Tesis sobre el tema "Cancer cell physiology"
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Choi, Mi-Yon. "P53 mediated cell motility in H1299 lung cancer cells". VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/109.
Texto completoLevitt, Randy J. "Aspects of insulin-like growth factor physiology in cancer". Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111826.
Texto completoAlthough the roles of the IGFs, IGF-IR and IGFBPs in cancer have been studied extensively, this thesis describes several new links between IGF physiology and neoplasia. In the first section, we demonstrate that IGF-I can attenuate growth inhibition and apoptosis induced by a class of drugs called COX-2 inhibitors in BxPC-3 pancreatic cancer cells. This effect could be attributed to opposite influences of IGF-IR signalling and COX-2 inhibitors on activation of Akt, with IGF-IR signalling increasing activity and COX-2 inhibitors decreasing activity. In the second section, we demonstrate that in 184htert cells, an immortal but untransformed breast epithelial cell line, COX-2 inhibitors can induce IGFBP-3 expression. We go on to show that IGFBP-3 can inhibit growth of this cell line in an IGF-dependent manner, and speculate that this action of COX-2 inhibitors may be relevant to data linking use of this class of drugs to decreased breast cancer risk. In the third section, we demonstrate that the expression of IGFBP-2 in U251 glioma cells is inhibited by the induction of the tumor suppressor PTEN. Furthermore, IGFBP-2 does not effect the growth of this cell line, indicating that published associations between tumor IGFBP-2 expression and grade of glioma may be a result of IGFBP-2 acting as a marker for loss of function of PTEN. In the fourth and final section, we demonstrate that in MDA-MB-231 breast cancer cells, over-expression of IGFBP-2 can enhance growth, indicating that the effect of IGFBP-2 on growth of neoplastic cells is tissue specific. Furthermore, antisense strategies targeting IGFBP-2 mRNA (antisense oligonucleotides and siRNA) can inhibit growth of IGFBP-2-expressing breast cancer cells both in vitro and in vivo.
Taken together, these results extend the existing body of evidence demonstrating that IGF physiology contributes to neoplastic growth, and suggest that strategies to inhibit IGF-IR signalling and/or IGFBP-2 expression may have therapeutic value for some types of cancers.
Tang, Haoran. "Scar/WAVE complex suppresses cell invasion and cancer cell transformation". Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3633/.
Texto completoBehmoaram, Emy. "Biological studies of fascin function in cancer cell invasion and cancer progression". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111596.
Texto completoGuerrini, Giuditta y Fabio Carraro. "Hedgehog signalling pathway and Carbonic Anhydrases in Breast cancer cell physiology". Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1071510.
Texto completoScott, Hannah Elizabeth. "PKC-δ, its C2 domain and breast cancer cell lines". Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12668/.
Texto completoKumar, Jothi Dinesh. "Novel stromal cell signalling systems in oesophageal cancer". Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/15257/.
Texto completoSwanson, Tara. "Physiological correlates of cancer-related fatigue in advanced non-small cell lung cancer patients". Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98503.
Texto completoMethods. Participants were evaluated by a physical therapist within the McGill Cancer Nutrition and Rehabilitation Program. Performance-based measures of physical function [upper limb strength and endurance (Jamar dynamometry), lower limb strength (30sec chair rise), cardiorespiratory function (2 minute walk - 2MW)] and a symptom questionnaire (Edmonton Symptom Assessment Scale) were conducted at one point in time. The primary endpoint of global fatigue rating was assessed using the Brief Fatigue Inventory (BFI).
Results. Fifty-eight patients (30M:28F, mean age 68 +/- 12) participated in the study. Forty-three percent were actively receiving treatment at the time of assessment. On the BFI, 67% had moderate or severe fatigue and 84% indicated fatigue had interfered with their functioning during the past 24 hours. Global fatigue scores were unrelated to hand grip strength or endurance measurements, hematological parameters or sleep quality but were significantly correlated with chair rise performance, overall rating of breathlessness, patient rating of pain and patient rated weakness. Multivariate regression analysis suggested the best model for global fatigue scores incorporates patients' ratings of weakness, breathlessness and chair rise performance.
Conclusions. Fatigue is prevalent and impacts on the function of advanced NSCLC patients. Several key factors contribute to this fatigue, with muscular and cardiorespiratory restrictions playing an important role. Such findings may have clinical implications in the recommendations of rest and exercise to best manage fatigue.
Christofakis, Emil Paul. "Effects of CXCL8 Overexpression on Tumor Cell Proliferation and Migration in an HNSCC Cell Model". VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd/1475.
Texto completoThomas, Mark Peter. "Differential tolerance of a cancer and a non-cancer cell line to amino acid deprivation : mechanistic insight and clinical potential". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/19912.
Texto completoENGLISH ABSTRACT: Introduction – Due to spatial separation from the native vascular bed, solid tumours develop regions with limited access to nutrients essential for growth and survival. The promotion of a process known as macroautophagy may facilitate in the maintenance of intracellular amino acid levels, through breakdown of cytoplasmic proteins, so that they remain available for macromolecular biosynthesis and ATP production. Several studies point to the potential ability of some cancers to temporarily increase autophagy and thereby prolong cell survival during metabolic stress. The validity of these claims is assessed when a commonly used breast cancer cell line and an epithelial breast cell line are starved of amino acids in this study. Furthermore, we go on to hypothesize that acute amino acid deprivation during treatment will result in an elevated sensitivity of MDAMB231 cells to doxorubicin toxicity but limit its cytotoxic side-effects in MCF12A cells. Methods and study design- Human breast cancer cells (MDAMB231) and breast epithelial cells (MCF12A) cultured in complete growth medium were compared to those incubated in medium containing no amino acids. Steady state autophagy levels were monitored using classical protein markers of autophagy (LC3-II and beclin-1) and the acidic compartmentalization in cells (Lysotracker™ red dye) in conjunction with autophagy inhibition (bafilomycin A1 and ATG5 siRNA). Cell viability was monitored using several techniques, including caspase 3/7 activity. ATP levels were assessed using a bioluminescent assay, while mass spectrometry based proteomics was used to quantify cellular amino acid levels. Similar techniques were used to monitor autophagy during doxorubicin treatment, while cellular doxorubicin localization was monitored using immunofluorescence microscopy. Finally, a completely novel GFP-LC3 mouse tumour model was designed to assess autophagy and caspase activity within tumours in vivo, during protein limitation and doxorubicin treatment. Results - Amino acid deprivation resulted in a transient increase in autophagy at approximately 6 hours of amino acid starvation in MDAMB231 cells. The amino acid content was preserved within these cells in an autophagy-dependent manner, a phenomenon that correlated with the maintenance of ATP levels. Inhibition of autophagy during these conditions resulted in decreased amino acid and ATP levels and increased signs of cell death. MCF12A cells displayed a greater tolerance to amino acid starvation during 24 hours of amino acid starvation. Evidence indicated that autophagy was important for the maintenance of amino acid and ATP levels in these cells and helped prevent starvation-induced cell death. Furthermore, data showed that concomitant amino acid withdrawal resulted in decreased cellular acidity in MDAMB231 cells, and increased acidity in MCF12A cells, during doxorubicin treatment. These changes correlated with evidence of increased cell death in MDAMB231 cells, but a relative protection in MCF12A cells. A novel model was used to apply these techniques in vivo, and although mice fed on a low protein diet during high dose doxorubicin treatment had increased mean survival and smaller tumour sizes, evidence suggested that autophagy is protecting a population of cells within these tumours. Conclusions - This novel approach to tumour sensitization could have several implications in the context of cancer therapy, and given the delicate relationship that autophagy has with the cancer microenvironment, efforts to determine the mechanisms involved in autophagy and sensitization could lead to new and innovative treatment opportunities for cancer management.
