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Variáveis de prognóstico em crianças maiores de um ano portadoras de neuroblastoma disseminado / Prognostic variables in children older than one year with advanced neuroblastomaJairo Cartum 31 January 2011 (has links)
Introdução: Os neuroblastomas apresentam grande diversidade de comportamento clínico, evoluindo desde remissão espontânea à rápida progressão e morte. Heterogeneidade clínica e biológica tem implicado em grande variedade de respostas terapêuticas, inclusive em crianças maiores de 1 ano e em estádios avançados. Objetivo: estudar quadro clínico, aspectos epidemiológicos, características laboratoriais, genéticas e histológicas em crianças maiores de 1 ano portadoras de neuroblastoma disseminado, correlacionando-os com a evolução clínica e tentando definir fatores de risco que possam influir na sobrevida e na possibilidade da indicação do transplante de medula óssea (TMO). Casuística e Métodos: as informações foram obtidas de 53 pacientes admitidos na Unidade de Oncologia (ITACI) do Instituto da Criança do HC-FMUSP no período de 1997 a 2007. Os pacientes foram estudados quanto aos seguintes fatores: sexo, idade, raça, estado nutricional, DHL, Hb, ferritina, VMA, características tumorais (tamanho, localização, metástases, histologia, MYCN), terapêutica utilizada e evolução clínica. Estudamos separadamente também os fatores preditivos para TMO. Resultados: devem ser destacados: 1) crianças submetidas à cirurgia retardada completa apresentam 5 vezes menor chance de óbito do que as demais; 2) pacientes submetidos a TMO apresentam maior sobrevida total e livre de eventos em relação ao grupo não submetido a essa modalidade terapêutica 3) a utilização de retinóides gera 14 vezes menor chance de óbito em relação ao grupo que não os utiliza. 4) surpreendentemente, pacientes com ferritina abaixo de 334 n/ug/l apresentam 8 vezes maior chance de óbito. Conclusões: Não identificamos parâmetros clínicos e laboratoriais, práticos e facilmente disponíveis, de prognóstico para subpopulações de neuroblastomas de prognóstico avançado, sendo o estudo de fatores de ordem molecular e biológicos essenciais, apesar das dificuldades em realizá-lo / Introduction: Neuroblastomas (NB) have widely diverse clinical behavior, moving from spontaneous remission to progression and death. Clinical and biological heterogeneity factors determine different survival, even with children older than 1 year in advanced stages. Objective: to study the clinical presentation, epidemiology, laboratory findings, genetics and histopathologic characteristics in children older than 1 year with advanced neuroblastoma and their correlation with the survival. Also defining prognostic variables for bone marrow transplantation (BMT) indication. Casuistic and Methods: 53 selected medical records from patients older than 1 year with advanced NB admitted to the Instituto da Criança do HC-FMUSP from 1997 to 2007 were reviewed. The following risk factors were analyzed: age, sex, race, nutritional status, LDH, hemoglobin level, ferritin level, urinary VMA, tumor characteristics such as: site, histology, size, metastases, MYCN, treatment and clinical course. Results: it should be mentioned that: 1) possibility of death in children who underwent complete second look is 5 times lower than remaining ones; 2) patients who underwent BMT have better overall survival and event-free survival in comparison to the group not receiving this treatment modality. 3) the use of retinoids generates 14 times less chance of death in comparison to the group not receiving them. 4) patients whose ferritin level was below 334 n/ug/l had surprisingly 8 times more chances to die from diseases Conclusions: no simple and easily obtainable prognostic variables in a subpopulation of patients with advanced stage neuroblastoma, suitable to be widely employed in a country as ours, were identified. The study of molecular and biologics factors remains essential for precise characterization of these patients
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Contribution to the study of diagnosis and prognosis of cutaneous melanoma : is Galectin-3 a relevant biomarker ?/ Contribution à l'étude du diagnostic et du pronostic du mélanome cutané : évalutation de la Galectine-3 comme biomarqueurVereecken, Pierre F P J 21 August 2008 (has links)
La galectine-3 (Gal-3), protéine de type lectine, de 29-35 kDa, étudiée comme marqueur d’aggressivité dans les gliomes, présente des caractéristiques biologiques importantes justifiant son étude dans le domaine du mélanome. En effet, la Gal-3 est une protéine qui peut se lier à la laminine, tout comme l’intégrine α6/β1 dont l’expression est réduite dans le mélanome. L’expression de cette intégrine peut d’ailleurs être modulée par la Gal-3 comme récemment montré dans des lignées cellulaires de cancer du sein (BT-549) et de glioblastome (U373).
