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1
KUHN, Elisabetta. "GATA3 IS AN ADJUNCT PROGNOSTIC FACTOR IN BREAST CANCER PATIENTS, ESPECIALLY WITH LESS AGGRESSIVE DISEASE". Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2488158.
Testo completoAbstract (sommario):
Recently, GATA3 has emerged as a sensitive lineage-specific marker for breast cancers (BCs) and their metastases. Interestingly, GATA3 expression is positively correlated with estrogen receptor (ER) expression. Moreover, some studies have investigated GATA3 as a prognostic marker in BC patients, with conflicting findings. Thus, we undertook the current study to evaluate the expression of GATA3 by immunohistochemistry in a large series of BCs with long-term follow-up and its prognostic value.
A total of 702 consecutive primary invasive BCs were diagnosed and resected between 1989 and 1993 in our institution. All BCs were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), Ki-67, HER2, p53, and GATA3. ER, PR, Ki-67, p53, and GATA3 were scored as the percentage of positive BC cells. Moreover, p53 was considered as with mutant pattern, if completely negative or with at least 60% of BC cell nuclei showing intense positivity, or with wild-type pattern, when showed a variable weak-moderate positivity in <60% of BC cells. HER2 was scored according to 2013 ASCO/CAP guidelines. Clinico-pathological data (including patient age, tumor histology, pathologic stage, grading, and follow-up data) were retrospectively collected. Statistical analyses with a p-value <0.05 were considered significant.
GATA3 was evaluable in 608 (87%) of 702 cases and resulted positive (≥1%) in 413 (68%) cases and negative (<1%) in 195 (32%) cases, with a GATA3 median percentage score of 50% (range 0%-100%). GATA3 positivity correlated significantly with lower histological grade (p<0.0001), size (p=0.0463), and stage (p=0.0049). Among the biological factors, GATA3 expression was associated with ER+ (p<0.0001), PR+ (p<0.0001), HER2- (p=0.373), and p53 wild-type pattern (p<0.0001). In our patients with a median follow-up of 183 months, after adjusting for age, GATA3 positivity correlated significantly with a better overall survival (hazard ratio [HR] 0.70, p=0.001), and its predictive power was retained in multivariate analysis. Moreover, GATA3 expression correlated with a better overall survival in BC patients with less aggressive characteristics: histologic grade 1 and 2 (HR 0.69, p=0.003), pT1-2 (HR 0.68, p=0.001), pN0 (HR 0.65, p=0.003), stage I-II (HR 0.65, p<0.0001), ER+ (HR 0.77, p=0.046), PR+ (HR 0.74, p=0.022), Ki-67<20% (HR 0.72, p=0.0008), HER2- (HR 0.64, p<0.0001), and in BC with wild-type p53 immunohistochemical pattern (HR 0.71, p=0.011). Among molecular subtypes, lack of GATA3 correlated with a worse overall survival only in luminal B BC. On the other hand, the predictive power of GATA3 in disease-free survival outcome was significant only at 48-month follow-up (HR 0.63, p=0.001), but was not independent of other variables in multivariate analysis.
Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC.Il fattore di trascrizione GATA3 è usato comunemente come marker immunoistochimico specifico di primitivita’ mammaria e uroteliale. Nel carcinoma della mammella l’espressione di GATA3 correla positivamente con quella dei recettori degli estrogeni (ER) e alcuni studi hanno investigato GATA3 come fattore prognostico, con risultati inconcludenti. In questo studio abbiamo valutato l’espressione di GATA3, mediante colorazione immunoistochimica, e il suo valore prognostico in un’ampia casistica di carcinomi infiltranti della mammella con follow-up lungo (con mediana di 15 anni). Abbiamo analizzato 702 casi consecutivi di carcinoma infiltrante primitivo della mammella diagnosticati presso il Servizio di Anatomia Patologica dell’Azienda Ospedaliero-Universitaria di Ferrara fra il 1989 e il 1993. Tutti i casi sono stati campionati per allestire dei tissue microarrays. Sezioni consecutive di tissue microarrays sono state immunocolorate per la valutazione di: ER, recettori del progesterone (PR), ki-67, HER2, p53 e GATA3. Tutti questi marcatori sono stati valutati come percentuale di cellule tumorali positive. A p53 è stato attribuito un pattern mutato, in caso di completa negatività o positività intensa pari o superiore al 60%, o un pattern “wild-type”, in caso di positività’ inferiore al 60%. HER2 è stato valutato in accordo con le linee guida ASCO/CAP del 2013. Le informazioni clinico-patologiche (età, istotipo, stadio patologico, grado e follow-up) sono state raccolte retrospettivamente. Le analisi statistiche con un p-value <0.05 sono state considerate significative. GATA3 è stato valutabile in 608 (87%) dei 702 casi ed è risultato positivo (≥1%) in 413 (68%) casi e negativo (<1%) in 195 (32%) casi, con una percentuale mediana di positività del 50% (intervallo 0%-100%). La positività di GATA3 correlava significativamente con basso grado istologico (p<0.0001), minor dimensione (p=0.0463) e basso stadio (p=0.0049). Rispetto ai fattori biologici, l’espressione di GATA3 era associata a ER positivi (p<0.0001), PR positivi (p<0.0001), HER2 negativo (p=0.373) e p53 con pattern wild-type (p<0.0001). Nelle nostre pazienti, con una mediana di follow-up pari a 183 mesi, dopo aver aggiustato per età, la positività di GATA3 correlava significativamente con una migliore overall survival (hazard ratio [HR] 0.70, p=0.001), e il potere predittivo era mantenuto in analisi mutivariata. Inoltre, l’espressione di GATA3 correlava con una miglior overall survival in pazienti con caratteristiche meno aggressive del carcinoma mammario: grado 1 e 2 (HR 0.69, p=0.003), pT1-2 (HR 0.68, p=0.001), pN0 (HR 0.65, p=0.003), stadio I-II (HR 0.65, p<0.0001), ER+ (HR 0.77, p=0.046), PR+ (HR 0.74, p=0.022), ki-67<20% (HR 0.72, p=0.0008), HER2- (0.64, p<0.0001) e pattern immunoistochimico di p53 wild-type (HR 0.71, p=0.011). Riguardo ai sottotipi molecolari, l’assenza di GATA3 correlava con una peggior overall survival solo nei carcinomi luminali B. D’altra parte, il potere predittivo di GATA3 per la disease-free survival e’ risultato significativo solo per follow-up pari a 48 mesi (HR 0.63, p=0.001), ma non si è dimostrato indipendente dalle altre variabili nell’analisi multivariata. I nostri risultati indicano che GATA3 è un marker prognostico positivo indipendente nelle pazienti con carcinoma mammario, specialmente con malattia biologicamente meno aggressiva.
2
Rowlands, Mari-Anne Elin. "The Insulin-Like Growth Factor System in Prostate Cancer Aetiology and Prognosis". Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525471.
Testo completo
3
Johnson, Lisa Godefroy. "The relationship of obesity-related metabolic hormones and prognosis in young women with breast cancer /". Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/10874.
Testo completo
4
Poon, Tung-ping Ronnie, e 潘冬平. "Prognostic significance of circulating vascular endothlial [sic] growth factor in patients with hepatocellular carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B36922249.
Testo completo
5
Ishigami, Shunichi. "Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer". Kyoto University, 1999. http://hdl.handle.net/2433/181241.
Testo completo
6
Amdani, Siti Nornadhirah. "The oocyte-activation factor, phospholipase C zeta (PLCζ) : clinical prognosis, diagnosis, and treatment of oocyte activation deficiency". Thesis, University of Oxford, 2018. https://ora.ox.ac.uk/objects/uuid:af4c4f98-497a-4666-9eec-a46bb579dd59.
Testo completoAbstract (sommario):
Oocyte activation deficiency (OAD) is an infertile condition observed in patients who have experienced recurrent total fertilisation failure (TFF) following intracytoplasmic sperm injection treatment. This condition was considered to be an idiopathic factor for a long time but strong clinical evidence now suggests that dysfunctional forms of phospholipase C zeta (PLCζ) may be predominant causative factors for OAD. Genetic contribution has played a role in patients suspected of having OAD, as four PLCζ exonic mutations have been discovered and characterised as being the cause of infertility. In this study, a novel nonsense mutation, PLCζK322Stop, was identified in the PLCζ XY-linker region of Patient LR. This variant results in the truncation of approximately half of PLCζ, therefore was non-functional when activity was tested. Patient LR, which also exhibited a previously reported mutation, PLCζH233L, may suggest that the patient is sub-fertile, as opposed to being infertile, as initially expected. Although research has purely focused upon the coding regions of PLCζ, it was obvious that our knowledge of PLCζ regulatory elements remain very limited. Next generation sequencing (NGS) was therefore employed to detect variants in the non-coding regions of PLCζ, promoter and introns, which may have resulted in the observed phenotypic diversity of PLCζ expression in fertile and infertile patients. As a result of mapping failure, an alternative approach was considered to identify variants within human PLCζ, and this involved using the single nucleotide polymorphism (SNP) database. Over 2500 SNPs were localised in the intronic regions of PLCζ and thus, it could be speculated that these variants may help elucidate the wide variation of PLCζ expression reported. Additionally, two particular patients with TFF (79 and 107) were investigated in this study to identify an association with PLCζ and their infertile state. For Patient 79, multiple PLCζ immunofluorescence analysis was performed and a significant improvement in PLCζ expression was observed one year after his first investigation. This may have been the result of an external factor, which influenced protein expression. As for Patient 107, a novel substitution mutation, PLCζV193E, was identified and was predicted to affect PLCζ stability and folding. There is global interest to create a safer and alternative OAD therapy, namely a human recombinant PLCζ protein (hrPLCζ). The first method, using a bacterial cell line resulted in successful purification and identification but the product proved to be inactive following mouse oocyte microinjection. The second method involved production of a mammalian-expressed hrPLCζ, which was successfully purified and identified but due to time restrictions, could not be tested for functionality. Concurrently, the findings in this thesis have reinforced the association between PLCζ and OAD, and provided improved options for the diagnosis and treatment of OAD.