AFRIKAANSE OPSOMMING: Inleiding – As gevolg van hul skeiding van die oorpronklike vaskulêre netwerk, ontwikkel soliede gewasse areas met beperkte toegang tot noodsaaklike voedingstowwe. Die bevordering van 'n proses wat as makro-autofagie bekend staan, kan die handhawing van intrasellulêre aminosuur vlakke fasiliteer. Voorafgenoemde proses word waarskynlik deur die afbreek van sitoplasmiese proteïene teweegebring om sodoende vir makro-molekulêre biosintese en ATP produksie beskikbaar te kan wees. Verskeie studies dui daarop dat sommige kankersoorte die vermoë het om autofagie tydelik te verhoog, en daarby sel oorlewing gedurende metaboliese stress te verleng. Die geldigheid van hierdie eise word evalueer wanneer 'n algemeen beskikbare borskanker sellyn, en 'n borsepiteelsellyn in hierdie studie van aminosure verhonger word. Verder, veronderstel ons dat akute aminosuur ontneming gedurende behandeling 'n verhoogde sensitiwiteit van MDAMB231 selle tot doxorubicin toksisiteit tot gevolg sal hê, maar terselfdetyd die middel se sitotoksiese newe-effekte in MCF12A selle sal beperk. Metodes en studie ontwerp – Menslike borskanker- (MDAMB231) en bors epiteel selle (MCF12A) wat in volledige groeimedium gekweek is, is vergelyk met selle wat in aminosuur vrye medium gekweek is. Basislyn autofagie-vlakke is gemonitor deur die gebruik van klassieke autofagie proteïen merkers (LC3-II en beclin-1) en die asidiese kompartementalisering in selle (Lysotracker™ rooi kleurstof) saam met autofagie inhibisie (bafilomycin A1 and ATG5 siRNA). Sellewensvatbaarheid is deur die gebruik van verskeie tegnieke, insluitend caspase 3/7 aktiwiteit, gemonitor. ATP-vlakke is deur die gebruik van 'n bioluminiserende tegniek gemeet, terwyl massa-spektrometrie-gebaseerde “proteomics” gebruik is om sel aminosuur vlakke te kwantifiseer. Soortgelyke tegnieke is gebruik om autofagie gedurende doxorubicin behandeling waar te neem, terwyl sellulêre doxorubicin lokalisasie deur die gebruik van immunofluoresensie mikroskopie gemonitor is. Ten slotte, is 'n unieke GFP-LC3 muismodel in hierdie studie ontwikkel. Hierdie model is gebruik om autofagie en caspase aktiwiteit in gewasse in vivo te bestudeer tydens proteïen beperking en doxorubicin behandeling. Resultate – Aminosuur ontneming het tot 'n tydelike verhoging in autofagie na ongeveer 6 ure van aminosuur verhongering in MDAMB231 selle gelei. Die aminosuur inhoud van hierdie selle het op 'n autofagie-afhanklike manier behoue gebly. Hierdie verskynsel het met die handhawing van ATP-vlakke gekorreleer. Autofagie inhibisie gedurende hierdie kondisies het 'n verlaging in aminosuur en ATP-vlakke teweeggebring, sowel as vermeerderde tekens van seldood tot gevolg gehad. MCF12A selle het 'n groter toleransie tot aminosuur verhongering tydens die 24 uur aminosuur verhongeringsperiode getoon. Getuienis het aangedui dat autofagie belangrik vir die handhawing van aminosuur en ATP-vlakke in hierdie selle was, en gehelp het om verhongerings-geïnduseerde seldood te voorkom. Verder het data gewys dat aminosuur ontrekking tot verminderde sellulêre asiditeit in MDAMB231 selle, en verhoogde asiditeit in MCF12A selle gedurende doxorubicin behandeling gelei het. Hierdie veranderinge stem ooreen met getuienis van toenemende seldood in MDAMB231 selle, maar 'n relatiewe beskerming in MCF12A selle. 'n Unieke model was gebruik om hierdie tegnieke in vivo toe te pas. Alhoewel verhoogde oorlewing en kleiner gewasse in muise op 'n lae proteïen dieet gedurende hoë dosis doxorubicin behandeling opgemerk is, het bewyse voorgestel dat autofagie 'n populasie selle binne die gewasse beskerm. Gevolgtrekkings – Hierdie unieke benadering tot tumor sensitisering kan verskeie implikasies in die konteks van kanker behandeling hê. Gegewe die delikate verhouding van autofagie met die kanker mikro-omgewing, kan pogings om die meganismes betrokke in autofagie en sensitisering te bepaal, tot nuwe en innoverende behandelings vir kanker lei.
Kay, Sophie Kate. "Cell fate mechanisms in colorectal cancer". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:f19bf73d-0c0e-4fff-9589-bf43f9ff12f0.
Texto completoArif, Khalid. "Evaluation of hormonal receptors in breast cancer drug therapy". Thesis, University of Lincoln, 2014. http://eprints.lincoln.ac.uk/14682/.
Texto completoAlvi, Mohammed M. "Lysosomal Targeting of a Gelatin-Doxorubicin Conjugate and Its Evaluation for Cell Damage in Two Model Breast Cancer Cell Lines". Thesis, University of the Sciences in Philadelphia, 2021. http://pqdtopen.proquest.com/#viewpdf?dispub=28154563.
Texto completoBONORA, Massimo. "Mithocondrial physiology and calcium signalling partnership: from regulation of differentiation to oncosuppressor activity". Doctoral thesis, Università degli studi di Ferrara, 2012. http://hdl.handle.net/11392/2389248.
Texto completoSafadi, Mohammed Fayez. "The potential role of Parathyroid Hormone-related Peptide (PTHrP) as an autocrine growth factor in the regulation of breast cancer cell proliferation". Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242412.
Texto completoMirbahai, Ladan. "Biomarkers of cell stress and cell death detected by proton high resolution magic angle spinning (¹H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in a rat glioma cell line". Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/619/.
Texto completoAdams, Katherine Jane. "Redirected T cell activity by high affinity TCR-ANTI-CD3 bispecific candidate therapeutics". Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/47578/.
Texto completoSandoval, Maria Luisa. "EVALUATING THE ROLE OF BREAST CANCER STEM CELL POPULATIONS AS PREDICTORS OF RESPONSE TO TRASTUZUMAB TREATMENT". Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1405093548.
Texto completoHirsch, Alexander M. "Embryonic Stem Cell-Derived Exosomes Increase the Antiproliferative Activity of Doxorubicin in Breast Cancer". VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5981.
Texto completoPereira, Lucy. "Validation of the 60-second chair rise as a measure of physical function in patients with non-small cell lung cancer". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116113.
