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Georgia Tech
1.
Baxter, James Thomas.
Studies in the synthesis of camptothecin.
Degree: MS, Chemistry, 1976, Georgia Tech
URL: http://hdl.handle.net/1853/27317 
Subjects/Keywords: Camptothecin
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APA (6th Edition):
Baxter, J. T. (1976). Studies in the synthesis of camptothecin. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/27317
Chicago Manual of Style (16th Edition):
Baxter, James Thomas. “Studies in the synthesis of camptothecin.” 1976. Masters Thesis, Georgia Tech. Accessed April 13, 2021.
http://hdl.handle.net/1853/27317.
MLA Handbook (7th Edition):
Baxter, James Thomas. “Studies in the synthesis of camptothecin.” 1976. Web. 13 Apr 2021.
Vancouver:
Baxter JT. Studies in the synthesis of camptothecin. [Internet] [Masters thesis]. Georgia Tech; 1976. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1853/27317.
Council of Science Editors:
Baxter JT. Studies in the synthesis of camptothecin. [Masters Thesis]. Georgia Tech; 1976. Available from: http://hdl.handle.net/1853/27317
Cornell University
2.
Greene, Ashlee.
Effect Of Peg Composition On The Dissociation Rate Of Camptothecin-Peg Conjugates.
Degree: M.S., Chemical Engineering, Chemical Engineering, 2015, Cornell University
URL: http://hdl.handle.net/1813/40883
► Camptothecin (CPT) is an anti-cancer drug that inhibits the enzyme DNA Topoisomerase 1, leading to the apoptosis of cancerous cells. Although several analogs of CPT…
(more)
▼ Camptothecin (CPT) is an anti-cancer drug that inhibits the enzyme DNA Topoisomerase 1, leading to the apoptosis of cancerous cells. Although several analogs of CPT have been synthesized as chemotherapy agents, a number issues remain that hinder its success including lack of stability of the active form, poor solubility and limited circulation time. To overcome these challenges, conjugation of the CPT drug to polymers such as polyethylene glycol (PEG), has been shown to improve CPT solubility and circulation time, thus leading to an increase in drug bioavailabity. However there is still limited understanding of how the properties of the polymer influence the dissociation of the drug from the drug-polymer complex. In this study, PEG polymers of varying molecular weights (MW) and polydispersities were conjugated to CPT and characterized via 1H NMR and mass spectrometry (MS). The extent of CPT dissociation from the CPT-PEG conjugate was monitored via liquid chromatography over two days at a variety of temperatures and pH. The data acquired from these studies showed distinct molecular weight effects on CPT-PEG dissociation rates. In addition, we also observed an increase in the rate and extent of dissociation as a function of hydroxide ion concentration. Future areas of investigation will include performing the dissociation studies with additional PEGs of different MW to further confirm the observed MW dependency as well as using PEGs with different end groups to study possible end group effects. The results of this work should lay the foundation for developing controlled-release CPT-PEG conjugates for a wide variety of drug delivery applications.
Advisors/Committee Members: Alabi,Christopher Akinleye (chair), Putnam,David A. (committee member).
Subjects/Keywords: Camptothecin; PEG; dissociation rate
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APA (6th Edition):
Greene, A. (2015). Effect Of Peg Composition On The Dissociation Rate Of Camptothecin-Peg Conjugates. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/40883
Chicago Manual of Style (16th Edition):
Greene, Ashlee. “Effect Of Peg Composition On The Dissociation Rate Of Camptothecin-Peg Conjugates.” 2015. Masters Thesis, Cornell University. Accessed April 13, 2021.
http://hdl.handle.net/1813/40883.
MLA Handbook (7th Edition):
Greene, Ashlee. “Effect Of Peg Composition On The Dissociation Rate Of Camptothecin-Peg Conjugates.” 2015. Web. 13 Apr 2021.
Vancouver:
Greene A. Effect Of Peg Composition On The Dissociation Rate Of Camptothecin-Peg Conjugates. [Internet] [Masters thesis]. Cornell University; 2015. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1813/40883.
Council of Science Editors:
Greene A. Effect Of Peg Composition On The Dissociation Rate Of Camptothecin-Peg Conjugates. [Masters Thesis]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/40883
University of Texas – Austin
3.
Arora, Sucheta.
Role of Sae2 in repair of TopoisomeraseI-DNA conjugates.
Degree: PhD, Cell and Molecular Biology, 2016, University of Texas – Austin
URL: http://hdl.handle.net/2152/68700
► Topoisomerase inhibitors are widely used chemotherapeutic drugs. They covalently trap the target topoisomerase on DNA, which interferes with the progression of replication and transcription machinery…
(more)
▼ Topoisomerase inhibitors are widely used chemotherapeutic drugs. They covalently trap the target topoisomerase on DNA, which interferes with the progression of replication and transcription machinery and induces lethal DNA damage. The ability of cells to repair this damage is a key determinant of the effectiveness of these drugs and elucidation of the repair pathways is of great clinical relevance. In this study, I investigate the role of Sae2 protein in protecting yeast cells from
camptothecin, a Topoisomerase I inhibitor. Sae2 is a key component of the DNA double strand break repair pathway and works in collaboration with the Mre11-Rad50-Xrs2 (MRX) protein complex in homologous recombination mediated repair. Sae2 null cells are highly sensitive to
camptothecin in survival assays. I show that this sensitivity is dependent on active replication as well as transcription in vivo. Sae2 preferentially localizes to highly transcribed regions after
camptothecin exposure in S phase, suggesting that it has a role in repair of TopoI-DNA conjugates at those sites. We find that
camptothecin sensitivity in the absence of Sae2 can be rescued by over-expression of Sen1, an RNA:DNA helicase that is part of the transcription termination NRD complex. Sen1 removes R-loops that form in the negatively supercoiled region behind a stalled or slow transcription unit. Sen1 over-expression also rescues a strain containing both a sae2 null allele and an Mre11 nuclease-deficient allele. I show that R-loops accumulate at the highly transcribed rDNA region after
camptothecin exposure in the absence of Sae2 function and that Sen1 over-expression reduces this accumulation. I propose that Sae2 and Mre11 have a role in processing the R loops induced by TopoI-DNA conjugates at highly transcribed regions in the genome.
It has been shown that Sae2 is a structure-specific endonuclease with a preference for 5’ flaps and ssDNA/dsDNA junctions in vitro. It also stimulates the nuclease activity of Mre11 on DNA ends containing protein adducts. In this study, I identify two mutant alleles of Sae2 that separate these two biochemical activities. The D285P K288P Sae2 mutant is proficient in the Sae2 nuclease activity but deficient for the stimulation of Mre11 activity on protein-blocked DNA ends. The E161P K163P mutation renders the protein deficient for its nuclease activity but the mutant can stimulate Mre11 activity. The survival complementation assay indicates that stimulation of Mre11 activity is the primary function of Sae2 and that its nuclease activity is required only in the absence of Mre11 nuclease activity. Sae2 is implicated in a variety of roles in DNA double-strand break repair and signaling pathways including stimulating resection, modulating Tel1 activation, removing MRX from the DSB sites, processing hairpin intermediates, removing Spo11 from meiotic DNA breaks and processing Topo1-DNA adducts. The mutant alleles described in this study provide useful reagents to elucidate the role of Sae2 enzymatic activity and its coordination with Mre11…
Advisors/Committee Members: Paull, Tanya T. (advisor), Johnson, Arlen W (committee member), Huibregtse, Jon M (committee member), Vasquez, Karen M (committee member), Jayaram, Makkuni (committee member).
Subjects/Keywords: Sae2; TopoisomeraseI; Sen1; Camptothecin
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APA (6th Edition):
Arora, S. (2016). Role of Sae2 in repair of TopoisomeraseI-DNA conjugates. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/68700
Chicago Manual of Style (16th Edition):
Arora, Sucheta. “Role of Sae2 in repair of TopoisomeraseI-DNA conjugates.” 2016. Doctoral Dissertation, University of Texas – Austin. Accessed April 13, 2021.
http://hdl.handle.net/2152/68700.
MLA Handbook (7th Edition):
Arora, Sucheta. “Role of Sae2 in repair of TopoisomeraseI-DNA conjugates.” 2016. Web. 13 Apr 2021.
Vancouver:
Arora S. Role of Sae2 in repair of TopoisomeraseI-DNA conjugates. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2016. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/2152/68700.
Council of Science Editors:
Arora S. Role of Sae2 in repair of TopoisomeraseI-DNA conjugates. [Doctoral Dissertation]. University of Texas – Austin; 2016. Available from: http://hdl.handle.net/2152/68700
Rutgers University
4.
Ibrahim, Sherif, 1981-.
Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer.
Degree: PhD, Pharmaceutical Science, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/47732/
► Lung cancer is the most common cause of cancer-related mortality among both men and women in the United States and worldwide, killing more people than…
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▼ Lung cancer is the most common cause of cancer-related mortality among both men and women in the United States and worldwide, killing more people than breast, prostate, and colon cancers combined. It is estimated that 1.37 million people worldwide die of the disease annually. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases worldwide and thus remains a primary focus of therapeutic lung cancer research. Currently used treatments for NSCLC include surgery, chemotherapy, radiotherapy, and targeted/biological therapy. Despite these treatment options, the disease remains a considerable cause of morbidity and mortality. Thus, more effective treatment options are highly sought after. NSCLC is most often diagnosed at late stages, at which time surgery can no longer offer a curative outcome. Thus, cytotoxic chemotherapy remains the first-line treatment for late-stage NSCLC. However, efficacy has been modest at best and toxicity remains a significant drawback. Improvements to current chemotherapeutic strategies are direly needed. The objective of this thesis is to evaluate a combination of camptothecin (CPT) and sodium-R-alpha lipoate (Na-RALA) for the treatment of NSCLC. Using a variety of concentration- and time-dependent in vitro assays, we found that a combination of CPT and Na-RALA: 1) exerted additive/synergistic cytotoxic effects against A549 human NSCLC adenocarcinoma cells; 2) has higher efficacy, higher cancer-selectivity, and lower toxicity towards normal cells than CPT alone; 3) simultaneously targets multiple hallmarks of cancer, including migration, invasion, senescence, and angiogenesis, and thus has the potential to reduce metastasis and general progression of NSCLC. In vivo evaluation of the combination began with the development of an orthotopic xenograft NSCLC model. The intrathoracic (IT) and intracardiac (IC) mouse models of NSCLC were deemed most fitting for our study design and objectives. A combination of CPT and Na-RALA deserves further evaluation as a treatment for NSCLC.
Advisors/Committee Members: Sinko, Patrick (chair), Colaizzi, John L. (internal member), Suh, Nanjoo (internal member), Prud'homme, Robert (outside member).
Subjects/Keywords: Lungs – Cancer – Treatment; Camptothecin
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APA (6th Edition):
Ibrahim, Sherif, 1. (2015). Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/47732/
Chicago Manual of Style (16th Edition):
Ibrahim, Sherif, 1981-. “Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer.” 2015. Doctoral Dissertation, Rutgers University. Accessed April 13, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/47732/.
MLA Handbook (7th Edition):
Ibrahim, Sherif, 1981-. “Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer.” 2015. Web. 13 Apr 2021.
Vancouver:
Ibrahim, Sherif 1. Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Apr 13].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/47732/.
Council of Science Editors:
Ibrahim, Sherif 1. Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/47732/
5.
Fernandes, Barbara Colatto [UNESP].
Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma.
Degree: 2018, Universidade Estadual Paulista (UNESP)
URL: http://hdl.handle.net/11449/166405
► Submitted by Barbara Colatto Fernandes ([email protected]) on 2018-12-04T12:41:44Z No. of bitstreams: 1 Dissertação Barbara Colatto Versão Final 22 novembro 2018 .pdf: 1255491 bytes, checksum: bce8f5a99361f8a5568891e4bf709fd3…
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▼ Submitted by Barbara Colatto Fernandes ([email protected]) on 2018-12-04T12:41:44Z No. of bitstreams: 1 Dissertação Barbara Colatto Versão Final 22 novembro 2018 .pdf: 1255491 bytes, checksum: bce8f5a99361f8a5568891e4bf709fd3 (MD5)
Approved for entry into archive by Maria Irani Coito ([email protected]) on 2018-12-06T20:08:29Z (GMT) No. of bitstreams: 1 fernandes_bc_me_arafcf.pdf: 1222277 bytes, checksum: 628bd9708ff9cf232f71392383c1f460 (MD5)
Made available in DSpace on 2018-12-06T20:08:29Z (GMT). No. of bitstreams: 1 fernandes_bc_me_arafcf.pdf: 1222277 bytes, checksum: 628bd9708ff9cf232f71392383c1f460 (MD5) Previous issue date: 2018-10-31
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
O câncer é um conjunto de alterações celulares que favorecem a proliferação descontrolada e a aquisição de propriedades metastáticas. A ativação de oncogenes e/ou a perda de genes supressores tumorais leva a desbalanços
nos mecanismos de controle do ciclo celular e/ou na inativação das vias apoptóticas, contribuindo para a instabilidade genômica presente em todos os tipos tumorais. Relatos na literatura têm sugerido que o estresse replicativo oriundo desse aumento proliferativo exacerbado é um fator importante na formação e progressão de muitos tipos de câncer. Dentro dessa perspectiva, é plausível pensar que as células tumorais tenham desenvolvido certas competências que as permitam lidar com o estresse replicativo para continuar se propagando. Resultados prévios de nosso laboratório sugerem que a proteína centromérica HJURP (Holliday Junction Recognizing Protein) esteja envolvida nesse ganho de competência. Dessa forma, esse trabalho teve como objetivo a análise do papel dessa proteína frente ao estresse replicativo em linhagens de glioblastoma. Nossos resultados demonstraram que a superexpressão de HJURP confere um aumento na capacidade proliferativa celular da linhagem U87MG. Além disso, vimos
que em baixas concentrações de camptotecina as células superexpressoras de HJURP possuíam um comportamento proliferativo muito semelhante à condição não tratada. Os ensaios de citotoxicidade revelaram uma maior capacidade de recuperação frente ao estresse replicativo exógeno nas situações em que HJURP estava superexpressa. Conjuntamente, esses dados sugerem que o incremento nos níveis celulares de HJURP parece conferir uma maior resistência ao estresse replicativo induzido por camptotecina nas células U87MG.