7
Durkan, Garrett Christopher. "Matrix metalloproteinase-1 and -9 and tissue inhibitor of metalloproteinase-1 in bladder cancer : pathophysiological significance and relationship to epidermal growth factor receptor expression". Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369832.
Testo completo
8
Dreilich, Martin. "Predictive Factors in Esophageal Carcinoma". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6831.
Testo completo
9
Ekdahl, Christer. "Infective Endocarditis : aspects of pathophysiology, epidemiology, management and prognosis". Doctoral thesis, Linköping : Department of Clinical and Experimental Medicine, Linköping University, 2008. http://www.bibl.liu.se/liupubl/disp/disp2008/med1017s.pdf.
Testo completo
10
Bello, Rodríguez Irene. "Trasplante pulmonar: la obesidad del receptor como factor pronóstico". Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/399331.
Testo completoAbstract (sommario):
La Disfunción Primaria del Injerto (DPI) en el trasplante pulmonar es un daño agudo que se manifiesta clínicamente en las primeras 72 horas postoperatorias. Se caracteriza por un daño alveolar inespecífico, baja compliance pulmonar e hipoxemia. La incidencia de DPI varia entre 11% y el 57% en función de las diferentes series.
La DPI es una importante causa de morbimortalidad después del trasplante pulmonar. Es la principal causa de mortalidad en los 30 días postrasplante (24,1%). Durante el primer año es la segunda causa de mortalidad (16,6%). La DPI influye en los resultados del trasplante, afectando a los días de ventilación mecánica (LOV), estancia en UCI(LOS), estancia hospitalaria (hLOS), mortalidad a corto plazo e incrementa el riesgo del síndrome de bronquiolitis obliterante (BOS).
Un elevado número de factores de riesgo se han asociado al desarrollo de DPI. Se pueden clasificar en tres grupos, los relacionados con el donante, con el receptor y con el periodo perioperatorio. Uno de los factores relacionados es la obesidad del receptor preoperatoria. Varios estudios han mostrado la asociación del IMC>30 Kg/m2 y un LOV, LOS y hLOS prolongado, un incremento de la mortalidad a corto plazo y de la incidencia de BOS. El consenso publicado por la Sociedad Internacional de Trasplante de Corazón y Pulmón (ISHLT) en 2015 considera como contraindicación relativa el IMC preoperatorio del receptor mayor de 30 Kg/m2 y como contraindicación absoluta el IMC>35 Kg/m2.
Se han revisado restrospectivamente 348 trasplantes pulmonares realizados entre Enero 2010 y Diciembre 2015. Los pacientes se agruparon por IMC>18 Kg/m2, IMC 18 to 24,9 Kg/m2, IMC 25 to 30 Kg/m2 and IMC >30 Kg/m2. Se usó como definición de DPI la de la ISHLT.
El 63,2% de los trasplantados fueron hombres y el 36,8% mujeres. La edad media de los receptores fue de 52,6 años (DE=11,6%). La principal indicación de trasplante fue el grupo de patologías restrictivas (45,5%) y la
enfermedad pulmonar obstructiva crónica (EPOC) (32,2%). El 61,21% de los trasplantes fue bilateral. El grupo con IMC<18 Kg/m2 incluía al 8,4% de los receptores, el grupo con IMC 18-25 Kg/m2 el 39,9%, el grupo con IMC 25-30 Kg/m2 el 37,9 y el grupo con IMC >30 Kg/m2 incluía al 14,5% de ellos. La incidencia de DPI fue de 41,28%. El grupo con IMC >30 Kg/m2 tuvo una incidencia mayor de DPI (64,58%, p=0,0006), no se observaron diferencias en el grado ni duración de la DPI. El grupo con IMC >30 Kg/m2 tenía un riesgo incrementado de DPI en el análisis univariante (OR: 3.68, 95% CI: 1,848 – 7,359; P .002) y en el multivariante (OR: 3,371, 95% CI: 1,623 – 7,004; P .001). No se observaron diferencias estadísticamente significativas en LOV, ICU LOS, hLOS, rechazo agudo, infección respiratoria, riesgo incrementado de BOS, tiempo libre de BOS ni en la supervivencia a los 30 días postoperatorios, 90 días postoperatorios, 1 año ni 3 años.
Observamos que un IMC >30 Kg/m2 está asociado con un riesgo incrementado de DPI, sin afectar esta asociación a LOV, ICU LOS, hLOS, rechazo agudo, infección respiratoria, riesgo incrementado de BOS, tiempo libre de BOS ni en la supervivencia a los 30 días postoperatorios, 90 días postoperatorios, 1 año ni 3 años.
En conclusión, identificamos una asociación entre la obesidad preoperatoria y la DPI. Ésta no afecta a la supervivencia a corto ni medio plazo, así como ni al pronóstico del trasplante pulmonar. Más estudios son necesarios para esclarecer el papel que juega la obesidad preoperatoria del receptor en el trasplante pulmonar.Primary Graft Dysfunction (PGD) in lung transplant is an acute lung injury that is clinically evident in the first 72 hours after lung transplantation. It’s characterized by nonspecific alveolar damage, poor lung compliance and hypoxemia. The incidence of PGD varies on different series, between 11%-57%. PGD remains responsible for significant early morbidity and mortality after lung transplant. PGD is the main cause of mortality in the first 30 days post transplant (24,1%). It is the second cause of mortality during the first year (16,6%). PGD leads to adverse short-term outcomes, including prolonged length of mechanical ventilation(LOV), ICU length of stay(LOS), hospital length of stay (hLOS), increased cost, short-term mortality and increased risk of bronchiolitis obliterants syndrome (BOS). A number of risk factors associated to PGD’s development have been investigated, but so far, conflicting results have been yielded. These risk factors can be classified into three groups. First those related with the donor, second those related with the recipient and finally those associated with the perioperative period. One of the risk factors related with the recipient is an elevated recipient body mass index (BMI). Several studies have showed an association between recipient obesity and prolonged LOV, LOS, hLOS, increased short-term mortality and increased risk of BOS. A consensus document about the selection criteria for recipients to lung transplant was published in 2015 by The International Society of Heart and Lung transplant (ISHLT). In this consensus the recipient obesity (BMI>30 Kg/m2) is a relative contraindication and a BMI>35 Kg/m2 is an absolute contraindication for lung transplant. We retrospectively reviewed a cohort of 348 recipients of lung transplants performed between January 2010 and December 2015. Patients were divided in 4 groups according to their BMI>18 Kg/m2, BMI 18 to 24,9 Kg/m2, BMI 25 to 30 Kg/m2 and BMI >30 Kg/m2. PGD was defined according to the ISHLT guidelines There were 63,2% male and 36,8% female recipients. Mean recipient age was 52,6 years (SD=11,6%). The main indications for transplantation were Idiopathic pulmonary fibrosis (45.5%) and Emphysema (32.2%). The 61,21% of the procedures were bilateral lung transplants. The group with BMI<18 Kg/m2 included 8,4% of recipients, the group with BMI 18-25 Kg/m2 39,9%, the group with BMI 25-30 Kg/m2 included 37,9% of recipients and BMI>30 Kg/m2 included 14,5% of them. The incidence of PGD was 41,28%. The group with BMI>30 Kg/m2 had an increased incidence of PGD (64,58%, p=0,0006), But differences between grade or time of PGD were not seen. The group group with BMI>30 Kg/m2 had an increased risk of PGD compared with the group with BMI 18-25 Kg/m2 in univariant analysis (OR: 3.68, 95% CI: 1,848 – 7,359; P .002) and multivariant analysis (OR: 3,371, 95% CI: 1,623 – 7,004; P .001). No differences were observed in LOV, ICU LOS, hLOS, acute rejection, respiratory infection, increased risk of BOS, free-time of BOS and in 30d postoperative survival, 90d postoperative survival,1-year and 3-year survival. We observed that a BMI > 30 Kg/m2 is associated with an increased risk of PGD, but this association doesn’t affect LOV, ICU LOS, hLOS, acute rejection, respiratory infection, increased risk of BOS, free-time of BOS and 30d postoperative survival, 90d postoperative survival, 1-year and 3-year survival. In conclusion, we identified an association between preoperative obesity and PGD This association does not impact survival and outcomes after lung transplantation. Further studies are required to clarify the role that preoperative obesity plays in lung transplant.
