Dissertations / Theses on the topic 'Metastatic carcinoma'
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Nordman, Ina IC Clinical School St Vincent's Hospital Faculty of Medicine UNSW. "Surrogate endpoints of survival in metastatic carcinoma." Publisher:University of New South Wales. Clinical School - St Vincent's Hospital, 2008. http://handle.unsw.edu.au/1959.4/42791.
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In most randomised controlled trials (RCTs), a large number of patients need to be followed over many years, for the clinical benefit of the drug to be accurately quantified (1). Using an early proxy, or a surrogate endpoint, in place of the direct endpoint of overall survival (OS) could theoretically shorten the duration of RCTs and minimise the exposure of patients to ineffective or toxic treatments (2, 3). This thesis examined the relationship between surrogate endpoints and OS in metastatic colorectal cancer (CRC), advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A review of the literature identified 144 RCTs in metastatic CRC, 189 in advanced NSCLC and 133 in MBC. The publications were generally of poor quality with incomplete reporting on many key variables, making comparisons between studies difficult. The introduction of the CONSORT statement was associated with improvements in the quality of reporting. For CRC (337 arms), NSCLC (429 arms) and MBC (290 arms) there were strong relationships between OS and progression free survival (PFS), time to progression (TTP), disease control rate (DCR), response rate (RR) and partial response (PR). Correlation was also demonstrated between OS and complete response (CR) in CRC and duration of response (DOR) in MBC. However, while strong relationships were found, the proportion of variance explained by the models was small. Prediction bands constructed to determine the surrogate threshold effect size indicated that large improvements in the surrogate endpoints were needed to predict overall survival gains. PFS and TTP showed the most promise as surrogates. The gain in PFS and TTP required to predict a significant gain in overall survival was between 1.2 and 7.0 months and 1.8 and 7.7 months respectively, depending on trial size and tumour type. DCR was a better potential predictor of OS than RR. The results of this study could be used to design future clinical trials with particular reference to the selection of surrogate endpoint and trial size.
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Lee, Yee-ki Carol. "Effect of dietary fatty acids on metastatic hepatocellular carcinoma /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39707349.
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Malek, Joël. "Genetic alterations of the metastatic lesions in ovarian carcinoma." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T109.
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Le cancer de l’ovaire est le cancer gynécologique avec la plus grande mortalité due à un diagnostique tardif au stade de maladie extensive péritonéale. Malgré les progrès de la chirurgie radicale et de la chimiothérapie les récurrences abdominales demeurent la cause la plus fréquente de mortalité. Il existe peu d’études de la maladie métastatique péritonéale. Notre hypothèse de travail est que les différences entre la maladie métastatique et la tumeur primaire sont primordiales dans la survenue d’une maladie résiduelle ou récurrente. Nous avons utilisé une approche exhaustive comprenant des études du transcriptome, des variations du nombre de copie (VNC) et des sequençages des exomes pour caractériser les différences entre lésions primaires, métastases péritonéales et métastases lymphatiques.Résultats: Notre étude démontre que les VNC varient de façon significative entre la tumeur primaire et la métastase peritonéale. Les différences d’expressions géniques bien que mineures permettent de retrouver les voies de signalisation primordiales pour le développement des métastases. Le séquençage des exomes montre très peu de différences en terme de polymorphisme. Par ailleurs la majorité des polymorphismes présents dans les métastases se retrouvent à une faible fréquence dans la tumeur primaire de façon concordante avec la théorie clonale. Conclusion: L’ensemble des résultats montre la possibilité d’une origine clonale de la maladie métastatique des cancers de l’ovaire comportant la majorité des anomalies au niveau des variations du nombre de copie. L’intégration de ces données permettrait d’optimiser les thérapeutiques cibléesOvarian cancer is the most deadly gynecological cancer. The high rate of mortality is due to the large tumor burden with extensive metastatic lesion of the abdominal cavity. There are few studies on genetic alterations and their consequences in peritoneal metastatic tumors when compared to their matched ovarian primary tumors. Our hypothesis is that differences between the metastatic and primary lesions might be the cause of residual disease and, most importantly may have a role in post-chemotherapeutic recurrences. Methods: We conducted integrated genomics analysis on matched primary and metastatic tumors from 9 patients. In the papers presented here we analyze genome-wide Copy Number Variations (CNVs) using SNP Arrays targeting peritoneal metastasis differences, Gene expression differences using Microarrays also targeting peritoneal metastasis differences, and for some patients, Single Nucleotide Polymorphisms (SNPs) in genes through Exome sequencing.Results: Here we show that CNVs vary significantly between primary and metastatic tumors and include genes that have been considered potential chemotherapeutic targets based on primary tumor only data. Gene expression differences, while minor, showed highly statistically significant enrichment of genes in ovarian cancer critical pathways. In agreement with findings in other cancers, exome sequencing data revealed very few SNP differences of which most metastasis enriched SNPs were present at very low levels in the primary tumor. The results presented here should allow better design of therapies to target residual ovarian cancer disease
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Bartrolí, Comellas Mariona. "Prognostic markers and therapeutic targets for metastatic renal cell carcinoma." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664198.
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Targeting cancer metastasis has gained considerable importance in the recent years when aiming to increase patients’ overall survival. In Renal Cell Carcinoma (RCC), the discovery of metastatic biomarkers and targets is still required, as most patients present metastatic disease at the time of diagnosis.
Therefore, the aim of this thesis is the discovery of new biomarkers and targets of metastatic RCC using two variants of a patient-derived orthoxenograft (PDOX) animal model of clear cell RCC (ccRCC). Indeed, PDOX models have recently gained significant relevance for studying the progression of cancer and metastasis, due to their better mimicking of the histology, the metastatic capacity and treatment responses of human cancers. To this purpose, previous results had sequenced the two variants of this PDOX model, both at DNA and at RNA level, and had performed a FISH analysis.
Firstly, Carboxypeptidase E (CPE), which was one of the highest expressed genes in the metastatic variant, has demonstrated to play a role in invasion when it is secreted to the medium, even though its overexpression alone is not sufficient to generate metastasis in vivo. In addition, it has showed a clear association to ccRCC and an inverse correlation with the overall survival of these patients. Secondly, we have studied two molecules of the coagulation pathway due to its relevance as one of the most upregulated pathways at RNA level. On the one hand, Factor XIII (FXIII or F13) has shown to be related to CPE in vivo, despite the overexpression of both molecules is not sufficient to develop all the metastatic cascade. However, it also affects the overall survival of ccRCC patients, highlighting these two molecules as possible biomarkers for this type of cancer. On the other hand, Coagulation Factor II Thrombin Receptor (F2R or PAR1) has demonstrated to play a role in metastasis, since its inhibition reduces both the early and late phases of this process. With the use of F2R inhibitors and the clinical association of the coagulation pathway to worse prognosis, this thesis opens new opportunities for the treatment of metastasis and cancer malignization.