Le mélanome, véritable problème de santé publique qui est susceptible d’atteindre 1 individu sur 75 dans nos contrées, reste un tumeur mal comprise avec des évolutions parfois incertaines, et des traitements dont l’efficacité est limitée. Le diagnostic histologique du mélanome lui-même peut parfois représenter une difficulté pour le clinicien et l’expert pathologiste ou dermatopathologiste. La couleur (hyperpigmentation d’un lésion pigmentée), dont l’évaluation d’ailleurs reste subjective à défaut de standardisation, ne peut à elle seule signer la malignité d’une lésion pigmentée. Globalement l’évolution d’un patient est prédite par l’indice de Breslow qui traduit en mm l’épaisseur de la tumeur. Si cet indice dépasse 1mm, le risque métastatique augmente, justifiant la réalisation de bilans extensifs de suivi. Ceci dit, certains mélanomes épais peuvent ne pas présenter de caractéristiques d’aggressivité, alors que des mélanomes fins sont parfois mortels. L’identification de marqueurs moléculaires est donc impérative, tant pour développer des stratégies thérapeutiques ciblées, que pour affiner le diagnostic et le pronostic d’un patient.
Après avoir mis en évidence par immunohistochimie une expression de Gal-3 par les mélanocytes, nous avons démontré une surexpression de cette protéine par les mélanocytes tumoraux. Nous avons démontré également sur des lésions primitives qu’à l’aggressivité mesurée selon l’indice de Breslow correspondait une diminution de cette surexpression. Cette observation a pu être confirmée par un modèle de greffe orthotopique chez la souris nude.
Nous nous somme intéressés par la suite à la détection de la protéine dans le sérum, et nous avons constaté, un taux élevé de Gal-3 dans le sérum de patients en stade métastatique avancé, ce taux élevé pouvant s’expliquer tant par la charge tumorale que par la présence d’une inflammation, d’ailleurs bien connue chez le patient cancéreux en stade avancé. Le rôle antiapoptotique de la Gal-3 nous a alors amené à préciser la valeur prédictive et pronostique de cette protéine. L’hypothèse d’une potentielle action bénéfique sur la réponse immunitaire des patients atteints de mélanome qui ont été vaccinés a été rejetée. La Gal-3 sérique s’est révélée comme facteur de mauvais pronostic chez les patients métastatiques, et une analyse multivariée avec la définition d’une valeur « cut-off » de 10 ng/ml a permis de montrer une valeur pronostique indépendante, supérieure à la S100B et à la CRP.
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Multi-marker detection approach for improving breast cancer treatment tailoringDesmedt, Christine 27 August 2008 (has links)
the majority of patients with early breast cancer receive some form of systemic adjuvant therapy (chemo-, endocrine, and/or targeted therapy). Despite the increase in adjuvant therapy prescription, little progress has been made with respect to assisting oncologists to determine which breast cancer patients, particularly those deemed at “lower risk” of relapse, require chemotherapy or other systemic therapy and which women can safely be treated with loco-regional treatment alone. For these reasons, the identification of prognostic and predictive markers that will assist the clinician in selecting the most suitable form of medical therapy has become very high priority as well as a real challenge in translational research.
Unfortunately, several problems have hampered the identification and/or clinical usefulness of prognostic and predictive markers.
