Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

The Tumour-Node-Metastasis (TNM) classification system of tumour stage does not always reflect the actual tumour mass present at diagnosis. Recent reports propose that volumetric analysis may allow improved stratification of disease recurrence and survival in head and neck squamous cell cancer (SCC). This study aims to assess the prognostic value of tumour volume on the outcome of patients with oral cavity and oropharyngeal SCC. / A retrospective review of 73 patients was completed. Tumours were outlined semi-automatically in digitized computed tomography scans, and volumes computed based on surface triangulations of three-dimensional reconstructions with novel software developed at McGill. / Results illustrate significant interstage variability within the current TNM model. Moreover, in oral cavity and oropharyngeal SCC, tumour volume as well as T-stage are significant and independent predictors of disease free survival and overall survival.

No description available.

No description available.

Wang Ya-ping. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 111-120). / CONTENT / ACKNOWLEDGMENT / ABSTRACT / Chapter Chapter 1. --- Introduction / Chapter Chapter 2. --- Review of relevant literature / Chapter 2.1 --- Mammary structure and embryology / Chapter 2.2 --- Pathology of breast cancer / Chapter 2.3 --- Risk factors in breast cancer / Chapter 2.4 --- Prognostic factors in breast cancer / Chapter 2.5 --- Treatment of breast cancer / Chapter 2.6 --- Breast cancer research by flow cytometry / Chapter 2.7 --- c-erbB-2 oncogene research in breast cancer / Chapter 2.8 --- Tables and figures of chapter2 / Chapter Chapter 3. --- Materials and methods / Chapter 3.1 --- Flow cytometry assay of breast cancer tissue / Chapter 3.1.1 --- Sample collection / Chapter 3.1.2 --- Sample preparation for flow cytometric assay / Chapter 3.1.3 --- DNA content assay by flow cytometry / Chapter 3.1.4 --- Solutions for flow cytometric analysis / Chapter 3.2 --- c-erbB-2 and EGF receptor protein detection by immunohistochemical methods / Chapter 3.2.1 --- Preparation of sections / Chapter 3.2.2 --- Methods of staining / Chapter 3.2.3 --- Methods of analysis / Chapter 3.2.4 --- Confirmation of expression of c-erbB-2 protein by immunoblotting method / Chapter 3.2.5 --- Solutions for immunohistochemical and immunoblotting methods / Chapter 3.3 --- Clinical data from 346 breast cancer patients and method of analysis / Chapter 3.4 --- Tables and figures of chapter3 / Chapter Chapter 4. --- Results / Chapter 4.1 --- Results of flow cytometric analysis / Chapter 4.1.1 --- Tumour characteristics of 94 breast cancer patients / Chapter 4.1.2 --- Survival analysis by results of flow cytometry / Chapter 4.2 --- Results of immunohistochemical assay of c-erbB-2 and EGFr / Chapter 4.2.1 --- C-erbB-2 and EGFr expression in breast cancer / Chapter 4.2.2 --- The distribution of c-erbB-2 and EGFr expression in breast cancer / Chapter 4.2.3 --- Analysis of clinical outcome by c-erbB-2 and EGFr expression / Chapter 4.3 --- Clinical data of 346 patients with breast cancer / Chapter 4.3.1 --- Patients' characteristics / Chapter 4.3.2 --- Analysis of clinical data and outcome / Chapter 4.3.3 --- Analysis of clinical outcome according to histopathological characteristics of breast tumour / Chapter 4.3.4 --- Types of operation and clinical outcome / Chapter 4.3.5 --- Postoperative adjuvant therapy and clinical outcome / Chapter 4.3.6 --- Results from statistical analysis by Cox-regression / Chapter 4.4 --- Tables figures of chapter4 / Chapter Chapter 5. --- Discussion and conclusion / Chapter 5.1 --- Flow cytometric analysis of paraffin-embedded breast cancer tissue / Chapter 5.1.1 --- Evaluation of DNA flow cytometric results / Chapter 5.1.2 --- Correlation between tumor DNA aneuploidy or cell subpopulation and clinical outcome / Chapter 5.1.3 --- Correlation between S-phase fraction of breast tumour and clinical outcome / Chapter 5.1.4 --- Observation of high proportion of DNA hypoaneuploidy in this study / Chapter 5.2 --- c-erbB-2 oncogene overexpression in breast cancer / Chapter 5.2.1 --- c-erbB-2 oncoprotein expression in other studies / Chapter 5.2.2 --- Correlation between c-erbB-2 oncoprotein expression status and breast cancer pathogenesis / Chapter 5.3 --- Evaluation of EGFr expression in breast cancer / Chapter 5.4 --- Analysis of clinical data / Chapter 5.4.1 --- Clinical characteristics of patients with breast cancer / Chapter 5.4.2 --- Clinical characteristics of breast cancer and clinical outcome / Chapter 5.4.3 --- Clinical outcome by types of postoperative treatment / Chapter 5.5 --- Prognostic factors / Chapter 5.5.1 --- Our observations in comparison to other studies / Chapter 5.5.2 --- Prognostic factors for clinical application / Chapter 5.6 --- Tables and figures of chapter5 / References:

Cancer/testis (CT) antigens are encoded by genes that are normally expressed only in the human germ-line, but are also expressed in various tumor types. CT antigens are also being studied for their roles in carcinogenesis as well as for their potentials as targets for anti-cancer therapy. A novel CT gene, NYD-SP8, (Accession No. AY014285.1) has recently been identified. It is located to human chromosome 19q13.31 and encodes a 27 kDa glucosylphosphatidylinositol (GPI) anchored cell surface protein, which shows structural homology to urokinase plasminogen activator receptor (uPAR). This thesis describes the characterization and functional roles of NYD-SP8 involved in cancer development. / In summary, the present findings have demonstrated the roles of NYD-SP8 in multi-step cancer development. Further investigations of NYD-SP8 in cancer development may provide new insights and ground for potential use of CT antigens in anti-cancer therapy. (Abstract: 428 words) / In the first set of experiments, the possible role(s) and underlying mechanism(s) of NYD-SP8 in regulating cell proliferation and apoptosis were investigated. Flow cytometric analysis, cell proliferation assay and Western blot analysis showed that NYD-SP8 promoted cell proliferation and protected cells against TNFalpha-induced apoptosis in Human embryonic kidney cells (HEK293) and human hepatocellular carcinoma cells (hHCC). In vitro studies showed that NYD-SP8 enhanced anchorage-independent growth of hHCC, further suggesting the pro-survival effect of NYD-SP8. These data demonstrated important functions of NYD-SP8 in promoting cell growth and preventing apoptosis during cancer development. / In the last part of thesis, the involvement of NYD-SP8 in epithelial-mesenchymal transitions (EMTs) was demonstrated. Upon TGFbeta stimulation or TGFbeta/TNFalpha co-stimulation, the mRNA and protein expression of NYD-SP8 was decreased in LIM1863 cells. Cell adhesion assay showed that the attachment ability of hHCC-SP8 was lowered in laminin and fibronectin coated plate, suggesting the possible role of NYD-SP8 in affecting cell-matrix interaction. These data indicate that NYD-SP8 is involved in the EMTs process and may serve as potential EMTs markers during cancer development. / In the second sets of experiments, the possible role(s) and underlying mechanism(s) of NYD-SP8 in regulating cancer invasion and metastasis were investigated. The results showed that NYD-SP8 could suppress multiple "tumor associated" proteases. Overexpression of NYD-SP8 resulted in reducing activities of the three major classes of proteases known to be involved in ECM degradation, including uPA, matrix metalloproteinases (MMPs) and cathepsin B, leading to suppression of both in vitro and in vivo cancer cell invasion and metastasis. Co-immunoprecipitation experiments showed binding of NYD-SP8 to uPA/uPAR complexes and interfering with active uPA production. These data demonstrated an important function of NYD-5P8 in regulating ECM degradation, providing a novel mechanism that modulates uPA/uPAR signaling in the suppression of cancer progression. / Chung, Chin Man. / "December 2009." / Adviser: H.C. Chan. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 124-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Breast cancer is a very heterogeneous disease. This heterogeneity can be observed at many levels, including gene expression, chromosomal aberrations, and disease pathology. A clear understanding of these differences is important since they impact upon treatment efficacy and clinical outcome. Recent studies have demonstrated that the tumour microenvironment also plays a critical role in cancer initiation and progression. Genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer, and have identified gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer-related pathways and processes. However, little work has been done in this context to examine the role of the tumour microenvironment in determining breast cancer outcome, or in defining breast cancer heterogeneity. Additionally, little is known about gene expression in histologically normal tissue adjacent to breast tumour, if this is influenced by the tumour, and how this compares with non-tumour-bearing breast tissue. By applying laser--capture microdissection and gene expression profiling to clinical breast cancer specimens the research presented in this thesis addresses these questions. / We have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty. We determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumour-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumour tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favourable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression data set for comparative studies of tumour expression profiles. / We compared gene expression profiles of tumour stroma from primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumour--derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node--negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumour progression. / We show that gene expression in the breast tumour microenvironment is highly heterogeneous, identifying at least six different classes of tumour stroma with distinct expression patterns and distinct biological processes. Two of these classes recapitulate the processes identified in the stroma-derived prognostic predictor, while the others are new classes of stroma associated with distinct clinical outcomes. One of these is associated with matrix remodelling and is strongly associated with the basal molecular subtype of breast cancer. The remainder are independent of the previously published molecular subtypes of breast cancer. Additionally, based on independent data from over 800 tumors, the combinations of stroma classes and breast cancer subtypes identify new subgroups of breast tumors that show better discrimination between good and poor outcome individuals than the molecular breast cancer subtypes or the stroma classes alone, suggesting a novel classification scheme for breast cancer. This research demonstrates an important role for the tumour microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes suggesting new avenues for individualized treatment.

