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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Modulation of breast cancer tumour-initiating cells in cell lines and patient-derived tumour xenografts

Sandoval, José Luis Bico Rosa Gamero January 2015 (has links)
No description available.
2

Isolation of pure cassava linamarin as an anti cancer agent

Idibie, Christopher Avwoghokoghene 03 April 2008 (has links)
ABSTRACT Cassava is a known source of linamarin, but difficulties associated with its isolation have prevented it from being exploited as a source. A batch adsorption process using activated carbon at the appropriate contact time proved successful in its isolation with ultrafiltration playing a pivotal role in the purification process. Result revealed that optimum purification was obtained with increasing amount of crude cassava extract (CCE) purified. 60g of CCE took 32 mins, 80 g, 34 mins while 100 g took 36 mins of contact time, where 1.7 g, 2.0 g and 2.5 g of purified product were obtained, respectively. The purification process in batch mode was also carried out at different temperatures ranging from 25 to 65oC. Results showed that purification increases with increase in temperature. In a bid to ascertain the moles of linamarin adsorbed per pore volume of activated carbon used, the composite isotherm was found to represent the measured adsorption data quite well. The adsorption of linamarin was used to study the goodness of fit criteria (R2) for the entire process. Results showed that R2 value was best with decreasing amount of CCE purified (R2=1 for 60 g) at the temperature of 45oC. Compound elucidation of purified product by Picrate paper test, IR and 1HNMR confirmed the structure of linamarin. Cytotoxic effects of linamarin on MCF-7, HT-29, and HL-60 cells were determined using the 3 - (4, 5 – dimethylthiazol-2-yl) – 2, 5 – diphenyltetrazolium bromide (MTT) assay. Cytotoxic effects were significantly increased in the presence of linamarase, which catalysed the hydrolysis of linamarin to hydrogen cyanide. A 10–fold decrease in the IC50 values obtained for linamarin or crude extract in the presence of linamarase was determined for HL-60 cells. This study thus describes a method for the isolation and purification of linamarin from cassava, as well as the potential of this compound as an anticancer agent.
3

A study of aqueous extracts from roots and leaves of Pluchea indica (L.) Less. on cancer cell lines

Tsao, Shu-chuan 12 September 2007 (has links)
Pluchea indica (L.) Less. is a shrub of the family Compositae and is widespread along the western coast in Taiwan. Previous studies indicated that the components of Pluchea indica have potent anti-inflammatory, anti-ulcer and antimicrobial activities. In the present study, the effects of aqueous extract of roots and leaves from P. indica on the cancer cell lines were investigated. Various experimental approaches including cell growth curves, MTT assay, MTS assay, focus formation assay and cell migration assay were performed on the aqueous extract-treated cancer cells. Our results demonstrate the aqueous extract of P. indica induced anti-proliferation activity on GBM8401 and HeLa cancer cell lines.
4

Application and Development of Novel Methods for Pathway Analysis and Visualization of the LINCS L1000 Dataset

White, Shana 04 October 2021 (has links)
No description available.
5

Characterization of Effects of Muc1 Expression on Epidermal Growth Factor Receptor Signaling in Breast Cancer