11
Nishimura, Takao. "SIX1 maintains tumor basal cells via transforming growth factor-β pathway and associates with poor prognosis in esophageal cancer". Kyoto University, 2019. http://hdl.handle.net/2433/236593.
Testo completo
12
Uchida, Shigeki. "In oesophageal Squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis". Kyoto University, 1999. http://hdl.handle.net/2433/181714.
Testo completo
13
Nakatani, Eiji. "Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease". Kyoto University, 2016. http://hdl.handle.net/2433/217720.
Testo completo
14
Berghmans, Thierry. "Du rôle de facteurs cliniques, métaboliques, biologiques et thérapeutiques dans le pronostic des patients atteints d'un cancer bronchique non à petites cellules localement avancé, stade III". Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210328.
Testo completoAbstract (sommario):
Au travers d’études cliniques et biologiques, de méta-analyses et de revues systématiques de la littérature, nous avons étudié les CBNPC de stade III sur le plan thérapeutique et cherché des facteurs pronostiques pour la survie dans le but d’améliorer la classification internationale et, à terme, de permettre une meilleure prise en charge des patients inclus dans ce groupe hétérogène de tumeurs.Dans le cadre d’essais randomisés, nous avons montré qu’un abord multimodal et multidisciplinaire permettait d’améliorer le pronostic des patients atteints d’un CBNPC de stade III. Le traitement des tumeurs non résécables implique une combinaison de chimiothérapie et de radiothérapie, dont l’administration concomitante doit être proposée aux patients aptes à la tolérer. La chimiothérapie doit être incluse dans le schéma thérapeutique des tumeurs potentiellement résécables. Elle permet une résection chirurgicale complète chez des patients sélectionnés dont la tumeur était initialement non résécable.
Nous avons déterminé que des caractéristiques cliniques (l’indice de performance et l’âge), biologiques (les taux sanguins de polynucléaires neutrophiles, d’hémoglobine et de plaquettes, la bilirubinémie) et propres à la tumeur (l’extension locale [T3-4] et ganglionnaire [N3]) avaient une valeur pronostique indépendante pour la survie. Ceci nous a permis d’aboutir à une proposition de modification de la classification internationale concernant les CBNPC de stade III.
Bien que pris individuellement, les facteurs biologiques que nous avons étudiés (p53, EGF-R, TTF-1, Mdm2) n’aient pas de valeur pronostique pour la survie, nous avons montré que la combinaison EGF-R+/TTF1- était un facteur pronostique indépendant en analyse multivariée pour la survie spécifique au cancer bronchique.
Nous avons finalement évalué le rôle pronostique de la tomodensitométrie par émission de positrons et de la mesure semi-quantitative de captation du 18F-FDG (SUV) sur la survie des patients atteints de CBNPC et montré qu’un SUV élevé était un facteur de mauvais pronostic pour la survie.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
15
Rahko, E. (Eeva). "Evaluation of tumor suppressor gene p53, oncogene c-erbB-2 and matrix-metalloproteinase-9 as prognostic and predictive factors in breast carcinoma". Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514284571.
Testo completoAbstract (sommario):
Abstract
Breast carcinoma is the most common malignancy in females in western countries. Classical prognostic factors such as the size of a primary tumor and the presence or absence of axillary lymph node metastases, malignancy grade and hormone receptor status reflect the subsequent risk of disease recurrence after primary therapy and the need for adjuvant therapies. However, most breast carcinomas are detected in the early stage of the disease and the value of these classical prognostic factors is limited. There is also a great need to find new factors predicting the clinical efficacy of the anticancer drugs available. In this thesis tumor suppressor gene p53, oncogene c-erbB-2 and matrix metalloproteinase-9 were evaluated for their prognostic relevance in breast carcinoma patients treated in Oulu University Hospital, and matrix metalloproteinase-9 was also analyzed in women with premalignant lesions in the breast tissue in order to examine its role in breast carcinogenesis. Histological analyses were carried out from formalin-fixed, paraffin-embedded primary tumor specimens and p53, c-erbB-2 and matrix metalloproteinase-9 (MMP-9) statuses were systematically analyzed by immunohistochemistry.
P53 expression correlated with disease-free survival and overall survival in patients with early-stage breast carcinoma, regardless of adjuvant antiestrogen therapy. The co-expression of p53 and c-erbB-2 characterizes a tumor type with a clinically aggressive course of breast carcinoma. The clinical efficacy of anthracyline-based chemotherapy in metastatic carcinoma might be limited in patients with p53 expression in a primary tumor. When postmenopausal patients with lymph node metastases and receiving adjuvant antiestrogen therapy were examined, MMP-9 expression indicated a slightly greater risk of breast carcinoma recurrence in patients with estrogen receptor negative tumors. Hyperplastic breast tissue and invasive breast carcinoma lesions expressed some MMP-9 immunopositivity. However, the strongest positivity was seen in ductal carcinoma in situ samples, suggesting that MMP-9 participates in breast carcinogenesis in the preinvasive phase.
16
Kamaly-Asl, Ian. "Molecular, genetic, patient and surgical factors involved in the development and outcome of central nervous system tumours". Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/molecular-genetic-patient-and-surgical-factors-involved-in-the-development-and-outcome-of-central-nervous-system-tumours(3e42d00e-b543-452e-bd71-ff53e194d944).html.
Testo completoAbstract (sommario):
Prognostic factors come in a variety of forms and may be patient, tumour or environmental related. This thesis examines the interaction of prognostic factors for a variety of tumour types. It particularly focuses on single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene. The first section on meningiomas describes the frequency of sex steroid receptors in meningiomas. In this study, absence of progesterone receptors is associated with high tumour grade and male gender. Tumours that are progesterone receptor negative have an odds ratio for recurrence of 5.Choroid plexus carcinomas are aggressive malignant tumours generally occurring in young children. Gross total surgical resection has been shown to be a highly significant factor in tumour recurrence and survival. This study describes a treatment paradigm of neoadjuvant ICE chemotherapy in these children which decreases the vascularity and increase the chance of a complete removal. The operative blood loss with this regimen is reduced to 0.22 blood volumes from 1.11 blood volumes without neoadjuvant chemotherapy. The VEGF gene is highly polymorphic and SNPs of the region have previously been shown to influence VEGF protein expression. This study looks at cohorts of both adult gliomas and a variety of paediatric brain tumours; comparing them to controls. There are several associations described between the development of certain tumours and specific SNP genotypes. In addition to this, certain genotypes and haplotypes have an influence on survival of adult grade 2 astrocytomas and paediatric medulloblastomas and ependymomas. There are consistent themes to the prognostic genotypes throughout both the adult and the paediatric tumours.Prognostic factors come in a variety forms as described in this thesis. It is vital to understand the complex interaction between factors to best utilise them for the benefit of patients.
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Eifler, Luciano Silveira. "Estadiamento e sobrevida no câncer gástrico : papel do factor de crescimento endotelial vascular (VEGF-A)". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/49034.
Testo completoAbstract (sommario):
Introdução: O Fator de Crescimento Endotelial Vascular - A (VEGF) é um dos principais promotores da angiogênese e demonstra relação com prognóstico no câncer gástrico (CG). Objetivos: Correlacionar a expressão imunoistoquímica do VEGF com o estadiamento e sobrevida no câncer gástrico. Métodos: 45 espécimes de adenocarcinomas foram avaliados para expressão imunoistoquímica do VEGF. O estadiamento patológico (pTNM), características histológicas e sobrevida foram avaliados empregando os testes ANOVA, análise multivariada e curva de Kaplan-Meier. Resultados: Foi observada maior expressão do VEGF na comparação entre os estadiamentos IA e IB vs II,III e IV (p<0,001). O VEGF menos expresso estava relacionado com maior penetração do tumor na parede gástrica (p<0,003) e presença de comprometimento linfonodal (p<0,001). Pacientes apresentando tumores com maior expressão de VEGF tiveram maior sobrevida (HR 0,37; IC 95%: 0,17-0,79). Conclusão: Houve associação inversa na expressão do VEGF com o estadiamento dos tumores gástricos. A análise multivariada demonstra a expressão do VEGF como fator prognóstico independente na sobrevida dos pacientes com câncer gástrico.Background: Vascular endothelial growth factor A (VEGF) is one of the main promoters of angiogenesis and correlates with gastric cancer (GC) prognosis. Aims: To evaluate the correlation between immunohistochemical VEGF expression and the gastric cancer stage and survival rate. Methods: VEGF expression was evaluated by immunohistochemistry in 45 adenocarcinoma specimens. Pathologic staging (pTNM), histological characteristics and survival were assessed using an ANOVA test, a multivariate analysis and the Kaplan-Meier method. Results: A higher VEGF expression level was observed in stages IA and IB compared with II, III and IV (p<0.001). A lower VEGF expression level correlated with a greater tumor penetration level in the gastric wall (p<0.003) and the extent of tumor spread to the lymph nodes (p<0.001). Higher VEGF scores correlated with a longer survival time (HR 0.37; 95% CI: 0.17 - 0.79). Conclusion: An inverse correlation was observed between VEGF expression and gastric tumor stage. A multivariate analysis demonstrates that VEGF expression is an independent prognostic factor for survival in gastric cancer.
