Дисертації з теми "High-grade serous ovarian carcinoma"
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Everitt, Gemma Louise Ann. "The inflammatory infiltrate of high-grade serous carcinoma omental metastasis." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8038.
Повний текст джерелаSheets, Jordan N. "Inhibitory Functions of SUSD2 in the Progression of High-Grade Serous Ovarian Carcinoma." Thesis, University of South Dakota, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10633628.
Повний текст джерелаSushi Domain Containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. A clinically annotated HGSOC tissue microarray was stained with an anti-SUSD2 antibody. Patients with tumors that had weak SUSD2 staining had a shorter median survival (31.7 months) compared to patients that had tumors with strong SUSD2 staining (49.1 months; p value = 0.0083).
To investigate the role of SUSD2 in HGSOC, stable OVCAR3, OVSAHO and KURAMOCHI cell lines were established through transfection of shRNA targeted to SUSD2 transcripts (SUSD2 knock-down [KD] cell lines) or non-targeting shRNA (SUSD2 NT) cell lines. Boyden chamber and wound healing assays demonstrated that OVCAR3, OVSAHO and KURAMOCHI SUSD2 KD cells migrated at significantly higher rates than their SUSD2 NT counterpart cell lines. RT-qPCR and western immunoblot analysis indicated an inverse relationship between SUSD2 and well characterized mesenchymal genes, such as TWIST1, ZEB1 and CHD2. In addition, OVCAR3 and KURAMOCHI SUSD2 KD spheroids displayed increased mesothelial clearance ability compared to SUSD2 NT spheroids.
To explore the potential for SUSD2 to inhibit late-stage HGSOC metastasis, female athymic nude mice were injected with either OVCAR3 NT or OVCAR3 KD cells. Fewer nodules were observed in the pancreas and omentum of the OVCAR3 NT mice when compared to the OVCAR3 KD mice. Furthermore, OVCAR3 KD mice had a significantly shorter median survival compared to OVCAR3 NT mice (175 days compared to 185.5 days, respectively; p-value = 0.0047).
KURAMOCHI lysate was immunoprecipitated for SUSD2-associated immunocomplexes and subjected to liquid chromatography, tandem mass spectrometry (LC-MS/MS) analysis, yielding a list of candidate SUSD2-interacting proteins associated with RNA processing. Immunofluorescence analysis of OVCAR3, KURAMOCHI and SKBR3 cells and western immunoblot analysis of their subcellular extracts revealed SUSD2 to be present in cell nuclei, mitochondria and cytoplasm; however, SUSD2 was relatively less abundant in SKBR3 nuclei.
Our findings suggest that increased SUSD2 expression in HGSOC impedes metastasis, consistent with prolonged survival observed in HGSOC patients with high SUSD2-expressing primary tumors. The differences in subcellular distribution between HGSOC cells and breast cancer cells may explain alternate functions of SUSD2 in different cancers.
Cole, Alexander John. "The role of p53 and histone H2B monoubiquitination in high-grade serous ovarian carcinoma." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17639.
Повний текст джерелаCheng, Jung-Chien. "Role of E-cadherin in the serous borderline ovarian tumor and low-grade serous ovarian carcinoma cell invasion." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43651.
Повний текст джерелаVirtanen, Siru Sirkku Pauliina. "Phenotypic and functional characterisation of cancer stem cells in human high-grade serous ovarian carcinoma." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648879.
Повний текст джерелаMurakami, Ryusuke. "Establishment of a novel histopathological classification of high-grade serous ovarian carcinoma correlated with prognostically distinct gene expression subtypes." Kyoto University, 2016. http://hdl.handle.net/2433/215449.
Повний текст джерелаDawson, Amy. "Targeted therapy in low-grade serous ovarian carcinoma : characterization of MEK inhibitor response in novel patient-derived cell lines." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59456.
Повний текст джерелаMedicine, Faculty of
Graduate
Howe, Eleanor Arden. "MicroRNA expression and activity in high-grade serous ovarian cancer." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:9d17590c-550b-4ae9-ac8d-15387cf70e5f.
