Дисертації з теми "Chemotherapy role"
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Allen, W. L. "The role of Fas in response to chemotherapy." Thesis, Queen's University Belfast, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403264.
Повний текст джерелаTran, Cuong Duy. "Intestinal zinc and metallothionein : role in chemotherapy-induced mucositis." Title page, contents and abstract only, 2001. http://web4.library.adelaide.edu.au/theses/09PH/09phc9736.pdf.
Повний текст джерелаBowen, Joanne Marie. "Chemotherapy-induced intestinal mucositis the role of apoptosis regulators /." Click here to access, 2006. http://thesis.library.adelaide.edu.au/public/adt-SUA20060831.142913/index.html.
Повний текст джерелаIncludes author's previously published papers. "March 2006" Bibliography: leaves 168-191. Also available in a print form.
Khongkow, Pasarat. "The role of FOXM1 in breast cancer chemotherapy resistance." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/42884.
Повний текст джерелаSimpson, Julie Ann. "The role of population pharmacokinetic- pharmacodynamic modelling in antimalarial chemotherapy." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367218.
Повний текст джерелаGustafson, Heather Lynn. "Role of Manganese Superoxide Dismutase in Chemotherapy-induced Oxidative Stress." Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/203510.
Повний текст джерелаKwan, Stanley. "The role of ASK1 in arsenic trioxide-induced cell death." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114442.
Повний текст джерелаL'arsenic trioxyde (ATO) est un traitement efficace contre la leucémie promyélocitaire aïgue (APL). Alors qu'il est testé dans le cadre de plusieurs essais cliniques sur différents cancers comme le myélome multiple, le syndrome myélodysplasique, le lymphome et les tumeurs solides, il ne montre qu'une efficacité limitée en tant qu'agent unique. Quoiqu'il en soit, il pourrait être prometteur au sein d'une thérapie combinée. Ainsi, l'étude des mécanismes d'action responsables des bénéfices cliniques apportés par l'arsenic trioxide pourrait mener à la mise au point de nouvelles thérapies combinées afin d'élargir le spectre thérapeutique d'ATO. Des travaux antérieurs ont décri une voix de signalisation, requise pour l'induction de l'apoptose par l'arsenic dans des cellules d'APL, qui implique la génération d'espèces actives de l'oxygène (ROS), ainsi que l'induction subséquente d'une cascade de protéine kinases mitogène-activées (MAPK) spécifique qui inclut à la fois la protéine kinase stress-activée (SAPK)/ERK kinase 1(SEK1) ainsi que l'activation de la kinase c-jun N-terminal (JNK). Néanmoins, le lien entre la production de ROS et l'activation de SEK1 reste à être élucidé. La kinase de signalisation de l'apoptose (ASK1) est une MAP3K en amont de SEK1 qui a été impliquée dans l'induction de la signalisation induite par le stress. En utilisant des fibroblastes d'embryions de souris (MEFs) dérivées de souris ASK-/-, nous montrons qu'ASK1 est un médiateur fort de l'apoptose et de l'activation de JNK par ATO. Dans une lignée cellulaire APL, nous montrons qu'ATO active ASK1 en fonction du temps et de la dose. Par contre, une sous-régulation d'ASK1 dans des cellules APL augmente la susceptibilité envers ATO, ce qui se traduit par une diminution de la croissance et une augmentation de l'apoptose par rapport aux cellules APL sauvages. Un impact similaire est observé lors d'une sous régulation de SEK1, une MAP2K directement en aval d'ASK1, ainsi que lors d'une sous régulation d'ASK1 dans des cellules MCF-7, des cellules de cancer du sein humain. Cela nous a conduit à postuler qu'ASK1 a une fonction pro-apoptotique dans les fibroblastes non-transformés, mais anti-apoptotique dans des cellules malignes. En effet, la transformation des cellules MEFs ASK-/- a restauré leur sensibilité envers l'arrêt de la croissance et l'apoptose induits par ATO, ce qui souligne les différences entre les cellules normales et les cellules transformées. Dans l'ensemble, ces résultats suggèrent qu'ASK1 a un rôle important dans la sensibilité à l'ATO qui dépend du contexte. Un des schémas de régulation d'ASK1 suggère qu'ASK1 est séquestré sous une forme inactive par la thioredoxine-1 réduite (Trx1). Durant le stress oxydatif, Trx1 est oxydée et libère ASK1 afin qu'il puisse être activé. L'immuno-précipitation d'ASK1 suivie d'un immuno-marquage for Trx1 dans des cellules APL montre une association basale forte qui est perdue lors du traitement avec ATO. De plus, l'activité de la réductase de la thioredoxine (TrxR1), une enzyme qui convertit Trx1 oxydée en Trx1 réduite, est diminuée de façon significative après traitement avec ATO. Cela suggère qu'ATO active la signalisation d'ASK1 en oxydant Trx1, via les ROS, ainsi qu'en inhibant la réduction de Trx1 en diminuant l'activité de TrxR1. De plus, nous montrons que l'inhibiteur de TrxR1, Auranofin, sensibilise les cellules APL à l'apoptose induite par ATO. Cela suggère que la régulation d'ASK1 dépend du statut redox de Trx1. Dans l'ensemble, nos résultats suggèrent que le fait de cibler Trx1 pourrait augmenter la signalisation d'ASK1 et l'apoptose induite par ATO au sein d'une nouvelle thérapie combinée.