In summary, we have discovered new metastatic biomarkers and targets which, together with further validations, especially in the clinical setting, are proposed to be useful for RCC patients in the future.Recentment, l’estudi de la metàstasi ha guanyat importància amb l’objectiu d’augmentar la supervivència dels pacients amb càncer. En el càncer renal (RCC), el descobriment de biomarcadors metastàtics i dianes terapèutiques és necessari degut a que la majoria de pacients presenten metàstasi en el moment del diagnòstic. L’objectiu d’aquesta tesi ha estat el descobriment de nous biomarcadors i dianes terapèutiques pel càncer renal metastàtic a través de dues variants d’un model animal orthoxenograft (PDOX) de RCC de cèl·lula clara (ccRCC). Els models PDOX han guanyat molta importància en l’estudi de la progressió del càncer i la metàstasi, ja que mimetitzen la histologia, la capacitat metastàtica i la resposta als tractaments. Prèviament, s’havien seqüenciat les dues variants d’aquest model PDOX tant a nivell de DNA com de RNA, juntament amb un anàlisi FISH. En primer lloc, la Carbxoxipeptidasa E (CPE), un dels gens més expressats en la variant metastàtica, ha demostrat ser important en la invasió quan és secretada al medi, tot i no ser suficient per generar metàstasi in vivo. A més, s’ha associat amb el ccRCC i anti-correlacionat amb la supervivència d’aquests pacients. En segon lloc, hem estudiat dues molècules de la cascada de coagulació, una de les més alterades en nivells de RNA. Hem demostrat que el Factor XIII (FXIII o F13) està relacionat amb CPE in vivo, malgrat que l’expressió de les dues molècules no és suficient per a que es desenvolupi la metàstasi. Tot i així, el F13 afecta la supervivència de pacients amb ccRCC, suggerint aquestes dues molècules com a possibles biomarcadors d’aquest tipus de càncer. A més, la inhibició del Receptor del Factor de Coagulació II (F2R) ha demostrat reduir les fases inicials i finals del procés metastàtic. Així doncs, l’ús d’inhibidors de F2R, juntament amb el fet que la cascada de coagulació es relaciona amb el pronòstic dels pacients, fa que aquesta tesi obri noves oportunitats per al tractament de la metàstasi i la malignització del càncer. En resum, hem descobert nous biomarcadors i dianes terapèutiques que, juntament amb futures validacions, sobretot en clínica, poden ser útils per als pacients metastàtics de ccRCC.
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Pilborough, Alice Elizabeth. "Tumour-stromal crosstalk in metastatic lymph nodes of oral squamous cell carcinoma." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22053/.
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Ho, Chi-lai, and 何志禮. "Dual-tracer positron emission tomography in the evaluation ofprimary & metastatic hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45205024.
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Griffin, Ryan D. "MULTISPECTRAL CO-OCCURRENCE ANALYSIS FOR AUTOMATED TUMOR DETECTION IN METASTATIC MEDULLARY THYROID CARCINOMA." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1285101309.
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Okuno, Tomoko. "Loss of heterozygosity on 10q23 is involved in metastatic recurrence of hepatocellular carcinoma." Kyoto University, 2011. http://hdl.handle.net/2433/142555.
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Kerr, Ian Balfour. "A study of metastasis in colorectal carcinoma using DNA recombinant and molecular hybridisation techniques." Thesis, University of Edinburgh, 1989. http://hdl.handle.net/1842/19010.
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Swofford, Brenen P., and Tomislav Dragovich. "Durable and Complete Response to Herceptin Monotherapy in Patients with Metastatic Gastroesophageal Cancer." KARGER, 2017. http://hdl.handle.net/10150/626424.
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Gastroesophageal cancer is the sixth leading cause of cancer-related death worldwide. The 2 most common histologies are squamous cell carcinoma and adenocarcinoma, which has seen an increase in incidence correlating with an increase in obesity in developed countries. Gastroesophageal adenocarcinoma has a preponderance to metastasize early, making it a highly lethal cancer with a low 5-year survival rate of similar to 15-25%. Therefore, for the majority of patients, treatment focuses on palliation and prolongation of survival. Combination chemotherapy regimens, mostly platinum-based, have only modestly prolonged survival in patients with stage IV disease. Recently, it was discovered that the activation of the HER2 receptor plays an important role in a minority of adenocarcinomas of the distal esophagus and stomach. This introduced the treatment option of trastuzumab (Herceptin), a monoclonal antibody directed at the HER2 receptor, which has demonstrated improvement in overall and progression-free survival as noted in the ToGA trial. Currently, the role of Herceptin therapy beyond first-line therapy and outside of combination regimens is not well established. In this case report we review 2 cases of patients with gastroesophageal cancer, with HER2 overexpression, who achieved a robust response to trastuzumab in combination with chemotherapy and were able to maintain a durable response with maintenance trastuzumab monotherapy. (c) 2017 The Author(s) Published by S. Karger AG, Basel.
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Forsyth, Leigh James. "Identification of DNA sequences involved in the metastatic phenotype of human prostatic carcinoma cells." Thesis, University of Liverpool, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269601.
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Dhanda, Jagtar. "Molecular indicators and tumour models of extracapsular spread in metastatic oral squamous cell carcinoma." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/19295/.
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Introduction Extracapsular spread (ECS) is the single most adverse prognosticator for recurrence and death in metastatic oral squamous cell carcinoma (OSCC) and relapse is common in both primary and metastatic sites. It is rarely exploited for biological investigation with limited study of its molecular determinants and the absence of a tumour model. The absence of a biomarker also means exhaustive histological examination after surgery is required for diagnosis. ECS is a late manifestation of the metastatic cascade and would be expected to be intimately related to interactions between tumour cells and the microenvironment. The importance of the tumour microenvironment has been highlighted by the discovery of a promising new stromal biomarker, alpha smooth muscle actin (ASMA), which has shown even greater prognostic value than ECS. The aims of this study are to identify and validate biomarkers for ECS and to develop and utilise ECS+ve primary cell culture-derived cell lines in organotypic models to investigate epithelial and mesenchymal interactions. Methods 102 patients treated with primary surgery for OSCC were utilised for biomarker discovery and validation. Diagnostic accuracy of MRI scanning for ECS was determined and compared to a previously determined 8-gene expression signature from primary site tissue, which was validated using quantitative real-time polymerase chain reaction (qRT-PCR). SERPINE1 and ASMA expression was assessed for prognostic capability by immunohistochemistry (IHC) on a case-matched tissue microarray with separate analysis of the tumour centre and the advancing-front. The explant technique was used with cell-type specific media to isolate fibroblast and keratinocyte single-cell populations from 47 OSCC biopsy tissues. Metastatic status of the originating tumours was correlated with establishment of cell lines, cell phenotypes, proliferation index, invasion in organotypic cultures and drug sensitivities. Short tandem repeat profiling and microsatellite instability analysis were used to determine the tissue of origin. Results MRI (n=88) showed very poor sensitivity for the detection of ECS (7%), while the 8 gene signature had a sensitivity of 78%. The qRT-PCR findings poorly correlated with the microarray findings, but SERPINE 1 and HEXIM1 were selected for IHC as the best performing genes from prediction models using receiver operating characteristic curves (AUC 0.59 and 0.64 respectively). IHC indicated that both SERPINE1 and ASMA expression at the tumour-advancing front was highly significantly associated with nodal/ECS status (p < 0.001). Both separately, and in combination, SERPINE1 and ASMA were superior to MRI and the 8-gene expression signature for the detection of ECS (sensitivity; SERPINE1: 95%; ASMA: 82%; combination: 81%). ECS was associated with expression of either or both proteins in all cases and ASMA+/SERPINE1+ expression, in combination, was highly significantly associated with adverse outcomes (p < 0.001). A significant association was found between nodal status and both successful generation of finite keratinocyte cell lines (p=0.04) and keratinocyte invasion (p < 0.001), with histopathological similarities observed between organotypic models of invasion and the corresponding in-situ tumour advancing fronts. Two out of 13 cell lines grew for >10 passages and both were associated with ECS and distant metastasis (p < 0.001). Morphological differences were observed between fibroblasts cultured from ECS-ve and ECS+ve disease, with increased Vimentin and ASMA expression associated with ECS+ disease together with an enhanced capacity to induce and alter invasive phenotypes in organotypic models (p < 0.001). The primary cell culture derived cells showed greater sensitivity to cisplatin and docetaxel (p=0.003 and p=0.007 respectively) compared to secondary cell lines. An incremental reduction in growth rates (p=0.005) and sensitivity to cisplatin (p=0.02) was seen with advancing passage and both cisplatin and docetaxel reduced invasion in organotypic models, with the effects of docetaxel more pronounced (p < 0.001). Microsatellite instability analysis suggested that the primary cell culture derived fibroblasts were not derived from tumour cells by epithelial to mesenchymal transition. Discussion These findings suggest that a combination of ASMA and SERPINE1 IHC offers promise in the search for biomarkers that can be used to stratify therapeutic approaches in OSCC using biopsy samples that include the invading edge of the tumour. Successful generation of keratinocyte cell lines and invasion in organotypic models is related to the aggressiveness of the primary tumour that can also predict for the presence of ECS thus showing both sites are related. Both the IHC and cell culture findings suggest a putative role for the tumour microenvironment in ECS. Organotypic models using primary cell culture derived cells simulate the morphological characteristics of invasion in the primary tissue advancing front supporting their role as an in vitro tumour model and, most significantly, indicate that fibroblasts influence the invasive phenotype. These cell lines have greater sensitivity to anti-cancer agents and may offer opportunities for investigating new stromal-targeted therapies for ECS.