Cancer is characterized by a subset of features that supports uncontrolled cell proliferation and acquisition of metastatic properties. Oncogene activation and/ or the deactivation of tumor suppressor genes lead to disbalances in cell cycle control progression and/or inactivation of apoptotic pathways, followed by genomic instability present in all types of tumors. According to the literature, replicative DNA stress arising from uncontrolled cell growth is the major driver in
the development and progression of many cancers. In this perspective, it is believed that cancer cells have…
Advisors/Committee Members: Universidade Estadual Paulista (UNESP), Valente, Valeria.
Subjects/Keywords: glioblastoma; camptotecina; HJURP; camptothecin
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APA (6th Edition):
Fernandes, B. C. [. (2018). Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma. (Masters Thesis). Universidade Estadual Paulista (UNESP). Retrieved from http://hdl.handle.net/11449/166405
Chicago Manual of Style (16th Edition):
Fernandes, Barbara Colatto [UNESP]. “Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma.” 2018. Masters Thesis, Universidade Estadual Paulista (UNESP). Accessed April 13, 2021.
http://hdl.handle.net/11449/166405.
MLA Handbook (7th Edition):
Fernandes, Barbara Colatto [UNESP]. “Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma.” 2018. Web. 13 Apr 2021.
Vancouver:
Fernandes BC[. Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma. [Internet] [Masters thesis]. Universidade Estadual Paulista (UNESP); 2018. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/11449/166405.
Council of Science Editors:
Fernandes BC[. Caracterização da atividade da HJURP na redução do estresse replicativo de linhagens de glioblastoma. [Masters Thesis]. Universidade Estadual Paulista (UNESP); 2018. Available from: http://hdl.handle.net/11449/166405
Texas A&M University
6.
Venditto, Vincent J.
Kilogram Scale Synthesis of a Triazine-based Dendrimer and the Development of a General Strategy for the Installation of Pharmacophores to Yield Potential Drug Delivery Agents.
Degree: PhD, Chemistry, 2011, Texas A&M University
URL: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7615
► Diverse dendrimer peripheries are often produced through convergent synthesis with multiple protection-deprotection steps. Achieving such diversity while maintaining monodispersity, has previously proven problematic. Interception of…
(more)
▼ Diverse dendrimer peripheries are often produced through convergent synthesis with multiple protection-deprotection steps. Achieving such diversity while maintaining
monodispersity, has previously proven problematic. Interception of an electrophilic poly(monochlorotriazine) dendrimer with a molecule of interest bearing a reactive, nucleophilic group presents an efficient method to achieve large quantities of dendrimers with biologically relevant peripheries.
Kilogram-scale synthesis of a triazine-based dendrimer relies on reaction of the dichlorotriazine monomer with the amine terminated dendrimer to afford a poly(monochlorotriazine) dendrimer. Normally, the dendrimer is then reacted with
piperidine, an inexpensive “cap” due to its chemically inert nature after reaction. The dendrimer then undergoes a global deprotection to afford an amine-terminated
dendrimer. Subsequent iterations with the dichlorotriazine monomer affords higher generation architectures. Intercepting the poly(monochlorotriazine) dendrimer with biologically relevant molecules containing reactive amines enables the development of a drug delivery vehicle. Desferrioxamine B, an iron chelate, and
camptothecin, and anticancer
drug, are two clinically approved drugs of interest investigated for macromolecular drug delivery. Upon acylation of each drug with BOC-isonipecotic
acid, substitution on the dendrimer may occur with varying levels of success depending on the drug in question. Upon successful substitution to afford the desired product,biological studies may be performed. Each synthetic approach will be discussed along
with alternative routes leading to this general strategy.
Advisors/Committee Members: Simanek, Eric E. (advisor), Darensbourg, Marcetta Y. (committee member), Connell, Brian T. (committee member), Cote, Gerard L. (committee member).
Subjects/Keywords: Triazine-based dendrimer; kilogram-scale; desferrioxamine; camptothecin
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APA (6th Edition):
Venditto, V. J. (2011). Kilogram Scale Synthesis of a Triazine-based Dendrimer and the Development of a General Strategy for the Installation of Pharmacophores to Yield Potential Drug Delivery Agents. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7615
Chicago Manual of Style (16th Edition):
Venditto, Vincent J. “Kilogram Scale Synthesis of a Triazine-based Dendrimer and the Development of a General Strategy for the Installation of Pharmacophores to Yield Potential Drug Delivery Agents.” 2011. Doctoral Dissertation, Texas A&M University. Accessed April 13, 2021.
http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7615.
MLA Handbook (7th Edition):
Venditto, Vincent J. “Kilogram Scale Synthesis of a Triazine-based Dendrimer and the Development of a General Strategy for the Installation of Pharmacophores to Yield Potential Drug Delivery Agents.” 2011. Web. 13 Apr 2021.
Vancouver:
Venditto VJ. Kilogram Scale Synthesis of a Triazine-based Dendrimer and the Development of a General Strategy for the Installation of Pharmacophores to Yield Potential Drug Delivery Agents. [Internet] [Doctoral dissertation]. Texas A&M University; 2011. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7615.
Council of Science Editors:
Venditto VJ. Kilogram Scale Synthesis of a Triazine-based Dendrimer and the Development of a General Strategy for the Installation of Pharmacophores to Yield Potential Drug Delivery Agents. [Doctoral Dissertation]. Texas A&M University; 2011. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7615
Boston University
7.
Swayze, Emma.
The effects of CTDSP1 on topoI degradation and cellular resistance to topoI inhibitors chemotherapy treatment.
Degree: MS, Medical Sciences, 2017, Boston University
URL: http://hdl.handle.net/2144/23723
► The anticancer drug Camptothecin (CPT) specifically targets topoisomerase I (topoI). While this class of drug is used to treat various solid tumors, CPT is only…
(more)
▼ The anticancer drug Camptothecin (CPT) specifically targets topoisomerase I (topoI). While this class of drug is used to treat various solid tumors, CPT is only effective in 13-30 percent of the patient population. Although the mechanism of the CPT resistance pathway is not fully understood, we found cancer cells degrade topoisomerase I (topoI) in response to CPT. The observed relationship between higher basal DNA-PKcs mediated phosphorylation of topoI, rapid degradation of topoI, and resistance to CPT suggested that DNA-PKcs is a critical regulator of the phosphorylation status of topoI and the rate of topoI degradation in response to CPT. The data shows CTDSP1 (a dual phosphatase) acts as a negative regulator of DNA-PKcs. Because CTDSP1 functionality plays a role in maintaining higher basal phosphorylation levels of topoI, CTDSP1 impairment contributes to greater CPT resistance. This renders the CPT chemotherapy treatment ineffective. We hypothesized inducing the catalytically inactive form of CTDPS1 via both knockdown and inhibition experiments would increase cancer cell resistance to CPT as a result of an overactive topoI degradation pathway. The function of CTDSP1 was impaired in the two colon cancer cell lines, HCT15 and HCT116, by silencing with siRNA and using Rabeprazole (a pharmacological agent known to inhibit CTDSP1). Inhibition of CTDSP1 phosphatase activity resulted in greater phosphorylation of DNA-PKcs and increased the rate of topoI degradation in the cells in response to CPT. Cellular resistance was also more notable in the sensitive HCT116 cell lines. HCT15 cells degrade topoI rapidly and are resistant to CPT. Thus, the effect of CPT is not as pronounced in this cell line. CTDSP1 knock down cells showed the greatest DNA-PKcs phosphorylation and topoI degradation when treated with CPT. In addition, the present study includes a clonogenic assay that shows a larger cell survival fraction in Rabeprazole treated HCT116 cells in comparison to controls after exposure to CPT. A higher survival fraction after CPT exposure is reflective of greater CPT resistance. This suggests that cell viability is enhanced during CPT chemotherapy treatment in CTDSP1 null colorectal cancer cells. Lastly, An EGFP read out experiment of topoI tagged to EGFP demonstrated CTDSP1 inhibition results in reduced topoI levels in colorectal cancer cells. The present study showed the potential link between lower topoI levels and greater resistance to CPT by showing that both effects are outcomes of silencing CTDSP1.
Subjects/Keywords: Oncology; Camptothecin; CTDSP1; Rabeprazole; Colorectal cancer
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APA (6th Edition):
Swayze, E. (2017). The effects of CTDSP1 on topoI degradation and cellular resistance to topoI inhibitors chemotherapy treatment. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/23723
Chicago Manual of Style (16th Edition):
Swayze, Emma. “The effects of CTDSP1 on topoI degradation and cellular resistance to topoI inhibitors chemotherapy treatment.” 2017. Masters Thesis, Boston University. Accessed April 13, 2021.
http://hdl.handle.net/2144/23723.
MLA Handbook (7th Edition):
Swayze, Emma. “The effects of CTDSP1 on topoI degradation and cellular resistance to topoI inhibitors chemotherapy treatment.” 2017. Web. 13 Apr 2021.
Vancouver:
Swayze E. The effects of CTDSP1 on topoI degradation and cellular resistance to topoI inhibitors chemotherapy treatment. [Internet] [Masters thesis]. Boston University; 2017. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/2144/23723.
Council of Science Editors:
Swayze E. The effects of CTDSP1 on topoI degradation and cellular resistance to topoI inhibitors chemotherapy treatment. [Masters Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/23723
Boston University
8.
Unan, Elizabeth Claire.
BRCA1 E3 ligase inhibitors induces synthetic lethality in CPT resistant cells.
Degree: MS, Medical Sciences, 2018, Boston University
URL: http://hdl.handle.net/2144/30867
► Camptothecin and its analogues (CPTs) represent one of the most potent classes of anticancer drugs used to treat several solid tumors. CPTs bind topoisomerase I…
(more)
▼ Camptothecin and its analogues (CPTs) represent one of the most potent classes of anticancer drugs used to treat several solid tumors. CPTs bind topoisomerase I during the replication process and cause DNA damage that results in cell death. However, its effectiveness is limited to 13-30 percent of patients. TopoI cuts and re-ligates DNA supercoiling but in the presence of CPT it fails to re-ligate DNA and collision of replication forks leads to DNA double strand break (DNA-DSB) and cell death. However, in resistant cells, due to deregulated kinase cascade, topoI is continually phosphorylated by DNA-PKcs and rapidly degraded by the ubiquitin proteasomal pathway (UPP). It has been found that BRCA1 plays a key role in imparting cellular resistance to topoI inhibitors. Importantly, BRCA1 ubiquitinates topoI in response to CPT. We hypothesize that disruption of BRCA1 binding to phosphorylated topoI would interrupt the resistance mechanism resulting in higher cellular sensitivity of CPT. Based on an in-silico drug screen, we identified a compound that inhibits topoI degradation by blocking BRCA1 binding. Imaging and survival assays findings are consistent with the hypothesis that BRCA1 plays a role in CPT resistance through its co-localization with topoI, and we speculate this role is through UPP degradation. CPTs are commonly used in combination with cytotoxic compounds, but this study focuses on discovering compounds that can overcome resistance without causing further cytotoxicity.
Advisors/Committee Members: Bharti, Ajit K. (advisor), Plant, Lucia (advisor).
Subjects/Keywords: Oncology; BRCA1; Camptothecin; Topoisomerase; E3 ligase
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APA (6th Edition):
Unan, E. C. (2018). BRCA1 E3 ligase inhibitors induces synthetic lethality in CPT resistant cells. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/30867
Chicago Manual of Style (16th Edition):
Unan, Elizabeth Claire. “BRCA1 E3 ligase inhibitors induces synthetic lethality in CPT resistant cells.” 2018. Masters Thesis, Boston University. Accessed April 13, 2021.
http://hdl.handle.net/2144/30867.
MLA Handbook (7th Edition):
Unan, Elizabeth Claire. “BRCA1 E3 ligase inhibitors induces synthetic lethality in CPT resistant cells.” 2018. Web. 13 Apr 2021.
Vancouver:
Unan EC. BRCA1 E3 ligase inhibitors induces synthetic lethality in CPT resistant cells. [Internet] [Masters thesis]. Boston University; 2018. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/2144/30867.
Council of Science Editors:
Unan EC. BRCA1 E3 ligase inhibitors induces synthetic lethality in CPT resistant cells. [Masters Thesis]. Boston University; 2018. Available from: http://hdl.handle.net/2144/30867
NSYSU
9.
Wang, Yung-Sheng.
Synthetic Studies toward Cerpegin, Actinidine and Camptothecin.