In Chapter 1, we sought to address some of the specific questions regarding prognosis:
- Are gene expression signatures robust and reproducible?
- Do the different gene signatures have similar prognostic performance? Are they concordant in their prediction for the individual patient?
- What is the role of individual genes in a signature and what is their biological interpretation?
- What is the relationship between the molecular classification defined by cluster analysis and the different prognostic signatures?
Through the following specific aims:
1. Independent validation study of a prognostic gene signature derived from microarray technology, to demonstrate its reproducibility, robustness and clinical utility compared with classical breast cancer prognostic factors in an appropriate validation cohort (Chapter 1A);
2. Independent comparison of three prognostic gene signatures (Chapter 1B);
3. Characterization of the biological foundation of the different prognostic signatures and refinement of our knowledge regarding breast cancer prognosis according to the molecular subgroups defined by ER and HER2 through a meta-analysis of publicly available gene expression data (Chapter 1C).
In Chapter 2, we sought to address some specific questions regarding the prediction of response for the most commonly given breast cancer treatments:
- What is the importance of proliferation genes in predicting clinical outcome in patients treated with endocrine therapy?
- What is the value of TOP2A in predicting the efficacy of anthracycline therapy?
- Can we identify a list of genes associated with response to anthracyline therapy?
- What is the best method and cutoff to determine HER2-positive patients eligible for trastuzumab therapy? Would an alternative quantitative method for HER2 expression and homodimerization discriminate patients with significantly different probabilities of clinical outcome following treatment with trastuzumab?
Through the following specific aims:
1. Investigation of molecular markers of response to endocrine therapy in hormono-sensitive patients (Chapter 2A);
2. Prospective evaluation of the predictive value of TOP2A and identification of genes associated with response in a cohort of patients treated with anthracyclines (Chapter 2B);
3. Investigation of the best method to select patients who should be treated by trastuzumab-based therapy and evaluation of a new technique to quantitatively assess HER2 expression (Chapter 2C).
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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).Berghmans, Thierry 03 March 2009 (has links)
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.
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The Association of XRCC1 Polymorphisms with Development and Prognosis of Oral and Pharyngeal Squamous Cell CarcinomasMing Yen, Liang 25 August 2011 (has links)
X-ray repair cross complementing Group 1 (XRCC1) protein plays an important role in base excision repair. Single nucleotide polymorphisms (SNPs) in XRCC1 gene may affect DNA repairing ability, genetic susceptibility, and prognosis to oral and pharyngeal squamous cell cancer (OPSCC). This study was carried out to evaluate the association of three XRCC1 SNPs with the risk and prognosis of OPSCC. A total of 509 OPSCC cases and 678 cancer-free controls were recruited to detect the genotypes of XRCC1 by PCR-RFLP. Then, 447 case patients with surgical treatment and safety margins were included in the survival analysis. No association was observed for XRCC1 194 and the risk of OPSCC. As compared with the wild Arg/Arg genotype, the combined genotypes of 280 Arg/His and His/His were with decreased risk (AOR=0.73, 95% CI, 0.52-1.03, p = 0.069) of OPSCC and with a significantly decreased risk (AOR=0.67, 95% CI, 0.47-0.97, p = 0.035) of oral cavity. As compared with the Arg/Arg genotype of XRCC1 399, the Gln/Gln genotype was with the increased risk of OPSCC (AOR=2.06, 95%CI: 1.21-3.51, p = 0.008) and oral cavity cancer (AOR=1.89, 95%CI: 1.08-3.33, p = 0.026). We defined the ¡§putative high risk haplotypes¡¨ as ¡§Arg-Arg-Gln and Trp-Arg-Gln¡¨. The AOR were 1.29 (95% CI, 1.04-1.60, p = 0.020) for the ¡§putative high risk haplotypes¡¨ as compared with other haplotypes for OPSCC. Then, two putative high risk haplotypes were combined