Teses / dissertações: "Antineoplastic agents"

1

Wan, Jung Wing. "Novel ether lipids as antineoplastic agents". Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242627.

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2

Molyneux, Gemma. "Studies on the haemotoxicity of antineoplastic agents". Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435080.

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3

Chen, Alina. "New polyamine analogues as potential antineoplastic agents". Scholarly Commons, 2000. https://scholarlycommons.pacific.edu/uop_etds/2680.

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The naturally occurring polyamines play an essential role in cell growth and proliferation. The levels of polyamines have been shown to increase in rapidly proliferating cancer cells. Therefore, compounds that inhibit enzymes in polyamine biosynthetic pathway may have therapeutic potential. Compounds capable of providing both in vitro and in vivo inhibition of almost all enzymes in the polyamine biosynthetic pathway are known. An exception is the lack of an agent that inhibits spermidine/spermine N 1 -acetyltransferase (SSAT), the rate-limiting enzyme in the catabolism of polyamines. The design, synthesis and characterization of five new polyamine analogues as potential inhibitors of SSAT are presented. Three compounds, N 1 -[3-(propenamido) propyl]-1,4-diaminobutane dihydrochloride 5 , N 1 -[3-(maleimido)propyl]-1,4-diamino-butane dihydrochloride 7 and N 1 -[3-(2-bromoacetamido)propyl]-1,4-diaminobutane dihydrochloride 9 , were designed as active-site-directed affinity label inhibitors. Two compounds, N-[N-(5-acetamido-2-hydroxypentyl-3-aminopropyl)]-1,4-diaminobutane trihydrochloride 12 and N-[3-(2-hydroxyethylamino)propyl]-1,4-diaminobutane trihydrochloride 14 , were designed as transition state-like analogue inhibitors. These compounds were synthesized using one key intermediate, N-(3-aminopropyl)-N,N ′ -bis-(tert-butoxycarbonyl)-1,4-diaminobutane 3 . Three of these synthesized compounds, 5 , 7 and 12 were evaluated for their ability to inhibit SSAT. The enzyme used was a crude extract of human large cell undifferentiated lung carcinoma cell line NCI H157 cells. These synthetic analogues when tested against the crude enzyme extract at concentrations of 0.05, 0.1, 1 and 5 μM appeared to show no effects on the activity of SSAT.

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4

Ganley, Brian. "Investigations into the chemical mechanisms of biological activity by heterocyclic di-N-oxides and 1,2 benzodithiolan-3-one 1-oxides". free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9999285.

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5

Ramirez, Daniel A. Kane Robert R. "Synthesis of protected amino thymidines and new thiol derivatives of the vascular targeting agent combretastatin A-4". Waco, Tex. : Baylor University, 2006. http://hdl.handle.net/2104/5008.

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6

Ganley, Brian Christopher. "Investigations into the chemical mechanisms of biological activity by heterocyclic di-N-oxides and 1,2 benzodithiolan-3-one 1-oxides /". free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9999285.

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7

Reese, Michael. "Drug design (STAT5 modulators), development (Glyceollin I) and improvement (Esmolol Plus) /". Connect to full text in OhioLINK ETD Center, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=toledo1265033116.

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Thesis (M.S.)--University of Toledo, 2009.
Typescript. "Submitted as partial fulfillment of the requirements for the Master of Science Degree in Medicinal Chemistry." "A thesis entitled"--at head of title. Bibliography: leaves 45-48.

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8

Kanyanda, Stonard Sofiel Elisa. "Screening of natural products and Alkylating agents for Antineoplastic Activity". Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_6433_1363357514.

