Дисертації з теми "Chemotherapy biomarker"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-40 дисертацій для дослідження на тему "Chemotherapy biomarker".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Muhammad, Aun. "Microbubble ultrasound as surrogate imaging biomarker for response to systemic and regional chemotherapy." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/44958.
Повний текст джерелаBunting, David Mark. "The performance of circulating biomarkers in the prediction of response to neoadjuvant therapy in patients with oesophago-gastric cancer." Thesis, University of Plymouth, 2016. http://hdl.handle.net/10026.1/6565.
Повний текст джерелаThornton, Michael. "The 78 kDa glucose regulated protein (GRP78) as a potential treatment predictive biomarker and therapeutic target in colorectal cancer adjuvant chemotherapy." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/17993/.
Повний текст джерелаZanjirband, Maryam. "The genomic and functional status of TP53 in ovarian cancer : biomarker for chemotherapy outcome and determinant of response to MDM2 inhibitors." Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3831.
Повний текст джерелаAit-Belkacem, Rima. "Caractérisation du glioblastome multiforme et suivi de ses chimiothérapies par imagerie MALDI couplée à l'approche top-down." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5503.
Повний текст джерелаGlioblastoma is the most aggressive of the gliomas, a collection of tumors arising from glia or their precursors within the central nervous system. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12-14 months survival period post-diagnosis. The glioblastoma is characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. In order to optimize the therapy effect, a pharmacokinetic monitoring and a better understanding and characterization of tumor biology are needed. For this purpose, matrix assisted laser desorption/ionization imaging mass spectrometry imaging mass spectrometry (MALDI IMS) technology was applied to identify diagnostic, prognostic and predictive markers of therapy response; and to understand/follow the pharmacokinetic of chemotherapies. The top-down in-source decay strategy was used for protein identification directly on tissue. This strategy allowed tubulin protein isoforms distinction and identification, which is one of the main targets in cancer therapy. MALDI imaging coupled to ISD identified tumorigenesis proteins within tumor structures. Bevacizumab and temozolmide distribution was followed within brain tissue sections. For the first time a monoclonal antibody was deciphered on tissue. Finally, markers that predict therapy response were demonstrated by a comparison between protein expression profiles from tumors with and without chemotherapy treatment. These results highlight the interest of MALDI imaging for chemotherapy improvement and open the way for its use in the clinics
Hendlisz, Alain. "Multimodality imaging for treatment response prediction in colorectal cancer." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209109.
Повний текст джерела1) Le premier projet explore l’imagerie multimodale comme un outil d’individualisation pour la radio-embolisation (microsphères chargées en 90Yttrium) chez des patients porteurs d’un CCR métastatique au niveau du foie, pour laquelle l’imagerie morphologique classique est incapable de mesurer l’effet thérapeutique. Nous montrons que l’usage non sélectif de la radio-embolisation améliore l’histoire clinique de ces patients, bien que certains d’entre eux ne semblent pas en bénéficier. Ensuite, par une analyse multimodale lésion par lésion intégrant angiographie-CT Scan, FDG-PET/CT et scintigraphie aux macro-agrégats d’albumine marqués au 99mTechnetium, nous démontrons que la distribution pré-thérapeutique des macro-agrégats d’albumine est hétérogène entre les différentes lésions des patients et prédictive de la réponse métabolique au sein de ces lésions, permettant le développement d’un outil de prédiction et de planification pour la radio-embolisation.
2) Le deuxième projet explore le domaine du CCR métastatique traité par chimiothérapie palliative. (i) Nous démontrons d’abord que la réponse métabolique (RM) tumorale après une cure de chimiothérapie cytolytique prédit plus vite et plus adéquatement que l’imagerie morphologique basée sur les critères RECIST les bénéfices cliniques du traitement. La RM précoce a une excellente valeur prédictive négative sur l’absence de réponse morphologique et met en évidence une variabilité de réponse inter-lésionnelle chez une proportion importante des patients. (ii) L’étude SoMore explore ensuite des patients présentant un CCR avancé et réfractaire, traités par capecitabine et sorafenib, et confirme l’importance pronostique des RM mixtes, suggérant une méthodologie de classification clinique basée sur la consistance de la RM. (iii) Cette classification cherche confirmation dans l’étude RegARd-C, encore en cours, évaluant les effets du regorafenib, et explorant également la signification génomique et épigénétique de la variabilité de RM.
3) Le troisième projet cherche à utiliser les propriétés de l’imagerie métabolique pour modifier l’algorithme de traitement adjuvant des patients porteurs d’un cancer du côlon de stade III. Ce projet, encore en cours, fait l’hypothèse que l’absence de RM de la lésion primitive après une cure de chimiothérapie prédit l’absence de bénéfice du traitement adjuvant complet. Une analyse intérimaire en démontre la faisabilité et confirme la présence de 40% de tumeurs présentant des caractéristiques métaboliques de chimio-résistance.
En conclusion, pour des patients porteurs d’un CCR, l’imagerie multimodale comprenant une évaluation du métabolisme tumoral permet une évaluation plus précoce et plus adéquate du bénéfice au traitement anticancéreux pour différentes modalités thérapeutiques comme la radio-embolisation, la chimiothérapie cytotoxique et les agents biologiques. L’imagerie multimodale permet de prédire et planifier les radio-embolisations et se révèle très prometteuse pour les traitements chimiothérapiques cytotoxiques ou combinés à des biologiques en situation adjuvante ou métastatique. Elle démontre par ailleurs une importante variabilité de réponse métabolique inter-lésionnelle qui représente un axe de recherche majeur sur les mécanismes moléculaires d’hétérogénéité génomique tumorale et de résistance aux traitements anti-cancéreux.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
Ferraioli, Domenico. "Assessment and relevance of the putative DNA/RNA helicase Schlafen-11 in ovarian and breast cancer." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1324/document.
