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Discovery of Novel Ovarian Cancer Biomarkers Via Proteomics and Mass Spectrometry

Discovery of Novel Ovarian Cancer Biomarkers Via Proteomics and Mass Spectrometry
Author: Chinthaka Geeth Gunawardana
Publisher:
Total Pages:
Release: 2010
Genre:
ISBN:

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Proteins secreted or shed by tumors can be found in serum. Detecting these proteins by mass spectrometry (MS) is difficult, due to the wide dynamic range of protein concentrations in serum. To circumvent this issue, we mined the conditioned media of epithelial ovarian cancer (EOC) cell lines which is a less complex fluid to work with. We hypothesize that some of the proteins shed or secreted by EOC cell lines are similar to those secreted or shed by EOC tumors and that some of these proteins can be used as biomarkers. We mined the conditioned medium of four ovarian cancer cell lines (HTB75, TOV-112D, TOV-21G and RMUG-S) by two-dimensional liquid chromatography-mass spectrometry. Our study identified 1208, 1252, 885, and 463 proteins from the HTB-75, TOV-112D, TOV-21G, and RMUG-S cell lines respectively. In all, we identified 2039 proteins from which we focused on 420 extracellular and plasma membrane proteins. High abundance proteins such as albumin and immunoglobulins, which are problematic for serum proteomics, did not interfere with our study. Several known markers of EOC including CA-125, HE4, Mesothelin, and KLK6, were identified in this study. The list of 420 extracellular and membrane proteins was cross-referenced with the proteome of ascites fluid to generate a final list of 51 potential candidates. According to Ingenuity Pathway Analysis, two of the top 10 diseases associated with our list of 51 proteins were cancer and reproductive diseases. Of the 51 candidates, 10 proteins were selected for verification in sera from ovarian cancer patients and healthy individuals. Clusterin showed a significant difference between cancer patients and normal, with sera from cancer patients showing higher levels. Another protein, NPC2, did not show a difference in sera between cancer and normals. Protein expression studies using immunohistochemistry showed that NPC2 is highly expressed in ovarian cancer tissue and absent in normal ovarian surface epithelium. In summary, clusterin and NPC2 appear to play a role in ovarian cancer pathobiology and their role in EOC need to be studied further.


Discovery of Novel Ovarian Cancer Biomarkers Via Proteomics and Mass Spectrometry

Discovery of Novel Ovarian Cancer Biomarkers Via Proteomics and Mass Spectrometry
Author:
Publisher:
Total Pages:
Release: 2006
Genre:
ISBN:

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Proteins secreted or shed by tumors can be found in serum. Detecting these proteins by mass spectrometry (MS) is difficult, due to the wide dynamic range of protein concentrations in serum. To circumvent this issue, we mined the conditioned media of epithelial ovarian cancer (EOC) cell lines which is a less complex fluid to work with. We hypothesize that some of the proteins shed or secreted by EOC cell lines are similar to those secreted or shed by EOC tumors and that some of these proteins can be used as biomarkers. We mined the conditioned medium of four ovarian cancer cell lines (HTB75, TOV-112D, TOV-21G and RMUG-S) by two-dimensional liquid chromatography-mass spectrometry. Our study identified 1208, 1252, 885, and 463 proteins from the HTB-75, TOV-112D, TOV-21G, and RMUG-S cell lines respectively. In all, we identified 2039 proteins from which we focused on 420 extracellular and plasma membrane proteins. High abundance proteins such as albumin and immunoglobulins, which are problematic for serum proteomics, did not interfere with our study. Several known markers of EOC including CA-125, HE4, Mesothelin, and KLK6, were identified in this study. The list of 420 extracellular and membrane proteins was cross-referenced with the proteome of ascites fluid to generate a final list of 51 potential candidates. According to Ingenuity Pathway Analysis, two of the top 10 diseases associated with our list of 51 proteins were cancer and reproductive diseases. Of the 51 candidates, 10 proteins were selected for verification in sera from ovarian cancer patients and healthy individuals. Clusterin showed a significant difference between cancer patients and normal, with sera from cancer patients showing higher levels. Another protein, NPC2, did not show a difference in sera between cancer and normals. Protein expression studies using immunohistochemistry showed that NPC2 is highly expressed in ovarian cancer tissue and absent in normal ovarian surface epithelium. In summary, clu.


Integrating High-throughput Technologies for the Identification and Validation of Novel Ovarian Cancer Biomarkers

Integrating High-throughput Technologies for the Identification and Validation of Novel Ovarian Cancer Biomarkers
Author: Felix Leung
Publisher:
Total Pages:
Release: 2016
Genre:
ISBN:

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Ovarian cancer is the most lethal gynaecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases significantly in late-stage diagnoses. The majority of cases are of epithelial origin, which can be classified into four major subtypes: serous, mucinous, endometrioid and clear cell carcinoma. Unfortunately, the clinically-approved markers for ovarian cancer - CA125 and HE4 alone - perform poorly for the mucinous, endometrioid and clear cell subtypes and thus, diagnosis of these subtypes remains a significant challenge. To this end, an integrated approach to ovarian cancer biomarker discovery was developed in this study through combining proteomics with other high-throughput platforms. Using proteomic analyses of ascites fluid from women with ovarian cancer and conditioned media of ovarian cancer cell lines, 15 high-priority candidates were identified as putative novel biomarkers using said integrated approach. Serum validation revealed two markers - folate receptor 1 and kallikrein 6 - to have comparable diagnostic ability to the clinically-approved markers, albeit with similar limitations in their ability to detect patients of the non-serous histotypes as well. Fortunately, the validation of the two in-house markers served as proof-of-principle of our integrated approach to biomarker discovery. As a result, the approach was employed on non-serous ovarian cancer tissues to identify novel markers specific to the mucinous, endometrioid and clear cell subtypes of ovarian cancer. Over 9000 unique proteins were identified in this exercise and with the use of an unbiased filtering algorithm based on transcriptomics and bioinformatics, a list of high-priority candidates for each subtype was generated. Several of the high-priority candidates have shown strong biological and molecular relevance to their respective subtypes, demonstrating the robustness and utility of the integrated approach. Future studies will need to investigate these candidates in independent serum cohorts to truly assess for their ability to diagnose their respective subtypes.