Texto completoSubjects completed the chair rise test, 6MWT, hand grip, and the SF-36 pre and post chemotherapy. Evidence for construct and discriminant validity but not predictive validity was provided for the chair rise test. The 60-second chair rise may be too strenuous for persons with severe disability but a standardized timed-based chair rise test is needed.
Biayna, Rodríguez Josep. "Using Phosphorodiamidate Morpholino Oligomers (PMOs) to characterize the role of neurofibromin in cell physiology". Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/378358.
Texto completoLa neurofibromina és el producte del gen NF1, que mutat causa la Neurofibromatosis de tipus 1. Tot i que en l'actualitat, encara ens cal entendre millor el rol d'aquesta proteïna en la fisiologia cel•lular, l'activitat Ras-GAP és la funció bioquímica més ben caracteritzada de la neurofibromina. Aquesta funció està regulada per l'splicing alternatiu de l'exó 23a (E23a). En aquesta tesi ens vàrem proposar comprendre millor el paper d'aquest splicing alternatiu durant el procés de diferenciació neuronal, amb l'objectiu de proporcionar nova informació sobre els problemes cognitius i d'aprenentatge associats a aquesta malaltia. Degut a la gran grandària de la neurofibromina i a la dificultat de manipular-la in vitxo, es varen utilitzar Phosphorodiamidate Morpholino Oligomers (PMOs) per modificar la composició exònica del mARN (per tant l'estructura resultant de la neurofibromina) sense alterar les condicions fisiològiques d'expressió del gen NF 1 . Es va desenvolupar un sistema basat en PMOs per forçar l'expressió de l'isoforma tipus II (+E23a) o tipus I (-E23a) del gen NF1 en cèl•lules PC12, un model de diferenciació neuronal, en presència o absència de Nerve Growth Factor (NGF). A més, per entendre la importància de 1'E23a es va establir un grup de metodologies i assajos funcionals per poder determinar diferents respostes cel•lulars i valorar la funció d'aquest en el procés de diferenciació neuronal. Els nostres resultats van mostrar que forçar l'isoforma tipus I (-E23a) no era suficient per induir la diferenciació de les cèl•lules PC12 en absència de NGF. No obstant això, qualsevol alteració en la relació entre les isoformes tipus I/II en presència de NGF, ja sigui d'una manera quantitativa o dependent del temps, interferia en el correcte procés de diferenciació neuronal, en particular, alterant la correcta formació de neurites, així com l'adequada regulació de les vies de senyalització RAS/MAPK i cAMP/PKA. En conjunt, els resultats d'aquesta tesi indiquen que la regulació de l'splicing alternatiu de 1'E23a del gen NF1 permet un ajust fi de les vies RAS/MAPK i cAMP/PKA a través de la activitat GAP de la neurofibromina, d'una forma oposada i coordinada al llarg del temps durant el procés de diferenciació neuronal.
Ryan, Nathan M. "Macrophage Migration Inhibitory Factor and Myeloid Derived Suppressor Cell Function in Oral Carcinogenesis". The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1618413341944817.
Texto completoPatel, Anisha Anilkumar. "Mechanisms of EPS8-mediated oncogenesis". VCU Scholars Compass, 2007. http://hdl.handle.net/10156/1148.
Texto completoLee, Man-yan y 李敏茵. "Analysis on chromosome 3p in smokers and non-smokers with non-small cell lung carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31226231.
Texto completoChang, Tsun-Kai. "A Novel Autophagy Regulatory Mechanism that Functions During Programmed Cell Death: A Dissertation". eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/686.
Texto completoChang, Tsun-Kai. "A Novel Autophagy Regulatory Mechanism that Functions During Programmed Cell Death: A Dissertation". eScholarship@UMMS, 2009. http://escholarship.umassmed.edu/gsbs_diss/686.
Texto completoChang, Cheng. "Function and Regulation of the α6 Integrins in Mammary Epithelial Biology and Breast Cancer: A Dissertation". eScholarship@UMMS, 2015. http://escholarship.umassmed.edu/gsbs_diss/734.
Texto completoTracy, Kirsten M. "Role and Regulation of Autophagy During Developmental Cell Death in Drosophila Melanogaster: A Dissertation". eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/769.
Texto completoTracy, Kirsten M. "Role and Regulation of Autophagy During Developmental Cell Death in Drosophila Melanogaster: A Dissertation". eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/769.
Texto completoVan, den Heever Martine. "A comparison of the effect of curcumin treatment on apoptosis, necrosis and autophagy in a MCF-7 mammary adenocarcinoma and a MCF-12A healthy mammary epithelial cell line". Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/2970.
Texto completoBreast cancer is currently the primary cause of cancer-related death in women worldwide. Conventional treatments such as radiation and chemotherapy have many deleterious and long lasting side-effects, some of which are permanent, such as infertility. As certain tumour cells can also acquire resistance to chemotherapy, the need for the development of a less severe, yet more effective, targeted anti-cancer treatment exists. Curcumin, a plant polyphenol from Curcuma longa, has long been thought to possess antitumour, antioxidant, anti-arthritic, anti-amyloid, anti-ischemic and anti-inflammatory properties. Numerous studies conducted over the past sixty years confirm this. We aimed at examining the effect of curcumin on cell viability and the different modes of cell death, namely apoptosis, necrosis and autophagy, in the MCF-12A (non-tumorigenic mammary epithelial) and MCF-7 (mammary adenocarcinoma) cell lines. Cells were incubated with different doses of curcumin to evaluate the dose response through a MTT assay. Thereafter, cells were incubated with 200 μM curcumin for 48 hrs and stained with markers and DNA stains for apoptosis (Hoechst, Caspase-3, PARP), necrosis (Propidium Iodide) and autophagy (LC3B and Beclin-1). Cells were examined via fluorescence microscopy, Western Blot- and FACS analyses. MTT results showed no significant decrease in viability in the MCF-12A cell line after curcumin treatment. However, a significant decrease in viability was observed in MCF-7 cells after treatment with 200 μM curcumin (p < 0.05). Treated MCF-7 cells also show clear LC3B expression. FACS results show a significant difference in Hoechst mean fluorescence intensity in MCF-7 cells after curcumin treatment (p < 0.05). This study provides evidence that MCF-7 cells respond to a 200 μM dose of curcumin treatment through metabolic change and induction of the autophagic pathway. The model system used in this study provides groundwork for further cell culture based studies regarding breast cancer and curcumin.
ENRICO, BENA CHIARA. "Stochasticity in biological systems: from modelling to experimental validation in cell growth and post-transcriptional gene regulation". Doctoral thesis, Politecnico di Torino, 2019. http://hdl.handle.net/11583/2743333.
Texto completoLangford, Peter R. "c-Met Initiates Epithelial Scattering through Transient Calcium Influxes and NFAT-Dependent Gene Transcription". BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/3186.
Texto completoTANTILLO, Elena. "Bidirectional Neuron-glioma interactions: effects of Glioma Cells on Synaptic activity and its impact on tumor growth". Doctoral thesis, Scuola Normale Superiore, 2020. http://hdl.handle.net/11384/94546.
Texto completoVallejo, Gracia Albert. "Kv1.3 and Kv1.5 channels in leukocytes". Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/397797.
Texto completoDi, Giovanni Pierluigi. "Pharmacokinetic modelling of breast tumour physiology by dynamic contrast enhanced MRI". Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158909.