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Solovey, Maria [Verfasser], e Andreas [Akademischer Betreuer] Burchert. "Nuclear factor of activated T-cells, NFATC1, governs FLT3-ITD-driven hematopoietic stem cell transformation and a poor prognosis in AML / Maria Solovey ; Betreuer: Andreas Burchert". Marburg : Philipps-Universität Marburg, 2019. http://d-nb.info/1202110460/34.
Testo completo
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Sartor, Ivaine Tais Sauthier. "Biologia computacional na identificação dos reguladores mestres da transcrição em câncer pancreático". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/96813.
Testo completoAbstract (sommario):
O adenocarcinoma de ducto pancreático é reconhecido mundialmente como uma doença extremamente agressiva a qual apresenta um prognóstico desfavorável para pacientes sem cirurgia de ressecção. Portanto, é fundamental ampliar o conhecimento sobre os mecanismos biológicos envolvidos no câncer pancreático a fim de permitir a identificação de marcadores moleculares e alvos terapêuticos com o intuito de melhorar o diagnóstico precoce e tratamento. Os fatores de transcrição, reconhecidos por serem os efetores finais de vias de sinalização, regulam diversas funções celulares e, alterações na expressão transcricional destes podem contribuir para a transformação celular bem como para a progressão tumoral. Assim, o objetivo do presente estudo foi identificar os reguladores mestres da transcrição, possivelmente envolvidos no câncer pancreático. Para tanto, utilizamos dados de microarranjos para associar os reguladores mestres com o fenótipo tumoral. As análises foram realizadas no ambiente estatístico R utilizando os pacotes RTN, Limma e Survival. O gene TULP3 foi identificado como um regulador mestre da transcrição em amostras de câncer pancreático. O valor prognóstico de TULP3 foi verificado através de análises de sobrevivência em três coortes independentes. Estas análises revelaram que pacientes com adenocarcinoma pancreático, exibindo altos níveis de expressão do gene TULP3, apresentam uma sobrevida global desfavorável. Os altos níveis transcricionais de TULP3 podem desempenhar um papel fundamental na progressão do adenocarcinoma pancreático e conduzir a um resultado clínico desfavorável. Contudo, este estudo destaca a potencial aplicação de TULP3 como um biomarcador de prognóstico clínico para pacientes com adenocarcinoma pancreático.Pancreatic ductal adenocarcinoma is world-wide recognized as an aggressive disease with poor prognosis in patients who did not undergo resection. Efforts to better comprehend the biological mechanisms of pancreatic cancer are needed to enable the identification of novel molecular markers and therapeutic targets for improving early diagnosis and treatment. Transcription factors are the final effectors of signaling pathways and regulate a number of cellular functions. Changes in expression of transcription factors may contribute to cellular transformation and tumor progression. Thus, the aim of the present study was to identify transcriptional master regulators potentially involved in pancreatic cancer disease. To achieve this goal, we utilized microarray data to associate master regulators with tumor phenotype. Analyses were performed with RTN, Limma, and Survival packages at R environment. We identified TULP3 as a master regulator of transcription in pancreatic cancer samples. TULP3 prognostic value was accessed in three independent cohort analyses. Our data demonstrate that patients with pancreatic cancer, exhibiting high TULP3 transcriptional levels, show a poor overall survival. High levels of TULP3 expression may play an essential role in pancreatic cancer progression and lead to poor clinical outcome. Our results highlight the potential use of TULP3 as a clinical prognostic biomarker for pancreatic adenocarcinoma.
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Arnerlöv, Conny. "Prediction of prognosis in human breast cancer : a study on clinicopathologic and cytometric prognostic factors". Doctoral thesis, Umeå universitet, Patologi, 1991. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100584.
Testo completoAbstract (sommario):
This study was undertaken to evaluate some important prognostic factors in human breast cancer. The prognostic value of accepted clinicopathological factors such as the presence of axillary lymph node métastasés, histologic grade, clinical and pathological stage was confirmed. In a cohort of stage T3,T4,M0 breast cancer with 91 patients (paper I) DNA ploidy by static cytometry (SCM) turned out to be the most important prognostic factor. In a cohort of stage T2,M0 breast cancer with 99 patients (paper III) the presence of involved axillary nodes and low histologic grade were independent prognostic factors. According to life-table analyses DNA ploidy by flow cytometty (FCM) and SCM were significant prognostic predictors for survival but S-phase fraction (SPF) was not. The significant discrimination between euploid and aneuploid tumours was seen also among the node-negative patients. In a patient material with 158 tumours of predominantly low stages (73% T0,T1, papers IV and V) and calculated mammographie tumour volume doubling time (DT) DNA ploidy by FCM gave no significant prognostic information. A computer program was used to calculate SPF from the histograms obtained by FCM. SPF with a cut-off value of 7.5% between tumours with high and low proliferation rate was a highly significant and independent prognostic factor for survival. The other independent prognostic predictors were low histologic grade, the presence of involved axillary nodes and stage II and III (versus stage I). DT values for 158 patients (papers IV and V) varied between 0.6 and 65.8 months (mean 10.9 months) and 11 tumours showed no growth at all between mammographies. The median value of 9.0 months was chosen as cut-off point between slow and fast growing tumours. The prognostic power of DT was however low, and the difference between slow and fast growing tumours was significant only for distant disease-free survival. Seventy-one of the 158 tumours were detected by mammographie screening. The screening detected carcinomas with predominantly long DT:s were discovered at an early stage and showed favourable characteristics concerning DNA ploidy and SPF. FCM was a rapid and reliable method for DNA analysis with a better prognostic discrimination between euploid and aneuploid groups than SCM (papers II and III). SPF, DNA ploidy and histologic grade are significantly correlated to one another but show no strong correlation to the presence of axillary lymph node métastasés. There is also a significant correlation between DT on one hand and DNA ploidy and SPF on the other hand. In conclusion the classic prognostic factors are still valuable. DNA ploidy as a single prognostic factor seems to have a relatively low prognostic power and seems to be of limited clinical value. SPF is a highly significant prognostic predictor for breast cancer of low stage, but the clinical value is not defined.S. 3-38: sammanfattning, s. 39-94: 5 uppsatser
digitalisering@umu
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Ticó, Falguera Neus. "Biomecànica dels dits de la mà com a factor pronòstic de la recuperació funcional de l'extremitat parètica en pacients amb ictus aguts". Doctoral thesis, Universitat Politècnica de Catalunya, 2016. http://hdl.handle.net/10803/403435.
