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Rutgers University
1.
Al-Asadi, Amer, 1980-.
Preventing and treating hepatic metastases of colon and pancreatic cancers by targeting cancer cell metabolism.
Degree: PhD, Physiology and Integrative Biology, 2018, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/57463/
► Alteration of glucose metabolism is a unique feature for a majority of cancers. Cancer cells exhibit aerobic glycolysis also known as the Warburg effect even…
(more)
▼ Alteration of glucose metabolism is a unique feature for a majority of cancers. Cancer cells exhibit aerobic glycolysis also known as the Warburg effect even in the presence of oxygen. During this mode of glucose metabolism, a majority of pyruvate is converted to lactate rather than entering mitochondria for complete oxidation through oxidative phosphorylation. The functional importance of aerobic glycolysis to cancer cells is becoming clear. Basically, aerobic glycolysis prevents pyruvate from complete oxidation inside mitochondria. This shunts glycolytic intermediates to pathways for synthesis of NADPH and building blocks of macromolecules, which are required for cell growth and proliferation. Pyruvate entrance into mitochondria is enhanced via mitochondrial uncoupling, a process that permits proton influx through the mitochondrial inner membrane without generating ATP. Consequently, mitochondrial uncoupling stimulates “idle ” oxidation of acetyl-CoA, leading to complete oxidation of glucose. Thus, we hypothesize that safe mitochondrial uncouplers could be strong anticancer agents to inhibit the anabolic role of the Warburg effect. We utilized two approaches to address this hypothesis. First, we tested two mitochondrial uncoupler compounds, NEN (niclosamide ethanolamine) and oxyclozanide, on their metabolic effects and anti-cancer activities. We used metabolomics NMR to study the effect of mitochondrial uncoupling on glucose metabolism in colon cancer MC38 cells. We further examined the anti-cancer effect of NEN and oxyclozanide in cell models and hepatic metastasis of colon cancer in animal model. We found that mitochondrial uncoupling stimulates pyruvate influx to mitochondria and decreases various anabolic pathway activities. Moreover, mitochondrial uncouplers arrest cell cycle progression, inhibit cell proliferation and reduce clonogenicity. Furthermore, oral treatment with mitochondrial uncouplers diminishes hepatic metastasis of colon cancer cells transplanted intrasplenically in mice. Second, we tested MB1-47, a novel mitochondrial uncoupler with good pharmacokinetic and toxicological profiles, in preventing and treating pancreatic cancer. Our study demonstrated that MB1-47 is effective in inducing mitochondrial uncoupling in pancreatic cancer cells and inhibits the proliferation of multiple murine and human pancreatic cancer cell lines. In the tumor xenograft mouse models, oral MB1-47 treatment exhibits excellent activity in preventing tumor growth and metastasis. Our data support a unique approach for targeting cancer cell metabolism for cancer prevention and treatment and identified prototype compounds for this mechanism.
Advisors/Committee Members: Fondell, Joseph (chair), Fan, Huizhou (internal member), Jin, Shengkan (internal member), Banerjee, Debabrata (outside member), School of Graduate Studies.
Subjects/Keywords: Cancer cells; Pancreas – Cancer
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APA (6th Edition):
Al-Asadi, Amer, 1. (2018). Preventing and treating hepatic metastases of colon and pancreatic cancers by targeting cancer cell metabolism. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/57463/
Chicago Manual of Style (16th Edition):
Al-Asadi, Amer, 1980-. “Preventing and treating hepatic metastases of colon and pancreatic cancers by targeting cancer cell metabolism.” 2018. Doctoral Dissertation, Rutgers University. Accessed January 21, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/57463/.
MLA Handbook (7th Edition):
Al-Asadi, Amer, 1980-. “Preventing and treating hepatic metastases of colon and pancreatic cancers by targeting cancer cell metabolism.” 2018. Web. 21 Jan 2021.
Vancouver:
Al-Asadi, Amer 1. Preventing and treating hepatic metastases of colon and pancreatic cancers by targeting cancer cell metabolism. [Internet] [Doctoral dissertation]. Rutgers University; 2018. [cited 2021 Jan 21].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/57463/.
Council of Science Editors:
Al-Asadi, Amer 1. Preventing and treating hepatic metastases of colon and pancreatic cancers by targeting cancer cell metabolism. [Doctoral Dissertation]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/57463/

Rhodes University
2.
Sterrenberg, Jason Neville.
Molecular chaperone expression and function in breast cancer and breast cancer stem cells.
Degree: Faculty of Science, Biochemistry, Microbiology and Biotechnology, 2012, Rhodes University
URL: http://hdl.handle.net/10962/d1016238
► The Cancer Stem Cell (CSC) theory suggests that cancers arise from and are maintained by a subpopulation of cancer cells with stem cell properties. Molecular…
(more)
▼ The Cancer Stem Cell (CSC) theory suggests that cancers arise from and are maintained by a subpopulation of cancer cells with stem cell properties. Molecular chaperones are key components of cellular regulation. The overexpression of chaperones has become synonymous with cancer cells with chaperones being recognized as bona fide anti-cancer drug targets. Although chaperone activity has been characterized in cancer cells, very little is known about the cellular functions of chaperones in cancer stem cells. We set out to compare the expression of selected molecular chaperones in non-stem cancer cell and cancer stem cell enriched populations isolated from breast cancer lines, in order to identify chaperones differentially expressed between the two populations for further biological characterization. In order to isolate breast cancer stem cells from the MCF-7 and MDA-MB-231 breast cancer cell lines, three cancer stem cell isolation and identification techniques were utilized based on (1) cell surface marker expression (CD44+/CD24- and CD44+/CD24-/EpCAM+ phenotypes), (2) aldehyde dehydrogenase enzyme activity (ALDHHi) and (3) ability to grow in anchorage-independent conditions. The MDA-MB-231 and MCF-7 breast cancer cell lines displayed CD44+/CD24- cell populations with the MCF-7 cell line additionally displaying a large CD44+/CD24-/EpCAM+ population. Although both cell lines showed similar ALDHHi populations, they differed substantially with respect to anchorage-independent growth. MCF-7 cells were able to form anchorage-independent colonies while the MDA-MB-231 cell line was not. Anchorage-independent MCF-7 cells showed enrichment in CD44+/CD24- and CD44+/CD24-/EpCAM+ cells compared to adherent MCF-7 cells, and were selected for gene expression studies. Gene expression studies identified 22 genes as being down-regulated at the mRNA level in the anchorage-independent MCF-7 cells, while only 2 genes (BAG1 and DNAJC12) were up-regulated. The down-regulation of selected chaperones in anchorage independent MCF-7 cells was confirmed at the protein level for selected chaperones, including DNAJB6, a type II DNAJ protein shown to be involved in the regulation of Wnt signaling. In order to characterize the effect of DNAJB6 expression on BCSCs we developed a pCMV mammalian expression plasmid for both DNAJB6 isoforms (DNAJB6L and DNAJB6S). We successfully constructed mutants of the conserved histidine-proline-aspartic acid (HPD) motif of the J domain of DNAJB6S and DNAJB6L. These constructs will allow the analysis of the role of DNAJB6 in cancer stem cell function. To the best of our knowledge, this is the first report to focus on the comparative expression of molecular chaperones in normal and cancer stem cell enriched breast cancer populations.
Subjects/Keywords: Breast – Cancer; Stem cells; Cancer cells
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APA (6th Edition):
Sterrenberg, J. N. (2012). Molecular chaperone expression and function in breast cancer and breast cancer stem cells. (Thesis). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1016238
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sterrenberg, Jason Neville. “Molecular chaperone expression and function in breast cancer and breast cancer stem cells.” 2012. Thesis, Rhodes University. Accessed January 21, 2021.
http://hdl.handle.net/10962/d1016238.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sterrenberg, Jason Neville. “Molecular chaperone expression and function in breast cancer and breast cancer stem cells.” 2012. Web. 21 Jan 2021.
Vancouver:
Sterrenberg JN. Molecular chaperone expression and function in breast cancer and breast cancer stem cells. [Internet] [Thesis]. Rhodes University; 2012. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10962/d1016238.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sterrenberg JN. Molecular chaperone expression and function in breast cancer and breast cancer stem cells. [Thesis]. Rhodes University; 2012. Available from: http://hdl.handle.net/10962/d1016238
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago
3.
Nikolova, Gergana.
Paracrine Regulation of Cancer Stem Cell Populations.
Degree: 2018, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/22696
► Stratified epithelial stem cells are responsible for skin and mucosal renewal and play an important role in homeostasis and wound healing. Lgr6 is a marker…
(more)
▼ Stratified epithelial stem
cells are responsible for skin and mucosal renewal and play an important role in homeostasis and wound healing. Lgr6 is a marker for a unique stem cell population giving rise to the different lineages in stratified epithelia. Keratin 15 expression marks a separate population of stem
cells in stratified epithelia. CXC family chemokine receptors (Cxcr) are expressed as transmembrane proteins in mammalian epidermal
cells. They recognize and specifically bind to chemokines of the CXC family. Recent studies have reported roles for chemokines in inflammation, tumor growth, angiogenesis, invasion, and metastasis in
cancer. Selective depletion of the small K15+ stem cell fraction resulted in dramatic reduction of Lgr6+
cells and inhibition of oral tumorigenesis via senescence. Gene expression studies revealed that K15+
cancer stem
cells regulate Lgr6+
cancer stem cell expansion via chemokine signaling. Genetic ablation of the chemokine receptor Cxcr2 inhibited
cancer stem cell expansion and tumorigenesis via senescence. The effects of chemokines were primarily mediated by PI3K signaling, which is a candidate for targeted therapy in head and neck
cancer.
Advisors/Committee Members: Crowe, David (advisor), Adami, Guy (committee member), Zhou, Xiaofeng (committee member), Crowe, David (chair).
Subjects/Keywords: Stem cells; cancer
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Nikolova, G. (2018). Paracrine Regulation of Cancer Stem Cell Populations. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22696
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Nikolova, Gergana. “Paracrine Regulation of Cancer Stem Cell Populations.” 2018. Thesis, University of Illinois – Chicago. Accessed January 21, 2021.
http://hdl.handle.net/10027/22696.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Nikolova, Gergana. “Paracrine Regulation of Cancer Stem Cell Populations.” 2018. Web. 21 Jan 2021.
Vancouver:
Nikolova G. Paracrine Regulation of Cancer Stem Cell Populations. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10027/22696.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Nikolova G. Paracrine Regulation of Cancer Stem Cell Populations. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/22696
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Cornell University
4.
Sullivan, Kelly.
Studies Of The Molecular Mechanisms Underlying Cancer Stem Cells And The Transformed Metabolic Phenotype.
Degree: PhD, Biochemistry, 2015, Cornell University
URL: http://hdl.handle.net/1813/41119
► Intense research throughout recent decades has significantly expanded our knowledge of the complexities that make cancer a highly diverse and therapeutically challenging disease. Recently, cancer…
(more)
▼ Intense research throughout recent decades has significantly expanded our knowledge of the complexities that make
cancer a highly diverse and therapeutically challenging disease. Recently,
cancer stem
cells (CSCs) and de-regulated cellular metabolism have become appreciated for their crucial roles in the development, growth, and therapy resistance of tumors, and are now being pursued as therapeutic targets for the treatment of
cancer. To better understand how these oncogenic events contribute to tumor malignancy, I carried out a mechanistic analysis of the CSC marker aldehyde dehydrogenase 1A3 (ALDH1A3) and the GTP-binding protein/crosslinking enzyme tissue transglutaminase (tTG), two proteins suspected to have key roles in tumor initiation and the development of the malignant state, in glioma stem
cells (GSCs). Additionally, I examined the contributions of two isoforms of glutaminase (GLS), given the critical role of elevated glutamine metabolism in maintaining the transformed state. In delineating the role of ALDH1A3 in GSCs, I discovered that it is an important regulator of gene expression through the production of retinoic acid (RA). Specifically, I demonstrated that the expression of tTG is induced downstream of ALDH1A3 via RA in highly aggressive GSCs. Furthermore, targeting tTG results in a dramatic reduction in the self-renewal of these
cells, suggesting that it may be a viable therapeutic target in ALDH1A3 + GSCs. Finally, I showed that combination therapies including a tTG inhibitor and radiation or chemotherapy are cytotoxic, indicating that tTG inhibitors enhance the effects of standard glioma therapies. Work described in this thesis has also been directed toward understanding the roles of different splice variants of the metabolic enzyme GLS in
cancer cell growth. An important question in the field has concerned whether the two known GLS splice variants, glutaminase C (GAC) and kidney-type glutaminase (KGA), have redundant or opposing functions. This becomes especially relevant when considering the importance of targeting one or both of these enzymes when designing strategies to inhibit the metabolic reprogramming of
cancer cells. Here, I show that although KGA is expressed at low levels in
cancer cells relative to GAC, these isoforms are functionally redundant in their abilities to support the transformed metabolic phenotype.
