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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Characterization of Kallikrein 6 N-glycosylation Patterns and Identification of Sialylated Glycoproteins in Ovarian Cancer

Kuzmanov, Uros 08 August 2013 (has links)
Ovarian cancer is the leading cause of death among all gynecological disorders. Aberrant glycosylation, or more specifically, increased sialylation of proteins has been observed in this malignancy. Several sialyltransferase genes have been shown to be up-regulated at both mRNA and and protein levels in a number of cancers, including that of the ovary. In the present study, we have analyzed the glycosylation patterns of kallikrein 6 in the context of ovarian cancer. We have discovered that the carbohydrate structures found at the single N-glycosylation site of kallikrein 6 derived from ovarian cancer cells found in the ascites fluid of ovarian cancer patients is enriched in sialic acid moieties and has an increased branching pattern when compared to controls. We have also developed a reliable anion-exchange HPLC-based methodology capable of quantifying different glycoform subpopulations of kallikrein 6 in serum and other biological fluids, which was capable of differentiating between samples from ovarian cancer patients and healthy controls. A variety of classic molecular biology and mass spectrometry based techniques were utilized in these experiments. Based on the results of the analysis of kallikrein 6 glycosylation and other literature reports showing upregulated sialylation of proteins in ovarian cancer, we have also identified sialylated glycoproteins from ovarian cancer proximal fluids and conditioned media of ovarian cancer cell lines. Sialylated proteins were enriched utilizing lectin affinity or hydrazide chemistry. In total, 333 sialylated glycoproteins and 579 glycosylation sites were identified. A list of 21 potential candidate ovarian cancer biomarkers was produced from proteins that were identified solely in ovarian cancer proximal fluids, which could form the basis for any future studies.
2

Clinical and veterinary applications of new immunoassays for inhibin

Tsigos, Anastasia January 2002 (has links)
No description available.
3

Molecular analysis of DNA damage induced by a novel trinuclear platinum complex (BBR 3464)

Colella, Gennaro Giovanni Domenico January 2001 (has links)
No description available.
4

Molecular genetic analysis of endometriosis

Jiang, Xiuxian January 1997 (has links)
No description available.
5

Somatic genetic analysis of p53 function and cisplatin resistance

Gallagher, William January 1996 (has links)
No description available.
6

Impact of Chemotherapy Dosing Schedule on Ovarian Cancer Tumor Responsiveness

De Souza, Raquel S. M. G. 21 August 2012 (has links)
In Canada, ovarian cancer kills about 67% of diagnosed patients, largely due to difficulties in early diagnosis. Current treatment consists of debulking surgery and intermittent chemotherapy every three weeks. This approach leads to insufficient drug concentrations at disease sites, and long treatment-free intervals cause accelerated tumor proliferation and drug resistance, resulting in a 5-year survival rate of only 25-35%. Drug resistance development is the ultimate cause of the majority of patient deaths. Improvements yielding more effective treatment are fundamental for successful management of this disease. This thesis investigated a continuous chemotherapy strategy devoid of treatment-free intervals for ovarian cancer treatment. A biocompatible, biodegradable polymer-lipid injectable formulation PoLigel, was used for continuous DTX delivery. The formulation was well tolerated; no alterations in body weight, behaviour, histology of peritoneal tissues, or interleukin-6 levels were seen in CD-1 mice treated with the PoLigel. Continuous DTX therapy via the PoLigel was considerably more efficacious than intermittent therapy, resulting in significantly less tumor burden and ascites fluid in models of human and murine ovarian cancer. Continuous therapy resulted in less tumor cell proliferation and angiogenesis, and more tumor cell death than intermittent DTX. The presence and length of treatment-free intervals was shown to contribute to the development of drug resistance. Eliminating these intervals by continuous dosing resulted in superior antitumor efficacy in both chemosensitive and chemoresistant xenograft models of human ovarian cancer, and prevented drug resistance increase after a 21-day treatment period. Survival studies revealed that intermittent dosing led to a mild survival prolongation of 36% and 10% in chemosensitive and chemoresistant models, respectively, whereas continuous DTX prolonged survival by a striking 114% and 95%. Although long-term continuous chemotherapy substantially improved survival, increased drug resistance mechanisms were found at the endpoint. Overall, results presented here encourage the clinical implementation of continuous chemotherapy due to greater achievable therapeutic advantages.
7

