Tesi sul tema "Acidic tumor microenvironment"
Cita una fonte nei formati APA, MLA, Chicago, Harvard e in molti altri stili
Vedi i top-18 saggi (tesi di laurea o di dottorato) per l'attività di ricerca sul tema "Acidic tumor microenvironment".
Accanto a ogni fonte nell'elenco di riferimenti c'è un pulsante "Aggiungi alla bibliografia". Premilo e genereremo automaticamente la citazione bibliografica dell'opera scelta nello stile citazionale di cui hai bisogno: APA, MLA, Harvard, Chicago, Vancouver ecc.
Puoi anche scaricare il testo completo della pubblicazione scientifica nel formato .pdf e leggere online l'abstract (il sommario) dell'opera se è presente nei metadati.
Vedi le tesi di molte aree scientifiche e compila una bibliografia corretta.
Audero, Madelaine. "Acidic tumor microenvironment and Ca2+ signaling interplay in Pancreatic Ductal Adenocarcinoma (PDAC) progression". Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS105.
Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer affecting the pancreas, characterized by an unsatisfactory 5-year survival rate of around 10%, and to date, there are no effective therapeutic options for PDAC. This is in part due to a highly desmoplastic and immunosuppressive microenvironment that contributes to therapeutic failure. Moreover, the PDAC tumor microenvironment is featured by high acidosis (˂ pHe 6.5), a result of the metabolic reprogramming ("Warburg effect"), and hypoxic conditions, which offers important cues for its aggressiveness by selecting cancer cell phenotypes with competitive benefits for PDAC progression. In this context, Ca2+-permeable ion channels are known to regulate several hallmarks of cancer, including in PDAC. Therefore, they represent good target candidates due to their ability to integrate signals from the TME. Ca2+ channels are indeed pH and hypoxia sensors able to transduce TME signals to activate intracellular downstream pathways linked to PDAC progression. Although the roles of tumor acidosis and Ca2+ signaling in cancer progression are well established, the hypothesis of acidic TME employing Ca2+ signaling as a preferential route for sustaining tumor progression has not yet been sufficiently explored.My Ph.D. work aimed to study the phenotypic and genetic changes of PDAC cells upon acidic stress along the different stages of selection and to evaluate how tumor acidosis modulates Ca2+ signals and phenotypes in the PDAC cell lines, with a particular focus on Ca2+ oscillations and Store-Operated Ca2+ entry (SOCE). To this end, PANC-1 and Mia PaCa-2 cells were subjected to short- and long-term acidic pressure and recovery to pHe 7.4. The latter treatment was to mimic PDAC edges and consequent cancer cell escape from the tumor. The impact of acidosis was assessed for cell morphology, proliferation, adhesion, migration, invasion, invadopodia activity, and epithelial-mesenchymal transition (EMT) via functional in vitro assays and RNA sequencing, and for intracellular Ca2+ signals using Fura-2. Our results indicate that short acidic treatment limits the growth, adhesion, invasion, and viability of PDAC cells. As the acid treatment progresses, it selects cancer cells with enhanced migration and invasion abilities induced by EMT, thereby further enhancing their metastatic potential when re-exposed to pHe 7.4. RNA-seq analysis of PANC-1 cells exposed to short-term acidosis and pHe-selected recovered to pHe 7.4 revealed distinct transcriptome rewiring. We noted an enrichment of genes relevant to proliferation, migration, EMT, and invasion in acid-selected cells. Interestingly, PANC-1 cells are characterized by slower Ca2+ oscillations during short-term acid exposure compared to control cells and a tendency of ORAI1 downregulation at mRNA levels, while long-term acidosis and recovery to neutral pHe determine the recovery of fast Ca2+ oscillations and upregulation of ORAI1. In all our cell models, Ca2+ oscillations are SOCE-dependent, as ORAI1 blockade with Synta66 and siORAI1 results in impaired Ca2+ oscillations' initiation and maintenance. These data correlate with SOCE in PANC-1 cells, which is decreased during the short-term acid treatment, and increased in acid-selected cells with and without recovery to pHe 7.4. Finally, ORAI1-mediated Ca2+ entry might be involved in the activation of signaling cascades that lead to the increased migration and invasion of all the cell models exposed to acidic pHe, as Synta66 treatment and siORAI1 didn't affect control cells' invasion and migration.In conclusion, our findings show that acid-induced selection contributes to the acquisition of a more aggressive phenotype in PDAC cells, characterized by upregulation of SOCE, required for the generation of fast Ca2+ oscillations which may trigger Ca2+-dependent signaling pathways involved in PDAC progression
Schnipper, Julie. "The impact of the acidic tumor microenvironment on ion channel expression and regulation, in the progression of pancreatic ductal adenocarcinoma". Electronic Thesis or Diss., Amiens, 2022. http://www.theses.fr/2022AMIE0071.
