Tesi sul tema "Cancer-On-Chip"
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Chatagnon, Amandine. "Spécificité de liaison et de répression de la " Methyl-CpG-Binding Domain protein 2 " (MBD2) : identification de gènes cibles impliqués dans les cancers". Phd thesis, Université Claude Bernard - Lyon I, 2009. http://tel.archives-ouvertes.fr/tel-00603777.
Maassarani, Mahmoud El. "Identification de gènes cibles d'ErbB380kDa et caractérisation de leur implication au cours de la progression du cancer de la prostate". Thesis, Poitiers, 2014. http://www.theses.fr/2014POIT2275/document.
Prostate cancer (PCa) is dependent on androgens and functional androgen-receptor (AR) for growth and proliferation. Androgen-directed therapy is used at the first stages of the disease but cancer cells frequently become resistant (CRPC) by inappropriate reactivation of AR activity. As ErbB receptors are expressed in PCa cells, therapies aiming at inactivate the pathways downstream have been tested in advanced prostate cancers alongside hormone-based therapy. Still, a significant proportion of CRPC treated by ErbB1/2 inhibitors resist to treatment. ErbB3 could be responsible for this failure through both its unexpected nuclear localization and the reactivation of the PI3K-Akt pathway in those advanced tumors.We have described a nuclear ErbB380kDa isoform, expressed in hormone-sensitive (LNCaP) and hormone-resistant (PC3) PCa cell lines that accumulates in the nucleus of tumor cells during cancer progression. ChIP-on-chip experiments led us to characterize 353 target promoters binding ErbB380kDa in both cell lines; 245 promoters specific to LNCaP and 925 specific to PC3 cells, among which the promoter of GATA2. We show that ErbB380kDa functions as a transcriptional co-regulator for the studied genes, potentially through its interaction with transcription factors. In silico analysis revealed binding sites for GATA2 and MZF1 transcription factors on the target promoters, and a complex GATA2-MZF1-ErbB380kDa has been found in LNCaP and PC3 cells. Recent publications have reported a role for GATA2 in the regulation of RA responsive-genes and in metastatic spreading. We propose that ErbB380kDa could act, upstream of GATA2, to induce resistance mechanisms and facilitate cancer progression. Thus, ErbB380kDa emerges as a putative target for the development of new therapies in prostate cancer
Alexander, Frank. "RTEMIS: Real-Time Tumoroid and Environment Monitoring Using Impedance Spectroscopy and pH Sensing". Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5168.
Han, Arum. "Microfabricated Multi-Analysis System for Electrophysiological Studies of Single Cells". Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/11639.
Veith, Irina. "Lung Cancer On-Chip for Immunotherapy Response Profiling Apoptosis Mapping in Space and Time of 3D Tumor Ecosystems Reveals Transmissibility of Cytotoxic Cancer Death". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL036.