Повний текст джерелаSchlafen 11 (SLFN11) is a putative DNA/RNA helicase, first described for its role in thymocyte development and differentiation in mouse models. SLFN11 is part of a family of proteins with various degree of homology across species, but intriguingly being consistently present only in vertebrates and especially in mammals. Recently, the role of this putative DNA/RNA helicase, SLFN11, was causally associated with sensitivity to DNA damaging agents, such as platinum salts, topoisomerase I and II inhibitors, and other alkylators in the NCI-60 panel of cancer cell lines. In the first study, we validate an anti-SLFN11 antibody in formalin-fixed paraffin-embedded (FFPE) high-grade serous ovarian carcinoma (HGSOC) samples, developing an immunohistochemistry (IHC) protocol in order to determinate the expression of SLFN11 in our series of HGSOC. Indeed, we tested and validated a reliable SLFN 11 antibody (Ab) in IHC choosing between two anti-SLFN11 Ab used normally for Western Blot (WB) in culture cell block (CCB) of ovarian carcinoma and in an independent series of HGSOCs tissue micro-array (TMA). For each case, we evaluated both the Intensity Score (IS) and the Distribution Score (DS) evaluating at least 300 cells. A Histological Score (HS)was obtained as follow: HS=IS x DS. Successively, we applied our protocol to a large case series of HGSOC samples to confirm our preliminary results. We found one antibody to be reliable in CCB and TMA series allowing to determinate clearly IHC expression of SLFN11. These results were confirmed in our large case series of FFPE HGSOC samples. Briefly, as for TMA independent series, we found that the HS for SLFN11 expression presents a normal distribution with a prevalent (≈ 60%) intermediate expression. Parallel SLFN11 was not expressed in practically 40% of cases that clinically corresponded to the platinum resistant patients in about 60% of cases (16/27). So, we believe that low IHC expression of SLFN 11 should be correlated to response to the platinum-based chemotherapy. In the second study, we investigate the transcriptional landscape of SLFN11 in breast cancer performing a gene expression microarray meta-analysis of more than 7000 cases from 35 publicly available data sets. By correlation analysis, we identified 537 transcripts in the top 95th percentile of Pearson’s coefficients with SLFN11 identifying “immune response”, “lymphocyte activation” and “T cell activation” as top Gene Ontology enriched processes. Furthermore, we reported very strong association of SLFN11 with immune signatures in breast cancer through penalized maximum likelihood lasso regression. Finally, through multiple corresponded analysis we discovered a subgroup of patients, defined “SLF11-hot cluster”, characterized by high SLFN11 levels, estrogen receptor(ER) negativity, basal-like phenotype, elevated CD3D, STAT1 signature, and young age. Using Cox proportional hazard regression, we characterized that SLFN11 high levels, high proliferation index, and ER negativity are independent parameters for longer disease-free interval in patients undergoing chemotherapy. We believe that our second work supports proof of concept that: i) A clear and specific role for SLFN11 in breast cancer, in likely connection with the immune system modulation in such disease entity, ii) a strong correlation between high SFLN 11 and specific molecular subtype of breast cancer (estrogen receptor negativity, basal-like phenotype). Further studies will be performed to confirm our hypothesis in order to: 1) better understand the function of SLFN 11 in cancer cell, 2) validate an easy, reliable and standardized IHC protocol to assessment SLFN11, 3) use SFLN11expression as a predictive biomarker of response to DDA and PARP inhibitors and 4) determinate the relationship with immune system
Nelmes, David-John. "Genetic biomarkers of chemotherapy response and resistance in lung cancer patients." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/109686/.
Повний текст джерелаBolze, Pierre-Adrien. "Recherche de biomarqueurs prédictifs de l’évolution et de la réponse au traitement dans les maladies trophoblastiques gestationnelles." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSEN016.
Повний текст джерелаHydatidiform moles are a pretumoral placental proliferation which can turn into a tumorrequiring chemotherapy. In order to reduce mortality and propose an optimal therapeuticmanagement, the aim of this thesis is to identify genes which are predictive of postmolartumor transformation and chemoresistance.Concerning the prediction of transformation, the expression analysis of candidate-geneson molar tissue shows a relocalization of Syncytin-1 at the syncytiotrophoblast apicalborder in moles followed by malignant transformation, without modification oftranscription of its receptors and two other retroviral placental envelopes. A wholetranscriptomeapproach using 3 different microarrays-based methods did not identify anydifferentially expressed gene according to the post molar evolution. This may reflect thatinter-individual variability and the different criteria used for tumor diagnosis impede theidentification of robust biomarkers.Concerning the prediction of chemoresistance, a broad-spectrum transcriptomicapproach on choriocarcinoma tumor tissue identifies a down regulation of HLA-G in case of monochemoresistance, confirmed at the protein level by immunohistochemistry.Pathway analysis of the differentially expressed genes suggests thatmonochemoresistance is associated with impaired T-cell differentiation, whereaspolychemoresistance is associated with impaired proliferation of blood cells.Ultimately, the evidence of trophoblastic ubiquitous expression of the PD-L1 immunecheckpoint led us to the evaluation of the efficacy of PD-L1 blockade in chemoresistantpatients. The encouraging results of this trial and the possibility of stratifying patientswith HLA-G and Syncytin-1 markers encourages the assessment of PD-L1 blockadecombined with monochemotherapy as a first line treatment for trophoblastic tumors
Hodgkinson, Victoria C. "The identification of biomarkers of chemotherapy resistance in breast cancer using comparative proteomics." Thesis, University of Hull, 2011. http://hydra.hull.ac.uk/resources/hull:5275.
Повний текст джерелаRüger, Alexandra [Verfasser]. "Einfluss einer kardiotoxischen Chemotherapie auf kardiovaskuläre Biomarker im klinischen Verlauf / Alexandra Rüger." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1241539480/34.
Повний текст джерелаParton, Marina. "An evaluation of proliferation apoptosis related biomarkers during primary chemotherapy for early breast cancer." Thesis, Institute of Cancer Research (University Of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511357.
Повний текст джерелаHussain, Tasadooq. "Proteomic identification of putative biomarkers of neo-adjuvant chemotherapy resistance in luminal (ER+) breast cancer." Thesis, University of Hull, 2013. http://hydra.hull.ac.uk/resources/hull:7395.
Повний текст джерелаNarayanaswamy, Hema Malini. "An exploratory study to investigate potential sensory biomarkers of chemotherapy-induced and diabetic peripheral neuropathy." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/9508.
Повний текст джерелаYarana, Chontida. "ROLE OF OXIDIZED EXTRACELLULAR VESICLES AS EARLY BIOMARKERS AND INFLAMMATORY MEDIATORS IN CHEMOTHERAPY-INDUCED NORMAL TISSUE INJURY." UKnowledge, 2018. https://uknowledge.uky.edu/toxicology_etds/23.
Повний текст джерелаZahir, Sheba Adam. "Evaluating the efficacy of DNA repair biomarkers to assess human cell response to chemotherapy using imaging flow cytometry." Thesis, Brunel University, 2013. http://bura.brunel.ac.uk/handle/2438/7768.
Повний текст джерелаLaufs, Valeria [Verfasser], and Martin [Gutachter] Fassnacht. "Evaluation von ERCC1 als prädiktiver Biomarker bei mit platinbasierter Chemotherapie behandeltem Nebennierenrindenkarzinom / Valeria Laufs ; Gutachter: Martin Fassnacht." Würzburg : Universität Würzburg, 2019. http://d-nb.info/1187140376/34.
Повний текст джерелаMartínez, González Sandra. "Metabolomic analysis of oxidative stress and inflammation biomarkers during chemotherapy treatment in pregnant women with breast cancer and their offspring." Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/671261.