Повний текст джерелаTodeschini, P. "NON-CODING RNAS IN HIGH-GRADE SEROUS EPITHELIAL OVARIAN CANCER." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/488108.
Повний текст джерелаMoore, Elizabeth. "Improving earlier non-invasive diagnosis of high-grade serous ovarian cancer." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/285405.
Повний текст джерелаShahabi, Shohreh. "Exploring Novel Precision Medicine Approaches in High Grade Serous Ovarian Cancer." Doctoral thesis, Universite Libre de Bruxelles, 2020. https://dipot.ulb.ac.be/dspace/bitstream/2013/312182/3/ToC.pdf.
Повний текст джерелаDoctorat en Sciences médicales (Santé Publique)
info:eu-repo/semantics/nonPublished
OPINATO, VIVIANA MARIA. "Role of Mesenchymal Stromal Cells in High-Grade Serous Ovarian Cancer." Doctoral thesis, Università degli Studi di Trieste, 2018. http://hdl.handle.net/11368/2924766.
Повний текст джерелаRUSSO, SPENA CONCETTA. "Pin1 protein: a druggable target in high grade serous ovarian cancer." Doctoral thesis, Università degli Studi di Trieste, 2019. http://hdl.handle.net/11368/2957167.
Повний текст джерелаKhalique, Lalarukh. "A Molecular Study of Clonality and Heterogeneity in High-Grade Serous Epithelial Ovarian Cancer." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518266.
Повний текст джерелаTIERNO, DOMENICO. "Comprehensive Characterization and Effective Combinatorial Targeting of Epithelial Ovarian Cancer and High-Grade Serous Ovarian Cancer via Single-cell Analysis." Doctoral thesis, Università degli Studi di Trieste, 2021. http://hdl.handle.net/11368/2996074.
Повний текст джерелаOvarian cancer kills more than 40 000 women in Europe and more than 150 000 women globally each year. The epithelial ovarian cancer (EOC) is the most common subtype and encompasses a collection of neoplasms with distinct clinical-pathological, molecular features and prognosis; among them the most common are the clear cells (CCOC), the mucinous (MOC), the endometrioid (ENOC), the low grade serous (LGSOC) and the high grade serous ovarian cancer (HGSOC). The HGSOC, in particular, is the most deadly form of EOC due to its high intratumor heterogeneity and lack of early diagnosis. The mechanical properties can be useful as new possible biomarkers of EOC subtypes in association to the classic ones used in clinical routine. In this thesis, the mechanical characterization of 9 ovarian cancer cell lines with different histological and morphological classification was carried out by AFM. Then, the achieved mechanical properties were evaluated on the same cell lines as markers of metastatic potential and drug sensitivity against 2C, a compound synthesized by the group of prof. Benedetti at the University of Trieste with anti-tumoral and cytoskeleton depolymerizing activity. Finally, an assessment of the effects of the culture medium composition on mechanical properties was performed. The mechanical characterization showed that the HGSOC cell lines had a high variability in the average Young’s modulus and resulted stiffer than the other cell lines with different histological classification. Moreover, the cell lines displayed two distinct single cell Young’s moduli distribution patterns: unimodal and bimodal. The cell lines with bimodal pattern showed two different populations with distinct mechanical behaviors. The invasion assay indicated a correlation between the stiffness decrease and the increase of invasion capacity. Accordingly, in cell lines with bimodal pattern only the “softer” population showed eventually the metastatic potential to invade. The cell lines with bimodal pattern were more resistant to 2C than the ones with unimodal pattern. For cell lines with bimodal pattern, the “stiffer” population had tendentially a higher resistance to 2C than the “softer” one. The F-actin network organization could influence the 2C resistance and the stiffness of cell lines: the HEY and OVCAR4 (high 2C resistance and high average Young’s modulus) had an Actin cytoskeleton more distributed over the cell than the TYKNU (low 2C resistance and low average Young’s modulus). Finally, variations in the culture medium components had an impact on the achieved Young’s moduli. This highlighted the need to develop optimized culture protocols for elasticity measurements, able to overcome the effects of different media on the mechanical properties.