Non-small cell lung cancer (NSCLC) is one of the few tumor diseases, with melanoma and vesical carcinoma, for which immuno-oncology drugs led to a therapeutic revolution. Only 20 to 30% of the NSCLC patients benefit from immune checkpoint inhibitors (ICI) monotherapy with durable responses, while combinations led up to 40% of long responder patients. Our study aims to better characterize the modulation of the tumor microenvironment upon ICI treatment, plus or minus concurrent chemotherapy, in order to guide more compelling immunotherapy strategies. Inspired by the organ-on-a-chip technology, we implemented the reconstitution ex vivo of a simplified immunocompetent lung tumor microenvironment by performing 3D co-cultures in microfluidic devices. This approach allowed us to perform live-imaging and quantification of the effects of ICI on the tumor ecosystem.The design of the chip consists of three parallel micro-chambers, separated by micro-pillars that allow the confinement of a biomimetic hydrogel in the central channel by capillarity. By co-culturing autologous NSCLC cells and cytotoxic T lymphocytes (harvested from the TILs of the same patient and furtherly amplified in vitro) we could recapitulate, visualize and quantify an efficient and specific cytotoxic activity of the T cells against the autologous cancer cells. For this purpose, we developed a novel algorithm that could localize the cancer cells and, thanks to a fluorescent reporter of the caspase activity, measure their death in a time- and space-specific manner. In these 3D co-cultures the cytotoxic activity of T cells was enhanced by the treatment with PD-1 inhibitor and PD-L1 inhibitor, therefore reconstituting on-chip an ICI response. Furthermore, this method allowed us to extract a parameter, the potential of death induction, which mathematically estimates the “contagiousness of death” by computing the proximity in space and time of death signals. Interestingly, this analysis revealed us that the death of cancer cells caused by either chemotherapy or cytotoxic T cells is contagious, whereas in control conditions the cancer cells death is stochastic. This observation may have biological and clinical implications, for instance regarding the bystander effect, observed after radiotherapy treatment. Furthermore, in order to have a molecular insight on the impact of the co-culture on T cells, in presence or absence of ICI, we analyzed by flow cytometry the expression of several T cell markers. After 3 days of co-culture on chip, the T cells showed an increased expression of activation markers, such as CD69 and CD25, as well as an increased expression of exhaustion markers, notably PD-1, TIGIT, TIM-3, LAG-3, CD137 and OX-40. The coupling of image analysis and the study of T cell plasticity, allowed us to associate for the first time the finely quantified cytotoxic activity of the T cells and their activation/exhaustion status and describe a responsive phenotype to immunotherapies. In this thesis, we demonstrated that the tumor-on-chip is suitable to evaluate the efficacy of immune checkpoint inhibitors, to potentially assess the effect of combined drugs and to study the mechanisms of cancer cell primary resistance
Browne, Andrew W. "Translational Lab-on-a-Chips with the Development of a Novel Cancer Screening Method". University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275659036.
Salmanzadehdozdabi, Alireza. "Microfluidic differentiation of subpopulations of cells based on their bioelectrical signature". Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/19370.
Microfluidics devices were engineered for differentiation of subpopulations of cells based on their bioelectrical properties. These microdevices were utilized for separating prostate, leukemia, and three different stages of breast cancer cells from hematologic cells with concentrations as low as 1:106 with efficiency of >95%. The microfluidic platform was also utilized to isolate prostate cancer stem cells (CSCs) from normal cancer cells based on their electrical signature. Isolating these cells is the first step towards the development of cancer specific therapies. The signal parameters required to selectively isolate ovarian cancer cells at different cancer stages were also compared with peritoneal cells as the first step in developing an early diagnostic clinical system centered on cell biophysical properties. Moreover, the effect of non-toxic concentrations of two metabolites, with known anti-tumor and pro-tumor properties, on the intrinsic electrical properties of early and late stages of ovarian cancer cells was investigated. This work is the first to show that treatment with non-toxic doses of these metabolites correlate with changes in cells electrical properties.
Ph. D.
Saint-Auret, Gaëlle. "Identification de la signature moléculaire de C/EBPβ dans la cellule d'hépatome humain Hep3B". Rouen, 2008. http://www.theses.fr/2008ROUES057.