The transient receptor potential canonical 1 channel (TRPC1) is one of the most prominent nonselective cation channels involved in several diseases, including cancer progression. TRPCs can be activated by different physio-chemical stimuli of their surroundings, for instance, pH. Another hallmark of cancer is the variable extracellular pH landscape, notably in epithelial cancers such as pancreatic ductal adenocarcinoma (PDAC). PDAC progression and development are linked to the physiology and microenvironment of the exocrine pancreas. There are strong indications that PDAC aggressiveness is caused by the interplay between the tumor acidic microenvironment and ion channel dysregulation. However, this interaction has never been studied before. Here, we investigate if TRPC1 is involved in PDAC progression in the form of proliferation and migration and if the pH fluctuations of the acidic tumor microenvironment affect these processes. We found that TRPC1 was significantly upregulated in PDAC tumor tissue compared to adjacent normal tissue, and in the aggressive PDAC cell line PANC-1, compared to a duct-like cell line, hTERT-HPNE. To investigate if fluctuations of the acidic tumor microenvironment affect TRPC1 dysregulation, PANC-1 cells were incubated in a medium with a pH of 7.4 or 6.5 over 30 days, where after cells were recovered in pH 7.4 for 14 days (7.4R). Acid adaptation (6.5) reduced TRPC1 protein expression but favored its membrane localization compared to the control (7.4). pH recovery treatment (7.4R) resulted in an upregulation of TRPC1 expression with a high membrane localization, both in 2D and 3D models. We found that pH fluctuations and the siRNA-based knock-down (KD) of TRPC1 affected 2D and spheroid PANC-1 proliferation, respectively. In our 2D model, flow cytometry and cell cycle regulating protein immunoblotting showed that TRPC1 KD affected the progression through G0/G1 phase under all conditions and S-phase under control pH 7.4, which shifts to the G2/M phase in pH 6.5 and 7.4R. In addition, pH 6.5 enhanced, and the KD of TRPC1 decreased cell migration, respectively. Furthermore, we found that TRPC1 interacted strongly with PI3K under acidic conditions and CaM under all conditions, and a KD of TRPC1 decreased both this interaction and the activation of AKT and ERK1/2. Finally, basal Ca2+ entry was significantly reduced upon the KD of TRPC1 in pH 6.5 and 7.4R, where the entry was enhanced. The reduction of extracellular Ca2+ concentration resulted in an additional decrease in proliferation and migration of cells transfected with siTRPC1 growing in pH 6.5 and 7.4R, but not in normal pH 7.4 conditions.Collectively, our results show that TRPC1 is upregulated in PDAC tissue and cell lines. The acidic tumor microenvironment favors its plasma membrane localization, and its interaction with PI3K/CaM and Ca2+ entry leads to PDAC cells proliferation and migration. In addition, we performed an expression profile screening of ORAI channels, their partner STIM1, and a voltage-activated sodium channel (Nav1.6), and an acid-sensing ion channel (ASIC1) in PDAC tissues and cell lines, and investigated whether the acidic tumor microenvironment affects epigenetic regulation of ion channel expression. We found that ORAI3 was upregulated in PDAC tissue compared to normal tissue, where STIM1 and NaV1.6 were significantly downregulated. Moreover, ORAI3 was more localized in the plasma membrane in tumor tissue. Acid-adaptation had a differential effect on Ca2+ channel expression. Furthermore, our preliminary results show that the acidic tumor microenvironment does not affect the methylation levels of the ASIC1 or TRPC1 promoter region, but so some extend the SCN8A gene promoter
Assi, E. "ROLE OF ACID SPHINGOMYELINASE IN THE TUMOUR MICROENVIRONMENT". Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229416.