into ¡§putative high risk diplotypes¡¨. The AOR for the ¡§high risk diplotypes¡¨ were 1.98 (95% CI, 1.18-3.33, p = 0.010) as compared with other diplotypes for OPSCC. No association between XRCC1 polymorphisms and clinicopathological outcomes, except XRCC1 280. Those carriers of XRCC1 280His allele (combined Arg/His and His/His genotypes) were associated with late onset (≥50 yrs) of oral cavity cancers. No association between genetic variants in XRCC1 and disease-specific survival except XRCC1 399. Patients with 399 Arg/Gln and Gln/Gln genotypes showed a significant better survival as compared to Arg/Arg genotype carriers (AHR 0.41 95% CI: 0.18-0.93), especially for those patients younger than 50 years (p = 0.012), in pathological stage III or IV (p = 0.044), and without postoperative radiotherapy (p = 0.012). In summary, XRCC1 280 Arg/His and His/His genotypes were associated with decreased risk of oral cavity cancer. 399 Gln/Gln genotype was associated with increased risk of OPSCC and oral cavity cancer. The putative ¡§high risk haplotypes and diplotypes¡¨ were with increased risk of OPSCC. However, 399 Arg/Gln and Gln/Gln genotypes were prognostic factors, especially for those with young age, aggressive tumor stage, and without postoperative radiotherapy for oro and hypopharynx patients. These findings suggest that XRCC1 polymorphisms may play a role in the development and prognosis of OPSCC.
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CDK2AP1 Expression Profile in Oral Cancer PrognosisHuang, Chih-hua 09 January 2007 (has links)
Oral cancer is now the fourth leading cause of male cancer mortality in Taiwan. Betel quid chewing is one of the main causes of oral cancer in Taiwan. CDK2AP1 is a growth suppressor gene that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12CDK2AP1 protein is reduced and/or lost in oral cancers. Mutations in microsatellite-like sequence of CDK2AP1 gene in microsatellite instability colorectal cancer are associated with down-regulated CDK2AP1 transcription. This mutation was due to down-regulation of one DNA repair protein, MLH1. In order to understand whether CDK2AP1 mRNA and protein expression levels associate with betel-chewing oral cancers, we firstly analyzed 44 oral cancer specimens (normal and tumor, in pairs) by quantitative reverse transcription polymerase chain reaction and Western blotting. Immunohistochemistry was used to examine p12CDK2AP1 protein expression in another 167 buccal mucosa squamous cell carcinoma tissues. We have demonstrated that the expression levels of CDK2AP1 mRNAs were slightly higher in normal oral tissues than those in tumor tissues (P>0.05). Similarly, p12CDK2AP1 and CDK2 protein expression levels were up-regulated in oral cancer tissues than in normal tissues by Western blot analysis (P<0.05). Among Ca9-22, CAL27, SAS and in betel-chewing oral cancer cells TW2.6 and human normal skin keratinolial cells (HaCaT) that we examined, p12CDK2AP1 and CDK2 proteins were detected to be highest expressed in Ca9-22 and TW2.6 cells, respectively, when compared to HaCaT cells. Immunocytochemistry indicated p12CDK2AP1 expressed in nucleus and cytoplasm in Ca9-22, CAL27, SAS and HaCaT cells, however predominant present in nucleus in TW2.6 cells. On the other hand, immunohistochemistry demonstrated that nuclear (P=0.157) and cytoplasmic p12CDK2AP1 (P=0.350) in 167 patients with buccal mucosa squamous cell carcinoma were slightly down-regulated. Reduction of nuclear p12CDK2AP1 was not significantly correlated with any clinicopathologic characteristics or prognosis. Direct sequencing indicated that lack of microsatellite-like instability of CDK2AP1 3¡¦-UTR in four oral cancer cell lines, HaCaT and six patients with down-regulated MLH1 protein. In conclusion, we demonstrated that: (1) p12CDK2AP1 was located in both the nucleus and cytoplasm in most oral cancer cell lines and HaCaT cells but predominate present in the nucleus in betel-chewing oral cancer cells, TW2.6; (2) Reduction of nuclear p12CDK2AP1 in buccal mucosa squamous cell carcinoma tissues were identified, however, not significantly correlated with any clinicopathologic characteristics, prognosis or betel chewing; (3) In six patients with down-regulated MLH1, lack of micorsatellite-like instability in the CDK2AP1 3¡¦-UTR region has been found.
