• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 25
  • 5
  • 4
  • 2
  • 1
  • 1
  • 1
  • 1
  • Tagged with
  • 47
  • 47
  • 31
  • 13
  • 13
  • 6
  • 5
  • 5
  • 5
  • 5
  • 5
  • 5
  • 4
  • 3
  • 3
  • 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

Identification of the genetic alterations in prostate cancer metastases

Stankiewicz, Elzbieta January 2017 (has links)
Prostate cancer (PCa) is the most common cancer among men in Western developed countries. While the majority of PCa diagnosed by PSA screening are indolent, advanced and metastatic disease has a significant mortality and morbidity. Bone metastases are extremely common in PCa and identification of bone metastasis associated genes may provide insights into PCa progression and assist in finding new drug targets. However, the genetic study of bone metastases is very limited due to the difficulty of sampling. We performed genome-wide analysis of six fresh frozen PCa bone metastases. We found several alterations commonly present in advanced PCa, including gains at: 1q32.1, broad gains of 8q (MYC, NCOA2), 9q33.2-34.3, 11q13.1-14.1 (CCND1), 12q24.23-24.31, 16p13.3, 16p12.1-11.2 and Xq12-13.1 (AR) as well as losses at: 5q11.1-22.1, 5q14.3-23.1, 6q14.1-22, 8p23.2-p21, 13q13.2-31.1 (RB1), 17p13.1-12 (TP53) and 18q11.1-22.3. Two cases also showed PTEN loss and one sample had deletion indicative of TMPRSS2-ERG fusion. For downstream analysis we concentrated on CCND1 oncogene at 11q13 and FBXL4 at 6q16 as potential drivers of these genomic changes. Using fluorescence in situ hybridisation we found common CCND1 gain and FBXL4 loss in PCa bone metastases (54.5%, 12/22 and 47.8%, 11/23, respectively), much less frequent in primary tumours (7%, 10/142 and 13.8%, 20/145, respectively) and absent in BPH cases (0/55). The expression levels of cyclin D1 protein, coded by CCND1 correlated with CCND1 copy number gain (p < 0.0001) and were higher in metastatic tumours than in primary PCa (p = 0.015), confirming cyclin D1 involvement in advanced PCa. Presence of FBXL4 loss in early stage primary PCa strongly correlated with current PCa prognostic markers and with worse patient survival. Therefore, we propose that FBXL4 may be a tumour suppressor gene in prostate, whose loss in early PCa could be indicative of more aggressive disease. Using in vitro experiments we demonstrated that FBXL4 regulates cells motility and invasion. We confirmed that ERLEC1, an ER lectin involved in ER stress response pathway is a degradation target of FBXL4. As activation of ER stress response pathway is linked to enhanced cell migration and invasion, loss of FBXL4 could be one of the mechanisms by which cancer cells increase their efficiency to respond to stress and to escalate their metastatic potential through stabilisation of ERLEC1. Further studies of FBXL4 - ERLEC1 axis are necessary to establish how they contribute to PCa progression. This knowledge can potentially help to develop novel targeted therapies for aggressive disease harbouring FBXL4 abnormalities.
2