Al-Husari, Maymona. "Mathematical modelling of the tumour microenvironment : the causes and consequences of tumour acidity". Thesis, University of Strathclyde, 2012. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=18965.
Timosenko, Elina. "Tryptophan catabolism and amino acid transporter reprogramming in the tumour microenvironment". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:33745777-7aab-4342-b997-fc4317ec34fb.
Silva, Lídia [Verfasser], e Rüdiger [Akademischer Betreuer] Hell. "Branched-chain amino acid metabolism in the tumor microenvironment interaction / Lidia Silva ; Betreuer: Rüdiger Hell". Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177148897/34.
Alruwaili, Waad A. "Conjugated Bile Acid and Sphingosine 1-phosophate prompt Cholangiocarcinoma Cell Growth via Releasing Exosomes". VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5715.
Dong, Jihu. "Physiopathologie de cellules souches cancéreuses isolées de glioblastomes primitifs et évaluation pré-clinique de molécules "tête de série" par une approche de biologie et de chimie médicinale". Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ036/document.
Glioblastomas are the most malignant primary brain tumors. The identification of glioblastoma stemcells (GSCs) has transformed our comprehension of those tumors by revealing a hierarchical organization. GSCs can self-renew, differentiate and enter into a quiescent state. They are considered as cells which fuel and as the main culprits of tumor relapse. The discovery of GSCs triggered a change in paradigm for cancer therapy. Indeed to gain in efficacy, therapies need to target, not only the cells forming the bulk of the tumor, but also GSCs particularly resistant and endowed with a high tumorigenic potential. Chemical screening of the Prestwick chemical library in our laboratory, unveiled bisacodyl with a specific activity on quiescent GSCs.This thesis presents work on the characterization of GSCs, study of the mode of action of bisacodyl on GSCs, as well as a preclinical evaluation of bisacodyl on a 3D model in vitro and animal models in vivo
Sadiq, Barzan A. "A dissection of class I phosphoinositide 3-kinase signalling in mouse embryonic fibroblasts and prostate organoids". Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/278056.
Tang, Ching-Chun, e 湯景鈞. "Study on Acidic Tumor Microenvironment in Oral Cancer". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/m37yv5.
國立臺灣大學
口腔生物科學研究所
107
The microenvironment of cancer cells is considered to be an important indicator of cancer progression. Studies have shown that due to the specific metabolic mechanisms of cancer cells, the extracellular matrix of cell has a higher hydrogen ion concentration than the cytoplasm. Exposure of cancer cells to this environment has an effect on their function, including changing in the metabolic system, mediating the growth processes, and expression of autophagy proteins. Compared with cancer within other parts of the body, the oral cavity is the only access to the digestive system. The cancer cells that grow in are more frequently affected by the external environment, especially with acidic environment due to food digestion of secreting seliva. Therefore, Oral cancer cells are not only influenced by endogenous micro-acidification, but also by the exogenous oral digestive system, we presumed that oral cancer should have higher research value in related field about how the microenvironment acidosis changing cell performance. However, there are few related studies using oral cancer as a subject. In this thesis, the influence of the slightly acidic environment on the growth of cancer cells is taken as the main story. We collaboration in vivo and in vitro experiment. Observing the performance of stemness and extented to drug resistance, proofing that both in vivo and in vitro test can show consistent results. The results show that acidification has significant impact on different types of oral cancer cells line. For tongue cancer (SAS), long-term acid stimulation its ability to upregulate stemness and further have its influence on proliferation and chemoresistance, at the meanwhile acidosis cancer cell can also improve its vasculogenic mimicry ability. But the acidosis stimulation has totally different influence on oral squamous cell carcinoma (OECM1), stemness of the OEMC1 was down regulation after acid treated but proliferation and chemoresistance ability was same as SAS. Nevertheless, OECM1 in vivo tumor incident rate showed dramatic different from in vitro side population data that OECM1 had much more lower tumor incident rate than SAS. Leak of vasculogenic mimicry ability may be one of the reason that tumor couldn’t form enough vascular-like tube to gain nutrient and lead awful in vivo tumor incident rate.