Pochampalli, Mamata Rani January 2006 (has links)
EGF receptors are key regulators of cell survival and growth in normal and transformed tissues. Ligand binding results in formation of homo/hetero dimers of these receptors, followed by activation of the kinase activity and subsequent tyrosine phosphorylation of many downstream molecules. The activation of these receptors is not only mediated by the binding of their cognate ligands, but by transactivaton by other molecules as well. Recent studies have identified an oncogenic glycoprotein MUC1 as a binding partner for EGFR and that MUC1 expression can potentiate EGFR-dependent signal transduction. After receptor activation, EGFR is typically downregulated via an endocytic pathway that results in receptor degradation or recycling. We report here that MUC1 expression inhibits the degradation of ligand-activated erbB1. In addition, MUC1 expression results in prolonged activation of Akt, but not ERK1,2 MAPKinase. The MUC1-mediated protection against degradation occurs with a decrease in EGF-stimulated ubiquitination of erbB1, and an increase in erbB1 recycling. We then utilized the WAP-TGFα transgenic mouse model of breast cancer and determined that a loss of Muc1 expression dramatically alters mammary tumor progression. While 100% of WAP-TGFα/Muc1^(+/+) mice form mammary gland tumors, only 37% of WAP-TGFα/Muc1^(-/-) form tumors. Furthermore, expression of cyclin D1 expression is significantly suppressed in tumors derived from WAPTGFα/Muc1^(-/-) animals, and loss of Muc1 expression resulted in a significant inhibition in the formation of hyperplastic lesions in the mammary gland. We also observed metastatic pulmonary adenocarcinoma (1/29) and perivascular lymphoma of unknown origin (28/29) in the WAP-TGFα transgenic mice but not in the WAP TGFα/Muc1^(-/-) animals. To determine the effects of Muc1 expression on metastasis in a model lacking perivascular lymphoma, we crossed MMTV-Wnt-1 and MMTV-MUC1 transgenic mice and evaluated interactions between Muc1 and EGFR. Although the MMTV-Wnt-1 mice are non-metastatic, a majority (6/10) of the bitransgenic MMTVWnt- 1/MMTV-MUC1 formed pulmonary metastases. Furthermore, overexpression of MUC1 increases the breast cancer cell invasion in vitro. The MUC1 induced increase in invasion is found to be EGF and EGFR-kinase dependent. Collectively, these data indicate that MUC1 expression contributes to many of the hallmarks of cancer and in addition, is an important modulator of EGFR-associated mammary tumor progression.
6

Cancer systems biology : is the devil in the glycolytic detail?

Blount, Kathryn January 2014 (has links)
An approach to investigating cancer that has recently seen resurgence of interest is the “Warburg effect”. Otto Warburg originally described the altered metabolism of cancer cells and identified that they exhibit an increase in glucose uptake and lactate production. This up-regulation of glycolytic flux and glucose transport is now associated with 90% of cancers. In order to improve the overall understanding of the “Warburg effect” two forms of systems biology have been implemented - comparative in vitro analysis of kinetic activities and dynamic modelling. In this analysis, human breast cancer cell lines MCF-7, MDA-MB-231 and T47D and a non transformed breast cell line MCF-10A were used to identify key similarities and differences in kinetic activities across the glycolytic pathway. Additionally, activities of key glycolytic enzymes hexokinase, pyruvate kinase and lactate dehydrogenase were compared under hypoxic conditions to further understand regulation of cancer cells. The most prominent feature that arose from comparing the kinetic activities of the three malignant and one non-malignant cell line is that each cell line has its own specific set of activities for glycolysis. This indicates that there are differences in regulation across the glycolytic pathway for each of these cell lines. This is of specific interest in the search for therapeutic targets. Further, we determined that despite the prominence of oncogenic HIF signalling activities of hexokinase, pyruvate kinase and lactate dehydrogenase were further modulated by growth under hypoxic conditions. Despite the lack of obvious distinct kinetic differences between the non-cancerous and cancerous cells lines some discernible differences are apparent when modelled in silico.
7

Vliv akalabrutinibu a ibrutinibu na účinek daunorubicinu v nádorových buňkách. / The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells.

Čermáková, Lucie January 2020 (has links)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lucie Čermáková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of acalabrutinib and ibrutinib on the efficacy of daunorubicin in cancer cells Leukemia presents malignant diseases of hematopoiesis, which essence is the malignant transformation of a hematopoietic stem cell at various levels of maturation and increased proliferative activity. Chemotherapy is the gold standard in the treatment of leukemia. One of the many treatments is the use of anthracycline chemotherapeutics, especially daunorubicin (DAU). Anthracyclines are widely used in clinical practice but have high cardiotoxic effects that limit their dosage. One of the main causes of side effects is the reduction of an anthracycline chemotherapeutic to the appropriate toxic metabolite, which accumulates in the heart. Carbonyl, reducing enzymes from the superfamily aldo-ketoreductase (AKR), and short-chain dehydrogenase/reductase (SDR) are involved in this reduction. At the same time, carbonyl reducing enzymes, has been shown to be involved in the mechanisms that cause tumor cells to be resistant to anthracyclines, thereby reducing the inhibition of the growth of these cells. In the diploma thesis we found that...
8