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Background and objectives: Apoptosis is a process in which a cell programmes its own death. It is a highly organized physiological mechanism in which injured or damaged cells are destroyed. Apart from physiological stimuli however, exogenous factors can induce apoptosis. Many anti-cancer drugs work by activating apoptosis in cancer cells. Natural substances have been found to have the ability to induce apoptosis in various tumour cells and these substances have been used as templates for the construction of
novel lead compounds in anticancer treatment. On the other hand, alkylating agents such as cisplatin, cis- [PtCl2 (NH3) 2] have been widely used as antineoplastic agents for a
wide variety of cancers including testicular, ovarian, neck and head cancers, amongst others. However, the use of cisplatin as an anticancer agent is limited due to toxicity and resistance problems. The aim of this present study was to screen the leaves of Rhus laevigata, a South African indigenous plant, for the presence of pro-apoptotic and
anti-proliferative natural compounds and also to screen newly synthesised palladium based complexes (15 and 57) and a platinum based complex (58) for their antineoplastic
activities tested against a panel of cell lines. Results. The results showed that crude methanol extracts from Rhus laevigata as well as the newly synthesised palladium based complexes (15 and 57) and a platinum based complex (58) induced apoptosis in the cell lines tested, as demonstrated by the externalization of phosphatidylserine, mitochondrial membrane permeabilization,caspase-3 activation, and DNA fragmentation. Caski (cervical cancer) and H157 (non small cell lung carcinoma) cell lines treated with the methanol extract from Rhus laevigata however, were more resistant to apoptosis induction. Among the metallocomplexes, complexes 15 and 57, palladium based complexes, were the most active. Conclusion: The methanol extract from the leaves of Rhus laevigata contain pro-apoptotic and antiproliferative natural compound(s), which need to be characterised and elucidated as they could provide the much-needed lead compounds in the fight against cancer. On the other hand the newly synthesized palladium complexes also need further evaluation to
see if they can be used as anticancer agents that can overcome the problems associated with cisplatin.

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9

Parker-, Johnson Kitani A. "An evaluation of novel antineoplastic agent on prostate cancer". DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2003. http://digitalcommons.auctr.edu/dissertations/3074.

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This study examines the effects of novel antineoplastic agents(isochalcones) on human metastatic prostate cancer cell lines by screening cells for their relative antiproliferative effects, measuring the protein expression levels of specific oncogenes by Western blotting, and evaluating an array of genes ( 5184) to determine possible mechanisms of action of these novel isochalcones. The array data were supported by real-time polymerase chain reaction (PCR) techniques. The antineoplastic agents were screened in human metastatic prostate cancer cell lines (LNCaP, DU145, PC-3, and MDA-PCa-2b) and non-cancerous prostate epithelial cell line PZ-HPV-7 in concentrations ranging from nanomolar to millimolar. The alamar blue exclusion dye assay, a redox indicator, was used to evaluate cell proliferation when compared to the untreated control. DJ52 demonstrated a growth inhibitory effect on LNCaP, PC-3, and DU145 cell lines at the micromolar concentration (p<0.05). Based on these data, 1 x 106 cells were treated, protein isolated, and expression levels of epidermal growth factor (EGF) and omithine decarboxylase (ODC) were measured and compared to theuntreated controls. These data indicated a dose-dependent decrease of expression of EGF and ODC, therefore, suggesting that other key oncogenes may also have a decrease in expression when treated with these novel antineoplastic agents. Therefore, gene arrays were used to identify possible families of genes and/or specific pathways that may be responsible for the antiproliferative effects noted. It was determined that the key families of genes significantly induced by these agents (Pathways 4®) were proapoptotic and cell cycle regulators. ABI 7700 Prism was used to perform quantitative RT-PCR via the AB Sequence Detector® software.

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10

Lin, Tung Yin. "Synthetic studies towards the stellettins /". View online, 2008. http://repository.eiu.edu/theses/docs/32211131443971.pdf.

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11

Hendrix, Martin. "Synthetic approaches toward pancratistatin". Thesis, Georgia Institute of Technology, 1993. http://hdl.handle.net/1853/27300.

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12

Tinkleman, Joseph M. Smith Forrest T. "Synthesis of 10, 11, 12, 12a, 12b, 13-hexahydro-5hbenzo[f]cyclopropa[d]pyrido[1,2-b] isoquinoline-5,7(9H)dione and related compounds". Auburn, Ala, 2009. http://hdl.handle.net/10415/1655.

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13

Lee, Seung-joo. "Molecular mechanism for DNA recognition by DNA alkylating antitumor agents /". Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.

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14

Younis, Islam Rasem. "In vitro elucidation of the metabolic fate of the anticancer drug busulfan". Morgantown, W. Va. : [West Virginia University Libraries], 2008. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=5576.

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Thesis (Ph. D.)--West Virginia University, 2008.
Title from document title page. Document formatted into pages; contains xi, 109 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 92-109).