Повний текст джерелаEl cáncer de mama asociado al embarazo (PABC en inglés) es definido como cáncer de mama diagnosticado durante el embarazo o un año después del parto. La quimioterapia administrada durante el embarazo puede aumentar la producción de estrés oxidativo e inflamación elevando el riesgo de problemas obstétricos. Para ello, examinamos diferentes marcadores de estrés oxidativo, inflamación y de defensa antioxidante en mujeres con PABC (N=17) antes del tratamiento, antes de cada ciclo (antraciclinas y paclitaxel) y al parto. También se obtuvo sangre de pacientes con cáncer de mama sin embarazo (N=10) antes y después de antraciclinas y mujeres embarazadas sanas (N = 16). Paralelamente, analizamos sangre de cordón umbilical (N=13) y de orina (N=5) 24h de vida de recién nacidos que recibieron quimioterapia en el útero. Muestras de cordón (N=14) y de orina (N=6) de bebés nacidos de madres sanas se utilizaron como controles. En general, las pacientes con PABC exhibían niveles similares de estrés oxidativo y de antioxidantes antes de la quimioterapia que las controles. Sin embargo, las pacientes con PABC tenían aumentada la actividad chitotriosidasa (P=0.004) en comparación con las controles, indicando inflamación. A consecuencia de la quimioterapia, observamos: la actividad chitotriosidasa fue reducida después del tratamiento con paclitaxel en comparación con las controles (P=0.018); la actividad de YKL-40 disminuyó también en comparación con los niveles de antes de la quimioterapia (P=0.047) y los grupos de proteínas-SH fueron significativamente reducidos después del tratamiento con antraciclinas para volver a incrementar seguidamente con paclitaxel en comparación con las controles. (P=0.010 y P=0.012 respectivamente). El efecto acumulativo de la quimioterapia se analizó comparando los niveles basales con los del parto. Encontramos un aumento de daño al ADN y de proteínas en las pacientes con PABC tal como se aprecia en los ratios 8-OHdG/2dG y o-Tyr/Phe (P=0.031; P=0.032 respectivamente). Además, observamos niveles significativamente elevados en tres metabolitos de peroxidación lipídica: 5-F2t-IsoP+5-epi-5-F2t-IsoP (P=0.031), 15-epi-2,3-dinor-15-F2t-IsoP + 2,3-dinor-11-PGF2α + 2,3-dinor-15-F2α-IsoP (P=3.72e-03) y 10-F4t-NeuroP (P=0.031), así como el biomarcador de inflamación, PGF2α (P=0.026) y el ratio antioxidante, GSH/GSSG (P=4.79e-03) en comparación con las controles. No se observó estas diferencias en los biomarcadores de daño al ADN y proteínas. Las mujeres con cáncer de mama no embarazadas, mostraron niveles elevados de daño en el ADN y proteínas (ratios 8-OHdG/ 2dG ratio; P =1.52e-03 y m-Tyr/Phe ratio; P=7.88e-04 respectivamente), pero una capacidad antioxidante reducida (GSH/GSSG ratio, P=5.67e-06) en comparación con las pacientes con PABC. Por otro lado, los recién nacidos expuestos a quimioterapia en el útero presentaron generalmente niveles más bajos de estrés oxidativo e inflamación que los controles. Excepcionalmente, encontramos incrementados los niveles plasmáticos de 15-F2T-isoP (P=8.05e-03) y los niveles urinarios de GSA (P =0.016). Por último, encontramos una correlación positiva entre los niveles de 15-epi-15-F2t-IsoP y 15-epi-2,3-dinor-15-F2t-IsoP + 2,3-dinor-11-PGF2α + 2,3-dinor-15-F2α-IsoP (R=-0.55, P=0.049 y R=-0.68, P=0.011 respectivamente) medidos en sangre de cordón de recién nacidos expuestos a quimioterapia en el útero con sus correspondientes madres al parto. En resumen, la quimioterapia durante el embarazo está significativamente asociado a una alteración del estado redox. Aun así las pacientes con PABC mostraron una alta capacidad antioxidante mientras que los neonatos no se vieron negativamente afectados. Por tanto, las complicaciones obstétricas reportadas en el estudio no fueron causadas por un aumento del estrés oxidativo e inflamación o si lo hubo, fueron eficientemente contrarrestados.
Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during pregnancy or one-year following postpartum. Chemotherapy treatment in pregnancy may aumentate the production of oxidative stress and inflammation increasing risk of obstetrics complications. For this purpose, we examined multiple oxidative stress, inflammation and antioxidant defence biomarkers in blood samples from PABC patients (N=17) prior to treatment, before each chemotherapy cycle (anthracyclines and paclitaxel) and at labour. Furthermore, the study also included blood samples from non-PABC patients (N=10) before and after treatment with anthracyclines and healthy pregnant women (N=16) as groups of control. We also assessed chemotherapy-induced oxidative stress and inflammation of neonates exposed to chemotherapy in utero using cord blood (N=13) and urine (N=5) samples. Additionally we also collected cord blood (N=14) and urine (N=6) samples from neonates born to healthy pregnant women. Overall, our data showed that PABC patients exhibited similar levels of oxidative stress and antioxidant defence markers as compared to pregnant controls before treatment with chemotherapy. However, we observed that PABC women have increase levels of chitotriosidase (P=0.004), a marker of inflammation. Following chemotherapy, some changes in oxidative stress markers and inflammation markers were found: chitotriosidase was reduced after paclitaxel as compared to healthy pregnant women (P=0.018); YKL-40 was decreased after paclitaxel as compared before treatment (P=0.047) and protein-SH groups were reduced as compared to healthy pregnant women following anthracyclines but then were again increased after paclitaxel (P=0.010 and P=0.012 respectively).The accumulative effect of chemotherapy treatment was analysed by comparing the baseline levels with those obtained at delivery, and our findings demonstrated that chemotherapy exposure during pregnancy increased the DNA and protein damage in PABC patients, as shown by an increase in 8-OHdG/2dG ratio and o-Tyr/Phe ratio, respectively (P=0.031; P=0.032). In addition, we found significant increased levels of three metabolites involved in lipid peroxidation: 55-F2t-IsoP+5-epi-5-F2t-IsoP (P=0.031), 15-epi-2,3-dinor-15-F2t-IsoP + 2,3-dinor-11-PGF2α + 2,3-dinor-15-F2α-IsoP (P=3.72e-03) and 10-F4t-NeuroP (P=0.031); as well as, PGF2α (P=0.026) metabolite of inflammation and antioxidant defence GSH/GSSG ratio (P=4.79e-03) biomarkers compared to controls at delivery. However, these differences were not observed regarding DNA and protein damage.Regarding non-PABC patients, they displayed elevated levels of DNA and protein damage markers (8-OH-dG/2dG ratio; P=1.52e-03 and m-Tyr/Phe ratio, P=7.88e-04 respectively) but reduced antioxidant capacity (GSH/GSSG ratio, P=5.67e-06) compared to PABC patients. On the other hand, neonates exposed to chemotherapy in utero generally displayed lower levels of oxidative stress and inflammation markers than neonates born to healthy women. Exceptionally, we found increased plasma levels of 15-F2f-IsoP (P=8.05e-03) and urine levels of GSA (P=0.016) compounds. Lastly, we found a positive correlation between 15-epi-15-F2t-IsoP and 15-epi-2,3-dinor-15-F2t-IsoP + 2,3-dinor-11-PGF2α + 2,3-dinor-15-F2α-IsoP (R=-0.55, P=0.049 y R=-0.68, P=0.011 respectively) in neonates with intrauterine exposure to chemotherapy and the corresponding mother. In summary, our data show that the administration of chemotherapy during pregnancy is significantly associated with a disruption of redox balance. However, PABC patients showed an elevated antioxidant capacity while the neonates were not negatively affected. Therefore, the obstetric outcomes reported in the study were not caused by an overproduction of oxidative stress and inflammation, or if increased, they were counteracted by the redox system.
Universitat Autònoma de Barcelona. Programa de Doctorat en Bioquímica, Biologia Molecular i Biomedicina
Hill, Esme. "Perfusion imaging and tissue biomarkers for colorectal cancer." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:4a309265-6f27-4839-9259-f19cf9648c2d.
Повний текст джерелаSooman, Linda. "Prognostic Biomarkers and Target Proteins for Treatment of High-grade Gliomas." Doctoral thesis, Uppsala universitet, Institutionen för radiologi, onkologi och strålningsvetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-215079.