Degree: PhD, Chemistry, 2008, NSYSU
URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0119108-193829
Subjects/Keywords: Actinidine and Camptothecin; Cerpegin
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APA ·
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MLA ·
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Wang, Y. (2008). Synthetic Studies toward Cerpegin, Actinidine and Camptothecin. (Doctoral Dissertation). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0119108-193829
Chicago Manual of Style (16th Edition):
Wang, Yung-Sheng. “Synthetic Studies toward Cerpegin, Actinidine and Camptothecin.” 2008. Doctoral Dissertation, NSYSU. Accessed April 13, 2021.
http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0119108-193829.
MLA Handbook (7th Edition):
Wang, Yung-Sheng. “Synthetic Studies toward Cerpegin, Actinidine and Camptothecin.” 2008. Web. 13 Apr 2021.
Vancouver:
Wang Y. Synthetic Studies toward Cerpegin, Actinidine and Camptothecin. [Internet] [Doctoral dissertation]. NSYSU; 2008. [cited 2021 Apr 13].
Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0119108-193829.
Council of Science Editors:
Wang Y. Synthetic Studies toward Cerpegin, Actinidine and Camptothecin. [Doctoral Dissertation]. NSYSU; 2008. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0119108-193829
Mahatma Gandhi University
10.
Joseph, Ginu.
In vivo and in vitro production of Camptothecin on
Ophiorrhiza species; -.
Degree: Botany, 2013, Mahatma Gandhi University
URL: http://shodhganga.inflibnet.ac.in/handle/10603/13239
None
Summary p.285-290, References
p.291-312
Advisors/Committee Members: Joseph, Joy P.Subjects/Keywords: Botany; Ophiorrhiza species; camptothecin; Ophiorrhiza
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Joseph, G. (2013). In vivo and in vitro production of Camptothecin on
Ophiorrhiza species; -. (Thesis). Mahatma Gandhi University. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/13239
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Joseph, Ginu. “In vivo and in vitro production of Camptothecin on
Ophiorrhiza species; -.” 2013. Thesis, Mahatma Gandhi University. Accessed April 13, 2021.
http://shodhganga.inflibnet.ac.in/handle/10603/13239.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Joseph, Ginu. “In vivo and in vitro production of Camptothecin on
Ophiorrhiza species; -.” 2013. Web. 13 Apr 2021.
Vancouver:
Joseph G. In vivo and in vitro production of Camptothecin on
Ophiorrhiza species; -. [Internet] [Thesis]. Mahatma Gandhi University; 2013. [cited 2021 Apr 13].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/13239.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Joseph G. In vivo and in vitro production of Camptothecin on
Ophiorrhiza species; -. [Thesis]. Mahatma Gandhi University; 2013. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/13239
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
North Carolina State University
11.
Nolan, Jason Michael.
The Synthesis of (S)-Camptothecin and Clinically Useful Analogs.
Degree: PhD, Chemistry, 2003, North Carolina State University
URL: http://www.lib.ncsu.edu/resolver/1840.16/3716
► A six-step synthesis of (S)-camptothecin (CPT) was completed relinquishing a fast, efficient route to this natural product. The key steps included the formation of the…
(more)
▼ A six-step synthesis of (S)-
camptothecin (CPT) was completed relinquishing a fast, efficient route to this natural product. The key steps included the formation of the 4-iodo-2,3-pyridylacetal intermediate 56 required to obtain the DE ring moiety of CPT, and an intramolecular Heck reaction for the closure of ring C.
The convergence of this synthesis provided a straightforward method for CPT-analog development. Application is displayed in the syntheses of the clinically useful CPT-derivatives Karenitecin BNP1350 and the Irinotecan precursor 66. These syntheses are highlighted by short, high-yielding routes to the tetra- and tri-substituted quinoline rings, respectively. The DE ring portion of homocamptothecin (hCPT) was completed utilizing the same key intermediate 56 of the CPT synthesis. Although racemic, this seminal synthesis is very concise, being significantly shorter than known protocols.
An investigation for the use of 2-haloquinolines as synthetic building blocks in CPT-analog development was completed. Attempts to use directed ortho-metallation (DoM) chemistry on 2-chloro-3-quinolinecarboxaldehyde and derivatives proved to be inapplicable. However, regioselective lithium-halogen exchange and palladium-catalyzed coupling reactions were discovered for 2,4-dihaloquinolines. This success provides a versatile method for synthesizing highly substituted quinolines.
Advisors/Committee Members: Daniel L. Comins, Committee Chair (advisor).
Subjects/Keywords: irinotecan; camptothecin; haloquinolines; karenitecin
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MLA ·
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APA (6th Edition):
Nolan, J. M. (2003). The Synthesis of (S)-Camptothecin and Clinically Useful Analogs. (Doctoral Dissertation). North Carolina State University. Retrieved from http://www.lib.ncsu.edu/resolver/1840.16/3716
Chicago Manual of Style (16th Edition):
Nolan, Jason Michael. “The Synthesis of (S)-Camptothecin and Clinically Useful Analogs.” 2003. Doctoral Dissertation, North Carolina State University. Accessed April 13, 2021.
http://www.lib.ncsu.edu/resolver/1840.16/3716.
MLA Handbook (7th Edition):
Nolan, Jason Michael. “The Synthesis of (S)-Camptothecin and Clinically Useful Analogs.” 2003. Web. 13 Apr 2021.
Vancouver:
Nolan JM. The Synthesis of (S)-Camptothecin and Clinically Useful Analogs. [Internet] [Doctoral dissertation]. North Carolina State University; 2003. [cited 2021 Apr 13].
Available from: http://www.lib.ncsu.edu/resolver/1840.16/3716.
Council of Science Editors:
Nolan JM. The Synthesis of (S)-Camptothecin and Clinically Useful Analogs. [Doctoral Dissertation]. North Carolina State University; 2003. Available from: http://www.lib.ncsu.edu/resolver/1840.16/3716
University of Vienna
12.
Schuckert, Christoph.
Untersuchungen zur Synthese eines 9-Amino-4-methoxy-Derivates des Naturstoffs Luotonin A.
Degree: 2019, University of Vienna
URL: http://othes.univie.ac.at/59598/
Das Ziel der vorliegenden Diplomarbeit war es ein besser lösliches und potenziell potenteres Derivat des Naturstoffs Luotonin A zu synthetisieren bzw. erstmals zugänglich zu machen und dieses an anderer Stelle auf seine zytotoxische Aktivität zu testen.
Subjects/Keywords: 35.59 Heterocyclische Verbindungen; Luotonin A / Tumorchemotherapie / Topoisomerase-1 / Camptothecin / pentacyclisches Alkaloid
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APA ·
Chicago ·
MLA ·
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CSE |
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APA (6th Edition):
Schuckert, C. (2019). Untersuchungen zur Synthese eines 9-Amino-4-methoxy-Derivates des Naturstoffs Luotonin A. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/59598/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Schuckert, Christoph. “Untersuchungen zur Synthese eines 9-Amino-4-methoxy-Derivates des Naturstoffs Luotonin A.” 2019. Thesis, University of Vienna. Accessed April 13, 2021.
http://othes.univie.ac.at/59598/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Schuckert, Christoph. “Untersuchungen zur Synthese eines 9-Amino-4-methoxy-Derivates des Naturstoffs Luotonin A.” 2019. Web. 13 Apr 2021.
Vancouver:
Schuckert C. Untersuchungen zur Synthese eines 9-Amino-4-methoxy-Derivates des Naturstoffs Luotonin A. [Internet] [Thesis]. University of Vienna; 2019. [cited 2021 Apr 13].
Available from: http://othes.univie.ac.at/59598/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Schuckert C. Untersuchungen zur Synthese eines 9-Amino-4-methoxy-Derivates des Naturstoffs Luotonin A. [Thesis]. University of Vienna; 2019. Available from: http://othes.univie.ac.at/59598/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Houston
13.
Kim, Yu Jin.
Pharmacokinetics and Enterohepatic Recycling of CZ48, a Lactone-Stabilized Camptothecin: Effects of Nanosuspension Formulation.
Degree: PhD, Pharmaceutics, 2017, University of Houston
URL: http://hdl.handle.net/10657/4841
► CZ48, a lactone-stabilized camptothecin (CPT), is a topoisomerase 1 enzyme inhibitor. Its strong potential as an anticancer agent has been demonstrated against various types of…
(more)
▼ CZ48, a lactone-stabilized
camptothecin (CPT), is a topoisomerase 1 enzyme inhibitor. Its strong potential as an anticancer agent has been demonstrated against various types of human tumors with a lack of toxicity in human tumor-xenografted mice. In addition, previous preclinical pharmacokinetic (PK) studies implied potential enterohepatic recycling of CZ48 and CPT responsible for their sustained concentrations in plasma for 6 hr after an oral dose of CZ48 in co-solvent formulation. The prolonged exposure of a drug by enterohepatic recycling may significantly alter drug PK and pharmacological effects, and cause unpredictable toxicity by multiple dosing. Hence, it is critical to characterize the hepatic metabolism, biliary excretion and enterohepatic recycling using preclinical models in early stages of drug discovery and development. Moreover, nanosuspension (NS) of CZ48 has been formulated in our laboratory to overcome its poor water solubility. Thus, the overall objective of this project was to evaluate the impacts of NS on biodistributions of CZ48 and CPT in human tumor-xenografted mice, and biliary excretions and enterohepatic recycling in rats. Different biodistribution patterns of CZ48 were observed between co-solvent (CoS) and NS groups in tumor-xenografted mice; however, the pattern of CPT was similar between CoS and NS groups. The highest exposure of CPT was in the liver and the lowest was in the brain. The extent of CPT exposure in tumor was comparable with those in kidney, spleen, and lung. Half-lives of CZ48 and CPT were 1.5 – 3.6 times increased in all tested organs and tumor. The prolonged exposure of CPT may offer a merit of NS for its antitumor activity as a topoisomerase 1 inhibitor of cell-cycle S-phase specific activity. In enterohepatic recycling study, biliary secretions of CZ48 and CPT were confirmed mainly by their parent forms not conjugates. After an intravenous (IV) dose of CZ48-CoS, the percentages of dose recovered in bile were 0.19 % and 3.05 % for CZ48 and CPT, respectively, indicating more favorable biliary secretion of CPT than CZ48. NS did not significantly increase biliary excretions of CZ48 and CPT, with comparable AUC0-12h ratios of CZ48 (or CPT) in bile to plasma (B/P) after an oral dose between CZ48-NS and CZ48-CoS. Enterohepatic recycling of CZ48 and CPT was minor, since their plasma concentration-time profiles and biliary secretions exhibited similar trends with or without interrupting the recycling. Our PK model adequately described plasma concentrations of CZ48 and CPT and biliary excretion of CPT when adopting compartments for enterohepatic recycling. In conclusion, this is the first report evaluating biliary excretions of CZ48 and CPT, and characterizing their enterohepatic recycling by employing in vitro, in vivo, and PK modeling approaches. Our findings on the metabolisms, biodistributions, biliary excretions, and enterohepatic recycling of CZ48 and CPT are significant, and has enabled us to rationalize the clinical PK of CZ48 and CPT in the currently ongoing phase 1…
Advisors/Committee Members: Chow, Diana Shu-Lian (advisor), Ghose, Romi (committee member), Hu, Ming (committee member), Rytting, Erik (committee member), Yeung, S.C. Jim (committee member).
Subjects/Keywords: CZ48; Camptothecin; Nanosuspensions; Biodistribution; Biliary Excretion; Enterohepatic Recycling
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kim, Y. J. (2017). Pharmacokinetics and Enterohepatic Recycling of CZ48, a Lactone-Stabilized Camptothecin: Effects of Nanosuspension Formulation. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4841
Chicago Manual of Style (16th Edition):
Kim, Yu Jin. “Pharmacokinetics and Enterohepatic Recycling of CZ48, a Lactone-Stabilized Camptothecin: Effects of Nanosuspension Formulation.” 2017. Doctoral Dissertation, University of Houston. Accessed April 13, 2021.
http://hdl.handle.net/10657/4841.
MLA Handbook (7th Edition):
Kim, Yu Jin. “Pharmacokinetics and Enterohepatic Recycling of CZ48, a Lactone-Stabilized Camptothecin: Effects of Nanosuspension Formulation.” 2017. Web. 13 Apr 2021.
Vancouver:
Kim YJ. Pharmacokinetics and Enterohepatic Recycling of CZ48, a Lactone-Stabilized Camptothecin: Effects of Nanosuspension Formulation. [Internet] [Doctoral dissertation]. University of Houston; 2017. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/10657/4841.
Council of Science Editors:
Kim YJ. Pharmacokinetics and Enterohepatic Recycling of CZ48, a Lactone-Stabilized Camptothecin: Effects of Nanosuspension Formulation. [Doctoral Dissertation]. University of Houston; 2017. Available from: http://hdl.handle.net/10657/4841
University of Washington
14.
Glukhova, Veronika.
Comprehensive analysis of WRN protein interaction network by Mass Spectrometry.