Wong, Chung-lim, and 黃仲廉. "The role of GEP on chemotherapy induced alterations in hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197132.
Повний текст джерелаpublished_or_final_version
Surgery
Doctoral
Doctor of Philosophy
McDermott, Ultan. "The role of Fas in chemotherapy-induced colorectal cancer cell death." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426703.
Повний текст джерелаGomes, Ana Rita. "The role and regulation of FOXO3a in cancer and chemotherapy resistance." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/14582.
Повний текст джерелаAl, Alami Usama Akram. "The role of nitric oxide in tumour biology." Thesis, University of Wolverhampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327151.
Повний текст джерелаGovender, Yogeshni. "The role of short-term starvation in sensitizing breast cancer to chemotherapy." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/80007.
Повний текст джерелаENGLISH ABSTRACT: Introduction: Breast cancer is a major contributor to mortality in women worldwide. Although, anthracyclines, such as doxorubicin, are among the most valuable treatments for breast cancer, their clinical use is limited due to detrimental side-effects such as cardiotoxicity. Additionally, evidence suggests that cancer cells are becoming increasingly resistant to chemotherapeutic agents. The consequence of poor vascularisation within tumours subsequently leads to a nutrient deprived microenvironment which cancer cells are known to adapt to via metabolic remodelling and increasing autophagy. Autophagy is an intracellular degradation system, which is induced as a survival mechanism in response to starvation and other environmental stressors. Recent studies have shown that starvation protects non-tumourigenic cells against chemotherapy-induced cell death. Furthermore, patients who starved prior to chemotherapy reported reduced side-effects. However, these studies investigated the effects of long-term starvation, which maybe clinically challenging. Therefore, this concept, under shorter and more tolerable periods of starvation still needs to be investigated. We hypothesis, that short-term starvation will sensitize breast cancer cells to doxorubicin-induced cell death. In order to test this hypothesis this study was approached by the following aims: (i) to establish a time point at which MCF12A breast epithelial cells are protected against starvation; (ii) to determine the effect of short-term starvation on doxorubicin induced cell death; (iii) to assess autophagy and; (iv) to assess these above mentioned aims using an in vivo model. Methods: MDAMB231 cells and MCF12A cells were starved for 0, 3, 6, 12, 24 and 48 hours using Hanks Balanced Salt Solution. Cell viability was assessed using the trypan blue, MTT and Caspase-Glo assays. MDAMB231 cells and MCF12A cells were subjected to the following conditions: (1) control; (2) 5 μM doxorubicin; (3) starvation of 3 hours and (4) a combination of starvation and doxorubicin. Following treatment an MTT assay to assess cell viability was performed. MDAMB231 cells were further examined using Live-Cell Imaging and western blot analysis. C57BL6 tumour bearing mice were treated with doxorubicin (5 mg/kg) or in combination with starvation of 24 hours. Upon termination of the protocol, tumour tissue was assessed using western blot analysis. In both in vitro and in vivo analyses cleaved-caspase 3 and cleaved-PARP were used as markers for apoptosis, LC3 and p62 as autophagic markers and p-AMPK and p-mTOR as markers of oxygen and energy sensing, respectively. Results and discussion: Three hours of starvation was chosen for in vitro experiments since no significant reduction in cell viability or increases in apoptosis occurred at this time-point in the normal MCF12A breast epithelial cells. As expected, doxorubicin induced a significant decrease in cell viability in the cancerous MDAMB231 cells. Short-term starvation in combination with doxorubicin treatment caused a further significant decrease in cell viability in MDAMB231 cells compared to the doxorubicin group alone. Interestingly, starved MCF12A cells were protected against doxorubicin-induced cytotoxicity as cell viability significantly increased. A significant decrease in autophagy was further observed with the combined treatment of doxorubicin and starvation which corresponded with a significant increase in cell death. In contrast, although the in vivo study also demonstrated a significant elevation in cell death and autophagy in response to doxorubicin treatment, the combined treatment (starvation and doxorubicin) did not have an additive effect when compared to the doxorubicin group alone. Conclusion: Our in vitro results clearly demonstrate that short-term starvation sensitizes breast cancer cells to doxorubicin-induced cell death. Additionally, decreased levels of autophagy appear to contribute to this phenomenon of sensitization. Although doxorubicin treatment resulted in increased apoptosis in vivo, 24 hours starvation in combination with doxorubicin did not sensitize the tumours to doxorubicin treatment. Thus, for future in vivo studies more time points should be considered in order to translate the beneficial effects of short-term starvation observed in our in vitro study to an animal model.
