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Dissertations / Theses on the topic 'Tumor chemosensitivity'

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Published: 5 June 2025

Last updated: 15 July 2025

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Maekawa, Hisatsugu. "A Chemosensitivity Study of Colorectal Cancer Using Xenografts of Patient-Derived Tumor Initiating Cells." Kyoto University, 2018. http://hdl.handle.net/2433/235985.

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Holton, Angela. "Microfluidic Biopsy Trapping Device for the Real-time Monitoring of the Tumor Microenvironment." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7036.

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The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent clinical drug response as they lack true tumor heterogeneity and are often performed in static culture conditions lacking stromal tumor components that significantly influence the metabolic activity and proliferation of cells. Recent microfluidic approaches aim to overcome such obstacles with the use of cell lines derived in artificial three-dimensional supportive gels or micro-chambers. However, absence of a true tumor microenvironment and full interstitial flow, leads to less than optimal evaluation of tumor response to drug treatment. Here we report a continuous perfusion microfluidic device coupled with microscopy and image analysis for the assessment of drug effects on intact fresh tumor tissue. We have demonstrated that fine needle aspirate biopsies obtained from patient-derived xenograft models of adenocarcinoma of the lung can successfully be analyzed for their response to ex vivo drug treatment within this biopsy trapping microfluidic device, wherein a protein kinase C inhibitor, staurosporine, was used to assess tumor cell death as a proof of principle. Lastly, we tested the model for its ability to demonstrate similar results found in clinic when using a Wee1 inhibitor on osteosarcoma and an epidermal growth factor receptor inhibitor, Erlotinib, and inhibitors of programmed death 1 receptor and programmed death ligand 1 on lung adenocarcinoma fine needle aspirate biopsies. This approach has the potential to study tumor tissue within its intact microenvironment to better understand tumor response to drug treatments and eventually to choose the most effective drug and drug combination for individual patients in a cost effective and timely manner.

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Pinello, Katia Cristina. "Avaliação da quimiosensibilidade de mastocitomas caninos graus I, II e III ao ácido retinóico todo-trans." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-02032007-090228/.

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O mastocitoma é o tumor cutâneo mais comum dos cães, representando 7% a 21% dos tumores da pele e tecidos moles, 11% a 27% dos tumores malignos cutâneos nessa espécie. Eles possuem uma grande variedade de aparência e comportamento, o qual o torna um desafio seu tratamento. Os retinóides são uma promessa na luta contra o câncer. Entretanto, há poucos estudos sobre os efeitos dos retinóides em neoplasias caninas. O presente trabalho teve como objetivo caracterizar a cultura primária de mastocitomas caninos assim como investigar a quimiosensibilidade deste tumor ao ácido retinóico todo-trans (ATRA). A cultura primária de mastocitomas caninos foi realizada em co-cultivo com fibroblastos, que demonstrou uma interação favorável entre mastócitos e fibroblastos, com uma sobrevida média de 30 dias. A quimiosensibilidade dos mastocitomas caninos ao ATRA não mostrou diferenças entre os graus de mastocitomas, ou seja, tanto um mastocitoma grau II ou III respondem igualmente ao ATRA nas doses estudadas. Foi constatado também que o mastocitoma é mais sensível na concentração 10-4M de ATRA (p < 0,002). Existe também um efeito já nas primeiras 24h, mas esse não se altera em 48h, entretanto se intensifica após 72h. Podemos inferir, então, que a maior quimiosensibilidade de mastocitomas caninos ao ATRA se dá após 72h de exposição na dose de 10-4M. Podemos concluir que o ATRA apresenta efeitos sobre as células de mastocitomas caninos e pode ser usado como potencial adjuvante no tratamento desta neoplasia. Mast cell tumor (MCT) is one of the most frequent neoplasms that affect the skin and soft tissue of the dog, representing about 7% a 21% of all skin tumors and 11% a 27% of malignant skin tumors in this specie. They present a great variety of appearance and behavior, which becomes a challenge to the treatment. The retinoids are well recognized as promising antitumor agents. However, there have only been a few reports about the effect of retinoids in canine cancers. The aim of this study was to characterize the primary mast cell tumor culture and to investigate the chemosensitivity of this tumor to all trans retinoic acid (ATRA). The primary cell culture of MCT was performed as co-cultive with fibroblasts, showing a positive interaction between mast cells and fibroblasts, with a lifetime of 30 days. The chemosensitivity of MCT to ATRA showed no difference between grade II or III, thus either a MCT grade II or grade III has the same response with ATRA at the doses studied. It has been shown that the MCT is more sensible at the dose 10-4M (p < 0,002). There is also an effect on first 24h untill 48h, changing after 72h. According to these results, it is possible to state that the great chemosensitivity of MCT to ATRA is after 72h of exposition at 10-4M. We can conclude that ATRA may be a potential adjunctive chemotherapeutic agent for the treatment of canine mast cell tumor.