Chen, Yu-Hsuan, e 陳羽萱. "Roles of Matrix Metalloproteinase 1 (MMP-1) in Acidic Pancreatic Tumor Microenvironment". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/j3hdvg.
Wen-JuChung e 鍾雯如. "Clinical implication of squamous cell carcinoma antigen(SCCA)overexpression in acidic tumor microenvironment". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/07924706339876000152.
國立成功大學
口腔醫學研究所
100
In clinical, tumor markers can be use to help cancer diagnosis , predict the patient’s response to particular therapies and follow-up disease. The squamous cell carcinoma antigen (SCCA) is a tumor marker and has a clinical value. In clinical diagnosis, patients with higher expression of SCCA show poor prognosis. However, SCCA in clinical use was more than 20 years, but the biological function and mechanism still remain unclear. Our previous studies, we found that overexpression of SCCA led to drug resistance, such as RSV (Resveratrol) and Cisplatin. Cancer cells usually grow faster than normal cells. In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed the “Warburg effect”. Many cancer cells consume glucose and produce lactic acid and cause acidification of the tumor extracellular environment. Acidification of the tumor extracellular environment may promote tumor formation and metastasis. In our previous studies showed the SCCA is a lysosomal proteases inhibitor and could inactivate cathepsin L and anti-cell death. This study we show the cancer cells cultured in low pH (Acidosis) media, increase SCCA expression. The cancer cells culture in low pH (Acidosis) media display drug resistance of RSV (Resveratrol) and Cisplatin. The acidosis enhances the formation of reactive oxygen species (ROS) and induces MAPK signaling pathway and transcription factor, CREB phosphorylation. The cancer cells treated with ROS scavenger reduce SCCA expression and CREB phosphorylation in acidosis condition. We found that, there is a CREB binding region in the promoter region of SCCA1 gene. These results suggested that acidosis increased phosphorylation of the transcription factor CREB via ROS, and them increased its transcriptional activity. Taken together, we suggest cancer resist drug-induced cell death in acidosis condition is through ROS-increased CREB transcriptional activity to promote SCCA1 gene expression .
BOUSSADIA, ZAIRA. "A new cell labelling strategy to study the biogenesis of exosomes and their role in human melanoma progression driven by microenvironmental acidic pH". Doctoral thesis, 2019. http://hdl.handle.net/11573/1227652.