Повний текст джерелаKoishi, Seiji. "Biomarkers in long survivors of Pediatric acute lymphoblastic leukemia Patients : late effects of cancer chemotherapyに関する研究". Kyoto University, 2000. http://hdl.handle.net/2433/151425.
Повний текст джерелаLabiad, Yasmine. "Contribution de l’approche transcriptomique dans la physiopathologie et le traitement des hémopathies malignes." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4068.
Повний текст джерелаThe aim of this research is to demonstrate transcriptomic approach contribution in the physiopathology and treatment of hematological malignancies. In particular, how microarrays technology is used to study several oncohematology difficulties; which remain deaths-related infection, as well as the failure to obtain remission and death related relapse. In the first part, our focus was to study natural killer cells (Nks) in patients affected with acute myeloid leukemia (AML). We compared transcriptomic AML-NKs signature with healthy donors-NKs signature and suggested that ETS-1 transcription factor is a good candidate able to regulate the natural cytotoxicity receptors (NCRs), whose coding genes, are located on two different chromosomes even if their expression remain strongly coordinated.Our second part, aimed to predict sepsis using a transcriptomic approach in the case of autologous stem cell transplantation (auto-HSCT). Using the same model, in the third part, we highlighted the melphalan high-dose chemotherapy effect on peripheral blood mononuclear cells and identified a potential good biomarker of early relapse in patients affected by myeloma in the case of auto-HSCT.Our final focus was to analyze gene expression profile of HIV-related large diffuse B-cell lymphoma type in order to verify the existence of subgroups described in immune-competent patients
Heinemann, Giovanna [Verfasser], and Andreas [Akademischer Betreuer] Jung. "miRNA-34, -192 und -215 sind potentielle prädiktive Biomarker für die Effektivität von Chemotherapie beim metastasierten kolorektalen Karzinom / Giovanna Heinemann ; Betreuer: Andreas Jung." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1132510848/34.
Повний текст джерелаBraman, Nathaniel. "Novel Radiomics and Deep Learning Approaches Targeting the Tumor Environment to Predict Response to Chemotherapy." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1586546527544791.
Повний текст джерелаPouessel, Damien. "Cancer de vessie : biomarqueurs associés à la rechute après chimiothérapie adjuvante et hétérogénéité de cibles thérapeutiques potentielles." Thesis, Paris Est, 2015. http://www.theses.fr/2015PESC0044.
Повний текст джерелаIntroduction: In muscle invasive urothelial carcinoma of the bladder (MI UCB), few progresses have been made in the last two decades, particularly in chemotherapy, both in localized and metastatic setting. The identification of new biomarkers that can improve the management and prognosis of patients appears essential. Such biomarkers will be clinically relevant if they can predict the response to systemic treatments. In this thesis, we studied biomarkers in two ways: (i) to identify predictive factors of relapse after cisplatin-based adjuvant chemotherapy (AC), (ii) to confirm that the molecular alterations targeted by new therapies and identified in bladder tumor are present in metastases.Objectives:(i) To examine the relationship between relapse after AC and expression of six biomarkers, ERCC1, Emmprin, Survivin, MDR1 p53 and topoisomerase IIα, in bladder tumor and / or lymph node metastases.(ii) To study the heterogeneity of FGFR3 mutations in locally advanced MI UCBMaterials and Methods: A retrospective cohort of 226 patients treated with cystectomy and AC, and tumor collection of representative samples of the primary tumor and lymph node metastases were constituted. The expression of six biomarkers was determined by immunohistochemistry on these samples and determined by morphometry. FGFR3 mutation status was determined by SNaPshot in 84 paired primary tumors and positive lymph nodes.Results: Survivals observed in the cohort were similar to those reported in the literature for patients of same stages, with tumor collection being representative of the MI UCB treated in France. None of the six biomarkers was found as an independent predictive factor of relapse after AC. FGFR3 mutation was found in 4 (4.7%) of the 84 paired samples with complete concordance between primary tumor and lymph node metastases.Conclusions: The expression of the six studied biomarkers by immunohistochemistry is not associated with risk of relapse following AC. FGFR3 mutation status is maintained during metastases process, and FGFR3 activating mutations are present in about 5% of locally advanced MI UCB. FGFR3 mutation remains a promising therapeutic target in a low subset of patients, and the evaluation of new therapies targeting the mutated FGFR3 receptor are needed. Finally, search for these mutations either in bladder tumor or in metastasis is relevant
Gay-Bellile, Mathilde. "Etude de l'instabilité génomique et du statut des télomères dans le cancer du sein." Thesis, Université Clermont Auvergne (2017-2020), 2017. http://www.theses.fr/2017CLFAS001.
Повний текст джерелаIn breast cancer, discovering new biomarkers, that can predict therapeutic response and prognosis, is important to find the best therapeutic options and improve our understanding of physiopathology. Our particular interest is in breast cancer treated by neoadjuvant chemotherapy (NCT). In pre-NCT biopsies and post-NCT tumors, we studied both telomeric parameters and DNA damage repair (DDR), because when these are dysfunctional, both result in high genomic instability. We correlated these parameters to neoadjuvant chemotherapy response and patient outcomes. First, we demonstrated that short telomeres, high telomerase (TERT) expression and low expression of ERCC1 (a protein involved in a number of DNA repair mechanisms) are markers of poor prognosis. Telomere and DDR dysfunction can contribute synergistically to tumor progression and chemoresistance. We then studied a triple negative breast cancer population. We demonstrated that short telomeres were associated with tumor aggressiveness and chemoresistance. Chemoresistance was also associated with high genomic instability. We analyzed genomic alterations specific to BRCA1-like status and demonstrated that BRCA1-like profile correlated with chemoresistance and high genomic instability. Finally, we performed a comprehensive study of telomerase reactivation in breast cancer. We demonstrated that high TERT expression in breast cancer is not associated with somatic enhancer mutations but more probably to TERT locus gains. These gains were correlated to chemoresistance and increased risk of relapse. TERT gain, combined with high MYC expression, was able to isolate a subgroup with a very poor prognosis, and this could be used to evaluate risk of relapse. Telomeric parameters and genomic instability seem to be predictive biomarkers for neoadjuvant chemotherapy response in triple negative breast cancer. These parameters also have strong prognostic value in breast cancer and could be used clinically as biomarkers for tailoring treatment
Lagrange, Anais. "Mutation de la chaperonne HSP110 et cancers MSI : étude de ses conséquences moléculaires, fonctionelles, physiopathologiques et cliniques." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066684/document.
Повний текст джерелаMSI cancers (MicroSatellite Instability) are characterized by widespread instability of DNA repeated sequences, known as microsatellites, due to MMR system (Mismatch Repair) deficiency. Since the detection of this tumor phenotype, most of the oncogenic events reported in these tumors are somatic mutations (1-2 bp insertions or deletions) that affect coding DNA repeats, resulting in frameshifts and inactivation of the corresponding proteins. They accumulate in tumor cells due to positive selection during the MSI-driven tumorigenic process when they promote tumor development by inactivating genes with tumor suppressor-related functions. This work reports the first somatic mutation of a chaperone protein in a cancer so far, i.e. HSP110 (Heat Shock Protein) in MSI colorectal cancer. This mutational event consists in the somatic deletion of the intronic microsatellite, located in the splice acceptor site of HSP110. We demonstrate that it is almost systematic and bi-allelic in these cancers, leading to inactivation of the oncogenic functions of the HSP110 chaperone (pro-apoptotic and anti-proliferative impact leading to chemosensitization of tumor cells and tumor growth decrease). Our findings support an unexpected and paradoxical anticancer impact of the microsatellite instability-driven pathway in mismatch repair-deficient colon cancer. From a pathophysiological and clinical point of view, they highlight HSP110 as a putative relevant prognostic marker (improvement of patients’ response to chemotherapy) and therapeutic target. According to these findings, I propose a therapeutic strategy targeting HSP110 and its mutant for personalized medicine of MSI colon cancer patients
Jobard, Elodie. "Identification of Systemic Markers of Cancer from NMR Metabolomic Investigation of Human Biofluids." Thesis, Lyon, École normale supérieure, 2014. http://www.theses.fr/2014ENSL0878.