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Kelly, Stephen Richard. "The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in metastatic colorectal carcinoma (CRC)." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412204.
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Yau, Wing-lung, and 邱泳龍. "Identification of miR-106b over-expression in metastatic hepatocellular carcinoma by using the orthotopic animal model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45204032.
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Land, Walker, Dan Margolis, Ronald Gottlieb, Elizabeth Krupinski, and Jack Yang. "Improving CT prediction of treatment response in patients with metastatic colorectal carcinoma using statistical learning theory." BioMed Central, 2010. http://hdl.handle.net/10150/610011.
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BACKGROUND:Significant interest exists in establishing radiologic imaging as a valid biomarker for assessing the response of cancer to a variety of treatments. To address this problem, we have chosen to study patients with metastatic colorectal carcinoma to learn whether statistical learning theory can improve the performance of radiologists using CT in predicting patient treatment response to therapy compared with the more traditional RECIST (Response Evaluation Criteria in Solid Tumors) standard.RESULTS:Predictions of survival after 8 months in 38 patients with metastatic colorectal carcinoma using the Support Vector Machine (SVM) technique improved 30% when using additional information compared to WHO (World Health Organization) or RECIST measurements alone. With both Logistic Regression (LR) and SVM, there was no significant difference in performance between WHO and RECIST. The SVM and LR techniques also demonstrated that one radiologist consistently outperformed another.CONCLUSIONS:This preliminary research study has demonstrated that SLT algorithms, properly used in a clinical setting, have the potential to address questions and criticisms associated with both RECIST and WHO scoring methods. We also propose that tumor heterogeneity, shape, etc. obtained from CT and/or MRI scans be added to the SLT feature vector for processing.
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Minata, Mutsuko. "Postoperative detection of α-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma." Kyoto University, 2002. http://hdl.handle.net/2433/149325.
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Sharma, Purva, James Kim, Devapiran Jaishankar, and Sakshi Singal. "EXTENDED PROGRESSION-FREE SURVIVAL ON FIRST LINE TREATMENT WITH DOCETAXEL IN PATIENT WITH METASTATIC TRIPLE NEGATIVE BREAST CARCINOMA." Digital Commons @ East Tennessee State University, 2021. https://dc.etsu.edu/asrf/2021/presentations/43.
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Docetaxel is a chemotherapeutic agent in the taxane group of drugs which is commonly used in the first line setting for metastatic hormone receptor negative breast cancer. We present a case of a 46 year old female who was diagnosed with de novo triple negative metastatic breast carcinoma, and has had an extended progression free survival (PFS) of almost 5 years on first line single agent treatment with Docetaxel.
46 year old female presented with a large left breast mass as well as axillary mass which revealed grade 3 invasive ductal carcinoma of breast on biopsy of both sites. Tumor was estrogen and progesterone receptor negative. Pathology showed discordance in HER2 testing between FISH and IHC, however on repeat testing, HER2 was confirmed to be negative. PET/CT scan for staging revealed large left sided pleural effusion and abnormal soft tissue in the lower anterior and posterior chest on the left concerning for pleural metastases. Patient underwent CT guided biopsy of left lower pleural space which was consistent with metastatic adenocarcinoma with breast primary.
She was started on first line single agent chemotherapy with Docetaxel 100mg/m2 every 3 weeks. Tumor markers were non-contributory to assess disease response. Repeat systemic imaging in 3 months showed excellent partial response with decrease in size of breast mass, conglomerate axillary lymph nodes as well as pleural based metastatic foci. Patient had grade 1 neuropathy secondary to Docetaxel which was tolerable. Patient also had significant fatigue with warranted dose reduction by 20% after 6 months. She also demonstrated other adverse effects of Docetaxel such as nail dystrophy and mild blepharitis which were also tolerable.
Patient showed good tolerance to chemotherapy, with intermittent treatment holidays. CT scans continued to demonstrate good response with stable size of breast and lung masses. After two years of stable disease and fair tolerance (after completing 34 cycles), chemo regimen was changed to every 4 weeks per patient’s wish. She was also started on Gabapentin for chemotherapy related neuropathy.
At the end of 4 years, patient had completed 55 cycles of agent Docetaxel, maintaining ECOG of 1, with grade 2 neuropathy controlled with gabapentin.
Patient is currently 56 months out from her initial diagnosis of metastatic triple negative breast cancer and follow-up scans continue to show stable disease. She has developed profound fatigue after several months of treatment. Patient has also faced challenges with fluid retention secondary to Docetaxel. Although her performance status remains fair, patient is contemplating changing frequency of chemotherapy to every 5 or every 6 weeks.
Triple negative breast cancer is an aggressive disease with limited options of treatment with chemotherapy agents and no role for endocrine therapy or HER2 targeted treatment options. Docetaxel has shown to have median survival ranging between 10.1 to 14.7 months depending on the dose. Our patient has so far shown extended PFS of 56 months, with single agent Docetaxel in first line setting which surpasses current national averages.
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Xu, Wei. "Cytogenetic analysis of a murine mammary carcinoma in vitro and during progression from primary to metastatic growth in vivo." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq20717.pdf.
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Shestowsky, William S. "Production and characterization of a monoclonal antibody to a highly metastatic and organ-selective variant of the Lewis lung carcinoma." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61747.
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Vinayan, Anup. "Targeted anti-angiogenic therapy in metastatic renal cell carcinoma and methodological improvements in assessment of therapeutic response with imaging biomarkers." Thesis, University of Hertfordshire, 2018. http://hdl.handle.net/2299/20960.