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Serafin, Antonio Mendes. "Chemosensitivity of prostatic tumour cell lines under conditions of G2 block abrogation." Thesis, Cape Technikon, 2000. http://hdl.handle.net/20.500.11838/2245.

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Thesis (MTech (Biomedical Technology))--Cape Technikon, 2011. Cancer of the prostate gland is now recognised as one of the principal medical problems in males. In the USA, cancer of the prostate is the second most commonly diagnosed cancer after skin cancer and the second most common cause of death from cancer after lung cancer. In South Africa, prostate cancer is the second most common cancer, with an estimated annual incidence of 19.1 per LOO000 men (Sitas, 1994). However, this incidence is probably under-estimated, due to incomplete records. Comparison of the incidence of prostate cancer in the different racial groups shows that it is the second most common malignancy in the White, Black (African) and Mixed (Coloured) race groups, and the fourth most common malignancy in Asian (Indian) men in South Africa. Metastatic prostate cancer is refractory to hormone therapy and remains incurable. Hence, novel therapeutic approaches are needed. These anticancer drugs can be tested in tumour cell lines, and cell culture methods also permit testing of optimum conditions.

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Pennati, Marzia. "Strategies for survivin down-regulation : effects on tumour cell growth potential and chemosensitivity profile." Thesis, Open University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446281.

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Hardelauf, Heike, Jean-Philippe Frimat, Joanna D. Stewart, et al. "Microarrays for the scalable production of metabolically relevant tumour spheroids: a tool for modulating chemosensitivity traits." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-138739.

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We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for the arrayed mass production of highly uniform 3-D human HT29 colon carcinoma spheroids. The spheroids have an organotypic density and, as determined by 3-axis imaging, were genuinely spherical. Critically, the array density impacts growth kinetics and can be tuned to produce spheroids ranging in diameter from 200 to 550 µm. The diffusive limit of competition for media occurred with a pitch of ≥1250 µm and was used for the optimal array-based culture of large, viable spheroids. During sustained culture mass transfer gradients surrounding and within the spheroids are established, and lead to growth cessation, altered expression patterns and the formation of a central secondary necrosis. These features reflect the microenvironment of avascularised tumours, making the array format well suited for the production of model tumours with defined sizes and thus defined spatio-temporal pathophysiological gradients. Experimental windows, before and after the onset of hypoxia, were identified and used with an enzyme activity-based viability assay to measure the chemosensitivity towards irinotecan. Compared to monolayer cultures, a marked reduction in the drug efficacy towards the different spheroid culture states was observed and attributed to cell cycle arrest, the 3-D character, scale and/or hypoxia factors. In summary, spheroid culture using the array format has great potential to support drug discovery and development, as well as tumour biology research Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

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Hardelauf, Heike, Jean-Philippe Frimat, Joanna D. Stewart, et al. "Microarrays for the scalable production of metabolically relevant tumour spheroids: a tool for modulating chemosensitivity traits." Royal Society of Chemistry, 2011. https://tud.qucosa.de/id/qucosa%3A27776.