Wang, Yiying, Lingmin Li, Yue Wang, Zeng Yuan, Wenjing Zhang, Kenneth Hatch, and Wenxin Zheng. "IMP3 as a cytoplasmic biomarker for early serous tubal carcinogenesis." BioMed Central, 2014. http://hdl.handle.net/10150/610179.
Повний текст джерелаFarquharson, Malcolm John. "Improving the understanding of platinum sensitivity and the tumour microenvironment in high grade serous ovarian cancer." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/31006/.
Повний текст джерелаAZZALINI, EROS. "Comprehensive characterization and effective combinatorial targeting of high-grade serous ovarian cancer via single-cell analysis." Doctoral thesis, Università degli Studi di Trieste, 2020. http://hdl.handle.net/11368/2967979.
Повний текст джерелаChen, Hao, Robert Klein, Stacy Arnold, Setsuko Chambers, and Wenxin Zheng. "Cytologic studies of the fallopian tube in patients undergoing salpingo-oophorectomy." BIOMED CENTRAL LTD, 2016. http://hdl.handle.net/10150/621541.
Повний текст джерелаLUONGO, RAFFAELE. "TOWARDS PATIENT-SPECIFIC MODELS IN HIGH GRADE SEROUS OVARIAN CANCER (HGSOC): LINKING EPIGENETIC TRACING OF CELL OF ORIGIN WITH ACTIONABLE ORGANOID MODELS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/883835.
Повний текст джерелаYamanoi, Kouji. "Suppression of ABHD2, identified through a functional genomics screen, causes anoikis resistance, chemoresistance and poor prognosis in ovarian cancer." Kyoto University, 2017. http://hdl.handle.net/2433/227585.
Повний текст джерелаSilva, Munasinghage Lakmali. "Determination of the kallikrein-related peptidase 7 degradome and Transciptome in ovarian cancer." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/92869/1/Munasinghage%20Lakmali_Silva_Thesis.pdf.
Повний текст джерелаZickgraf, Franziska Maria [Verfasser], and Andreas [Akademischer Betreuer] Trumpp. "SPDEF is a mediator of tumorigenicity in SSEA1- tumor-initiating cells in high grade serous ovarian cancer / Franziska Maria Zickgraf ; Betreuer: Andreas Trumpp." Heidelberg : Universitätsbibliothek Heidelberg, 2021. http://d-nb.info/1230067167/34.
Повний текст джерелаJiménez, Sánchez Alejandro. "Characterisation of the tumour microenvironment in ovarian cancer." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/287935.
Повний текст джерелаGarnier, Camille. "Rôle de la protéine MAP3K8 et impact de la rigidité dans les cancers ovariens sereux de haut grade." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC223/document.
Повний текст джерелаOvarian cancers, which develop in a silent manner in the peritoneal cavity, resulting in a late diagnosis and a poor prognosis, urgently require new therapeutic strategies. In this context, my thesis aimed at better characterize the physical and biological properties of the High Grade Serous ovarian cancers (HGSOCs), accounting for 75% of the tumours.First, we found that the protein MAP3K8 accumulates in HGSOC and is a potential prognostic marker for these tumours. We demonstrated that MAP3K8 controls cancer cell proliferation and migration by regulating key players in Gl/S transition and adhesion dynamics. Importantly, we highlighted that MAP3K8 function is mainly mediated by the MEK pathway, and exhibits a predictive potential for MEK inhibitors, defining them as a promising therapeutic option, in combination with conventional therapy, for HGSOC patients.In a second part of my thesis, we showed that tumor stiffness is increased during tumor growth in HGSOC presenting a "Fibrosis" molecular signature. Moreover, tumor stiffening is associated with high stromal content and remodeling of the collagen network. Interestingly, the MEK kinase was specifically activated upon tumor stiffening. Furthermore, tumor stiffness accompanies a glycolytic metabolic switch, restricted to the central part of stiff tumors. Indeed, the periphery of stiff tumors remains softer than the central part with stromal cells secreting high levels of collagens and showing an OXPHOS metabolism. Thus, tumor stiffness could be at the crossroad of three major processes, i.e. matrix remodeling, MEK activation and stromal metabolic switch, that might explain, at least in part, the progression of HGSOC
Liu, Yueyang [Verfasser], Viktor [Akademischer Betreuer] Magdolen, Birgit [Gutachter] Luber, and Viktor [Gutachter] Magdolen. "Kallikrein-related peptidase 10: a novel independent prognostic marker in advanced high-grade serous ovarian cancer and triple-negative breast cancer / Yueyang Liu ; Gutachter: Birgit Luber, Viktor Magdolen ; Betreuer: Viktor Magdolen." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1183910061/34.