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15

Ekborn, Andreas. "Cisplatin induced ototoxicity : pharmacokinetics, prediction and prevention /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-721-5.

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16

Carroll, Brian J. "Studies on the biosynthesis of naturally occurring antitumor agents /". Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/11562.

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17

Reader, Michael. "Studies towards the synthesis of the macrolide portion of ulapualide A". Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294255.

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18

Genovino, Julien. "Studies towards the total synthesis of (+)-spirastrellolide A". Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608940.

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19

Law, Kin Bon. "Mechanistic study of type I ribosome-inactivating protein as anti-influenza and anti-tumour agent". HKBU Institutional Repository, 2000. http://repository.hkbu.edu.hk/etd_ra/253.

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20

Erdal, Hamdiye. "Characterization of the mechanisms of action of anticancer agents in vitro and monitoring their effects in vivo /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-202-0/.

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21

Flynn, Allison. "Transition metals as anti-tumoral agents : some structure-function relationships of the platinum group metals /". Master's thesis, This resource online, 1994. http://scholar.lib.vt.edu/theses/available/etd-03022010-020016/.

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22

Arthasery, Phyllis Pinney Kevin G. "Discovery and development of unique small molecule chromene based ligands and combretastatin analogs as potential second generation vascular disrupting agents towards cancer chemotherapy". Waco, Tex. : Baylor University, 2005. http://hdl.handle.net/2104/3020.

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23

Ellenberger, William Paul. "Synthesis of DEF ring synthons to nogarol anthracyclines /". Full text open access at:, 1987. http://content.ohsu.edu/u?/etd,136.

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24

Baghdanov, Vaceli M. "Synthetic studies of naturally occurring hydroxylated polycyclic compounds : daunomycinone and pillaromycinone /". Full text open access at:, 1987. http://content.ohsu.edu/u?/etd,142.

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25

Johansson, Magnus. "Cloning and characterization of human deoxyribonucleoside kinases : phosphorylation of anti-cancer and anti-viral nucleoside analogs /". Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2696-4.

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26

Zhu, Chaoyong. "Deoxyribonucleoside kinases in nuclear and mitochondrial DNA precursor synthesis : phosphorylation of anti-cancer nucleoside analogs in different subcellular compartments /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4367-2/.

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27

Mancini, Michael. "Approaches to the synthesis of xanthone analogs of the anthracycline class of anticancer agents". Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=72059.

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Several strategies outlining approaches to the synthesis of the heteroanthracyclinones 4-demethoxyxanthodaunomycinone and 4-demethoxyisoxanthodaunomycinone (7,8,9,10-tetrahydrobenzo(b)-6,7,9,11-tetrahydroxy-9-acetylxanthen-12 and 5-one) are described.
The condensation of tetralin 2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol with o-methoxybenzoic acid was investigated and useful large-scale syntheses of important 1,4-dimethoxy-substituted xanthone intermediates were developed.
Diels-Alder cycloaddition reaction between a xanthone-derived o-quinodimethane intermediate and an olefin afforded a low yield of adduct. On the other hand, excellent yields of isolable but labile adducts were obtained in the cycloaddition reaction between xanthoquinone (and also thioxanthoquinone) and Danishefsky's dienes. The formation of linear vs internal adducts was rationalized on the grounds of resonance and FMO theory. Efforts to induce unactivated dienes to cycloadd using catalysts as well as annulation studies on model compounds using the novel reagent (E)-N-vinylpyrrolidine-(beta)-(2-lithio-1,3-dithian-2-yl) (as a synthon of the (alpha),(beta)-dianion of acetaldehyde) are discussed.
The synthesis of daunomycin and xanthodaunomycin analogs carrying a carbon substituent at position 7 were not accessible using the Diels-Alder cycloaddition reaction as diene 1-carbomethoxy-3-triethylsilyloxy-1,3-butadiene failed to react with either quinizarinquinone or xanthoquinone even at elevated temperatures.
The compound 4-hydroxy-1- 2- (2-hydroxyethyl)amino ethyl amino xanthone and the 4-methoxy derivative were prepared and found to be inactive in the in vivo P-388 mouse leukemia model system.

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28

Williams, Elizabeth G. L. "Total synthesis of novel analogues and hybrids of the anti-cancer agents dictyostatin and discodermolide". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610776.