The liver plays an essential part in complex metabolic regulations which widely contribute to the body homeostasis. Moreover, this organ conducts the qualitative and quantitative changes in the production of specific proteins immediately induced during the acute phase response and allowing a progressive come back to homeostasis. The liver-enriched transcription factor CCAAT enhancer-binding protein beta (C/EBPβ) is widely involved in these processes, but its precise the role isnot still defined. Conflicting studies have described contradictory functions for this transcription factor which could be explained by the complex mechanisms regulating the C/EBPβ activity. Indeed, C/EBPβ encodes an intronless gene that generates a single mRNA that is alternatively translated into two major isoforms : an active LAP (liver-enriched activator protein) and a dominant negative LIP (liver-enriched inhibitory protein). Today, few studies have really taken into account the present isoform. In order to better understand the precise role of each isoform, we first engineered the Hep3B human hepatoma cell line with a Tet-off inducible LAP or LIP isoform. The antagonistic role of the both isoforms in C/EBPβ target-genes transcription has been used as a strategy to better define the C/EBPβ-regulated genes. Then, the identity and the transcription (direct or indirect) of all these target-genes were determined by two functional genomic approaches : the transcriptome analysis by cDNA arrays and the chromatine immunoprecipitation on chip (ChIP on chip). Using a cDNA microarray which provides a complete coverage of the liver transcriptome, we identified 676 genes inversely regulated by LAP and LIP in the Hep3B hepatoma line. The analysis of the biological functions regulated by these genes brought into the flore an induction by LAP and a repression by LIP of several pathways including hepatic metabolism (fat, detoxification), transcription, translation, apoptosis and regulation of the cell proliferation. Moreover, the ChIP on chip study allowed the identification of 38 C/EBPβ new direct targets. According to the data resulting from the transcriptome analysis, several functional studies have been carried out. They allowed us to prove, for the first time, that LAP was, not only able to suppress the cell proliferation in the absence of RB and P53, but that this isoform also increased the staurosporine-induced apoptosis in Hep3B cells while LIP had a protector effect. Furthermore, the Hep3B cells expressing LAP or LIP have been stimulated by a conditioned medium rich in proinflammatory cytokines in order to mimic the hepatic response to the acute phrase of inflammation. In this experimental context, and still by transcriptome analysis, we brought into the fore a group of 77 genes regulated by LAP and LIP which interestingly seem to be involved during the acute phrase response. To conclude, our original approach characterized by the identification of genes inversely regulated by LAP and LIP allowed us to better understand how these two isoforms of C/EBPβ manage several physiological and pathological liver processes
Ahmad-Cognart, Hamizah. "Study of the Metastatic Process of Circulating Tumour Cells by Organ-on-a-Chip In Vitro Models". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC139/document.
90% of cancer mortality arises from metastases, due to cells that escape from a primary tumor, circulate in the blood as circulating tumor cells (CTCs), leave blood vessels and nest in distant organs. The processes by which CTCs invade distant organs, remodel their environment to create a “micrometastatic niche”, the eventual triggering of a proliferation leading to a macroscopic metastases, are poorly known, mostly because of a lack of experimental models. These events are rare; occur in the body at unknown places and on a microscopic scale. The loss of cell adhesion of tumor cells detaching from the primary tumor tissues will undergo a transformation phenomenon known as epithelial-to mesenchymal transition (EMT) leading to the loss of epithelial characteristics with different expression patterns of EMT markers (E-cadherin, N-cadherin, Vimentin, Snail1/2, Twist1/2, ZEB1/2). The changes in mechanical and physical properties of interacting cells during morphological and malignant transformation are investigated and their quantifications measured. Here, microfluidic models containing mechanical constrictions in order to mimic the blood microcirculation have been designed and fabricated. Metastatic breast cancer cells are subjected and confined to the microfluidic channels using a flow control system. These cells are circulated under optimal culture conditions, and monitored in the channels for the observance of biophysical occurrences from continuous mechanical cellular deformations. The biophysical effects of circulation and confinement on tumor cell morphogenesis will be investigated
Baka, Zakaria. "Élaboration de cancers sur puce pour des applications en thérapies anticancéreuses". Electronic Thesis or Diss., Université de Lorraine, 2023. http://www.theses.fr/2023LORR0175.