Degree: PhD, 2014, University of Washington
URL: http://hdl.handle.net/1773/25376
► Cells that have lost WRN function exhibit a shortened replicative lifespan, accumulation of chromosomal aberrations, and demonstrate sensitivity to a number of chemotherapeutic agents, including…
(more)
▼ Cells that have lost WRN function exhibit a shortened replicative lifespan, accumulation of chromosomal aberrations, and demonstrate sensitivity to a number of chemotherapeutic agents, including DNA Topoisomerase I inhibitor
camptothecin (CPT). On organismal level, the lack of this protein results in the progeroid syndrome Werner Syndrome, which is characterized by increased incidence of cancers, cardiovascular disease, cataracts, and other age-associated pathologies. In this study we examined the network of proteins that associate with WRN protein, and then expanded this picture when the cells were challenged with CPT. We detail the profiling analysis used for unbiased detection of all interacting proteins using LC-MS/MS, followed by data analysis and selection of targets for follow-up. We then focus on the method development, complexities of data analysis, and application of selected reaction monitoring (SRM), a method for targeted MS. Using RNAi we demonstrate the power of this technique for relative protein quantitation of human proteins WRN and TP53, and a number of small, low-abundance seminal fluid proteins from D.melanogaster flies. SRM was applied for two studies of the WRN interactome: 1) to partially validate findings of the profiling screen after short-term treatment with CPT, and 2) to describe the dynamics of association of these proteins with WRN as a function of time, by expanding the treatment time course to 6 and 12 hours. We report on our description of WRN protein interaction complexes in unperturbed cells, and how these interaction complexes become reorganized in response to DNA damage. Our results demonstrate that the newly recruited proteins participate in chromatin remodeling, negative regulation of cell cycle progression, and double-strand break repair. We focus on 40 proteins to test their differential interaction with WRN after 1, 6, and 12 hours of treatment with CPT. We specifically focus on the functional importance of the chromatin-remodeling factors, and present the list of WRN interacting proteins that have emerged as high-priority targets for functional validation. Finally, we discuss how our work has expanded the understanding of the functional roles of WRN, and how targeted, hypothesis-driven application of mass spectrometry can be used to answer complex questions about protein interaction.
Advisors/Committee Members: Monnat, Raymond J (advisor).
Subjects/Keywords: Camptothecin; Mass Spectrometry; Proteomics; Werner Syndrome; Biochemistry; Cellular biology; pathology
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APA ·
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APA (6th Edition):
Glukhova, V. (2014). Comprehensive analysis of WRN protein interaction network by Mass Spectrometry. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/25376
Chicago Manual of Style (16th Edition):
Glukhova, Veronika. “Comprehensive analysis of WRN protein interaction network by Mass Spectrometry.” 2014. Doctoral Dissertation, University of Washington. Accessed April 13, 2021.
http://hdl.handle.net/1773/25376.
MLA Handbook (7th Edition):
Glukhova, Veronika. “Comprehensive analysis of WRN protein interaction network by Mass Spectrometry.” 2014. Web. 13 Apr 2021.
Vancouver:
Glukhova V. Comprehensive analysis of WRN protein interaction network by Mass Spectrometry. [Internet] [Doctoral dissertation]. University of Washington; 2014. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1773/25376.
Council of Science Editors:
Glukhova V. Comprehensive analysis of WRN protein interaction network by Mass Spectrometry. [Doctoral Dissertation]. University of Washington; 2014. Available from: http://hdl.handle.net/1773/25376
Universidade Estadual de Campinas
15.
Lima, João Paulo da Silveira Nogueira, 1980-.
Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise.
Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Ciências Médicas, 2012, Universidade Estadual de Campinas
URL: LIMA,
João
Paulo
da
Silveira
Nogueira.
Análogo
da
platina
associado
à
camptotecina
ou
ao
etoposídio
em
quimioterapia
de
primeira
linha
para
câncer
de
pulmão
pequenas
células,
doença
extensa
=
revisão
sistemática
e
metanálise.
2012.
111
p.
Tese
(doutorado)
-
Universidade
Estadual
de
Campinas,
Faculdade
de
Ciências
Médicas,
Campinas,
SP.
Disponível
em:
<http://www.repositorio.unicamp.br/handle/REPOSIP/313867>.
Acesso
em:
19
ago.
2018.
;
http://repositorio.unicamp.br/jspui/handle/REPOSIP/313867
► Orientadores: André Deeke Sasse, Carmen Silvia Passos Lima
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-20T01:24:11Z…
(more)
▼ Orientadores: André Deeke Sasse, Carmen Silvia Passos Lima
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-20T01:24:11Z (GMT). No. of bitstreams: 1 Lima_JoaoPaulodaSilveiraNogueira_D.pdf: 5411736 bytes, checksum: d1c0f5a06bb4361a4b7416cd43d94af5 (MD5) Previous issue date: 2012
Resumo: Introdução: a superioridade de regimes baseados em camptotecinas sobre os regimes baseados em etoposidio para câncer de pulmão de células pequenas, doença extensa, (CPCP-DE) e assunto amplamente debatido com achados contraditórios nos estudos randomizados que compararam estas combinações. Variações farmacogenomicas entre etnias surgiram como hipótese para justificar estas diferenças. Com objetivo de elucidar esta duvida e mensurar a extensão de um eventual beneficio, realizamos uma revisão sistemática e metalize. Métodos: Revisão sistemática da literatura com metanalise. Foram elegíveis
estudos randomizados controlados que comparassem o uso de análogo de platina associado ou a camptotecina (irinotecano ou topotecana) ou ao etoposidio como tratamento de primeira linha para CPCP-DE. Buscamos estes estudos nas bases PubMed, EMBASE, CENTRAL, LILACS e nos sítios eletrônicos dos congressos da ASCO, ESMO, ECCO e IASLC. As avaliações de sobrevida global (SG) e sobrevida livre de progressão mediana (SLP) foram apresentadas como hazard ratio (HR) enquanto a taxa de resposta tumoral (RT), toxicidades graves e sobrevida global em um e dois anos foram expressas através de odds ratio (OR). Os intervalos de confiança de 95% foram calculados para cada desfecho. A metalize utilizou método de efeitos randomicos, sendo a heterogeneidade entre estudos expressa através do índice de heterogeneidade I². Avaliação de subgrupos conforme origem geográfica dos estudos foi realizada e o teste de interação foi utilizado para identificar eventuais diferenças. Irinotecano-platina (IP) e
topotecana-platina (TP) foram avaliados separadamente. Resultados: 615 referencias foram avaliadas, sendo selecionados nove estudos (3527 pacientes). Dois estudos compararam TP versus EP enquanto sete compararam IP versus EP. A metanalise demonstrou que IP e capaz de aumentar a sobrevida global (1965 pacientes, HR = 0,87; 95% CI 0,80-0,95; P=0,002; I²=0%) e sobrevida global em um ano (HR = 0,74; IC95% 0,60-0,91; P = 0,004; I² = 14%), sem contudo, aumentar claramente a sobrevida livre de progressão, ou resposta tumoral. IP levou a maior incidência de toxicidades gastrointestinais e menos hematológicas. A avaliação de subgrupos conforme origem geográfica não identificou diferença na extensão de beneficio em sobrevida global e em um ano (interação ocidente versus oriente P = 0,34 e P = 0,08 respectivamente) com IP. Na analise de sobrevida global em dois anos, IP e superior a EP em pacientes europeus e asiáticos, sem contudo trazer ganho para pacientes da América do Norte (OR 1,05; IC95%
0,65-1,69; P = 0,85; interação América do Norte versus Europa, P = 0,009; interação América do Norte versus Ásia, P =…
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Lima, Carmen Silvia Passos, 1957-, Sasse, André Deeke, Teixeira, Luiz Carlos, Carvalheira, José Barreto Campello, Martins, Sandro José, Ferreira, Carlos Gil Moreira.
Subjects/Keywords: Neoplasias pulmonares; Revisão; Quimioterapia; Camptotecina; Lung neoplasms; Chemotherapy; Meta-analysis; Camptothecin
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MLA ·
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APA (6th Edition):
Lima, João Paulo da Silveira Nogueira, 1. (2012). Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. (Doctoral Dissertation). Universidade Estadual de Campinas. Retrieved from LIMA, João Paulo da Silveira Nogueira. Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. 2012. 111 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/313867>. Acesso em: 19 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/313867
Chicago Manual of Style (16th Edition):
Lima, João Paulo da Silveira Nogueira, 1980-. “Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise.” 2012. Doctoral Dissertation, Universidade Estadual de Campinas. Accessed April 13, 2021.
LIMA, João Paulo da Silveira Nogueira. Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. 2012. 111 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/313867>. Acesso em: 19 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/313867.
MLA Handbook (7th Edition):
Lima, João Paulo da Silveira Nogueira, 1980-. “Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise.” 2012. Web. 13 Apr 2021.
Vancouver:
Lima, João Paulo da Silveira Nogueira 1. Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. [Internet] [Doctoral dissertation]. Universidade Estadual de Campinas; 2012. [cited 2021 Apr 13].
Available from: LIMA, João Paulo da Silveira Nogueira. Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. 2012. 111 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/313867>. Acesso em: 19 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/313867.
Council of Science Editors:
Lima, João Paulo da Silveira Nogueira 1. Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. [Doctoral Dissertation]. Universidade Estadual de Campinas; 2012. Available from: LIMA, João Paulo da Silveira Nogueira. Análogo da platina associado à camptotecina ou ao etoposídio em quimioterapia de primeira linha para câncer de pulmão pequenas células, doença extensa = revisão sistemática e metanálise. 2012. 111 p. Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/313867>. Acesso em: 19 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/313867
NSYSU
16.
Yang, Chun-feng.
The disturbance effect of phthalate DEHP on camptothecin-treated human breast cancer cells in vitro and in zebrafish xenograft model.
Degree: Master, Institute of Biomedical Sciences, 2016, NSYSU
URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0115116-075905
► Breast cancer is a leading cause of death in women worldwide, and chemotherapy is one of the primary strategies for breast cancer treatment. However, the…
(more)
▼ Breast cancer is a leading cause of death in women worldwide, and chemotherapy is one of the primary strategies for breast cancer treatment. However, the chemoresistance often causes the poor prognosis of breast cancer patients. Phthalate derivatives have been shown to affect the expression of genes, and could take effects on genotoxic sensitivity and the ability of DNA repair in cells. Recent evidence suggested that phthalate exposure may be closely correlated with the chemoresistance of breast cancer cells. However, the underlying mechanism that phthalate causes chemoresistance is largely unclear. In the study, we investigated whether phthalates affect the chemoresistance by reinforcing the ability of DNA repair. Our results showed that phthalate Bis(2-ethylhexyl) phthalate (DEHP) attenuates the
camptothecin (CPT)-induced DNA damage in breast cancer cells MCF-7. Moreover, phthalate DEHP pre-treatment significantly inhibits the two hallmarks of double-strand breaks (DSB) of DNA, including γH2AX and the phosphorylation of ATM, which were significantly reduced in CPT-treated MCF-7 cells. Consistently, the results of zebrafish xenograft assay confirmed the protective effect of DEHP on CPT-induced cytotoxicity of breast cancer. Accordingly, our present work suggests that phthalate DEHP may affect the anti-breast cancer effect of CPT through attenuating the induction of DNA damage.
Advisors/Committee Members: Jeff Yi-Fu Chen (chair), Kuang-hung Cheng (chair), Chien-Chih Chiu (committee member), Hung-Wen Huamg (committee member).
Subjects/Keywords: DNA double-strand breaks; camptothecin; Phthalate; Bis(2-ethylhexyl) phthalate; DEHP; zebrafish; chemoresistance; breast cancer
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APA (6th Edition):
Yang, C. (2016). The disturbance effect of phthalate DEHP on camptothecin-treated human breast cancer cells in vitro and in zebrafish xenograft model. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0115116-075905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yang, Chun-feng. “The disturbance effect of phthalate DEHP on camptothecin-treated human breast cancer cells in vitro and in zebrafish xenograft model.” 2016. Thesis, NSYSU. Accessed April 13, 2021.
http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0115116-075905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yang, Chun-feng. “The disturbance effect of phthalate DEHP on camptothecin-treated human breast cancer cells in vitro and in zebrafish xenograft model.” 2016. Web. 13 Apr 2021.
Vancouver:
Yang C. The disturbance effect of phthalate DEHP on camptothecin-treated human breast cancer cells in vitro and in zebrafish xenograft model. [Internet] [Thesis]. NSYSU; 2016. [cited 2021 Apr 13].
Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0115116-075905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yang C. The disturbance effect of phthalate DEHP on camptothecin-treated human breast cancer cells in vitro and in zebrafish xenograft model. [Thesis]. NSYSU; 2016. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0115116-075905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Universiteit Utrecht
17.
Lin, F.
Targeted therapies for malignant gliomas: novel agents, same barrier.
Degree: 2013, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/268384
► Malignant gliomas are common and devastating brain malignancies. Despite this extensive treatment the mean overall survival is still only 14.6 months and more effective treatments…
(more)
▼ Malignant gliomas are common and devastating brain malignancies. Despite this extensive treatment the mean overall survival is still only 14.6 months and more effective treatments are urgently needed. Targeted therapy holds the promise for the new generation of chemotherapy due to the selectively target inhibition of deregulated signaling pathways in cancer cell but not normal cells. However, recent researches suggested that the blood-brain barrier (BBB) restricting the brain delivery of most traditional chemotherapies, are still a major factor that limiting the therapeutic effects of targeted agents. Importantly, like conventional chemotherapeutics, most of the small molecular inhibitors are also substrates of one or several ABC (ATP-binding cassette) multidrug efflux transporters expressed at the BBB as well as in tumor cells. Therefore, these small molecular pumps such as ABCB1/Abcb1 (P-glycoprotein, P-gp or MDR) and ABCG2/Abcg2 (BCRP) could severely compromise their target inhibitory effects.