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29

Naylor, Guy James. "Studies of novel anticancer agents : progress towards leiodermatolide and the total synthesis of analogues and hybrids of dictyostatin, discodermolide and taxol". Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609305.

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30

Rotella, David Paul. "The synthon concept in medicinal chemistry : synthesis and applications of cyclohexane diol diamines /". The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487263399027046.

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31

陳志強. "中醫藥抗腫瘤復發轉移文獻研究". HKBU Institutional Repository, 2012. http://repository.hkbu.edu.hk/etd_ra/1336.

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32

Neidigh, Kurt Alan. "Studies on the biosynthesis of podophyllotoxin : synthesis of labelled yatein and matairesinol, two potential precursors of podophyllotoxin /". This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-09192009-040255/.

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33

Xie, Yanqi. "SEMISYNTHETIC AURONES: A FAMILY OF NEWLY DISCOVERED TUBULIN INHIBITORS AS ANTINEOPLASTIC AGENTS". UKnowledge, 2019. https://uknowledge.uky.edu/biochem_etds/44.

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Aurones belong to an uncommon class of plant flavonoids that provide the bright yellow coloration of some ornamental flowers and that possess a range of biological activities. Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the biologically active analogs developed in the course of this dissertation work were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5r). These two aurones 5a and 5r inhibited in vitro PC-3 prostate cancer cell proliferation with IC50 values below 100 nM. A xenograft study in nude mice using 10 mg/kg of 5a for 18 days had no effect on mice weight, and aurone 5a did not inhibit, as desired, the human ether-à-go-go-related (hERG) potassium channel. Cell cycle arrest data, comparisons of the inhibition of cancer cell proliferation by aurones and known antineoplastic agents, and in vitro inhibition of tubulin polymerization indicated that aurone 5a disrupted tubulin dynamics. Based on a National Cancer Institute COMPARE analysis, studies using computer-based molecular docking and liquid chromatography-electrospray ionization-tandem mass spectrometry studies, aurone 5a targets the colchicine-binding site on tubulin. In addition to solid tumors, aurones 5a and 5r strongly inhibited in vitro a panel of human leukemia cancer cell lines and the in vivo myc-induced T cell acute lymphoblastic leukemia (T-ALL) in a zebrafish model. In summary, aurones possess a pharmacophore of considerable potential in the search for new antineoplastic agents for the clinical treatment of human cancers.

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34

McCandless, Stewart Grant. "The synthesis of some novel 1,2,3-benzotriazine-platinum complexes with potential antineoplastic activity". Thesis, Heriot-Watt University, 1988. http://hdl.handle.net/10399/999.

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35

Saylor, Melissa Anne. "Isolation of plant-derived signal transduction inhibitors : potential antitumor agents". Thesis, Georgia Institute of Technology, 1992. http://hdl.handle.net/1853/30989.

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36

McPherson, John Peter. "DNA topoisomerase IIÃ, role in resistance to antineoplastic agents and induction of apoptosis". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0009/NQ35248.pdf.

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37

Jönsson, Videsäter Kerstin. "Expression of multidrug resistance genes and proteins and effect of selenite in anthracycline-resistant human tumor cell lines /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-889-0/.

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38

Doetsch, Natalie, Kimberly Harder-Ibarola e Aliyah Sheth. "Exploration of Classic Confounders in Lymphoblastoid Cell Lines used to Study Select Antineoplastic Agents". The University of Arizona, 2010. http://hdl.handle.net/10150/623750.