AFRIKAANSE OPSOMMING: Inleiding: Borskanker is ‘n belangrike faktor wat bydrae tot sterftes in vrouens wêreldwyd. Alhoewel antrasikliene soos doxorubicin, waardevol is vir die behandeling van borskanker, word die kliniese gebruik daarvan beperk deur newe-effekte soos kardiotoksisiteit. Verder, word daar al hoe meer bewys dat kankerselle toenemend weeerstandbiedend word teen chemoterapeutiese middels. Swak vaskularisasie van tumore lei tot ‘n mikro-omgewing met beperkte voedingstowwe waaby kankerselle kan aanpas deur middel van metaboliese hermodelering en ‘n toename in autofagie. Autofagie is ‘n intrasellulêre degraderingsisteem wat as ‘n oorlewingsmeganisme aangewend word tydens verhongering en ander omgewingstressors. Onlangse studies het getoon dat verhongering nie-tumourigeniese (normale) selle teen chemoterapie-geïnduseerde seldood beskerm. Verder is daar ook geraporteer dat pasiënte wat gevas het voor chemoterapie, verminderde newe-effekte getoon het. Hierdie studies het egter gefokus op ‘n relatief lang-termyn vas, wat klinies nogal uitdagend kan wees. Daarom moet hierdie konsep nog op korter, meer hanteerbare tye getoets word. Ons hipotese is dus dat kort-termyn vas borskankerselle kan sensitiseer tot doxorubicin-geïnduseerde seldood. Om hierdie hipotese te toets, is die volgende doelwitte gestel: (i) om ‘n tydspunt te bepaal waar MCF12A borsepiteelselle beskerm is teen verhongering; (ii) om die effek van kort-termyn verhongering op doxorubicin-geïnduseerde seldood te toets; (iii) om autofagie te karakteriseer in ons model en; (iv) om hierdie doelwitte ook in ‘n in vivo model te toets. Metodes: MDAMB231 en MCF12A selle is verhonger vir 0, 3, 6, 12, 24 and 48 ure deur van Hanks se gebalanseerde soutoplossing gebruik te maak. Sellewensvatbaarheid is bepaal deur middel van trypan blou, MTT en die Caspase-Glo tegnieke. MDAMB231 en MCF12A selle is onderwerp aan die volgende omstandighede: (1) kontrole; (2) 5 μM doxorubicin; (3) verhongering van 3 ure en (4) ‘n kombinasie van verhongering en doxorubicin. Na behandeling is die sellewensvatbaarheid deur middel van die MTT tegniek bepaal. MDAMB231 selle is verder ondersoek deur middel van “Live-Cell Imaging” en die westelike klad tegniek. C57BL6 tumor-draende muise is behandel met doxorubicin (5 mg/kg) of met ‘n kombinasie van verhongering van 24 ure en doxorubicin. Aan die einde van die protokol, is die kankerweefsel geanaliseer deur die westelike klad tegniek. In beide in vitro en in vivo analises, is gekliefde- caspase 3 en -PARP as merkers vir apoptose, LC3 and p62 as merkers vir autofagie en p-AMPK en p-mTOR as suurstof- en energie sensors respektiewelik gemeet. Resultate en bespreking: Vir die in vitro eksperimente, is ‘n tydspunt van 3 ure gekies as gevolg van die feit dat geen afname in sellewensvatbaarheid en ‘n toename in apoptose in hierdie tydsgleuf tydens verhongering in die normale MCF12A borsepiteelselle plaasgevind het nie. Soos verwag, het doxorubicin behandeling ‘n insiggewende afname in sellewensvatbaarheid in die kankeragtige MDAMB231 selle veroorsaak. Die kombinasie-terapie van verhongering en doxorubicin het ‘n verdere verhoging in seldood teweeg gebring in die MDAMB231 selle, maar het die normale MCF12A borsepiteelselle teen doxorubicin-geïnduseerde toksisiteit beskerm. Die kombinasie-behandeling is ook geassosieer met ‘n afname in autofagie. Alhoewel, die in vivo studie ook getoon het dat doxorubicin alleen insiggewende hoeveelheid seldood teweeggebring het, het die kombinasie-behandeling nie die additiewe effek, soos