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We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for the arrayed mass production of highly uniform 3-D human HT29 colon carcinoma spheroids. The spheroids have an organotypic density and, as determined by 3-axis imaging, were genuinely spherical. Critically, the array density impacts growth kinetics and can be tuned to produce spheroids ranging in diameter from 200 to 550 µm. The diffusive limit of competition for media occurred with a pitch of ≥1250 µm and was used for the optimal array-based culture of large, viable spheroids. During sustained culture mass transfer gradients surrounding and within the spheroids are established, and lead to growth cessation, altered expression patterns and the formation of a central secondary necrosis. These features reflect the microenvironment of avascularised tumours, making the array format well suited for the production of model tumours with defined sizes and thus defined spatio-temporal pathophysiological gradients. Experimental windows, before and after the onset of hypoxia, were identified and used with an enzyme activity-based viability assay to measure the chemosensitivity towards irinotecan. Compared to monolayer cultures, a marked reduction in the drug efficacy towards the different spheroid culture states was observed and attributed to cell cycle arrest, the 3-D character, scale and/or hypoxia factors. In summary, spheroid culture using the array format has great potential to support drug discovery and development, as well as tumour biology research. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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Evans, Hayley R. "Synthesis of bespoke matrices to investigate a novel anti-tumour molecular target using affinity chromatography. The design, synthesis and evaluation of biotinylated biarylheterocycles used as novel affinity probes in the identification of anti-tumour molecular targets." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/4420.

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Three novel, synthetic biarylheterocycles bearing imidazole terminal groups had previously been discovered with high cytotoxicity (IC50 16¿640 nM) against a number of human tumour cell lines. Notably, this biological activity was independent of duplex DNA binding affinity. The compounds were tested in the NCI 60-cell line panel and COMPARE analysis suggests they have a novel mechanism of action, targeting the product of a ¿gene-like sequence¿ of unidentified function. The identity of likely protein targets was explored using a chemical proteomic strategy. Bespoke affinity matrices for chromatography were prepared in which test compounds were attached to a solid support through a biotin tag. A synthetic route to hit compounds containing a biotin moiety in place of one of the imidazole sidechains was developed. Chemosensitivity studies confirmed that the biotinylated compounds retained their activity showing IC50 = 6.25 ¿M in a susceptible cell line, compared with > 100 ¿M for an insensitive cell line. The biotinylated ligands were complexed to a streptavidin-activated affinity column and exposed to cell lysates from the susceptible cell lines. Bound proteins were eluted from the column and separated using SDS-PAGE. Proteins were characterised by MALDI MS and MS/MS and identified using Mascot database searches. Heterogeneous nuclear ribonuclear protein A2/B1 was found to selectively bind to the affinity probes. Yorkshire Cancer Research, BMSS, School of Life Sciences and the Frank Hudson Memorial Fund

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Evans, Hayley Ruth. "Synthesis of bespoke matrices to investigate a novel anti-tumour molecular target using affinity chromatography : the design, synthesis and evaluation of biotinylated biarylheterocycles used as novel affinity probes in the identification of anti-tumour molecular targets." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/4420.

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Three novel, synthetic biarylheterocycles bearing imidazole terminal groups had previously been discovered with high cytotoxicity (IC₅₀ 16-640 nM) against a number of human tumour cell lines. Notably, this biological activity was independent of duplex DNA binding affinity. The compounds were tested in the NCI 60-cell line panel and COMPARE analysis suggests they have a novel mechanism of action, targeting the product of a 'gene-like sequence' of unidentified function. The identity of likely protein targets was explored using a chemical proteomic strategy. Bespoke affinity matrices for chromatography were prepared in which test compounds were attached to a solid support through a biotin tag. A synthetic route to hit compounds containing a biotin moiety in place of one of the imidazole sidechains was developed. Chemosensitivity studies confirmed that the biotinylated compounds retained their activity showing IC₅₀ = 6.25 μM in a susceptible cell line, compared with > 100 μM for an insensitive cell line. The biotinylated ligands were complexed to a streptavidin-activated affinity column and exposed to cell lysates from the susceptible cell lines. Bound proteins were eluted from the column and separated using SDS-PAGE. Proteins were characterised by MALDI MS and MS/MS and identified using Mascot database searches. Heterogeneous nuclear ribonuclear protein A2/B1 was found to selectively bind to the affinity probes.

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Gutekunst, Matthias [Verfasser], and Peter [Akademischer Betreuer] Scheurich. "Chemosensitivity of testicular germ cell tumors is based on high constitutive Noxa protein levels and a functional p53 response / Matthias Gutekunst. Betreuer: Peter Scheurich." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2013. http://d-nb.info/1042442568/34.