The thesis first describes the two major limiting factors, namely, drug efflux transporters and intrinsic resistance of tumor cells that challenging the therapeutic effects of current small molecular targeted therapies in malignant gliomas. In the following chapters, we firstly describe two sensitive analytic assays for determining Palomid 529, a dual mTORC1 and mTORC2 inhibitor, and NVP-BEZ235, a dual PI3K and mTOR inhibitor in murine and human plasma and tissue samples. Furthermore, the roles of Abcb1 (P-glycoprotein) and Abcg2 (Bcrp1) in brain penetrations and anti-glioma therapeutic effects of several selected targeted agents have been investigated. Two agents, Palomid 529 and ZSTK474 (PI3K inhibitor) have been identified as non- or poor substrates of Abcb1 and Abcg2, so their brain penetrations have not been compromised by these transporters. We also reports Abcb1 and Abcg2 could cause severe impacts on the brain penetrations of agents which are substrates of one of them, like rapamycin and NVP-BEZ235; or both of them, like ABT-888. However, co-administration of elacridar could reverse the drug efflux of Abcb1 and Abcg2 at both blood-brain barrier and at tumor cells, and consequently improve the therapeutic effect of targeted agents. The last chapter describes an important role of another drug efflux transporters expressed at blood-brain barrier, ABCC4 (Mrp4) in brain pharmacokinetics of
camptothecin analogs topotecan, gimatecan, irinotecan and SN-38; and also reports that sildenafil (viagra) is not a useful inhibitor of ABCB1 and ABCG2 mediated drug resistance in vivo
Advisors/Committee Members: Beijnen, J.H., Tellingen, O. van.
Subjects/Keywords: Farmacie; glioblastoma; blood-brain barrier; ABCB1; ABCG2; ABCC4; targed therapy; camptothecin analogs; HPLC
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APA (6th Edition):
Lin, F. (2013). Targeted therapies for malignant gliomas: novel agents, same barrier. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/268384
Chicago Manual of Style (16th Edition):
Lin, F. “Targeted therapies for malignant gliomas: novel agents, same barrier.” 2013. Doctoral Dissertation, Universiteit Utrecht. Accessed April 13, 2021.
http://dspace.library.uu.nl:8080/handle/1874/268384.
MLA Handbook (7th Edition):
Lin, F. “Targeted therapies for malignant gliomas: novel agents, same barrier.” 2013. Web. 13 Apr 2021.
Vancouver:
Lin F. Targeted therapies for malignant gliomas: novel agents, same barrier. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2013. [cited 2021 Apr 13].
Available from: http://dspace.library.uu.nl:8080/handle/1874/268384.
Council of Science Editors:
Lin F. Targeted therapies for malignant gliomas: novel agents, same barrier. [Doctoral Dissertation]. Universiteit Utrecht; 2013. Available from: http://dspace.library.uu.nl:8080/handle/1874/268384
18.
Kusari, Souvik.
Endophytic fungi harbored in
Camptotheca acuminata, Hypericum perforatum and Juniperus communis
plants as promising sources of camptothecin, hypericin and
deoxypodophyllotoxin.
Degree: 2010, Technische Universität Dortmund
URL: http://hdl.handle.net/2003/27441
► Endophytic microorganisms are a diverse group of microbes that colonize living, internal tissues of plants without causing any immediate, overt negative effects within the hosts.…
(more)
▼ Endophytic microorganisms are a
diverse group of microbes that colonize living, internal tissues of
plants without causing any immediate, overt negative effects within
the hosts. A number of novel endophytic microorganisms are capable
of producing host plant-specific secondary metabolites with
therapeutic potential. The main objective of this study was
isolation, identification, biological and biochemical
characterization of endophytic fungi capable of indigenously
producing
camptothecin (CPT), hypericin and deoxypodophyllotoxin,
harbored in Camptotheca acuminata, Hypericum perforatum and
Juniperus communis plants, respectively. Secondary metabolites were
identified and quantified by highly selective and sensitive
LC-ESI-MS/MS and LC-ESI-HRMSn. C. acuminata plants were sampled
from different botanical gardens and tissue culture laboratories
across Germany as well as from China. The aerial parts were
extracted and analyzed for CPT, 9-methoxycamptothecin and
10-hydroxycamptothecin. Chemometric evaluation revealed CPT to be
positively correlated with both the metabolites. Endophytic fungi
were isolated and characterized from all plants, only one of which
was capable of producing CPT, 9-methoxycamptothecin and
10-hydroxycamptothecin in rich mycological media under axenic
submerged shake-flask fermentation. The fungus was identified as
Fusarium solani by its morphology and authenticated by ITS-5.8S
rDNA analysis. CPT along with both the metabolites were
additionally identified by 1H NMR spectroscopy, and confirmed by
comparison with authentic standards. A substantial decrease in the
production of CPT by the in vitro cultured endophyte over repeated
subculturing was observed. The survival strategy of the endophyte
against CPT toxicity was evaluated by identifying the typical amino
acid residues Asn352, Glu356, Arg488, Gly503, and Gly717 (numbered
according to human topoisomerase I) which prevent CPT binding to
topoisomerase I, and the point mutation Met370Thr on the
CPT-binding and catalytic domain of its topoisomerase I enzyme
(encoded by Top1). A cross-species biosynthetic pathway was then
deciphered where the fungal endophyte utilizes indigenous G10H
(geraniol 10-hydroxylase), SLS (secologanin synthase), and TDC
(tryptophan decarboxylase) to biosynthesize CPT precursors.
However, to complete CPT biosynthesis, the endophyte requires the
host STR (strictosidine synthase). The fungal CPT biosynthetic
genes destabilize ex planta over successive subculture generations.
The seventh subculture predicted proteins exhibited reduced
homologies to the original enzymes proving that such genomic
instability leads to dysfunction at the amino acid level. The
endophyte with an impaired CPT biosynthetic capability was
artificially inoculated into the living host plants and then
recovered after colonization. CPT biosynthesis could still not be
restored. This demonstrated that the observed phenomenon of genomic
instability is irreversible. Several Hypericum species were sampled
from the natural populations of Slovakia and
India,…
Advisors/Committee Members: Spiteller, Michael.
Subjects/Keywords: Camptothecin; Camtotheca
acuminata; Deoxypodophyllotoxin; Endophytic fungi; Hypericin;
Hypericum perforatum; Juniperus communis; 540
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APA (6th Edition):
Kusari, S. (2010). Endophytic fungi harbored in
Camptotheca acuminata, Hypericum perforatum and Juniperus communis
plants as promising sources of camptothecin, hypericin and
deoxypodophyllotoxin. (Thesis). Technische Universität Dortmund. Retrieved from http://hdl.handle.net/2003/27441
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kusari, Souvik. “Endophytic fungi harbored in
Camptotheca acuminata, Hypericum perforatum and Juniperus communis
plants as promising sources of camptothecin, hypericin and
deoxypodophyllotoxin.” 2010. Thesis, Technische Universität Dortmund. Accessed April 13, 2021.
http://hdl.handle.net/2003/27441.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kusari, Souvik. “Endophytic fungi harbored in
Camptotheca acuminata, Hypericum perforatum and Juniperus communis
plants as promising sources of camptothecin, hypericin and
deoxypodophyllotoxin.” 2010. Web. 13 Apr 2021.
Vancouver:
Kusari S. Endophytic fungi harbored in
Camptotheca acuminata, Hypericum perforatum and Juniperus communis
plants as promising sources of camptothecin, hypericin and
deoxypodophyllotoxin. [Internet] [Thesis]. Technische Universität Dortmund; 2010. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/2003/27441.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kusari S. Endophytic fungi harbored in
Camptotheca acuminata, Hypericum perforatum and Juniperus communis
plants as promising sources of camptothecin, hypericin and
deoxypodophyllotoxin. [Thesis]. Technische Universität Dortmund; 2010. Available from: http://hdl.handle.net/2003/27441
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Kansas
19.
Stavropoulos, Kathy.
Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery.
Degree: MS, Pharmaceutical Chemistry, 2011, University of Kansas
URL: http://hdl.handle.net/1808/8188
► Abstract Overcoming obstacles like multidrug resistance, short circulation half-life, and nonspecific systemic distribution is an ongoing challenge in cancer therapy. One application to address these…
(more)
▼ Abstract Overcoming obstacles like multidrug resistance, short circulation half-life, and nonspecific systemic distribution is an ongoing challenge in cancer therapy. One application to address these concerns is to engineer a drug delivery vehicle that has versatile functionality, good serum stability, circulates in the body long enough to reach the targeting tissues, and is biocompatible. A promising formulation platform that embodies these features is the lipid-polymer hybrid nanoparticles. The surface characteristics of these nanoparticles such as charge, lipid density, and targeting ligands can be modified to allow for specific cellular uptake, controlled drug releases kinetics, and enhanced pharmacokinetics. In this work, it was found that the hybrid nanoparticles could easily be fabricated with negatively and positively charged lipids in order to change the overall surface charge. The particle size remained in the desirable range and the distribution was narrow. The lipid-polymer hybrid nanoparticle by design has the capacity to co-encapsulate hydrophobic and lipophilic drugs. To investigate,
camptothecin and a cisplatin derivative were dually loaded within the hybrid nanoparticle system. This combination formulation was characterized by dynamic light scattering for particle size, zeta potential, and polydispersity index as well as in vitro drug release and cytotoxicity. The particle size was below 100 nm and the distribution was narrow. The release studies showed that the addition of the two drugs within the lipid-polymer hybrid nanoparticle system did not affect the release profiles of the individual drugs. The ability for co-encapsulation and the similar overall drug release profiles for
camptothecin and cisplatin derivative in the combination compared to single drug loaded controls valuates this already useful drug delivery platform.
Advisors/Committee Members: Schöneich, Christian (advisor), Stobaugh, John F. (cmtemember), Aryal, Santosh (cmtemember).
Subjects/Keywords: Pharmaceutical sciences; Camptothecin; Cisplatin; Hybrid nanoparticles; Lipid shell; Peg corona; Polymeric core
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APA (6th Edition):
Stavropoulos, K. (2011). Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/8188
Chicago Manual of Style (16th Edition):
Stavropoulos, Kathy. “Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery.” 2011. Masters Thesis, University of Kansas. Accessed April 13, 2021.
http://hdl.handle.net/1808/8188.
MLA Handbook (7th Edition):
Stavropoulos, Kathy. “Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery.” 2011. Web. 13 Apr 2021.
Vancouver:
Stavropoulos K. Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery. [Internet] [Masters thesis]. University of Kansas; 2011. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1808/8188.
Council of Science Editors:
Stavropoulos K. Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery. [Masters Thesis]. University of Kansas; 2011. Available from: http://hdl.handle.net/1808/8188
University of Kentucky
20.
Tsakalozou, Eleftheria.
PRECLINICAL AND CLINICAL DEVELOPMENT OF THE LIPOPHILIC CAMPTOTHECIN ANALOGUE AR-67.
Degree: 2013, University of Kentucky
URL: https://uknowledge.uky.edu/pharmacy_etds/18
► AR-67 is a lipophilic third generation camptothecin analogue, currently under early stage clinical trials. It acts by targeting Topoisomerase 1 (Top1), a nuclear enzyme essential…
(more)
▼ AR-67 is a lipophilic third generation camptothecin analogue, currently under early stage clinical trials. It acts by targeting Topoisomerase 1 (Top1), a nuclear enzyme essential for DNA replication and transcription and is present in two forms, the pharmacologically active lipophilic lactone and the charged carboxylate. In oncology patients participating in a phase I clinical trial, AR-67 lactone was the predominant species in plasma. Similarly to other camptothecins, the identified dose-limiting toxicities for AR-67 were neutropenia, thrombocytopenia and fatigue. In addition, in vitro metabolism studies indicated AR-67 lactone as a substrate for CYP3A4/5 as well as the UGT1A7 and UGT1A8 enzymes localizing in the liver and the gut.
Numerous studies have demonstrated the over-expression of transporters in certain tumor types. Here, the effect of interactions between AR-67 and efflux or uptake transporters on the antitumor efficacy of AR-67 in vitro was studied. We showed that BCRP and MDR1 overexpression confers resistance to AR-67.
Moreover, we demonstrated the therapeutic superiority of protracted dosing over more intense dosing regimens of AR-67 using xenografts models. Our studies indicated the schedule-dependent expression of Top1 and the preferential partitioning of AR-67 in the tumor tissue. We reason that these are factors that need to be taken into consideration when designing dosing schedules aiming to maximize efficacy.
As most cytotoxic drugs, AR-67 has a narrow therapeutic window. Thus, it is essential to identify the variables influencing exposure to this camptothecin analogue. A thorough compartmental pharmacokinetic analysis was performed on the patient data obtained in a phase 1 clinical trial on AR-67. Moreover, sources of intersubject variability associated with obtaining pharmacokinetic parameter estimates were identified and a population covariate pharmacokinetic model was developed.
In conclusion, the drug development of AR-67 is a work in process. Findings presented above provide an insight on the factors contributing to its efficacy and toxicity when given to cancer patients.
Subjects/Keywords: AR-67; Camptothecin; Transporter; Dosing Schedule; Population Pharmacokinetics; Pharmacy and Pharmaceutical Sciences
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APA ·
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CSE |
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APA (6th Edition):
Tsakalozou, E. (2013). PRECLINICAL AND CLINICAL DEVELOPMENT OF THE LIPOPHILIC CAMPTOTHECIN ANALOGUE AR-67. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/pharmacy_etds/18
Chicago Manual of Style (16th Edition):
Tsakalozou, Eleftheria. “PRECLINICAL AND CLINICAL DEVELOPMENT OF THE LIPOPHILIC CAMPTOTHECIN ANALOGUE AR-67.” 2013. Doctoral Dissertation, University of Kentucky. Accessed April 13, 2021.
https://uknowledge.uky.edu/pharmacy_etds/18.