in die in vitro studie, teweeg gebring nie. Gevolgtrekking: Die in vitro resultate het duidelik getoon dat kort-termyn verhongering borskankerselle kan sensitiseer vir doxorubicin terapie. Verder het dit geblyk dat ‘n afname in autofagie tot die fenomeen van sensitisering bygedrae het. Alhoewel doxorubicin behandeling in vivo tot ‘n toename in apoptose in die tumor gelei het, het die kombinasie behandeling nie die kankerweefsel ten op sigte van doxorubicin gesensitiseer nie. Daar sal dus vir toekomstige in vivo studies meer tydsgleuwe van behandeling ondersoek moet word om die optimum verhongeringsperiode te vind sodat die in vitro resultate ook in vivo van toepassing kan wees.
NRF and CANSA for financial support
Kondratska-Klymenko, Kateryna. "Role of calcium-permeable channels in pancreatic ductal adenocarcinoma resistance to chemotherapy." Thesis, Lille 1, 2015. http://www.theses.fr/2015LIL10099/document.
Повний текст джерелаPancreatic ductal adenocarcinoma (PDAC) representing the most prevalent pancreatic neoplasm accounting for about 90% of all pancreatic tumors, is one of the leading causes of cancer death in men and women. The current five-year relative survival rate is about 6% . One of the reasons of this is that early stage pancreatic cancer usually has no symptoms and thus the majority of cases are diagnosed at the late metastatic or invasive stages which are not suitable for surgery. Pancreatic cancer cells have been shown to exhibit a number of genetic mutations leading to uncontrolled cell proliferation, as well as evasion of programmed cell death (apoptosis). Changes in the cytosolic free Ca2+ concentration, play a central role in many fundamental cellular processes and disturbance of the Ca2+ homeostasis regulatory mechanisms leads to a vast variety of severe pathologies, including cancer. Among these, store-operated calcium channels (SOCs) have been shown to regulate a variety of calcium dependent cellular processes altered in different cancers. However, although the role of Ca2+ and calcium-permeable channels is well established in many signaling pathways in a variety of cell types, the information of the role of calcium-permeable channels in PDAC cells is limited. Therefore, identification of the molecular nature as well as functions of calcium-permeable channels in these cells is of great importance as it can reveal novel approaches for treating pancreatic cancer through targeting calcium-dependent processes
Weaver, Andrew. "Dose intensive chemotherapy in ovarian cancer and the role of stem cell factor." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287931.
Повний текст джерелаWilson, T. R. "The role of c-FLIP in mediating resistance to chemotherapy in colorectal cancer." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426918.
Повний текст джерелаKennedy, R. D. "Investigation of the role played by BRCA1 in modulating the response to chemotherapy." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411374.
Повний текст джерелаLo, Maisie K. Y. "Role of transporters in pancreatic cancer drug resistance." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/361.
Повний текст джерелаFinn, Nnenna Adimora. "Role of redox systems in doxorubicin metabolism and doxorubicin-mediated cell signaling: a computational analysis." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/41149.
Повний текст джерелаDoherty, J. E. "The role of ADAM 17 in regulating resistance to Chemotherapy Treatment in Colorectal Cancer." Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527684.