Повний текст джерелаMetabolomics offers an approach based on the study of a comprehensive and dynamic metabolic response of an organism to biological stimuli or genetic mutations and thus constitutes a tool for translational research with a strong potential in oncology. We applied the metabonomic approach by high field NMR for the analysis of blood samples from clinical studies coordinated by the Centre Léon Bérard and for the prospective E3N cohort ( Etude Epidémiologique auprès de femmes de la MGEN ) in order to identify systemic cancer markers from human biological fluids . First, the statistical analysis of metabolic serum profiles from patients with breast cancer has highlighted a metabolic signature discriminating patients with localized cancer and metastatic patients and reveal biomarkers associated with severity of this cancer. Furthermore , this approach allows investigations on the effects of chemotherapy. Thus, during the study of sera from patients with metastatic renal cell carcinoma treated with experimental chemotherapy, a characteristic metabolic signature of faster modification of the host metabolism has been demonstrated for this treatment in comparison to two standard therapies. Finally, analysis of blood plasma from the E3N cohort interests the identification of biomarkers associated with the development of breast cancer and its etiology . After identification and quantification of sources of systematic variations affecting the metabolic profiles obtained, a stratified analysis of the "prospective case "- controls cohort is presented in this thesis
Landmann, Hannes. "Drug Metabolism Determines Resistance of Colorectal Cancer to Resorcinol-Based HSP90 Inhibitors." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-9928-4.
Повний текст джерелаCorreia, Bruna Filipa Campos. "Unveiling the clinical relevance of low density neutrophils in Breast Cancer patients." Master's thesis, 2020. http://hdl.handle.net/10362/114038.
Повний текст джерелаBöckmann, Lars. "Untersuchungen zur Wirksamkeit von Dacarbazin und Temozolomid bei der Behandlung des kutanen Melanoms in Assoziation mit DNA-Reparatur." Doctoral thesis, 2010. http://hdl.handle.net/11858/00-1735-0000-000D-F25D-D.
Повний текст джерелаJirásková, Kateřina. "Genetická variabilita u sporadické formy kolorektálního karcinomu: hledání nových diagnostických, prognostických a prediktivních biomarkerů." Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-410888.
Повний текст джерелаTai, Yi-Jou, and 戴依柔. "Biomarkers for prediction of chemotherapy response and survival in ovarian cancer patients." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/77776153659966865537.
Повний текст джерела國立臺灣大學
臨床醫學研究所
102
According to the 2011 annual cancer registry report in Taiwan, epithelial ovarian cancer (EOC) ranked eighth in cancer-related death and 1240 women was diagnosed in 2011 with an incidence 8.3 per 100000 women. Ovarian cancer, especially epithelial ovarian carcinoma (EOC), has become an extremely important disease in recent years because it has the highest mortality rate of all gynecological malignancies [2,3,21]. with an overall 5-year survival rate of only 20-30% [2]. It became a more and more important disease in recent years [18,27] and the incidence of ovarian cancer also increased in recent year in Taiwan. Initial evaluation for these patients includes a thorough history and physical examination, imaging studies, assessment of tumor markers (CA-125, CA-199, HE4), and/or colonoscopy and upper panendoscopy [23]. The lack of symptoms, difficulties in early diagnosis, insufficient accurate tumor markers, and lack of information about ovarian tumor biology contribute to the poor prognosis in ovarian cancer patients [9]. The prognostic parameters for ovarian carcinomas are tumor stage, histologic subtype, degree of malignancy, and residual tumor after surgical treatment [24,29]. These factors present an incomplete picture of the tumor biology of ovarian cancer and are frequently interrelated [26]. For these reasons, many patients may be delay diagnosed. Thus, the identification of new biologic factors predictive of individual disease course and prognosis would be extremely useful. From the above-mentioned data, ovarian cancer indeed is a disease that should be respected it in Taiwan. We used immunohistochemical staining combined with tissue microarray for evaluation of gene expression;combined with bioformatics with clinicopathological data in search of biomarkers related to chemotherapy response and disease prognosis
Laufs, Valeria. "Evaluation von ERCC1 als prädiktiver Biomarker bei mit platinbasierter Chemotherapie behandeltem Nebennierenrindenkarzinom." Doctoral thesis, 2019. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-180230.
Повний текст джерелаObjective: Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predictive marker for the response to PBC in ACC had reported conflicting results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to be not specific. The aim of this study was to evaluate the predictive role of ERCC1 with the new specific antibody in a larger series of ACC. Design and methods: 146 ACC patients with available FFPE slides were investigated. All patients underwent PBC (median cycles=6), including cisplatin (n=131) or carboplatin (n=15), in most cases combined with etoposide (n=144), doxorubicin (n=131) and mitotane (n=131). Immunostaining was performed with the novel ERCC1-antibody clone 4F9. The relationship between ERCC1 expression and clinico-pathological parameters, as well as best objective response to therapy and progression-free survival (PFS) during PBC was evaluated. Results: High ERCC1 expression was observed in 66% of ACC samples. During PBC, 43 patients experienced objective response (29.5%), 49 stable disease (33.6%), 8 mixed response (5.5%) and 46 progressive disease (31,5%) without any relationship with the ERCC1 immunostaining. No significant correlation was also found between ERCC1 expression and progression-free survival (median 6.5 vs 6 months, P=0.33, HR=1.23, 95%CI=0.82-2.0). Conclusion: ERCC1 expression is not directly associated with sensitivity to PBC in ACC. Thus, other predictive biomarkers are required to support treatment decisions in patients with ACC
Skálová, Helena. "Studium biomarkerů karcinomu prsu po neoadjuvantní léčbě." Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-410798.
Повний текст джерелаMartins, Rosana Fernandes. "Avaliação de Biomarcadores de resposta à terapêutica para o cancro do pulmão: Estudos in vitro." Master's thesis, 2021. http://hdl.handle.net/10316/99070.