Impact of Chemotherapy Dosing Schedule on Ovarian Cancer Tumor Responsiveness

De Souza, Raquel S. M. G. 21 August 2012 (has links)
In Canada, ovarian cancer kills about 67% of diagnosed patients, largely due to difficulties in early diagnosis. Current treatment consists of debulking surgery and intermittent chemotherapy every three weeks. This approach leads to insufficient drug concentrations at disease sites, and long treatment-free intervals cause accelerated tumor proliferation and drug resistance, resulting in a 5-year survival rate of only 25-35%. Drug resistance development is the ultimate cause of the majority of patient deaths. Improvements yielding more effective treatment are fundamental for successful management of this disease. This thesis investigated a continuous chemotherapy strategy devoid of treatment-free intervals for ovarian cancer treatment. A biocompatible, biodegradable polymer-lipid injectable formulation PoLigel, was used for continuous DTX delivery. The formulation was well tolerated; no alterations in body weight, behaviour, histology of peritoneal tissues, or interleukin-6 levels were seen in CD-1 mice treated with the PoLigel. Continuous DTX therapy via the PoLigel was considerably more efficacious than intermittent therapy, resulting in significantly less tumor burden and ascites fluid in models of human and murine ovarian cancer. Continuous therapy resulted in less tumor cell proliferation and angiogenesis, and more tumor cell death than intermittent DTX. The presence and length of treatment-free intervals was shown to contribute to the development of drug resistance. Eliminating these intervals by continuous dosing resulted in superior antitumor efficacy in both chemosensitive and chemoresistant xenograft models of human ovarian cancer, and prevented drug resistance increase after a 21-day treatment period. Survival studies revealed that intermittent dosing led to a mild survival prolongation of 36% and 10% in chemosensitive and chemoresistant models, respectively, whereas continuous DTX prolonged survival by a striking 114% and 95%. Although long-term continuous chemotherapy substantially improved survival, increased drug resistance mechanisms were found at the endpoint. Overall, results presented here encourage the clinical implementation of continuous chemotherapy due to greater achievable therapeutic advantages.
8

Evaluation of novel prognostic factors In ovarian carcinoma

Advikolanu, Kavitha Muralidhar 01 January 1999 (has links)
Clinical information was collected from 283 randomly chosen ovarian cancer cases from at the Saskatoon Cancer Centre between the years 1983-1995. The data was evaluated for its significance in predicting survival and relapse free survival (RFS) using univariate and multivariate analysis. Several clinical prognostic factors were identified by univariate analysis. Additionally, using Cox's regression model the independent markers of survival and RFS were FIGO stage, and residual disease in 173 and 178 patients respectively. Data on CA 125 serum level, (available in 89 patients) was a marker of prognostic significance in the patients treated with platinum based chemotherapy. CA 125 and CEA antigen expression were also evaluated in seventy one cases. It was found that mucinous neoplasms exclusively expressed CEA antigen. This study indicates that the evaluation of serum level CEA may be a complementary tool for patients with cancers not expressing CA 125. In this retrospective study, DNA from paraffin embedded tissue (PET) in patients with ovarian carcinoma was examined to identify gene abnormalities in p53, p16INK4A, RB-1, p21WAF1/CIP1, Cyclin D1, Erb-B2, and MSH2. Adverse outcome was also examined in addition to survival and RFS, to identify novel molecular prognostic markers. P53 overexpression in 44 of 112 (39%) was associated with reduced survival and RFS (' p' = '0.04' and 'p' = '0.008 '). Aneuploid DNA content, found in 34 of 112 (30%) cases, was associated with shorter survival and RFS ('p' = '0.03' and 'p' = '0.01'). Dot blot hybridization of G1-S control genes (p16INK4A, Cyclin D1, RB-1, and CDK4) did not identify amplification or deletion events to be associated with adverse outcome. A number of gene alterations in 59 of 63 (94%) ovarian cancer cases were detected by dot blot hybridization; the lack of association with clinical outcome indicated that there may be some other genes in addition to those examined that are of prognostic significance. For eighteen cases, microsatellite instability (MSI) was evaluated by using fluorescently labeled primers at nine loci. LOH was a common event in ovarian carcinoma but MSI was infrequent. Molecular and clinical marker multivariate analysis indicated: (a) residual disease for survival, (b) stage and residual disease for RFS, were independent markers of prognosis.
9

Characterization of Kallikrein 6 N-glycosylation Patterns and Identification of Sialylated Glycoproteins in Ovarian Cancer

Kuzmanov, Uros 08 August 2013 (has links)
Ovarian cancer is the leading cause of death among all gynecological disorders. Aberrant glycosylation, or more specifically, increased sialylation of proteins has been observed in this malignancy. Several sialyltransferase genes have been shown to be up-regulated at both mRNA and and protein levels in a number of cancers, including that of the ovary. In the present study, we have analyzed the glycosylation patterns of kallikrein 6 in the context of ovarian cancer. We have discovered that the carbohydrate structures found at the single N-glycosylation site of kallikrein 6 derived from ovarian cancer cells found in the ascites fluid of ovarian cancer patients is enriched in sialic acid moieties and has an increased branching pattern when compared to controls. We have also developed a reliable anion-exchange HPLC-based methodology capable of quantifying different glycoform subpopulations of kallikrein 6 in serum and other biological fluids, which was capable of differentiating between samples from ovarian cancer patients and healthy controls. A variety of classic molecular biology and mass spectrometry based techniques were utilized in these experiments. Based on the results of the analysis of kallikrein 6 glycosylation and other literature reports showing upregulated sialylation of proteins in ovarian cancer, we have also identified sialylated glycoproteins from ovarian cancer proximal fluids and conditioned media of ovarian cancer cell lines. Sialylated proteins were enriched utilizing lectin affinity or hydrazide chemistry. In total, 333 sialylated glycoproteins and 579 glycosylation sites were identified. A list of 21 potential candidate ovarian cancer biomarkers was produced from proteins that were identified solely in ovarian cancer proximal fluids, which could form the basis for any future studies.
10

Physical mapping of a commonly deleted region on chromosome 17q in ovarian carcinoma

Burrows, James Frederick January 1999 (has links)
No description available.

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