemically sensitised mice to prevent the onset of the disease. We used RosacreERT2IL-4Rα-/lox mice, a novel, tamoxifen inducible IL-4Rα knockdown model to investigate the role of IL-4/IL-13 signalling during the effector phase of ovalbumin induced allergic airway disease (AAD) and for the onset of the disease. The deletion of the IL-4Rα had a therapeutic effect on established AAD and prevented the development of ovalbumin induced airway hyperreactivity, goblet cell metaplasia and eosinophilia in allergensensitised mice. We concluded that the abrogation of IL-4Rα signalling after allergic sensitisation would have significant therapeutic benefit for TH2 type allergic asthma. Objective 2: The canonical IL-4Rα-signalling, was investigated on its role on Foxp3+ Tregs in allergic asthma with aims to re-establish tolerance during allergic asthma. We used transgenic Foxp3cre IL-4Rα-/lox mice IL-4Rα-/lox mice to investigate the role of IL-4/IL-13 signalling during the induction or maintenance of tolerance in house dust mite-induced ADD. The depletion of IL-4Ra on Foxp3+ Tregs exacerbated airway hyperreactivity and airway inflammation in allergen- sensitised mice. Interestingly, a reduced induction of Foxp3+ Tregs in peripheral tissue and an accompanying increased IL-33 induced ILC2 driven inflammation in the lung responsible for the exacerbation of TH2 acute disease. Conclusively, the IL-4Rα responsive Foxp3+ T regulatory cells are key in maintaining tolerance in type 2 innate immune driven allergic asthma, therefore the TH2 environment has both an innate immune specific regulative role in local lung tissue and induction of Foxp3+ Tregs in peripheral tissue during AAD. A combined targeting of the pathogenic TH2 environment in anti-TH2 therapy and the augmentation of regulatory T cell function in the local lung tissue is necessary to inhibit both adaptive and innate drivers of TH2 inflammation in allergic disease. Advisors/Committee Members: Brombacher, Frank (advisor), Kirstein, Frank (advisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Khumalo, J. (2019). The temporal requirement of IL-4Rα signalling in allergic asthma and the role of IL-4Rα-responsive Regulatory T cells in restraining allergic airway inflammation. (Doctoral Dissertation). University of Cape Town. Retrieved from http://hdl.handle.net/11427/31728

Chicago Manual of Style (16^th Edition):

Khumalo, Jermaine. “The temporal requirement of IL-4Rα signalling in allergic asthma and the role of IL-4Rα-responsive Regulatory T cells in restraining allergic airway inflammation.” 2019. Doctoral Dissertation, University of Cape Town. Accessed March 01, 2021. http://hdl.handle.net/11427/31728.

MLA Handbook (7^th Edition):

Khumalo, Jermaine. “The temporal requirement of IL-4Rα signalling in allergic asthma and the role of IL-4Rα-responsive Regulatory T cells in restraining allergic airway inflammation.” 2019. Web. 01 Mar 2021.

Vancouver:

Khumalo J. The temporal requirement of IL-4Rα signalling in allergic asthma and the role of IL-4Rα-responsive Regulatory T cells in restraining allergic airway inflammation. [Internet] [Doctoral dissertation]. University of Cape Town; 2019. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/11427/31728.

Council of Science Editors:

Khumalo J. The temporal requirement of IL-4Rα signalling in allergic asthma and the role of IL-4Rα-responsive Regulatory T cells in restraining allergic airway inflammation. [Doctoral Dissertation]. University of Cape Town; 2019. Available from: http://hdl.handle.net/11427/31728

Columbia University

9. Woo, Seung-Hyun. Identification and characterization of epithelial progenitor niches in skin.

Degree: 2011, Columbia University

URL: https://doi.org/10.7916/D82231Q9

► The skin contains a highly regionalized stem and progenitor cell niche system, where a particular epithelial progenitor population primarily displays unipotent or bipotent behavior by… (more)

▼ The skin contains a highly regionalized stem and progenitor cell niche system, where a particular epithelial progenitor population primarily displays unipotent or bipotent behavior by contributing to their local niche under homeostatic conditions. Some of these populations, however, can also contribute to lineages beyond their local niche in response to wounding or other traumas. The goal of this thesis was to identify additional epithelial progenitor niches in the skin and characterize them. I focused on identifying and investigating the role of epithelial progenitors residing in two discrete compartments, the upper isthmus (UI) of the hair follicle and the touch dome (TD) in the epidermis, during skin development and homeostasis. The UI niche was identified by immunofluorescence studies based on the expression profile of a6 integrin low, Sca-1 negative, CD34 negative cells. The progenitor characteristics of UI keratinocytes were confirmed using skin reconstitution and in vitro colony formation assays. The transcriptional profiling of UI cells led to the identification of Tbc1d10c, one of the uniquely upregulated genes in UI cells. The comprehensive characterization of the UI niche by immunofluorescence led to the identification of a neural complex called palisade nerve endings (PN) present outside of the UI. Further investigation of PN using immunofluorescence and animal models revealed the presence of a glutamate transport to the HF via sensory nerve fibers. I elucidated that the presence of glutamate was critical for the organization of Schwann cells in the developing HF. Although the relationship between UI keratinocytes and PN still needs to be investigated, the presence of PN in the UI niche implicates that there is more function ascribed to UI cells in addition to serving as epithelial progenitors. The next epithelial progenitor niche I identified and characterized was the touch dome (TD) in the epidermis of hairy skin. The TD is a specialized niche, in which both epidermal Merkel cells and TD keratinocytes reside. The unexpected and exclusive presence of both Tbc1d10c and CD200 proteins in TD keratinocytes eventually led us to find that they were epidermal Merkel cell progenitors. Their progenitor characteristics were validated using skin reconstitution assay and in vivo lineage tracing by EdU incorporation. Our results collectively suggested that TD keratinocytes were bipotent progenitors that gave rise to both squamous and neuroendocrine epidermal lineages. Lastly, I generated a UI-specific Cre transgenic mouse line driven by the Tbc1d10c promoter, which will be utilized for further characterization of UI keratinocytes, including in vivo lineage tracing. I also generated Tbc1d10c complete knockout mice, which I will investigate to determine whether Tbc1d10c plays a role during skin development and homeostasis.

Subjects/Keywords: Pathology

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APA (6^th Edition):

Woo, S. (2011). Identification and characterization of epithelial progenitor niches in skin. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D82231Q9

Chicago Manual of Style (16^th Edition):

Woo, Seung-Hyun. “Identification and characterization of epithelial progenitor niches in skin.” 2011. Doctoral Dissertation, Columbia University. Accessed March 01, 2021. https://doi.org/10.7916/D82231Q9.

MLA Handbook (7^th Edition):

Woo, Seung-Hyun. “Identification and characterization of epithelial progenitor niches in skin.” 2011. Web. 01 Mar 2021.

Vancouver:

Woo S. Identification and characterization of epithelial progenitor niches in skin. [Internet] [Doctoral dissertation]. Columbia University; 2011. [cited 2021 Mar 01]. Available from: https://doi.org/10.7916/D82231Q9.

Council of Science Editors:

Woo S. Identification and characterization of epithelial progenitor niches in skin. [Doctoral Dissertation]. Columbia University; 2011. Available from: https://doi.org/10.7916/D82231Q9

Boston University

10. Varian, Bernard. The impact of delay to fixation on PD-L1 expression in human tissue.

Degree: MS, Pathology, 2017, Boston University

URL: http://hdl.handle.net/2144/20793

► The effects of tissue preservation techniques are known to have meaningful impact on diagnostic and prognostic variables. This study aims to evaluate and improve the… (more)

Subjects/Keywords: Pathology

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APA (6^th Edition):

Varian, B. (2017). The impact of delay to fixation on PD-L1 expression in human tissue. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/20793

Chicago Manual of Style (16^th Edition):

Varian, Bernard. “The impact of delay to fixation on PD-L1 expression in human tissue.” 2017. Masters Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/20793.

MLA Handbook (7^th Edition):

Varian, Bernard. “The impact of delay to fixation on PD-L1 expression in human tissue.” 2017. Web. 01 Mar 2021.

Vancouver:

Varian B. The impact of delay to fixation on PD-L1 expression in human tissue. [Internet] [Masters thesis]. Boston University; 2017. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/20793.

Council of Science Editors:

Varian B. The impact of delay to fixation on PD-L1 expression in human tissue. [Masters Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/20793

Boston University

11. Friedberg, Jacob Sands. Apolipoprotein E alters the association of neuroinflammation with Alzheimer's disease.

Degree: MS, Medical Sciences, 2018, Boston University

URL: http://hdl.handle.net/2144/30748

► Alzheimer’s disease (AD) is a chronic neurodegenerative disease with a multitude of contributing genetic factors. The apolipoprotein E (APOE) allele e4 imparts a dramatic increase… (more)

▼ Alzheimer’s disease (AD) is a chronic neurodegenerative disease with a multitude of contributing genetic factors. The apolipoprotein E (APOE) allele e4 imparts a dramatic increase in the risk of developing Alzheimer’s disease, but the exact mechanism of this relationship is unknown. The e4 allele is associated with increased Ab plaques, neurofibrillary tangles, and a heightened inflammation state, all pathological hallmarks of Alzheimer’s disease. To test the hypothesis that microglia and related cytokines were differentially associated with Alzheimer’s disease pathology based on the presence of e4, we compared individuals with and without the APOE e4 allele within a community based aging cohort (n = 186). Cellular density of Iba1, a marker of microglia, was positively associated with tau pathology as measured by AT8 immunostaining (B = 0.459, p = 0.028) in e4 positive participants but not in e4 negative participants. Analysis of cytokines implicated in AD, i.e. IL-10, IL-13, IL-4, IL-1a, revealed a significant negative association with AT8 in e4 negative participants. The association of the anti-inflammatory cytokines IL-10, IL-13, and IL-4 on tau pathology appeared to be mediated by ApoE protein levels, suggesting that these cytokines and the ApoE protein may interact to prevent increased tau pathology within e4 negative individuals. The pro-inflammatory cytokine, IL-1, was negatively associated with AT8 (B = -0.241, p = 0.009) independent of Ab1-42 in e4 negative participants but not in e4 positive participants, suggesting a potential novel protective association. Overall, in e4 negative participants, elevated levels of IL-10, IL-13, IL-4, IL-1a are associated with less tau pathology. These associations are largely absent in the presence of e4 where tau pathology is significantly associated with microglial cell density. Taken together, these results suggest that APOE e4 mediates an altered inflammatory response and increased tau pathology independent of Ab pathology. Advisors/Committee Members: Levy, Simon (advisor), Stein, Thor (advisor).