Texto completoLeisching, Gina Renata. "Manipulation of the autophagic pathway sensitises cervical cancer cells to cisplatin treatment". Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/80107.
Texto completoENGLISH ABSTRACT: Introduction Cisplatin has been widely used to treat solid tumours and much success has come from the use of this drug in the treatment of head and neck, ovarian, testicular, cervical and small-cell lung cancers. However, the success of cisplatin treatment is limited due to its dose-limiting toxicity and its resulting side-effects, such as nephro- and ototoxicity. The devastating side-effects induced by cisplatin treatment provided the platform for this study whereby the aim was to lower the concentration of cisplatin while maintaining its cancer-specific cytotoxic action. Equally concerning is, cisplatin resistance which is becoming increasingly common, and this radically limits the clinical efficacy and utility of the drug. Adjuvant therapy has thus become necessary in an attempt to possibly curb or lessen the extent of cisplatin resistance. Due to the large body of evidence implicating the importance of autophagy in cancer, the prospect of targeting this mechanism has generally been accepted. Various chemotherapy agents induce autophagy in cancer cells; however the effect of cisplatin on autophagic induction has not been very well explored. We thus hypothesise that the manipulation of the autophagic pathway will sensitise cancer cells to a low concentration of cisplatin treatment. Furthermore, due to the functional interaction between Bcl-2 and Beclin-1 and its role in the regulation of autophagy, ratio analysis of Beclin-1 to Bcl-2 as means of detecting the role of autophagy within the cell under homeostatic and treatment/stress conditions has been conducted. Additionally, Bcl-2 has a prominent role in the malignant cell and it’s over-expression has been found to confer resistance in a variety of cancerous cell lines. We therefore hypothesise that the silencing of Bcl-2 prior to cisplatin treatment will sensitise cervical cancer cells to apoptosis and increase the Beclin-1/Bcl-2 ratio in favour of apoptosis. Materials and Methods Three human cervical cell lines were used: a non-cancerous ectocervical epithelial cell line (Ect1/E6E7) and two cancerous cervical cell lines (HeLa and CaSki). In order to determine a concentration of cisplatin that was non-toxic to the non-cancerous Ect1/E6E7 cell line, a dose-response was performed. With the use of an autophagy inhibitor (bafilomycin A1) and an autophagy inducer (rapamycin), autophagic flux capacities were assessed in each cell line through the Western blotting technique. In order to assess whether the chosen concentration of cisplatin induced autophagy, flow cytometry with the use of a Lysotracker™ dye was utilised, as well as analysis of autophagy protein levels (LC-3 II, Beclin-1 and p62). Autophagy modulation was achieved through two methods: pharmacological modulation with use of two recognised agents, namely bafilomycin A1 and rapamycin, and biological manipulation with the use of ATG5 and mTOR mRNA silencing. The effects of different treatment regimes on cell death was assessed with the use of PARP and caspase-3 cleavage through Western blotting, caspase-3/-7 activity (Caspase-Glo®), PI inclusion, LDH release and MTT reductive capacity. Additionally the effects of these treatment regimes on cell-cycle progression were also analysed. Beclin-1 and Bcl-2 expression was determined through Western blotting and immunocytochemistry before and after treatment with cisplatin in HeLa and CaSki cells. To assess the reliance of the cervical cancer cells on Bcl-2 after cisplatin treatment, Bcl-2 knock-down was achieved through RNA interference, where after the Beclin-1/Bcl-2 ratio was assessed as well as apoptosis with the use of cleaved PARP analysis (Western blotting) and Caspase-Glo©. For the ex vivo analysis, biopsies were collected from patients undergoing routine colposcopy screenings and hysterectomies at Tygerberg Hospital, Tygerberg, Western Cape. A total of 10 normal, 29 low-grade squamous intraepithelial lesions (LSIL), 33 high-grade squamous intraepithelial lesions (HSIL) and 13 carcinoma biopsies were collected for analysis, where after the expression profiles of two autophagy markers (mTOR and LC-3 II), as well as one anti-apoptotic marker (Bcl-2) were assessed. Protein levels were analysed through Western blot and confirmed through immunohistochemistry. Results Dose-response curves revealed that 15 μM of cisplatin did not induce cell death in the normal cervical epithelial cell line (Ect1/E6E7) and was therefore utilised through-out the remainder of the study. It was additionally determined that the CaSki cells were more resistant to cisplatin treatment when compared to the HeLa and Ect1/E6E7 cells. Autophagic flux analysis revealed that, although all three cell lines were cervix derived, their autophagic flux capacities differed. It was observed that the chosen concentration of cisplatin was able to induce autophagy in all three cell lines, with the HeLa cells demonstrating a particularly pronounced response. Autophagy modulation in conjunction with cisplatin treatment revealed the following: Autophagy inhibition with bafilomycin A1 lead to significant increases in caspase-3 and PARP cleavage and LDH release in both cervical cancer cell lines. The inhibition of autophagy through silencing of ATG5 induced caspase-3 cleavage and agrees with results obtained from pharmacological inhibition of autophagy with bafilomycin A1. In addition to autophagic induction, a low concentration of cisplatin induced the up-regulation of Bcl-2, which when silenced significantly improved cisplatin-induced apoptosis in both cervical cancer cell lines. Analysis of the expression profiles of mTOR and LC-3 in normal, pre-malignant (LSIL and HSIL) and cancerous cervical tissue revealed that autophagy is significantly up-regulated in HSILs and carcinoma of the cervix. Additionally, Bcl-2 expression is significantly increased in cervical carcinoma tissue, which agrees with results from other studies. Conclusion Autophagic flux capacities between the three cell lines investigated, derived from the same organ, differ significantly. This should be taken into consideration when autophagic modulation is being used as an adjuvant treatment. With regard to chemotherapy treatment in cervical cells, a low-concentration of cisplatin significantly induces autophagy in malignant and non-malignant cervix-derived cell lines where it serves a pro-survival mechanism. Inhibition of autophagy with bafilomycin A1 and ATG5 siRNA confirmed this survival effect in both cancerous cell lines where apoptosis was significantly increased. Interestingly, rapamycin pre-treatment together with cisplatin did not induce significant levels of apoptosis in HeLa cells where autophagy induction may have provided additional protection from the cytotoxic effects of cisplatin. Therefore the inhibition of autophagy through pharmacological and biological inhibition improves the cytotoxicity of a low concentration of cisplatin and provides a promising new avenue for the future treatment of cervical cancer. Bcl-2 up-regulation in response to cisplatin treatment also serves as a protective mechanism by which cervical cancer cells survive. The extent of apoptotic cell death observed after biological inhibition of Bcl-2 reiterates the fact that this response may be exploited in order to favour the use of lower concentrations of cisplatin. Analysis of clinical specimens emphasised the value of the in vitro work: Cervical cancer biopsies had increased expression of both LC-3 II and Bcl-2, indicating autophagy induction and apoptosis inhibition, respectively. Thus two novel methods of improving cisplatin cytotoxicity have been demonstrated in the following study. Treatment regimens may administer more frequently and prolonged due to the minimal side-effects that accompanies low-dose cisplatin treatment.