Advisors/Committee Members: Cerione,Richard A (chair), Emr,Scott David (committee member), Linder,Maurine E. (committee member).
Subjects/Keywords: Cancer stem cells; Cancer metabolism; Cancer therapies
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sullivan, K. (2015). Studies Of The Molecular Mechanisms Underlying Cancer Stem Cells And The Transformed Metabolic Phenotype. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/41119
Chicago Manual of Style (16th Edition):
Sullivan, Kelly. “Studies Of The Molecular Mechanisms Underlying Cancer Stem Cells And The Transformed Metabolic Phenotype.” 2015. Doctoral Dissertation, Cornell University. Accessed January 21, 2021.
http://hdl.handle.net/1813/41119.
MLA Handbook (7th Edition):
Sullivan, Kelly. “Studies Of The Molecular Mechanisms Underlying Cancer Stem Cells And The Transformed Metabolic Phenotype.” 2015. Web. 21 Jan 2021.
Vancouver:
Sullivan K. Studies Of The Molecular Mechanisms Underlying Cancer Stem Cells And The Transformed Metabolic Phenotype. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1813/41119.
Council of Science Editors:
Sullivan K. Studies Of The Molecular Mechanisms Underlying Cancer Stem Cells And The Transformed Metabolic Phenotype. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/41119

McMaster University
5.
Yan, Judy.
Characterizing prostate cancer stem-like cells and their contribution to prostate cancer tumorigenesis.
Degree: PhD, 2014, McMaster University
URL: http://hdl.handle.net/11375/16285
► On average, 65 Canadian men will be diagnosed with prostate cancer (PC) every day, making it the most common male cancer in Canada. Despite the…
(more)
▼ On average, 65 Canadian men will be diagnosed with prostate cancer (PC) every day, making it the most common male cancer in Canada. Despite the prevalence, the etiology of PC is unknown. Evidence nonetheless supports the role of prostate cancer stem cells (PCSCs) in PC initiation and metastasis. In spite of almost a decade worth of research on PCSCs our knowledge on their biology remains fragmented. By taking advantage of the availability of DU145 cell-derived PCSCs in our laboratory, this thesis research focuses on investigating the unique properties of PCSCs and their function in promoting PC tumorigenesis.
We identified two PCSC-specific proteins, ALDH3A1 and CNTN1. In mouse models of xenograft tumors, ALDH3A1 was expressed at higher levels in PCSC-derived tumors than in DU145 non-PCSC-produced tumors and in lung metastases than local tumors. In clinical settings, elevation of ALDH3A1expression was observed from normal prostate tissues to carcinomas and from local PCs to the paired lymph node metastases. Additionally, ALDH3A1 was clearly detected in bone metastases. Similar to ALDH3A1, CNTN1 expression associates with PC progression and biochemical recurrence following radical prostatectomy. The clear presence of CNTN1 in lymph node and bone metastases was also demonstrated. Furthermore, CNTN1 expression promoted PC metastasis to the lungs and tumor initiation in NOD/SCID mice. Mechanistically, CNTN1 increased AKT activation and reduced E-cadherin expression. Collectively, our research revealed important roles of both PCSC proteins in promoting PC tumorigenesis and progression.
PC develops chemotherapy resistance in which PCSCs play a major role. In supporting this knowledge, we demonstrated that PCSCs are innately more resistant to the chemotherapeutic drugs, etoposide and docetaxel and that this resistance was in part attributable to their enhanced DNA damage response. Taken together, the findings of this thesis advances our knowledge on two specific PCSC markers and their association with prostate cancer progression and metastasis. As well as to the mechanism whereby PCSCs promote resistance to chemotherapeutic drugs.
Thesis
Doctor of Philosophy (PhD)
Advisors/Committee Members: Tang, Damu, Medical Sciences.
Subjects/Keywords: Cancer; Cancer stem cells; Prostate Cancer
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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APA (6th Edition):
Yan, J. (2014). Characterizing prostate cancer stem-like cells and their contribution to prostate cancer tumorigenesis. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/16285
Chicago Manual of Style (16th Edition):
Yan, Judy. “Characterizing prostate cancer stem-like cells and their contribution to prostate cancer tumorigenesis.” 2014. Doctoral Dissertation, McMaster University. Accessed January 21, 2021.
http://hdl.handle.net/11375/16285.
MLA Handbook (7th Edition):
Yan, Judy. “Characterizing prostate cancer stem-like cells and their contribution to prostate cancer tumorigenesis.” 2014. Web. 21 Jan 2021.
Vancouver:
Yan J. Characterizing prostate cancer stem-like cells and their contribution to prostate cancer tumorigenesis. [Internet] [Doctoral dissertation]. McMaster University; 2014. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/11375/16285.
Council of Science Editors:
Yan J. Characterizing prostate cancer stem-like cells and their contribution to prostate cancer tumorigenesis. [Doctoral Dissertation]. McMaster University; 2014. Available from: http://hdl.handle.net/11375/16285

Rutgers University
6.
Nashed, Mary.
Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells.
Degree: MS, Nutritional Sciences, 2011, Rutgers University
URL: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000061389
► Cancer cells activate lipogenic enzymes, including StearoylCoA Desaturase-1 (SCD1), the key enzyme that converts saturated fatty acids (SFA) into monounsaturated fatty acids (MUFA). Previously, we…
(more)
▼ Cancer cells activate lipogenic enzymes, including StearoylCoA Desaturase-1 (SCD1), the key enzyme that converts saturated fatty acids (SFA) into monounsaturated fatty acids (MUFA). Previously, we established that SCD1 regulates lipogenesis, cell proliferation and invasiveness in lung
cancer cells, as well as tumor formation in mice. We recently reported that SCD1 modulates the PI3K/Akt pathway, a central signaling cascade, along with ERK, which are involved in the regulation of lipid biosynthesis, growth and survival of mammalian
cells. Growth factor-activated tyrosine kinase receptors, such as epidermal growth factor (EGF) receptors (EGFR), are main activators of Akt and ERK signals, two cascades that are most often deranged in
cancer. A hallmark of
cancer is the metabolic shift towards macromolecular synthesis to support cell replication. SCD1 expression increases in
cancer cells. The molecular mechanisms by which SCD1 regulates the biological phenotype of
cancer cells is still unknown. The poor prognosis and ineffective treatments of some cancers, such as lung
cancer, calls for better understanding of their mechanisms and for finding novel targets that, like SCD1, modulate the Akt and ERK pathways. Here we provide evidence that SCD1 activity controls the activation of EGFR and its downstream signaling targets, Akt and ERK. Using H460 human lung
cancer cells, we observed that the activating phosphorylation of Tyr1068 and Tyr1086 residues in EGFR upon EGF stimulation was markedly impaired when SCD1 activity was blocked with CVT-11127, a novel small molecule SCD inhibitor. In addition, supplementation with oleic acid, the product of SCD1, restored EGF-induced phosphorylation of EGFR but not the full phosphorylation of Akt. Finally, abrogation of SCD1 dramatically altered distribution of rafts and non-raft domains, suggesting that the regulation of EGFR function by SCD1 may involve the alteration of membrane lipid domains. All results are representative of 3 separate experiments. In conclusion, our data indicate that SCD1 may coordinate the regulation of lipid biosynthesis and the transduction signals that control
cancer cell metabolism, proliferation, survival and tumorigenesis by modulating EGFR activation, which subsequently modifies the Akt and ERK signaling platforms. Our findings also suggest SCD1 is a potential target for novel pharmacological interventions in lung
cancer.
Advisors/Committee Members: Nashed, Mary (author), Igal, R. Ariel (chair), Storch, Judith (internal member), Dixon, Joseph (internal member).
Subjects/Keywords: Cancer cells – Growth – Regulation; Lungs – Cancer; Cancer cells – Proliferation; Enzymes
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nashed, M. (2011). Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells. (Masters Thesis). Rutgers University. Retrieved from http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000061389
Chicago Manual of Style (16th Edition):
Nashed, Mary. “Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells.” 2011. Masters Thesis, Rutgers University. Accessed January 21, 2021.
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000061389.
MLA Handbook (7th Edition):
Nashed, Mary. “Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells.” 2011. Web. 21 Jan 2021.
Vancouver:
Nashed M. Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells. [Internet] [Masters thesis]. Rutgers University; 2011. [cited 2021 Jan 21].
Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000061389.
Council of Science Editors:
Nashed M. Role of Stearoyl-CoA desaturase-1 (SCD1) in the activation of epidermal growth factor receptor (EGFR) in lung cancer cells. [Masters Thesis]. Rutgers University; 2011. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000061389

Universiteit Utrecht
7.
Ampatziadis Michailidis, G.
Cancer Stem Cells.
Degree: 2010, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/179568
Review on the Cancer Stem Cells (CSCs) theory. Topics include introduction on the stem cells and CSCs field. Moreover the CSCs are viewed under the blood malignancies and solid tumors (breast, brain, colorectal) classification.
Advisors/Committee Members: Vries, Robert.
Subjects/Keywords: Geneeskunde; Cancer Stem Cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Ampatziadis Michailidis, G. (2010). Cancer Stem Cells. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/179568
Chicago Manual of Style (16th Edition):
Ampatziadis Michailidis, G. “Cancer Stem Cells.” 2010. Masters Thesis, Universiteit Utrecht. Accessed January 21, 2021.
http://dspace.library.uu.nl:8080/handle/1874/179568.
MLA Handbook (7th Edition):
Ampatziadis Michailidis, G. “Cancer Stem Cells.” 2010. Web. 21 Jan 2021.
Vancouver:
Ampatziadis Michailidis G. Cancer Stem Cells. [Internet] [Masters thesis]. Universiteit Utrecht; 2010. [cited 2021 Jan 21].
Available from: http://dspace.library.uu.nl:8080/handle/1874/179568.
Council of Science Editors:
Ampatziadis Michailidis G. Cancer Stem Cells. [Masters Thesis]. Universiteit Utrecht; 2010. Available from: http://dspace.library.uu.nl:8080/handle/1874/179568

University of Hong Kong
8.
Lui, Ka-luen.
Review on solid cancer
stem cell: overview and future directions.
Degree: 2009, University of Hong Kong
URL: http://hdl.handle.net/10722/56771
Subjects/Keywords: Cancer
cells.
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lui, K. (2009). Review on solid cancer
stem cell: overview and future directions. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/56771
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lui, Ka-luen. “Review on solid cancer
stem cell: overview and future directions.” 2009. Thesis, University of Hong Kong. Accessed January 21, 2021.
http://hdl.handle.net/10722/56771.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lui, Ka-luen. “Review on solid cancer
stem cell: overview and future directions.” 2009. Web. 21 Jan 2021.
Vancouver:
Lui K. Review on solid cancer
stem cell: overview and future directions. [Internet] [Thesis]. University of Hong Kong; 2009. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10722/56771.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lui K. Review on solid cancer
stem cell: overview and future directions. [Thesis]. University of Hong Kong; 2009. Available from: http://hdl.handle.net/10722/56771
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Cornell University
9.
Pratt, Erica.
Characterizing Cancer Cells Using Gedi Microdevices: Capture, In-Situ Analysis And Elution For Ex-Situ Analysis And Culture.
Degree: PhD, Biomedical Engineering, 2015, Cornell University
URL: http://hdl.handle.net/1813/41091
► Several methodologies exist for the isolation of circulating tumor cells (CTCs) from cancer patient blood samples. However, there are few straightforward functional analyses for these…
(more)
▼ Several methodologies exist for the isolation of circulating tumor
cells (CTCs) from
cancer patient blood samples. However, there are few straightforward functional analyses for these
cells, either downstream or in-situ, particularly in immunocapture-based systems. My thesis work has focused on two methods of cell extraction, and one in-situ assay, that can enable single-cell CTC interrogation using Geometrically Enhanced Differential Immunocapture (GEDI) microdevices. I will also present a non-mechanical, non-enzymatic, method of whole-cell release by substituting standard biotin-avidin immunochemistry with reversible biotin analogues. These data are one of the first demonstration of linker chemistry substitution for release of
cancer cells, and can be combined with various biomechanical assays (e.g. traction force microscopy) to quantify an individual
cells properties. Together, these methods provide a toolbox for straightforward extraction of
cancer cells from CTC-capture devices, which can enable characterization of individual cell genotype and phenotype. I will also outline experiments which combine high-efficiency, high-purity GEDI cell capture with single-nucleus sequencing (SNS) for single-cell copy-number variation analyses (GEDI-SNS). I will show that GEDI-SNS is comparable to standard methods, can be used to identify key
cancer-related genetic variations, and can differentiate between different
cancer cell populations of the same tissue ori- gin. Finally, I will present the development of an on-chip assay to monitor Ca2+ homeostasis, which has been shown to be critical in taxane chemoresistance, as well as acquisition of a hormonally-independent phenotype. Using real-time, time-lapse, microscopy, I will monitor Ca2+ flux in
cancer cells as a functional assay to inform drug treatment.