Subjects/Keywords: Pathology

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APA (6^th Edition):

Friedberg, J. S. (2018). Apolipoprotein E alters the association of neuroinflammation with Alzheimer's disease. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/30748

Chicago Manual of Style (16^th Edition):

Friedberg, Jacob Sands. “Apolipoprotein E alters the association of neuroinflammation with Alzheimer's disease.” 2018. Masters Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/30748.

MLA Handbook (7^th Edition):

Friedberg, Jacob Sands. “Apolipoprotein E alters the association of neuroinflammation with Alzheimer's disease.” 2018. Web. 01 Mar 2021.

Vancouver:

Friedberg JS. Apolipoprotein E alters the association of neuroinflammation with Alzheimer's disease. [Internet] [Masters thesis]. Boston University; 2018. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/30748.

Council of Science Editors:

Friedberg JS. Apolipoprotein E alters the association of neuroinflammation with Alzheimer's disease. [Masters Thesis]. Boston University; 2018. Available from: http://hdl.handle.net/2144/30748

Boston University

12. Ambaah, Ekow. Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling.

Degree: MS, Pathology, 2019, Boston University

URL: http://hdl.handle.net/2144/36259

► Sepsis is among the leading causes of death in health facilities worldwide. Even with adequate treatment, severe sepsis results in approximately 50% mortality, which indicates… (more)

▼ Sepsis is among the leading causes of death in health facilities worldwide. Even with adequate treatment, severe sepsis results in approximately 50% mortality, which indicates that the individual response to the infection is variable. (Moitra, Beal, Belikoff, & Remick, 2012) In a previous paper published by the Remick laboratory it was determined that the presence of pre-existing, plasma IgG antibodies in mice prior to the onset of sepsis could be responsible for differences in their survival. A Plasma Enhanced Killing (PEK) assay was used to calculate the PEK capacity of plasma i.e. the ability of plasma to augment phagocytic killing of bacteria. PEK was calculated as PEK= (1/log (N)) X 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing(Moitra et al., 2012). The prior study also determined that inhibitory IgG probably binds inhibitory Fc receptors on phagocytic cells to result in reduced killing of bacteria. This published work used the value of the PEK to predict which mice would live and which mice would die when subjected to sepsis from cecal bacteria through the method of cecal ligation and puncture (CLP) to induce sepsis. The goal of this study was to build on what was already found and go further to demonstrate the pathway of how the blocking of IgG occurs via the Fc𝛄R in bacteria. In prior experiments by the Remick lab it was determined that the plasma from the in vitro plasma enhanced killing assay was related to the survival status of septic mice subjected to cecal ligation and puncture (CLP) model of bacterial peritonitis. The PEK assay relies on the presence of pre-existing antibodies in the plasma augmenting the killing of bacterial cells by polymorphonuclear cells. A high PEK value mean the plasma had the capability to kill bacteria and the mice were more likely to survive compared to those with a lower PEK value who were more likely to die from sepsis. Two sets of plasma were used, plasma collected with Ethylenediaminetetraacetic acid (EDTA) and plasma collected with heparin as anticoagulants. The data showed the likely presence of inhibitory IgG to be present more in the plasma sample collected with heparin than in those collected with EDTA. Advisors/Committee Members: Remick, Daniel G. (advisor).

Subjects/Keywords: Pathology

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APA (6^th Edition):

Ambaah, E. (2019). Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/36259

Chicago Manual of Style (16^th Edition):

Ambaah, Ekow. “Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling.” 2019. Masters Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/36259.

MLA Handbook (7^th Edition):

Ambaah, Ekow. “Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling.” 2019. Web. 01 Mar 2021.

Vancouver:

Ambaah E. Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling. [Internet] [Masters thesis]. Boston University; 2019. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/36259.

Council of Science Editors:

Ambaah E. Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling. [Masters Thesis]. Boston University; 2019. Available from: http://hdl.handle.net/2144/36259

Boston University

13. Langlois, Sarah Elizabeth. IHC validation in clinical settings; how lab developed assays drive clinical therapies.

Degree: MS, Pathology, 2019, Boston University

URL: http://hdl.handle.net/2144/36575

► Diagnostic laboratory tests are critical to patient care as they help dictate the most appropriate treatments and procedures. To that end, hospitals and laboratories must… (more)

▼ Diagnostic laboratory tests are critical to patient care as they help dictate the most appropriate treatments and procedures. To that end, hospitals and laboratories must ensure their diagnostic assays are optimized so as to afford patients their best chance for recovery. The pathology laboratory at Boston Medical Center, like all testing labs, must validate their IHC protocols yearly according to ASCO/CAP guidelines. Furthermore, BMC has a diverse patient population similar to the Atlanta population-based study published by Lund, et al. in 2010. Based on the results of the yearly ASCO/CAP testing and compared with the results of the Atlanta study, it was found that BMC’s HER2 testing was most likely not capturing all positive cases consistently. This prompted an optimization procedure for HER2 to be implemented. In addition to HER2 testing, BMC is looking at ways to optimize and implement PD-L1 IHC protocols as a way to identify those patients who might benefit from more targeted therapy. METHODS: HER2 IHC was performed with an altered protocol to attempt a higher concordance rate with PhenoPath, a reference lab in Seattle, and the Atlanta study data. ER and PR validation IHC protocols were also performed to ensure adequate concordance with required yearly testing. RESULTS: ER and PR protocols were found to be >95% accurate as compared to reference lab results. The new HER2 protocol yielded more vibrant staining results when compared to known positive reference data and previous BMC testing of the same sample. DISCUSSION: Optimizing lab assays is a critical step in ensuring proper clinical therapies are being utilized. Regular testing of a lab’s IHC output must be continuously verified, and continued data collection of the improved HER2 protocol is needed to make sure appropriate standards are being met. Further testing of PD-L1 IHC protocols will be warranted to maintain maximum efficiency. Advisors/Committee Members: Duffy, Elizabeth (advisor), Andry, Christopher (advisor).

Subjects/Keywords: Pathology

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Langlois, S. E. (2019). IHC validation in clinical settings; how lab developed assays drive clinical therapies. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/36575

Chicago Manual of Style (16^th Edition):

Langlois, Sarah Elizabeth. “IHC validation in clinical settings; how lab developed assays drive clinical therapies.” 2019. Masters Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/36575.

MLA Handbook (7^th Edition):

Langlois, Sarah Elizabeth. “IHC validation in clinical settings; how lab developed assays drive clinical therapies.” 2019. Web. 01 Mar 2021.

Vancouver:

Langlois SE. IHC validation in clinical settings; how lab developed assays drive clinical therapies. [Internet] [Masters thesis]. Boston University; 2019. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/36575.

Council of Science Editors:

Langlois SE. IHC validation in clinical settings; how lab developed assays drive clinical therapies. [Masters Thesis]. Boston University; 2019. Available from: http://hdl.handle.net/2144/36575

Boston University

14. Wei, Yibing. Utility of an ex vivo human whole blood assay for bacterial killing ability qualification.

Degree: MS, Pathology, 2019, Boston University

URL: http://hdl.handle.net/2144/36729

► Infectious diseases caused by antibiotic resistant bacteria are difficult to treat using traditional antibiotics and have emerged as a global public health problem (Bartlett, Gilbert,… (more)

▼ Infectious diseases caused by antibiotic resistant bacteria are difficult to treat using traditional antibiotics and have emerged as a global public health problem (Bartlett, Gilbert, & Spellberg, 2013). An alternative strategy to bypass antibiotic resistance in bacteria is to enhance the host immune system (Hancock, & Sahl, 2006), especially innate immunity (Ajesh, & Sreejith, 2009), in order to combat bacterial infections. To verify the augmentation of innate immunity under certain stimuli, a quantifiable measurement of bacterial killing ability is needed. A new method of using heparinized human peripheral whole blood and mild heated blood samples from the same individuals as comparisons has been developed. This assay was used to quantify the bacterial killing ability of phagocytic cells by measuring the bacterial load after co-culturing with the Gram negative bacteria Pseudomonas aeruginosa. The assay shows that peripheral whole blood of healthy humans is capable of being activated ex vivo upon bacterial challenge and suppressing the bacterial load, while blood gently heated at 48 °C for one hour failed to do so. The morphology of the phagocytic cells was examined microscopically. Phagocytosis of bacteria in neutrophils is observed in intact blood, and no such changes were found in heated blood. The level of inflammatory cytokine interleukin 8 (IL-8) was elevated in intact blood after bacteria inoculation, while in the heated blood the cytokine level stayed at baseline, indicating a persistence of leukocyte viability in whole blood and damaged leukocyte activity in gently heated blood. The data show that the human peripheral whole blood assay is suitable as a method for ex vivo bacterial killing quantification with the mildly heated blood sample from the same individual as a comparison. When kept at 37 °C ex vivo, human whole blood can be activated upon bacterial challenge, produce inflammatory cytokines, reduce bacterial load, and phagocytes in the whole blood can successfully maintain their cell viability and capacity to phagocytose bacteria. Advisors/Committee Members: Remick, Daniel G. (advisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wei, Y. (2019). Utility of an ex vivo human whole blood assay for bacterial killing ability qualification. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/36729

Chicago Manual of Style (16^th Edition):

Wei, Yibing. “Utility of an ex vivo human whole blood assay for bacterial killing ability qualification.” 2019. Masters Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/36729.

MLA Handbook (7^th Edition):

Wei, Yibing. “Utility of an ex vivo human whole blood assay for bacterial killing ability qualification.” 2019. Web. 01 Mar 2021.

Vancouver:

Wei Y. Utility of an ex vivo human whole blood assay for bacterial killing ability qualification. [Internet] [Masters thesis]. Boston University; 2019. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/36729.