MLA Handbook (7th Edition):
Tsakalozou, Eleftheria. “PRECLINICAL AND CLINICAL DEVELOPMENT OF THE LIPOPHILIC CAMPTOTHECIN ANALOGUE AR-67.” 2013. Web. 13 Apr 2021.
Vancouver:
Tsakalozou E. PRECLINICAL AND CLINICAL DEVELOPMENT OF THE LIPOPHILIC CAMPTOTHECIN ANALOGUE AR-67. [Internet] [Doctoral dissertation]. University of Kentucky; 2013. [cited 2021 Apr 13].
Available from: https://uknowledge.uky.edu/pharmacy_etds/18.
Council of Science Editors:
Tsakalozou E. PRECLINICAL AND CLINICAL DEVELOPMENT OF THE LIPOPHILIC CAMPTOTHECIN ANALOGUE AR-67. [Doctoral Dissertation]. University of Kentucky; 2013. Available from: https://uknowledge.uky.edu/pharmacy_etds/18
The Ohio State University
21.
Neidrich, Keisha L.
Self-Assembly, Characterization, and Cytotoxicity Studies of
a Camptothecin-Dipeptide Library.
Degree: MS, Chemistry, 2016, The Ohio State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1452178852
► Nanoscience is the study of scientific manipulations that occur between 1 nM and 1 µM. This vignette of science opens the doors to novel methodologies…
(more)
▼ Nanoscience is the study of scientific manipulations
that occur between 1 nM and 1 µM. This vignette of science opens
the doors to novel methodologies with which to solve some of the
most challenging obstacles currently facing science. Study at this
level has created nanomaterials, which can be assembled in an
assortment of ways. Perhaps one of the most common is
self-assembly, in which singular molecules will order themselves
into three dimensional structures based on their intermolecular
interactions. Peptides are commonly used as building blocks for
these assemblies due to their availability, convenient synthesis,
and biocompatibility. These self-assembling nanomaterials can lead
to “materials by design”, giving the researcher complete control
over the size, properties, and overall chemistry of the
structure.One way in which these materials have been applied is
through the encapsulation of hydrophobic chemotherapeutics. Through
this encapsulation, hydrophobic drugs that experience instability
in water can be not only protected, but better solubility as well.
One example of this class of drugs is
camptothecin, a highly
effective drug in vitro that results in a high toxicity in vivo due
to a reversible ring opening. By protecting this drug, not only can
its effectiveness be retained, but its solubility in vivo can be
improved dramatically.In this study, we have provided a library of
dipeptide-
camptothecin molecules that self-assemble into
three-dimensional nanostructures. The library was accomplished
across sixty-six different compounds; containing 11 different amino
acids in 6 different configurations. An additional study was
completed in order to determine the effect of oxidation or
reduction on a cysteine based
camptothecin-nanostructure. These
studies have demonstrated that a wide variety of peptides will
self-assemble, as well as trends in their zeta potential and
cytotoxicity, and environmental effects.
Advisors/Committee Members: Parquette, Jon (Advisor).
Subjects/Keywords: Chemistry; Biology; Nanotechnology; Nanoscience; Self-assembly; Peptide Amphiphiles; Camptothecin; Drug Delivery; Nanostructures; Nanoscience; Peptide Library
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APA ·
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MLA ·
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Export
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Manager
APA (6th Edition):
Neidrich, K. L. (2016). Self-Assembly, Characterization, and Cytotoxicity Studies of
a Camptothecin-Dipeptide Library. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1452178852
Chicago Manual of Style (16th Edition):
Neidrich, Keisha L. “Self-Assembly, Characterization, and Cytotoxicity Studies of
a Camptothecin-Dipeptide Library.” 2016. Masters Thesis, The Ohio State University. Accessed April 13, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1452178852.
MLA Handbook (7th Edition):
Neidrich, Keisha L. “Self-Assembly, Characterization, and Cytotoxicity Studies of
a Camptothecin-Dipeptide Library.” 2016. Web. 13 Apr 2021.
Vancouver:
Neidrich KL. Self-Assembly, Characterization, and Cytotoxicity Studies of
a Camptothecin-Dipeptide Library. [Internet] [Masters thesis]. The Ohio State University; 2016. [cited 2021 Apr 13].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1452178852.
Council of Science Editors:
Neidrich KL. Self-Assembly, Characterization, and Cytotoxicity Studies of
a Camptothecin-Dipeptide Library. [Masters Thesis]. The Ohio State University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1452178852
22.
Mouly, Laetitia.
Rôle de la GTPase Rho RND1 dans la réponse cellulaire à la camptothécine, inhibiteur de la topoisomérase I : Role of the RHO GTPASE RND1 in the cellular response to the topoisomerase I inhibitor camptothecin.
Degree: Docteur es, Pharmacologie, 2018, Université Toulouse III – Paul Sabatier
URL: http://www.theses.fr/2018TOU30030
► La famille des GTPases Rho, comprenant 20 membres, contrôle la dynamique du cytosquelette d'actine et différents processus cellulaires comme la migration. En plus de leurs…
(more)
▼ La famille des GTPases Rho, comprenant 20 membres, contrôle la dynamique du cytosquelette d'actine et différents processus cellulaires comme la migration. En plus de leurs rôles bien établis, certaines GTPases Rho, notamment RhoB et Rac1, ont émergé en tant que gènes de réponse précoce aux dommages à l'ADN. En effet, RhoB est induite en réponse à divers stress génotoxiques, y compris la camptothécine (CPT), les UV et le cisplatine, et protège principalement les cellules de l'apoptose. Le rôle des autres GTPases Rho en réponse précoce aux génotoxiques reste largement méconnu. Dans ce projet, nous avons utilisé la camptothécine, un inhibiteur de la topoisomérase I (TOP1), qui stabilise sélectivement les complexes de clivage TOP1-ADN (TOP1cc) sur la chromatine, afin de cribler les GTPases Rho induites de façon précoce par les dommages à l'ADN. En plus de RhoB, nous avons identifié RND1 comme un gène rapidement induit par la CPT. L'induction de RND1 est réversible et étroitement corrélée à la présence de TOP1cc induit par la CPT. En accord avec ces observations, les rayons UV et le péroxyde d'hydrogène, qui stabilisent indirectement les TOP1cc, induisent également RND1. La CPT augmente la transcription de RND1 indépendamment de l'activité de son promoteur minimal. De plus, la CPT augmente l'activité de la poly ADP-ribose polymérase (PARP1), dont l'inhibition prévient la transcription de RND1. La surexpression de RND1 augmente également l'expression de PARP1, suggérant une régulation positive entre PARP1 et RND1 en réponse aux TOP1cc. Ainsi, nous proposons qu'en réponse à la CPT, les TOP1cc activent PARP1, qui à son tour favorise la transcription de RND1, initiant ainsi une boucle de rétrocontrôle positive. Enfin, nous avons montré que RND1 protège les cellules contre l'apoptose induite par la CPT et entraîne leur résistance à la CPT. L'ensemble de ces résultats ont permis d'identifier RND1 comme nouvelle GTPase Rho impliquée dans la réponse au stress et proposent un nouveau mécanisme de régulation de la transcription des gènes en réponse aux TOP1cc via l'activation de PARP1. Ces résultats suggèrent par ailleurs qu'inhiber la signalisation de RND1 pourrait sensibiliser les cellules tumorales aux dérivés cliniques de la CPT.
Rho GTPase family comprises 20 members that regulate key cellular functions such as actin cytoskeleton organization and migration. Beside their canonical functions, certain Rho GTPases, including RhoB and Rac1, emerged as early DNA damage-inducible genes. Indeed, RhoB is readily induced in response to various genotoxic stress, including camptothecin (CPT), UV and cisplatin, and primarily protect cells against apoptotic cell death. Whether other Rho GTPases also respond early to genotoxics is largely unknown. In this project, we used camptothecin, a topoisomerase I (TOP1) inhibitor that selectively stabilized TOP1-DNA cleavage complexes (TOP1cc) onto chromatin, to screen for early DNA damage-inducible Rho GTPases. Besides RhoB, we identified RND1 as a gene rapidly induced by CPT. RND1 induction is…
Advisors/Committee Members: Monferran, Sylvie (thesis director), Sordet, Olivier (thesis director).
Subjects/Keywords: RND1; Camptothécine; Topoisomérase I; PARP1; Transcription; Apoptose; RND1; Camptothecin; Topoisomerase I; PARP1; Transcription; Apoptose
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APA (6th Edition):
Mouly, L. (2018). Rôle de la GTPase Rho RND1 dans la réponse cellulaire à la camptothécine, inhibiteur de la topoisomérase I : Role of the RHO GTPASE RND1 in the cellular response to the topoisomerase I inhibitor camptothecin. (Doctoral Dissertation). Université Toulouse III – Paul Sabatier. Retrieved from http://www.theses.fr/2018TOU30030
Chicago Manual of Style (16th Edition):
Mouly, Laetitia. “Rôle de la GTPase Rho RND1 dans la réponse cellulaire à la camptothécine, inhibiteur de la topoisomérase I : Role of the RHO GTPASE RND1 in the cellular response to the topoisomerase I inhibitor camptothecin.” 2018. Doctoral Dissertation, Université Toulouse III – Paul Sabatier. Accessed April 13, 2021.
http://www.theses.fr/2018TOU30030.
MLA Handbook (7th Edition):
Mouly, Laetitia. “Rôle de la GTPase Rho RND1 dans la réponse cellulaire à la camptothécine, inhibiteur de la topoisomérase I : Role of the RHO GTPASE RND1 in the cellular response to the topoisomerase I inhibitor camptothecin.” 2018. Web. 13 Apr 2021.
Vancouver:
Mouly L. Rôle de la GTPase Rho RND1 dans la réponse cellulaire à la camptothécine, inhibiteur de la topoisomérase I : Role of the RHO GTPASE RND1 in the cellular response to the topoisomerase I inhibitor camptothecin. [Internet] [Doctoral dissertation]. Université Toulouse III – Paul Sabatier; 2018. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2018TOU30030.
Council of Science Editors:
Mouly L. Rôle de la GTPase Rho RND1 dans la réponse cellulaire à la camptothécine, inhibiteur de la topoisomérase I : Role of the RHO GTPASE RND1 in the cellular response to the topoisomerase I inhibitor camptothecin. [Doctoral Dissertation]. Université Toulouse III – Paul Sabatier; 2018. Available from: http://www.theses.fr/2018TOU30030
23.
Deysi Viviana Tenazoa Wong.
MediaÃÃo dos receptores TLR2, NOD1, e da ProteÃna MYD88 na modulaÃÃo da mucosite intestinal induzida pelo irinotecano.
Degree: 2013, Universidade Federal do CearÃ; Programa de PÃs-GraduaÃÃo em Farmacologia; UFC; BR
URL: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13506
► Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
O cÃncer colorretal (CCR) Ã uma das neoplasias mais prevalentes em todo o mundo, sendo uma das principais…
(more)
▼ Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
O cÃncer colorretal (CCR) Ã uma das neoplasias mais prevalentes em todo o mundo, sendo uma das principais causas de Ãbito por cÃncer. Dentre as drogas utilizadas como primeira linha no tratamento do CCR e do CCR metastÃtico hepÃtico, o irinotecano apresenta destaque pelo impacto sobre o aumento da sobrevida dos pacientes. Contudo, o surgimento de efeitos colaterais associados ao irinotecano (IRI), como a mucosite intestinal (MI), tem impactado negativamente no curso terapÃutico do paciente, observando-se atrasos nos ciclos subsequentes de quimioterapia, reduÃÃo de doses e, por vezes, interrupÃÃo do tratamento. A MI e a diarrÃia grave sÃo efeitos colaterais frequentes que pode atingir de 15-25% dos pacientes em quimioterapia. Objetivos: Estudar os parÃmetros funcionais da barreira intestinal e os mecanismos envolvidos na mucosite intestinal induzida pelo Irinotecano e seu metabÃlito
ativo, SN-38. MÃtodos: Camundongos C57BL/6 machos (WT), 20-25g, foram divididos em grupos (n=6-8), administrados por 4 dias com salina (5 mL/Kg, i.p) ou com irinotecano (IRI, 75 mg/Kg, i.p). Os animais foram analisados no 5Â dia [D5] ou 7Â dia [D7] quanto ao peso corpÃreo, escores de diarreia, contagem de leucÃcitos. ApÃs sacrifÃcio, uma amostra de intestino foi coletada para dosagem de mieloperoxidase, anÃlise histopatolÃgica, morfomÃtrica, e imunohistoquÃmica para TLR4. Adicionalmente, realizou-se o teste de permeabilidade e perfusÃo intestinal in vivo. Avaliou-se tambÃm a bacteremia e a translocaÃÃo bacteriana em linfonodo mesentÃrico e fÃgado. Em adiÃÃo, a participaÃÃo de receptores Toll-like 2 (TLR2), 4 (TLR4) e 9 (TLR9) da proteÃna adaptadora MyD88 e NOD1 na mucosite intestinal foi verificada pelo uso de camundongos knockout com deleÃÃo gÃnica especÃfica para aqueles receptores e seus respectivos camundongos selvagens (WT). Adicionalmente, realizou-se a avaliaÃÃo dos efeitos in
vivo e in vitro do SN-38. Os dados foram analisados com ANOVA/teste de Bonferroni ou Kruskal Wallis/teste de Dunn. P<0,05 foi aceito. (Protocolo CEPA 99/10). Resultados: A injeÃÃo de IRI causou uma significativa (P<0,05) perda ponderal, leucopenia e diarreia, associada a um aumento da infiltraÃÃo de neutrÃfilos no jejuno, Ãleo e pulmÃo, com alteraÃÃes morfomÃtricas e uma intensa destruiÃÃo da arquitetura dos vilos e criptas, apoptose celular em camundongos WT versus animais injetados com salina. AlÃm disso, o IRI induz uma alteraÃÃo da barreira intestinal evidenciada pela diminuiÃÃo da excreÃÃo de lactulose, aliado a um aumento significativo (P<0,05) da secreÃÃo intestinal de sÃdio, potÃssio e cloreto. Os camundongos injetados com Irinotecano apresentaram bacteremia e translocaÃÃo bacteriana (P<0,05) no linfonodo mesentÃrico e fÃgado, quando comparados ao grupo salina. A identificaÃÃo bioquÃmica das bactÃrias translocadas evidenciou a presenÃa de
Escherichia coli (75%), Citrobacter sp. (17,2%), BactÃrias Gram-Negativas NÃo-Fermentadoras e Pseudomona aeruginosa (18%) no grupo injetado com…
Advisors/Committee Members: Ronaldo de Albuquerque Ribeiro, Gerly Anne de Castro Brito, Sara Maria Thomazzi, Markus Andret Cavalcante Gifoni.