Advisors/Committee Members: Kirby, Brian (chair), Lammerding, Jan (committee member), Collins, Lance (committee member).
Subjects/Keywords: microfluidics; circulating tumor cells; cancer
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APA (6th Edition):
Pratt, E. (2015). Characterizing Cancer Cells Using Gedi Microdevices: Capture, In-Situ Analysis And Elution For Ex-Situ Analysis And Culture. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/41091
Chicago Manual of Style (16th Edition):
Pratt, Erica. “Characterizing Cancer Cells Using Gedi Microdevices: Capture, In-Situ Analysis And Elution For Ex-Situ Analysis And Culture.” 2015. Doctoral Dissertation, Cornell University. Accessed January 21, 2021.
http://hdl.handle.net/1813/41091.
MLA Handbook (7th Edition):
Pratt, Erica. “Characterizing Cancer Cells Using Gedi Microdevices: Capture, In-Situ Analysis And Elution For Ex-Situ Analysis And Culture.” 2015. Web. 21 Jan 2021.
Vancouver:
Pratt E. Characterizing Cancer Cells Using Gedi Microdevices: Capture, In-Situ Analysis And Elution For Ex-Situ Analysis And Culture. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1813/41091.
Council of Science Editors:
Pratt E. Characterizing Cancer Cells Using Gedi Microdevices: Capture, In-Situ Analysis And Elution For Ex-Situ Analysis And Culture. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/41091

Drexel University
10.
Ho, Christine Maylin.
The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells.
Degree: 2013, Drexel University
URL: http://hdl.handle.net/1860/4471
► The tumor microenvironment contains a multitude of biomolecules, stromal cells such as fibroblasts, endothelial cells, inflammatory cells, and signaling molecules that support the tumor’s growth…
(more)
▼ The tumor microenvironment contains a multitude of biomolecules, stromal cells such as fibroblasts, endothelial cells, inflammatory cells, and signaling molecules that support the tumor’s growth and progression. Particularly around the site of tumors, fibroblasts are “primed” to adopt a myofibroblastic phenotype, and are known as cancer associated fibroblasts (CAFs) that promote tumor growth and progression instead of aiding the body. Much interest has been taken in the individual cellular interactions between tumor cells and the surrounding cancer-associated fibroblasts. Systems are constantly being designed to better emulate the complex internal environment around the tumor in order to understand how the tumor stroma communicates and affects the tumor growth. In this thesis, a 3D microenvironment model was developed that simulates the native extracellular matrix and allows for the study of individual cellular interactions between cancer cells and fibroblasts, particularly those involving transmission of cell-generated contractile forces. The final system design in brief involves spatially constraining MDA-MB-231 human breast adenocarcinoma cells and human dermal fibroblasts on fibronectin micropatterns on a polydimethylsiloxane (PDMS) substrate. A poly-L-lysine/glutaraldehyde treated PDMS gasket was placed around the cells, and a collagen overlay was added, to allow cells to interact with a 3D environment. Live cell microscopy was used to track cell movement over time, and the images were analyzed with MATLAB. Additionally, a protocol for differentiating myofibroblasts was optimized for the inclusion into the system. The significance of this study is that it offers a novel 3D cell culture system that boasts of the ability for control over individual cell positions in order to observe the effects of fibroblasts and cancer cells in a 3D environment that resembles the in vivo environment more than that of the standard 2D culture system.
M.S., Biomedical Engineering – Drexel University, 2013
Advisors/Committee Members: Shieh, Adrian C..
Subjects/Keywords: Biomedical engineering; Fibroblasts; Cancer cells
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Ho, C. M. (2013). The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells. (Thesis). Drexel University. Retrieved from http://hdl.handle.net/1860/4471
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ho, Christine Maylin. “The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells.” 2013. Thesis, Drexel University. Accessed January 21, 2021.
http://hdl.handle.net/1860/4471.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ho, Christine Maylin. “The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells.” 2013. Web. 21 Jan 2021.
Vancouver:
Ho CM. The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells. [Internet] [Thesis]. Drexel University; 2013. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1860/4471.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ho CM. The design of a novel 3D micropatterned tumor microenvironment model to study the intercellular effects of fibroblasts and cancer cells. [Thesis]. Drexel University; 2013. Available from: http://hdl.handle.net/1860/4471
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
11.
Sulaiman, Andrew.
New Approaches for the Treatment of Triple Negative Breast Cancer
.
Degree: 2019, University of Ottawa
URL: http://hdl.handle.net/10393/39100
► Triple‐negative breast cancer (TNBC) is the most refractory subtype of breast cancer to current treatments and accounts disproportionately for the majority of breast cancer‐related deaths.…
(more)
▼ Triple‐negative breast cancer (TNBC) is the most refractory subtype of breast cancer to current treatments and accounts disproportionately for the majority of breast cancer‐related deaths. Research has not yet identified specific therapies for TNBC and chemotherapy remains the conventional therapy in the clinic. While conventional chemotherapy regimens have demonstrated success at reducing bulk tumor burden, they have been shown to enrich cancer stem cells (CSCs). CSCs promote chemoresistance, metastasis, heterogeneous tumor regeneration and disease relapse. Owing to tumor plasticity and the conversion between CSC and non-CSC subpopulations development of a strategy capable of inhibiting both non-CSC and CSC subpopulations is crucial for TNBC therapy. In this compilation of my main research projects, several new approaches for the treatment of TNBC were identified which target not only the bulk tumor population but also the CSC populations residing within the tumor:
1. Co-suppression of Wnt, HDAC, and ESR1 using clinically relevant low‐dose inhibitors effectively repressed both bulk and CSC subpopulations and converted CSCs to non‐CSCs in TNBC cells.
2. Co-inhibition of mTORC1, HDAC, and ESR1 was capable of reducing both bulk and CSC subpopulations as well as the conversion of fractionated non-CSC to CSCs in in a human TNBC xenograft model and hampered tumorigenesis following treatment.
3. Inhibition of Wnt and YAP retarded tumor growth of TNBC cells in either epithelial or mesenchymal states, and both CD44high/CD24low and ALDH+ CSC subpopulations were diminished in a human xenograft model reducing tumorigenicity following treatment.
Subjects/Keywords: TNBC;
Cancer Stem Cells
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Sulaiman, A. (2019). New Approaches for the Treatment of Triple Negative Breast Cancer
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/39100
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sulaiman, Andrew. “New Approaches for the Treatment of Triple Negative Breast Cancer
.” 2019. Thesis, University of Ottawa. Accessed January 21, 2021.
http://hdl.handle.net/10393/39100.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sulaiman, Andrew. “New Approaches for the Treatment of Triple Negative Breast Cancer
.” 2019. Web. 21 Jan 2021.
Vancouver:
Sulaiman A. New Approaches for the Treatment of Triple Negative Breast Cancer
. [Internet] [Thesis]. University of Ottawa; 2019. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10393/39100.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sulaiman A. New Approaches for the Treatment of Triple Negative Breast Cancer
. [Thesis]. University of Ottawa; 2019. Available from: http://hdl.handle.net/10393/39100
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Erasmus University Rotterdam
12.
S.G. Roth (Sabrina).
Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer.
Degree: 2012, Erasmus University Rotterdam
URL: http://hdl.handle.net/1765/76036
► markdownabstract__Abstract__ The Introduction summarizes the current literature on quiescence in adult stem cell niches and the various methods for the isolation of quiescent stem cells,…
(more)
▼ markdownabstract__Abstract__
The Introduction summarizes the current literature on quiescence in adult stem cell
niches and the various methods for the isolation of quiescent stem cells, outlines
the complexity of the intestinal stem cell niche, and formulates the hypothesis that
quiescent stem cells are involved in inflammation-associated tumours. Moreover,
quiescent cancer stem cells and their clinical relevance are reviewed.
In Chapter 1 and 2 we describe the generation of tightly regulated doxycyclineinducible
models for studying mouse intestinal and esophageal biology respectively.
The mouse model developed and characterized in Chapter 1 was employed in
Chapter 3 to isolate and characterize a quiescent label-retaining cell population
present within the intestinal epithelium.
Chapters 4 to 6 describe the role of quiescent cells during tissue injury and their
presence in full-blown tumors. In Chapter 4, we describe the induction of colonic
inflammation in tumor-prone Apc1638N/+/villin-KRASG12V animals. These mice develop
colon cancer characterized by the presence of Paneth-like cells. In Chapter 5, a rare villin-expressing, quiescent population of tumor cells is shown to be present in stomach
tumors of the intestinal type from Apc1638N/+ animals. Moreover, we characterized
quiescent, label-retaining tumor cells in small intestinal adenocarcinomas of
Apc1638N/+/villin-KRASG12V animals, as outlined in Chapter 6.
Finally, the Discussion summarizes the main finding of this thesis and gives
directions for future research.
Subjects/Keywords: homeostasis; cancer; stem cells; gastroenterology
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
(Sabrina), S. R. (2012). Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer. (Thesis). Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/76036
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
(Sabrina), S.G. Roth. “Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer.” 2012. Thesis, Erasmus University Rotterdam. Accessed January 21, 2021.
http://hdl.handle.net/1765/76036.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
(Sabrina), S.G. Roth. “Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer.” 2012. Web. 21 Jan 2021.
Vancouver:
(Sabrina) SR. Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer. [Internet] [Thesis]. Erasmus University Rotterdam; 2012. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1765/76036.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
(Sabrina) SR. Silent Waters Run Deep. Quiescent stem cells in homeostasis and cancer. [Thesis]. Erasmus University Rotterdam; 2012. Available from: http://hdl.handle.net/1765/76036
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manitoba
13.
Liang, Lisa.
Functional characterization and selective targeting of CD271+ cells in sonic hedgehog medulloblastoma.
Degree: Biochemistry and Medical Genetics, 2019, University of Manitoba
URL: http://hdl.handle.net/1993/33726
► The extensive heterogeneity between and within medulloblastoma (MB) subgroups underscores a critical need for subtype-specific biomarkers and therapeutic strategies. Here, we employed a high throughput…
(more)
▼ The extensive heterogeneity between and within medulloblastoma (MB) subgroups underscores a critical need for subtype-specific biomarkers and therapeutic strategies. Here, we employed a high throughput flow cytometry screening platform to identify CD271/p75NTR as a tumor propagating cell marker for SHH MB. In addition, we demonstrated the clinical utility of CD271 as a novel diagnostic marker using immunohistochemical (IHC) analysis and transcriptome profiling of MB patient samples. RNA sequencing analysis performed on CD271+ vs. CD271- SHH primary cultures revealed that these two subpopulations are molecularly distinct with CD271+
cells associated with an increase in cell survival, proliferation and migration. Importantly, we showed that MAPK signaling is upregulated in the CD271+ population, and treatment with MEK inhibitor selumetinib reduces endogenous CD271 levels, proliferation and migration in vitro. Selumetinib treatment in an intracerebellar xenograft mouse model also extended survival and reduced CD271 levels in vivo. Collectively, the data presented in this thesis demonstrate the utility of CD271 as a stem/progenitor marker, potential diagnostic and therapeutic target for SHH MB.
Advisors/Committee Members: Werbowetski-Ogilvie, Tamra (Biochemistry and Medical Genetics) (supervisor), Merz, David (Biochemistry and Medical Genetics) McManus, Kirk (Biochemistry and Medical Genetics) Raouf, Afshin (Immunology) Huang, Annie (University of Toronto) (examiningcommittee).