Council of Science Editors:

Wei Y. Utility of an ex vivo human whole blood assay for bacterial killing ability qualification. [Masters Thesis]. Boston University; 2019. Available from: http://hdl.handle.net/2144/36729

University of Manitoba

15. Bay, Diane. Serrated polyps of the colon: the Winnipeg experience.

Degree: Pathology, 2011, University of Manitoba

URL: http://hdl.handle.net/1993/4885

► BACKGROUND: The pathological distinction between hyperplastic polyps and sessile serrated adenoma/polyps of the right colon is often difficult and may result in misdiagnosed polyps. OBJECTIVE:… (more)

▼ BACKGROUND: The pathological distinction between hyperplastic polyps and sessile serrated adenoma/polyps of the right colon is often difficult and may result in misdiagnosed polyps. OBJECTIVE: To review the proportion and accuracy of serrated polyp diagnosis within a one year retrospective review of colorectal polyp samples, focusing on hyperplastic polyps of the right colon, using criteria set forth by previous studies. MATERIALS & METHODS: 4096 Winnipeg patient cases from January 2009 to December 2009 were reviewed. The proportion of sessile serrated adenoma/polyps, traditional serrated adenoma and serrated adenoma were determined in the patient population. Additionally, pathological morphological variables were reassessed by two study pathologists to determine the frequency of sessile serrated adenoma/polyp initially diagnosed as hyperplastic polyps within the right colon. RESULTS: Approximately 5% of all polyps in the patient population where diagnosed as non-hyperplastic serrated polyps (SSA/P, TSA and SA) and 12.5% as hyperpalstic polyps. Of the non-hyperplastic serrated polyps, a majority were diagnosed as SA. Upon reassessment of right sided HP (n=121), 34% were re-classified as SSA/P. CONCLUSIONS: Winnipeg pathologists diagnose non-hyperplastic serrated polyps with a frequency similar to literature, but are not fully utilizing modern terminology, as majority of non-hyperplastic serrated polyps are reported as SA without further categorisation. Furthermore, a significant proportion of right sided hyperplastic polyps could be re-classified as sessile serrated adenomas on review. Given the difficulty in distinguishing sessile serrated adenomas from hyperplastic polyps, closer endoscopic surveillance should be considered for all individuals with all serrated polyps (including hyperplastic polyps) in the right colon or alternatively all such polyps should be routinely reviewed by two pathologists. Advisors/Committee Members: Wightman, Robert H. (Pathology) (supervisor), Gartner, John (Pathology) Singh, Harminder (Internal Medicine) Fuczek, Lance (Pathology) (examiningcommittee).

Subjects/Keywords: Pathology

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APA (6^th Edition):

Bay, D. (2011). Serrated polyps of the colon: the Winnipeg experience. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/4885

Chicago Manual of Style (16^th Edition):

Bay, Diane. “Serrated polyps of the colon: the Winnipeg experience.” 2011. Masters Thesis, University of Manitoba. Accessed March 01, 2021. http://hdl.handle.net/1993/4885.

MLA Handbook (7^th Edition):

Bay, Diane. “Serrated polyps of the colon: the Winnipeg experience.” 2011. Web. 01 Mar 2021.

Vancouver:

Bay D. Serrated polyps of the colon: the Winnipeg experience. [Internet] [Masters thesis]. University of Manitoba; 2011. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/1993/4885.

Council of Science Editors:

Bay D. Serrated polyps of the colon: the Winnipeg experience. [Masters Thesis]. University of Manitoba; 2011. Available from: http://hdl.handle.net/1993/4885

Boston University

16. Jang, Sunyoung. Characterization of the recruitment of intimal smooth muscle cells in vascular disease.

Degree: 2014, Boston University

URL: http://hdl.handle.net/2144/14329

► Intimal hyperplasia occurs as a response to a variety of vascular insults and results in vascular stenosis, and organ ischemia. This process represents a fundamental… (more)

Subjects/Keywords: Pathology

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APA (6^th Edition):

Jang, S. (2014). Characterization of the recruitment of intimal smooth muscle cells in vascular disease. (Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/14329

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jang, Sunyoung. “Characterization of the recruitment of intimal smooth muscle cells in vascular disease.” 2014. Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/14329.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jang, Sunyoung. “Characterization of the recruitment of intimal smooth muscle cells in vascular disease.” 2014. Web. 01 Mar 2021.

Vancouver:

Jang S. Characterization of the recruitment of intimal smooth muscle cells in vascular disease. [Internet] [Thesis]. Boston University; 2014. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/14329.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jang S. Characterization of the recruitment of intimal smooth muscle cells in vascular disease. [Thesis]. Boston University; 2014. Available from: http://hdl.handle.net/2144/14329

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

17. Araujo, Amanda G. Assessment and visualization of neuronal remodeling in association with various cardiovascular conditions.

Degree: MS, Pathology, 2020, Boston University

URL: http://hdl.handle.net/2144/41170

► It has been reported in previous works that there is a greater neuron density in the stellate ganglion of patients with cardiovascular disease. However, an… (more)

▼ It has been reported in previous works that there is a greater neuron density in the stellate ganglion of patients with cardiovascular disease. However, an analysis of this effect on neuron density and how it may differ between the different conditions falling under the realm of cardiovascular disease has yet to be studied. Analysis of this relationship between the Autonomic Nervous System (ANS) and cardiovascular function can provide insight into the disease process of each of the studied conditions, and more specifically, whether the ANS plays more of a causative or compensatory role in these instances. In this study, stellate ganglion pathology from patients with Coronary Artery Disease (CAD), Myocardial Infarction (MI), or Heart Failure (HF) were studied and compared to subjects with little to no cardiovascular pathology. We hypothesized that cardiovascular disease patients would have higher levels of neural remodeling, and perhaps more so in chronic conditions like CAD and HF as opposed to single events like MI. Stellate ganglia were harvested from one or both sides of 17 human cadavers and prepared slides from the middle section of each ganglion were scanned digitally for analysis. Neurons were counted using an automated algorithm accounting for size and shape to specifically select for nerve cell bodies, and for further analysis, heat maps of neuron nearest neighbor density were created. Analysis considering the variables of neuron size, number of neurons, and percent area of the ganglion occupied by neurons resulted in a statistical main effect of disease cohort but not side of the ganglion or the interaction of cohort and side. Between subject effects showed that only average neuron size was a significant factor in the model. Overall, patients with cardiovascular disease displayed neural remodeling in comparison to those with little to no cardiovascular pathology, and these effects were different across the several different conditions. Some caveats to this study were sample size, especially for MI patients, and analysis of only the middle section of each ganglion. A further analysis including more of the ganglion outside of a representative section, and more subjects in each cohort, especially with MI pathology, shows promise of more definitive conclusions. Advisors/Committee Members: Wisco, Jonathan (advisor).

Subjects/Keywords: Pathology

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APA (6^th Edition):

Araujo, A. G. (2020). Assessment and visualization of neuronal remodeling in association with various cardiovascular conditions. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/41170

Chicago Manual of Style (16^th Edition):

Araujo, Amanda G. “Assessment and visualization of neuronal remodeling in association with various cardiovascular conditions.” 2020. Masters Thesis, Boston University. Accessed March 01, 2021. http://hdl.handle.net/2144/41170.

MLA Handbook (7^th Edition):

Araujo, Amanda G. “Assessment and visualization of neuronal remodeling in association with various cardiovascular conditions.” 2020. Web. 01 Mar 2021.

Vancouver:

Araujo AG. Assessment and visualization of neuronal remodeling in association with various cardiovascular conditions. [Internet] [Masters thesis]. Boston University; 2020. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/2144/41170.

Council of Science Editors:

Araujo AG. Assessment and visualization of neuronal remodeling in association with various cardiovascular conditions. [Masters Thesis]. Boston University; 2020. Available from: http://hdl.handle.net/2144/41170

University of Cape Town

18. Majara, Lerato Charlotte. HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution.

Degree: Image, Clinical Laboratory Sciences, 2016, University of Cape Town

URL: http://hdl.handle.net/11427/28263

► It is widely held that for an HIV-1 vaccine to provide sterilizing immunity, it would need to elicit broadly neutralizing antibodies (bnAbs). However, factors underlying… (more)

Subjects/Keywords: Pathology

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APA (6^th Edition):

Majara, L. C. (2016). HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution. (Thesis). University of Cape Town. Retrieved from http://hdl.handle.net/11427/28263

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Majara, Lerato Charlotte. “HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution.” 2016. Thesis, University of Cape Town. Accessed March 01, 2021. http://hdl.handle.net/11427/28263.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Majara, Lerato Charlotte. “HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution.” 2016. Web. 01 Mar 2021.

Vancouver:

Majara LC. HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution. [Internet] [Thesis]. University of Cape Town; 2016. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/11427/28263.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Majara LC. HIV-1 strain-specific neutralizing antibody responses and the dynamics of viral evolution. [Thesis]. University of Cape Town; 2016. Available from: http://hdl.handle.net/11427/28263

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Duke University

19. Bao, Xuhui. Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors .

Degree: 2016, Duke University

URL: http://hdl.handle.net/10161/13365

► Glioblastoma is the most common and aggressive malignant brain tumor among all primary brain and central nervous system (CNS) tumors. The median survival time… (more)

▼ Glioblastoma is the most common and aggressive malignant brain tumor among all primary brain and central nervous system (CNS) tumors. The median survival time for glioblastoma patients given the current standard of care treatment (surgery, radiation, and chemotherapy) is less than 15 months. Medulloblastoma is another major malignant brain tumor that most frequently occurs in children. Although recent advances in surgery, radiotherapy, and chemotherapy have led to an increase in 5-year survival rates of medulloblastoma patients, treatment-related toxicity often has a major impact on long-term quality of survival. As a result, there is an urgent need to develop more efficient and novel therapeutic approaches that specifically target tumor cells while preserving the surrounding normal CNS to improve the poor survival and quality of life of patients with malignant brain tumors. To address this need, we have developed two novel targeted immunotoxins (ITs), D2C7-(scdsFv)-PE38KDEL (D2C7-IT) and NZ-1-(scdsFv)-PE38KDEL (NZ-1-IT). D2C7-IT was developed by fusing the single-chain variable fragment (scFv) of the D2C7 monoclonal antibody (mAb) with domains II and III of Pseudomonas exotoxin A (PE38KDEL), and NZ-1-IT was developed by fusing the scFv of the NZ-1 mAb with PE38KDEL. D2C7-IT reacts with both the wild-type epidermal growth factor receptor (EGFRwt) and the EGFR variant III (EGFRvIII), two overexpressed proteins in glioblastomas. NZ-1-IT reacts with podoplanin (PDPN), a protein that has a high expression in glioblastomas and medulloblastomas. In vitro cytotoxicity data shows that both ITs effectively inhibited protein synthesis in a variety of epitope-expressing glioblastoma and medulloblastoma xenograft cells and human tumor cell lines. Furthermore, the direct anti-tumor efficacy of D2C7-IT was examined in orthotopic glioma models in immunocompromised mice, while the direct anti-tumor efficacy of NZ-1-IT was observed in medulloblastoma xenograft-bearing immunocompromised mice. Both immunotoxins showed a robust anti-tumor efficacy in the preclinical brain tumor models. D2C7-IT was first investigated in the subsequent studies to accelerate its translation to the clinic. The preclinical toxicity of intracerebral D2C7-IT infusion was subsequently determined in normal Sprague-Dawley (SD) rats. The maximum tolerated dose (MTD) of D2C7-IT was determined to be between a total dose of 0.10 and 0.35 μg, and the no-observed-adverse-effect level (NOAEL) of D2C7-IT was a total dose of 0.05 μg in SD rats. Both the MTD and NOAEL were utilized as references for the D2C7-IT clinical trial design. In addition to direct tumor cell killing, immunotoxin monotherapy has been shown to induce a secondary anti-tumor immune response through the engagement of T cells. Therefore, the D2C7-IT-induced secondary anti-tumor immune response was investigated using syngeneic mouse glioma models in immunocompetent mice. Moreover, previous studies have demonstrated that immune checkpoint inhibitors have a robust anti-tumor efficacy… Advisors/Committee Members: Bigner, Darell D (advisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bao, X. (2016). Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/13365

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bao, Xuhui. “Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors .” 2016. Thesis, Duke University. Accessed March 01, 2021. http://hdl.handle.net/10161/13365.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bao, Xuhui. “Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors .” 2016. Web. 01 Mar 2021.