Exosomes, nanosized vesicles of endosomal origin, are worldwide recognized for their ability to transfer biological molecules, from cell to cell, crucial for both physiological and pathological processes. Hundred studies have been focused on exosome application also to clinics although biogenesis modalities are under investigation. Therefore, we set up a new effective fluorescent labelling strategy to trace exosome biogenesis and release with the aim to seek in human melanoma cell lines the impact that tumor progression may exert on their secretion and composition. Cells exposed to a fluorescent analogue of palmitic acid (Bodipy FL C16) were able to promptly synthetize fluorescent phospholipids, constituents of exosome membrane bilayer. Afterwards, we were able to follow exosome biogenesis from the intracellular sites of origin to cell secretion, chasing over time by direct cytofluorimetric analysis. To get insight into their function, we focused our studies on exosomes derived from melanoma cells maintained at low pH, which is a microenvironmental leverage for primary tumor to be transformed into widespread metastasis. When melanoma cells at specific intermediate stage were subjected to an acidic microenvironment, showed an increase in exosome release and transfer capability. Most importantly, when control melanoma cells were incubated with exosomes secreted in acidic medium acquired migratory and invasive capacities, demonstrating that exosomes carrying molecular payload can modify recipient cell program. Finally, meta-analysis and ex vivo studies confirmed the importance of acidic exosomes molecule content as marker of melanoma progression and so exosomes prognostic and diagnostic value.
BELLENGHI, MARIA. "Fatty acids role in cancer: Stearoyl-CoA desaturase 5 and its product oleic acid reduce melanoma dissemination by impairing tumor microenvironment". Doctoral thesis, 2017. http://hdl.handle.net/11573/936855.
Lima, Beatriz Vargas Cruz Antunes de. "Engineering Chitosan/Poly-(y-glutamic acid) nanoparticles to reshape the tumor microenvironment". Master's thesis, 2020. https://hdl.handle.net/10216/131418.
Lima, Beatriz Vargas Cruz Antunes de. "Engineering Chitosan/Poly-(y-glutamic acid) nanoparticles to reshape the tumor microenvironment". Dissertação, 2020. https://hdl.handle.net/10216/131418.
Bai, Yu-Chi, e 白育齊. "Mechanism analysis and effect of tumor microenvironment properties on the uptake of boric acid in human hepatoma HepG2 cells". Thesis, 2017. http://ndltd.ncl.edu.tw/handle/7yt4a3.
Hsieh, Chia-Yuan, e 謝佳芫. "Betulinic acid, a potent anticancer triterpenoid, induces endoplasmic reticulum stress in human gastric cancer cells and modulates the tumor microenvironment". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/6266aw.
高雄醫學大學
藥學研究所
102
Gastric cancer is a high prevalent carcinoma and the leading cause of cancer-related mortality in Taiwan. Betulinic acid (BA), a triterpene isolated from the white birch tree, has been reported to exhibit anti-inflammatory and anti-tumor properties. However, the mechanisms of BA responsible for the induction of gastric cancer death remain unclear. The endoplasmic reticulum (ER) is a membranous network within cells, and it is important for several cellular functions, including translation, folding of secretory proteins and sequestration of Ca2+. ER homeostasis is very sensitive to perturbations in cellular homeostasis and activates an adaptive response when it senses stressful conditions. This can occur in response to conditions such as, disturbed Ca2+ homeostasis, accumulation of misfolded proteins and oxidative stress. Numerous studies have also shown that ER stress-related chaperone proteins are overexpressed in many cancers, and are important for tumor development. Therefore, elimination of pro-survival chaperone proteins and induction of excessive ER stress may promote cancer cell apoptosis. Recently, cancer-associated fibroblasts (CAFs) in cancer microenvironments have been implicated in tumor growth and metastasis of various cancers. TGF-?? signaling may link with promoting fibroblast activation by up-regulation of ??-SMA expression during tumor development. In this regard, the present study assessed the anticancer effects of BA on human gastric cancer cells. A mechanistic analysis demonstrated that BA-induced human gastric cancer cell death was down-regulation of ER stress-related pro-survival chaperones and activation of mitochondrial-dependent apoptosis pathway. BA not only induced gastric cancer cell death, attenuated TGF-?? expression partially through HOXA9-mediated pathway, but also inhibited TGF-??-induced human fibroblasts (HS68) activation. In conclusions, these results provide a molecular basis for the ability of BA to mediate gastric cancer death, suppress fibroblasts activation. BA may be regarded as a promising agent in anti-gastric tumor therapy.