Повний текст джерелаGeng, Xiaocong [Verfasser], Viktor [Akademischer Betreuer] Magdolen, Birgit [Gutachter] Luber, and Viktor [Gutachter] Magdolen. "Clinical relevance of kallikrein-related peptidases in advanced high-grade serous ovarian (KLK11, KLK15) and in triple-negative breast cancer (KLK11) / Xiaocong Geng ; Gutachter: Birgit Luber, Viktor Magdolen ; Betreuer: Viktor Magdolen." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1200098668/34.
Повний текст джерелаGong, Weiwei [Verfasser], Viktor [Akademischer Betreuer] Magdolen, Karl-Friedrich [Gutachter] Becker, and Viktor [Gutachter] Magdolen. "Assessment of kallikrein-related peptidases 4, 5, 7 and 12 as prognostic biomarkers in advanced high-grade serous ovarian cancer and triple-negative breast cancer / Weiwei Gong ; Gutachter: Karl-Friedrich Becker, Viktor Magdolen ; Betreuer: Viktor Magdolen." München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/1213898986/34.
Повний текст джерелаChen, Shuhui. "Étude des mutations des gènes KRAS, NRAS, BRAF, PIK3CA, MET et de l’expression des protéines P53 et PTEN et leurs implications cliniques dans le carcinome ovarien de haut grade." Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0093/document.
Повний текст джерелаObjectives: Despite the great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinoma remains univo-cal. As a major subgroup of ovarian carcinoma, high-grade ovarian carci-nomas (HGOC) need novel therapy. Additionally to conventional histolog-ical prognostic markers and oncogenetic investigations, molecular diag-nostic was performed using PCR-HRM (Polymerase Chain Reaction High Resolution Melting) and NGS (Next Generation Sequencing) to identify "druggable" targets that could provide access to innovative personalized therapy. Methods: This study was performed in 53 patients (pts) (mean age 58.9 years, range 25-87) with histologically proven HGOC of which 45 pts with serous carcinoma. BRCA1/2 germline mutations had been screened in 19 pts with familial/personal history of breast/ovarian cancer justifying on-cogenetic investigations. P53 and PTEN expression was assessed on for-malin fixed paraffin-embedded tissues using immunohistochemistry. So-matic mutations of KRAS, NRAS, BRAF, PIK3CA and MET were screened using PCR-HRM and then confirmed using NGS on DNA extracts from frozen tumor specimens taken at diagnosis. Results: Seven pts had BRCA1 / 2 germline mutations, all had serous carcinomas. One mutation of KRAS (exon 2), 2 mutations of NRAS (exon 3), 6 mutations of PIK3CA (exon 5, 10 and 21) and 5 mutations of MET (exon 14 and 18) were identified using NGS, of which 2 mutations of NRAS and 2 mutations de PIK3CA detected previously by PCR-HRM, no multiple mutation was detected. P53 overexpression and PTEN loss of expression was detected respectively in 32 of 53 (60%) and 19 of 46 (41%) of all the tumors. Because of the efffective of the study, statistical analyses were restricted to pts with serous carcinoma. With a median follow-up of 38 months (range 6-93), 35 pts had disease progression and 25 pts died during the follow-up. The 2-year progression-free survival (PFS) rate was 28% and 5-year overall survival (OS) rate was 37%. Overexpression of mutant P53 was found to be associated with chemosensitivity and longer PFS and OS. Conclusion: In HGOC, beside P53 and PTEN alterations, somatic genetic abnormalities of PI3K and MAPK signaling pathways can be detected us-ing NGS and provide molecular rationale for targeted therapies, potential-ly offering new therapeutic opportunities to the patients
Milea, Anca. "Abrogation of the Retinoblastoma Pathway Defines Clinical Outcome in High Grade Serous Carcinoma." Thesis, 2012. http://hdl.handle.net/1807/42403.