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Background: Drugs targeting angiogenic pathway remain the mainstay of treatment for metastatic renal cell carcinoma (mRCC). Tyrosine Kinase Inhibitors (TKI) as Sunitinib, Pazopanib as single agents and humanised monoclonal antibody bevacizumab (Bev) in combination with Interferon- α2a (IFN) have established as the first-line therapy for mRCC. Despite improvements in treatment, there are multiple questions which remain unanswered. In the combination of Bev and IFN, the respective role of each drug and whether any additional anti-angiogenic activity is gained by adding IFN to Bev remains unknown. As the clinical benefit obtained with these cytostatic agents does not always correlate with the conventional response assessment techniques as RECIST, it is necessary to reconsider the methods by which we assess benefit from these therapies. In this thesis, I report three studies aiming to answer these questions. Methods: With the clinical trial reported here, I explore whether Bev induced changes in vascular parameters measured by Dynamic Contrast Enhanced MRI (DCE-MRI) is significantly enhanced by the addition of IFN. In a phase II, randomised, open labelled, multicentre trial, treatment naïve mRCC patients were randomised to receive Bev on its own or in combination with a low dose (3MU) or standard dose (9MU) IFN. DCE-MRI was used to assess the changes in vascularity with the primary endpoint being, changes in transfer coefficient (Ktrans) after six weeks of treatment. I also report two retrospective imaging-based studies, using contrast-enhanced CT scans, performed to improve the methodology of response assessment for these antiangiogenic therapeutics. Here I explore the use of a) combining changes in size and arterial phase contrast enhancement measured using CT scan and b) changes in CT texture as methods of therapeutic response assessment in mRCC patients treated with TKI. Results: With the phase 2 clinical trial, we faced significant difficulty in recruitment as a result of restrictions in access to treatment in NHS, other competing studies and restrictions proposed by the DCE-MRI inclusion criteria. With slow recruitment, an unplanned analysis was performed after 21 patients were recruited. Analysis of primary endpoint showed no trend in the difference between arms with no correlation found between change in Ktrans and addition of IFN to bevacizumab. Effect size analysis performed due to the small numbers recruited failed to show any significance in the observed difference in Ktrans. Change in Ktrans and Kep may identify a group of patients likely to have PFS > 6 months, but this observation needs to evaluation in a larger sample size. Measuring size and change in arterial phase enhancement retrospectively using CT, a new criterion "modified" Choi, which prerequisite a combination of a decrease in arterial phase density by 15% and a decrease in size by 10% for response was proposed. Response assessment was measured with RECIST, Choi and modified Choi individually in 20 evaluable patients retrospectively and clinical benefit compared with Kaplan-Meier statistics and Log-Rank test. Response assessment as defined by the modified Choi criteria successfully identified patients who received clinical benefit from the treatment. Time to progression (TTP) was 448 days for the partial response and 89 days for stable disease as per the new criteria which were statistically significant with a p-value of 0.002. The second retrospective analysis explored the textural changes in enhanced CT scan. Performed in collaboration with researchers from Brighton University who developed the software algorithm used to assess changes in entropy and uniformity, 87 metastases from 39 patients with mRCC were analysed at baseline and after two cycles of TKI treatment. Textural parameters and response assessment criteria were correlated with TTP. After two cycles of TKI, the decrease in tumour entropy was 3%-45%, and increase in uniformity was 5%-21%. At a threshold change of -2% with uniformity, on a coarse scale of 2.5, the textural change was able to separate responders from non-responders. With Kaplan-Meier analysis comparing all four criteria, the percentage change in uniformity was statistically more significant than for RECIST, Choi, and Modified Choi criteria. Cox regression analysis showed that texture uniformity was an independent predictor of time to progression. Discussion: With the studies reported here, I was able to demonstrate the importance of improving the methodology in assessment of therapeutic response to targeted anti-angiogenic therapy in metastatic renal cell carcinoma. Even though the clinical trial, terminated early due to slow recruitment, did not reach its primary endpoint, changes in other vascular parameters as Kep combined with changes Ktrans showed tendency towards identifying a group of patients who derived clinical benefit of >6months with these therapies. This is particularly exciting as given the vascular stabilisation effect proposed for bevacizumab, the effusion parameter Kep may be a better tool in assessing response rather than Ktrans and warrants further assessment in a larger cohort. Modified choi criterion and textural analysis are two important methodological improvements in response assessment of cytostatic anti-angiogenic therapy. In the analyses reported here, both techniques have shown superiority over RECIST in response assessment and differentiating mRCC patients who is likely to gain clinical benefit by TKI therapy. Validation of these criteria on a larger patient cohort is important. As these criterions are assessed on standard enhanced CT scans, incorporating these criteria, especially modified choi criterion, as part of standard CT assessment could be performed and will provide a real world validation. Retrospective assessment using larger cohort of patients from previous phase 3 trials or inclusion of these parameters prospectively in phase 3 trials would also help us in evaluating these modalities further.
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Kale, Hrishikesh P. "Economic Burden of Renal Cell Carcinoma (RCC) and Treatment Patterns, Overall Survival and Healthcare Costs among Older Metastatic RCC Patients." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5555.
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Background
Renal cell carcinoma (RCC) is the most common type of kidney cancer. Patients diagnosed with metastatic RCC (mRCC) have shorter overall survival compared to those diagnosed at earlier stages. Several targeted therapies, which cost from $7,000 - $16,000 per month have been approved since 2005 to treat mRCC. In addition, there is a growing interest in the use of cytoreductive nephrectomy (CN) with targeted therapies among mRCC patients. However, little is known regarding the economic burden of RCC and role of CN and prescribing patterns of targeted therapies among older mRCC patients.
Objectives
1) To assess the economic burden of RCC among older adults in the targeted therapy era 2) To compare the overall survival (OS) and total healthcare cost (THC) among older mRCC patients receiving CN and targeted therapy versus patients receiving targeted therapy alone 3) To describe prescribing patterns of targeted therapies and associated OS and THC among older mRCC patients.
Methods
This dissertation was conducted using the Surveillance Epidemiology and End Results (SEER) - Medicare linked data. For the first objective, the study included a prevalent cohort of RCC patients from 2013, diagnosed during 2005 - 2013 and continuously enrolled in Medicare. RCC patients were matched to non-cancer beneficiaries using propensity score matching. Generalized linear models estimated the incremental healthcare costs. Incremental total healthcare cost (THC) was multiplied by the estimated number of RCC patients on Medicare to calculate the total economic burden of RCC. For the second objective, we included patients diagnosed with mRCC between 2007-2014 and compared overall survival (OS), and THC between patients who received CN + targeted therapy and targeted therapy alone. A propensity score based inverse probability of treatment weighting (IPTW) method was used to balance the two treatment groups. A Cox proportional hazard model assessed the risk for death and a GLM compared healthcare costs between the groups. For the third objective, patients with mRCC were defined as patients who were diagnosed at stage-IV or at earlier stages but were currently using targeted therapies. Further, we restricted our sample to patients who initiated targeted therapy. We described the frequencies of the most common first and second line targeted therapies. We also described OS and THC per month for clear-cell and non-clear cell mRCC for each therapy and line of therapy.
Results
The first study included 10,392 each of RCC and control patients. The average THC associated with RCC was $7,419. The average THC was $4,584 for patients diagnosed at stage-I, $4,727 for stage-II, $9,331 for stage-III, and $31,637 for stage-IV. The annual economic burden of RCC on Medicare was estimated to be $1.5 billion. The second study included 471 mRCC patients that received CN + targeted therapy or targeted therapy alone. The median OS from the adjusted survival curves was significantly higher (p
Conclusions
The economic burden of RCC varied substantially between early stage and metastatic patients. Among mRCC patients, use of CN among targeted therapy users was associated with a higher median OS and similar monthly THC over a lifetime. Sunitinib and everolimus were the most common first and second line targeted therapies among mRCC patients. The descriptive analysis suggested that OS and THC were similar across types of targeted therapy sequences.
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Wu, Rita Shiu-fung. "Effects of B7.1, IFN-gamma, and antisense TGF-beta gene transfer on the tumorigenicity of murine 4T1 metastatic mammary carcinoma cells." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/280475.
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Cancer progression is attributed in part to immune evasion strategies that include lack of co-stimulation, down-regulation of cell surface MHC molecules, and secretion of immunosuppressive factors such as transforming growth factor-β (TGF-β). Gene therapy has been employed to counter these mechanisms of immune evasion by transference of B7.1, IFN-γ or antisense TGF-β genes into tumor cells resulting in cell surface expression of B7.1, upregulation of MHC class I and class II molecules, or elimination tumor-derived TGF-β, respectively. Although each of these transgenes has been shown to alter tumorigenicity in murine models, a direct comparison of their efficacy has not been performed. To compare the effectiveness of these transgenes in eliciting an anti-tumor response, a very aggressive, poorly immunogenic and highly metastatic mammary tumor cell line 4T1, was genetically modified to express B7.1, IFN-γ and antisense TGF-β transgenes. Both IFN-γ and antisense TGF-β gene expression significantly reduced the tumorigenicity of these cells compared to mock transduced cells, with IFN-γ having a greater effect. In contrast, B7.1 gene transfer did not affect the tumorigenicity of 4T1 cells. The anti-tumor response directed against antisense TGF-β-expressing 4T1 tumors was mediated by CD4+ and CD8+ T cells. However, CD8+ T cells and not CD4+ T cells, appeared to mediate the anti-tumor response against IFN-γ-expressing tumors. Treatment of tumor-bearing animals with IFN-γ or antisense TGF-β gene-modified tumor cell vaccines reduced the number of clonogenic metastases to the lungs and liver compared to treatment with mock-transduced cells. Finally, in a residual disease model in which the primary tumor was excised and mice were vaccinated with irradiated tumor cells, treatment of mice with vaccinations consisting of 4T1 cells expressing both antisense TGF-β and IFN-γ genes was the most effective in prolonging survival.
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Hall, Charles. "Ex vivo reprogramming of tumor-reactive immune cells from FVBN202 mice bearing lung metastatic mammary carcinoma: an immunotherapeutic opportunity revealed against recurrence." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3176.