Subjects/Keywords: Medulloblastoma; CD271; Cancer stem cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Liang, L. (2019). Functional characterization and selective targeting of CD271+ cells in sonic hedgehog medulloblastoma. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/33726
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Liang, Lisa. “Functional characterization and selective targeting of CD271+ cells in sonic hedgehog medulloblastoma.” 2019. Thesis, University of Manitoba. Accessed January 21, 2021.
http://hdl.handle.net/1993/33726.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Liang, Lisa. “Functional characterization and selective targeting of CD271+ cells in sonic hedgehog medulloblastoma.” 2019. Web. 21 Jan 2021.
Vancouver:
Liang L. Functional characterization and selective targeting of CD271+ cells in sonic hedgehog medulloblastoma. [Internet] [Thesis]. University of Manitoba; 2019. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1993/33726.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Liang L. Functional characterization and selective targeting of CD271+ cells in sonic hedgehog medulloblastoma. [Thesis]. University of Manitoba; 2019. Available from: http://hdl.handle.net/1993/33726
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago
14.
Lagunas, Angelica Maria.
Telomere DNA Damage Response Regulates Cancer Stem Cell Phenotype.
Degree: 2018, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/22726
► Chromosome ends are protected by telomeres that prevent DNA damage response and degradation. When telomeres become critically short, the DNA damage response is activated at…
(more)
▼ Chromosome ends are protected by telomeres that prevent DNA damage response and degradation. When telomeres become critically short, the DNA damage response is activated at chromosome ends which induces cellular senescence or apoptosis. Telomeres are protected by the double stranded DNA binding protein TRF2 and maintained by telomerase or a recombination based mechanism known as alternative lengthening of telomeres (ALT). Telomerase is expressed in the basal layer of the epidermis, and stem
cells in epidermis have longer telomeres than proliferating populations. Stem cell expansion has been associated with epithelial-mesenchymal transition (EMT) in
cancer. EMT is a critical process in
cancer progression in which
cells acquire spindle morphology, migrate from the primary tumor, and spread to distant anatomic sites. Loss of TRF2 expression observed in human squamous cell carcinomas expanded metastatic
cancer stem
cells during mouse skin carcinogenesis. To determine if telomerase inhibition could block the TRF2-null mediated expansion of metastatic clones, we characterized skin carcinogenesis in a conditional TRF2/Terc double null mutant mouse. Loss of TRF2 and Terc expression resulted in telomere DNA damage, severely depleted CD34 + and Lgr6+
cancer stem
cells, and induced terminal differentiation of metastatic
cancer cells. However a novel
cancer stem cell population evolved in primary tumors exhibiting genomic instability, ALT, and EMT. Surprisingly we discovered that metastatic clones evolved prior to histopathologic onset of primary tumors. These results have important implications for understanding the evolution and treatment of metastatic
cancer.
Advisors/Committee Members: Crowe, David L (advisor), Diamond, Alan M (committee member), George, Anne (committee member), Adami, Guy (committee member), Zhou, Xiaofeng (committee member), Crowe, David L (chair).
Subjects/Keywords: telomeres; EMT; cancer stem cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lagunas, A. M. (2018). Telomere DNA Damage Response Regulates Cancer Stem Cell Phenotype. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22726
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lagunas, Angelica Maria. “Telomere DNA Damage Response Regulates Cancer Stem Cell Phenotype.” 2018. Thesis, University of Illinois – Chicago. Accessed January 21, 2021.
http://hdl.handle.net/10027/22726.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lagunas, Angelica Maria. “Telomere DNA Damage Response Regulates Cancer Stem Cell Phenotype.” 2018. Web. 21 Jan 2021.
Vancouver:
Lagunas AM. Telomere DNA Damage Response Regulates Cancer Stem Cell Phenotype. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10027/22726.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lagunas AM. Telomere DNA Damage Response Regulates Cancer Stem Cell Phenotype. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/22726
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
15.
POULSEN, BJORN LA COUR.
Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-Cancer Agents.
Degree: School of Chemistry. Discipline of Chemistry, 2018, Trinity College Dublin
URL: http://hdl.handle.net/2262/82721
► Ruthenium-polypyridyl complexes containing extended aromatic ring systems exhibit attractive photophysical properties and have been shown to bind strongly to DNA. Such properties make complexes like…
(more)
▼ Ruthenium-polypyridyl complexes containing extended aromatic ring systems exhibit attractive photophysical properties and have been shown to bind strongly to DNA. Such properties make complexes like these suitable for a broad range of biological applications. This thesis, entitled ?Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-
Cancer Agents?, is focusing on DNA binding and treatment of
cancer and aims to develop novel Ru(II) polypyridyl complexes, which can be used as luminescence dyes for imaging or as photodynamic therapeutic (PDT) agents in
cancer treatments.
Chapter 1 gives a basic introduction to the background of the problem treated in the thesis by, firstly, providing an overview of DNA and its structure and a brief description of the various binding modes, by which molecular species can interact with DNA. Following this overview, relevant Ru(II) polypyridyl complexes are described, including their application as DNA binding, cellular imaging, or anti-
cancer agents. A critical literature review of multivalent binding is given to help with a conceptual understanding. New, more accurate methods to calculate binding parameters are also introduced. This chapter then concludes by outlining recent examples of similar Ru(II) polypyridyl complexes and other biologically relevant molecules developed in the Gunnlaugsson group.
In Chapter 2, synthesis, characterisation and photophysical properties of two Ru(II) polypyridyl complexes are explored with a new, extended aromatic moiety as one of the ligands. The photophysical properties of the compounds show promising features for use in imaging by being emissive in aqueous and/or organic solvents. The DNA binding properties of the two new Ru(II) complexes are investigated. Their binding interactions with DNA are evaluated using various spectroscopic techniques and both complexes are seen to bind strongly to DNA through intercalation. The potential use as imaging probes of one of the complexes is demonstrated by a dramatic enhancement of the emission by the compound in aqueous environment upon binding to DNA.
In Chapter 3 the synthesis and characterisation of compounds based on 1,10-phenanthroline-5,6-dione are described. In Chapter 4 the activity at the cellular level for these and the two new DNA binding complexes is evaluated. The behaviour of the complexes in HeLa cervical
cancer cells has been studied, their cytotoxicity has been described, and their ability to act as luminescent dyes and PDT agents has been explored. One of the two new complexes showed great potential for use in PDT with a large increase in toxicity at photoactivation. Further, Ru(II) complexes with naphthalimide based Tr?ger?s bases as bridging ligands are evaluated for use in PDT. The naphthalimide based Tr?ger?s bases that are tested do not show potential for use in PDT, however some of them show anti-
cancer activity or potential for use in cellular imaging.
Chapter 5 describes the investigation into the site specific and cooperative binding of the two…
Advisors/Committee Members: Gunnlaugsson, Thorfinnu.
Subjects/Keywords: cells; Cancer; Ruthenium; DNA
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
POULSEN, B. L. C. (2018). Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-Cancer Agents. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/82721
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
POULSEN, BJORN LA COUR. “Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-Cancer Agents.” 2018. Thesis, Trinity College Dublin. Accessed January 21, 2021.
http://hdl.handle.net/2262/82721.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
POULSEN, BJORN LA COUR. “Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-Cancer Agents.” 2018. Web. 21 Jan 2021.
Vancouver:
POULSEN BLC. Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-Cancer Agents. [Internet] [Thesis]. Trinity College Dublin; 2018. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/2262/82721.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
POULSEN BLC. Ruthenium Polypyridyl Complexes for Biological Applications in Imaging and as Anti-Cancer Agents. [Thesis]. Trinity College Dublin; 2018. Available from: http://hdl.handle.net/2262/82721
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University
16.
Morrissette, Audrey L., 1993-.
Clinical presentation of patients with mutations in moderate penetrance genes: a case series.
Degree: MS, Microbiology and Molecular Genetics, 2019, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/60900/
► Although there is evidence in the literature of a connection between germline mutations in moderate penetrance genes and breast and/or ovarian cancer susceptibility, there is…
(more)
▼ Although there is evidence in the literature of a connection between germline mutations in moderate penetrance genes and breast and/or ovarian
cancer susceptibility, there is much to be discovered about genotype-phenotype correlations and
cancer spectrums. This case series adds to the descriptive literature regarding clinical presentation and family history in patients with germline mutations in moderate penetrance breast and/or ovarian
cancer genes. Eleven patients were included in this case series who were identified to have a pathogenic or likely pathogenic variant, in a moderate penetrance breast and/or ovarian
cancer gene. Genes included ATM (n = 4), BARD1 (n = 1), CHEK2 (n = 2), PALB2 (n = 2), and RAD51C (n = 2). Results from this case series illustrate areas for future research and add to the existing knowledge regarding phenotype seen in patients who harbor pathogenic variants in moderate penetrance genes.
Advisors/Committee Members: Joines, Jessica (chair), Heiman, Gary (internal member), Vig, Hetal (internal member), School of Graduate Studies.
Subjects/Keywords: Germ cells; Cancer – Genetic aspects
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morrissette, Audrey L., 1. (2019). Clinical presentation of patients with mutations in moderate penetrance genes: a case series. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/60900/
Chicago Manual of Style (16th Edition):
Morrissette, Audrey L., 1993-. “Clinical presentation of patients with mutations in moderate penetrance genes: a case series.” 2019. Masters Thesis, Rutgers University. Accessed January 21, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/60900/.
MLA Handbook (7th Edition):
Morrissette, Audrey L., 1993-. “Clinical presentation of patients with mutations in moderate penetrance genes: a case series.” 2019. Web. 21 Jan 2021.
Vancouver:
Morrissette, Audrey L. 1. Clinical presentation of patients with mutations in moderate penetrance genes: a case series. [Internet] [Masters thesis]. Rutgers University; 2019. [cited 2021 Jan 21].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60900/.
Council of Science Editors:
Morrissette, Audrey L. 1. Clinical presentation of patients with mutations in moderate penetrance genes: a case series. [Masters Thesis]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60900/
17.
Fekir, Karim.
Biomarqueurs et nouvelles approches thérapeutiques ciblant les cellules souches cancéreuses dans le carcinome hépatocellulaire : Biomarkers and new therapeutic approches targeting cancer stem cells in hepatocellular carcinoma.
Degree: Docteur es, Biologie et sciences de la santé, 2015, Rennes 1
URL: http://www.theses.fr/2015REN1B007
► Le cancer primitif du foie, ou carcinome hépatocellulaire (CHC), est l’un des premiers cancers dans le monde chez l’homme adulte. L'identité des cellules à l'origine…
(more)
▼ Le cancer primitif du foie, ou carcinome hépatocellulaire (CHC), est l’un des premiers cancers dans le monde chez l’homme adulte. L'identité des cellules à l'origine des CHC est controversée, toutefois l'existence de cellules souches/progénitrices (CS/P) dans certaines tumeurs a été rapportée. Ces tumeurs ont un phénotype très agressif, sont associées à un mauvais pronostic et ont tendance à échapper aux thérapies conventionnelles. Ainsi, des traitements ciblant spécifiquement les cellules souches cancéreuses pourraient constituer des compléments thérapeutiques efficaces aux traitements actuels. Pour cela, il est nécessaire de disposer de biomarqueurs afin d’identifier les sous-types de CHC dérivant de CS/P mais également de modèles cellulaires permettant de tester des molécules thérapeutiques. Les CS/P pourraient provenir soit du compartiment de cellules souches hépatiques soit de la dédifférenciation d’hépatocytes à l'intérieur de la tumeur. Aussi dans le cadre de cette thèse nous nous sommes attachés à étudier les mécanismes cellulaires et moléculaires impliqués 1) dans la retrodifférenciation des hépatocytes en CS/P et 2) dans le maintien des propriétés souches. Pour cette étude nous avons utilisé la lignée HepaRG issue d’un CHC sur infection virale C qui présente des caractéristiques de progéniteurs hépatiques se différenciant en hépatocytes et cholangiocytes. Dans la première partie de ce travail nous avons montré qu’un environnement inflammatoire favorise la retrodifferenciation d’hépatocytes HepaRG en CS/P. Alors que les voies activées par le TNF et l’IL-6 sont impliquées dans la perte du phénotype hépatocytaire, la voie TGF induit une transition épithélio-mésenchymateuse. Dans ces CS/P, nous observons l’enrichissement de signatures moléculaires associées à des souches embryonnaires et à des CHC avec mauvais pronostic. De plus, nous avons identifié plusieurs molécules pouvant inhiber ce processus de rétrodifférenciation des hépatocytes-HepaRG comme la trichostatine A. Dans une seconde partie nous avons montré que l’acquisition et le maintien des caractéristiques souches des cellules HepaRG étaient associés à une production de cytokines, à l’expression de métalloprotéinases impliquées dans les processus de migration et d’invasion, de facteur pro-angiogenique et à un changement dans l’activité mitochondriale conduisant à une reprogrammation métabolique. Les voies de signalisation impliquant l’angiopoïétine-like 4, PI3K et ERK régulent ces changements. De façon intéressante, nous montrons que le rétablissement de l’activité mitochondriale réduit la résistance des CS/P aux anticancéreux. Notre étude nous a permis d’acquérir une meilleure compréhension des voies de signalisation activées dans les cellules souches/progénitrices hépatiques cancéreuses et des mécanismes impliqués dans la rétro-différenciation des cellules matures tumorales, deux phénomènes probablement impliqués dans la récidive tumorale et la chimiorésistance.