Testo completoAbstract (sommario):
Stroke is one of the most serious and common public health problems. Impairment of the upper extremity (UE) following stroke affects 50 - 80 % of patients. Full UE function is achieved in 79 % of patients with initial mild paresis, but only in 15 % of patients with severe initial impairment of the UE. The most reliable prognostic factors associated with UE recovery are localised motor impairments, especially in the musculature of the hand and abduction of the shoulder in the first days after a stroke. Evaluation of the biomechanics of the hand allows an accurate identification of the motion arcs of the digital joints. Objective: Assess the prognostic value of the range of motion of the finger joints using an instrumental glove (CyberGlove II) one week after stroke for UE functional recovery at 6 months. Methods: A prospective, longitudinal, observational study with follow-ups at 3 - 4 days, 1 week, 3 and 6 months of patients with UE motor impairment. Variables collected included: demographic data, level of stroke severity (NIHSS), deep sensitivity, sphincter incontinence, Fugl Meyer of UE (FM-UE), muscle balance with Medical Research Council (MRC), muscle tone (Modified Ashworth Scale) and pre- and post- stroke functional ability (Barhel Index amb Modified Rankin Scale). Active range of motion of the metacarpophalangeal and interphalangeal joints of the index, middle finger, annulary, and little finger was assessed with CyberGlove II without and against gravity. The dependent variable UE function was evaluated with the Action Research Arm Test (ARAT) categorized as good function (ARAT>=10) and poor function (ARAT<10). Results: 31 patients were included, 18 of which completed the 6-month follow-up. Mean age was 68.2 years (SD = 9.1) and 72,2 % were men. A total of 77,8 % of strokes were ischemic, and 50 % of these were lacunar. Mean NIHSS score was 9.2 (SD = 5.5). Motor NIHSS of UE, FM-UE and MRC of the flexion-extension musculature of the digits and wrist were prognostic factors for the recovery of UE function. At 1-week follow-up, statistically significant differences were observed in the range of motion of proximal and distal interphalangeal joints of the index and annulary against gravity between the two ARAT groups and in maxium flexion for the same joints of the index, middle finger and annulary in both positions. At 3-month follow-up, statistically significant differences were observed in the range of motion for: the proximal and distal interphalangeal joints of the index, middle, annulary and little finger in both positions; the metacarpophalangeal joints of the annulary and little for both positions and only of the middle finger for the zero-gravity position. Statistically significan differences were also found in maxium flexion, for interphalangeal joints of the same digits and positions and for the metacarophalanela joint of the little finger in the zero-gravity position. Conclusions: The biomechanical assessment of the range of motion of the proximal and distal interphalangeal joints of the index,middle finger and annulary of the hand one week post stroke has prognostic value for UE function recovery after stroke.L’ictus constitueix uns dels problemes de salut pública més importants i és una de les patologies mèdiques més freqüents. Els dèficits a nivell de l’extremitat superior (ES) estan presents entre un 50 - 80 % dels pacients que han sofert un ictus. La funcionalitat de l’ES es recupera en el 79 % dels pacients amb una parèsia inicial lleu, i solament es recupera en el 15 % dels pacients amb afectació inicial greu de l’ES. Els factors pronòstics amb més evidència de recuperació de l’ES són els dèficits motors localitzats, sobretot en la musculatura de la mà i en l’abducció de l’espatlla, en els primers dies post ictus. La valoració biomecànica de la mà permet objectivar de manera més acurada els arcs de moviments de les articulacions dels dits. Objectiu: avaluar la capacitat pronòstica del balanç articular de les articulacions dels dits mesurada amb el guant CyberGlove II® a la setmana post ictus en la recuperació funcional de l’ES als 6 mesos de l’ictus. Metodologia: estudi observacional prospectiu, longitudinal amb seguiment als 3-4 dies, a la setmana, als 3 i als 6 mesos de pacients amb afectació motora de l’ES. S’han recollit variables demogràfiques, de severitat de l’ictus (NIHSS), sensibilitat profunda, incontinència d’esfínters, Fugl Meyer de l’ES (FM-ES), balanç muscular amb el Medical Research Council (MRC), to muscular (escala d’Ashworth modificada) i estat funcional previ i post ictus (índex de Barthel i escala de Rankin modificada). S’ha avaluat el balanç articular actiu de les articulacions metacarpofalàngiques i interfalàngiques del segon, tercer, quart i cinquè dit de la mà amb el guant CyberGlove II® en dues posicions, sense i contra gravetat. La variable depenent ha estat la funcionalitat de l’ES avaluada amb l’Action Research Arm Test (ARAT), categoritzada en bona funcionalitat (ARAT ≥ 10) i mala funcionalitat (ARAT < 10). Resultats: vam incloure 31 pacients, dels quals 18 van fer un seguiment complet de 6 mesos. La mitjana d’edat va ser de 68,2 anys (DE = 9,1) i el 72,2 % eren homes. El 77,8 % dels ictus eren isquèmics, dels quals un 50 % eren lacunars. La puntuació mitjana en el NIHSS va ser de 9,2 (DE = 5,5). El NIHSS motor de l’ES, el FM-ES i el MRC de la musculatura flexora i extensora dels dits i canell eren factors pronòstics per a la recuperació de la funció de l’ES. En l’avaluació a la setmana, es van observar diferències estadísticament significatives en el rang de moviment de les articulacions interfalàngiques proximals i distals del segon i quart dit en la posició de contra gravetat entre els dos grups ARAT. I per la flexió màxima, per les mateixes articulacions del segon, tercer i quart dit en ambdues posicions. En l’avaluació dels 3 mesos, es van observar diferències estadísticament significatives en el rang de moviment de les articulacions interfalàngiques proximals i distals del segon, tercer, quart i cinquè dit en ambdues posicions i per les articulacions metacarpofalàngiques del quart i cinquè dit per ambdues posicions, i solament del tercer dit per la posició sense gravetat. I per la flexió màxima, per les articulacions interfalàngiques dels mateixos dits i posicions, i per l’articulació metacarpofalàngica del cinquè dit en la posició sense gravetat. Conclusions: l’avaluació biomecànica del balanç articular de les articulacions interfalàngiques proximals i distals del segon, tercer i quart dit de la mà a la setmana de l’ictus té capacitat pronòstica per a la recuperació funcional de l’ES als 6 mesos post ictus.
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Skírnisdóttir, Ingirídur. "Prognostic Factors in Early Stages (FIGO I-II) of Epithelial Ovarian Carcinoma". Doctoral thesis, Uppsala University, Department of Women's and Children's Health, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1729.
Testo completoAbstract (sommario):
From January, 1988, to December, 1993, 113 patients with FIGO stage IA-IIC epithelial ovarian carcinoma were treated with postoperative radiotherapy. The median follow-up period was 74 months. Tumor recurrences were recorded in 33 cases (30%). The cancer-specific survival rate was 72%. Tumor grade was a significant (P = 0.007) and independent prognostic factor in the multivariate analysis. In a smaller series of 106 patients, a number of prognostic factors (age, FIGO stage, histopathological type, and tumor grade) were studied in relation to regulators of apoptosis (p53, bcl-2, and bax) and growth factor receptors (HER-2/neu and EGFR). Immunohistochemical techniques were used. In a separate series of 103 patients, the DNA content (flow cytometry) and p53 status of the tumors were also studied and related to the same clinicopathological factors. P53 was associated with tumor grade (P = 0.007) and survival status (P = 0.046). In a Cox multivariate analysis, tumor grade (P = 0.0006), bax status (P = 0.020), and EGFR status (P = 0.018) were significant and independent prognostic factors. DNA ploidy of the tumors was strongly associated with tumor grade.
From January, 1994, to December, 1998, a series of 109 patients with ovarian carcinomas (FIGO IA-IIC) were treated with postoperative adjuvant chemotherapy. The same prognostic factors were studied in this series. The median follow-up was 48 months and the cancer-specific survival rate was 75%. Twenty-five (25%) tumor recurrences were recorded. The most favorable survival rate was seen in patients with tumors negative for p53 and positive for bcl-2 or bax. In a multivariate analysis, tumor grade (P = 0.014) and p53 status (P = 0.020) were independent prognostic factors.
Clinical, histopathological and biological prognostic factors should be combined in prognostic models to render patient-tailored therapy possible and to define different prognostic groups for future clinical studies of adjuvant therapy in early stage ovarian carcinomas.
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Botosová, Kristýna. "Hodnocení finanční situace podniku a návrhy na její zlepšení". Master's thesis, Vysoké učení technické v Brně. Fakulta podnikatelská, 2013. http://www.nusl.cz/ntk/nusl-223761.
Testo completoAbstract (sommario):
This master’s thesis is focused on an evaluation of certain financial situation. In the first part theoretical methods used in the financial analysis are described. The second part consists of a presentation of the company, its field of activity and developed financial analysis. Measures leading to an improvement of company’s economy are presented in the last part of this thesis.
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Rasheed, Shahnawaz. "Factors influencing prognosis in rectal cancer". Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539275.
Testo completo
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Hallquist, Arne. "Thyroid cancer : studies on etiology and prognosis". Doctoral thesis, Umeå universitet, Onkologi, 1994. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100596.
Testo completoAbstract (sommario):
Thyroid cancer constitutes about 1% of all malignant tumours and the incidence is increasing in Sweden. It is rare in children before the age of 10. During puberty the female to male ratio increases to be two to three times more common in females. The ratio remains constant until menopause and thereafter declines. The etiology of this gender-dependent incidence difference is unclear. Ionizing radiation is the only well-established risk factor for the disease, while the impact of other etiological factors is not clear. A retrospective study based upon medical records of 218 females and 91 males with papillary, mixed or follicular types of thyroid cancer was conducted. Prognostic factors were compared by multivariate analysis using Cox's semiparametric hazard model. Differences in prognosis between women and men were found. There was a higher relapse rate and mortality risk among men. Distant metastasis, age >50 years, regional lymph node metastasis, low or moderate differentiation, and tumour related symptoms at diagnosis were also independent factors related to increased tumour mortality risk. A population-based case-control study including 180 cases and 360 controls was carried out to identify risk factors for thyroid cancer. Information on exposure was obtained by mailed questionnaires. The first part of the study investigated connections between medical ionizing radiation and thyroid cancer. The results showed that diagnostic X rays were a significant risk factor for papillary thyroid cancer in women between 20 and 50 years at diagnosis. Exposure to iodine-131 caused no increased risk for thyroid cancer. The result supports that external radiotherapy is a risk factor for thyroid cancer in women. The second part of the case-control study dealt with occupation and different exposures. Work with diagnostic X-ray investigations and work as a lineman was associated with thyroid cancer. Exposure to impregnating agents increased the risk. The third part of this study showed that one pregnancy increased the risk for papillary thyroid cancer. A medical history of asthma or allergy decreased the risk. Another case-control study using medical records as the source for assessment of exposure gave a non significantly increased risk for thyroid cancer in patients who had been treated with external radiotherapy including the thyroid gland.Diss. (sammanfattning) Umeå : Umeå universitet, 1994, härtill 5 uppsatser.
digitalisering@umu
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Pennlert, Johanna. "Recurrent stroke : risk factors, predictors and prognosis". Doctoral thesis, Umeå universitet, Medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127304.