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Class of 2012 Abstract
OBJECTIVES: Therapeutic response to chemotherapeutic agents in vitro can be studied using immortalized lymphoblastoid cell lines (LCLs). While LCLs provide a valuable model to study heritable factors and anticancer drug reponse in large populations, the results may be confounded by properties inherent to the model. This study is used to explore possible confounders in Choy et al.’s publicially available dataset (Accession#: GSE11582). METHODS: This study utilized Affymetrics U133A array gene expression and phenotypic data for 162 unrelated LCLs. SPSS was used for two-tailed bivariate Pearson correlation analysis comparing relative 6-mercaptopurine (6-MP), 5-fluorouracil (5-FU), and methotrexate sensitivities, growth rate and ATP levels. GeneSpring was used to compare the top and bottom quartiles of relative ATP levels using the unpaired T-test with a significance threshold of 0.001 and Benjamin-Hochberg FDR (n=82). RESULTS: It was found that relative sensitivities of 5-FU and 6-MP are significantly correlated (r2= 0.627, p<0.0001). Furthermore, it was determined that 5-FU sensitivity and growth rate and ATP levels are also correlated; however, no significant correlation was found between growth rate and ATP levles (r2=0.127, p=0.107). Relative ATP level was found to be a more significant determinant of 5-FU sensitivity than growth rate. GeneSpring analysis showed that 1500 genes are differentially regulated based on ATP levels. The gene ontology related to nucleic acid metabolism was overrepresented (p=1.425E-15). CONCLUSIONS: The results above suggest that growth rate and, to a greater extent, baseline ATP levels influence genetic expression of LCLs and may confound in vitro studies of antineoplastic agents.

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39

Higginbotham, Mary Lynn. "Preclinical pharmacokinetic and tolerance assessment and phase I clinical trial of MU-gold, a novel chemotherapeutic agent /". Free to MU Campus, others may purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p1421141.

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40

Oosthuizen, Lukas Marthinus. "New platinum coordination compounds : their synthesis, characterization and anticancer application". Thesis, Nelson Mandela Metropolitan University, 2009. http://hdl.handle.net/10948/d1018795.

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The aim of this thesis was to investigate the properties of novel platinum compounds with possible potential as anticancer agents, and to determine how their behaviour could lead to a better understanding of the chemistry involved. The final criteria were improvement of their anticancer behaviour. Since many questions are still unanswered as to the role of sulfur in anticancer action, studies were undertaken to synthesize novel platinum(II) complexes having non-leaving groups consisting of a combination of an aromatic nitrogen and thioetherial sulfur capable of forming a five membered ring upon coordination. The structural unit was 1-methyl-2-methylthioalkyl/aryl. Numerous complexes formed by these ligands each having chloro, bromo, iodo and oxalato leaving groups were then fully characterized. The results obtained by the various synthetic methods were compared and explained in terms of the chemistry involved. The role of the sulfur donor was indicated in both the halo- and oxalato-complexes and proved to be strongly influenced by the nature of the leaving groups. Their differences are reflected in their anticancer behaviour. The study was extended to mononitroplatinum(IV) complexes, in view of the kinetically stable platinum(IV) compounds and advantages related to this. A specific mononitroplatinum(IV) complex which proved to have good anticancer and STAT 3 properties could according to the literature not be synthesized successfully in a good yield and a high degree of purity. The results of extensive studies showed that the main problem centred around the simultaneous reactions in equilibrium during the synthesis. A number of these species formed as a result of side reactions could be identified and their close separation factors indicated chromatographically. The mechanism of these reactions and the unstable intermediate species involved could be rationalized and compared to analogues in the literature. All the complexes studied were characterized by spectral and thermal methods both in solution as well as the solid state. Their anticancer behaviour towards three anticancer cell lines (Hela, MCF 7, Ht 29) were determined and acted as a guide towards possible structural modifications for their improved capability. Three crystal structures of platinum(II) complexes were determined. The extent of the ionization of the platinum(II) complexes as well the redox potentials (Pt(II) / Pt(IV)) of the platinum(IV) complexes were particularly important factors pertaining to their anticancer action.

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41

Chu, Qingjun. "S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), water soluble garlic derivatives, suppress growth and invasion of androgen-independent prostate cancer, under in vitro and in vivo conditions". View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36749540.

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42

Gomes, Erica Manuela Tong Alex W. "Anti-tumor properties of CD40 ligand when delivered as a transgene by the conditional replicative oncolytic adenovirus AdEH to breast cancer cells". Waco, Tex. : Baylor University, 2006. http://hdl.handle.net/2104/4901.

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43

Lindemalm, Synnöve. "Pharmacokinetic studies on cladribine /". Stockholm : [Karolinska institutets bibl.], 2001. http://diss.kib.ki.se/2001/91-7349-043-1/.

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44

Martinsson, Petra 1974. "Pharmacological studies of CHS 828 and etoposide induced tumour cell death /". Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5157-8/.