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Metastatic breast cancer treatment has seen few advances in recent years, yet treatment resistance continues to rise, causing disease recurrence. A pilot study was performed to determine the efficacy of ex vivo expansion and reprogramming of tumor-reactive immune cells from experimental metastatic tumor-sensitized mice. Also, phenotypic changes in tumors due to metastasis or tumor microenvironment influences were characterized. Metastatic neu+ mouse mammary carcinoma (mMMC) and its distant relapsing neu-antigen-negative variant (mANV) were investigated in FVBN202 mice. Tumor-reactive central memory CD8+ T cells and activated NK/NKT cells were successfully reprogrammed and expanded during 6-day expansion from mMMC- and/or mANV-sensitized mice, resulting in tumor-specific cytotoxicity. mMMC exhibited a flexible neu-expression pattern and acquired stem-like, tumorigenic phenotype following metastasis while mANV remained stable except decreased tumorigenicity. Myeloid-derived suppressor cell (MDSC) levels were not increased. Adoptive cellular therapy (ACT) with reprogrammed tumor-reactive immune cells may prove effective prophylaxis against metastatic or recurrent breast cancer.
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Duffie, Gordon Patrick. "Tumoricidal activity of pulmonary alveolar macrophages isolated from C57BL/6 mice bearing either a cloned metastatic or nonmetastatic variant of Lewis lung carcinoma." Virtual Press, 1988. http://liblink.bsu.edu/uhtbin/catkey/558376.
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The spontaneous tumoricidal ability of pulmonary alveolar macrophages (PAM) isolated from C57B1/6 mice bearing either a metastatic or a nonmetastatic cloned variant of Lewis lung carcinoma (LLC) was examined in vitro. During the early weeks of tumor development the cytotoxicity mediated by macrophages was enhanced in the tumor-bearing mice, especially in the metastatic tumor bearers. Later in tumor progress (week 4) the spontaneous cytotoxicity of both groups typically declined to levels less than those of normal macrophages. Experiments were performed to determine if macrophages could be activated further in vitro by incubation in a mixture of lymphokine and lipopolysaccha ride. The macrophages from the metastatic tumor bearers were consistently activated in vitro. However, macrophages isolated from mice bearing large tumors and whose spontaneous cytotoxicity was suppressed could not be activated.The secretion of prostaglandin E2 (PGE2) by macrophages at different times during tumor development was measured to determine if PGE2 levels corresponded with the ability or inability of macrophages to kill tumor cells. Secretion of PGE2 typically corresponded with the capacity to kill rather than with an inability to kill target cells. Similarly, the production of PGE2 by macrophages was not responsible for the decline in the ability of macrophages to kill tumor cells.These results suggest that PAM are activated to be cytotoxic during the period when pulmonary metastases are developing. The successful establishment of these metastases does not appear to depend on the capacity of the tumor to suppress alveolar macrophage cytotoxicity.Department of Biology
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Raposo-Ferreira, Talita Mariana Morata [UNESP]. "Estudo em larga escala da expressão gênica de carcinomas mamários em cadelas." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/143484.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Os tumores mamários são os principais tumores que acometem as cadelas, sendo também os tumores mais frequentes em mulheres e, entre ambas as espécies, são observadas semelhanças relacionadas ao comportamento biológico e molecular dessa neoplasia. Assim, as cadelas podem ser um excelente modelo comparativo para o entendimento do processo carcinogênico desta neoplasia. A metástase é uma consequência comum e a principal causa de mortalidade em decorrência dessa enfermidade, em ambas as espécies. O perfil de expressão gênica global permite o melhor entendimento do processo de carcinogênese e de metástases, por permitir a identificação de inúmeros genes que possam estar envolvidos com esses processos. Assim, o objetivo desse estudo foi a realização do estudo em larga escala, através da técnica de microarray, em amostras de tecidos mamários caninos, considerando amostras de glândulas mamárias normais, tumores mamários benignos e tumores mamários malignos (carcinomas simples e mistos), além da avaliação de carcinomas mamários metastáticos e não metastáticos, para identificação de genes diferencialmente expressos entre esses grupos e relacionados com a tumorigênese e o desenvolvimento de metástases dos tumores mamários caninos. Observou-se, aproximadamente 1000 genes diferencialmente expressos entre as amostras tumorais e as glândulas mamárias normais e 465 genes diferencialmente expressos entre os tumores mamários benignos e malignos, sendo observados genes relacionados com o ciclo celular, desenvolvimento da glândula mamária e supressores tumorais. Em relação aos carcinomas mamários metastáticos e não metastáticos, verificou-se 633 genes diferencialmente expressos. Os genes supressores tumorais, como pertencentes a via de sinalização do ATM e do BRCA1, sugeriram importante papel tanto na progressão tumoral quanto no desenvolvimento de metástases. Outras vias observadas foram as relacionadas com angiogênese e de organização da matriz extracelular. Portanto, a análise do perfil gênico em larga escala permitiu a identificação de inúmeros genes e vias envolvidas tanto no processo de progressão tumoral como envolvidas com o desenvolvimento de metástases, permitindo a realização de estudos futuros em busca de marcadores prognósticos específicos.
Mammary tumors are the main tumors that affect female dogs, as well as in women and in both species, it is observed similarity related to the biological and molecular behavior of this neoplasia. So, female dogs are considered an excellent model for the understanding of carcinogenesis process from mammary tumors. Metastasis occurs frequently and it is the main responsible for the mortality by this neoplasia in both species. Global gene expression profile allows the better understanding of carcinogenesis and metastasis process by the identification of several genes that may be involved with these processes. Therefore, the aim of study was to perform a large-scale study by microarray technique using samples from canine mammary tissues, as normal mammary gland, benign tumors and malignant tumors (simple and mixed carcinomas), beyond metastatic and non-metastatic mammary carcinomas for the identification of differentially expression genes among these groups and related to canine mammary tumors tumorigenesis and metastasis. It was observed next to 1000 differentially expression genes between tumors and normal mammary glands samples and 465 differentially expression genes between benign and malignant mammary tumors mostly related to cell cycle, mammary gland development and tumor suppressors. Related to metastatic and non-metastatic mammary carcinomas was identified 633 differentially expression genes. ATM and BRCA1, associated with tumor suppressor gene pathway, showed to play an important role in both tumor progression and metastasis development. Other networks observed were related to angiogenesis and extracellular matrix organization. Thus, large-scale gene profile analysis allowed the identification of numerous genes and networks involved with both tumor progression and metastasis, allowing new studies in search of specific prognostic markers.
FAPESP: 2013/03940-4
FAPESP: 2013/25220-3
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Miller, Kurt, Rudolf Morant, Arnulf Stenzl, Manfred P. Wirth, and Ivan Zuna. "A Phase II Study of the Central European Society of Anticancer-Drug Research (CESAR) Group: Results of an Open-Label Study of Gemcitabine plus Cisplatin with or without Concomitant or Sequential Gefitinib in Patients with Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium." Karger, 2016. https://tud.qucosa.de/id/qucosa%3A70589.
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Introduction: This phase II trial evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, in combination with first-line chemotherapy in advanced urothelial cancer. Methods: Chemotherapy-naïve patients with advanced or metastatic urothelial carcinoma were randomized 1:1:1 to receive six cycles of chemotherapy (gemcitabine 1,250 mg/m 2 on days 1 and 8, and cisplatin 70 mg/m 2 on day 1 of every cycle) concomitantly with gefitinib 250 mg/day (arm A); or with sequential gefitinib (arm B); or alone (arm C). The primary endpoint was the time to progression (TTP). Results: A total of 105 patients received study treatment. Median TTP for arms A, B, and C were 6.1, 6.3, and 7.8 months, respectively. There were no significant differences between treatment arms for any outcomes measured. The most common adverse events were nausea and vomiting. Conclusion: Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.
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Pretscher, Dominik. "Distribution of immune cells in head and neck cancer : CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma." kostenfrei, 2010. http://d-nb.info/1000329054/34.