Testo completoAbstract (sommario):
Background Many risk factors for stroke are well characterized and might, at least to some extent, be similar for first-ever stroke and for recurrent stroke events. However, previous studies have shown heterogeneous results on predictors and rates of stroke recurrence. Patients who survive spontaneous intracerebral hemorrhage (ICH) often have compelling indications for antithrombotic (AT) treatment (antiplatelet (AP) and/or anticoagulant (AC) treatment), but due to controversy of the decision to treat, a large proportion of these patients are untreated. In the absence of evidence from randomized controlled trials (RCTs), there is need for more high- quality observational data on the clinical impact of, and optimal timing of AT in ICH survivors. The aims of this thesis were to assess time trends in stroke recurrence, to determine the factors associated with an increased risk of stroke recurrence – including socioeconomic factors – and to determine to what extent ICH survivors with and without atrial fibrillation (AF) receive AT treatment and to determine the optimal timing (if any) of such treatment. Methods The population-based Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) stroke incidence register was used to assess the epidemiology and predictors of stroke recurrence after ischemic stroke (IS) and ICH from 1995 to 2008 in northern Sweden. Riksstroke, the Swedish stroke register, linked with the National Patient Register and the Swedish Dispensed Drug Register, made it possible to identify survivors of first-ever ICH from 2005 to 2012 with and without concomitant AF to investigate to what extent these patients were prescribed AP and AC therapy. The optimal timing of initiating treatment following ICH in patients with AF 2005–2012 was described through separate cumulative incidence functions for severe thrombotic and hemorrhagic events and for the combined endpoint “vascular death or non-fatal stroke”. Riksstroke data on first-ever stroke patients from 2001 to 2012 was linked to the Longitudinal Integration Database for Health Insurance and Labour market studies to add information on education and income to investigate the relationship between socioeconomic status and risk of recurrence. Results Comparison between the cohorts of 1995–1998 and 2004–2008 showed declining risk of stroke recurrence (hazard ratio: 0.64, 95% confidence interval (CI): 0.52-0.78) in northern Sweden. Significant factors associated with an increased risk of stroke recurrence were age and diabetes. Following ICH, a majority (62%) of recurrent stroke events were ischemic. The nationwide Riksstroke study confirmed the declining incidence, and it further concluded that low income, primary school as highest attained level of education, and living alone were associated with a higher risk of recurrence beyond the acute phase. The inverse effects of socioeconomic status on risk of recurrence did not differ between men and women and persisted over the study period. Of Swedish ICH-survivors with AF, 8.5% were prescribed AC and 36.6% AP treatment, within 6 months of ICH. In patients with AF, predictors of AC treatment were less severe ICH, younger age, previous anticoagulation, valvular disease and previous IS. High CHA2DS2-VASc scores did not seem to correlate with AC treatment. We observed both an increasing proportion of AC treatment at time of the initial ICH (8.1% in 2006 compared with 14.6% in 2012) and a secular trend of increasing AC use one year after discharge (8.3% in 2006 versus 17.2% in 2011) (p<0.001 assuming linear trends). In patients with high cardiovascular event risk, AC treatment was associated with a reduced risk of vascular death and non-fatal stroke with no significantly increased risk of severe hemorrhage. The benefit appeared to be greatest when treatment was started 7–8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within three years was 17.0% when AC treatment was initiated eight weeks after ICH and 28.6% without any antithrombotic treatment (95% CI for difference: 1.4% to 21.8%). For high-risk men, the corresponding risks were 14.3% vs. 23.6% (95% CI for difference: 0.4% to 18.2%). Conclusion Stroke recurrence is declining in Sweden, but it is still common among stroke survivors and has a severe impact on patient morbidity and mortality. Age, diabetes and low socioeconomic status are predictors of stroke recurrence. Regarding ICH survivors with concomitant AF, physicians face the clinical dilemma of balancing the risks of thrombosis and bleeding. In awaiting evidence from RCTs, our results show that AC treatment in ICH survivors with AF was initiated more frequently over the study period, which seems beneficial, particularly in high-risk patients. The optimal timing of anticoagulation following ICH in AF patients seems to be around 7–8 weeks following the hemorrhage.
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Cunningham, Janet Lynn. "Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7906.
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Bonnett, Laura. "Prognostic factors for epilepsy". Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/8933/.
Testo completoAbstract (sommario):
Introduction and Aims: Epilepsy is a neurological disorder and is a heterogeneous condition both in terms of cause and prognosis. Prognostic factors identify patients at varying degrees of risk for specific outcomes which facilitates treatment choice and aids patient counselling. Few prognostic models based on prospective cohorts or randomised controlled trial data have been published in epilepsy. Patients with epilepsy can be loosely categorised as having had a first seizure, being newly diagnosed with epilepsy, having established epilepsy or frequent unremitting seizures despite optimum treatment. This thesis concerns modelling prognostic factors for these patient groups, for outcomes including seizure recurrence, seizure remission and treatment failure. Methods: Methods for modelling prognostic factors are discussed and applied to several examples including eligibility to drive following a first seizure and following withdrawal of treatment after a period of remission from seizures. Internal and external model validation techniques are reviewed. The latter is investigated further in a simulation study, the results of which are demonstrated in a motivating example. Mixture modelling is introduced and assessed to better predict whether a patient would achieve remission from seizures immediately, at a later time point, or whether they may never achieve remission. Results: Multivariable models identified a number of significant factors. Future risk of a seizure was therefore obtained for various patient subgroups. The models identified that the chance of a second seizure was below the risk threshold for driving, set by the DVLA, after six months, and the risk of a seizure following treatment withdrawal after a period of remission from seizures was below the risk threshold after three months. Selected models were found to be internally valid and the simulation study indicated that concordance and a variety of imputation methods for handling covariates missing from the validation dataset were useful approaches for external validation of prognostic models. Assessing these methods for a selected model indicated that the model was valid in independent datasets. Mixture modelling techniques begin to show an improved prognostic model for the frequently reported outcome time to 12-month remission. Conclusions: The models described within this thesis can be used to predict outcome for patients with first seizures or epilepsy aiding individual patient risk stratification and the design and analysis of future epilepsy trials. Prognostic models are not commonly externally validated. A method of external validation in the presence of a missing covariate has been proposed and may facilitate validation of prognostic models making the evidence base more transparent and reliable and instil confidence in any significant findings.
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Trivella, Maria Heleni. "Systematic reviews of prognostic factor studies". Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423353.
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Slind, Olsen Renate. "Circulating and genetic factors in colorectal cancer : Potential factors for establishing prognosis?" Doctoral thesis, Linköpings universitet, Avdelningen för läkemedelsforskning, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-136841.
Testo completoAbstract (sommario):
Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression. In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis. The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment. To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment. The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation. In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.Kolorektal cancer är en tumör i kolon eller rektum. I Sverige diagnosticerades år 2014 ca6300 individer med denna cancertyp och ca 2550 personer dör årligen till följd av kolorektalcancer. Operation är det huvudsakliga behandlingsalternativet för kolorektal cancer och vidfjärrmetastaser är överlevnaden < 10 %. Det är därför viktigt att hitta markörer somtillsammans med TNM-stadium kan ge tidig information om sjukdomens prognos och lämpliguppföljning av patienter. Utveckling av kolorektal cancer sker genom ackumulering av genetiska mutationer ochepigenetisk nedreglering av tumörsuppressorgener. Därutöver spelar interaktionen mellantumören och dess närmaste omgivning, innehållande tillväxt- och inflammatoriska faktorer,en viktig roll i tumörens utveckling och metastasering. Syftet med avhandlingen var att studera associationen mellan CD93, PLA2G4C, PDGF-D samtinflammatoriska cytokiner och kolorektal cancer progression. En prospektiv studie visade att CD93 och PLA2G4C SNP var potentiellt viktiga förbedömningav kolorektal cancer prognos. T/T genotypen av SNP rs2749817 i CD93 var associerad medhögre uttryck av CD93 i kolorektal cancer vävnad, främst bland patienter i stadium IV.Därutöver observerades fler återfall efter operation hos patienter med T/T genotypen. Aallelen hos PLA2G4C SNP rs1549637 är en möjligtvis bättre markör för cancerspecifiköverlevnad vid stadium II än faktorer som idag används för att selektera patienter tilladjuvant behandling. Sammantaget antyder detta att T/T genotypen av CD93 och A allelenav PLA2G4C kan vara genetiska markörer relaterade till allvarlig tumörsjukdom ochspridning. Därutöver kan de eventuellt selektera patienter som kräver tätare uppföljning ochadjuvant behandling. För att studera den förmodade inblandningen av PDGF-D i kolorektal cancer undersöktesdess effekt på PDGF-D signalering in vitro. PDGF-D signaleringen förändradegenexpressionen av gener involverade i tumörutveckling och spridning, vilken kundeblockeras av tyrosinkinashämmaren imatinib. Det antyder att PDGF-D signalering kan vara enviktig faktor vid kolorektal cancer progression och ett potentiellt mål för behandling. Analysen av ett flertal inflammatoriska cytokiner visade en korrelation mellan högacytokinnivåer och ökad cancerspecifik och total dödlighet två år efter operation. Höga CCL1och CCL24 nivåer var de enda faktorerna som förblev signifikant associerade medcancerspecifik mortalitet vid fördjupad statistisk analys och bör studeras vidare. Sammanfattningsvis presenterar denna avhandling cirkulerande och genetiska faktorersåsom CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 som eventuellt är viktiga vid bedömning avkolorektal cancer progression tillsammans med TNM stadium.