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45

Nylén, Urban D. "Interactive antiproliferative mechanisms when 5-fluorouracil is combined with cisplatin or ionizing radiation : an in vivo and in vitro experimental study /". Stockholm, 2000. http://diss.kib.ki.se./2000/91-628-4480-6/.

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46

Howard, Edward William. "The potential clinical applications of garlic-derived S-allylmercaptocysteine in the treatment of hormone refractory prostate cancer". View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38165156.

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47

Li, Hoi-yee. "Signaling pathways modulated by gold-1A in its anti-tumour effects against hepatocellular carcinoma". Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B38838849.

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48

Zhu, Yanting. "Exploring alternative cytotoxic strategies for cancer treatment". HKBU Institutional Repository, 2014. https://repository.hkbu.edu.hk/etd_oa/65.

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Triggering direct cytotoxicity has been the most common strategy for developing cancer treatments. The cytotoxic regimens currently used in the clinic mainly include radiation therapy, classic chemotherapeutic drugs (e.g. DNA damaging drugs and anti-mitotic drugs) and selected new targeted drugs. Although these therapies are the standard of care for most cancer patients, they suffer significant limitations: responses to these therapies vary significantly between cancer types and patients; sensitive cancers tend to acquire resistance; and they cause serious toxicity, particularly to dividing cells in the bone marrow and gut, and to neurons. It is not clear whether major improvements in cytotoxic anticancer therapies are possible; if they are, progress is likely to come from either new methods for identifying sub-populations of patients that respond well to current drugs, or developing new therapies with novel cytotoxic mechanisms. To pursue the above two avenues towards potential improvement of cytotoxic therapies, this thesis investigates: biomarkers that determine the sensitivity of distinct cancer cell types to common anti-mitotic chemotherapeutics; and the mechanistic basis to employ alternating electric field and Natural Killer cells as alternative methods to trigger cancer cell death. The study uses time-lapse microscopy as the major technique to characterize and quantify response dynamics to the different cytotoxic treatments, and the results provide important new insight not only for understanding existing cytotoxic anticancer drugs but also for developing novel cytotoxic regimens.

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49

Xiao, Zhe. "Biosynthetic studies of tetrodotoxin and its anticancer activities assessment in vitro". HKBU Institutional Repository, 2014. https://repository.hkbu.edu.hk/etd_oa/56.

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In this study, the synthesis of TTX by three species of TTX-producing bacteria (Vibrio alginolyticus, Microbacterium arabinogalactanolyticum and Serratia marcescens) was conducted in a 10-L fermentor under the same controlled fermentation conditions for each of a period of 60 hours. The bacterial growth curves were monitored and the TTX synthesized in the culture medium was determined by HPLC. The TTX biosynthesis was found limited at the microgram level per L of culture medium with toxicities 14.7 MU (mouse unit) and 13.0 MU per mL in the partially purified culture medium of V. alginolyticus and M. arabinogalactanolyticum respectively by mouse bioassay. In the studies on SW480 and SW620 colorectal carcinoma cell lines, the expression, distribution, invasion and proliferation of voltage-gated sodium channels (VGSCs) were investigated by MTT assay (24-48 hours) and wound healing assay (0-120 hours). The different subtypes of VGSCs were expressed by semiquantitative RT-PCR and the locations of Nav1.5 and Nav 1.7 were detected by immunofluorescence microscopy. In the MTT assay, 40μmol/L of TTX showed significant inhibitory effect on both cell lines, with maximum inhibition rate, 33% and 40%, in SW480 and SW620 respectively. In the wound-healing assay, the inhibitory rate of 80μmol/L of TTX on SW480 reached 22% after 120 hours, compared with 30% in the control group. Moreover, VGSCs were highly expressed in both SW480 and SW620, with the main subtypes of Nav1.5 and Nav1.7 located on the cell surface, which might increase the metastatic rate of the cell lines. Keywords: Tetrodotoxin (TTX), Bacterial synthesis, Anticancer, VGSCs

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Fannon, Nanette Gayle 1962. "BOUVARDIN ANALOGS (DEOXYBOUVARDIN, IODINATION, IODODEOXYBOUVARDIN, O-METHYL-N-BOC-L-TYROSINE, ANTITUMOR AGENTS)". Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/291590.

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