Ovarian cancer is a major public health issue. Moreover, new treatments still face very high failure rates. This is mainly due to the unreliability of conventional preclinical models such as 2D cell culture. Thus, new tools based on 3D cell culture have emerged such as spheroids and organoids. However, these models have their own limitations (cost, difficulty of application). 3D bioprinting is a new approach to create tunable and reproducible tumor models. However, very few bioprinted tumor models have been reported so far. Besides the “third dimension”, it is important to consider the dynamic conditions of the tumor environment. This has been possible for some years now thanks to microfluidics-based cancer-on-a-chip technology. However, this technology currently does not simulate the drug vascular transport before its interaction with the tumor cells. In this PhD project, we set out to create a dynamic, three-dimensional model of ovarian cancer by combining 3D bioprinting and microfluidics. First, 3D bioprinting was used to create the tumor structure itself. For that, we formulated a bio-ink comprising SKOV-3 ovarian cancer cells and MeWo cancer fibroblasts embedded in a gelatin – alginate hydrogel. The bioprinted tumor structures were then characterized by various techniques to demonstrate their viability and biological relevance. Their response to anticancer drug cisplatin was also assessed. In the second step, we integrated the bioprinted tumor model into a microfluidic support for culture under physiological flow. This support was also intended to simulate the drug's vascular transport prior to interaction with the tumor tissue. We then used computational fluid dynamics to design an improved version of the first system. The aim of this improved version was to simultaneously assess multiple drug concentrations. This PhD project demonstrated the ability of 3D bioprinting to create viable and functional ovarian tumor models. It has also brought interesting research prospects with regard to the possibilities of combining 3D bioprinting and microfluidics to improve preclinical modeling of ovarian tumors
Miollis, Frédérick de. "Développement d’un système de culture in vitro 3D et microfluidique pour étudier les interactions tumeur-stroma et la résistance aux drogues de l’adénocarcinome du pancréas". Thesis, Lille, 2021. http://www.theses.fr/2021LILUI015.
Pancreatic cancer is one of the deadliest cancers with an extremely poor prognosis. In 2020, the 5-year survival rate remains very low (only 3 to 9%) and the median is less than 6 months. Despite significant progress in the patient care, current therapies do not have the expected effectiveness. This is due to the strong chemoresistance observed in this cancer. The key factor of this resistance is the complex tumor microenvironment mainly composed of stroma and a dense extracellular matrix limiting the access of therapies to the tumor. The current models’ limitations, particularly in terms of physiological relevance, are a major obstacle in understanding this chemoresistance. In response to this issue, researchers are turning to different approaches by developing brand new models that are alternatives to those already available (in vitro and in vivo).The objectives of this work were: (i) to develop an in vitro 3D microfluidic culture device allowing to reproduce the tumor microenvironment both biologically and mechanically, as well as to model the flows and mass transport present in a pancreatic tumor, and (ii) to approach the morphological changes of the co-culture by studying epithelio-mesenchymal markers and to study the impact of FOLFIRINOX chemotherapy in this model.First, we have shown numerically and experimentally the feasibility of such an in vitro model. The chosen extracellular matrix is a combination of collagen I and hyaluronic acid creating a rigid structure close to in vivo conditions. It allows long-term culture maintenance under the effect of the perfusion as well as the activation of pancreatic stellate cells. The chosen perfusion rate allows to apply an interstitial flow in the model equivalent to the one observed in the in vivo microenvironment, inducing hydrostatic pressure and shear stress on the cancerous cells.Then, we demonstrated the biological contribution of this model by showing an increased chemoresistance to the FOLFIRINOX protocol of tumor cells both in mono- and in co-culture in the microfluidic device. We also show the establishment of a process presenting characteristics of epithelial-mesenchymal transition and a possible promotion of a dedifferentiated phenotype of tumor cells by activated pancreatic stellate cells.In conclusion, we present in this thesis an original microfluidic model allowing to mimic a tumor (co-culture of epithelial and mesenchymal cells) and to study the kinetics of a complex multidrug chemotherapy. In the future, the device should allow us to further study the mechanisms of drug resistance and tumor-stroma interactions in pancreatic cancer
Bourg, Samantha. "Développement de systèmes miniaturisés à base d’aptamères pour la détection de biomarqueurs de cancer". Thesis, Paris Sciences et Lettres (ComUE), 2019. http://www.theses.fr/2019PSLEC020.