AFRIKAANSE OPSOMMING: Inleiding Sisplatien word algemeen gebruik vir die behandeling van soliede gewasse. Baie sukses is reeds deur die gebruik van díe middel behaal in die behandeling van kop en nek, ovariale, terstikulêre, servikale en klein-sel kankers. Die sukses van Sisplatien-behandeling word wel ingeperk deur die dosis-beperkende toksisiteit en die gevolglike newe-effekte soos nefrotoksisiteit. Hierdie verwoestende newe-effekte wat deur sisplatien behandelings geïnduseer word, het as die platform vir hierdie studie gedien. Die doel was om die sisplatien konsentrasies te verlaag, maar terselfdertyd die kankerspesifieke sitotoksisiteit te behou. Nog ʼn punt van kommer is dat sisplatien-weerstandigheid aan die toeneem is, wat die kliniese effektiwiteit en gebruik van hierdie middel geweldig beperk. Byvoegmiddels het dus noodsaaklik geraak in die poging om die sisplatien-weerstandigheid te verhoed. As gevolg van verskeie bewyse wat die belangrikheid van outofagie in kanker impliseer, is die vooruitsig om hierdie meganisme te teiken, algemeen aanvaar. Verskeie chemoterapeutiese middels induseer outofagie in kanker selle, hoewel die effek van Sisplatien op outofagiese induksie nog nie goed ondersoek is nie. Ons hipotese is dus dat die manipulasie van die outofagiese pad die kankerselle sensitiseer tot ʼn lae konsentrasie van sisplatien. Verder, as gevolg van die funksionele interaksie tussen Bcl-2 en Beclin-1, en hul rol in die regulering van outofagie, is verhouding-analises van Beclin-1 tot Bcl-2 uitgevoer met die doel om die rol van outofagie in die sel onder homeostatiese en behandeling/stres kondisies te bepaal. Verder is Bcl-2 bekend daarvoor om ʼn prominente rol te speel in kwaadaardige selle, en die ooruitdrukking daarvan is gevind om weerstandigheid aan te help in ʼn verskeidenheid van kankeragtige sellyne. Ons hipotetiseer dus dat geenonderdrukking van Bcl-2 voor die behandeling met sisplatien die servikale kanker selle sal sensitiseer tot apoptose en ʼn verhoging in die verhouding van Beclin-1/Bcl-2 veroorsaak, wat in die guns van apoptose is. Materiale en Metodes Drie menslike servikale sellyne was gebruik: ʼn nie-kankeragtige servikale epiteel sellyn (Ect/E6E7) en twee kankeragtige servikale sellyne (HeLa en CaSki). Om ʼn konsentrasie van sisplatien te bepaal wat nie-toksies tot die nie-kankeragtige Ect1/E6E7 sellyn is, was ʼn dosisrespons uitgevoer. Met die gebruik van ʼn outofagiese inhibeerder (bafilomycin A1) en ʼn outofagiese induseerder (rapamycin), is die outofagiese-fluks kapasiteite van elke sellyn deur die Western Blotting tegniek geassesseer. Om te bepaal of die gekose konsentrasie van sisplatien outofagie induseer, is vloeisitometrie met ʼn Lysotracker™ kleurstof gebruik, sowel as analises op outofagie proteïenvlakke (LC-3 II, Beclin-1 en p62). Outofagie modulering is behaal deur twee metodes: farmakologiese modulering met twee erkende middels, naamlik bafilomycin A1 en rapamycin, en biologiese manipulasie met die gebruik van ATG5 en mTOR geenonderdrukking. Die effekte van die verskillende behandeling skedules op seldood was geassesseer deur gebruik te maak van PARP en kaspase-3 splitsing deur Western Blotting, kaspase-3/-7 aktiwiteit deur Caspase-Glo ®, PI-insluiting, LDH vrystelling en MTT reduserende kapasiteit. Verder is die effekte van hierdie behandeling skedules op selsiklus progressie ook geanaliseer. Beclin-1 en Bcl-2 uitdrukking was ook bepaal deur Western Blotting en immunohistochemie voor en na behandeling met sisplatien in HeLa en CaSki selle. Om die afhanklikheid van die servikale kankerselle op Bcl-2 na sisplatien behandelings te toets, is Bcl-2 onderdruk deur RNA-inmenging, waarna Beclin-1/Bcl-2 verhouding geassesseer is, sowel as opoptose deur die gebruik van gesplitste PARP analises (Western Blotting) en Caspase-Glo©. Vir die ex vivo analises is biopsies vanaf pasiënte wat roetine kolposkopie en histerektomies ondergaan, verkry (Tygerberg Hospitaal, Tygerberg, Westelike Provinsie). ʼn Totaal van 10 normale, 29 lae-graad plaveisel intraepiteel letsels (LSIL), 33 hoe-graad plaveisel intraepiteel letsels (HSIL) en 13 karsinoom biopsies is verkry vir analises. Die uitdrukkingsprofiel van twee outofagiese merkers (mTOR en LC-3 II), asook een merker vir apoptose (Bcl-2), was geassesseer. Proteïen vlakke was ook deur Western Blotting geanaliseer en deur immunohistochemie bevestig. Resultate Dosisrespons kurwes het getoon dat 15 μM sisplatien nie seldood in die normale sellyn (Ect1/E6E7) geïnduseer het nie, en was daarom gebruik deur die res van hierdie studie. Verder is daar ook gevind dat CaSki selle meer weerstandig tot sisplatien behandelings is wanneer vergelyk word met die HeLa en Ect1/E6E7 selle. Outofagiese-fluks analises het getoon dat, alhoewel al drie sellyne vanaf die serviks afkomstig is, daar verskille is in hul outofagiese-fluks kapasiteit. Daar is ook waargeneem dat die gekose konsentrasie van sisplatien in staat was om outofagie te induseer in al drie sellyne, met HeLa selle wat die mees merkbare respons getoon het. Modulering van outofagie in samewerking met sisplatien behandelings het die volgende onthul: inhibisie van outofagie deur bafilomycin A1 het gelei tot ʼn beduidende verhoging in kaspase-3, PARP splitsing en LDH vrylating in beide servikale kankersellyne. Geenonderdrukking van ATG5 induseer kaspase-3 splitsing en stem ooreen met resultate wat verkry is deur farmakologiese inhibisie van outofagie met bafilomycin A1. Bykomend tot outofagiese indusering, het ʼn lae konsentrasie sisplatien die opregulering van Bcl-2 geïnduseer. Wanneer Bcl-2 geenonderdrukking in hierdie scenario toegepas was, het dit ʼn beduidende verbetering in sisplatien-geïnduseerde apoptose in beide servikale kankersellyne getoon. Analises van die uitdrukkingsprofiel van mTOR en LC-3 in normale, pre-maligne (LSIL en HSIL) en kankeragtige servikale weefsel, het getoon dat outofagie beduidend opgereguleer is in HSILs en servikale karsinome. Verder is Bcl-2 uitdrukking ook gevind om beduidend verhoog te wees in servikale karsinoomweefsel, wat ooreenstem met resultate verkry in ander studies. Gevolgtrekking Outofagiese-fluks kapasiteite tussen die drie sellyne, afkomstig van dieselfde orgaan, toon beduidende verskille. Hierdie bevinding moet in ag geneem word wanneer outofagiese-modulering as ʼn bevorderingsbehandeling gebruik word. Met betrekking tot chemoterapie behandeling in servikale selle; ʼn lae konsentrasie van sisplatien veroorsaak ʼn beduidende indusering van outofagie in kwaadaardige en nie-kwaadaardige serviks-afkomstige sellyne, en dien as ʼn oorlewingsmeganisme. Inhibisie van outofagie met bafilomycin A1 en ATG5 siRNA het hierdie beskermings effek bevestig, aangesien apoptose beduidend verhoog was in beide kankersellyne. Interessant genoeg het rapamycin pre-behandeling tesame met sisplatien nie beduidende vlakke van apoptose in HeLa selle geïnduseer nie. Outofagie induksie mag dalk addisionele beskerming teen die sitotoksiese effekte van sisplatien gebied het. Daarom het die inhibisie van outofagie deur farmakologiese en biologiese inhibering die sitotoksisiteit van ʼn lae konsentrasie sisplatien bevorder, wat ʼn belowende bevinding is vir die toekomstige behandeling van servikale kanker. Bcl-2 opregulering as gevolg van sisplatien behandelings dien ook as beskermings meganisme waarby servikale kankerselle oorleef. Die mate van apoptotiese seldood wat waargeneem word na biologiese inhibering van Bcl-2, wys weer op die feit dat hierdie respons uitgebuit kan word vir die gebruik van laer konsentrasies van sisplatien. Analises van die kliniese monsters het ook die waarde van die in vitro werk versterk: Servikale kanker biopsies het verhoogde uitdrukking van beide LC-3 II en Bcl-2 getoon, wat aandui dat outofagie geïnduseer en apoptose geïnhibeer word. Daar is dus twee nuwe metodes vir die verbetering van sisplatien-toksisiteit in hierdie studie gedemonstreer. Behandeling regimes kan meer gereeld en vir langer tydperke toegepas word, aangesien die newe-effekte van lae-dosis sisplatien behandelings minimaal is.