Biomarkers and new therapeutic approches targeting cancer stem cells in…
Advisors/Committee Members: Corlu, Anne (thesis director).
Subjects/Keywords: Foie; Cancer; Cellules souches; Liver cells; Cancer
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Fekir, K. (2015). Biomarqueurs et nouvelles approches thérapeutiques ciblant les cellules souches cancéreuses dans le carcinome hépatocellulaire : Biomarkers and new therapeutic approches targeting cancer stem cells in hepatocellular carcinoma. (Doctoral Dissertation). Rennes 1. Retrieved from http://www.theses.fr/2015REN1B007
Chicago Manual of Style (16th Edition):
Fekir, Karim. “Biomarqueurs et nouvelles approches thérapeutiques ciblant les cellules souches cancéreuses dans le carcinome hépatocellulaire : Biomarkers and new therapeutic approches targeting cancer stem cells in hepatocellular carcinoma.” 2015. Doctoral Dissertation, Rennes 1. Accessed January 21, 2021.
http://www.theses.fr/2015REN1B007.
MLA Handbook (7th Edition):
Fekir, Karim. “Biomarqueurs et nouvelles approches thérapeutiques ciblant les cellules souches cancéreuses dans le carcinome hépatocellulaire : Biomarkers and new therapeutic approches targeting cancer stem cells in hepatocellular carcinoma.” 2015. Web. 21 Jan 2021.
Vancouver:
Fekir K. Biomarqueurs et nouvelles approches thérapeutiques ciblant les cellules souches cancéreuses dans le carcinome hépatocellulaire : Biomarkers and new therapeutic approches targeting cancer stem cells in hepatocellular carcinoma. [Internet] [Doctoral dissertation]. Rennes 1; 2015. [cited 2021 Jan 21].
Available from: http://www.theses.fr/2015REN1B007.
Council of Science Editors:
Fekir K. Biomarqueurs et nouvelles approches thérapeutiques ciblant les cellules souches cancéreuses dans le carcinome hépatocellulaire : Biomarkers and new therapeutic approches targeting cancer stem cells in hepatocellular carcinoma. [Doctoral Dissertation]. Rennes 1; 2015. Available from: http://www.theses.fr/2015REN1B007

University of Melbourne
18.
Abubaker, Khalid Ramadan.
Molecular mechanisms regulating chemotherapy resistance in ovarian carcinomas.
Degree: 2013, University of Melbourne
URL: http://hdl.handle.net/11343/39886
► Epithelial ovarian cancer is the second most common and most lethal gynaecological malignancy. Due to lack of early diagnostic modalities this aggressive form of cancer…
(more)
▼ Epithelial ovarian cancer is the second most common and most lethal gynaecological malignancy. Due to lack of early diagnostic modalities this aggressive form of cancer is frequently diagnosed once it is at an advanced stage with a low 30% five year survival rate. Following primary cytoreductive surgery, ovarian cancer patients are treated with adjuvant or neo-adjuvant systemic administration of platinum and taxane based chemotherapy as part of first line chemotherapy regimens. A positive response to this form of treatment is seen in the majority of cases, with patients enjoying a short remission period. However, treatment is rarely curative and in nearly all cases within 16-22 months there is an emergence of fatal chemoresistant recurrent disease. It is believed that this phenomenon of chemoresistance and recurrence is attributed to the activation of specific cell signalling pathways associated with cancer cell survival and the emergence of cancer stem cell-like populations within the chemotherapy treated residual ovarian tumours. In order to increase the low 30% five year survival rate for this distressing disease, an understanding of the molecular processes that govern the enrichment of cancer stem cell-like cells and the activation of pro-survival signalling pathways in chemotherapy surviving residual cells is needed, as these are the ultimate source of the recurrent disease.
Hence with the aim of elucidating such molecular processes, this thesis aimed to answer the following two critical questions:
1. Do first line taxane based chemotherapies facilitate the activation of pro-survival pathways such as the JAK2/STAT3 pathway which is involved in the enrichment of cancer stem cell-like characteristics and cancer cell survival in epithelial ovarian cancer?
2. Does targeting the JAK2/STAT3 pathway with small molecule inhibitors enhance the efficacy of current taxane based therapies?
To answer the above question, this thesis diligently characterised the cancer stem cell-like profiles that emerged in response to taxane based chemotherapy of ovarian cancer cell lines as well as ovarian tumour cells isolated from the ascites of advanced stage ovarian cancer patients. Moreover, this thesis assessed the effects of inhibiting the JAK2/STAT3 pathway on chemoresistance and enrichment of cancer stem cell-like phenotypes. Finally, using an in vivo mouse xenograft model, this thesis validated the demonstrated results obtained from in vitro experimentations.
The results of this thesis demonstrate that treatment with taxane and platinum based therapies does indeed activate the JAK2/STAT3 pathway in both ovarian cancer cell lines as well as tumour cells isolated from the ascites fluid of advanced stage ovarian cancer patients. Moreover, this thesis is the first to demonstrate that the activation of the…
Subjects/Keywords: ovarian cancer; cancer stem cells; JAK2; STAT3
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Abubaker, K. R. (2013). Molecular mechanisms regulating chemotherapy resistance in ovarian carcinomas. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/39886
Chicago Manual of Style (16th Edition):
Abubaker, Khalid Ramadan. “Molecular mechanisms regulating chemotherapy resistance in ovarian carcinomas.” 2013. Doctoral Dissertation, University of Melbourne. Accessed January 21, 2021.
http://hdl.handle.net/11343/39886.
MLA Handbook (7th Edition):
Abubaker, Khalid Ramadan. “Molecular mechanisms regulating chemotherapy resistance in ovarian carcinomas.” 2013. Web. 21 Jan 2021.
Vancouver:
Abubaker KR. Molecular mechanisms regulating chemotherapy resistance in ovarian carcinomas. [Internet] [Doctoral dissertation]. University of Melbourne; 2013. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/11343/39886.
Council of Science Editors:
Abubaker KR. Molecular mechanisms regulating chemotherapy resistance in ovarian carcinomas. [Doctoral Dissertation]. University of Melbourne; 2013. Available from: http://hdl.handle.net/11343/39886

University of Southern California
19.
Madhav, Anisha.
The noncanonical role of telomerase in prostate cancer
cells: exploring a non-telomeric signaling role for telomerase
protein (TERT) in a cancer cell line.
Degree: MS, Biochemistry and Molecular Biology, 2012, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30249/rec/7034
► The telomerase reverse transcriptase (TERT) component of telomerase has reverse transcriptase activity capable of elongating telomeres during each replication cycle of the cell. TERT plays…
(more)
▼ The telomerase reverse transcriptase (TERT) component
of telomerase has reverse transcriptase activity capable of
elongating telomeres during each replication cycle of the cell.
TERT plays a dual role in activating normal stem cell niches and in
potentiating tumorigenicity and malignancy. Recently, there has
been mounting evidence that TERT may exert some of its effects in
stem
cells through functions independent of its ability to maintain
telomere ends. Therefore, we hypothesized that TERT has a
non-canonical (non-telomeric)
cancer signaling role that
potentiates and expands a highly tumorigenic and drug resistant
subpopulation of
cancer stem-like
cells. To test this hypothesis,
we ectopically expressed either a wild type or a catalytically dead
TERT (or control vector) in DU145 prostate
cancer cells and
measured the effects on a spectrum of
cancer stem-like related
phenotypes. We found that ectopically expressing TERT resulted in a
slower overall rate of proliferation with downregulation of the
cell cycle checkpoint proteins c-myc and cyclinD1. At the same time
TERT-expressing DU145 had a significant increase in a CD44+CD24-
subpopulation, which has been associated with a
cancer stem-like
tumorigenic, clonogenic, and metastatic phenotype. TERT-expressing
DU145 was also more invasive and expressed lower transcript levels
of E-cadherin, an important mediator of cell-cell adhesion.
Furthermore, TERT-expressing DU145 had an overall trend, although
not significant, in the
cancer stem-like ability to form spheres,
and had significant downregulation of axin2, a transcriptional
target of β-catenin previously shown to be regulated by TERT in
stem cell models. Most remarkably, this spectrum of phenotypic
changes (surface markers, proliferation, sphere formation,
invasiveness, gene expression) occurred in response to either wild
type or catalytically dead TERT, suggesting that TERT may indeed
potentiate a phenotypic shift towards a
cancer-stem like state that
is independent of its enzymatic telomere-lengthening
role.
Advisors/Committee Members: Tokes, Zoltan A. (Committee Chair).
Subjects/Keywords: telomerase; TERT; prostate cancer; cancer stem cells
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Madhav, A. (2012). The noncanonical role of telomerase in prostate cancer
cells: exploring a non-telomeric signaling role for telomerase
protein (TERT) in a cancer cell line. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30249/rec/7034
Chicago Manual of Style (16th Edition):
Madhav, Anisha. “The noncanonical role of telomerase in prostate cancer
cells: exploring a non-telomeric signaling role for telomerase
protein (TERT) in a cancer cell line.” 2012. Masters Thesis, University of Southern California. Accessed January 21, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30249/rec/7034.
MLA Handbook (7th Edition):
Madhav, Anisha. “The noncanonical role of telomerase in prostate cancer
cells: exploring a non-telomeric signaling role for telomerase
protein (TERT) in a cancer cell line.” 2012. Web. 21 Jan 2021.
Vancouver:
Madhav A. The noncanonical role of telomerase in prostate cancer
cells: exploring a non-telomeric signaling role for telomerase
protein (TERT) in a cancer cell line. [Internet] [Masters thesis]. University of Southern California; 2012. [cited 2021 Jan 21].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30249/rec/7034.
Council of Science Editors:
Madhav A. The noncanonical role of telomerase in prostate cancer
cells: exploring a non-telomeric signaling role for telomerase
protein (TERT) in a cancer cell line. [Masters Thesis]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/30249/rec/7034
20.
Fabrizi, Eros.
Identification of novel therapeutic targets for colon adenocarcinoma.
Degree: 2011, Università degli Studi di Catania
URL: http://hdl.handle.net/10761/95
► Colorectal cancer (CRC) is the third most common form of cancer in the Western world. Despite the emergence of new targeted agents and the use…
(more)
▼ Colorectal cancer (CRC) is the third most common form of cancer in the Western world.
Despite the emergence of new targeted agents and the use of various therapeutic
combinations, none of the treatment options available is curative in patients with advanced
cancer. A growing body of evidence is increasingly supporting the idea that malignancies
originate from a small fraction of cancer cells, called Cancer Stem Cells (CSC), that show
self-renewal and pluripotency and are capable of initiating and sustaining tumor growth.
Several studies have shown that, with respect to the bulk of tumor cells, CSC posses a
higher degree of resistance to chemotherapy and radiotherapy that could explain the
inefficacy of current therapies. The ability to isolate and study these tumor cells provided a
powerful tool for the investigation of drug-and radio-resistance mechanisms thus paving
the way for the development of novel targeted therapies aimed at the tumor complete
eradication.
The aim of this PhD thesis was to use CSC lines, derived from CRC specimens, to
individuate new potential molecular targets for the development of novel therapies. To this
end four colon-CSC lines were subjected to phosphoproteomic analysis by RPPA (Reverse
Phase Protein Array) technology. Through this analysis phosphorylation levels of various
protein kinases and their substrates were evaluated in order to create an activation map of
the main colon-CSC proliferation and cell survival pathways. In parallel colon-CSC lines
have been screened in vitro to the action of 80 commercially available protein-kinase
inhibitors. This screening has revealed a partial correlation between in vitro sensitivity and
phosphoproteomic analysis, but in this study, was not possible to identify predictive factors
to infer colon-CSC sensitivity to specific kinase inhibitors. Colon-CSC was sensitive to the
inhibition of protein kinase C (PKC), known regulator of cell proliferation and survival.