Uveal melanoma is the most common primary malignant intraocular tumour in adults and despite advances in treatment of the primary tumour, the 10-year survival rate remains unchanged. The most frequent cause of death for patients of this disease is liver metastases. Removal of the primary tumour before clinical presentation of metastases, however, has no effect on patient outcome. / In order to understand the interactions between single malignant cells or sub-clinical metastases and affected organs, we have successfully developed a novel animal model of uveal melanoma. We utilized the unique properties of green fluorescent protein, a skin-flap in vivo imaging technique, and nude mice to accomplish this goal. The precision of green fluorescent protein imaging has allowed us to observe single cells interacting with organ tissues and reveal that these malignant cells are only capable of surviving in the liver.

The Ras signaling cascade is a vital component in the processes that mediate cell survival, growth, differentiation and transformation through activation of MAP kinase (mitogen-activated protein kinase). The recent discovery of a new scaffold of the Ras signaling pathway, Kinase Suppressor of Ras (KSR), is found to be a positive effector of Ras signaling which further contributes to proliferation and transformation in the ERK/MAPK pathway. This thesis describes the roles of Ras and Kinase Suppressor of Ras 1 (KSR-1) in regulating the expression of tumor promoting genes such as urokinase plasminogen activator (uPA) in the development and progression of breast cancer in vitro and in vivo. Ras and KSR increase the proliferative capacity and migration of MDAMB-231 human breast cancer cells in vitro. In contrast, Ras and KSR decrease the invasiveness of MDA-MB-231 human breast cancer cells in vitro. Furthermore, uPA gene expression levels do not correlate with uPA protein expression levels suggesting a possible mutation induced by KSR and/or Ras. In vivo studies reveal that Ras and KSR increase tumor volume in mice, as well as more advanced osteolytic bone metastases. Collectively, these results indicate that Ras and KSR play significant roles in breast cancer development and metastasis.