MRC for funding
Storniolo, Carolina Emilia. "Efecto de componentes de la Dieta Mediterránea sobre la cascada del ácido araquidónico y la proliferación de células epiteliales intestinales". Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/458019.
Texto completoAdherence to Mediterranean Diet has been associated with colorectal cancer prevention, this fact has been linked to moderate consumption of wine and olive oil, two characteristic foods of Mediterranean Diet. Both are a complex mixture of components among which polyphenols stand out. Stilbenes and tyrosols are polyphenols present in wine and olive oil. The objective of this work was to study the effect of bioactive components of wine and olive oil on intestinal epithelial cell growth. For this purpose, Caco-2 cells ware used as experimental model. Resveratrol (RV), a polyphenol representative of wine, is able to regulate intestinal epithelial cells growth in vitro and sulphated and glucuronidated RV metabolites maintain their antioxidant, antiproliferative and apoptotic activity. Trans-piceid is the RV aglycone more present in wine, has antioxidant, anti-mitotic and pro-apoptotic effect similar to that of RV. The antioxidant capacity of RV is related to the presence of hydroxyl groups in 3, 5 and 4 'position, been the last determinant for this activity. The substitution of these hydroxyls for chloro or methoxy groups, despite reducing their antioxidant activity, retains its biological effects on Caco-2 cells growth. Monounsaturated fatty acids, and especially oleic acid, which is the major fatty acid in olive oil, induce Caco-2 cell growth, probably through the synthesis of metabolites from lipoxygenase pathway. Some polyunsaturated fatty acids (PUFA), such as eicosapentaenoic and docosahexaenoic, had a dual effect, since at low concentration they induced cell proliferation, while at high concentration these PUFA had an opposite effect on cell growth and induced apoptosis. Is interesting to note that the mitogenic effect of oleic acid was reversed by some minor components of olive oil such as hydroxytyrosol, oleuropein, squalene, maslinic acid and pinoresinol. Some of which inhibited the release of arachidonic acid and the synthesis of eicosanoids, elements involved in the control of intestinal epithelial cells growth. In conclusion, the amount and type of fatty acids consumed together with minor components of wine and olive oil, as well as their metabolites, may play an important role in arachidonic acid cascade regulation and intestinal epithelial Caco-2 cell proliferation.
Rachakatla, Rajashekar. "Targeted use of umbilical cord matrix stem cells for cancer therapy". Diss., Manhattan, Kan. : Kansas State University, 2008. http://hdl.handle.net/2097/547.
Texto completoSobantu, Mandisa Pamela. "The antioxidative and cytotoxic effects of hibiscus sabdariffa on mcf7 and mcf12a breast cell lines". Thesis, Cape Peninsula University of Technology, 2015. http://hdl.handle.net/20.500.11838/2235.
Texto completoCancer is the leading cause of death in both developed and developing countries. In particular, breast cancer is regarded as the most common neoplastic disease in females and accounts for the high mortality rates in women. Increased mortality rates could be attributed to ineffective current cancer treatment modalities that have been implicated to cause multidrug resistance, high toxicity and induction of several side effects. In addition, oxidative stress appears to play a role in the development of breast cancer. Therefore, current cancer research aims to search for plant based anticancer compounds with less side effects and toxicity towards the human body. An example of such a plant is Hibiscus sabdariffa also known as roselle and is reported to have bioactive compounds that exhibit anticancer and antioxidant effects. However, the effects of Hibiscus sabdariffa on breast cancer in relation to oxidative stress and apoptosis have not been investigated. In this research study, the aim was to evaluate the cytotoxic and antioxidant effects of water and methanolic extracts of Hibiscus sabdariffa (HS) on cancerous MCF7 and non-cancerous MCF12A breast cell lines with special reference to oxidative stress and apoptosis. This was done based on the fact that HS has been documented for its traditional use against cancer and other ailments.
Du, Toit Joe-Lin. "The modulation of various signal transduction pathways in colorectal carcinoma cells by docosahexaenoic acid". Thesis, Stellenbosch : University of Stellenbosch, 2006. http://hdl.handle.net/10019.1/17350.