Common methods of cancer diagnosis are invasive, expensive and rarely allow early cancer diagnosis. The discovery of cancer biomarkers present in the early stage of the disease, well before the development of symptoms make them interesting candidate for early cancer diagnosis. These markers are still not widely used, particularly because of their low concentration in healthy patient samples, but also because of their lack of specificity taken individually. Nowadays, clinical analyses for the diagnosis are performed by dividing samples and separate measurements of the concentration of the various clinically relevant analytes. In this context, the development of devices for the simultaneous detection of these markers in biological fluids is a real challenge. In addition, the miniaturization of measurement devices and their integration on a chip opens the way to automated analysis units that can be transported to the bedside and meet the needs of hospitals for fast, low-volume, low-cost, high throughput, sensitive and specific analyses. The objective of this thesis is to develop methods for the localized immobilization of selective ligands based on molecular recognition (aptamers) on different microsystem materials for the simultaneous detection of several biomarkers. Aptamers are a new classe of synthetic DNA/RNA molecules, known for their high affinity and excellent specificity for a selected target or family of targets. They also have the advantage of being easy to handle at room temperature and easily regenerated after denaturation. Despite these advantages, very few publications have been published on aptamer-based technologies for the selective extraction and analysis of biomarker traces in microfluidic devices. The creation of such localized zones ensures the overconcentration of target analytes to improve detection performance
Shah, Pranjul, Joëlle V. Fritz, Enrico Glaab, Mahesh S. Desai, Kacy Greenhalgh, Audrey Frachet, Magdalena Niegowska et al. "A microfluidics-based in vitro model of the gastrointestinal human–microbe interface". NATURE PUBLISHING GROUP, 2016. http://hdl.handle.net/10150/614760.
Carvalho, Mariana Rodrigues de. "Tissue engineered in vitro models on a chip for cancer research". Doctoral thesis, 2019. http://hdl.handle.net/1822/64605.
By 2030, the global burden is expected to grow to 21.7 million new cancer cases and 13 million cancer deaths simply due to the growth and aging of the population. Among all types of cancer, colorectal cancer is a major cause of morbidity and mortality worldwide, and accounts for over 9 % of all cancer incidence. It is the third most common cancer worldwide and affects men and women equally. In order to win the battle against cancer, further advances are in great need to unveil identification of cancer-causing agents in in vitro and in vivo animal models, as well as for the development of personalized therapies, drug screening, and to provide insightful knowledge on the mechanisms of tumor growth and metastasis. Microfluidic devices, together with tissue engineering strategies and nanotechnology have emerged as a powerful platform to tackle the previously mentioned hurdles. These themes are the focus of Section 1, in Chapters I, II and III. In this thesis we focus on the application of CMCht/PAMAM dendrimer nanoparticles.as the synthesis, uptake efficiency/internalization and cytotoxic effect of fluorescent-labeled CMCht/PAMAM dendrimer nanoparticles was investigated using different cancer cell lines in both traditional culture flasks and under physiological flow inside a microfluidic platform (Chapter V). Other than nanoparticles, the use of different biomaterials to modulate 3D microenvironment of tumors is of the utmost importance. Therefore, the use of HRP-crosslinked SF hydrogels with spatial tunable properties was proposed in a colorectal cancer extravasation 3D model on a commercial chip Vena4™ (Chapter VI). To increase the complexity of the cancer models, a microfluidic chip was designed and fabricated for the incorporation of tumor and vascular parts, allowing for gradients of gemcitabine released from CMCht/PAMAM nanoparticles to be tested (Chapter VII). Chemical modification in the CMCht/PAMAM dendrimer nanoparticles in order to target colorectal cancer was also achieved in Chapter VIII. In Chapter IX, a new proof of concept consisting of a microfluidic silk platform, flexible and implantable, was developed in house. The results and platforms developed in this thesis are discussed in Chapter X and represent a strong advance in the field of lab-on-chip research and will be a useful tool for drug discovery and study of migration/metastasis phenomena, allowing for a versatile choice of tissues, biomaterials and biological assays.