Early Detection of Breast Cancer

Early Detection of Breast Cancer
Author: S. Brünner
Publisher: Springer Science & Business Media
Total Pages: 253
Release: 2012-12-06
Genre: Medical
ISBN: 364282031X

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The enormous expansion seen over the last decade in the mammo graphic detection of breast cancer lesions, especially the use of screen ing procedures for the early detection of clinically unsuspected tumors, has made it necessary to summarize the experience made by various centers in the world. The 2nd International Copenhagen Symposium on Detection of Breast Cancer afforded an opportunity of gathering scientists from all over the world to discuss the various problems of early breast cancer detection with special reference to screening procedures. This book forms a synthesis of the information presented by leading scientists from many of the world's mammo graphic centers, particularly those in Sweden and the USA. Hence, the reader will have the opportunity to study the outstanding work carried out by various institutes and centers of breast cancer screening. It is our sincere hope that a study of this volume will encourage other scientists to join in the work on screening procedures. S. Brunner B. Langfeldt P. E. Andersen Contents S. A. Feig: 1 Hypothetical Breast Cancer Risk from Mammography S. A. Feig: Benefits and Risks of Mammography 11 R. L. Egan and M. B. McSweeney: Multicentric Breast Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . 28 M. B. McSweeney and R. L. Egan: Breast Cancer in the Younger Patient: A Preliminary Report 36 M. B. McSweeney and R. L. Egan: Bilateral Breast Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . ' 41 N. Bjurstam: The Radiographic Appearance of Normal and Metastatic Axillary Lymph Nodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 M. Moskowitz, S. A. Feig, C. Cole-Beuglet, S. H.


The Handbook of Metabonomics and Metabolomics

The Handbook of Metabonomics and Metabolomics
Author: John C. Lindon
Publisher: Elsevier
Total Pages: 573
Release: 2011-08-11
Genre: Science
ISBN: 0080468004

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Molecular biology operates at three levels – genes, proteins and metabolites. This book is unique in that it provides a comprehensive description of an approach (metabonomics) to characterise the endogenous metabolites in a living system, complementing gene and protein studies (genomics and proteomics). These "omics" methods form the basis for understanding biology at a systems level. The Handbook of Metabonomics and Metabolomics aims to be the definitive work on the rapidly expanding subjects of metabolic profiling, metabolite and biomarker identification, encompassing the fields of metabonomics and metabolomics. It covers the principles of the subject, the analytical and statistical techniques used and the wide variety of applications. * comprehensive description of an approach (metabonomics) to characterise the endogenous metabolites in a living system, complementing gene and protein studies* aims to be the definitive work on the rapidly expanding subjects of metabolic profiling, metabolite and biomarker identification* covers the principles of the subject, the analytical and statistical techniques used and the wide variety of applications.


Gynecologic Oncology

Gynecologic Oncology
Author: Robert C. Knapp
Publisher:
Total Pages: 680
Release: 1986
Genre: Medical
ISBN:

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The Evaluation of Surrogate Endpoints

The Evaluation of Surrogate Endpoints
Author: Geert Molenberghs
Publisher: Springer Science & Business Media
Total Pages: 440
Release: 2005-02-28
Genre: Mathematics
ISBN: 9780387202778

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Covers the latest research on a sensitive and controversial topic in a professional and well researched manner. Provides practical outlook as well as model guidelines and software tools that should be of interest to people who use the software tools described and those who do not. Related title by Co-author Geert Molenbergh has sold more than 3500 copies world wide. Provides dual viewpoints: from scientists in the industry as well as regulatory authorities.


Ovarian Cancer

Ovarian Cancer
Author: M. Sharon Stack
Publisher: Springer Science & Business Media
Total Pages: 411
Release: 2009-09-18
Genre: Medical
ISBN: 0387980946

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Ovarian carcinoma continues to be responsible for more deaths than all other gynecologic malignancies combined, due to a continued inability to achieve detection of early (rather than advanced) stage disease and the lack of effective tumor-specific therapeutics. Ovarian carcinogenesis, invasion, and metastatic dissemination require a complex cascade of interrelated genetic, molecular, and biochemical events that regulate the neoplastic transition of normal ovarian surface epithelium. This updated second edition includes exciting new advances in ovarian cancer detection and treatment and provides an analysis of current research into aspects of malignant transformation, growth control, and metastasis. A more detailed understanding of these processes may ultimately translate into the development of novel approaches for the detection and control of ovarian cancer.


Biomarkers in Oncology

Biomarkers in Oncology
Author: Heinz-Josef Lenz
Publisher: Springer Science & Business Media
Total Pages: 456
Release: 2012-09-18
Genre: Medical
ISBN: 1441997547

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This integrated book covers the entire spectrum of cancer biomarkers in development and clinical use. Predictive and prognostic markers are explored in the context of colon cancer, breast cancer, lung cancer, prostate cancer, and GIST. International experts provide insight into toxicity markers and surrogate markers. Attention is also given to biomarker assay development, validation, and strategies. A powerful tool for determining decisions on therapy, selecting drug regimens, monitoring the efficacy of treatment, and performing individualized surveillance, biomarkers represent the forefront of cancer research and treatment. As these technologies become increasingly available for clinical use, this book will be an essential resource for oncologists and translational researchers.