Vancouver:

Bao X. Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors . [Internet] [Thesis]. Duke University; 2016. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10161/13365.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bao X. Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors . [Thesis]. Duke University; 2016. Available from: http://hdl.handle.net/10161/13365

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

McGill University

20. AlGhamdi, Sarah. Modeling intra-abdominal high grade serous ovarian cancer of human origin in nude mice.

Degree: MS, Department of Pathology, 2018, McGill University

URL: https://escholarship.mcgill.ca/downloads/5425kc98x.pdf ; https://escholarship.mcgill.ca/concern/theses/m613n0943

► Contexte: Le cancer de l'ovaire est la maladie la plus mortelle de l'appareil reproducteur féminin. Au moment du diagnostic, dans la plupart des cas, la… (more)

▼ Contexte: Le cancer de l'ovaire est la maladie la plus mortelle de l'appareil reproducteur féminin. Au moment du diagnostic, dans la plupart des cas, la maladie a déjà progressé au-delà des ovaires, dans les structures pelviennes adjacentes et divers autres sites dans la cavité péritonéale. Le cancer ovarien séreux de haut grade (HGSOC) est le sous-type le plus commun, représentant près de 70% de tous les cas de cancer de l'ovaire. Avoir un modèle de souris HGSOC avec un phénotype de la maladie aussi proche qu'il se développe chez les humains, devrait permettre une meilleure évaluation des options thérapeutiques précliniques ainsi qu'une meilleure compréhension de la progression de la maladie. Les modèles de souris orthométastatiques de HGSOC péritonéale sont mal décrits dans la littérature. La plupart des lignées de cellules ovariennes étudiées chez des souris immunodéprimées sont implantées par voie sous-cutanée plutôt qu'intra-péritonéale, ne reflétant ainsi pas la nature de la maladie et, par conséquent, ne permettant pas une évaluation claire des réponses au traitement. De plus, la plupart des études publiées utilisaient des lignées cellulaires de cancer de l'ovaire qui ont une faible fidélité génétique avec HGSOC. Par conséquent, nous avons créé des modèles murins de HGSOC en utilisant des lignées cellulaires avec une fidélité génétique à HGSOC, visant à permettre une meilleure évaluation des options thérapeutiques précliniques ainsi qu'une meilleure compréhension de la progression de la maladie.Méthodes: Des souris nudes athymiques ont été injectées par voie intrapéritonéale avec l'une des lignées cellulaires suivantes: OVCAR-4, PEO14 ou OVSAHO. Les trois lignées cellulaires ont montré l'expression de ARID1A, PAX8 et mutant p53, avec une expression variable de CA125 et WT1. Nous avons comparé entre les modèles le temps nécessaire pour que la maladie se développe, les tissus ciblés et les anomalies histopathologiques détectées. Nous avons également effectué des tests fonctionnels pour tester et comparer la capacité des lignées cellulaires pour la migration et l'invasion.Résultats: Le temps écoulé pour que la maladie se développe pour toutes les lignées cellulaires allait de 4 à 11 mois. Ce résultat est en contraste avec les moins de 3 mois nécessaires à l'évolution de la maladie dans la cavité péritonéale lors de l'injection de cellules de fidélité HGSOC improbable, telles que SKOV-3 ou A2780. Au sein des trois lignées cellulaires utilisées, nous avons trouvé des points communs et des différences en termes de comportement in vivo. Parmi les points communs, toutes les cellules se sont dirigées vers la zone omentale-rate-pancréatique, la base hépatique, le mésentère et le diaphragme. Parmi les différences, les cellules PEO14 ont développé des masses considérables qui n'envahissaient pas les organes abdominaux. Les cellules OVSAHO ont développé des masses plus discrètes, entourant étroitement les organes sans les envahir. Enfin, les cellules OVCAR-4 ont provoqué une invasivité totale dans les organes de la cavité… Advisors/Committee Members: Carlos Telleria (Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

AlGhamdi, S. (2018). Modeling intra-abdominal high grade serous ovarian cancer of human origin in nude mice. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/5425kc98x.pdf ; https://escholarship.mcgill.ca/concern/theses/m613n0943

Chicago Manual of Style (16^th Edition):

AlGhamdi, Sarah. “Modeling intra-abdominal high grade serous ovarian cancer of human origin in nude mice.” 2018. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/5425kc98x.pdf ; https://escholarship.mcgill.ca/concern/theses/m613n0943.

MLA Handbook (7^th Edition):

AlGhamdi, Sarah. “Modeling intra-abdominal high grade serous ovarian cancer of human origin in nude mice.” 2018. Web. 01 Mar 2021.

Vancouver:

AlGhamdi S. Modeling intra-abdominal high grade serous ovarian cancer of human origin in nude mice. [Internet] [Masters thesis]. McGill University; 2018. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/5425kc98x.pdf ; https://escholarship.mcgill.ca/concern/theses/m613n0943.

Council of Science Editors:

AlGhamdi S. Modeling intra-abdominal high grade serous ovarian cancer of human origin in nude mice. [Masters Thesis]. McGill University; 2018. Available from: https://escholarship.mcgill.ca/downloads/5425kc98x.pdf ; https://escholarship.mcgill.ca/concern/theses/m613n0943

McGill University

21. Pareek, Swati. RelB regulation of cigarette smoke-induced pulmonary inflammation.

Degree: MS, Department of Pathology, 2018, McGill University

URL: https://escholarship.mcgill.ca/downloads/qn59q6514.pdf ; https://escholarship.mcgill.ca/concern/theses/sb397b60r

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Le système immunitaire produit de l'inflammation en réponse à une blessure ou une infection. Bien que l'inflammation aiguë a un rôle protecteur, l'inflammation chronique peut… (more)

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Le système immunitaire produit de l'inflammation en réponse à une blessure ou une infection. Bien que l'inflammation aiguë a un rôle protecteur, l'inflammation chronique peut entraîner des lésions persistantes dans les tissus et les organes. Par exemple, les poumons sont vulnérables aux irritants provenant de l'environnement extérieur et sont donc susceptibles de développer des lésions et de l'inflammation. RelB est un membre de la voie non-canonique du facteur transcriptionel NF-κB qui joue un rôle important dans l'inflammation et la mort cellulaire. Notre laboratoire a précédemment montré que RelB protège contre l'apoptose et l'inflammation induites in vitro par la fumée de cigarette ; un puissant irritant et une cause majeure de morbidité et de mortalité dans le monde. Cependant, le rôle protecteur de RelB dans les poumons est moins connu. Nous avons émis l'hypothèse que RelB protège contre l'inflammation pulmonaire induite par la fumée de cigarette. Pour valider notre hypothèse, nous avons exposé des souris de type sauvage (RelB+/+) ou déficientes en RelB (RelB-/-) à la fumée de cigarette Nous avons trouvé que l'exposition à la fumée de la cigarette entraîne une diminution du nombre de granulocytes des voies respiratoires chez les souris RelB-/-; cette diminution des granulocytes est surtout liée à une diminution de nombre des neutrophiles. L'inflammation pulmonaire causée par d'autres irritants, y compris la chlorine, l'ovalbumine (pour imiter les caractéristiques de l'asthme), et les lipopolysaccharides n'est pas affectée par l'absence de RelB. L'analyse différentielle des cytokines par dosage multiplexe suggère que les altérations de l'expression de cytokines et chimiokines n'expliquent pas pleinement la diminution de nombre de neutrophiles chez les souris RelB-/- exposées à la fumée de cigarette. L'analyse par cytométrie de flux du lavage broncho-alvéolaire et des cellules de moelle osseuse révèle également qu'il est peu probable que la diminution de neutrophiles soit provoquée par une mort cellulaire excessive ou une diminution de l'hématopoïèse. Dans l'ensemble, nos résultats indiquent que RelB régule l'inflammation pulmonaire aiguë induite par la fumée de cigarette par un mécanisme non identifié. La compréhension du mécanisme par lequel RelB régule l'inflammation induite par la fumée de cigarette pourrait mener à la découverte de nouvelles stratégies thérapeutiques ciblant des maladies inflammatoires infligées par une exposition prolongée à la fumée de cigarette.

Inflammation is a response to injury and infection. Although protective under physiological conditions, excessive and persistent inflammation is linked to disease. As the lungs are continuously exposed to the external environment and subjected to injury by irritants, it is particularly liable to inflammation. RelB is a member of the non-canonical NF-κB pathway that may control lung inflammation and cell death caused by cigarette smoke (CS), a potent irritant and a leading cause of morbidity and mortality around the world. Our lab has…

Advisors/Committee Members: Carolyn Baglole (Internal/Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pareek, S. (2018). RelB regulation of cigarette smoke-induced pulmonary inflammation. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/qn59q6514.pdf ; https://escholarship.mcgill.ca/concern/theses/sb397b60r

Chicago Manual of Style (16^th Edition):

Pareek, Swati. “RelB regulation of cigarette smoke-induced pulmonary inflammation.” 2018. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/qn59q6514.pdf ; https://escholarship.mcgill.ca/concern/theses/sb397b60r.

MLA Handbook (7^th Edition):

Pareek, Swati. “RelB regulation of cigarette smoke-induced pulmonary inflammation.” 2018. Web. 01 Mar 2021.

Vancouver:

Pareek S. RelB regulation of cigarette smoke-induced pulmonary inflammation. [Internet] [Masters thesis]. McGill University; 2018. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/qn59q6514.pdf ; https://escholarship.mcgill.ca/concern/theses/sb397b60r.