Among PKC inhibitors, the most interesting was the UCN-01, a staurosporine derivative
that can also inhibit PDK1 and Chk1. This compound has been already used in clinical
trials as antineoplastic agent in combination with conventional chemotherapy. The in vitro
treatment of colon-CSC with UCN-01 has demonstrated its ability to enhance the
irinotecan cytotoxicity by increasing the apoptotic response. The combined action of
UCN-01 and irinotecan caused a marked reduction in the levels of antiapoptotic proteins
such as Bcl-XL and Mcl-1 and the activation of caspase 3.
The in vivo administration of UCN-01/irinotecan combination, in a mouse model of
subcutaneous xenograft, confirmed the observations obtained in vitro, leading to a
significant reduction in tumor growth compared to the single treatments. UCN-01 has also shown efficacy in the inhibition of Chk1, as demonstrated by the reduction of the
phosphorylation of its target protein cdc25. Inhibition of Chk1, an important regulator of
cell cycle, in combination with chemotherapy, could help in…
Subjects/Keywords: Colon cancer; Colon cancer stem cells
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fabrizi, E. (2011). Identification of novel therapeutic targets for colon adenocarcinoma. (Thesis). Università degli Studi di Catania. Retrieved from http://hdl.handle.net/10761/95
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fabrizi, Eros. “Identification of novel therapeutic targets for colon adenocarcinoma.” 2011. Thesis, Università degli Studi di Catania. Accessed January 21, 2021.
http://hdl.handle.net/10761/95.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fabrizi, Eros. “Identification of novel therapeutic targets for colon adenocarcinoma.” 2011. Web. 21 Jan 2021.
Vancouver:
Fabrizi E. Identification of novel therapeutic targets for colon adenocarcinoma. [Internet] [Thesis]. Università degli Studi di Catania; 2011. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10761/95.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fabrizi E. Identification of novel therapeutic targets for colon adenocarcinoma. [Thesis]. Università degli Studi di Catania; 2011. Available from: http://hdl.handle.net/10761/95
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University
21.
Salman Noori, Faranak, 1986-.
Stem cell-based ovarian cancer suicide gene therapy.
Degree: PhD, Pharmaceutical Science, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48643/
► Cancer is a leading cause of death worldwide, resulting in 8.2 million deaths in 2012. Tumor suicide gene therapy is among the novel targeted therapeutics…
(more)
▼ Cancer is a leading cause of death worldwide, resulting in 8.2 million deaths in 2012. Tumor suicide gene therapy is among the novel targeted therapeutics that has demonstrated promising results. There are two important factors that specify the efficiency and safety of the suicide gene therapy systems. One is vector safety and efficiency and the other enzyme/prodrug anticancer efficacy. Among the vectors employed for delivery of therapeutics, mesenchymal stem cells (MSCs) have attracted tremendous amount of attention due to their unique features such as inherent tumor tropism and low immunogenicity. The objective of this research was to take advantage of MSCs as cell-based vectors to develop an efficient and safe suicide gene therapy system for cancer. As a first step towards achieving the objective, I engineered a panel of MSCs that were genetically modified to express five different suicide genes and compared their anti-tumor efficiency in vitro and in vivo. Among the enzyme/prodrug systems tested, genetically modified MSCs that expressed yeast cytosine deaminase enzyme (yCD-UPRT) in combination with prodrug 5-fluorocytosine (5FC) demonstrated the highest anti-tumor efficacy. In the next step we focused on developing a safe and efficient method for stem cell engineering. Since current commercially available transfection agents are inefficient and toxic to MSCs, I made an attempt to develop a safe and efficient gene delivery system suitable for MSC engineering. Using a previously developed vector in Dr. Hatefi’s lab as a template, I recombinantly engineered a new vector for MSC transfection. This vector is comprised of a cell penetrating peptide for penetration into MSCs, four histone H2A repeats to condense plasmid DNA (pDNA) into nanosize particles and a fusogenic peptide named GALA to facilitate endosomal escape. The results of this study illustrated that the newly developed recombinant vector could efficiently and safely transfect MSCs. In conclusion we not only successfully developed a safe and efficient method for stem cell engineering but also identified an enzyme/prodrug system that could be used for effective treatment of ovarian cancer.
Advisors/Committee Members: Minko, Tamara (chair).
Subjects/Keywords: Cancer – Gene therapy; Ovaries – Cancer; Stem cells
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Salman Noori, Faranak, 1. (2015). Stem cell-based ovarian cancer suicide gene therapy. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48643/
Chicago Manual of Style (16th Edition):
Salman Noori, Faranak, 1986-. “Stem cell-based ovarian cancer suicide gene therapy.” 2015. Doctoral Dissertation, Rutgers University. Accessed January 21, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/48643/.
MLA Handbook (7th Edition):
Salman Noori, Faranak, 1986-. “Stem cell-based ovarian cancer suicide gene therapy.” 2015. Web. 21 Jan 2021.
Vancouver:
Salman Noori, Faranak 1. Stem cell-based ovarian cancer suicide gene therapy. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Jan 21].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48643/.
Council of Science Editors:
Salman Noori, Faranak 1. Stem cell-based ovarian cancer suicide gene therapy. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48643/

University of Manchester
22.
Ablett, Matthew Paul.
Discovery and Investigation of CXCR4 Signalling in Breast
Stem Cell-Enriched Populations.
Degree: 2012, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159339
► C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling via stromal cell-derived…
(more)
▼ C-X-C chemokine receptor type 4 (CXCR4) is known to
regulate lung, pancreatic and prostate
cancer stem
cells. In breast
cancer, CXCR4 signalling via stromal cell-derived factor-1 (SDF-1)
has been reported to be a mediator of metastasis, and is linked to
poor prognosis. However its role in normal and malignant breast
stem cell function has not been investigated.Anoikis-resistant (AR)
cells were collected from mammosphere culture from 2 immortalised
(MCF10A, 226L) and 3 malignant (MCF7, T47D, SKBR3) breast cell
lines. For all cell lines, AR
cells had a significantly higher
mammosphere forming efficiency (MFE) than unsorted
cells. The AR
cells of the normal cell lines also demonstrated increased
formation of 3D structures using the Matrigel assay. In vivo, MCF7
and T47D AR
cells demonstrated increased capacity to form tumours
compared with unsorted
cells. This suggests that AR
cells are
enriched for normal and malignant breast stem
cells.We performed an
Agilent custom gene microarray and demonstrated up-regulation of
CXCR4 mRNA expression in AR
cells. CXCR4 protein expression was
also higher in AR
cells, shown by flow cytometry. The effects of
AMD3100 (CXCR4 antagonist) and SDF-1 (CXCR4 ligand) on stem cell
activity were investigated in the mammosphere assay. In the normal
cell lines, SDF-1 significantly reduced MFE and this decrease was
rescued by AMD3100. Incubation with AMD3100 increased MFE in the
estrogen receptor positive breast
cancer cell lines (MCF7 and T47D)
and patient-derived metastatic tumour samples. AMD3100 reduced the
self-renewal of T47D
cells, as assessed by second generation
mammospheres. MCF7
cells were retro-virally transfected to
over-express CXCR4 or sorted for CXCR4 cell surface expression.
Mammosphere formation was significantly increased in CXCR4+ and
CXCR4 over-expressing
cells compared with CXCR4- and parental
cells. There was a greater reduction in self-renewal following
AMD3100 treatment in the CXCR4 over-expressing
cells compared with
parental
cells. AMD3100 has been shown to have an agonistic effect
on the novel chemokine receptor CXCR7, a scavenging receptor for
SDF-1. All cell lines demonstrated cell surface expression of
CXCR7, measured by flow cytometry and mRNA expression. Potential
interactions between CXCR4, CXCR7 and SDF-1 must be considered in
future investigation of the role of CXCR4 signalling.Our data
establish that CXCR4 signalling has contrasting effects on normal
and malignant breast stem cell activity. CXCR4 influences
self-renewal of malignant stem
cells which may account for its role
in tumorigenesis. CXCR4 signalling may be important in tumour
formation at the sites of metastases as well as in cell migration.
Its role in stem cell migration merits further investigation. In
conclusion, CXCR4-targeted therapy, alongside current standards of
care, may improve breast
cancer outcomes.
Advisors/Committee Members: Clarke, Robert.
Subjects/Keywords: CXCR4; Breast Cancer; Stem Cells; Breast Cancer Stem Cells
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ablett, M. P. (2012). Discovery and Investigation of CXCR4 Signalling in Breast
Stem Cell-Enriched Populations. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159339
Chicago Manual of Style (16th Edition):
Ablett, Matthew Paul. “Discovery and Investigation of CXCR4 Signalling in Breast
Stem Cell-Enriched Populations.” 2012. Doctoral Dissertation, University of Manchester. Accessed January 21, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159339.
MLA Handbook (7th Edition):
Ablett, Matthew Paul. “Discovery and Investigation of CXCR4 Signalling in Breast
Stem Cell-Enriched Populations.” 2012. Web. 21 Jan 2021.
Vancouver:
Ablett MP. Discovery and Investigation of CXCR4 Signalling in Breast
Stem Cell-Enriched Populations. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Jan 21].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159339.
Council of Science Editors:
Ablett MP. Discovery and Investigation of CXCR4 Signalling in Breast
Stem Cell-Enriched Populations. [Doctoral Dissertation]. University of Manchester; 2012. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:159339
23.
木村,洋平.
CD44variant exon 9 plays an important role in colon cancer initiating cells. : CD44 variant exon 9は大腸癌幹細胞において重要な役割を示す.
Degree: 博士(医学), 2014, University of Fukui / 福井大学
URL: http://hdl.handle.net/10098/8439
以下に掲載 : Oncotarget 4(5) pp.785-791 2013. Impact Journals. 共著者 : Youhei Kimura, Takanori Goi, Toshiyuki Nakazawa, Hirono Yasuno, Kanji Katayama, Takeshi Urano, Akiko Yamaguchi
Subjects/Keywords: colon cancer; CD44 variant exon; stem cells; Cancer initiating cells
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
木村,洋平. (2014). CD44variant exon 9 plays an important role in colon cancer initiating cells. : CD44 variant exon 9は大腸癌幹細胞において重要な役割を示す. (Thesis). University of Fukui / 福井大学. Retrieved from http://hdl.handle.net/10098/8439
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
木村,洋平. “CD44variant exon 9 plays an important role in colon cancer initiating cells. : CD44 variant exon 9は大腸癌幹細胞において重要な役割を示す.” 2014. Thesis, University of Fukui / 福井大学. Accessed January 21, 2021.
http://hdl.handle.net/10098/8439.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
木村,洋平. “CD44variant exon 9 plays an important role in colon cancer initiating cells. : CD44 variant exon 9は大腸癌幹細胞において重要な役割を示す.” 2014. Web. 21 Jan 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
木村,洋平. CD44variant exon 9 plays an important role in colon cancer initiating cells. : CD44 variant exon 9は大腸癌幹細胞において重要な役割を示す. [Internet] [Thesis]. University of Fukui / 福井大学; 2014. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10098/8439.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
木村,洋平. CD44variant exon 9 plays an important role in colon cancer initiating cells. : CD44 variant exon 9は大腸癌幹細胞において重要な役割を示す. [Thesis]. University of Fukui / 福井大学; 2014. Available from: http://hdl.handle.net/10098/8439
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester
24.
Ablett, Matthew.
Discovery and investigation of CXCR4 signalling in breast stem cell-enriched populations.