Até 2030, o número global de novos casos de cancro deverá crescer para 21,7 milhões, com cerca de 13 milhões de mortes, simplesmente devido ao crescimento e envelhecimento da população. Entre todos os tipos de cancro, o cancro colorretal é uma das principais causas de morbidade e mortalidade em todo o mundo, representando mais de 9 % entre todos os tipos de cancro. Com o objectivo de ganhar a guerra contra o cancro, novos avanços são rapidamente precisos, a fim de identificar, em modelos animais in vitro e in vivo os agentes causadores de cancro, bem como para o desenvolvimento de terapias personalizadas, teste de novos fármacos e aumentar o conhecimento actual sobre os mecanismos de crescimento tumoral e metástases. Dispositivos de microfluídica juntamente com estratégias de engenharia de tecidos e nanotecnologia surgiram como uma poderosa plataforma para lidar com os obstáculos mencionados anteriormente. Esses temas são o foco da Secção 1, nos Capítulos I, II e III. Nesta tese damos enfâse à aplicação de nanopartículas CMCht/PAMAM. A síntese, eficiência, internalização e efeito citotóxico das mesmas foram investigados usando diferentes linhas de células tumorais em frascos de cultura tradicionais e dentro de uma plataforma microfluídica (Capítulo V). Além das nanopartículas, o uso de diferentes biomateriais para modular o microambiente 3D de tumores é de extrema importância. Portanto, o uso de hidrogéis SF reticulados com HRP com propriedades mecânicas ajustáveis foi proposto num modelo 3D de extravasamento de cancro colorretal num chip comercial VenaT4™ (Capítulo VI). Para aumentar a complexidade dos modelos de cancro em chips, uma plataforma microfluídica foi projetada e fabricada para a incorporação de ambas as partes tumorais e vasculares, permitindo testar gradientes de gemcitabina libertados das nanopartículas CMCht/PAMAM (Capítulo VII). Modificações químicas nas nanopartículas para atingir especificamente células cancerígenas também foram alcançadas no Capítulo VIII. No Capítulo IX, uma nova prova de conceito consistindo numa plataforma microfluídica de seda, totalmente flexível e implantável, foi desenvolvida. Os resultados e plataformas desenvolvidos nesta tese representam um forte avanço no campo da investigação do cancro, e serão uma ferramenta útil para a descoberta de drogas e estudo de metastases, permitindo uma escolha versátil de tecidos, hidrogéis e ensaios biológicos.
Sultana, Ruksar. "Lab-on-a-chip tissue engineered 3D cancer model for in-vitro anti-cancer drug screening". Thesis, 2014. http://ethesis.nitrkl.ac.in/6401/1/E-2.pdf.
Raamanathan, Archana. "Programmable bio-nano-chip immunosensor for multiplexed detection of ovarian cancer biomarkers". 2011. http://hdl.handle.net/2152/20658.
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Goldvasser, Pavel. "Identification of Novel Notch Target Genes in Breast Cancer". Thesis, 2011. http://hdl.handle.net/1807/30607.
Jokerst, Jesse Vincent. "Next generation transduction pathways for nano-bio-chip array platforms". Thesis, 2009. http://hdl.handle.net/2152/26880.
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Weigum, Shannon Elise. "Development of a cell-based lab-on-a-chip sensor for detection of oral cancer biomarkers". 2008. http://hdl.handle.net/2152/9817.
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Tsao, Chia-Ling, e 曹嘉玲. "Using on-chip cytokine immunofluorescence assay (CIFA) to study lung cancer cell responses to external stimulations". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/sm74us.
Hsieh, Hui-Hsia, e 謝蕙霞. "A Gene Chip Approach to Anti-cancer Effect of Tien-Shen Lingzhi Ethanol Extracts on Non-Small Cell Lung Cancer Cell Line". Thesis, 2010. http://ndltd.ncl.edu.tw/handle/31056900584822048788.