Повний текст джерелаChung, I.-Jiuan, and 鍾怡娟. "Determining Cooperative Lethal Effect of Targeted therapy in High-Grade Serous Ovarian Carcinoma." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/txg6nv.
Повний текст джерелаTone, Alicia. "The Role of Luteal Phase Fallopian Tube Epithelium in High-grade Ovarian Serous Carcinoma." Thesis, 2010. http://hdl.handle.net/1807/32954.
Повний текст джерелаYeo, Hsin Yueh, and 姚欣樂. "Investigating Cooperative Lethal Effect of EGFR and MDM2 Inhibitors on High-Grade Serous Ovarian Carcinoma." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/45108402529231371681.
Повний текст джерелаAlrubaish, Sarah. "Role of zinc transporter LIV-1 protein in high-grade serous ovarian cancer." Thèse, 2018. http://hdl.handle.net/1866/21364.
Повний текст джерелаLin, Han-Wei, and 林漢威. "High Alpha-Folate Receptor Correlates with Poorer Survival in Serous Ovarian Carcinoma." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/26149725544105240508.
Повний текст джерела臺灣大學
分子醫學研究所
98
Objectives: To investigate the relationship between alpha-folate receptor (α-FR) expression levels to the clinico-pathologic features and outcomes of patients with serous ovarian carcinoma. Methods: Semi-quantitative reverse-transcription polymerase chain reaction detected α-FR expression in 91 patients with serous ovarian carcinoma. Clinico-pathologic parameters and biomarkers, including FIGO stage, tumor grade, optimal surgery, lymph nodes metastasis, pre-operative serum CA-125, and α-FR expression levels in cancerous tissues to evaluate disease-free interval (DFI) and overall survival (OS), were analyzed. Results: There were 4, 6, 65, and 16 patients with stages I, II, III, and IV ovarian carcinoma, respectively. Forty (44%) underwent optimal debulking surgery. Patients with advanced stages (stage I: 0.451, stage II: 0.415, stage III: 0.652, stage IV: 0.768, p=0.004) or those with sub-optimal debulking surgery (optimal: 0.490, sub-optimal: 0.766, p=0.003) had significantly higher α-FR expression levels compared to those with early stages or optimal debulking surgery. In prognostic analysis, high α-FR expression level (HR: 2.70 (1.20-6.05), p=0.016) was an independent poor prognostic factor for DFI and had a negative impact on OS with marginal significance (HR: 3.51 (0.93-13.29), p=0.065) using multivariate analyses. Conclusions: Patients of serous ovarian carcinoma with high α-FR expression in cancerous tissue have shorter DFI and OS. α-FR may be a potential biomarker for predicting the outcome of serous ovarian carcinoma patients. Key words: alpha-folate receptor, CA-125, ovarian serous carcinoma, survival
ANGELICO, GIUSEPPE. "Aquaporin-1 expression as predictive marker of chemoresistance in ovarian high-grade serous carcinoma: a comparative study between preoperative peritoneal biopsies and surgical samples." Doctoral thesis, 2020. http://hdl.handle.net/11570/3181787.
Повний текст джерелаLangthasa, Jimpi. "A study of extracellular matrix dynamics in epithelial cancer progression with a special focus on ovarian cancer spheroidogenesis." Thesis, 2022. https://etd.iisc.ac.in/handle/2005/5979.
Повний текст джерелаWANG, KAI-HUNG, and 王凱弘. "Epigenetic Study in Gynecological Cancers: Discovery of New DNA Methylation Biomarker in Detecting Cervical Cancer and Downregulation of Tumor Suppressor Gene CNN1 in the Development of Ovarian High-Grade Serous Carcinoma." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/f2xv8b.