Radiotherapy for bone metastases and neuropathic bone pain

Roos, D. E. January 2005 (has links)
I have a background of active research in Radiation Oncology since passing the final examination of the Royal Australian and New Zealand College of Radiologists ( RANZCR ) at the first attempt in 1992. My first two papers were published the following year [ 1,2 - see curriculum vitae ], and there are currently 49 publications ( 26 first authorships ). My primary research interest has involved the use of radiotherapy ( RT ) for palliation of painful bone metastases. This interest originated from a year at Mt Vernon Hospital, UK, as the inaugural RANZCR Windeyer Fellow in Clinical Oncology ( 1993 ). I worked with Dr Peter Hoskin, a leading figure in the British Bone Pain Trial Working Party responsible for three randomised fractionation trials on this subject. These and many other previous and subsequent studies have demonstrated ( counter - intuitively ) that low dose single fraction RT is as effective as higher dose fractionated schedules in relieving bone pain, with intention - to - treat overall response rates ( RRs ) of about 60 %. However, the studies provided virtually no data on the efficacy of RT specifically for bone pain with a neuropathic component ( NBP ), a scenario occurring in perhaps as many as 20 % of patients with bone metastases during the course of their disease. On returning to Australia as a consultant radiation oncologist at the Royal Adelaide Hospital in 1994, I joined the Trans - Tasman Radiation Oncology Group ( TROG ), the major radiotherapy clinical trials group in Australasia. During the following year, I developed a protocol for a randomised controlled trial comparing one with five fractions of RT for NBP ( TROG 96.05 ). The first patient was registered in February 1996, and a total of 15 centres in Australia ( 11 ), New Zealand ( 3 ) and UK ( 1 ) took part. A National Health and Medical Research Council Project Grant of $ 172,000 was awarded for the study ( 1998-2000 ). Preliminary findings ( blinded to trial arm ) were published in 2000 [ 23 ], and extensive quality assurance activities for the trial were summarised in two further publications [ 21,38 ]. The accrual target was met in December 2002 ( n = 272 ) and the final analysis was reported as an oral presentation at the 12th European Cancer Congress, Copenhagen, September 2003. The essential findings were that NBP responds similarly to localised pain ( overall intention - to - treat RR 57 % ) with no statistically significant difference in RR or time to treatment failure between randomisation arms [ 43 ]. A subsequent cost analysis quantified the relative cost to the Australian healthcare system for the two fractionation schedules [ 47 ]. During the conduct of the trial, I undertook and published a survey confirming the reluctance of Australasian radiation oncologists to use single fractions for painful bone metastases despite the emerging randomised trial results [ 24 ]. I also contributed to the international debate on this controversial subject as co - author with three high profile researchers in a Letter - to - the - Editor [ 20 ], and was a member of an International Consensus Panel on palliative radiotherapy endpoints for future bone metastases trials [ Chow E et al. Radiother Oncol 2002 ; 64 : 275 - 80 ]. I presented invited lectures entitled : Fractionation regimens for metastatic bone pain ( RANZCR Scientific Meeting, Brisbane, 1998 ) ; Neuropathic pain and bone metastases ( Royal College of Radiologists Second Consensus Workshop in Palliative Radiotherapy and Symptom Control, London, 2000 ) [ 27 ] ; Radiotherapy for neuropathic bone pain : TROG 96.05 update ( International Congress of Radiation Oncology, Melbourne, 2001 ) [ 30 ]. My recognised expertise in this field also led to invitations to write an Editorial on the published overviews of bone pain studies [ 40 ], and a book chapter on bone metastases from lung cancer [ 49 ]. My active role in bone pain research continues. The abovementioned International Consensus Panel collaboration led to the development of the first randomised trial on re - treatment of bone metastases with RT. This National Cancer Institute of Canada sponsored international Intergroup trial ( NCIC SC.20 / TROG 03.08 ) has an accrual target of 650 patients and was activated in January 2004. I am the Australasian Co - Chair, securing $ 40,000 funding for local capitation from Cancer Council Australia in February 2004. I believe this body of work constitutes a significant contribution to the literature on RT for bone metastases, and NBP in particular. My research on the latter constitutes the first prospective data ever obtained on RT for this clinical problem, enabling informed selection of single or multiple fraction treatment schedules. / Thesis (M.D.)--Department of Medicine, 2005.
3

The putative role of matrix metalloproteinase 13 and oncostatin M in the establishment of bone metastases

Mancini, Stephanie Sarah Jane 11 1900 (has links)
Breast cancer has a high propensity to metastasize to bone. While the genetic and epigenetic changes associated with metastatic breast cancer progression are being identified, the changes that drive metastatic progression are poorly understood. Proteases, and in particular matrix metalloproteinases (MMPs), have been shown to play a pivotal role in certain aspects of tumor metastasis by modifying the affected microenvironment. Bone matrix-depositing mouse MC3T3 osteoblasts were co-cultured with metastatic human MDA-MB-23 1 (MDA23 1) cells or the bone-homing MDA-MB 231-1 833/TR (1 833/TR) variant in an effort to identify novel, osteoclast-independent, changes to the tumor/bone microenvironment. Co-culture-induced changes in the complete “protease and inhibitor” expression profile in the osteoblasts and the tumor cells were then determined using targeted murine and human specific microarray chips (CLIP-CHIP TM ). This analysis revealed an increase in the RNA expression of collagenase-3 (MMP 13) in the co-cultured osteoblasts that was confirmed by qPCR. Further, Western blotting indicated increased MIvIP13 protein secretion into the bone matrixltumor microenvironment by the co-cultured MC3T3 cells. The elevation in osteoblast-produced MMP13 was observed when the co- cultured tumor cells were in direct contact or separated by filters. Additionally, the elevation was also induced by conditioned medium derived from separate MDA23 1 or 1 833/TR cultures, which indicates that a soluble factor produced by the tumor cells is capable of inducing MMP 13. One soluble factor that appears to be produced by 1 833iTR cultures is oncostatin M. Oncostatin M is an interleukin-6 family cytokine that is known to upregulate MMP13 synthesis and secretion during chondrogenesis. Genome-wide Affymetrix® analysis revealed, and qPCR analysis confirmed, that oncostatin M receptor-specific subunit RNA was also significantly upregulated in co-cultured osteoblasts. Therefore, breast tumor cells may be capable of initiating protein degradative changes in the bone microenvironment that are independent of the much studied osteolytic degradation initiated by osteoclast activation.
4

The putative role of matrix metalloproteinase 13 and oncostatin M in the establishment of bone metastases