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Ostheimer, Christian Emil Arthur Verfasser], Dirk [Akademischer Betreuer] Vordermark, Bernd [Akademischer Betreuer] Schmidt, and Daniel [Akademischer Betreuer] [Zips. "Prognostic and predictive significance of osteopontin and other hypoxia-related plasma proteins in the radiotherapy of locally advanced and metastatic bronchial carcinoma / Christian Emil Arthur Ostheimer. Betreuer: Dirk Vordermark ; Bernd Schmidt ; Daniel Zips." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2015. http://d-nb.info/1089085419/34.
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Kwok, Mon-sze. "Study of metastatic suppressing genes on ovarian carcinomas /." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36586328.
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Kwok, Mon-sze, and 郭夢思. "Study of metastatic suppressing genes on ovarian carcinomas." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B45010729.
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LeBedis, Christina. "Lymph node involvement in breast carcinoma metastasis." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=31255.
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Since lymph node stromal cells remain largely uncharacterized with respect to cell surface markers and function, their role in regulating the growth and invasion of disseminated cancer cells, including breast carcinoma has, to date, been virtually unexplored. In the present study, we asked whether peripheral lymph node cells could modulate the growth of breast carcinoma cells and, thereby, contribute to the progression of the metastatic process. Primary cultures of rat peripheral lymph node stromal cells were obtained by limiting dilution and two sublines, STA4 and STB12, with breast carcinoma growth-promoting activities were isolated. Immunocytochemistry performed on these cells revealed that they express vimentin, S-100 and fibronectin, but neither cytokeratin nor von Willebrand factor indicating that they are stromal and dendritic in origin. Several functional studies were performed using media conditioned by STA4 and STB12 cells. (Abstract shortened by UMI.)
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吳曉靑 and Xiaoqing Wu. "Post-radiotherapy cervical metastasis in nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31222018.
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Wu, Xiaoqing. "Post-radiotherapy cervical metastasis in nasopharyngeal carcinoma /." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20843252.
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Silva, Maria João da Costa Soares da. "Clinical and molecular characterization of feline mammary carcinomas overexpressing HER2 proto-oncogene (FMC-HER2+) : new strategies for effective diagnostic and cancer therapy." Doctoral thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2016. http://hdl.handle.net/10400.5/12008.
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Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicasmariajosoares@gmail.com
Considering the scarce data available in feline mammary carcinoma (FMC) and despite its importance in veterinary clinical practice, this thesis emerges in order to increase the knowledge of this tumor type, especially the FMC-HER2 positive. In the first two studies, the protocols for detection and quantification of the fHER2 and Ki-67 biomarkers were optimized and validated. These studies demonstrated that, in cats, the incidence of fHER2 overexpression were similar to women (about 30%), although no gene amplification was detected. It was also demonstrated that high levels of Ki-67 index were associated with a worse prognosis. Using a panel of protein biomarkers, the FMC were divided into six different groups that demonstrated prognostic value, similarly to what is described in women. In fact, cats with triple negative basal-like or HER2-positive subtypes were associated with shorter overall survival, contrasting with cats presenting luminal A tumors. Moreover, these studies also indicated that luminal B and triple negative basal-like subtypes are the most common in cats. When the metastatic lesions were evaluated, a marked loss of receptor expression was found, which was associated with an increase of the triple negative basal-like subtype, highlighting the importance of immunophenotyping all lesions (primary and metastatic) in cats. Considering these results, the development of diagnostic methodologies that allows the continuous follow-up of the patients would be very useful. Therefore, the last study presented in this thesis evaluates the fHER2 serum levels in cats with FMC using two different immunoassays (ELISA and dot blot). The serum levels of fHER2 were significantly associated with the fHER2 in tissue samples of FMC (assessed by IHC). This is consistent to what is described for humans and suggests that serum quantification could be an important tool for monitoring cats after the surgery. In sum, the results presented herein provide new diagnostic and prognostic tools for veterinary oncology. Considering the high prevalence and similarities with the human counterpart, cat can also represent a potential animal model for the study of luminal B and triple negative subtypes. Considering fHER2-positive FMC more studies are required in order to determine the aetiology of the protein overexpression.
RESUMO - Os tumores mamários felinos (TMF) são umas das neoplasias mais comuns em Oncologia Felina, com uma incidência que pode atingir os 40%, pelo que assumem um papel relevante na prática clínica veterinária. Estes tumores apresentam habitualmente uma etiologia maligna (carcinomas) e um comportamento agressivo, estando associados a um prognóstico reservado. Atualmente, existem poucas opções terapêuticas que permitam aumentar a qualidade e a esperança média de vida dos animais afectados por esta neoplasia. Assim, estudos que permitam uma melhor caracterização dos tumores, identificando potenciais biomarcadores que possam ser utilizados como factores de prognóstico ou preditivos, são fundamentais para o desenvolvimento da Medicina Felina. Por outro lado, os carcinomas mamários que ocorrem espontaneamente nos animais de companhia têm sido sugeridos como potenciais modelos biológicos para o estudo do Cancro da Mama, com vantagens, comparativamente aos animais de laboratório que são atualmente utilizados. De facto, nesses animais, os tumores são quimicamente induzidos ou xenotransplantados, pelo que são considerados modelos mais artificiais. Deste modo, esta tese de doutoramento surge com o objetivo de aumentar o conhecimento sobre os tumores mamários felinos, com especial interesse no recetor transmembranar para o fator de crescimento epidérmico de tipo 2 (HER2), quer numa perspetiva clínica, de forma a melhorar a qualidade de vida destes animais de companhia, abrindo portas a novos meios de diagnóstico e potenciais novos alvos terapêuticos, quer no sentido de investigar a viabilidade de a Gata ser um bom modelo animal para o estudo do Cancro da Mama na Mulher. Relativamente à Mulher, a investigação oncológica desenvolveu grandes esforços para encontrar biomarcadores que permitam otimizar o diagnóstico e o tratamento do cancro da mama. Entre estes, encontra-se a proteína HER2, uma oncoproteína que pode estar sobreexpressa em vários tumores da espécie humana (mama, pâncreas, cólon, próstata, bexiga, entre outros) e que lhes confere elevada agressividade e prognóstico reservado. No Cancro da Mama, estima-se que entre 10 a 40% dos tumores apresentem amplificação do gene HER2, o que se traduz na sobreexpressão da proteína. Estas alterações são rotineiramente detetadas através de duas técnicas moleculares, a hibridação in situ (ISH) e a imunohistoquímica (IHC), respetivamente. A avaliação do status da proteína HER2 é importante, não só pelo seu valor de prognóstico, mas também como fator preditivo, já que pacientes com sobreexpressão desta proteína são elegíveis para tratamento com terapêuticas específicas dirigidas contra o HER2, tais como os anticorpos anti-HER2 (sendo o trastuzumab o mais conhecido), o que veio aumentar consideravelmente a sobrevida destas doentes. Contrastando com a medicina humana, a literatura disponível em medicina veterinária apresenta ainda escassos estudos sobre a importância da proteína HER2 nos TMF, ou sobre os novos sistemas de classificação que subdividem os tumores mamários conforme o seu perfil imunofenotípico.(...)
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Clark, Richard R. "Lymph node metastasis in auricular squamous cell carcinoma." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/547/.