亞洲大學
生物資訊學系碩士班
98
Background: Lung cancers are among the neoplastic diseases with the worst prognosis. More treatment modalities are needed to improve clinical outcome. It’s being a new trend to search for bioactive traditional Chinese medicines (TCM). Ganoderma, also known as Lingzhi, is a TCM and has been widely used for improving human health for centuries. We have addressed the anticancer effects of Ganoderma on various cancers. In this study, a comprehensive genomic profiling was used to further explore the signal pathway for the anticancer effects of Tien Shen Lingzhi(TSL),an improved strain of Ganoderma tsugae. Methods: A comparative genomics study was performed to search for TSL-mediated differential expressions on H23/0.3 cells. Bioinformatics tool, e.g., GeneGo Meta CoreTM ,was used to analyze the experimental results based on Affymetrix Human Genome U133 Plus 2.0 microarray. Results: The whole-genome expression profiles of H23/0.3 with or without TSL treatment were resolved by multidimentional scaling (MDS) analysis. It indicated a TSL-mediated cell cycle perturbation. Bioinformatics analysis showed cell cycle was the most affected pathway. GeneGo Meta CoreTM derived cellular pathway map revealed dramatic hits (17/26) on the signal transduction of DNA replication. The microarray results were confirmed by Q-PCR. Conclusion: The genomic microarray data demonstrates the TSL-induced cell cycle deregulation in H23/0.3 cells. TSL-mediated cell cycle perturbation on H23/0.3 cells is consistent with the cellular pathway map resulting from GeneGo Meta CoreTM analysis.
Lu, Chung-Huan, e 呂仲桓. "The on-chip high- efficient electrofusion of dendritic cells and tumor cells for efficient cancer vaccine generation". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/r7vqda.
國立清華大學
動力機械工程學系
102
Because people lifestyle changed, cancer has been the top ten causes of death for 13 years. In every 100 people, 28 people were dead because of cancer. Cancer is caused by either the congenital mutations or the overexpression of oncogenes. It has a powerful ability to transform proliferative and transfer. Because the activation of oncogenes mutations takes months, the diagnosis need a long time. Therefore, the cancer was considered a terminal illness. However, with the medical improvement, the surgery and chemotherapy have been used to cure malignant tumors. Although surgery is easy to remove the tumor directly, this method can only postpone the disease if the cancer has moved to other organs. The chemotherapy can effective cure the cancer, but the patients might usually suffer from the significant side effects. However, both of these methods are unable to effectively cure the cancer. There are many kinds of therapies proposed in recent years, such as gene therapy, inhibition of angiogenesis, inhibition of pro-cancer protein and immunotherapy. Immunotherapy has the potential among a variety of treatments. Cancer immunotherapy is a popular medical technology. On April 29, 2010, the FDA approved cancer treatment vaccine which was called Provenge. Provenge is used for the treatment of advanced prostate cancer. It represents the customization of new medical era. It can be used to make different vaccines according to different types of cancer. Among all strategies, cancer immunotherapy of dendritic cells / tumor fusion vaccine is a therapeutic option. Dendritic cells are phagocytes and have the strongest antigen expression. When dendritic cells swallow the antigen, they will activate the adaptive immune system. Therefore, the fusion of dendritic cells / tumor can make dendritic cells divide faster and mass-produce the vaccine. In tradition, either polyethylenglycol or randomness method was used for electric fusion. The efficiency and the quality of the vaccine were both unstable. Through this research we develop a cell electrofusion lab chip which combined the rapid and precise cell pairing micro-structures and the high yield electrofusion micro-electrodes to improve the cell fusion techniques and overcome the key barriers. We wish to build and develop an automated, mass-produced and efficient dendritic cell / tumor fusion vaccine.