31
Uddenfeldt, Monica. "A Longitudinal Study of Asthma : Risk Factors and Prognosis". Doctoral thesis, Uppsala universitet, Arbets- och miljömedicin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-133218.
Testo completoAbstract (sommario):
The aim of this thesis was to identify risk factors for the onset of adult asthma. Other objectives were to study determinants of smoking habits and the association between sensitization and outcome of asthma. In 1990, a questionnaire was distributed to 12,732 individuals from three age groups (16, 30-39 and 60-69 years) in two counties of Sweden. In a second phase, 2538 subjects who had reported respiratory symptoms and 600 controls were invited to clinical investigations, 81% participated. At the follow-up in 2003 subjects of the remaining cohort (11,282) were re-invited. Analyses are based on the 67% (n=7563) who responded to both questionnaires 1990 and 2003. In 2003, 17.2% of the young adults, 11.4% of the middle-aged and 10.3% of the elderly reported having, or having had, asthma. A total of 791 subjects reported onset of asthma during the 13-year study period. Lifestyle factors such as smoking, obesity, hard physical training and a low consumption of fruit and fish were constant risk factors for onset of asthma after adjusting for socioeconomic group. A smoker’s risk of asthma onset was increased by 37%. The impact of risk factors differed between the age-groups. BMI had a significantly higher impact in the middle-aged and elderly. In subjects participating in the clinical investigations in 1990, sensitization to pets, were determinants of both persistent asthma and onset of asthma in 2003. The risk for persistent asthma was threefold. The risk for onset of asthma was more than doubled. Smoking at baseline in 1990 was the strongest determinant of being a smoker in 2003. Allergic sensitization and clinically verified asthma were not associated with smoking habits in 2003. No differences in changing smoking habits could be identified between smokers with or without asthma. In conclusion, modifiable lifestyle factors are important risk factors for adult onset asthma. The co-occurrence and interplay between asthma and cigarette smoking is still puzzling.
32
Hutchinson, Gillian J. "Investigation of factors affecting prognosis in ano-genital cancers". Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499919.
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Ali, Alaa Mostafa Galal. "Factors affecting prognosis after a diagnosis of breast cancer". Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648891.
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34
Bolander, Åsa. "Prognostic Factors in Malignant Melanoma". Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9511.
Testo completoAbstract (sommario):
Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis. This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers. In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers. In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7. We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67. DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors. None of the investigated markers in study III and IV correlated with disease free survival or overall survival. In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
35
Harder, Susan. "Prognostic factors in whiplash injury". Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68179.
Testo completoAbstract (sommario):
A historical cohort of 3014 individuals who sustained a whiplash injury resulting from a motor vehicle accident in Quebec in 1987 was assembled and followed up to six years using data obtained from the computerised databases of the province's universal automobile insurance plan. The prognostic factors that were found to be associated with the time to recovery from whiplash were gender, age, number of dependents, marital status, accident severity, vehicle type, seatbelt use, and the presence of multiple injuries. Factors that were predictive of the risk of recurrence of symptoms were age, number of dependents, and accident severity. None of the prognostic factors studied were found to be useful predictors of the amount of medically-related costs reimbursed by the insurance plan.The results of this study will be used in a future study involving more numerous and precise medical prognostic factors to assess their role in the management of whiplash patients.
36
Blessing, Karen. "Prognostic factors in malignant melanoma". Thesis, University of Aberdeen, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305319.
Testo completoAbstract (sommario):
Malignant melanoma is a relatively uncommon tumour in this country, but it accounts for most of the deaths attributable to skin cancer. Additionally, there is an established increasing incidence rate in every white population studied to date; it is therefore assuming greater importance. Despite the cutaneous location with the potential for early diagnosis, treatment and effective cure, the clinical behaviour of malignant melanoma still remains to a certain extent unpredictable. Today the Breslow measurement (thickness) of the tumour is regarded as the most sensitive prognostic indicator. Nonetheless, tumour thickness alone is not sufficient to predict the clinical outcome for the individual patient, with a 5-10% of 'thin' melanomas resulting in metastasis or death of the patient, and conversely it is recognised that a certain subgroup of 'thick' lesions will behave in a less aggressive than expected manner. Other features cited as influencing prognosis include patient age, sex, anatomical location, histogenetic type, mitotic counts, ulceration, vascular invasion, host response with a conflicting opinion on the role of regression. This thesis confirms the increasing incidence of melanoma in the Grampian Area, in keeping with other large studies and also that patients are presenting earlier with thin lesions. This thesis also confirms that some patients with thin melanomas develop metastasis and factors that may be important additional to the Breslow depth include lesion size, histological regression, Clark level and depth of the uninvolved dermis. Also, some thick melanomas do not metastasise and patients have a good disease free survival. Factors that appear to be important in this group of patients include anatomical location, vascular invasion and the nature of the lower tumour margin.
37
Bolander, Åsa. "Prognostic factors in malignant melanoma /". Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9511.
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38
Mejhert, Märit. "Heart failure : aspects on treatment and prognosis /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-604-2/.
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39
Jolly, Jessica. "Screening of tMTHFR, Factor V Leiden and hyperhomocyst(e)inemia, emerging prognostic factors in myocardial infarction?" Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0006/MQ45530.pdf.
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40
Bedenice, Daniela. "Prognose und Risikofaktoren der röntgenologischen Lungenveränderungen neonataler Fohlen Risk factors and prognostic variables of radiographic pulmonary disease in neonatal foals /". [S.l. : s.n.], 2004. http://www.diss.fu-berlin.de/2004/128/index.html.
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41
McCosker, Helen Clare. "Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients". Thesis, Queensland University of Technology, 2012. https://eprints.qut.edu.au/53580/1/Helen_McCosker_Thesis.pdf.
Testo completoAbstract (sommario):
Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM).
Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome.
To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins.
This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2).
Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models.
The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.
42
Potrony, Mateu Míriam. "Characterization of genetic factors associated with melanoma susceptibility and prognosis". Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663477.
Testo completoAbstract (sommario):
Melanoma is the malignant tumor arising from melanocytes and is the most aggressive of the common skin cancers. Melanoma is the tumor with the highest heritability (58%) and around 10% of cases occur in a familial context. Genetic susceptibility can be explained due to the inheritance of low, medium or high-risk variants, or a combination of them. To date, germline mutations in high-risk genes have been detected in 20-30% of melanoma-prone families. Interestingly, there is an important relationship between genetic factors associated with the risk to develop melanoma and genetic factors modulating melanoma outcome.
The thesis hypotheses were:
a) The proper characterization of known melanoma risk genes in a specific population context will facilitate genetic counseling in melanoma
b) The use of genome-wide linkage can allow the identification of new melanoma susceptibility loci in our population.
c) Melanoma susceptibility and nevus-related genes can play a role in melanoma prognosis.
d) Variants in immune checkpoints genes can play a role in melanoma prognosis.
Based on those hypotheses, the aims of this thesis were:
1) To characterize known risk genes in patients at high-risk to develop melanoma in Spain to refine genetic counseling.
2) To identify new familial melanoma loci using genome-wide linkage analysis.
3) To study the role of candidate genes in melanoma prognosis.
To answer those aims we designed six studies. In the first study, we evaluated the prevalence of CDKN2A germline mutations in patients at high risk to develop melanoma in our population and characterize families with mutation. We identified a higher prevalence of lung, breast and pancreatic cancer cases in families with mutation. Based on the study results, CDKN2A mutation carriers, besides sun protection advice and dermatologic surveillance, should receive recommendations on avoiding smoking and can be included in early detection programs for pancreatic, lung and breast cancers. In the second study, we evaluated the prevalence of MITF p.Glu318Lys carriers and assessed their characteristics detecting fast-growing melanoma among carriers. Thus, MITF p.Glu318Lys should be given fast-track visits to dermatology as they may be at risk to develop fast-growing melanomas and can be included in early detection programs for renal cancer. In the third study we identified that POT1 is mutated in a subset of melanoma families in Spain, thus genetic testing in melanoma should include the analysis of this gene. In the fourth study we identified a new melanoma locus at 11q associated with familial melanoma. Next-generation sequencing studies focused on the analysis of this region may allow the identification of new melanoma susceptibility genes or variants. Finally, in the last two studies, we focused on melanoma prognosis. We determined that IRF4 rs12203592 T functional variant, associated with a low melanogenesis (and low nevus count) and immune tolerance, correlates with a worse melanoma survival. Moreover, inherited functional variants of the lymphocyte receptor CD5, associated with more immune reactivity, correlated with better melanoma outcome.