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Introduction Squamous cell carcinoma of the auricle has an unusually high rate of lymph node metastases when compared to similar tumours at other sites. The lymph nodes affected are close to the base of the skull and in the neck. Development of metastasis carries a poor prognosis and most patients will subsequently die of failure of loco-regional control. Despite the likelihood of a poor outcome nothing can be done for patients prior to development of metastasis, as the risk of spread is not sufficiently high to warrant intervention in all patients. They are therefore treated with a ‘wait and see policy’ and only offered treatment once clinical evidence of metastatic spread is detected. This thesis sets out to examine what can be done, at the time of initial presentation with an auricular squamous cell carcinoma to identify patients who would benefit from treatment to the regional lymph node basins. Materials and Methods The thesis is divided into four separate studies. A systematic review examines the evidence available to date, an anatomical study examines the lymphatic drainage of the auricle in cadavers, a sentinel lymph node biopsy study examines the use of this technique to identify early tumour spread and a retrospective analysis of cases of auricular squamous cell carcinoma in our unit examines histopathological prognostic indictors of metastatic spread. Results The systematic review found that these tumours have a metastatic rate of about 11%. Patients developing metastasis usually die from failure of loco-regional control. Depth of tumour invasion, tumour size and mode of invasion seem to be potential indicators of metastatic risk. There is a strong argument for prophylactic intervention to the regional lymph nodes but there is no consensus of opinion as to when this should be carried out The anatomical study comprised 5 cadaveric dissections. They showed that the first echelon nodes draining the auricle lie in the superficial parotid gland, post-auricular/ mastoid nodal group and level II of the neck. There are anastamotic pathways around the mastoid and post-auricular nodes that could permit embolic tumour cells to bypass them. Five lymphatic pathways draining the auricle are described and some of these lie on the lateral and anterior surfaces of the mastoid bone and traverse the insertion of sternocleidomastoid. 28 cases of auricular squamous cell carcinoma were enrolled for sentinel lymph node biopsy. None of them were found to have any metastatic spread. One case showed non-viable tumour cells in a lymph node. There was a high incidence of complications (14%) directly related to the sentinel node biopsy procedure. The retrospective analysis identified 229 cases of auricular squamous cell carcinoma treated in our unit from 1992 - 2004. 212 of these cases had the primary pathology available for analysis. 24 (of 212) patients developed metastasis. 17 patients died as a result of their disease usually due to failure of control at the regional lymph node basin. Primary tumours with a depth of invasion greater than 8mm have metastatic rate of 56%. Tumours with a depth of invasion between 2-8mm and evidence of cartilage destruction, lymphovascular invasion or a non-cohesive invasive front have 24% metastatic rate. Tumours outwith these high-risk groups did not metastasise. Conclusions Elective lymph node dissections of the superficial parotid gland, post-auricular/mastoid and level II nodes should be considered in patients with primary auricular squamous cell carcinomas with a depth of invasion >8mm or a depth of invasion between 2 - 8 mm and evidence of cartilage destruction, lymphatic invasion or a non-cohesive invasive front. This should ideally be done as part of an observational study to evaluate the cost / benefit ratio for these patients. The neck dissection must clear the mastoid bone to a sub-periosteal level on its anterior and lateral surfaces. This will require the removal of the upper portion of sternocleidomastoid. Sentinel lymph node biopsy requires further study to evaluate it as a method for early detection of metastatic spread in auricular squamous cell carcinoma. This could be done as part of an observational study of elective neck dissections.
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Yuen, Po-wing. "The study of nodal metastasis of oral tongue carcinoma." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B39793837.
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Haq, Mahmudul. "Host-tumor interactions in skeletal metastasis of prostate carcinoma." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=56996.
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Approximately 70% of patients with prostatic cancer develop bone metastases. Metastatic prostate adenocarcinomas are associated with high mortality rates and represent a leading cause of cancer-related deaths among males. To study the host-tumor interactions underlying the predilection of prostate cancer cells for skeletal bone, an experimental model was developed using rat Dunning carcinoma Mat-LyLu cells. Inoculations of these cells into the left ventricle of the heart led to the development of spinal metastases in 100% of inoculated animals. A subline of Mat-LyLu (Mat-LyLu-B5) was subsequently selected through sequential inoculation of bone marrow derived carcinoma cells into the left ventricle of the heart and was found to have an increased metastatic potential compared to the parental line. The possible role of tumor cell adhesion to host cells in the process of bone marrow colonization was then investigated in vitro using the metastatic line and primary cultures of rat bone marrow-derived stromal cells. It was found that the adhesion of the metastatic Mat-LyLu cells to a bone marrow stromal cell culture highly enriched for endothelial cells (BMEC) was significantly higher than the adhesion to other bone-derived cells including non-endothelial BM stromal cells (3x) and osteoblasts (1.4x). It was also significantly higher than the adhesion to rat fibroblasts (5.5x) and to hepatic endothelial cells (7x). The results suggest that the adhesion of prostate carcinoma cells to the bone marrow endothelium may play a role in their metastasis to bone.
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Ip, Ying-chi. "MT1-MMP in relation to metastasis of hepatocellular carcinoma." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31490189.
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韋霖 and William I. Wei. "Surgery for post-radiotherapy cervical metastasis in nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1991. http://hub.hku.hk/bib/B31979543.
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Ip, Ying-chi, and 葉瑩芝. "MT1-MMP in relation to metastasis of hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31490189.
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Yuen, Po-wing, and 袁寶榮. "The study of nodal metastasis of oral tongue carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B39793837.
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Volk, Andreas, Stephan Kersting, Ralf Konopke, Frank Dobrowolski, Stefan Franzen, Detlef Ockert, Robert Grützmann, Hans Detlev Saeger, and Hendrik Bergert. "Surgical Therapy of Intrapancreatic Metastasis from Renal Cell Carcinoma." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-136489.
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Background: Pancreatic métastases from renal cell carcinoma (RCC) are clinically rare but highly resectable. The aim of this article is to identify patients who profit from pancreatic resection of RCC despite the invasiveness of the surgery. Methods: Between January 1996 and December 2007, data from 744 patients were collected in a prospective pancreatic surgery database, and patients with metastasis into the pancreas from RCC were identified. Results: Resective surgery was performed in 14 patients with metastasis to the pancreas from RCC. Most patients were clinically asymptomatic. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 94 months (range 32–158). The morbidity rate was 42.8%. Patients with a metastasis size <2.5 cm had a much better survival after resection (100 months) than those with a metastasis size >2.5 cm (44 months). Moreover, the number of métastases predicts the survival after resection. Conclusions: In patients with pancreatic métastases from RCC who have only limited disease, complete resection of all lesions can be successfully performed with a low rate of complications. Thus, patients with a history of RCC should be monitored for more than 10 years after nephrectomy to detect recurrenceDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Volk, Andreas, Stephan Kersting, Ralf Konopke, Frank Dobrowolski, Stefan Franzen, Detlef Ockert, Robert Grützmann, Hans Detlev Saeger, and Hendrik Bergert. "Surgical Therapy of Intrapancreatic Metastasis from Renal Cell Carcinoma." Karger, 2009. https://tud.qucosa.de/id/qucosa%3A27708.
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Background: Pancreatic métastases from renal cell carcinoma (RCC) are clinically rare but highly resectable. The aim of this article is to identify patients who profit from pancreatic resection of RCC despite the invasiveness of the surgery. Methods: Between January 1996 and December 2007, data from 744 patients were collected in a prospective pancreatic surgery database, and patients with metastasis into the pancreas from RCC were identified. Results: Resective surgery was performed in 14 patients with metastasis to the pancreas from RCC. Most patients were clinically asymptomatic. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 94 months (range 32–158). The morbidity rate was 42.8%. Patients with a metastasis size <2.5 cm had a much better survival after resection (100 months) than those with a metastasis size >2.5 cm (44 months). Moreover, the number of métastases predicts the survival after resection. Conclusions: In patients with pancreatic métastases from RCC who have only limited disease, complete resection of all lesions can be successfully performed with a low rate of complications. Thus, patients with a history of RCC should be monitored for more than 10 years after nephrectomy to detect recurrence.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Khan, Humma. "The influence of tumour angiogenesis on the metastatic potential of colorectal carcinomas." Thesis, Kingston University, 2007. http://eprints.kingston.ac.uk/20386/.