Повний текст джерелаLung cancer worldwide is a major cause of mortality. Pathologically, lung cancer is a heterogeneous disease, classically divided into two main categories, namely NSCLC (non-small cell lung cancer) and SCLC (small cell lung cancer). NSCLC represent 85% of malignant lung cancer and are subdivided into three categories: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. The therapeutic option chosen for the treatment of any type of cancer is always dependent on the stage of the tumour at the diagnosis and on its biological characteristics. In lung cancer, this decision is a substantial challenge, since most of the patients are diagnosed at advanced stages, with a 5-years survival estimate. Thus, constant research in an area of intervention as important as cancer is unquestionably necessary. One of these areas is metabolomics, defined as the study of biological processes involving low molecular weight compounds (metabolites), present in cells or organisms, which participate in the maintenance of cellular functions. The main objective of this research project is to understand the altered metabolism of NSCLC cell lines, using metabolomics. Thus, it is intended to study changes in the metabolomic profile after different treatment regimens, namely after exposure to drugs regularly used in clinical practice within classic QT regimens (carboplatin/cisplatin) in which these are used in combination with pemetrexed and gemcitabine. In immunotherapy, namely ICPIs (immune checkpoint inhibitors) such as nivolumab and pembrolizumab, to reveal potential biomarkers.The first part of this work included the characterization of two lung cancer tumour cell lines (A549 and H1299) in terms of morphological and immunohistochemical characterization.Subsequently, the effect of different drugs and their combinations was evaluated on cell proliferation, using the study metabolic activity, through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The second part of this work aimed to quantify intra or intercellular metabolites in view of the exposure of cells to different therapies using nuclear magnetic resonance spectroscopy. Finally, to support the study of metabolomics, cell viability and the profile of cell death caused by the different therapeutic approaches studied were evaluated, using double labelling with annexin V and propidium iodide by flow cytometry. The characterization of the cell lines showed that H1299 cell line is representative of large cell carcinoma and A549 cell line is representative of adenocarcinoma. Both cell lines do not express the PD-L1 receptor (Programmed death ligand 1), so studies with ICPIs, namely nivolumab and pembrolizumab, were not followed up, as their mode of action is dependent on this receptor. The drugs and combinations, which showed greater anti-proliferative activity in the H1299 cell line, were cisplatin associated with gemcitabine. In the A549 cell line, it can be concluded that cisplatin administered alone showed greater anti-proliferative activity. Thus, the association between cisplatin and gemcitabine is seen as an excellent candidate for combination therapy, as it is associated with moderate side effects and toxicity is dependent on the dose administered. The study of cell viability did not verify that there was only a decrease of approximately 10% of viable cells, without compromising the metabolomic analysis. The technique of spectroscopy by nuclear magnetic resonance allows quantifying several metabolites and obtaining the metabolic profile of cells after exposure to different chemotherapeutic treatment regimens. In addition to the existing constraints due to the pandemic, technical issues associated with a failure in the nuclear magnetic resonance equipment in which these samples would be analyzed hampered the obtaining of the metabolomics results. Thus, the continuity of this work comprises the quantification of the metabolites present in the samples of the cell lines under study and subsequent identification of possible biomarkers in vitro and the translate this preclinical study into a clinical study, whose main objective is to validate the identification of these biomarkers in biofluids, in order to understand if they could be considered specific biomarkers for lung cancer.
O cancro do pulmão, a nível mundial, constitui uma das principais causas de mortalidade. Em termos patológicos o cancro do pulmão é uma doença heterogénea, classicamente dividida em duas categorias principais, os NSCLC (do inglês, non-small cell lung cancer) e os SCLC (do inglês, small cell lung carcinoma). Os NSCLC, representam cerca de 85% das neoplasias malignas do pulmão e subdividem-se em três subcategorias: adenocarcinoma, carcinoma de células escamosas e carcinoma de grandes células. A opção terapêutica recomendada para o tratamento de qualquer tipo de cancro é sempre condicionada pelo estádio em que se encontra o tumor no momento do diagnóstico e pelas características biológicas do mesmo. No cancro do pulmão esta tomada de decisão torna-se um desafio ainda mais substancial, já que a maioria dos doentes são diagnosticados em estádios avançados, estimando-se uma sobrevida de 5 anos. A investigação constante, numa área de intervenção tão importante como o cancro, é inquestionavelmente necessária. Uma dessas áreas é a metabolómica, definida como o estudo de processos biológicos envolvendo compostos de baixo peso molecular (metabolitos), presentes em células ou organismos, que participam na manutenção das funções celulares.O principal objetivo deste projeto de investigação foi compreender as alterações do metabolismo de células de linhas de cancro do pulmão do tipo não pequenas células, com recurso à metabolómica. Pretendemos estudar as alterações no perfil metabolómico após diferentes regimes de tratamento, nomeadamente após exposição a fármacos utilizados regularmente na prática clínica nos regimes clássicos de quimioterapia (QT) (carboplatina/cisplatina) em que estes são usados em combinação com o pemetrexede e a gemcitabina. Na imunoterapia, nomeadamente os ICPIs (do inglês immune checkpoint inhibitors), tais como o nivolumab e o pembrolizumab, foram igualmente alvo de estudo, a fim de tentar revelar potenciais biomarcadores.A primeira parte do trabalho consistiu na caracterização de duas linhas celulares tumorais de NSCLC (A549 e H1299) em termos de morfologia e de imunocitoquímica. Posteriormente, avaliou-se o efeito dos diferentes fármacos e suas combinações, na proliferação celular, recorrendo ao estudo da atividade metabólica, por espetrofotometria, através do ensaio MTT ( do inglês, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide).A segunda parte deste trabalho teve como objetivo quantificar os metabolitos intra ou intercelulares, face à exposição das células às diferentes terapias, com recurso à espetroscopia por ressonância magnética nuclear. Por último, para apoiar o estudo da metabolómica, foram avaliadas a viabilidade celular e o perfil de morte celular provocadas pelos diferentes regimes terapêuticos, com recurso à dupla marcação com anexina V e iodeto de propídeo, através da técnica de citometria de fluxo.A caracterização das linhas celulares mostrou que a linha celular H1299 é representativa do carcinoma de grandes células e a linha celular A549 é representativa de adenocarcinoma. Ambas as linhas celulares não expressam o recetor PD-L1 (do inglês, Programmed death ligand 1) pelo que não foi dado seguimento aos estudos com os ICPIs, nivolumab e pembrolizumab, visto o seu mecanismo de ação estar na dependência deste recetor. Os fármacos e as combinações que revelaram maior atividade anti-proliferativa na linha celular H1299 foram a cisplatina associada à gemcitabina. Por outro lado, na linha celular A549, concluiu-se que a cisplatina administrada isoladamente foi a que apresentou maior atividade anti-proliferativa. Assim, a associação entre a cisplatina e a gemcitabina é um excelente candidato à terapia combinada, pois está associada a efeitos adversos moderados e a toxicidade está dependente da concentração administrada.O estudo da viabilidade celular permitiu-nos verificar que apenas houve uma diminuição de aproximadamente 15% de células viáveis, não comprometendo a análise metabolómica.A técnica de espetroscopia por ressonância magnética permite quantificar diversos metabolitos e obter o perfil metabolómico das células após exposição a diferentes regimes de tratamento quimioterapêuticos. Além dos constrangimentos existentes devido à pandemia, questões técnicas associadas a uma avaria no equipamento de ressonância magnética nuclear, no qual estas amostras seriam analisadas, impediram a obtenção dos resultados da análise metabolómica. Assim, a continuidade deste trabalho prende-se com a quantificação dos metabolitos presentes nas amostras das linhas celulares em estudo e posterior identificação de possíveis biomarcadores in vitro, como também a translação deste estudo pré-clínico para um estudo clínico, cujo principal objetivo consiste na validação da identificação desses biomarcadores em biofluídos, de forma a perceber se poderão efetivamente ser considerados biomarcadores específicos para o cancro do pulmão.