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Hamy, Anne-Sophie. "Identification of Factors Predicting Sensitivity or Resistance to Neoadjuvant Chemotherapy in Breast Cancer Neoadjuvant treatment : the future of patients with breast cancer Neoadjuvant treatment for intermediate/high-risk HER2-positive and triple-negative breast cancers: no longer an “option” but an ethical obligation Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status BIRC5 (survivin) : a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort The presence of an in situ component on pre-treatment biopsy is not associated with response to neoadjuvant chemotherapy for breast cancer Chemosensitivity, tumor infiltrating lymphocytes (TILs), and survival of postpartum PABC patients treated by neoadjuvant chemotherapy Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels Biological network-driven gene selection identifies a stromal immune module as a key determinant of triple-negative breast carcinoma prognosis A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer Interaction between molecular subtypes, stromal immune infiltration before and after treatment in breast cancer patients treated with neoadjuvant chemotherapy COX2/PTGS2 Expression Is Predictive of Response to Neoadjuvant Celecoxib in HER2-negative Breast Cancer Patients Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS129.

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La chimiothérapie néoadjuvante (CNA) est utilisée dans les cancers du sein agressifs ou localement avancés (CS). Au delà des bénéfices cliniques, elle représente une opportunité pour monitorer in vivo la sensibilité d’une tumeur à un traitement.A partir de l’analyse de sets de données de patients traités par CNA, nous souhaitons identifier des mécanismes associes à la résistance ou sensibilité au traitement. Dans la première partie, nous avons évalué des paramètres, cliniques, anatomopathologiques et transcriptomiques. Nous avons démontré que des éléments non explorés comme la présence d’embols après CNA revêtaient une information pronostique importante. Dans une 2ème partie, nous avons analysé l’impact de l’infiltrat immunitaire dans le cancer du sein, et avons décrit les changements observés entre des échantillons avant et après CNA. Nous avons montré que l’impact pronostique des TILs était différent avant et après CNA, et était opposé dans les CS triple négatif ou HER2-positif. Finalement, nous avons analysé l’impact des comédications pendant la CNA. Nous avons trouvé des effets positifs – via l’augmentation de l’infiltrat immunitaire et la réponse au traitement – et des effets négatifs avec des effets délétères dans certains sous groupes de patients. En conclusion, la situation néoadjuvante représente une plateforme pour générer et potentiellement valider des hypothèses de recherche. La mise à disposition de jeux de données de patients traités par chimiothérapie néoadjuvante constituerait une ressource majeure pour accélérer la recherche contre le cancer du sein Neoadjuvant chemotherapy (NAC i.e. chemotherapy before surgery) is increasingly being used for aggressive or locally advanced breast cancer (BCs). Beyond clinical benefits, it represents an opportunity to monitor in vivo sensitivity to treatment. Based on the analysis of datasets of BCs patients treated with NAC, we aimed at identifying mechanisms associated with resistance or sensitivity to treatment.In the first part, we evaluated biological, clinical, pathological and transcriptomic patterns. We demonstrated that unexplored pathological features such as post-NAC lymphovascular invasion may carried an important prognostic information.In a second part, we analyzed impact of imune infiltration in BC and we described extensively the changes of tumor infiltrating lymphocytes (TILs) between pre and post-NAC samples. We showed that the prognostic impact of TILs was different before and after NAC, and was opposite in TNBC and HER2-positive BCs. Finally, we investigated the impact of comedications use during NAC. We found both positive effects - while enhancing immune infiltration and response to treatment - and negative effects with deleterisous oncologic outcomes in specific patients subgroups. In conclusion, the neoadjuvant setting represents a platform to both generate and potentially validate research hypotheses aiming at increasing the efficacy of treatment. The public release of real-life datasets of BC patients treated with NAC would represent a major resource to accelerate BC research

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Hsin-Hsin, Hsu. "Correlation of Epidermal Growth Factor Receptor Gene Mutations in Tumor Tissue and Clinical Chemosensitivity in Patients with Advanced Non-Small Cell Lung Cancer." 2006. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2907200602134800.

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Hsu, Hsin-Hsin, and 徐心馨. "Correlation of Epidermal Growth Factor Receptor Gene Mutations in Tumor Tissue and Clinical Chemosensitivity in Patients with Advanced Non-Small Cell Lung Cancer." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/68951299770262968227.