To conclude, we have established the genetic bases of melanoma susceptibility in our population and refined genetic counseling, knowing the mutation prevalence of each gene and adapting secondary prevention measures in melanoma and other tumors according to the genetic testing results. Genome-wide linkage analysis in melanoma-prone families from Spain has allowed the identification of a new locus at 11q involved in familial melanoma. We have identified new genes modulating melanoma outcome based on the study of candidate genes involved in melanoma susceptibility, nevi count, and immune regulation.El melanoma és el més agressiu dels càncers de pell comuns. És el tumor amb una major heretabilitat. La susceptibilitat genètica depèn de variants d’alt, mig o baix risc, o la seva combinació. Hi ha una gran correlació entre factors genètics associats al risc i al pronòstic del melanoma. Els objectius d’aquesta tesi han estat: 1. Caracteritzar gens coneguts en pacients amb alt risc a desenvolupar melanoma per millorar el consell genètic. 2. Identificar nous loci implicats en la susceptibilitat a melanoma mitjançant anàlisi de lligament massiu. 3. Estudiar el paper de gens candidats en el pronòstic del melanoma En els primers tres estudis, es va avaluar la prevalença de mutacions a CDKN2A, POT1, promotor de TERT i la variant p.Glu318Lys a MITF en pacients amb alt risc a desenvolupar melanoma. També es van estudiar les característiques de les famílies i portadors d’aquestes variants. Els resultats observats mostren que els portadors de mutació a CDKN2A, a banda de les mesures de fotoprotecció i seguiment dermatològic, haurien d’evitar el tabac i es poden incloure en programes de detecció precoç de càncer de pàncrees, pulmó o mama. Els portadors de la variant p.Glu318Lys a MITF haurien de tenir accés ràpid a la consulta dermatològica pel risc a desenvolupar melanoma de ràpid creixement. POT1 s’hauria d’incloure en el test genètic. En el quart, hem identificat un nou locus a 11q associat a la susceptibilitat del melanoma familiar. Finalment, en els dos últims treballs, hem observat que la variant funcional d’IRF4 rs12203592 T, associada a un recompte de nevus baix i immunotolerància, correlaciona amb un pitjor pronòstic. A més, variants funcionals de CD5 associades amb una major reactivitat immunològica correlacionen amb un millor pronòstic. En conclusió, hem establert les bases genètiques de la susceptibilitat del melanoma en la nostra població i millorat el consell genètic. Estudis de lligament massiu han permès la identificació d’un nou locus associat al melanoma familiar. Per acabar, hem identificat nous gens que modulen el pronòstic del melanoma basant-nos en l’estudi de candidats relacionats amb la susceptibilitat a melanoma, el recompte de nevus i la regulació del sistema immune.
43
Heuts-van, Raak Elisabeth Petronella Maria. "Seizures following a first cerebral infarct risk factors and prognosis /". Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1996. http://arno.unimaas.nl/show.cgi?fid=6647.
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44
Kunzmann, Andrew. "Risk factors (including biomarkers) for colorectal cancer development and prognosis". Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.679238.
Testo completoAbstract (sommario):
Based on indications of a possible prognostic role of prostaglandin endoperoxide synthase-2 expression (PTGS2) in colorectal cancer, a systematic review was conducted to assess the prognostic significance among colorectal cancer patients. Despite indications of an association between PTGS2 expression and tumour recurrence, there was insufficient evidence to indicate an independent association between PTGS2 expression and colorectal cancer prognosis. Previous studies had indicated a potentially large prognostic benefit associated with use of low-dose aspirin following a diagnosis for colorectal cancer, but could be subject to reverse causality. Therefore, the association between low-dose aspirin use and survival among colorectal cancer patients was assessed using a design to reduce reverse causality. The results did not support an association between low-dose aspirin use and survival in colorectal cancer patients and suggested reverse causality was likely in previous studies. A systematic review with meta-analyses was conducted to assess the prognostic significance of vitamin D-related factors such as vitamin D status among colorectal cancer patients. The pooled results from all primary studies identified suggested that vitamin D status appears to be associated with coloreclal cancer survival. A prospective cohort analysis was used to assess the association between intakes of fibre and fruits and vegetables with risk of colorectal adenomas and cancer in screened individuals. The analyses provided evidence that fibre, but not fruit and vegetable, intakes were associated with a reduced risk of incident colorectal adenoma. Overall the thesis findings support a potential prognostic benefit associated with vitamin D concentrations, but not tumour PTGS2 expression or aspirin use among colorectal cancer patients. The findings also indicate that dietary fibre may act early in the development of colorectal cancer by reducing risk of incident colorectal adenomas
45
Miller, Kimberly Suzanne. "Factors Associated with Parents’ Understanding of their Child’s Cancer Prognosis". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1274838634.
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46
Grabowski, Pawel. "Telomere length as prognostic parameter in chronic lymphocytic leukemia". Doctoral thesis, Umeå universitet, Patologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-39463.
Testo completoAbstract (sommario):
B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia among the adult population in western countries and accounts for 30-40% of all leukemias. With survival time ranging from months to decades, the clinical course of individual CLL patients is highly variable. This heterogeneity and in the end the need for means to identify the patients with less favorable disease has encouraged the search for biomarkers that can predict the prognosis. Telomeres are repetitive structures protecting the chromosomal endings and shorten at each cell division. Telomere length (TL) has been indicated as a prognostic factor both in hematological malignancies and solid tumors. In B-CLL, TL is associated with mutation status of the immunoglobulin heavy chain variable (IGHV) gene and with clinical course. In the present thesis the main aim was to evaluate TL as a biomarker in B-CLL using a quantitative PCR-based method for TL determination. In paper I, TL was shown to be a prognostic factor for stage A and stage B/C patients, whereas IGHV mutation status predicted outcome only in stage A patients. Moreover, IGHV mutated CLL cases were subdivided by TL into two groups with different prognosis, a subdivision not seen for unmutated cases. Interestingly, the IGHV-mutated group with short telomeres had en overall survival close to that of the unmutated cases. Thus, a combination of IGHV mutation status and telomere length gave an improved subclassification of CLL identifying previously unrecognized patient groups with different outcomes. TL correlates with cellular origin of B-cell malignancies in relation to the germinal center (GC). In paper II different B-cell lymphoma/leukemia subtypes were analyzed. Shortest telomeres were found in IGHV unmutated CLLs, differing significantly from IGHV mutated cases. Contrary to this, mantle cell lymphomas (MCL) demonstrated similar TL regardless of IGHV mutation status. TL differed significantly between GC-like and non-GC-like diffuse large B-cell lymphomas (DLBCL) and follicular lymphomas (FL) had shorter telomeres than GC-like DLBCL. Hairy cell leukemias, which display Ig gene intraclonal heterogeneity, had longer telomeres than FLs and non-GC-DLBCL, but shorter than GC-DLBCL. In conclusion, TL seemed not to simply correlate with GC origin. Paper III presents a B-CLL cohort assessed for TL, genomic aberrations, IGHV mutation status, CD38 and ZAP-70 expression. An inverse correlation existed between TL and IGHV homology, CD38 and ZAP-70 expression. The presence of genomic aberrations was similar among patients regardless of TL. In contrast, 13q deletion, a favorable biomarker, was more frequent in patients with long telomeres, while 11q and 17p deletions (markers of less favorable outcome) were more frequent in the subgroup with short telomeres. In paper IV a large group of mainly indolent CLL cases from a population based cohort was studied again showing an association between TL and prognosis, especially in “good” prognosis cases as defined by other biomarkers. Multivariate analysis indicated a strong connection between IGHV mutation status, lipoprotein lipase (LPL) expression and TL. A comparison of TL in diagnostic and follow up samples demonstrated a significant correlation, and also in the follow samples TL constituted a significant biomarker for survival.
47
Moskowitz, Chaya S. "Quantifying and comparing the predictive accuracy of prognostic factors /". Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/9610.
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48
Jansen, R. L. H. "Prognostic factors in primary breast cancer". [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1998. http://arno.unimaas.nl/show.cgi?fid=8422.
Testo completo
49
Fearfield, Louise Anne. "Prognostic factors in very thin melanoma". Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413971.
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50
Al-Sharhan, Mouza Abdulla. "Prognostic factors in renal cell carcinoma". Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285788.
Testo completo