Liu, Xudong. "COMBINING BIOMARKERS AND CLINICOPATHOLOGIC FACTORS FOR PREDICTION OF RESPONSE TO ADJUVANT CHEMOTHERAPY FOR BREAST CANCER: COX MODEL AND SUPPORT VECTOR MACHINE (SVM) METHODS." Thesis, 2010. http://hdl.handle.net/1974/5589.
Повний текст джерелаThesis (Master, Community Health & Epidemiology) -- Queen's University, 2010-04-27 10:16:11.811
Arrais, Débora Gomes. "Relatórios de Estágio e Monografia intitulada “Novas Estratégias Biomédicas: Modulação do Epigenoma e Terapia do Cancro"." Master's thesis, 2018. http://hdl.handle.net/10316/84634.
Повний текст джерелаO estágio curricular é a última etapa de uma formação de 5 anos conferida pelo Mestrado Integrado em Ciências Farmacêuticas na Faculdade de Farmácia da Universidade de Coimbra. É a ligação entre a formação teórica adquirida até então e a realidade prática. Este relatório pretende explicar a minha experiência do estágio realizado na Farmácia Feliz em Mangualde sob a forma de uma análise SWOT. A análise SWOT divide as experiências vividas em Pontos fortes (Strenghts); Pontos fracos (Weaknesses); Oportunidades(Opportunities); e Ameaças (Threats).O farmacêutico não está só presente na farmácia comunitária, mas em todas as etapas do medicamento e portanto é importante que a formação incida em todas essas áreas. Tive a oportunidade de realizar um estágio em indústria farmacêutica além do estágio em farmácia comunitária, único que é obrigatório no plano curricular do MICF. Este relatório pretende explicar a minha experiência do estágio realizado nos laboratórios Basi, em Mortágua, sob a forma de uma análise SWOT. A análise SWOT divide as experiências vividas em Pontos fortes (Strenghts); Pontos fracos (Weaknesses); Oportunidades (Opportunities); e Ameaças (Threats).A epigenética pode ser definida como mecanismos que modulam a expressão genéticas em alterar a sequência primária de DNA. Os três principais grupos de alterações epigenéticas que podemos enumerar são a modificação química das bases do DNA,nomeadamente a metilação do DNA por adição de um grupo metilo ao quinto carbono de uma citosina, reação esta que é catalisada pelas DNMT’s; modificações pós-translacionais de histonas e RNAs não codificantes, sendo os mais relevantes os miRNAs. O epigenoma de cada indivíduo não é, assim, constante ao longo da nossa vida, podendo ser alterado pela dieta, pelo metabolismo, ambiente, xenobióticos e, também por doença, como acontece no cancro. Com base nesse conhecimento foram desenvolvidos fármacos que atuam na maquinaria epigenética, modulando o perfil epigenético (o epigenoma) da célula como, por exemplo, DNMTi, HDACi, inibidores de acetiltransferases, demetilases e metiltrasferasesdas histonas e ainda fármacos que atuam nas proteínas reconhecedoras de marcas epigenéticas. Uma das maiores causas de insucesso no tratamento do cancro é o desenvolvimento de resistência à quimioterapia e as alterações epigenéticas podem estar na base de alguns casos. Fármacos epigenéticos estão a ser associados às quimioterapias mais clássicas para contornar este problema e aumentar e eficiência do tratamento. Por outro lado, o diagnóstico precoce é mais uma ferramenta que pode aumentar a taxa de sucesso do tratamento do cancro por isso é importante o estudo de biomarcadores que sejam específicos, precoces e o menos invasivos possível e aqui, mais uma vez, a epigenética releva a sua importância nas futuras direções da ciência. Neste trabalho discutem-se novas estratégias biomédicas que utilizam a modificação do epigenoma com vista à terapia do cancro.
The curricular internship is the last stage of a 5-year training conferred by theIntegrated Master's Degree in Pharmaceutical Sciences at the Faculty of Pharmacy of theUniversity of Coimbra. It is the link between the theoretical training acquired up until thenand the practical reality. This report is meant to explain my experience from the stage heldat Farmácia Feliz in Mangualde in the form of a SWOT analysis. The SWOT analysis dividesthe lived experiences in Strenghts; Weaknesses; Opportunities and Threats.The pharmacist is not only present in the community pharmacy, but in all drug stagesand therefore it is important that the training focuses on all these areas. I had theopportunity to undertake an internship in the pharmaceutical industry beyond the internshipin community pharmacy, which is the only mandatory in the curricular plan of the MICF. Thisreport is meant to explain my experience from the stage held at Laboratórios Basi in Mortáguain the form of a SWOT analysis. The SWOT analysis divides the lived experiences inStrenghts; Weaknesses; Opportunities and Threats.Epigenetics can be defined as the mechanisms that modulate gene expression but don’talter the primary DNA sequence. The three major groups of epigenetic changes that can beenumerated are the chemical modifications of DNA bases, namely DNA methylation, byaddition of a methyl group to the fifth carbon position of a cytosine, reaction catalyzed byDNMT’s; posttranslational changes of histones and non-coding RNAs, the most relevantbeing miRNAs. The epigenome of each isn’t constant throughout life, it can be altered, byseveral factors, including diet, environment, xenobiotics, metabolism and by disease states.Based on that knowledge, new drugs that act in the epigenetic machinery have beendeveloped to modulate the epigenome, such as DNMTi, HDACi, acetyltransferases,demethylases and methyltransferases inhibitors as well and drugs that act on epigeneticreader proteins. One of the biggest causes of failure in the cancer treatments is theresistance to chemotherapy and epigenetic alterations may be one of the underlying causes.Epigenetic drugs are being associated with more classical chemotherapy drugs to circumventthis problem and increase the efficiency of the treatment. The early diagnosis is an importanttool to increase the rate of success in the cancer treatment and because of this is importantthe study of biomarkers that are specific and less invasive as possible, and here again, theepigenetics reveals its importance in the future directions of science. In this work wesummarize these new avenues of biomedical research with emphasis in the epigeneticsapproaches to cancer therapy.
Abreu, Miguel Maciel. "Tumores de células germinativas do testículo: Análise retrospetiva dos doentes tratados no Centro Hospitalar e Universitário de Coimbra entre 2009-2016." Master's thesis, 2017. http://hdl.handle.net/10316/82602.