Texto completoENGLISH ABSTRACT: Introduction: The ability of different polyunsaturated fatty acids (PUFAs), especially n-3 PUFAs, to prevent the development of cancer has been under intense investigation the past three decades. Numerous studies have shown that these fatty acids can kill cancer cells in vitro as well as in vivo whilst normal cells remain unaffected. Unfortunately, the cellular and molecular mechanisms responsible for this phenomenon are still poorly understood. This study investigated the signalling pathways modulated by docosahexaenoic acid (DHA) in an adenocarcinoma cell line, in order to shed some light on these unknown mechanisms. Materials & Methods: NCM460 (normal colon epithelial) and CaCo2 (colon adenocarcinoma) cells were cultured and treated with low doses of palmitic acid (PMA), oleic acid (OA), arachidonic acid (AA), and DHA. The effects of these fatty acids on the proliferation of the cells were measured with the MTT assay. The composition of membrane phospholipids of CaCo2 cells was determined after 48h supplementation with different fatty acids by gas chromatography. Also, CaCo2 cells were treated with DHA (10 μM) only and proteins were harvested at fixed time points ranging from 2 minutes to 48 hours. The protein inhibitors wortmannin (PI3 kinase inhibitor), PD 98059 (MEK inhibitor) and SB 203580 (p38 inhibitor) and also RNA interference (RNAi) of the p38 MAPK protein were used to investigate cross-talk between signalling pathways. ERK, p38 MAP kinase, Akt, and p53 were then analysed by Western blotting using phospho-specific and total antibodies. The cleavage of the apoptotic proteins, caspase-3 and PARP were also analysed. Results and discussion: MTT assays revealed that none of the fatty acids were toxic to normal cells. In addition, DHA was shown to be most effective to kill CaCo2 cells whilst protecting NCM460 cells and a subsequent dose response experiment revealed that lower concentrations are most suitable for this purpose. DHA was also shown to be readily incorporated into phospholipids, along with AA. This is associated with increased membrane fluidity, which could affect the localisation, and downstream effects, of various signalling proteins within the membrane. Western blot analysis revealed a rapid increase in activity in most proteins under investigation, especially ERK and Akt (Ser473). Long-term DHA supplementation suppressed the full activation of Akt. This down regulation of survival signalling could lead to cell death in CaCo2 cells. In addition, it was shown that after 48h, DHA induced the cleavage of caspase-3 and PARP, which is indicative of apoptosis. RNAi experiments suggested a possible role for p38 MAPK in the phosphorylation of p53 at Ser15, a site which is associated with DNA damage. Conclusion: DHA exerts its effects by means of cellular signal transduction pathways, particularly by suppression of the important survival-related kinase, Akt. This could have implications for future therapeutic interventions in cancer patients, as fatty acids are safe to use and do not interfere with the functionality of normal tissue.
AFRIKAANSE OPSOMMING: Inleiding: Die vermoë van verskillende poli-onversadigde vetsure (POVSe), veral n-3 POVSe, om die ontstaan van kanker te voorkom, is intens nagevors die afgelope drie dekades. Menigte studies het aangevoer dat hierdie vetsure kankerselle in vitro asook in vivo kan doodmaak, terwyl normale selle nie daardeur beïnvloed word nie. Ongelukkig word die sellulêre and molekulêre meganismes onderliggend tot hierdie verskynsel nie goed begryp nie. Hierdie studie het verskeie seintransduksie-paaie wat deur dokosaheksaenoësuur (DHS) in ‘n adenokarsinoom sellyn gemoduleer word, ondersoek. Materiale & Metodes: NCM460 (normale kolonepiteel) en CaCo2 (kolon adenokarsinoom) selle is onderhou in ‘n selkultuur-laboratorium en behandel met lae dosisse palmitiensuur (PMS), oleïensuur (OS), aragidoonsuur (AS), en DHS. Die invloed van hierdie vetsure op die proliferasie van die selle is d.m.v. die MTT toets bepaal. The samestelling van membraan-fosfolipiede van CaCo2 selle is na 48h behandeling met die verskillende vetsure bepaal deur middel van gaschromatografie. Die CaCo2 selle is ook met DHA (10 μM) alleenlik behandel en teen vaste tydpunte wat wissel van 2 minute tot 48h, waarna proteïene geëkstraeer is. Die proteïen-inhibitore wortmannin (PI3 kinase inhibitor), PD 98059 (MEK inhibitor), en SB 203580 (p38 inhibitor) asook RNAinterferensie (RNAi) teen die p38 MAPK proteïen is ingespan om oorvleueling tussen seintransduksie–weë te ondersoek. ERK, p38 MAPK, Akt, en p53 is geanaliseer deur middel van die Western–klad metode met fosfo–spesifieke en totale antiliggame. Die kliewing van die apoptotiese proteïene caspase-3 en PARP is ook bepaal. Resultate en bespreking: MTT toetse het ontul dat geen vetsure toksies was vir die normale selle nie. Daar is ook gevind dat DHS die mees effektiewe vetsuur was om CaCo2 selle te dood, terwyl NCM460 selle beskerm word. Gevolglik het ‘n dosis-respons eksperiment getoon dat laer konsentrasies die beste geskik is vir hierdie doel. Daar is ook gevind dat DHA maklik in fosfolipiede geïnkorporeer word, tesame met AS. Dit word geassosieer met verhoogde membraan-vloeibaarheid, wat die ligging, en ook stroom-af werking, van verskeie seintransduksie proteïene in die membraan, kan beïnvloed. Westernklad analises het ‘n vinnige verhoging in die aktiwiteite van die meeste proteïene onder die soeklig, getoon, veral ERK en Akt (Ser473). Langdurige DHS behandeling het die maksimale aktiwiteit van Akt onderdruk. Hierdie afname van oorlewing-gerigte seine kan lei tot seldood in CaCo2 selle. Daar is boonop geving dat DHS die kliewing van caspase-3 en PARP geïnduseer het na 48, wat dui op apoptose. Uit die RNAi eksperiment kon daar ook ‘n moontlike rol vir p38 MAPK in die fosforilering van p53 by Ser15, wat geassosieer word met DNS-skade, getoon word. Gevolgtrekking: DHS beoefen sy effekte deur middel van seintransduksie paaie, veral deur die oorlewing-geassosieerde kinase, Akt, te onderdruk. Dit kan implikasies hê vir toekomende terapeutiese ingrypings in kankerpasiënte, aangesien vetsure veilig is om te gebruik en nie skadelik is vir normale weefsel nie.
Leung, Chun-to y 梁鎮濤. "Cellular and molecular characterization of mammary tumor development in wild type and adiponectin deficient MMTV-PyVT mice". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50712640.
Texto completopublished_or_final_version
Pharmacology and Pharmacy
Master
Master of Medical Sciences
Mon, Père Nathaniel. "Statistical biophysics of hematopoiesis and growing cell populations". Doctoral thesis, Universite Libre de Bruxelles, 2020. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/314684.
Texto completoLes populations cellulaires du corps humain forment des systèmes complexes, leur comportement étant déterminé par d'innombrables processus au sein des cellules elles-mêmes ainsi que par leurs interactions entre elles et avec leur environnement. Une approche mathématique de la description de leurs phénomènes émergents au niveau des tissus nécessite généralement l'abstraction de ces systèmes sous-jacents afin d'obtenir des modèles traitables et interprétables, ce qui à son tour conduit souvent à des descriptions impliquant des processus stochastiques. Dans cette thèse de doctorat, deux de ces systèmes cellulaires sont étudiés.Le premier est le système hématopoïétique humain :la machinerie par laquelle les cellules précurseurs du sang sont cultivées et maturées dans la moelle osseuse. Ce processus est essentiel pour permettre la physiologie des mammifères, depuis la fourniture d'érythrocytes porteurs d'oxygène jusqu'à la préservation du système immunitaire. L'obtention d'une compréhension quantitative des aspects clés de ce système peut fournir des informations précieuses et des prévisions vérifiables concernant l'origine et la dynamique de diverses maladies liées au sang. Cependant, les études in vivo de la maturation des cellules sanguines posent des défis importants, et les études in vitro n'offrent qu'un pouvoir prédictif limité. Par ailleurs, l'architecture hiérarchique du système est bien adaptée à l'application de techniques mathématiques reposant uniquement sur quelques hypothèses et paramètres. Cette recherche vise à contribuer à deux questions plus larges concernant l'hématopoïèse, la première étant "Quelle est la forme de ce système" et la seconde "Comment se comporte-t-il ?Ces deux questions doivent recevoir une réponse suffisante avant que des modèles quantitatifs puissent être développés avec un pouvoir prédictif suffisant pour faciliter la recherche clinique et les applications.Le deuxième projet découle de questions en oncologie concernant les capacités locomotrices de divers types de cellules cancéreuses, mais les pose finalement dans un contexte plus large, en essayant de comprendre le mouvement des cellules dans le disposition d'une population croissante mais limitée dans l'espace. En s'appuyant sur le domaine de la mécanique statistique du non-équilibre appliquée aux particules en mouvement actif, un objectif important est de comprendre les effets d'une prolifération accrue sur le mouvement collectif.