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Colon cancer is the fourth most common cause of cancer death in the world. It kills approximately 529,000 people annually and around two thirds of these deaths are in the developed world. These figures can be attributed to the fact that colorectal cancers are well advanced before they are detected. Effective prevention of the disease is early detection and removal of pre-cancerous polyps. In cases where cancer has already developed, early detection still significantly improves the chances of cure by surgically removing the cancer before the disease is able to metastasise. However, in metastatic colorectal cancers, in order to ascertain an effective treatment regimen and determine the prognosis of a patient after surgery a prognostic tool that accurately portrays the extent of the disease needs to be developed. Currently, the most commonly used prognostic tool to assess colorectal cancer spread is the clinicopathological staging system. However, there is a need for additional markers of metastasis as nearly one-third of patients with a clinical diagnosis of Dukes' B, a commonly used pathological staging system for colorectal cancer prognosis, will die of the disease despite complete resection of the primary tumour. In several human cancers such as breast, prostate and the lung, tumour vascularity has been shown to be of prognostic value. However, studies correlating the significance of the number of tumour vessels to prognosis in colorectal cancers are relatively lacking or show conflicting results. Moreover, it is not yet fully understood if factors involved in the complicated cascade of tumour blood vessel formation (tumour angiogenesis), such as proteases cathepsin B and dipeptidyl peptidase IV aid colorectal cancer progression. Two of the most potent angiogenic growth factors: vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) playa significant role in the development of tumour vessels; however, their influence on the production of these proteases is not clear. Therefore, this study set out to i) establish a reliable method to quantify colorectal tumour vessels ii) to assess the correlation between vessel counts and prognostic parameters associated with metastasis iii) to ascertain the pattern of spatial distribution of tumour vessels in order to defme the relationship between the positions of the vessels in relation to areas of tumour growth iv) investigate the levels of the enzyme expression of tumour associated proteases cathepsin B and dipeptidyl peptidase IV, at both protein and mRNA level, in colorectal tumours of varying clinicopathological grades and to v) assess the influence of VEGF and bFGF on CB and DPPIV proteolytic enzyme activity in human colon, rectal cancer cells and normal human umbilical vein endothelial cells. The study established that an effective method to examine tumour vascularity, was by immunolocalising tumour endothelial cells by CD31 and quantifying all of stained vessels present within each cross-sectional area. As a result of tumour endothelial cell marker assessment it was noted that CD34 was highly specific to certain vessels and distinctly immunonegative to others and that the same vessels were positive to CD31. These vessels were morphologically assessed by using the standard histological criteria identified as lymph vessels. Tumour blood and lymph vessels were quantified and a positive correlation to prognostic parameters relating to cancer spread was identified. The pattern of distribution of colorectal tumour vessels was also examined and a distinct pattern was observed in metastatic tumours with greater numbers of vessels in the peripheral regions and the invasive fronts. Qualitative analysis of protease expression and mRNA intensity, in colorectal tumours, revealed increased levels of CB and DPPIV in tumours with clinicopathological parameters associated with metastasis. mRNA localization near tumour vessels highlighted the potential for, not only cancer cells but also tumour endothelial cells, to produce proteolytic enzymes to aid the process of tumour angiogenesis and hence tumour growth and metastasis. The study also demonstrated that the angiogenic factors VEGF and bFGF up-regulated CB and DPPIV activity in human colon, rectal cancer cells and normal human umbilical vein endothelial cells.The presence of tumour lymph vessels and their positive correlation to metastatic parameters signifies an important role for such vessels in the process of colorectal cancer spread. The positive relationship of tumour blood vessels to parameters associated with metastasis re-instates the important role of tumour angiogenesis in colorectal cancer. Other factors that were investigated such as tumour associated proteases CB and DPPIV and the influence of the potent angiogenic proteins upon their activity suggests that these factors have a direct role in colorectal cancer metastasis. Therefore, it can be concluded from the results of this thesis that tumour blood vessel counts can be used as a reliable prognostic marker in colorectal cancer. Tumour angiogenic factors as well as the colorectal tumour lymph vessels have the potential to be used as additional prognostic markers in clinical prognostic evaluations. This has important implications in allowing clinicians to accurately assess post-operative survival rates and to devise an effective treatment regimen in order to prolong the lives and possibly cure colorectal cancer patients.
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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.
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The aim of this thesis is to investigate the role of inflammatory infiltrates and chemokines in metastasis of high-grade serous ovarian cancer, HGSC, to the omentum using human tissue biopsies and a 3- dimensional (3D) cell culture model. In ten patients with metastatic HGSC, omental tumour deposits contained a prominent leukocyte infiltrate of CD3+ T cells (9% of total cells) and CD68+ macrophages (11% of total cells). The presence of CD68+ macrophages showed a significant positive correlation with tumour cell proliferation analysed by Ki67 expression. Four ovarian cancer cell lines were co-cultured on a 3D model mimicking the microenvironment of the omentum for two weeks. The model was composed of collagen embedded human fibroblasts covered in a confluent layer of human primary mesothelial cells. The mesothelial cells in the 3D model significantly increased the growth (p = 0.002) and invasion (p = 0.0004) of the ovarian cancer cells. CXCL12 is the macrophage chemoattractant and ligand for the major chemokine receptor expressed on ovarian cancer cells. An association between CXCL12 and extracellular matrix remodelling was identified in two independent gene expression microarrays of ovarian cancer biopsies. The expression of CXCL12 in the HGSC omental metastases measured by quantitative Real Time-PCR positively correlated with decorin expression. Antibody mediated neutralisation of CXCL12 reduced growth (p = 0.012) and invasion (p = 0.029) in the 3D model. Mimicking an infiltrate of CD68+ macrophages in this multicellular 3D in vitro system also produced measurable changes in inflammatory cytokine and chemokine expression. There is currently a demand for more accurate models of HGSC and a necessity to study its metastasis that presents itself as the major clinical problem in patients. Therefore the development of this 3D model to mimic tumour-promoting inflammation in HGSC metastasis will provide researchers with an essential tool for testing novel therapeutic strategies.
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Nwogu, Nnenna Onyinyechi Uchechi. "The role of MCPyV ST in Merkel cell carcinoma metastasis." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/19356/.
Full textAbstract:
Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for metastasis via the dermal lymphatic system. In 2008, Merkel cell polyomavirus (MCPyV) was discovered monoclonally integrated within the host genome of at least 80% of MCC tumours. MCPyV transforms and maintains MCC tumours via the expression of the large and small tumour (LT and ST) antigens. Unlike other polyomaviruses, MCPyV ST is thought to be the major viral transforming factor required for MCC development. Since the discovery of MCPyV, a number of novel functions for ST have been identified which contribute to tumourigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the highly metastatic nature of MCC. Previously, the Whitehouse Laboratory have demonstrated the ability of MCPyV ST to enhance cell motility and migration, suggesting a potential role of MCPyV ST in the highly metastatic nature of MCC. In this thesis, the link between MCPyV ST and MCC metastasis is further explored by focusing on the role of MCPyV ST in promoting early events of initiating cell migration and metastatic spread. Results show that MCPyV ST expression disrupts the integrity of cell-to-cell junctions, thereby enhancing cell dissociation and scatter. Moreover, the functional requirement of cellular sheddases is highlighted in this process, specifically the A disintegrin and metalloproteinase (ADAM) 10 and 17 proteins. These findings therefore suggest MCPyV ST-mediated cell surface accumulation of cellular sheddases play a role in the highly metastatic nature of MCC and may also provide novel therapeutic interventions for disseminated MCC. Furthermore, results explore he potential of MCPyV ST to initiate an Epithelial to mesenchymal transition [EMT]. In addition to disruption of the cell junctions, other hallmarks of EMT are examined including loss of apical to basal polarity, expression of EMT associated Transcription factors and upregulation of Matrix metalloproteinases. Results show that MCPyV ST expression leads to phenotypic changes suggestive of characteristic EMT mechanisms which may further contribute to the metastatic spread associated with MCC.
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Chan, Pui-man Poemen. "Micrometastases of esophageal cancer /." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36404652.
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Dabare, Abeysinghe Arachchige Nandike Prashanth M. "Development of new monoclonal antibodies and colorimetric assays for improved detection of testicular germ cell tumours (TGCTs) and determining the relevance of over-expressed P53 in TGCT sensitivity to treatment." Thesis, Queen Mary, University of London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312172.
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Homer, Jarrod James. "Studies on angiogenesis in head and neck squamous cell carcinoma." Thesis, University of Hull, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342866.
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Xu, Haitao. "Overexpression of PAK4 and its relevance in hepatocellular carcinoma." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B38703944.
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