Council of Science Editors:

Pareek S. RelB regulation of cigarette smoke-induced pulmonary inflammation. [Masters Thesis]. McGill University; 2018. Available from: https://escholarship.mcgill.ca/downloads/qn59q6514.pdf ; https://escholarship.mcgill.ca/concern/theses/sb397b60r

McGill University

22. Lasiste, Jade Marie Edenvirg. Metformin inhibits epithelial-to-mesenchymal transition in lens epithelial cells.

Degree: MS, Department of Pathology, 2017, McGill University

URL: https://escholarship.mcgill.ca/downloads/vt150m575.pdf ; https://escholarship.mcgill.ca/concern/theses/2227ms42r

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Purpose: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, affecting up to 50% of patients 2-5 years post-operatively. Epithelial-to-mesenchymal transition (EMT)… (more)

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Purpose: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, affecting up to 50% of patients 2-5 years post-operatively. Epithelial-to-mesenchymal transition (EMT) is the main pathophysiology underlying PCO. Metformin, a drug with an excellent safety profile used primarily for diabetes, has been shown to suppress EMT. The objective of this study was to test the effectiveness of metformin in inhibiting EMT in an in vitro model of PCO. Methods: The human lens epithelial cell (LEC) line HLE-B3 was exposed to transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF) to induce EMT. Subsequently, the effect of metformin on the following cellular parameters were determined: (1) survival, using a viability assay and drug concentrations ranging from 0-100 mM; (2) expression of epithelial (Pax6, E-cadherin) and mesenchymal (α-smooth muscle actin or α-SMA, fibronectin) markers via Western blot; (3) morphology, via microscopy and image analysis; (4) and migration, using the wound assay. The presence of the metformin uptake receptor SLC22A1 in the cell line and the ratio of active to inactive protein kinase B (pAkt/Akt) were assessed via Western blot. SLC22A1 expression was confirmed with immunohistochemistry on donor eyes. Statistical analysis of variance (ANOVA) with Tukey post-hoc test was done for analysis of cytotoxicity, morphology and migration data. Results: Metformin is lethal to half (LC50) and all cells at 30 and 80 mM, respectively. A decrease in viability (P<0.05) was noted at 5 mM. Compared to untreated cells, EMT-induced LECs treated with 1 mM metformin showed increased Pax6 and E-cadherin and decreased α-SMA and fibronectin expression. LECs treated with metformin also maintained the roundness and circularity consistent with an epithelial phenotype. In addition, migration was significantly inhibited with 0.5 mM metformin (P<0.05). The HLE-B3 cell line and lens ocular epithelium in donor eyes were found to express SLC22A1, and treated HLE-B3 cells showed a decreased pAkt/Akt ratio. Conclusion: Metformin inhibits EMT in LECs, decreasing survival and migration and maintaining the epithelial phenotype. These findings suggest that metformin entry into the cell is through the SLC22A1 receptor, and its action mediated via decreased Akt activation. Metformin thus has potential as an adjunct to treatment. Toxicity to proximal eye tissues and effectiveness in vivo must be tested to determine dose, route and timing of administration.

Objectif: L'Opacification de la capsule postérieure (OCP) est la complication la plus courante suite à la chirurgie d'une cataracte et affecte environ la moitié des patients dans les 2-5 années suivant l'opération. Un phénomène appelé transition épithéliale-à-mésenchymale (TEM) est le principal mécanisme sous-jacent l'OCP. La metformin, un médicament principalement utilisé chez les diabétiques et ayant un excellent profil thérapeutique, est reconnue pour sa capacité d'inhibition de la TEM. L'objectif de cette étude est de vérifier et…

Advisors/Committee Members: Miguel Noel Burnier (Internal/Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lasiste, J. M. E. (2017). Metformin inhibits epithelial-to-mesenchymal transition in lens epithelial cells. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/vt150m575.pdf ; https://escholarship.mcgill.ca/concern/theses/2227ms42r

Chicago Manual of Style (16^th Edition):

Lasiste, Jade Marie Edenvirg. “Metformin inhibits epithelial-to-mesenchymal transition in lens epithelial cells.” 2017. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/vt150m575.pdf ; https://escholarship.mcgill.ca/concern/theses/2227ms42r.

MLA Handbook (7^th Edition):

Lasiste, Jade Marie Edenvirg. “Metformin inhibits epithelial-to-mesenchymal transition in lens epithelial cells.” 2017. Web. 01 Mar 2021.

Vancouver:

Lasiste JME. Metformin inhibits epithelial-to-mesenchymal transition in lens epithelial cells. [Internet] [Masters thesis]. McGill University; 2017. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/vt150m575.pdf ; https://escholarship.mcgill.ca/concern/theses/2227ms42r.

Council of Science Editors:

Lasiste JME. Metformin inhibits epithelial-to-mesenchymal transition in lens epithelial cells. [Masters Thesis]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/vt150m575.pdf ; https://escholarship.mcgill.ca/concern/theses/2227ms42r

McGill University

23. Mastromonaco, Christina. Intraocular lens biocompatibility: a novel, objective approach to understanding posterior capsular opacification.

Degree: MS, Department of Pathology, 2017, McGill University

URL: https://escholarship.mcgill.ca/downloads/ht24wm799.pdf ; https://escholarship.mcgill.ca/concern/theses/6m311r97q

►

Posterior capsular opacification (PCO) is the leading complication following cataract surgery. Understanding factors that contribute to PCO development is a significant public concern as treatment… (more)

▼

Posterior capsular opacification (PCO) is the leading complication following cataract surgery. Understanding factors that contribute to PCO development is a significant public concern as treatment can lead to complications. PCO depends on the biocompatibility of the patient and the artificial lens; known as an intraocular lens (IOL), implanted within the capsular bag of the eye after cataract surgery. In order to prevent PCO, a better understanding of IOL characteristics, including design and material, and how it interacts with patients is required. Herein, this study investigates three main objectives: to invent a new objective PCO quantification system in post-mortem eyes, to validate this methodology, and to perform a retrospective multivariable analysis to determine which factors (IOL and patient-based) are least likely to result in PCO. The ultimate goal is to find the optimum IOL platform for patients. In total, 180 post-mortem eyes with implanted IOLs were collected from the Minnesota Eye Bank, along with their clinical history, including date of cataract surgery and IOL model number. The capsular bag (CB) with the IOL implant was removed from all eyes to obtain digital images. PCO outcome was quantified on CB images using an objective, novel automated custom image analyzer. The software measured intensity and area of the opacification within the IOL optic edge, intra-optic edge (IOE= intensity/area), and the opacities found within the capsular bag just outwards of the IOL optic, known as Soemmering's ring (SR= intensity/area). Software-derived PCO outcomes were statistically analyzed with previously used subjective PCO grading to verify validity. Epidemiologic analysis determined which IOL characteristics and patient-related factors correlated with PCO. IOL factors included material, edge design, lens filter, decentration and time of IOL implantation. Patient factors included sex, age and diabetes mellitus, among others.The software PCO grading system correlated well with previous scoring methods. Multivariate analyses showed non-diabetic patients had less SR (P= 0.05). Individuals 50-80 years old compared to 80+ had lower SR PCO (P= 0.01). Square and frosted optic edge design had lower SR and IOE PCO rates compared to OptiEdge (P= 0.001, 0.03). Patients with an IOL implanted for less then 25 months had lower SR and IOE PCO. (P= 0.0001, 0.004). In order to generate a lens that does not develop PCO, it is critical to understand the IOL- and patient-related factors that lead to PCO development. Based on our data, the most susceptible patients are elderly and diabetic, and it may be preferable to implant a square and frosted edge lens.

L'opacification capsulaire postérieure (OCP) est la principale complication après une chirurgie de la cataracte. Les éléments qui contribuent au développement de l'OCP sont une préoccupation majeure du public car le traitement peut provoquer des complications. L'OCP dépend de la biocompatibilité du patient envers la lentille artificielle; appelée lentille intraoculaire (LIO).…

Advisors/Committee Members: Miguel Noel Burnier (Internal/Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mastromonaco, C. (2017). Intraocular lens biocompatibility: a novel, objective approach to understanding posterior capsular opacification. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/ht24wm799.pdf ; https://escholarship.mcgill.ca/concern/theses/6m311r97q

Chicago Manual of Style (16^th Edition):

Mastromonaco, Christina. “Intraocular lens biocompatibility: a novel, objective approach to understanding posterior capsular opacification.” 2017. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/ht24wm799.pdf ; https://escholarship.mcgill.ca/concern/theses/6m311r97q.

MLA Handbook (7^th Edition):

Mastromonaco, Christina. “Intraocular lens biocompatibility: a novel, objective approach to understanding posterior capsular opacification.” 2017. Web. 01 Mar 2021.

Vancouver:

Mastromonaco C. Intraocular lens biocompatibility: a novel, objective approach to understanding posterior capsular opacification. [Internet] [Masters thesis]. McGill University; 2017. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/ht24wm799.pdf ; https://escholarship.mcgill.ca/concern/theses/6m311r97q.

Council of Science Editors:

Mastromonaco C. Intraocular lens biocompatibility: a novel, objective approach to understanding posterior capsular opacification. [Masters Thesis]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/ht24wm799.pdf ; https://escholarship.mcgill.ca/concern/theses/6m311r97q

McGill University

24. Aldrees, Sultan. The effects of varying intensities of blue light on the proliferation of human uveal melanoma cell lines by using multiple blue light filters.