Subjects/Keywords: ProteÃna Adaptadora de SinalizaÃÃo NOD1; Camptothecin; Mucositis; Toll-like Receptors; Nod1 Signaling adaptor protein; FARMACOLOGIA
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APA (6th Edition):
Wong, D. V. T. (2013). MediaÃÃo dos receptores TLR2, NOD1, e da ProteÃna MYD88 na modulaÃÃo da mucosite intestinal induzida pelo irinotecano. (Doctoral Dissertation). Universidade Federal do CearÃ; Programa de PÃs-GraduaÃÃo em Farmacologia; UFC; BR. Retrieved from http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13506
Chicago Manual of Style (16th Edition):
Wong, Deysi Viviana Tenazoa. “MediaÃÃo dos receptores TLR2, NOD1, e da ProteÃna MYD88 na modulaÃÃo da mucosite intestinal induzida pelo irinotecano.” 2013. Doctoral Dissertation, Universidade Federal do CearÃ; Programa de PÃs-GraduaÃÃo em Farmacologia; UFC; BR. Accessed April 13, 2021.
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13506.
MLA Handbook (7th Edition):
Wong, Deysi Viviana Tenazoa. “MediaÃÃo dos receptores TLR2, NOD1, e da ProteÃna MYD88 na modulaÃÃo da mucosite intestinal induzida pelo irinotecano.” 2013. Web. 13 Apr 2021.
Vancouver:
Wong DVT. MediaÃÃo dos receptores TLR2, NOD1, e da ProteÃna MYD88 na modulaÃÃo da mucosite intestinal induzida pelo irinotecano. [Internet] [Doctoral dissertation]. Universidade Federal do CearÃ; Programa de PÃs-GraduaÃÃo em Farmacologia; UFC; BR; 2013. [cited 2021 Apr 13].
Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13506.
Council of Science Editors:
Wong DVT. MediaÃÃo dos receptores TLR2, NOD1, e da ProteÃna MYD88 na modulaÃÃo da mucosite intestinal induzida pelo irinotecano. [Doctoral Dissertation]. Universidade Federal do CearÃ; Programa de PÃs-GraduaÃÃo em Farmacologia; UFC; BR; 2013. Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13506
NSYSU
24.
Chou, Han-Lin.
Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound.
Degree: PhD, Institute of Biomedical Sciences, 2018, NSYSU
URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0712118-213436
► Lung cancer is one of the highly lethal cancers among all cancer types. Non-small cell lung cancer (NSCLC) is the most common types in lung…
(more)
▼ Lung cancer is one of the highly lethal cancers among all cancer types.
Non-small cell lung cancer (NSCLC) is the most common types in lung cancer,
accounting for 85%. Chemotherapy is currently the main treatment for patients with
NSCLC. However, clinical statistics found that the treatment of a single
chemotherapy drug is not effective for lung cancer patients. Drug resistance is one of
the reasons for the poor efficacy of chemotherapeutic agents for lung cancer. In order
to increase the effectiveness of anti-cancer therapy, the combination of two or more
chemotherapeutic agents is currently the main treatment for NSCLC. The strategy of
this treatment is mainly to enhance the effectiveness of drugs in inhibiting cancer cells
growth. The main direction of this document is the treatment of NSCLC cells with the
combination of chemotherapeutic agents, and evaluate the effect and mechanism of
inhibiting cell growth in NSCLC cells. This report is divided into two parts, the first
part of the thesis is to investigate the effect of quinone compounds on cell apoptosis
induced by
camptothecin (CPT) in non-small cell lung cancer. In this section, we used
a combination of 4-[2, 3, 5, 6-tetrafluoro-4-(4-hydroxyphenoxy) phenoxy] phenol
(abbreviated as TFPP) and CPT to treat NSCLC cells. The study found that the
combination of CPT and TFPP to inhibit the growth of NSCLC through inducing
apoptosis. In addition, I have found that TFPP can enhance CPT-induced oxidative
stress, and inhibit the activity of ERK/MAPK (mitogen-activated protein kinases) to
increase the induction of apoptosis in NSCLC cells. In view of this, drug combination
may still cause side effects or toxicity to patients. Low-toxic sensitizer has been
widely evaluated and applied to treat various cancer patients, including lung cancer.
Therefore, the second part of the thesis is mainly to explore the effect of acetamide
derivative on CPT-induced apoptosis in NSCLC cells. This part of the use of a combined agent is different from the previous one. I used an acetamide derivative
N-[2-(morpholin-4-yl) phenyl]-2-{8-oxatricyclo [7.4. 0. 0, 2, 7] trideca-1 (9), 2 (7), 3,
5, 10, 12-hexaen-4-yloxy} acetamide (abbreviated as NPOA). Although it does not
have the ability to kill cancer cells by NPOA, we have found that it can sensitize
NSCLC cells to CPT treatment. Our results showed that NPOA can significantly
increase CPT-induced apoptosis and inhibit cellular growth in NSCLC cells. In
addition, we found that NPOA can enhance CPT-induced oxidative stress, and
activates the activity of JNK/MAPK, and increase the loss of mitochondrial
membrane potential to induce apoptosis. Both of these parts are based on CPT-based
treatment, and then combined with other different types of agents as a strategy for
cancer treatment. Therefore, in the future, it can provide a platform for screening
CPT-derived drugs (such as irinotecan or topotecan). In addition, the experimental
spindle is to increase the active oxide in cancer cells as a regulator of cell apoptosis,
which can provide the…
Advisors/Committee Members: Huang Hung-wen (committee member), Chiu Chien-chih (committee member), Chang Hsueh-wei (chair), Cheng Kuang-hung (chair), Wang Hui-min (chair).
Subjects/Keywords: quinone-containing compound; acetamide-containing compound; apoptosis; human non-small cell lung cancer cells; oxidative stress; camptothecin
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APA ·
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APA (6th Edition):
Chou, H. (2018). Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound. (Doctoral Dissertation). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0712118-213436
Chicago Manual of Style (16th Edition):
Chou, Han-Lin. “Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound.” 2018. Doctoral Dissertation, NSYSU. Accessed April 13, 2021.
http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0712118-213436.
MLA Handbook (7th Edition):
Chou, Han-Lin. “Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound.” 2018. Web. 13 Apr 2021.
Vancouver:
Chou H. Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound. [Internet] [Doctoral dissertation]. NSYSU; 2018. [cited 2021 Apr 13].
Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0712118-213436.
Council of Science Editors:
Chou H. Induction of oxidative stress and apoptosis in human non-small cell lung cancer cells by camptothecin combined with quinone- or acetamide-containing compound. [Doctoral Dissertation]. NSYSU; 2018. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0712118-213436
University of Houston
25.
Dong, Dong.
Sustained Delivery of CZ48, A Lactone-Stabilized Camptothecin, by Nanosuspensions.
Degree: Pharmaceutics, Pharmaceutics, University of Houston
URL: http://hdl.handle.net/10657/2968
► CZ48, a novel C20-propionate ester of camptothecin (CPT), shows promising antitumor activity as a topoisomerase I (Topo-I) inhibitor. Compeling evidence indicates that CZ48 is more…
(more)
▼ CZ48, a novel C20-propionate ester of camptothecin (CPT), shows promising antitumor activity as a topoisomerase I (Topo-I) inhibitor. Compeling evidence indicates that CZ48 is more effective and less toxic than other anticancer agents, many of which are in clinical use such as Adriamycin, Alkeran, and 5-FU. However, poor solubility and the effective delivery challenges have been the obstacles for application of the drug to patients.
Interestingly, many studies have shown that a prolonged exposure of Topo-I inhibitors with low concentrations is more efficacious in cancer treatment compared with a short term exposure with high concentrations, though the exact mechanism remains unknown. In an attempt to accelerate the development process and promote the clinical trials of CZ48, we hypothesized that CZ48 can be formulated into nanosuspensions which deliver CZ48 in a sustained fashion. Sustained delivery of CZ48 could provide a prolonged exposure of CPT, the actual active compound, thus leading to an enhanced antitumor activity. The success in formulating the CZ48 nanosuspension will overcome the limitaions of the drug (e.g., the poor solubility and short half-life) and push it into the first line option in cancer chemotherapy based on the achieved outstanding efficacy and low toxicity. Further, the passive targeting property of nanosuspension may provide additional merits for CZ48 chemotherapy.
Toward the goal, our specific aims are: (1) to prepare by wet media milling method and characterize CZ48 nanosuspensions. We aim to obtain two types of nanosuspensions that differ considerably in the particle size. In vitro release study will be carried out by dialysis bag diffusion technique; (2) to determine the pharmacokinetics and organ distribution of CZ48 (and CPT) from CZ48 nanosuspensions in Sprague-Dawley (SD) rat and Swiss nude mouse models. The pharmacokinetic profiles and biodistribution patterns of CZ48 (and CPT) will be established by administering CZ48 as a nanosuspension following intravenous (i.v.) administration; (3) to determine the efficacy of CZ48 nanosuspension in tumor-bearing athymic mouse model. The lead formulation with the most favorable pharmacokinetic properties will be selected to validate the antitumor activity in a well-established tumor-bearing mouse model. The efficacy will be mainly measured by the suppression of tumor growth and the survival rate.
Two types of CZ48 nanosuspensions with particle sizes of 200 nm (NS-S) and 600 nm (NS-L), respectively, were successfully formulated and extensively characterized. The in vitro release study showed a sustained release of CZ48 from nanosuspensions compared with the release from cosolvent (reference). Pharmacokinetic studies in SD rats and Swiss nude mice demonstrated that compared to CZ48 cosolvent, CZ48 nanosuspensions increased the systemic exposure of CZ48 and prolonged the blood circulation of CPT. Moreover, the half-life was much longer and AUC was much larger of CPT from NS-S than those of NS-L. In tested organs, CZ48 nanosuspensions showed…
Subjects/Keywords: Sustained drug delivery; CZ48; Camptothecin; Nanosuspensions; Anticancer
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APA ·
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APA (6th Edition):
Dong, D. (n.d.). Sustained Delivery of CZ48, A Lactone-Stabilized Camptothecin, by Nanosuspensions. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/2968
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Chicago Manual of Style (16th Edition):
Dong, Dong. “Sustained Delivery of CZ48, A Lactone-Stabilized Camptothecin, by Nanosuspensions.” Doctoral Dissertation, University of Houston. Accessed April 13, 2021.
http://hdl.handle.net/10657/2968.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
MLA Handbook (7th Edition):
Dong, Dong. “Sustained Delivery of CZ48, A Lactone-Stabilized Camptothecin, by Nanosuspensions.” Web. 13 Apr 2021.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Vancouver:
Dong D. Sustained Delivery of CZ48, A Lactone-Stabilized Camptothecin, by Nanosuspensions. [Internet] [Doctoral dissertation]. University of Houston; [cited 2021 Apr 13].
Available from: http://hdl.handle.net/10657/2968.
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Council of Science Editors:
Dong D. Sustained Delivery of CZ48, A Lactone-Stabilized Camptothecin, by Nanosuspensions. [Doctoral Dissertation]. University of Houston; Available from: http://hdl.handle.net/10657/2968
Note: this citation may be lacking information needed for this citation format:
No year of publication.
Delft University of Technology
26.
Koster, D.A.
Topoisomerase and the unwinding of stressed DNA.
Degree: 2007, Delft University of Technology
URL: http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9
;
urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9
;
urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9
;
http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9
Subjects/Keywords: dna-protein interactions; topoisomerase; camptothecin; topotecan; single-molecule; nanofabrication
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APA (6th Edition):
Koster, D. A. (2007). Topoisomerase and the unwinding of stressed DNA. (Doctoral Dissertation). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9
Chicago Manual of Style (16th Edition):
Koster, D A. “Topoisomerase and the unwinding of stressed DNA.” 2007. Doctoral Dissertation, Delft University of Technology. Accessed April 13, 2021.
http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9.