Degree: PhD, 2012, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/discovery-and-investigation-of-cxcr4-signalling-in-breast-stem-cellenriched-populations(feed5c92-01b0-4a07-95fe-72e4babda0b0).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764232
► C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling via stromal cell-derived…
(more)
▼ C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling via stromal cell-derived factor-1 (SDF-1) has been reported to be a mediator of metastasis, and is linked to poor prognosis. However its role in normal and malignant breast stem cell function has not been investigated. Anoikis-resistant (AR) cells were collected from mammosphere culture from 2 immortalised (MCF10A, 226L) and 3 malignant (MCF7, T47D, SKBR3) breast cell lines. For all cell lines, AR cells had a significantly higher mammosphere forming efficiency (MFE) than unsorted cells. The AR cells of the normal cell lines also demonstrated increased formation of 3D structures using the Matrigel assay. In vivo, MCF7 and T47D AR cells demonstrated increased capacity to form tumours compared with unsorted cells. This suggests that AR cells are enriched for normal and malignant breast stem cells. We performed an Agilent custom gene microarray and demonstrated up-regulation of CXCR4 mRNA expression in AR cells. CXCR4 protein expression was also higher in AR cells, shown by flow cytometry. The effects of AMD3100 (CXCR4 antagonist) and SDF-1 (CXCR4 ligand) on stem cell activity were investigated in the mammosphere assay. In the normal cell lines, SDF-1 significantly reduced MFE and this decrease was rescued by AMD3100. Incubation with AMD3100 increased MFE in the estrogen receptor positive breast cancer cell lines (MCF7 and T47D) and patient-derived metastatic tumour samples. AMD3100 reduced the self-renewal of T47D cells, as assessed by second generation mammospheres. MCF7 cells were retro-virally transfected to over-express CXCR4 or sorted for CXCR4 cell surface expression. Mammosphere formation was significantly increased in CXCR4+ and CXCR4 over-expressing cells compared with CXCR4- and parental cells. There was a greater reduction in self-renewal following AMD3100 treatment in the CXCR4 over-expressing cells compared with parental cells. AMD3100 has been shown to have an agonistic effect on the novel chemokine receptor CXCR7, a scavenging receptor for SDF-1. All cell lines demonstrated cell surface expression of CXCR7, measured by flow cytometry and mRNA expression. Potential interactions between CXCR4, CXCR7 and SDF-1 must be considered in future investigation of the role of CXCR4 signalling. Our data establish that CXCR4 signalling has contrasting effects on normal and malignant breast stem cell activity. CXCR4 influences self-renewal of malignant stem cells which may account for its role in tumorigenesis. CXCR4 signalling may be important in tumour formation at the sites of metastases as well as in cell migration. Its role in stem cell migration merits further investigation. In conclusion, CXCR4-targeted therapy, alongside current standards of care, may improve breast cancer outcomes.
Subjects/Keywords: 616.99; Breast Cancer Stem Cells; Stem Cells; Breast Cancer; CXCR4
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ablett, M. (2012). Discovery and investigation of CXCR4 signalling in breast stem cell-enriched populations. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/discovery-and-investigation-of-cxcr4-signalling-in-breast-stem-cellenriched-populations(feed5c92-01b0-4a07-95fe-72e4babda0b0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764232
Chicago Manual of Style (16th Edition):
Ablett, Matthew. “Discovery and investigation of CXCR4 signalling in breast stem cell-enriched populations.” 2012. Doctoral Dissertation, University of Manchester. Accessed January 21, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/discovery-and-investigation-of-cxcr4-signalling-in-breast-stem-cellenriched-populations(feed5c92-01b0-4a07-95fe-72e4babda0b0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764232.
MLA Handbook (7th Edition):
Ablett, Matthew. “Discovery and investigation of CXCR4 signalling in breast stem cell-enriched populations.” 2012. Web. 21 Jan 2021.
Vancouver:
Ablett M. Discovery and investigation of CXCR4 signalling in breast stem cell-enriched populations. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Jan 21].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/discovery-and-investigation-of-cxcr4-signalling-in-breast-stem-cellenriched-populations(feed5c92-01b0-4a07-95fe-72e4babda0b0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764232.
Council of Science Editors:
Ablett M. Discovery and investigation of CXCR4 signalling in breast stem cell-enriched populations. [Doctoral Dissertation]. University of Manchester; 2012. Available from: https://www.research.manchester.ac.uk/portal/en/theses/discovery-and-investigation-of-cxcr4-signalling-in-breast-stem-cellenriched-populations(feed5c92-01b0-4a07-95fe-72e4babda0b0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764232

University of Toronto
25.
Vanner, Robert James.
Defining the Mode of Medulloblastoma Growth using the Ptch1 Heterozygous Mouse Model.
Degree: PhD, 2015, University of Toronto
URL: http://hdl.handle.net/1807/71396
► Single cancers can be comprised of highly heterogeneous cell populations. In brain tumours, including the malignant pediatric brain tumour medulloblastoma, how the distinct cell types…
(more)
▼ Single cancers can be comprised of highly heterogeneous cell populations. In brain tumours, including the malignant pediatric brain tumour medulloblastoma, how the distinct cell types that comprise a tumour contribute to growth and relapse are unclear. Transplantation of human and mouse medulloblastomas have prospectively identified
cells with the cardinal stem cell properties of self-renewal and differentiation capacity, but the identity, biology and relevance of these
cells in primary tumours are unknown. Here, using Ptch1 heterozygous mice irradiated at birth, I define the cellular mechanism of mouse medulloblastoma growth. Kinetic studies using thymidine analogues showed that rare, Sox2+
cells are relatively quiescent compared to the common, proliferating progenitors expressing Doublecortin (DCX) that differentiate into post-mitotic NeuN+
cells. Transplantation and lineage tracing experiments show that Sox2+
cells act as medulloblastoma stem
cells: self-renewing and differentiating to drive growth in transplants and primary tumours. Lineage tracing revealed that tumours grow as a caricature of a neurogenic system. Investigating cell-type specific drug responses revealed that Sox2+
cells are selected for by anti-mitotic and Shh pathway-targeted therapies, creating a reservoir for relapse. Accordingly, high expression of a Sox2+ cell gene signature and high frequencies of Sox2+
cells in human tumours predict poor prognosis. Sox2-expressing primary medulloblastoma cultures were screened in serum free conditions in vitro to identify compounds that inhibit Sox2+ medulloblastoma cell growth. The aureolic acid mithramycin triggered Sox2+ cell apoptosis in vitro, blocked self-renewal and extended Ptch1+/- mouse survival in vivo, and completely prevented tumour regrowth in transplantation experiments. Therefore, targeting self-renewal in medulloblastoma by disrupting the stem cell hierarchy may be of therapeutic benefit. These findings confirm the hierarchical growth paradigm described for medulloblastoma based on transplantation experiments, define the biology of tumours’ constituent cell types and identify a novel approach to prolong medulloblastoma remission by targeting self-renewing
cells.
Advisors/Committee Members: Dirks, Peter B, Molecular and Medical Genetics.
Subjects/Keywords: Cancer; Cancer stem cells; Medulloblastoma; Quiescence; Sox2; Stem cells; 0379
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vanner, R. J. (2015). Defining the Mode of Medulloblastoma Growth using the Ptch1 Heterozygous Mouse Model. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/71396
Chicago Manual of Style (16th Edition):
Vanner, Robert James. “Defining the Mode of Medulloblastoma Growth using the Ptch1 Heterozygous Mouse Model.” 2015. Doctoral Dissertation, University of Toronto. Accessed January 21, 2021.
http://hdl.handle.net/1807/71396.
MLA Handbook (7th Edition):
Vanner, Robert James. “Defining the Mode of Medulloblastoma Growth using the Ptch1 Heterozygous Mouse Model.” 2015. Web. 21 Jan 2021.
Vancouver:
Vanner RJ. Defining the Mode of Medulloblastoma Growth using the Ptch1 Heterozygous Mouse Model. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1807/71396.
Council of Science Editors:
Vanner RJ. Defining the Mode of Medulloblastoma Growth using the Ptch1 Heterozygous Mouse Model. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/71396

Kyoto University / 京都大学
26.
Oshima, Nobu.
Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors : 特定因子による大腸癌細胞への癌幹細胞特性の誘導.
Degree: 博士(医学), 2014, Kyoto University / 京都大学
URL: http://hdl.handle.net/2433/192147
;
http://dx.doi.org/10.14989/doctor.k18547
Oshima N, Yamada Y, Nagayama S, Kawada K, Hasegawa S, et al. (2014) Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors. PLoS ONE 9(7): e101735. doi:10.1371/journal.pone.0101735
新制・課程博士
甲第18547号
医博第3940号
Subjects/Keywords: Cancer Stem Cells; Reprogramming; iPS cells; Colon Cancer; Serial transplantation; Dye-efflux; Stem cells
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Oshima, N. (2014). Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors : 特定因子による大腸癌細胞への癌幹細胞特性の誘導. (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/192147 ; http://dx.doi.org/10.14989/doctor.k18547
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Oshima, Nobu. “Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors : 特定因子による大腸癌細胞への癌幹細胞特性の誘導.” 2014. Thesis, Kyoto University / 京都大学. Accessed January 21, 2021.
http://hdl.handle.net/2433/192147 ; http://dx.doi.org/10.14989/doctor.k18547.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Oshima, Nobu. “Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors : 特定因子による大腸癌細胞への癌幹細胞特性の誘導.” 2014. Web. 21 Jan 2021.
Vancouver:
Oshima N. Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors : 特定因子による大腸癌細胞への癌幹細胞特性の誘導. [Internet] [Thesis]. Kyoto University / 京都大学; 2014. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/2433/192147 ; http://dx.doi.org/10.14989/doctor.k18547.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Oshima N. Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors : 特定因子による大腸癌細胞への癌幹細胞特性の誘導. [Thesis]. Kyoto University / 京都大学; 2014. Available from: http://hdl.handle.net/2433/192147 ; http://dx.doi.org/10.14989/doctor.k18547
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Medical Center
27.
Kwak, Changsoo.
Stromal Fibroblasts Restrain the Rate of Colon Cancer Progression and Metastasis by Suppressing Regulatory T Cells and Colon Cancer Stem Cells.
Degree: PhD, 2017, Texas Medical Center
URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/775
► The initiation, progression, and metastasis of tumors involve not only cancer cells, but also the tumor microenvironment, which consists of immune or inflammatory cells,…
(more)
▼ The initiation, progression, and metastasis of tumors involve not only
cancer cells, but also the tumor microenvironment, which consists of immune or inflammatory
cells, fibroblasts, endothelial
cells, and extracellular matrix components (ECM). Fibroblasts are ubiquitous stromal
cells that can influence other neighboring cell types through the secretion of chemokines, cytokines, ECM, ECM remodeling enzymes, and other metabolites. Myofibroblasts are a distinct subtype of fibroblasts characterized by expression α-smooth muscle actin (αSMA). These
cells are a dominant component of the microenvironment, and a FSP1 and FAP could be a different clone of fibroblasts. Myofibroblasts also have been known to contribute to
cancer progression and metastasis in multiple
cancer types including breast and pancreas
cancer, both of which are associated with extensive desmoplasia. However, the role of αSMA+ myofibroblasts in the context of colorectal
cancer has remained largely descriptive and functionally unknown. The studies outlined in this project explored the functional contribution of αSMA+ myofibroblasts in the disease progression of colorectal
cancer. To address this, we used the spontaneous colorectal
cancer model, which consists of 6 alleles: Villin-Cre-ERT2; APCflox/flox; p53flox/flox; tetO-LSL-KrasG12D; Rosa26-LSL-Luc; Rosa26-LSL-rtTA- eGFP. These mice were bred with αSMA-TK and αSMA-RFP transgenic mice for selective targeting and monitoring of myofibroblasts in the tumor microenvironment in these eight allelic transgenic mice.
Mice with αSMA+ myofibroblast-depleted tumors exhibited hind limb paresis, which likely contributed to their decreased overall survival. Intraluminal tumor burden appeared reduced in myofibroblast-depleted tumors; however, the tumors were depressed resulting in more invasion to both the vascular and lymphatic vessels. The depletion of myofibroblast surprising resulted in increased deposition of ECM and generation of an immunosuppressive microenvironment with the accumulation of CD4+ Foxp3+ Treg. Furthermore, we discovered that the population of
cancer stem
cells expressing Lgr5 and Dclk1 was increased in αSMA+ myofibroblast-depleted tumors. In conclusion, our study reveals the unknown functional role of myofibroblasts in regulating T cell-meditated anti- tumor immunity and stemness features in colon
cancer cells.
Advisors/Committee Members: Raghu Kalluri, MD, PhD, Jian Hu, PhD, Honami Naora, PhD.
Subjects/Keywords: Myofibroblasts; Cancer stem cells; Regulatory T cells; Colorectal cancer; Cancer Biology; Immunity
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kwak, C. (2017). Stromal Fibroblasts Restrain the Rate of Colon Cancer Progression and Metastasis by Suppressing Regulatory T Cells and Colon Cancer Stem Cells. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/775
Chicago Manual of Style (16th Edition):
Kwak, Changsoo. “Stromal Fibroblasts Restrain the Rate of Colon Cancer Progression and Metastasis by Suppressing Regulatory T Cells and Colon Cancer Stem Cells.” 2017. Doctoral Dissertation, Texas Medical Center. Accessed January 21, 2021.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/775.
MLA Handbook (7th Edition):
Kwak, Changsoo. “Stromal Fibroblasts Restrain the Rate of Colon Cancer Progression and Metastasis by Suppressing Regulatory T Cells and Colon Cancer Stem Cells.” 2017. Web. 21 Jan 2021.