Degree: MS, Department of Pathology, 2017, McGill University

URL: https://escholarship.mcgill.ca/downloads/bn9999253.pdf ; https://escholarship.mcgill.ca/concern/theses/cz30pw330

► L'exposition répétée à la lumière bleue (LB) est considérée comme un facteur de risque pour le développement de mélanomes de l'uvée (MU). Ce risque est… (more)

▼ L'exposition répétée à la lumière bleue (LB) est considérée comme un facteur de risque pour le développement de mélanomes de l'uvée (MU). Ce risque est augmenté chez les individus au teint et aux iris clairs. De plus, un effet angiogénique de la LB fut établi pour des modèles cellulaires humains de MU. Ceci est d'une importance particulière étant donné que les MU métastasent par voie sanguine. Il fut démontré dans plusieurs études in vitro et in vivo que certaines lentilles intraoculaires (LIO) commerciales ayant la capacité de filtrer 50% de la LB offrent une protection contre le développement et la progression des MU. L'objectif de cette étude est de vérifier la possibilité de réduire le pouvoir de filtration des LIOs tout en maintenant leur effet protecteur dans un modèle cellulaire de MU. Par le fait même, la relation entre les propriétés angiogéniques de ces lignées cellulaires et la quantité de LB filtrée sera établie.Cette étude vise à permettre le développement de lentilles ayant une capacité de filtration de LB ajustée selon les facteurs de risques de chaque individu, tel que proposé par la notion de médecine personnalisée.Dans le cadre de ce projet, les lignées cellulaire 92.1 et UW-1, deux modèles de MU humains au pouvoir prolifératif et métastatique différents, ont été utilisées. Le design expérimental requiert une source lumineuse de 10 000 lux, des filtres infra-rouges et ultra-violets ainsi que deux filtres commerciaux ayant différents pouvoir de filtration de la LB (16% et 20%).Pour chaque essai, un groupe contrôle fut complètement exposé à la lumière, tandis que les deux autres groupes étaient protégés par l'un des filtres à LB (16% et 20%). Les cellules furent quotidiennement exposées à la source lumineuse pour une période de trois heures, et cela pour quatre jours consécutifs. La prolifération cellulaire fut déterminée par un test cytotoxique (CCK-8, Cell Counting Kit 8) à la suite de chaque séance d'exposition à la lumière.Le même design expérimental fût utilisé afin de quantifier les niveaux de facteurs d'angiogenèse sécrétés par chacune des lignées cellulaires. Pour ce faire, la méthode immuno-enzymatique ELISA en sandwich (enzyme-linked Immunosorbent assay) fût utilisée.Les résultats suggèrent une diminution significative du taux de prolifération de la lignée 92.1 lorsque 20% de la LB est filtrée (P= <0.01). Par contre, la filtration de 16% de la LB n'est pas suffisante pour obtenir un effet semblable. Inversement, la filtration de 16% de la LB démontre un ralentissement significatif de la prolifération cellulaire pour la lignée UW-1 en comparaison au groupe contrôle complètement exposé à la source lumineuse (P= <0.01). D'un autre côté, la filtration de 20% et 26% de la LB pour la lignée 92.1 et UW-1 respectivement entraine une diminution non-significative du niveau de facteurs d'angiogenèse.Le modèle d'étude in vitro ici-décrit vient appuyer l'hypothèse que la filtration de lumière bleue entraine un effet protecteur contre la prolifération de cellules humaine de mélanome de l'uvée. À ce jour,… Advisors/Committee Members: Miguel Noel Burnier (Internal/Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Aldrees, S. (2017). The effects of varying intensities of blue light on the proliferation of human uveal melanoma cell lines by using multiple blue light filters. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/bn9999253.pdf ; https://escholarship.mcgill.ca/concern/theses/cz30pw330

Chicago Manual of Style (16^th Edition):

Aldrees, Sultan. “The effects of varying intensities of blue light on the proliferation of human uveal melanoma cell lines by using multiple blue light filters.” 2017. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/bn9999253.pdf ; https://escholarship.mcgill.ca/concern/theses/cz30pw330.

MLA Handbook (7^th Edition):

Aldrees, Sultan. “The effects of varying intensities of blue light on the proliferation of human uveal melanoma cell lines by using multiple blue light filters.” 2017. Web. 01 Mar 2021.

Vancouver:

Aldrees S. The effects of varying intensities of blue light on the proliferation of human uveal melanoma cell lines by using multiple blue light filters. [Internet] [Masters thesis]. McGill University; 2017. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/bn9999253.pdf ; https://escholarship.mcgill.ca/concern/theses/cz30pw330.

Council of Science Editors:

Aldrees S. The effects of varying intensities of blue light on the proliferation of human uveal melanoma cell lines by using multiple blue light filters. [Masters Thesis]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/bn9999253.pdf ; https://escholarship.mcgill.ca/concern/theses/cz30pw330

McGill University

25. Alabdulkarim, Balqis. Imaging mass spectrometry application in colorectal cancer liver metastasis pathological evaluation.

Degree: MS, Department of Pathology, 2016, McGill University

URL: https://escholarship.mcgill.ca/downloads/g158bm068.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq16z

►

Le cancer colorectal (CCR) est la deuxième cause la plus importante de mortalité dérivée du cancer en Amérique du Nord. La mort causée par le… (more)

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Le cancer colorectal (CCR) est la deuxième cause la plus importante de mortalité dérivée du cancer en Amérique du Nord. La mort causée par le CCR peut être attribuée à la métastase du cancer. Le site le plus fréquent de métastase éloignée de l'origine du CCR est le foie. Si cela est possible, la chirurgie donne la seule occasion de traitement pour les patients avec des métastases hépatiques du cancer colorectal (MHCCR). Les soins administrés après résection ainsi que le choix de chimiothérapie adjuvante dépendent de l'évaluation pathologique du grade de la tumeur. Plusieurs méthodes d'évaluation histopathologique ont été dévelopées, mais leurs corrélations avec les résultats des patients sont variables. Jusqu'à date, le « Tumor Regression Grade » (TRG) avait la plus forte corrélation avec les résultats des patients. Celui-ci marque les lésions selon la proportion de fibrose sur la somme de tumeurs viables et de nécrose. Pourtant, l'usage répandu d'agents anti-angiogéniques qui causent la nécrose lors de la période préopératoire a poussé le TRG à évoluer en TRG modifié (mTRG). Le mTRG différencie entre deux types de nécrose qui ont des rôles prognostiques différents : la Nécrose Commune (NC) et la Necrose qui ressemble à une infarctus (ILN). De plus, les évaluations pathologiques restent quand-même limitées par leur nature subjective. Le projet présenté dans ce mémoire décrit l'utilisation de l'imagerie de spectroscopie de masse (ISM) par Désorption/Ionisation Laser assistée par Matrice (MALDI) afin de définir les signatures lipidiques signatures pour des topographies différentes. Nous avons initialement appliqué une approche histologique semi-supervisée afin de construire notre banque spectrale par une méthode automatique de classification (k-means) et des corrélations histologiques visuelles directes (panneau de 5 couleurs) sur une série d'échantillons préparatoire (n=12). Nous avons identifié six signatures lipidiques qui sont mises en corrélation par histologie et puis, nous les avons exploitées afin de découvrir des marqueurs lipidiques discriminants. Nous avons utilisé la méthode d'analyse « Partial Least Squares-Discriminant » (PLS-DA) afin de mettre en place notre banque spectrale sur une cohorte de validation indépendante de 40 patients. De plus, en analysant les signatures lipidiques, nous avons identifié des fractions lipidiques uniques distinguant les NC et les ILN, qui peuvent potentiellement être utilisées comme biomarqueurs pour évaluer la réaction au traitement. En utilisant ces signatures et marqueurs lipidiques, nous avons obtenu un score de mTRG quantifié par histologie et objectif.

Colorectal Cancer (CRC) is the second leading cause of cancer mortality in North America. Death from CRC is largely due to metastatic disease and the liver is the most common site of distant metastasis. Surgery when feasible carries the only chance of cure for Colorectal Cancer Liver Metastasis (CRCLM) patients. Post surgical resection further patient management and choice of adjuvant chemotherapy relies on…

Advisors/Committee Members: Peter Metrakos (Internal/Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alabdulkarim, B. (2016). Imaging mass spectrometry application in colorectal cancer liver metastasis pathological evaluation. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/g158bm068.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq16z

Chicago Manual of Style (16^th Edition):

Alabdulkarim, Balqis. “Imaging mass spectrometry application in colorectal cancer liver metastasis pathological evaluation.” 2016. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/g158bm068.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq16z.

MLA Handbook (7^th Edition):

Alabdulkarim, Balqis. “Imaging mass spectrometry application in colorectal cancer liver metastasis pathological evaluation.” 2016. Web. 01 Mar 2021.

Vancouver:

Alabdulkarim B. Imaging mass spectrometry application in colorectal cancer liver metastasis pathological evaluation. [Internet] [Masters thesis]. McGill University; 2016. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/g158bm068.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq16z.

Council of Science Editors:

Alabdulkarim B. Imaging mass spectrometry application in colorectal cancer liver metastasis pathological evaluation. [Masters Thesis]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/g158bm068.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq16z

McGill University

26. Janssen, Sanne. Deciphering the role of BORIS/CTCFL in melanoma.

Degree: PhD, Department of Pathology, 2019, McGill University

URL: https://escholarship.mcgill.ca/downloads/ww72bd95f.pdf ; https://escholarship.mcgill.ca/concern/theses/f1881p29q

► La molécule BORIS (Brother of Regulator of Imprinted Sites) est une protéine de liaison à l'ADN qui est présente dans les testicules mais qui est… (more)

▼ La molécule BORIS (Brother of Regulator of Imprinted Sites) est une protéine de liaison à l'ADN qui est présente dans les testicules mais qui est exprimée d'une manière aberrante dans plusieurs types de cancer, d'où la désignation de BORIS comme un antigène du cancer testiculaire. La présence aberrante de BORIS dans certains cancers altère l'expression des gènes et engendre des modifications épigénétiques qui impactent des processus biologiques clés. Dans le cas des mélanomes, l'expression de BORIS est plus élevée dans les métastases que dans la tumeur primaire, ce qui indique que BORIS joue un rôle dans la progression des mélanomes. Actuellement, la fonction de BORIS dans les mélanomes reste à élucider. Ici, nous étudions les effets de l'expression de BORIS sur les processus biologiques de la progression des mélanomes. Dans la première partie de cette thèse, nous utilisons des résultats antérieurs de notre laboratoire, qui avaient démontré que des modifications dans l'expression de BORIS altérent l'expression génique du chromosome X. Ceci est important, car les différences d'expression génique du chromosome X contribuent probablement à la survie supérieure des femmes atteintes de mélanome comparativement aux hommes. En exploitant des polymorphismes mononucléotidiques dans des gènes localisés sur le chromosome X, nous révélons pour la première fois que l'expression ectopique de BORIS peut altérer l'expression génique d'une manière allèle-spécifique. Plus précisément, nous démontrons que l'expression de ZBTB33, un régulateur transcriptionnel impliqué dans la migration et l'invasion de cellules cancéreuses, est augmentée lors de l'expression de BORIS à partir de l'allèle situè sur le chromosome X inactif. Afin de cibler l'implication de BORIS dans les processus et les voies biologiques des mélanomes, nous avons évalué les changements transcriptionnels induits par BORIS ainsi que les protéines interagissant avec BORIS en utilisant le séquençage d'ARN et la spectrométrie de masse. Nous démontrons que l'expression ectopique de BORIS dans les cellules de mélanome favorise le passage d'un état prolifératif à un état invasif au niveau transcriptionnel et phénotypique. Grâce à une analyse in silico, nous identifions de potentiels régulateurs transcriptionnels qui contribuent à ce passage. Les changements d'expression génique induits par BORIS ainsi que par ses partenaires protéiques nouvellement identifiés suggèrent un rôle de BORIS dans la réponse aux dommages de l'ADN. Ceci est étayé par nos observations que BORIS augmente les dommages à l'ADN, active la réponse aux dommages de l'ADN, rehausse la sensibilité aux dommages de l'ADN et ralentit le processus de réparation, ce qui suggère que BORIS favorise l'instabilité génomique.Dans la dernière partie de cette thèse, nous utilisons l'immunoprécipitation de la chromatine, le séquençage au bisulfite et l'étude de la chromatine accessible aux transposases (ATAC) pour élucider les mécanismes sous-jacents à l'expression génique altérée par BORIS. Nous démontrons que pour six… Advisors/Committee Members: Alan Spatz (Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Janssen, S. (2019). Deciphering the role of BORIS/CTCFL in melanoma. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/ww72bd95f.pdf ; https://escholarship.mcgill.ca/concern/theses/f1881p29q

Chicago Manual of Style (16^th Edition):

Janssen, Sanne. “Deciphering the role of BORIS/CTCFL in melanoma.” 2019. Doctoral Dissertation, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/ww72bd95f.pdf ; https://escholarship.mcgill.ca/concern/theses/f1881p29q.