Повний текст джерелаTse, Tak-fong, and 謝德芳. "Role of RON activation on chemoresistance in gastric cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38592253.
Повний текст джерелаYang, Sitian, and 楊斯恬. "Novel role of drug-induced non homologous end joining factor 1 in the chemoresistance of hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2015. http://hdl.handle.net/10722/209505.
Повний текст джерелаHasim, Mohamed Shaad. "The Role of Activating Transcription Factor 3 as a Regulator of DNA-Damaging Chemotherapy Cytotoxicity." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39897.
Повний текст джерелаErrington, Fiona. "An investigation into the cytotoxic mechanisms of DNA topoisomerase II poisons and catalytic inhibitors : the role of DNA topoisomerase II alpha and beta." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340718.
Повний текст джерелаTai, Kin-ki Emily, and 戴健琦. "Defining the protective role of cathelicidin on ulcerative colitis in mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B40203542.
Повний текст джерелаCarser, J. C. "The role of BRCA1 as a marker of clinical outcome following chemotherapy in sporadic ovarian cancer." Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517246.
Повний текст джерелаHotama, Peggy Yulia [Verfasser]. "The role of Herpes Simplex Virus in chemotherapy-induced Mucositis in pediatric patients / Peggy Yulia Hotama." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052530168/34.
Повний текст джерелаHall, Andrew G. "The role of glutathione S-transferases in the development of resistance to chemotherapy in lymphoid malignancies." Thesis, University of Newcastle Upon Tyne, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287172.
Повний текст джерелаSobhakumari, Arya. "Dual Role of Oxidative Stress in Head and Neck Cancer Chemotherapy: Cytotoxicity and Pro-survival Autophagy." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/4913.
Повний текст джерелаYao, Jia. "Synthesis of silver nanoparticles and their role against a thiazolekinase enzyme from Plasmodium falciparum." Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1020894.
Повний текст джерелаSantos, Cravo Ana Maria. "The role of epithelial cell de-differentiation in the context of improved chemotherapy applied to pancreatic cancer." Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.642055.
Повний текст джерелаRodrigues, Andréia Catarina Dias. "Predictive factors for chemotherapy-induced oral mucositis in colorectal cancer patients: role of inflammatory related genes polymorphisms." Master's thesis, Instituto de Ciências Biomédicas Abel Salazar, 2008. http://hdl.handle.net/10216/9150.
Повний текст джерелаForestrania, Roshamur Cahyan. "Secondary Metabolites from Garcinia daedalanthera Pierre Leaves and Their Role in Cancer Chemotherapy and Chemoprevention." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1557191838034824.
Повний текст джерелаMiddleton, Justin David. "Defining the early stages of chemotherapy-exacerbated cancer colonization of the lung: A role for host-ATF3." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1594999911940819.
Повний текст джерелаRodrigues, Andréia Catarina Dias. "Predictive factors for chemotherapy-induced oral mucositis in colorectal cancer patients: role of inflammatory related genes polymorphisms." Dissertação, Instituto de Ciências Biomédicas Abel Salazar, 2008. http://hdl.handle.net/10216/9150.
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 джерелаIngram, Judy. "An explanation of the role of family participation in a medication information program on schizophrenic clients' medication adherence behaviors." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/276561.
Повний текст джерелаHassan, Mohammed Hashim Abdalraheem. "Characterization of ATP-binding cassette drug transporters and their role in breast cancer treatment using in silico approach." University of the Western Cape, 2019. http://hdl.handle.net/11394/7255.