Повний текст джерелаObjectives: Analyse the results of the treatment of Testicular Germ Cell Tumours (TGCT) patients orchiectomized at Centro Hospitalar e Universitário de Coimbra (CHUC) over a period of seven years, comparing the results with international data and previous studies (1990-2009) regarding CHUC. Identify new factors that justify the increase in worldwide incidence values described in the literature and new prognostic approaches based on tumoural biomarkers.Methods: 77 clinical registries were analysed, corresponding to the patients orchiectomized due to suspect of testicular cancer, diagnosed with TGCT, between January 2009 and November 2016 at CHUC. For comparison of diagnosis, treatment and follow-up, the European Association of Urology’s 2016 guidelines were followed.Results: An average of 11 surgeries per year were performed, with a mean age of 32.9 years (17-58). The seminomas had a mean age of 35.8 years (29-51) and non-seminomatous (NSGCT) 31 years (17-58). Testicular prosthesis was inserted in 48 (62.3%) cases. Regarding the histopathological diagnosis, 47 (61%) were classified as NSGCT and 30 (39%) as seminoma. Metastasis were detected in 24 (31.2%) of the cases, 20 (83.3%) of them corresponding to NSGCT. According to the 2009 TNM classification, 67.5% were staged as stage I, 14.3% stage II and 18.2% as stage III. Stage I seminomas were treated mainly with a single cycle of Carboplatin (11 patients, 40.1%) as well as active surveillance (also 40.1%). In stage II and III seminomas and NSGCT stage I, II and III the most frequent first adjuvant therapy was chemotherapy with BEP. One seminoma (3.7%) and four (8.5%) NSGCT required second-line chemotherapy. A statistically significant correlation between survival and post-orchiectomy values, absolute and percentual variation of β-HCG was found (respectively p=0.01, ρ=0.384; p=0.003, ρ=0.355; p=0.004, ρ=0.337). Complete remission was achieved in 79.2% of the sample, with relapse in six (7.8%) patients and death after refractory disease in seven (9.1%) patients. Disease free survival was on average 33.9 months All patients treated with second-line chemotherapy died, with a mean survival time of 10.8 months (7-17). Survival at the of the first year was achieved in 96% of the patients and 90% at the end of third and fifth (Seminoma:100%, 96%, 96%; NSGCT: 93%, 85%, 85%).Discussion and Conclusions: There was an average of 11 cases per year (comparatively to 4.5 from 1990 e 2009). The sample mean age increased, from 30.1 to 32.9 years, due to the increase in NSGCT mean age (27.1 to 31.0). There was an increase in the adhesion to the testicular prosthesis (42.2% to 62.3%). Compared to the previous study, we found a higher rate of diagnosis at earlier stages (NSGCT stage III decreased from 42.9% to 27.7%; stage I seminomas increased from 79.3% to 90%). Based on the statistically significant correlation between the variation β-HCG and survival, we propose that, when interpreted by itself, a decrease in β-HCG may be considered a predictor of patient’s survival. When compared to previous studies, a higher rate of survival was attained but still inferior the internationally published data. In localized and regional disease, the 5-year survival of 100% was superior to the described in the literature.
Objetivos: Analisar os resultados do tratamento de Tumores de Células Germinativas do Testículo (TCGT) orquidectomizados no Centro Hospitalar e Universitário de Coimbra (CHUC) num período de sete anos comparando-os com o panorama internacional e estudos anteriores (1990-2009) desenvolvidos no CHUC. Identificar novos fatores que justifiquem o aumento da incidência mundial descrito na literatura e novas abordagens prognósticas a partir dos biomarcadores tumorais.Métodos: Foram analisados 77 processos clínicos, correspondentes aos doentes orquidectomizados por suspeita de tumor testicular, diagnosticados com TCGT entre janeiro de 2009 e novembro de 2016 no CHUC. Para comparação do diagnóstico, tratamento e seguimento foram seguidas as recomendações de 2016 da Associação Europeia de Urologia.Resultados: Foram realizadas, em média, 11 cirurgias por ano, com uma média de idades de 32,9 anos (17-58). Os seminomas apresentaram uma média de idades de 35,8 anos (29-51) e os Não Seminomatosos (TCGNS) 31 anos (17-58). Foi colocada prótese testicular em 48 (62,3%) casos. No diagnóstico histopatológico, 47 (61%) foram classificados como TCGNS e 30 (39%) como seminoma. Foi detetada doença metastática em 24 (31,2%) casos, correspondendo 20 (83,3%) a TCGNS. De acordo com a classificação TNM 2009, 67,5% dos tumores foram estadiados como estadio I, 14,3% estadio II e 18,2% estadio III. No tratamento dos seminomas estadio I, as estratégias mais usadas foram um ciclo de Carboplatina em 11 (40,1%) casos e vigilância ativa no mesmo número (40,1%). Nos seminomas estadio II e III e TCGNS estadio I, II e III a primeira terapêutica adjuvante mais frequente foi quimioterapia com BEP. Um (3,7%) seminoma e quatro (8,5%) TCGNS necessitaram de terapêuticas de segunda linha. Observou-se uma correlação estatisticamente significativa entre a sobrevivência e a variação absoluta, percentual e o valor β-HCG pós-orquidectomia (respetivamente p=0,003, ρ=0,355; p=0,004, ρ=0,337; p=0,01, ρ=0,384). Foi alcançada remissão completa em 79,2% da amostra estudada, ocorrendo recidiva em seis (7,8%) e óbito após doença refratária ao tratamento em sete (9,1%) doentes. Registámos uma sobrevivência média livre de doença de 33,9 meses. Todos os doentes que necessitaram de quimioterapia de segunda linha faleceram, com sobrevivência média de 10,8 meses (7-17). Observámos sobrevivência ao fim do primeiro ano de 96% e 90% ao fim de três e cinco anos (Seminomas: 100%, 96%, 96%; TCGNS: 93%, 85%, 85%).Discussão e conclusão: Registámos, em média, 11 casos por ano (comparativamente a 4,5 entre 1990 e 2009). A idade média da amostra aumentou, de 30,1 para 32,9 anos, à custa do aumento da idade nos TCGNS (27,1 para 31,0). Também na adesão à prótese testicular encontrámos um aumento (42,2% para 62,3%). Verificou-se uma maior taxa de diagnósticos em estadios mais precoces (TCGNS estadio III: 42,9% para 27,7%; seminomas estadio I: 79,3% para 90%). Com base na correlação estatisticamente significativa entre a variação da β-HCG e a sobrevivência, propomos que, quando interpretada isoladamente, uma diminuição da β-HCG possa ser considerada um preditor da sobrevivência do doente. Registou-se uma taxa de sobrevivência superior aos estudos anteriores, mas ainda inferior aos dados publicados internacionalmente. Na doença localizada e regional, a sobrevivência de 100% a 5 anos registada, supera o descrito na literatura.
Abboud, Olivier-Michel. "Rôles de K-RAS et de ERCC1 dans le traitement des carcinomes épidermoïdes avancés de la tête et du cou traités par chimioradiothérapie concomitante." Thèse, 2012. http://hdl.handle.net/1866/9178.
Повний текст джерелаBackground: RAS gene mutations have been shown to occur in certain malignancies and have an impact treatment response and overall prognosis. Excision repair cross- complementation group 1 (ERCC1) is a gene implicated in deoxyribonucleic acid (DNA) repair, whose polymorphism at codon 118 has been linked to treatment response. Studies of these two genes in head and neck oncology literature have shown inconsistent results. Objectives: Determine the influence of K-RAS mutations (codons 12 and 13) and the polymorphism of ERCC1 codon 118 in patients with locally advanced head and neck cancer treated with concomitant platinum-based chemoradiation therapy. Methods: DNA extraction from paraffin-embedded biopsy specimens of patients with advanced head and neck squamous cell carcinoma treated with concomitant chemoradiation and followed prospectively for at least two years. Identification of K- RAS mutations (codons 12 and 13) and ERCC1 codon 118 polymorphism in the extracted DNA. Correlation of these markers with treatment response. Results: K-RAS codon 12 mutations were associated with a worse locoregional control than tumors without any mutations (32% vs 83% p=0.03); however, mutational status did not influence overall survival. No K-RAS codon 13 mutation was identified in our specimens. The different ERCC1 polymorphisms did not have an impact on treatment response. Conclusion: K-RAS mutational status (codon 12 and 13) and ERCC1 codon 118 polymorphism does not seem to discriminate between patients for whom another treatment option should be sought in patients with locally advanced head and neck squamous cell carcinoma.