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碩士 國立臺灣大學 臨床藥學研究所 94 Based on current available evidences, the mutations in tyrosine kinase domain of epidermal growth factor receptor (EGFR) was significantly associated with clinical responsiveness to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC). Retrospective studies showed that EGFR tyrosine kinase mutation in tumor specimen was as an independent predictive factor of clinical outcomes for TKI treated patients. Patients with mutations would have better clinical response to TKI and longer overall survival in comparison with wild-type patients. The mutation rate was 30 to 42% in Asian patients, higher than Caucasian patients. However, the relationship between clinical responsiveness to chemotherapy and its impact on survival and EGFR mutations was unclear in patients with advanced NSCLC. In this study, we investigated the influence of EGFR mutations in tumor specimens on the clinical outcomes of advanced NSCLC patients who received chemotherapy as 1st or 2nd line treatment. In total, 86 patients with available tumor specimens were selected from these clinical trials of NSCLC, which conducted at the Department of Oncology, National Taiwan University Hospital. Tumor sequencing in exon 18 through 21 of EGFR, and retrospective collection of clinical data of patients were performed. RESULTS: 34.9% of patients had EGFR mutations. 44.2% of patients had a partial response to chemotherapy. The mutations in subgroups – more frequently found in patients with adenocarcinoma than patients with other histologic types (40.3% vs 13.3%, p=.05), in female than male (39.4% vs 32.1%, p=.49). The mutation rates were 34.9%, 25.9%, 50.0%, respectively in patients who had never smoked, currently smoked, and formerly smoked. The L858R substitution mutation in exon 21 was the most common mutation in 53.3% of all mutations. The in-frame deletions located around E746-A750 in exon 19 were second frequent in 26.7% of all mutations. The response rate to chemotherapy was 40.0% in EGFR mutation-positive subgroup compared to 46.4% in EGFR mutation-negative subgroup (p=.57). The median time-to-progression (TTP) and overall survival (OS) for the patients with EGFR mutations were 4.9 months (95% CI, 3.0-7.2 months), and 19.0 months (95% CI, 14.7-26.1 months), respectively, compared to the median TTP and OS of patients with wild-type (6.9 months, 95% CI, 6.2-8.2 months in TTP; and 22.6 months, 95% CI, 18.9-24.6 months in OS), there were no statistically significant differences in TTP and OS. Therefore, clinical responsiveness to chemotherapy was not associated with EGFR mutations in advanced NSCLC patients. In comparison with other related researches, our results were consistent with recent report published by Lee et al, but different from the results of researches (Bell and Eberhard et al) in INTACT and TRIBUTE studies. Bell et al showed that EGFR mutated patients treated with chemotherapy alone had a better overall survival compared with mutation negative patients (median OS, 19.4 months vs 9.2 months), but there were only 6.9% of East Asian patients in INTACT study. In our study, both mutated and wild-type advanced NSCLC patients had long survival (median OS, 19.6 and 22.6 months, respectively). Therefore, it was possible that EGFR mutational status was not a good predictive factor in East Asian patients with advanced NSCLC.

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Wajapeyee, Narendra. "Functional Characterization Of Transcription Factor Activator Protein 2 Alpha (AP-2α)". Thesis, 2005. https://etd.iisc.ac.in/handle/2005/1687.

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Wajapeyee, Narendra. "Functional Characterization Of Transcription Factor Activator Protein 2 Alpha (AP-2α)". Thesis, 2005. http://etd.iisc.ernet.in/handle/2005/1687.

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Dodbiba, Lorin. "Characterization of Primary Esophageal/Gastro-esophageal Junction Cancer Xenograft Models and their Effectiveness in Studying Chemosensitivity." Thesis, 2013. http://hdl.handle.net/1807/65431.

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Primary esophageal (E) and gastro-esophageal junction (GEJ) cancer xenografts have the potential to become useful pre-clinical models of disease. In this study, we determined that p16 negative tumors that have not been exposed to neo-adjuvant chemo-radiation have higher engraftment chances. Morphological features and expression of certain molecular markers (p53, p16, Ki-67, EGFR, Her-2/neu) suggest that no major changes occur between primary tumors and xenografts or between early passage and late passage xenografts. Global gene expression data supported these results but revealed that approximately 2000 genes differed significantly between passage one xenografts and human tumors. Most of these genes, however, might coincide with stromal signals present in patient tumors but absent in xenografts. Primary E/GEJ cancer xenografts also showed a wide range of chemosensitivities to cisplatin-paclitaxel treatment, confirming the usefulness of these models in drug testing. These models also revealed potential ways to interrogate tumor initiating cell (TIC) dynamics after chemotherapy.

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