Повний текст джерела慈濟大學
醫學科學研究所
105
Gynecologic cancers contain five main types: cervical, ovarian, uterine, vaginal, and vulvar, whereas the first 2 types are high morbidity and mortality. Except genetic changes, epigenetic alteration is also a common phenomenon in cancer development, which is used to downregulate the expression of tumor suppressor genes. DNA methylation is one of the mechanisms of epigenetic alterations. There are several DNA methylation biomarkers that had been identified by isolating the DNA from Pap smear in cervical cancer patients. However, the biomarker for detecting early stage of cervical is lack. Therefore, this study surveyed the cohorts from Buddhist Tzu Chi General Hospital, and tried to discover new DNA methylation biomarkers for early detection of cervical cancers. The results demonstrated that one non-clustered PCDH gene, PCDH10, and two clustered PCDH genes, PCDHA4 and PCDHA13 were hypermethylated since cervical intraepithelial neoplasia 2 (CIN2) stage. The methylation test of these PCDH genes is more specific but less sensitive than high risk human papilloma virus (HPV) test. In this regard, combination of DNA methylation and HPV test could generate new triage strategy for early detecting cervical and precancerous lesion. On the other hand, more and more evidences proved that the cell origin of ovarian high-grade serous carcinoma (HGSC) is from fallopian tube epithelium (FTE). However, the detail mechanisms of this process and HGSC carcinogenesis are largely unknown. Thus, our group generated HGSC cell model by immortalization of FTE cells, named FE25, and further transformation to HGSC-like cells, named FE-RAS. By using this cell model, this study examined the function of the putative tumor suppressor gene, Calponin h1 (CNN1). The results showed that CNN1 were downregulated in FE-RAS and malignant ovarian cancer cells as well as HGSC tissues. Overexpressed CNN1 colocalized with Actin stress fiber structure, leading cells in a flatten morphology. Overexpression of CNN1 in FE-RAS cells significantly reduced cell motility, invasiveness, tumorigenesis and increased anoikis and adhesion. Conversely, when knocking-down CNN1 in FE25 cells, the malignant properties were increased. Microarray analysis showed overexpression of CNN1 may upregulate the genes contained kinase and phosphatase activities, Integrin binding, and Actin biding but downregulate others which has chemokine activity. Indeed, Integrin α2 and Integrin β1 were positively expressed with CNN1, explaining why the flatten morphology formed and adhesion increased. Besides, this study found that the microenvironment of ovarian stroma favored the growth of FE-RAS cells, which fits the theory of “HGSC originated from FTE,” and overexpression of CNN1 could significantly inhibits FE-RAS migrating toward to ovarian microenvironment. In summary, this study identified new methylation markers, PCDH10, PCDHA4, and PCDHA13, for detecting early cervical cancers and demonstrated the tumor suppressor, CNN1, which has to be turned down before the tubal originating HGSC can exfoliate and survival the anoikis. This tumor suppressor mechanism is likely through the modification of cell scaffolds and the associated signal transductions. Integrin α2 and Integrin β1 are the important mediators.
Jadhav, Rohit. "ROLE OF OVARIAN CANCER-INITIATING CELLS IN HIGH-GRADE SEROUS OVARIAN CARCINOGENESIS." Thesis, 2012. http://hdl.handle.net/1805/2773.
Повний текст джерелаA subpopulation of tumor cells known as ovarian cancer initiating cells (OCICs) have been shown to be the cells that propagate the tumor phenotype in ovarian cancer. Studies have showed that a very small population (100) of these cells is sufficient to induce a tumor phenotype; while a large quantity of tumor cells (5 X 105) are required to induce such a phenotype. In this study we studied the functional changes in genes expressed in the OCIC phenotype which were important for such efficient propagation of cancers. To enable this analysis, we generated mRNA expression and DNA methylation profiles of OCICs and compared them with those of tumor and normal ovarian surface epithelial cells. We identified four pathways which regulated most of the observed changes and were predicted to be important factors in distinguishing the OCICs from tumors and normal cells. The gene signatures for these pathways were analyzed by unsupervised clustering in order to determine the similarities of OCICs with respect to tumor and normal samples. We further believed that the OCICs can be used as indicators towards the genesis and progression of early events in the ovarian cancers. In light of this, we considered two hypotheses which are currently addressing the genesis of ovarian cancer. The first hypothesis proposed ovarian surface epithelial cells to be cells of origin of the ovarian cancer while the other proposed the fallopian tube cells to be contributing the cell of origin for these cancers. It is also believed that these two cells can be reciprocal cells of origin for the cancer phenotype. In order to test these hypotheses, we integrated the in-house dataset with a public domain fallopian tube gene expression data. The integration of the results obtained from these analyses provided better understanding of the early events in ovarian carcinogenesis.