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Risk Factors of Recipient Receiving Living Donor Liver Transplantation in the Comprehensive Era of Indication and Perioperative ManagementsIshigami, Masatoshi, Katano, Yoshiaki, Hayashi, Kazuhiko, Ito, Akihiro, Hirooka, Yoshiki, Onishi, Yasuharu, Nakamura, Taro, Kiuchi, Tetsuya, Goto, Hidemi 08 1900 (has links)
No description available.
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Clinical outcome and prognosis of childhood epilepsy (1996-2006)Yung, Wing-yan, Ada., 楊穎欣. January 2010 (has links)
published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences
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A study of pharmacogenomics for therapeutic and prognostic guidance towards hepatitis C virus (HCV) for patients co-infected with HIVYuen, King-tai, 袁敬弟 January 2013 (has links)
The cost effectiveness of using novel HCV treatment option, telaprevir and boceprevir, should depend on patients’ respond to conventional PEG-INFα and ribavirin therapy. The study of pharmacogenomics, interleukin-28B (IL-28B) polymorphisms, accompanied with the information of HCV genotypes are suggested to have the strongest predictive value of treatment outcomes and prognosis of disease in individuals infected with HCV who are undergoing conventional PEG-INFα and ribavirin therapy. It is extremely valuable in HCV/HIV co-infected patients as these groups of patients require a complex treatment regimen and demonstrate poor sustained viral response (SVR) rate. The development of a fast and promising IL-28B genotyping assay is urgently needed.
A total of 47 blood samples randomly selected from HCV and HIV co-infected patients were used in this investigation. The aims of this study are to evaluate and compare the performance of newly developed IL-28B HybProbe real-time PCR assay using LightCycler® system against Sanger Sequencing method in determining IL-28B polymorphisms on rs12979860 and rs8099917 and to estimate the prevalence of IL-28B polymorphisms among HCV/HIV co-infected patients in Hong Kong. In addition, the genotypic distribution of HCV among the same patient group is identified by using in-house Sanger Sequencing method.
It was found that the newly developed IL-28B real-time HybProbe assay resulted in 100% concordance with the traditionally used Sanger Sequencing method. The allele frequencies of C and T were 96% and 4% in rs12979860 and T and G were 97% and 3% in rs8099917 respectively. The CC and TT wild type are predominating in rs12979860 and rs8099917 with frequencies of 93.62% and 95.74% respectively. The most favorable compound genotype CC/TT with both homozygous wild types on both SNPs was the most predominant type with a high prevalence of 93.61%. Among all the samples, 50% samples were found to be HCV genotype 1, 41.18% were genotype 6 and 8.82% were genotype 3.
A simple and efficient IL-28B real-time HybProbe assay was developed in this study and proved to show excellent performance on IL-28B genotyping although further optimization is suggested before it can be applied in the clinical setting. The favourable wild type genotypes of rs12979860 and rs8099917 accounted for the most predominant genotypes which is similar to other findings obtained from an Asian population. A comparatively high prevalence of HCV genotype 6 was found in the HCV/HIV co-infected group. Future study with the information of treatment outcomes (HCV viral load) can further evaluate the predictive value of IL-28B polymorphisms on SVR in different HCV genotypes. / published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
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Patho-biological prognostic factors in hepatocellular carcinomaNg, Oi-lin, Irene., 呂愛蓮 January 1994 (has links)
published_or_final_version / Medicine / Master / Doctor of Medicine
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