Lin, Wei-Liang, e 林威良. "Suppression of myofibroblast-induced cancer cell migration by macrophages: studies on a multi-chamber cell culture chip". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/89071614835484923035.
國立陽明大學
生醫光電工程研究所
99
In the tumor microenvironment, a lot of stromal cells secret growth factors to enhance the metastasis, proliferation, and survival of cancer cells. A number of cells including fibroblasts and macrophages are involved in the metastasis of a primary tumour. We develop microfluidic cell culture chips that contain three culture chambers to co-culture lung cancer cells, macrophages, and fibroblasts to study the interactions amount them. The results showed that cancer cells were activated fibroblasts into myofibroblasts by conditional medium of cancer cell. The myofibroblast conditional medium will promote the mobility of cancer cells, but macrophages secreted TNF-? will inhibit the myofibroblastic ability of autocrine TGF-?? The ??SMA fluorescence intensity and aspect ratio both decreased, so myofibroblasts to promote cancer cell the ability of migration speed will be reduced. But myofibroblasts and macrophages conditional medium together effect on the cancer cells, that will synergies enhance the metastasis of cancer cells. We find that the effect of myofibroblast to increase the migration speed of cancer cells is suppressed by the conditioned medium of the macrophage. Therefore, macrophages interactions between stromal cells in the tumor micro-environment play a very important role in tumor growth and metastasis.
Kao, Feng-Sheng, e 高豐生. "Chip-based protein-protein interaction force measurement and cancer drug effect on cell’s Young’s modulus by atomic force microscopy". Thesis, 2013. http://ndltd.ncl.edu.tw/handle/54530650874466921725.
國立交通大學
機械工程系所
101
In this dissertation, we demonstrated that the direct and accurate measurement of protein-protein interaction force can be done by atomic force microscopy (AFM) via immobilization of one protein on chip (imm-protein) and another on probe tip of AFM (afm-protein). Preliminarily, we observed the binding between T-cell receptor, CD28 (imm-CD28), and B-cell receptor, CD80 (afm-CD80), with an immuno-suppressive blocker, cynarin. Average unbinding forces were reduced from 61.4 pN to 38.9 pN with a blocking effect of ~37% as compared with ~9% by SPR. Using AFM as a detection tool, the significant quantity differences caused by drug target binding therefore can be applied as an efficient and accurate drug screening or protein-protein interaction measurement. The other subject in this dissertation is to discuss the drug effect on cell’s mechanical property. A less side-effect and non-harmful custom anti-cancer peptide (CB1a) composed by 33 amino acids was created. The results showed that the peptide drug has cytotoxicity effect on cancer cells in solution (in vitro). The elastic property differences of single cell surface while interacted with anticancer drug CB1a were estimated by AFM. The changes of elastic force of cell with/without CB1a was illustrated and reflected as Young’s modulus. After adding CB1a, the normal cell, MRC-5, almost remained its original Young’s modulus value. For cancer cell NCI-H460, the Young’s modulus reduced to only below 50%. It means that the quantity variation can be considered as a good selectivity of CB1a and provided another cytotoxicity mechanism effect on cancer cell surface. Furthermore, we also compared with the commercial anti-cancer drug, Doxorubicin (Dox), to study the differences of morphology and physical property changes under drugs treating. The results prove that CB1a prefers to damage cell membrane from outside, and Doxorubicin leads cell to death by stopping the functions inside the cells.
Oliveira, Ana Beatriz Brito de. "A novel approach for chip-based digital LAMP towards the quantification of prostate cancer biomarkers". Master's thesis, 2019. http://hdl.handle.net/10362/88336.
SEPE, ELISABETTA. "Cancer biomarkers detection in cell lysates by means of anisotropic fluorescence at the surface of 1D photonic crystal biochips". Doctoral thesis, 2020. http://hdl.handle.net/11573/1362079.
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Title from PDF file main screen (viewed on Apr. 1, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Electrical and Computer Engineering, University of Alberta. Includes bibliographical references.