Celpopulaties in het menselijk lichaam vormen complexe systemen. Het individuele celgedrag wordt gedreven door zowel talloze processen binnenin de cellen zelf, als door interacties met elkaar en hun omgeving. Een wiskundige beschrijving van fenomenen op het niveau van de weefsels vereist abstracties van deze onderliggende systemen om hanteerbare en interpreteerbare modellen te verkrijgen, waarbij vaak stochastische processen betrokken zijn. In dit proefschrift worden twee van dergelijke cellulaire systemen onderzocht. Het eerste is het menselijke hematopoëtische systeem: de machinerie waarmee voorlopercellen van het bloed worden ontwikkeld in het beenmerg. Dit proces is essentieel om de fysiologie van zoogdieren mogelijk te maken, van het leveren van zuurstofdragende rode bloedcellen tot het onderhoud van het immuunsysteem. Het verkrijgen van een kwantitatief inzicht in aspecten van dit systeem kan waardevolle inzichten en testbare voorspellingen opleveren met betrekking tot de oorsprong en de dynamiek van verschillende bloedgerelateerde ziekten. Echter, in vivo studies van ontwikkelende bloedcellen vormen een aanzienlijke uitdaging en in vitro studies leveren slechts een beperkt voorspellend vermogen op. De hiërarchische architectuur van het systeem verleent zich daarentegen handig naar het toepassen van wiskundige technieken op basis van slechts enkele aannames en parameters. Dit onderzoek heeft als doel bij te dragen aan twee bredere vragen met betrekking tot hematopoëse, de eerste zijnde "Wat is de structuur van dit systeem?" en de tweede "Hoe gedraagt het zich?". Beide vragen moeten voldoende worden beantwoord voordat kwantitatieve modellen kunnen worden ontwikkeld met voldoende voorspellende kracht om klinisch onderzoek te kunnen bijstaan.Het tweede project komt voort uit vraagstukken in de oncologie over de motorische capaciteiten van verschillende kankerceltypes, maar plaatst deze uiteindelijk in een bredere context, waarbij getracht wordt de stochastische beweging van cellen te begrijpen in de context van een groeiende maar ruimtelijk beperkte populatie. Uitgaande van het domein van de niet-evenwicht statistische mechanica toegepast op actief bewegende deeltjes, is een belangrijk doel het begrijpen van de effecten van een verhoogde proliferatie op de collectieve beweging.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Cha, Esther. "MARRYING IMMUNOTHERAPY AND CHEMOTHERAPY: A CANCER THERAPY BASED ON T LYMPHOCYTE EXPANSION AUGMENTED BY ALTERNATE GAMMA CHAIN CYTOKINES AND GEMCITABINE-MEDIATED INHIBITION OF MYELOID DERIVED SUPPRESSOR CELLS". VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1905.
Texto completoGrachan, Jeremy J. "Characterization of Hypoxia-Inducible Lipid Droplet Associated Protein (HILPDA) Dependent Lipid Droplet Abundance in Pancreatic Cancer Tumors Cells". The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1586437335477715.
Texto completoZimmerman, Shawn. "Regulated expression of follicle stimulating hormone receptor type III in cancer causing mouse ovarian surface epithelial cells". Thesis, Manhattan, Kan. : Kansas State University, 2007. http://hdl.handle.net/2097/495.
Texto completoKobia, F. M. "TARGETING NOTCH TRAFFICKING IN HUMAN CANCER CELLS: A. PHARMACOLOGIC INHIBITION OF THE VACUOLAR H+ ATPASE REDUCES PHYSIOLOGIC AND ONCOGENIC NOTCH SIGNALING. B. HIGH CONTENT SCREEN FOR NOVEL MODULATORS OF THE NOTCH PATHWAY". Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/365255.
Texto completoEl, Helou Rita. "Rôle des programmes épigénétiques dans la régulation de l'identité des cellules souches cancéreuses mammaires". Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5019.
Texto completoTumor heterogeneity observed in breast cancer is the main cause of clinical failures despite a significant therapeutic arsenal. This heterogeneity is explained by the presence of a minority population of cells, the cancer stem cells (CSC). CSC are resistant to conventional therapies causing relapse and metastasis. Deciphering programs regulating the cardinal properties of these cells, self-renewal and differentiation, is a crucial step for the development of new therapies. The identity of CSC is regulated by epigenetic mechanisms. The work of this thesis focused on the study of two epigenetic mechanisms: DNA methylation and microRNAs. We first identified a signature of 68 regions hypomethylated in CSC. This signature showed an enrichment of the TGF-ß pathway and had a prognostic impact on patient survival. We then were interested in the regulation of CSC by miRNAs. We identified miR-600, a bimodal microRNAs, regulating the self-renewal-differentiation balance. MiR-600 regulates Wnt pathway via SCD1. The identification of the miR-600/SCD1/Wnt axis opens a new therapeutic perspective to target CSCs. Our work deciphered epigenetic programs, regulating breast CSC-fate and open new perspective to improve breast cancer care
Shearstone, Jeffrey R. "Global DNA Demethylation During Erythropoiesis: A Dissertation". eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/549.
Texto completoSalameh, Ahlam Ibrahim. "METABOLIC ACIDOSIS AND THE DIVERSE ROLES OF THE Cl/HCO3 EXCHANGER (AE3) IN INTRACELLULAR pH HOMEOSTASIS". Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1473852052811835.
Texto completoCascales, Élodie. "L’enzyme CD10 : un acteur clé dans l’identification et la régulation des cellules souches mammaires humaines". Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10313/document.
Texto completoIn breast, the existence of cancer stem cells has been demonstrated and that explain a number of observations as tumour heterogeneity. Other studies have demonstrated the resistance of radio and chemotherapy by different innate or acquired stem cell specific mechanisms that could explain relapse few years after the traitment. For all these reasons, that is very important to understand these mechanisms and to know physiological actors both implicated in the regulation of normal or cancer stem cells. CD10 is a zinc-dependant metallo-endopeptidase that inactivates a number of signalling peptides that could be implicated in mammary growth and differentiation. We have showed that CD10+ cell sorted population is enriched in Stem Cells/Early Common Progenitors/MyoEPithelial cells. We demonstrate that the protease activity of CD10 and the adhesion function of beta1-integrin are required to prevent differentiation of mammary stem cells/early progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signalling factors by CD10 are key elements in the microenvironment that maintains the progenitor and stem cell pools in the mammary gland. Adipose tissue is also a major component of the mammary microenvironment implicated in its homeostasis by the secretion of soluble factors. Our results suggested that the adipose tissue could be considered as a potential source of stem cells that differentiated into the luminal epithelial lineage involved in some breast cancers