MLA Handbook (7^th Edition):

Janssen, Sanne. “Deciphering the role of BORIS/CTCFL in melanoma.” 2019. Web. 01 Mar 2021.

Vancouver:

Janssen S. Deciphering the role of BORIS/CTCFL in melanoma. [Internet] [Doctoral dissertation]. McGill University; 2019. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/ww72bd95f.pdf ; https://escholarship.mcgill.ca/concern/theses/f1881p29q.

Council of Science Editors:

Janssen S. Deciphering the role of BORIS/CTCFL in melanoma. [Doctoral Dissertation]. McGill University; 2019. Available from: https://escholarship.mcgill.ca/downloads/ww72bd95f.pdf ; https://escholarship.mcgill.ca/concern/theses/f1881p29q

McGill University

27. Guerrina, Necola. Reduced aryl hydrocarbon receptor (AhR) expression drives the pathogenesis of cigarette smoke-induced emphysema.

Degree: PhD, Department of Pathology, 2019, McGill University

URL: https://escholarship.mcgill.ca/downloads/79408039v.pdf ; https://escholarship.mcgill.ca/concern/theses/5t34sm66g

► Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and complex respiratory disorder primarily caused by inhalational exposure to cigarette smoke (CS). However, only approximately 15%… (more)

▼ Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and complex respiratory disorder primarily caused by inhalational exposure to cigarette smoke (CS). However, only approximately 15% of cigarette smokers develop COPD, suggesting that genetic or epigenetic factors may contribute to disease susceptibility. One feature of COPD is emphysema, which is characterized by permanent alveolar wall destruction leading to airspace enlargement. The alveolar wall destruction in emphysema is a consequence of multiple pathogenic mechanisms including chronic inflammation, a protease: anti-protease imbalance and the upregulation of cell death programs such as apoptosis, autophagy and endoplasmic reticulum (ER) stress. However, molecular mechanism(s) that regulate these pathogenic events, and thus the development of emphysema, are poorly understood. This regulation may involve the aryl hydrocarbon receptor (AhR), which is a ligand-activated transcription factor whose involvement in COPD pathogenesis is unknown. Our lab has previously published that AhR-deficiency exacerbates CS-induced cell death and inflammation in lung structural cells. Thus, we hypothesized that AhR-deficiency would promote the development of CS-induced emphysema and COPD pathogenesis.Using a preclinical model of CS-exposure, we demonstrate that AhR deficiency worsens the development of a CS-induced emphysema-like phenotype in the murine lung. AhR ablation promoted the CS-induced: (1) upregulation of pathogenic mechanisms underlying emphysema development (i.e. inflammation, an antiprotease imbalance, and the activation of cell death machinery), (2) lung parenchymal destruction, and (3) declines in lung function. In COPD subjects, there was less pulmonary and systemic AHR expression. In humans, systemic AHR mRNA levels also positively correlated with lung function. There was no alteration in the frequency of AHR single nucleotide polymorphisms (SNPs) that could explain this decrease in AHR in COPD subjects. However, elevated expression of the AhR Repressor (AHRR), which is a negative regulator of the AHR, in the COPD lung may contribute to reduced AHR expression in these subjects.We also utilized an in vitro model of CS exposure to evaluate if the AhR attenuation of CS-induced cell death in lung structural cells involves its regulation of cell death modalities such as autophagy and/or ER stress. We show that the expression of the autophagy and ER stress protein LC3II was significantly elevated in cigarette smoke extract (CSE)-exposed AhR-deficient lung structural cells; these cells were primary mouse lung fibroblasts (MLFs), mouse lung epithelial cells (MLE12) and alveolar epithelial cells (A549). Heightened LC3II expression could not be explained by the transcriptional upregulation of key autophagy genes (Gabarapl1, Beclin1, Lc3b), upregulation of upstream autophagic machinery (ATG5-12, ATG3) or impaired autophagic flux. This suggested that elevated LC3II in CSE-treated AhR-deficient cells is likely mediated by an autophagy-independent mechanism. This was… Advisors/Committee Members: Carolyn Baglole (Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Guerrina, N. (2019). Reduced aryl hydrocarbon receptor (AhR) expression drives the pathogenesis of cigarette smoke-induced emphysema. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/79408039v.pdf ; https://escholarship.mcgill.ca/concern/theses/5t34sm66g

Chicago Manual of Style (16^th Edition):

Guerrina, Necola. “Reduced aryl hydrocarbon receptor (AhR) expression drives the pathogenesis of cigarette smoke-induced emphysema.” 2019. Doctoral Dissertation, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/79408039v.pdf ; https://escholarship.mcgill.ca/concern/theses/5t34sm66g.

MLA Handbook (7^th Edition):

Guerrina, Necola. “Reduced aryl hydrocarbon receptor (AhR) expression drives the pathogenesis of cigarette smoke-induced emphysema.” 2019. Web. 01 Mar 2021.

Vancouver:

Guerrina N. Reduced aryl hydrocarbon receptor (AhR) expression drives the pathogenesis of cigarette smoke-induced emphysema. [Internet] [Doctoral dissertation]. McGill University; 2019. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/79408039v.pdf ; https://escholarship.mcgill.ca/concern/theses/5t34sm66g.

Council of Science Editors:

Guerrina N. Reduced aryl hydrocarbon receptor (AhR) expression drives the pathogenesis of cigarette smoke-induced emphysema. [Doctoral Dissertation]. McGill University; 2019. Available from: https://escholarship.mcgill.ca/downloads/79408039v.pdf ; https://escholarship.mcgill.ca/concern/theses/5t34sm66g

McGill University

28. Lisio, Michael-Anthony. Evaluation of platinum-sensitivity in a cell line model of high grade serous ovarian cancer and the induction of re- sistance from a chemo-sensitive cell line through the re- population of cells following short-term cisplatin treatment.

Degree: MS, Department of Pathology, 2019, McGill University

URL: https://escholarship.mcgill.ca/downloads/nv935522n.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj55t

► Introduction La résistance au traitement à base de platine se développe chez la plupart des patients traités pour le cancer de l'ovaire séreux de haut… (more)

▼ Introduction La résistance au traitement à base de platine se développe chez la plupart des patients traités pour le cancer de l'ovaire séreux de haut grade (HGSOC), un fait qui explique en grande partie la mortalité élevée de cette maladie. Cooke et ses collègues (Oncogene, 2010) ont montré précédemment que la résistance au platine (Pt) résulte de l'expansion des populations sous-clonales de cellules résistantes présentes avant le traitement. Les modèles en-vitro actuels de résistance au Pt peuvent être confondus par un manque de fidélité à la signature génétique du HGSOC ou par les méthodes utilisées pour provoquer l'apparition d'une résistance pouvant être dépourvue de pertinence clinique. Ce projet vise à déterminer si la résistance aux Pt peut être développée à partir d'une population de cellules sensibles au Pt exposées au cisplatine (CDDP) d'une manière cliniquement pertinente en utilisant des lignes cellulaires dérivées de patients telles que PEO1. L'objectif central était de découvrir quelle hétérogénéité pourrait exister dans cette lignée cellulaire et de déterminer si la résistance à la Pt dérivée en-vitro pouvait résulter de la sélection d'une fraction de cellules préexistants, comme cela se produit en-vivo. Méthodes La sensibilité au platine des lignes cellulaires utilisées a été établie en exposant les cellules en culture au CDDP pendant 1 heure. Le nombre de cellules vivantes et le pourcentage de viabilité ont été évalués 72 heures après le retrait de la drogue en utilisant une microcytométre Guava Muse. L'évaluation à long terme de la toxicité du Pt a été réalisée avec l'aide du test de survie clonogénique. Pour atteindre la résistance au Pt en-vitro, une culture de PEO1 a été exposée à 10 µM de CDDP pendant 1 heure et laissée se repeupler. Ces cellules ont été passé en culture et utilisées pour établir une nouvelle ligne cellulaire (PEO1X) avec une sensibilité à la Pt diminuée de 20 fois, ce qui a été confirmée par le test de survie clonogénique. Les cellules PEO1X ont été testées pour les marqueurs histopathologiques et de l'état EMT par l'immunohistochimie et comparées à PEO1. La capacité de migration a été évaluée par la méthode de la chambre Boyden, tandis que le statut du cycle-cellulaire 72 heures après l'exposition au CDDP a été interrogé en utilisant une coloration à l'iodure de propidium. Le temps de doublage a également été déterminé et une signature génétique partielle a été établie en séquençant un panel de 33 gènes liés au cancer. Résultats PEO1 exige une asymétrie morphologique, avec une dichotomie entre les phénotypes épithéliaux et mésenchymateux. Ceci est encore démontré par l'expression hétérogène de marqueurs tels que E-Cadherin, Vimentin et CA125. Bien que similaires au taux de prolifération de PEO1, les cellules PEO1X présentent des différences de morphologie évidentes, étant plus petites et ayant un aspect plus homogène avec une expression modifiée de marqueurs tels que E-Cadhérine, Vimentine, CA125 et CD133. Contrairement à le PEO1, le cycle cellulaire de PEO1X est… Advisors/Committee Members: Carlos Telleria (Internal/Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lisio, M. (2019). Evaluation of platinum-sensitivity in a cell line model of high grade serous ovarian cancer and the induction of re- sistance from a chemo-sensitive cell line through the re- population of cells following short-term cisplatin treatment. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/nv935522n.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj55t

Chicago Manual of Style (16^th Edition):

Lisio, Michael-Anthony. “Evaluation of platinum-sensitivity in a cell line model of high grade serous ovarian cancer and the induction of re- sistance from a chemo-sensitive cell line through the re- population of cells following short-term cisplatin treatment.” 2019. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/nv935522n.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj55t.