Mancini, Stephanie Sarah Jane 11 1900 (has links)
Breast cancer has a high propensity to metastasize to bone. While the genetic and epigenetic changes associated with metastatic breast cancer progression are being identified, the changes that drive metastatic progression are poorly understood. Proteases, and in particular matrix metalloproteinases (MMPs), have been shown to play a pivotal role in certain aspects of tumor metastasis by modifying the affected microenvironment. Bone matrix-depositing mouse MC3T3 osteoblasts were co-cultured with metastatic human MDA-MB-23 1 (MDA23 1) cells or the bone-homing MDA-MB 231-1 833/TR (1 833/TR) variant in an effort to identify novel, osteoclast-independent, changes to the tumor/bone microenvironment. Co-culture-induced changes in the complete “protease and inhibitor” expression profile in the osteoblasts and the tumor cells were then determined using targeted murine and human specific microarray chips (CLIP-CHIP TM ). This analysis revealed an increase in the RNA expression of collagenase-3 (MMP 13) in the co-cultured osteoblasts that was confirmed by qPCR. Further, Western blotting indicated increased MIvIP13 protein secretion into the bone matrixltumor microenvironment by the co-cultured MC3T3 cells. The elevation in osteoblast-produced MMP13 was observed when the co- cultured tumor cells were in direct contact or separated by filters. Additionally, the elevation was also induced by conditioned medium derived from separate MDA23 1 or 1 833/TR cultures, which indicates that a soluble factor produced by the tumor cells is capable of inducing MMP 13. One soluble factor that appears to be produced by 1 833iTR cultures is oncostatin M. Oncostatin M is an interleukin-6 family cytokine that is known to upregulate MMP13 synthesis and secretion during chondrogenesis. Genome-wide Affymetrix® analysis revealed, and qPCR analysis confirmed, that oncostatin M receptor-specific subunit RNA was also significantly upregulated in co-cultured osteoblasts. Therefore, breast tumor cells may be capable of initiating protein degradative changes in the bone microenvironment that are independent of the much studied osteolytic degradation initiated by osteoclast activation.
5

Differential contributions of host-derived matrix metalloproteinases in mammary tumor growth in the bone microenvironment

Thiolloy, Sophie. January 2009 (has links)
Thesis (Ph. D. in Cancer Biology)--Vanderbilt University, Aug. 2009. / Title from title screen. Includes bibliographical references.
6

Pathogenesis of osteoblastic metastasis in prostate cancer role of animal models /

Thudi, Nanda Kumar, January 2009 (has links)
Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. 228-268).
7

The putative role of matrix metalloproteinase 13 and oncostatin M in the establishment of bone metastases

Mancini, Stephanie Sarah Jane 11 1900 (has links)
Breast cancer has a high propensity to metastasize to bone. While the genetic and epigenetic changes associated with metastatic breast cancer progression are being identified, the changes that drive metastatic progression are poorly understood. Proteases, and in particular matrix metalloproteinases (MMPs), have been shown to play a pivotal role in certain aspects of tumor metastasis by modifying the affected microenvironment. Bone matrix-depositing mouse MC3T3 osteoblasts were co-cultured with metastatic human MDA-MB-23 1 (MDA23 1) cells or the bone-homing MDA-MB 231-1 833/TR (1 833/TR) variant in an effort to identify novel, osteoclast-independent, changes to the tumor/bone microenvironment. Co-culture-induced changes in the complete “protease and inhibitor” expression profile in the osteoblasts and the tumor cells were then determined using targeted murine and human specific microarray chips (CLIP-CHIP TM ). This analysis revealed an increase in the RNA expression of collagenase-3 (MMP 13) in the co-cultured osteoblasts that was confirmed by qPCR. Further, Western blotting indicated increased MIvIP13 protein secretion into the bone matrixltumor microenvironment by the co-cultured MC3T3 cells. The elevation in osteoblast-produced MMP13 was observed when the co- cultured tumor cells were in direct contact or separated by filters. Additionally, the elevation was also induced by conditioned medium derived from separate MDA23 1 or 1 833/TR cultures, which indicates that a soluble factor produced by the tumor cells is capable of inducing MMP 13. One soluble factor that appears to be produced by 1 833iTR cultures is oncostatin M. Oncostatin M is an interleukin-6 family cytokine that is known to upregulate MMP13 synthesis and secretion during chondrogenesis. Genome-wide Affymetrix® analysis revealed, and qPCR analysis confirmed, that oncostatin M receptor-specific subunit RNA was also significantly upregulated in co-cultured osteoblasts. Therefore, breast tumor cells may be capable of initiating protein degradative changes in the bone microenvironment that are independent of the much studied osteolytic degradation initiated by osteoclast activation. / Medicine, Faculty of / Graduate
8

The role of Rho and Rac GTPases in prostate cancer bone metastasis

Dubyk, Cara W.. January 2009 (has links)
Thesis (M.S.)--University of Delaware, 2009. / Principal faculty advisor: Kenneth L. Van Golen, Dept. of Biological Sciences. Includes bibliographical references.
9

Human mesenchymal stromal cells enhance bone marrow metastases of neuroblastoma via SDF-1 related pathways

Ma, Ming, 馬明 January 2010 (has links)
published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy
10

Complexing ability and activity of N-containing bisphosphonates in bone cancer treatment

Castelo Branco, Jose Soares January 2008 (has links)
Thesis (MSc.(Chemistry))--University of Pretoria, 2008. / Includes bibliographical references.

Page generated in 0.0985 seconds