Повний текст джерелаBreast cancer is the most common cancer in women worldwide, and is the second most common cancer in the world, responsible for more than 500 000 deaths annually. Estimates are that 1 in 8 women will develop breast cancer in their lifetime. In South Africa, breast cancer in women affects about 16.6 % of the population and could see a 78 % increase in cases by 2030. Comprehensive therapy on breast cancer including surgical operation, chemotherapy, radiotherapy, endocrinotherapy, etc. could help, but still has serious side effects. The Chemotherapy resistance against anticancer drugs is an emerging concern. Biomarkers have been identified as a viable option for early detection and progression of disease. Examples of biological indicators for disease could be the ATP-binding cassette (ABC) drug transporters that utilizes the energy derived from ATP hydrolysis to efflux many chemically diverse compounds across the plasma membrane, thereby playing a critical and important physiological role in protecting cells from xenobiotics. These transporters are also implicated in the development of multidrug resistance (MDR) in cancer cells that have been treated with chemotherapeutics. High expression of these membrane proteins as a family of ABC drug transporters are one of the main reasons for drug resistance by increasing the efflux rate of the anti-cancer drug from cancer cells. ABC drug transporters are considered to be one of the largest protein families in living organisms. There are 48 genes in the human genome that encode ABC transporters, which are divided into seven subfamilies (ABCA-ABCG). Studies revealed that ABC transporter genes has been shown to be associated with tumour development, progression and response to therapy, suggesting their possible use as diagnostic, prognostic and predictive biomarkers. The aim of this study was to investigate and identify novel ABC transporter genes that could be implicated in breast cancer and MDR and potentially would be a therapeutic target for successful chemotherapy treatment and disease progression and survival in breast cancer patients. An in silico approach was used to identify 10 ABC transporter genes (ABCB2, ABCB9, ABCB10, ABCC1, ABCC4, ABCC5, ABCC10, ABCC11, ABCC12, ABCD1) implicated in breast cancer by conferring drug resistance through over-expression in cancer cells. The in silico study investigated the tissue expression specificity, protein interaction/s, pathways, and comparative toxicogenomics of the identified ABC transporter genes using several computational software such as Tissue-specific Gene Expression and Regulation (TiGER), the Human Protein Atlas (HPA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and The Comparative Toxicogenomics Database (CTD). The 48 ABC transporter genes were shortlisted through very selective criteria that narrowed the genes down to 10. Differential expression analysis of the genes using TiGER and HPA compared expression in normal versus cancerous tissue of the candidate genes. The result showed that ABCC11 was preferentially expressed in breast tissue with an enrichment value higher than 10.0. The results also showed ABCC10 overexpressed in breast cancer tissue, making these two genes top candidates for further analysis. Result from STRING database showed a strong functional interaction network between the prioritized genes through protein homology, co-expression and text mining as evidence for the observed interactions. Furthermore, the prioritized list of genes was submitted to the CTD for intersectional analysis to obtain the toxicity relationship between the genes and the Tamoxifen as the first line chemotherapeutic treatment for breast cancer. Venn diagrams obtained from CTD showed intersectional relation between ABCB2, ABCC1, ABCC4, ABCC11, and ABCD1 genes and Tamoxifen. Furthermore, an in silico validation of the prognostic/predictive values of the 10 prioritized genes (list 2) was carried out using an online biomarker validation tool and database for cancer gene expression data using survival analysis (SurvExpress) and gene expression based survival analysis web application for multiple cancer (PROGGENE). Results obtained from the PROGGENE survival and predictive analysis showed good prognostic values for the genes ABCB2, ABCC1, ABCC4, ABCC10 and ABCC12 with their significance measured by the probability value (Pv) (0.053, 0.001118, 0.01286, 0.00604, 0.00157 respectively). From this study ABCC1, ABCC4, ABCC5, ABCC10, and ABCC11 genes could serve as putative therapeutic target biomarkers for breast cancer treatment following further in depth analysis. However, the variance in the effectiveness of individual genes suggests that the set of genes would perform better than individual gene in the management of breast cancer. The modulating roles of ABCC4, ABCC5 ABCC10, and ABCC11 in drug induced apoptosis, suggest they could probably play an important role in personalized medicine and could serve as biomarkers to monitor the prognosis and/or therapeutic outcome of chemotherapy drugs in breast cancer patients. The use of modern genomics, proteomics, bioinformatics, and systems biology approaches has resulted in a substantial increase in our ability to identify molecular mechanisms that are involved in MDR in cancer and to find drugs that may block or reverse the development of drug resistance. By using an in silico approach in this study, a list of five ABC transporter genes were identified, of which two (ABCC10 and ABCC11) could potentially serve as prognostic and predictive biomarkers for the management of breast cancer treatment.
2022-04-30
Purcell, C. "Evaluating the role of chemokine and nuclear factor kappa B signalling in mediating chemotherapy resistance in gastrointestinal cancer." Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517058.
Повний текст джерелаDemgenski, Janine [Verfasser]. "Role of Bim and Kinases in the Synergistic Induction of Cell Death by TRAIL and Chemotherapy / Janine Demgenski." Konstanz : KOPS Universität Konstanz, 2019. http://d-nb.info/1204829349/34.