Stewart, Jocelyn Melissa. "Organizing Cellular Heterogeneity in High-grade Serous Cancer." Thesis, 2013. http://hdl.handle.net/1807/36007.
Повний текст джерелаChen, Hsiang-Ju Helen, and 陳香儒. "The Investigation of the Role of GATA3 in High-Grade Serous Ovarian Cancer Stem Cells." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/5xagny.
Повний текст джерела國防醫學院
生命科學研究所
106
Ovarian cancer (OC) is the most lethal gynecological malignancy. The novel diagnostic and prognostic biomarkers are urgently needed to aid in the prevention and management of ovarian cancer. However, all attempts to date, have not improve the overall survival rate of OC. To circumvent this limit, there are two approaches in this project were investigated. Firstly, identify DNA methylation biomarker for improvement of diagnosis and secondly, to identify cancer stem- specific factor for better prognosis. Unfortunately, studies of DNA methylation biomarkers were not successfully completed, but for the cancer-stem related studies, we had a more completed discoveries. For cancer stem related study, we analyzed differential transcriptomes at early differentiation of OC stem cells and identified the transcription factor GATA3 as highly expressed in stem, compared to progenitor cells. GATA3 recruit the H3K27me3 demethylase, UTX, activate stemness markers, and promote stem-like phenotypes in OC. Targeting UTX by its inhibitor, GSKJ4, impeded GATA3-driven stemness, and enhanced apoptosis of GATA3-expressing cancer cells. Combinations of gemcitabine or paclitaxel with GSKJ4, resulted in a synergistic cytotoxic effect. Our findings provide evidence for a new role for GATA3 in OC stemness, and demonstrate that GATA3 may serve as a biomarker for precision epigenetic therapy in the future.
Calvo, Gonzalez Llilians. "Dissection moléculaire de la sénescence cellulaire induite par le stress et la thérapie dans le cancer de l’ovaire et son impact sur la réponse des patientes." Thèse, 2015. http://hdl.handle.net/1866/13853.
Повний текст джерелаHuman ovarian cancer (OvCa) is the deadliest gynecologic malignancy and existing surgical/chemotherapeutic treatment options have been relatively static for decades. We propose that understanding OvCa cell fate decisions taken in response to chemotherapy could guide new therapeutic opportunities. Damage-induced cellular senescence is often associated with TP53 activity, which is heavily mutated in high grade serous (HGS) OvCa (>90%), the most common form of this disease. Here, using patient derived tissues, we show that primary HGS-OvCa cultures predominantly trigger CDKN2A- associated (p16INK4A isoform) senescence following exposure to stress or chemotherapy. Key senescence hallmarks including altered morphology, senescence-associated-Betagalactosidase, DNA damage, cell cycle arrest and the senescence-associated secretory phenotype were evaluated and detected in damaged cells. Using tissue microarrays built from pre- and post-treatment human HGS-OvC tissue samples with accompanying clinical data, we quantified post-treatment hallmarks of senescence including reduced cell proliferation weeks after chemotherapy. Importantly, p16INK4A expression in pretreatment HGS-OvC samples correlated with increased patients survival, suggesting for the first time that senescence-competence in human cancer cells may have a beneficial impact on treatment outcomes for patients. In order to guide the potential improvement of existing human therapies via pharmacological senescence manipulation, our results suggests that it is important to determine for many types of human cancer whether treatment-induced senescence positively or negatively impacts disease progression and patient survival.
Ondič, Ondrej. "Praktická aplikace imunohistochemických a molekulárně - genetických metod v diferenciální diagnostice lézí urogenitálního a gynekologického traktu." Doctoral thesis, 2018. http://www.nusl.cz/ntk/nusl-391332.
Повний текст джерелаFleury, Hubert. "Implication des inhibiteurs de PARP dans le cancer de l’ovaire." Thèse, 2017. http://hdl.handle.net/1866/20221.
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