Vancouver:
Kwak C. Stromal Fibroblasts Restrain the Rate of Colon Cancer Progression and Metastasis by Suppressing Regulatory T Cells and Colon Cancer Stem Cells. [Internet] [Doctoral dissertation]. Texas Medical Center; 2017. [cited 2021 Jan 21].
Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/775.
Council of Science Editors:
Kwak C. Stromal Fibroblasts Restrain the Rate of Colon Cancer Progression and Metastasis by Suppressing Regulatory T Cells and Colon Cancer Stem Cells. [Doctoral Dissertation]. Texas Medical Center; 2017. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/775

University of Delaware
28.
Modarai, Shirin Raya.
Stem cell and neuroendocrine cell phenotypes in normal and malignant colonic cells.
Degree: PhD, University of Delaware, Department of Biological Sciences, 2014, University of Delaware
URL: http://udspace.udel.edu/handle/19716/16768
► In the development of colorectal cancer (CRC), stem cell (SC) overpopulation underlies tumor initiation and progression, but the underlying mechanisms are poorly understood. We hypothesize…
(more)
▼ In the development of colorectal
cancer (CRC), stem cell (SC) overpopulation underlies tumor initiation and progression, but the underlying mechanisms are poorly understood. We hypothesize that neuroendocrine
cells (NE)
cells play a key role in maintaining the SC population in the normal colon and, aberrant signaling from NE
cells contributes to increased "stemness" and tumor growth. Indeed, NE
cells and SCs reside in close proximity to each other in the SC niche at the bottom of the normal human colonic crypt. Therefore, it seems feasible that the communication between NE
cells and SCs is crucial to normal crypt homeostasis and that dysregulation of the interactions between the two cell types could lead to SC overpopulation during
cancer progression. Our studies on human colonic tissues show that in normal crypts, ALDH1 + ,SSTR1+ and GLP-2R+ expressing
cells are located in the SC niche and are less than 5% of the total colonic crypt
cells. During stepwise progression to
cancer there is a progressive increase in the proportion of ALDH+
cells and small decrease in SSTR1 and GLP-2R
cells. We did further studies to assess how specific NE factors might be regulating SCs. Because we found, by flow cytometric analysis, that various CRC cell lines (COL0320, DiFi, LoVo, SW480, HCT116 & HT29) each maintains a unique proportion of SCs and NE
cells over time, we surmised these proportions are maintained constant through feedback mechanisms involving SC and NE cell subpopulations. When these cell lines were induced to differentiate along the NE lineage upon retinoid treatment, they showed a decrease in the proportion of ALDH1 +
cells and an increase in NE cell differentiation. Retinoid treatment that induces NE differentiation also decreased the sphere-forming ability of
cells in terms of the number and sizes of spheres that were formed from each cell line. Furthermore, co-cultures with ALDH1 + and SSTR1+
cells and the addition of exogenous somatostatin to ALDH+
cells resulted in a maintenance of ALDH+ population size in the HT29
cells while in the SW480
cells, the same treatment resulted in the same maintenance of ALDH+
cells, but a decrease in total cell number and cell viability. Interestingly, inhibition of SSTR signalling resulted in a decreased percentage of ALDH+
cells and total cell number. Lastly, co-cultures with ALDH1+ and GLP-2R+
cells with the addition of exogenous glucagon-like peptide 2 to ALDH+
cells resulted in a decrease in the ALDH+ population size in both cell lines and a slight increase in total cell number. Taken together, our findings support the hypothesis that: (1) specific NE factors maintain or decrease the colonic SC population size via a paracrine mechanism in the normal colon, and (2) dysregulation of these mechanisms contributes to increased "stemness" and tumor growth.
Advisors/Committee Members: Galileo, Deni S.Boman, Bruce.
Subjects/Keywords: Stem cells.; Paraneurons.; Cancer cells.; Colon (Anatomy); Colon (Anatomy) – Cancer – Cytopathology.; Colon (Anatomy) – Cancer – Etiology.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Modarai, S. R. (2014). Stem cell and neuroendocrine cell phenotypes in normal and malignant colonic cells. (Doctoral Dissertation). University of Delaware. Retrieved from http://udspace.udel.edu/handle/19716/16768
Chicago Manual of Style (16th Edition):
Modarai, Shirin Raya. “Stem cell and neuroendocrine cell phenotypes in normal and malignant colonic cells.” 2014. Doctoral Dissertation, University of Delaware. Accessed January 21, 2021.
http://udspace.udel.edu/handle/19716/16768.
MLA Handbook (7th Edition):
Modarai, Shirin Raya. “Stem cell and neuroendocrine cell phenotypes in normal and malignant colonic cells.” 2014. Web. 21 Jan 2021.
Vancouver:
Modarai SR. Stem cell and neuroendocrine cell phenotypes in normal and malignant colonic cells. [Internet] [Doctoral dissertation]. University of Delaware; 2014. [cited 2021 Jan 21].
Available from: http://udspace.udel.edu/handle/19716/16768.
Council of Science Editors:
Modarai SR. Stem cell and neuroendocrine cell phenotypes in normal and malignant colonic cells. [Doctoral Dissertation]. University of Delaware; 2014. Available from: http://udspace.udel.edu/handle/19716/16768

Rhodes University
29.
Willmer, Tarryn.
The role of Hsp90/Hsp70 organising protein (Hop) in the Proliferation, Survival and Migration of Breast Cancer Cells.
Degree: MS, Faculty of Science, Biochemistry, Microbiology and Biotechnology, 2012, Rhodes University
URL: http://hdl.handle.net/10962/d1015720
► Hop (the Hsp90/Hsp70 organising protein) is a co-chaperone that acts as an adapter between the major molecular chaperones Hsp90 and Hsp70 during the cellular assembly…
(more)
▼ Hop (the Hsp90/Hsp70 organising protein) is a co-chaperone that acts as an adapter between
the major molecular chaperones Hsp90 and Hsp70 during the cellular assembly of the Hsp90
complex. The Hsp90 complex regulates the stability and conformational maturation of a range
of important cellular proteins, many of which are deregulated in
cancer. In this study, we
hypothesised that Hop knockdown inhibits proliferation and migration of
cancer cells. We
characterised the expression of Hop in cell models of different cancerous status, and provided
evidence that Hop was upregulated in tumour
cells compared to normal cell counterparts.
Using an RNA interference approach, a 60-90% knockdown of Hop was achieved for up to 144
hours in the MDA-MB-231 and Hs578T breast
cancer cell lines. Hop knockdown resulted in
downregulation of the Hsp90 client proteins, Akt and Stat3, as well as a change in the
expression of other Hsp90 co-chaperones, p23, Cdc37 and Aha1, while no change in the levels
of Hsp90 or Hsp70 was observed. Silencing of Hop impaired cell proliferation in Hs578T
cells but
an increase in proliferation in MDA-MB-231, suggesting that the role of Hop in
cancer cell
proliferation was dependent on type of
cancer cell. Hop knockdown in Hs578T and MDA-MB-
231
cells did not lead to any significant changes in the half maximal inhibitory concentrations
(IC50) of selected small molecule inhibitors (paclitaxel, geldanamycin and novobiocin) in these
cell lines after 72 hours. Hop knockdown
cells were however, more sensitive than control
cells
to the Hsp90 inhibitors geldanamycin and novobiocin at earlier time points and in the presence
of the drug transporter inhibitor, verapamil.
Hop knockdown caused a decrease in cell migration as measured by the wound healing assay in
both Hs578T and MDA-MB-231
cells. Hop was present in purified pseudopodia fractions of
migrating
cells, and immunofluorescence analysis showed that Hop colocalised with actin at the
leading edges of pseudopodia, points of adhesion and at intercellular junctions of
cells that have
been stimulated to migrate with the chemokine stromal derived factor-1. Hop was able to bind
to actin in vitro using actin cosedimentation assays, and silencing of Hop dramatically reduced
the capacity of Hs578T
cells to form pseudopodia. These results establish a correlation between
Hop and actin dynamics, pseudopodia formation and migration in the context of Hop silencing,
and collectively suggest that Hop plays a role in
cancer cell migration. This study presents
experimental evidence for a promising alternative to targeting Hsp90 and Hsp70 chaperones, a
novel drug target in
cancer therapy.
Advisors/Committee Members: Edkins, A..
Subjects/Keywords: Cancer – Treatment; Heat shock proteins; Cancer cells; Breast – Cancer
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Willmer, T. (2012). The role of Hsp90/Hsp70 organising protein (Hop) in the Proliferation, Survival and Migration of Breast Cancer Cells. (Masters Thesis). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1015720
Chicago Manual of Style (16th Edition):
Willmer, Tarryn. “The role of Hsp90/Hsp70 organising protein (Hop) in the Proliferation, Survival and Migration of Breast Cancer Cells.” 2012. Masters Thesis, Rhodes University. Accessed January 21, 2021.
http://hdl.handle.net/10962/d1015720.
MLA Handbook (7th Edition):
Willmer, Tarryn. “The role of Hsp90/Hsp70 organising protein (Hop) in the Proliferation, Survival and Migration of Breast Cancer Cells.” 2012. Web. 21 Jan 2021.
Vancouver:
Willmer T. The role of Hsp90/Hsp70 organising protein (Hop) in the Proliferation, Survival and Migration of Breast Cancer Cells. [Internet] [Masters thesis]. Rhodes University; 2012. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/10962/d1015720.
Council of Science Editors:
Willmer T. The role of Hsp90/Hsp70 organising protein (Hop) in the Proliferation, Survival and Migration of Breast Cancer Cells. [Masters Thesis]. Rhodes University; 2012. Available from: http://hdl.handle.net/10962/d1015720

Georgia Tech
30.
Vermeersch, Kathleen A.
Systems-level characterization of ovarian cancer metabolism.
Degree: PhD, Chemical and Biomolecular Engineering, 2014, Georgia Tech
URL: http://hdl.handle.net/1853/54258
► The purpose of this thesis was to characterize cancer metabolism in vitro using epithelial ovarian cancer as a model on an untargeted, systems-level, basis with…
(more)
▼ The purpose of this thesis was to characterize
cancer metabolism in vitro using epithelial ovarian
cancer as a model on an untargeted, systems-level, basis with particular attention paid to the difference between
cancer stem cell metabolism and
cancer cell metabolism. Two-dimensional gas chromatography coupled to mass spectrometry was used to measure the metabolite profiles of the ovarian
cancer and
cancer stem cell lines under normal baseline conditions and also under chemotherapeutic and environmental perturbations. These two cell lines exhibited significant metabolic differences under normal baseline conditions and results demonstrated that metabolism in the ovarian
cancer stem cell line was distinct from that of more differentiated isogenic
cancer cells, showing similarities to stem cell metabolism that suggest the potential importance of metabolism for the
cancer stem cell phenotype. Glucose deprivation, hypoxia, and ischemia all perturbed ovarian
cancer and
cancer stem cell metabolism, but not in the same ways between the cell types. Chemotherapeutic treatment with docetaxel caused metabolic changes mostly in amino acid and carbohydrate metabolism in ovarian
cancer cells, while ovarian
cancer stem cell metabolism was not affected by docetaxel. Overall, these metabolic differences between the two cell types will deepen our understanding of the metabolic changes occurring within the in vivo tumor and will help drive development of
cancer stem cell targeted therapeutics.
Advisors/Committee Members: Styczynski, Mark P. (advisor), Chen, Rachel (committee member), Bommarius, Andreas S. (committee member), Dawson, Michelle R. (committee member), McDonald, John F. (committee member).
Subjects/Keywords: Cancer stem cells; Cancer metabolism; Ovarian cancer; Metabolomics
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APA (6th Edition):
Vermeersch, K. A. (2014). Systems-level characterization of ovarian cancer metabolism. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54258
Chicago Manual of Style (16th Edition):
Vermeersch, Kathleen A. “Systems-level characterization of ovarian cancer metabolism.” 2014. Doctoral Dissertation, Georgia Tech. Accessed January 21, 2021.
http://hdl.handle.net/1853/54258.
MLA Handbook (7th Edition):
Vermeersch, Kathleen A. “Systems-level characterization of ovarian cancer metabolism.” 2014. Web. 21 Jan 2021.
Vancouver:
Vermeersch KA. Systems-level characterization of ovarian cancer metabolism. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Jan 21].
Available from: http://hdl.handle.net/1853/54258.
Council of Science Editors:
Vermeersch KA. Systems-level characterization of ovarian cancer metabolism. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/54258
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