Повний текст джерелаSwami, Priyanka. "Understanding the Role of the Receptor for Advanced Glycation End-Products (Rage) in Pancreatic Cancer." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29865.
Повний текст джерелаNorth Dakota State University. College of Health Professions
NIH Grant # P20 GM109024 from the National Institute of General Medicine
Geng, Wei, and 耿瑋. "The role of proline rich tyrosine kinase 2 (Pyk2) on cisplatin resistance in HCC." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43224106.
Повний текст джерелаSöderdahl, Gunnar. "Liver transplantation and the role of adjuvant therapy for advanced primary liver tumours /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-579-8/.
Повний текст джерелаEklund, Birgitta I. "Role of Multiple Glutathione Transferases in Bioactivation of Thiopurine Prodrugs : Studies of Human Soluble Glutathione Transferases from Alpha, Kappa, Mu, Omega, Pi, Theta, and Zeta Classes." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7102.
Повний текст джерелаMartinsson, Lisa. "Quality improvement in palliative care : the role of a national quality register and perceptions of information during palliative chemotherapy." Doctoral thesis, Umeå universitet, Onkologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-102264.
Повний текст джерелаBarthe, Anaïs. "Role of the p53 family in chemotherapy-related side effects on the enteric nervous system and skeletal muscle homeostasis." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ072.
Повний текст джерелаOne of the major complications of cancer treatments is the important side effects associated with conventional chemotherapy compounds including platinum salts and anthracyclines. They cause respectively an alteration of the enteric nervous system (ENS) and severe muscular atrophy which can be lethal; unfortunately, their origins are still poorly understood, and few treatments are effective or developed to limit them. The objective of this work was to identify the molecular mechanisms responsible for the neuronal loss of the ENS and the excessive degradation of muscle proteins to prevent these alterations and develop new therapeutic approaches. This work proved for the first time the existence of the p53 family in the ENS through its involvement in cisplatin-related cell death, as well as its major role in activating the doxorubicin-related catabolic process in muscle. Overall, these results show the importance of the p53 family in the toxicities of chemotherapy and point out the emergence of potential therapeutic tools based on the targeting of the p53 family
Fung, Tak-kwan James, and 馮德焜. "Development of anti-HBs in patients with chronic hepatitis B after liver transplantation using lamivudine prophylaxis: the possible role of adoptive immunity transfer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B31980934.
Повний текст джерелаPich, Roselló Oriol 1992. "The Role of mutational processes in the evolution of somatic tissues and malignancy." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2021. http://hdl.handle.net/10803/671532.
Повний текст джерелаLes cèl·lules del nostre cos estan constantment exposades a esdeveniments que poden lesionar l’ADN. Si aquestes lesions no són eliminades pels mecanismes de reparació, poden causar mutacions. Alguns d’aquests podrien ajudar a transformar una cèl·lula sana en una maligna. Aquesta tesi doctoral té com objectiu estudiar la generació de les mutacions i com són seleccionades positivament als teixits somàtics. Primer, estudiem el panorama de drivers en zones codificant i no codificant en més de 2500 pacients. També intentem distingir quines mutacions són driver de les passenger, i les relacionem amb els processos mutacionals. Després estudiem les mutacions relacionades amb la quimioteràpia en cèl·lules sanes i tumorals, i també l’efecte que tenen a la hematopoesi clonal. D’aquest últim fenomen en descobrim els gens drivers. Per últim, estudiem la relació entre el dany a l’ADN i els mecanismes de reparació quan la molècula s’empaqueta en nucleosomes. Aquesta relació deixa una periodicitat de 10 parells de bases que pot haver influenciat la composició del genoma dels eucariotes.
Chen, Jie, and 陈洁. "The role of FOXO3a in the development of chemoresistance in breast cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47234519.
Повний текст джерелаpublished_or_final_version
Pathology
Doctoral
Doctor of Philosophy
Steer, Henry John. "Combining chemotherapy with immunotherapy to treat mesothelioma : an investigation into the role of CD4+ T cells in a murine model." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13672/.
Повний текст джерелаCarey, Hulyer Alex Robert. "Bioenergetic coupling in P-glycoprotein: determining the relative position, topography and role of transmembrane helices six and twelve." Phd thesis, Canberra, ACT : The Australian National University, 2018. http://hdl.handle.net/1885/156454.
Повний текст джерела