Facile Synthesis of Anticancer Drug NCX 4040 in Mild Conditions

Xiao, Mei, Yang, Hongsong, Klein, Suzane M., Muenyi, Christian M., Stone, William L., Jiang, Yu L. 01 October 2008 (has links)
A simple method is reported to synthesize an anticancer drug, NCX 4040, conveniently in mild conditions using silicon chemistry. A starting material, 4-hydroxybenzyl alcohol, was silylated selectively first to give t-butyldimethylsilyl 4-hydroxybenzyl ether, which was then converted to NCX 4040 by esterification, desilylation, hydrochlorination and nitration.
9

Development Of Bio-Photonic Sensor Based On Laser-Induced Fluorescence

Kim, Chan Kyu 15 December 2007 (has links)
Laser-induced fluorescence (LIF) has been shown to be potentially useful for identifying microorganisms in real time. It is a selective and sensitive technique because the excitation is performed at one wavelength while the emission is monitored at longer wavelengths so that background from the excitation source can be eliminated. This specialized optical property of LIF can be applied to development of an optical sensor capable of quickly, non-invasively, and quantitatively probing complex biochemical transformations in microorganisms. Various bio-photonic optical fiber sensors based on laser-induced fluorescence (LIF) spectroscopy were developed as diagnostic tools for microorganisms. In the first phase, the enhancement of the sensitivity and selectivity of the optical sensor system focused on diagnosis of human breast cancer cell lines and Azotobacter vinelandii (an aerobic soil-dwelling organism). Autoluorescence spectra from human breast cancer cell lines and Azotobacter vinelandii corresponding to different growth environments were investigated. Then, the study has expanded to include the use of gold nanoparticles for specific DNA detection. The use of gold nanoparticales opens a door into construction of a compact, highly specific, inexpensive and userriendly optical fiber senor for specific DNA detection. An optical fiber laser-induced fluorescence (LIF) sensor based has been developed to detect single-strand (ss) DNA hybridization at the femtomolar level. Effects of various experimental parameters and configuration were investigated in order to optimize sensor performance and miniaturize sensor size.
10

Development of in vivo tumour models for non-invasive proof-of-principle investigation of novel therapeutic agents : engineering and characterisation of bioluminescent cell reporter systems for in vivo analysis of anti-cancer therapy pharmacodynamics

O'Farrell, Alice Claire January 2011 (has links)
Despite significant advances in cancer treatment, clinical response remains suboptimal and there is a continued requirement for improved chemotherapeutics. The attrition rate for new therapies is high, due principally to lack of in vivo efficacy and poor pharmacodynamics. Consequently better systems are required to determine in vivo preclinical efficiency and drug-target interactions. Engineering of cancer cells to express fluorescent or bioluminescent proteins, either endogenously or under the control of specific gene promoters, and their detection by noninvasive optical imaging has the potential to improve preclinical drug development. In this study, a panel of colorectal cancer cell lines were engineered to express fluorescent and luminescent proteins either constitutively or under control of gene-promoters for the DNA damage response gene p53 or the cell cycle regulator p21, both important pharmacodynamic sensors. These cell lines were characterised for their potential as in vivo models of primary and metastatic tumour therapy response, several showing significant potential. In addition to the development of these models, this study also addressed the pharmacokinetics of different luciferase substrates and identified optimal temporal and dose characteristics for each. Furthermore, a new application for bioluminescent imaging was developed and validated for use in preclinical evaluation of vascular disrupting agents, a new generation of cancer therapeutic. This study demonstrates that despite the dynamic and variable nature of fluorescent and bioluminescent imaging, reproducible results can be obtained if appropriate precautions are taken. The models developed herein will expedite cancer drug development whilst reducing and refining the use of animals in research.

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