MLA Handbook (7^th Edition):

Lisio, Michael-Anthony. “Evaluation of platinum-sensitivity in a cell line model of high grade serous ovarian cancer and the induction of re- sistance from a chemo-sensitive cell line through the re- population of cells following short-term cisplatin treatment.” 2019. Web. 01 Mar 2021.

Vancouver:

Lisio M. Evaluation of platinum-sensitivity in a cell line model of high grade serous ovarian cancer and the induction of re- sistance from a chemo-sensitive cell line through the re- population of cells following short-term cisplatin treatment. [Internet] [Masters thesis]. McGill University; 2019. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/nv935522n.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj55t.

Council of Science Editors:

Lisio M. Evaluation of platinum-sensitivity in a cell line model of high grade serous ovarian cancer and the induction of re- sistance from a chemo-sensitive cell line through the re- population of cells following short-term cisplatin treatment. [Masters Thesis]. McGill University; 2019. Available from: https://escholarship.mcgill.ca/downloads/nv935522n.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj55t

McGill University

29. Redpath, Margaret. Unraveling the role of the X chromosome in cancer: characterization of FOXP3 Isoforms and PR70 in cutaneous melanoma.

Degree: PhD, Department of Pathology, 2019, McGill University

URL: https://escholarship.mcgill.ca/downloads/sb397b522.pdf ; https://escholarship.mcgill.ca/concern/theses/rf55zb00r

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De nombreux cancers ont une incidence, un comportement et une réponse au traitement différents chez les hommes et chez les femmes. Traditionnellement, ces variations spécifiques… (more)

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De nombreux cancers ont une incidence, un comportement et une réponse au traitement différents chez les hommes et chez les femmes. Traditionnellement, ces variations spécifiques liées au sexe ont été attribuées à des différences entre les sexes dans les habitudes, l'exposition professionnelle et le statut hormonal. Plus récemment, il a été reconnu que certaines de ces différences peuvent être attribuées à la génétique. Nous avons été particulièrement frappés par l'augmentation significative de l'incidence et de la mortalité du mélanome chez l'homme. L'objectif de ce projet était de caractériser la contribution du chromosome X à cet effet. L'analyse globale des altérations génomiques a révélée qu'une perte somatique d'un chromosome X chez les femmes est associée de manière significative à un pronostic plus défavorable du mélanome. Nous avons en outre montré que c'est le X inactif qui est perdu dans tous les cas. Cela a conduit à l'hypothèse qu'une mutation activatrice d'un oncogène, ou une mutation inactivatrice d'un gène suppresseur de tumeur sur le chromosome X restant chez ces patients contribuent à l'agressivité de la tumeur. PPP2R3B et FOXP3 ont été identifiés comme des gènes justifiant une investigation plus poussée en tant que gènes suppresseurs de tumeurs liés au chromosome X dans le mélanome en raison de leur comportement dans d'autres types de tumeurs. Nous avons démontré que ces gènes sont exprimés dans la majorité de nos lignées cellulaires au niveau de l'ARNm et des protéines. L'expression de PR70 endogène et exogène est significativement corrélée à une diminution de la prolifération. Dans le mélanome humain, il existe une forte corrélation entre les faibles taux d'expression de l'ARNm du PR70 et la faible survie sans métastase à distance par les analyses multivariées. Dans cette optique, une expression nulle ou faible de la protéine PR70 est associée à une faible survie globale dans trois cohortes indépendantes de mélanome. La surexpression de PR70 exogène diminue la prise de tumeur et la croissance chez les souris nues, contrairement à la baisse de l'expression de PR70 induite par shRNA qui l'augmente. PR70 et le FOXP3 sont tous deux associés à une diminution dose-dépendante de la prolifération cellulaire du mélanome avec une accumulation de cellules dans la phase G1 du cycle cellulaire. Ces résultats sont d'importance in vivo car la prolifération est l'un des facteurs pronostiques indépendants les plus forts dans le mélanome.

Many cancers have a different incidence, behavior and response to treatment in men and women. Traditionally these sex-specific variations have been attributed to differences in habits, occupational exposures and hormones. More recently it has been recognized that some of the dissimilarities can be attributed to genetics. We were particularly struck by the significant increase in the incidence and mortality of melanoma in men. The objective of this project was to characterize how the X chromosome contributes to this effect. Global analysis of genomic alterations revealed that a…

Advisors/Committee Members: Alan Spatz (Supervisor).

Subjects/Keywords: Pathology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Redpath, M. (2019). Unraveling the role of the X chromosome in cancer: characterization of FOXP3 Isoforms and PR70 in cutaneous melanoma. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/sb397b522.pdf ; https://escholarship.mcgill.ca/concern/theses/rf55zb00r

Chicago Manual of Style (16^th Edition):

Redpath, Margaret. “Unraveling the role of the X chromosome in cancer: characterization of FOXP3 Isoforms and PR70 in cutaneous melanoma.” 2019. Doctoral Dissertation, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/sb397b522.pdf ; https://escholarship.mcgill.ca/concern/theses/rf55zb00r.

MLA Handbook (7^th Edition):

Redpath, Margaret. “Unraveling the role of the X chromosome in cancer: characterization of FOXP3 Isoforms and PR70 in cutaneous melanoma.” 2019. Web. 01 Mar 2021.

Vancouver:

Redpath M. Unraveling the role of the X chromosome in cancer: characterization of FOXP3 Isoforms and PR70 in cutaneous melanoma. [Internet] [Doctoral dissertation]. McGill University; 2019. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/sb397b522.pdf ; https://escholarship.mcgill.ca/concern/theses/rf55zb00r.

Council of Science Editors:

Redpath M. Unraveling the role of the X chromosome in cancer: characterization of FOXP3 Isoforms and PR70 in cutaneous melanoma. [Doctoral Dissertation]. McGill University; 2019. Available from: https://escholarship.mcgill.ca/downloads/sb397b522.pdf ; https://escholarship.mcgill.ca/concern/theses/rf55zb00r

McGill University

30. Jin, Eva. Functional and proteomics analysis of GNAQ mutant melanocytes.

Degree: MS, Department of Pathology, 2020, McGill University

URL: https://escholarship.mcgill.ca/downloads/q524jt27z.pdf ; https://escholarship.mcgill.ca/concern/theses/mk61rn696

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Le mélanome uvéal (MU) est une maladie rare mais mortelle qui n’a actuellement aucun traitement préventif ou systémique efficace. Des événements génétiques clés à différents… (more)

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Le mélanome uvéal (MU) est une maladie rare mais mortelle qui n’a actuellement aucun traitement préventif ou systémique efficace. Des événements génétiques clés à différents stades de la maladie ont été identifiés au cours des dernières années. Cependant, une compréhension du rôle mécaniste de chaque événement dans le développement de la maladie fait toujours défaut.Nous nous intéressons à l'une des premières mutations qui se produit dans la progression de cette maladie, dans la sous-unité ???? de la protéine de liaison de nucléotides de guanine G(q) (GNAQ). Fait intéressant, des mutations GNAQ ont également été trouvées dans plus de 80% des cas de naevus, qui restent pour la plupart bénins. Cela indique que la mutation GNAQ seule n'est pas suffisante pour la malignité dans le MU. Afin d'étudier les effets biologiques d'une mutation GNAQ dans les cellules à l’origine de la maladie, nous avons cherché à créer un système in vitro utilisant des mélanocytes choroïdiens normaux humains (NCM) et un système de transduction lentiviral.De plus, la lumière bleue (LB) a été impliquée comme facteur de risque pour l'UM. Pour tester s’il y a un effet de la LB en conjonction avec l'effet de la mutation GNAQ qui mène à une évolution vers une tumeur maligne dans les mélanocytes, nous avons exposé les NCM mutant GNAQ à la LB dans la gamme de longueurs d'onde de 400 à 500 nm, à une intensité de 0,3 soleil pendant 3 heures par jour pour 4 jours, et observé les changements fonctionnels et protéomiques qui ont eu lieu.Nous avons démontré qu'un système de transduction lentiviral utilisant des NCM fournit un système viable et utile pour étudier le développement du MU in vitro. Nos résultats ont caractérisé la mutation GNAQ(Q209L) comme un événement oncogène faible dans les NCM. Bien que nos résultats n'aient pas capturé un effet oncogène de l'exposition à la LB dans les mélanocytes transduits par le GNAQ(Q209L), comme nous l'avons fait l'hypothèse, nous avons montré que la LB agit comme un facteur de stress environnemental pour les cellules NCM non malignes mais pas les cellules UM. Notre étude pourrait ouvrir la voie à de futures investigations pour clarifier le rôle de la LB dans le développement du MU, car il pourrait être utile de promouvoir l'utilisation de lentilles intraoculaires filtrant le LB ou d'autres protections oculaires si une valeur préventive est établie

Uveal melanoma (UM) is a rare but deadly disease that currently lacks effective preventative or systemic treatment. Key genetic events at different stages of disease progression have been identified in recent years. However, a clear understanding of the mechanistic role of each event in the development of the disease is still lacking. We are interested in one of the early mutations identified, guanine nucleotide-binding protein G(q) subunit ???? (GNAQ). Interestingly, GNAQ mutations have also been found in over 80% of nevi cases, which mostly remain benign. This indicates that GNAQ mutation alone is not sufficient for malignancy in UM. In order to study the biological…

Advisors/Committee Members: Julia Burnier (Supervisor).

Subjects/Keywords: Pathology

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jin, E. (2020). Functional and proteomics analysis of GNAQ mutant melanocytes. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/q524jt27z.pdf ; https://escholarship.mcgill.ca/concern/theses/mk61rn696

Chicago Manual of Style (16^th Edition):

Jin, Eva. “Functional and proteomics analysis of GNAQ mutant melanocytes.” 2020. Masters Thesis, McGill University. Accessed March 01, 2021. https://escholarship.mcgill.ca/downloads/q524jt27z.pdf ; https://escholarship.mcgill.ca/concern/theses/mk61rn696.

MLA Handbook (7^th Edition):

Jin, Eva. “Functional and proteomics analysis of GNAQ mutant melanocytes.” 2020. Web. 01 Mar 2021.

Vancouver:

Jin E. Functional and proteomics analysis of GNAQ mutant melanocytes. [Internet] [Masters thesis]. McGill University; 2020. [cited 2021 Mar 01]. Available from: https://escholarship.mcgill.ca/downloads/q524jt27z.pdf ; https://escholarship.mcgill.ca/concern/theses/mk61rn696.

Council of Science Editors:

Jin E. Functional and proteomics analysis of GNAQ mutant melanocytes. [Masters Thesis]. McGill University; 2020. Available from: https://escholarship.mcgill.ca/downloads/q524jt27z.pdf ; https://escholarship.mcgill.ca/concern/theses/mk61rn696

Open Access Theses and Dissertations