MLA Handbook (7th Edition):
Koster, D A. “Topoisomerase and the unwinding of stressed DNA.” 2007. Web. 13 Apr 2021.
Vancouver:
Koster DA. Topoisomerase and the unwinding of stressed DNA. [Internet] [Doctoral dissertation]. Delft University of Technology; 2007. [cited 2021 Apr 13].
Available from: http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9.
Council of Science Editors:
Koster DA. Topoisomerase and the unwinding of stressed DNA. [Doctoral Dissertation]. Delft University of Technology; 2007. Available from: http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; urn:NBN:nl:ui:24-uuid:b495e54e-523e-48d4-8305-394dc53fd1b9 ; http://resolver.tudelft.nl/uuid:b495e54e-523e-48d4-8305-394dc53fd1b9
27.
STEFFIE MANO.
ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES.
Degree: 2019, National University of Singapore
URL: https://scholarbank.nus.edu.sg/handle/10635/182541
Subjects/Keywords: Peptide amphiphiles; Self-assembly; Coassembly; Coumarin-6; Chloramphenicol; Camptothecin
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APA (6th Edition):
MANO, S. (2019). ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES. (Thesis). National University of Singapore. Retrieved from https://scholarbank.nus.edu.sg/handle/10635/182541
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
MANO, STEFFIE. “ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES.” 2019. Thesis, National University of Singapore. Accessed April 13, 2021.
https://scholarbank.nus.edu.sg/handle/10635/182541.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
MANO, STEFFIE. “ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES.” 2019. Web. 13 Apr 2021.
Vancouver:
MANO S. ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES. [Internet] [Thesis]. National University of Singapore; 2019. [cited 2021 Apr 13].
Available from: https://scholarbank.nus.edu.sg/handle/10635/182541.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
MANO S. ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES. [Thesis]. National University of Singapore; 2019. Available from: https://scholarbank.nus.edu.sg/handle/10635/182541
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
28.
Daniella de Souza e Silva.
Síntese e caracterização de derivados 3,6-O,O\'-dimiristoil quitosana para encapsulação e liberação de fármacos antitumorais.
Degree: 2017, University of São Paulo
URL: http://www.teses.usp.br/teses/disponiveis/75/75134/tde-15092017-094952/
► O presente trabalho teve como objetivo produzir 3,6-O, O´-dimisritoilquitosana (QDM) com baixo grau médio de substituição ((GS) ̅ ≤ 10%) a partir da reação de…
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▼ O presente trabalho teve como objetivo produzir 3,6-O, O´-dimisritoilquitosana (QDM) com baixo grau médio de substituição ((GS) ̅ ≤ 10%) a partir da reação de quitosana com cloreto de miristoíla, de maneira a conferir caráter anfifílico às cadeias poliméricas. Neste estudo foram empregadas diferentes quitosanas de partida, a saber, quitosana de origem comercial (QC), que apresenta baixo grau médio de acetilação ((GA) ̅ = 5 %) e baixa massa molar média viscosimétrica ((Mv) ̅ = 87,000 g/mol), e quitosana DAIUS (QD), produzida a partir da desacetilação de beta-quitina assistida por irradiação de ultrassom de alta intensidade, que apresenta( GA) ̅ = 15 % e (Mv) ̅ = 300,000 g/mol.
Para obtenção dos derivados QDM, diferentes razões molares quitosana/cloreto de miristoíla (Q/CM) foram empregadas (1:0,075; 1:0,1; 1:0,2 e 1:0,5), e as reações foram executadas por 1 h a 25 °C. As características estruturais e morfológicas das amostras geradas neste trabalho foram determinadas pelo emprego de espectroscopias de ressonância magnética nuclear e no infravermelho e difração de raios-X. A solubilidade das amostras foi investigada por espectroscopia UV/visível e a estabilidade térmica foi estudada através de análise termogravimétrica. A partir da análise de espectroscopia no infravermelho, foi possível evidenciar a ocorrência da reação de acilação seletiva dos grupos OH das quitosanas, através da
presença da banda observada em 1740 cm-1, referente à deformação axial de carbonila de éster, resultante da reação de O-acilação. A banda em 1577 cm-1 referente a N-acilação não foi evidenciada. Na segunda etapa deste estudo as amostras QCM1 ((DS) ̅ = 6,6%) e QCM4 ((DS) ̅ = 11 %), que apresentaram concentrações críticas de agregação (CAC) 8,9 × 10-3 mg/ mL e 13,2 × 10-3 mg/ mL, respectivamente, foram empregadas nos estudos de encapsulação e liberação de paclitaxel e camptotecina, fármacos hidrofóbicos anti-câncer insolúveis em água. A análise de microscopia eletrônica de transmissão (MET) mostrou que as micelas de QCM apresentaram
formas aproximadamente esféricas, enquanto que o espalhamento dinâmico de luz (DLS) permitiu a determinação do diâmetro médio das micelas carregadas e vazias, que variou no intervalo 280 nm - 481 nm, enquanto o potencial zeta foi ≥ +30 mV. As micelas de QCM foram capazes de encapsular o paclitaxel e a camptotecina com elevada eficiência de encapsulação (EE > 60 %), como confirmado por…
Advisors/Committee Members: Sergio Paulo Campana Filho, Odilio Benedito Garrido de Assis, Bruno Filipe Carmelino Cardoso Sarmento.
Subjects/Keywords: camptotecina; derivado anfifílico; liberação de fármaco; micelas; paclitaxel; quitosana; amphiphilic derivatives; camptothecin; chitosan; drug delivery; micelles
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APA (6th Edition):
Silva, D. d. S. e. (2017). Síntese e caracterização de derivados 3,6-O,O\'-dimiristoil quitosana para encapsulação e liberação de fármacos antitumorais. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/75/75134/tde-15092017-094952/
Chicago Manual of Style (16th Edition):
Silva, Daniella de Souza e. “Síntese e caracterização de derivados 3,6-O,O\'-dimiristoil quitosana para encapsulação e liberação de fármacos antitumorais.” 2017. Doctoral Dissertation, University of São Paulo. Accessed April 13, 2021.
http://www.teses.usp.br/teses/disponiveis/75/75134/tde-15092017-094952/.
MLA Handbook (7th Edition):
Silva, Daniella de Souza e. “Síntese e caracterização de derivados 3,6-O,O\'-dimiristoil quitosana para encapsulação e liberação de fármacos antitumorais.” 2017. Web. 13 Apr 2021.
Vancouver:
Silva DdSe. Síntese e caracterização de derivados 3,6-O,O\'-dimiristoil quitosana para encapsulação e liberação de fármacos antitumorais. [Internet] [Doctoral dissertation]. University of São Paulo; 2017. [cited 2021 Apr 13].
Available from: http://www.teses.usp.br/teses/disponiveis/75/75134/tde-15092017-094952/.
Council of Science Editors:
Silva DdSe. Síntese e caracterização de derivados 3,6-O,O\'-dimiristoil quitosana para encapsulação e liberação de fármacos antitumorais. [Doctoral Dissertation]. University of São Paulo; 2017. Available from: http://www.teses.usp.br/teses/disponiveis/75/75134/tde-15092017-094952/
Universidade Estadual de Campinas
29.
Souza, Kellen Ketty de.
Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon.
Degree: Faculdade de Ciências Médicas; Programa de Pós-Graduação em Clínica Médica, 2007, Universidade Estadual de Campinas
URL: SOUZA,
Kellen
Ketty
de.
Irinotecano
ativa
a
via
PI3-quinase/AKT/mTOR
em
linhagem
de
adenocarcinoma
de
colon.
2007.
100p.
Dissertação
(mestrado)
-
Universidade
Estadual
de
Campinas,
Faculdade
de
Ciencias
Medicas,
Campinas,
SP.
Disponível
em:
<http://www.repositorio.unicamp.br/handle/REPOSIP/309953>.
Acesso
em:
9
ago.
2018.
;
http://repositorio.unicamp.br/jspui/handle/REPOSIP/309953
► Orientador: Jose Barreto Campello Carvalheira
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-10T01:08:04Z (GMT). No. of…
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▼ Orientador: Jose Barreto Campello Carvalheira
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-10T01:08:04Z (GMT). No. of bitstreams: 1 Souza_KellenKettyde_M.pdf: 1724833 bytes, checksum: 44f766e2043af515b2f3f9462dc5c5e3 (MD5) Previous issue date: 2007
Resumo: A resistência dos tumores aos quimioterápicos é um problema clínico comum. Recentemente, foi demonstrado que o bloqueio. da via de sinalização da PI3-quinase aumenta a apoptose induzida pelo SN-38, um metabólito ativo do irinotecano. Entretanto, os mecanismos moleculares destas mudanças ainda não são esclarecidos. Para investigar os eventos moleculares envolvidos no aumento da sinalização na via da PI3-quinase associada ao irinotecano, aspirina e rapamicina foram utilizadas para modular esta via de sinalização. Nós observamos que a aspirina é capaz de inibir a fosforilação do IRS-l, através de seus alvos JNK
e IKK, e aumentar o crescimento dos tumores em camundongos Scid previamente injetados com linhagem de adenocarcinoma de cólon (HT29). Adicionalmente, demonstramos que o bloqueio da mTOR reduz a proliferação celular induzida pelo irinotecano. Assim, a ativação da via PI3-quinase/ Akt/mTOR pode contribuir para a quimiorresistência induzi da pelo irinoteco
Resistance of tumors to chemotherapeutic agents is a common clinical problem in human cancer. Recently, the blocking of PI3-kinase signaling pathway was shown to enhance apoptosis induced by SN-38, an active form of irinotecan. To gain further insight into the molecular events of irinotecan-associated increase in PI3-kinase signaling pathway, aspirin and rapamycin were used to modulate this signaling pathway. We describe here that aspirin is able to further inhibit IRS-l serine phosphorylation induced by irinotecan through targeting JNK and IKK, thus agonist activation of IRS-l/PI3-kinase pathway blocked the growth-inhibitory
effect of irinotecan in HT -29 colon cancer xenografts; our data also demonstrate a synergistic effect of mTOR inhibition and irinotecan on tumor growth. Activation of PI3-kinase/ Akt/mTOR pathway may thus contribute to refTactoriness to treatment with irinotecan
Mestrado
Ciencias Basicas
Mestre em Clinica Medica
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS, Carvalheira, José Barreto Campello, 1971-, Alvarenga, Marcelo, Chammas, Roger.
Subjects/Keywords: Aspirina; Neoplasias do cólon; Camptotecina; Aspirin; Colonic neoplasms; Camptothecin
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APA (6th Edition):
Souza, K. K. d. (2007). Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. (Masters Thesis). Universidade Estadual de Campinas. Retrieved from SOUZA, Kellen Ketty de. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. 2007. 100p. Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/309953>. Acesso em: 9 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/309953
Chicago Manual of Style (16th Edition):
Souza, Kellen Ketty de. “Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon.” 2007. Masters Thesis, Universidade Estadual de Campinas. Accessed April 13, 2021.
SOUZA, Kellen Ketty de. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. 2007. 100p. Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/309953>. Acesso em: 9 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/309953.
MLA Handbook (7th Edition):
Souza, Kellen Ketty de. “Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon.” 2007. Web. 13 Apr 2021.
Vancouver:
Souza KKd. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. [Internet] [Masters thesis]. Universidade Estadual de Campinas; 2007. [cited 2021 Apr 13].
Available from: SOUZA, Kellen Ketty de. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. 2007. 100p. Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/309953>. Acesso em: 9 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/309953.
Council of Science Editors:
Souza KKd. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. [Masters Thesis]. Universidade Estadual de Campinas; 2007. Available from: SOUZA, Kellen Ketty de. Irinotecano ativa a via PI3-quinase/AKT/mTOR em linhagem de adenocarcinoma de colon. 2007. 100p. Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas, Campinas, SP. Disponível em: <http://www.repositorio.unicamp.br/handle/REPOSIP/309953>. Acesso em: 9 ago. 2018. ; http://repositorio.unicamp.br/jspui/handle/REPOSIP/309953
30.
Slingerland, Marije.
Exploring novel formulations and new classes of anticancer drugs in solid tumors.
Degree: 2014, Department of Clinical Oncology and Clincal Pharmacy and Toxicology, Faculty of medicine / Leiden University Medical Center (LUMC), Leiden University
URL: http://hdl.handle.net/1887/28692
► Many current anticancer drugs have non-ideal pharmaceutical and pharmacological properties, which can lead to adverse consequences, including lack of or suboptimal therapeutic activity, dose-limiting side…
(more)
▼ Many current anticancer drugs have non-ideal pharmaceutical and pharmacological properties, which can lead to adverse consequences, including lack of or suboptimal therapeutic activity, dose-limiting side effects and poor patient quality of life. In this thesis we focused on some novel formulations, especially camptothecin glycoconjugate BAY 56-3722 and liposomal drug formulations, hoping to overcome some of these problems. We also focused on ‘old drugs’ for new indications, as an example HDAC inhibitors and cardiac glycosides. Unfortunately, the outcomes of some of the presented studies were disappointing: a clinical hold during the phase II study of BAY 56-3722, no benefit of LiPlaCis over standard cisplatin formulations and a non-completed clinical phase I trial with UNBS1450. Besides the disappointing outcomes of some of the presented studies, we demonstrated that LEP-ETU and Taxol® met the required 80-125% bioequivalence criteria and we showed that patients with mild or moderate hepatic function could be safely treated with the same dose of panobinostat as patients with normal hepatic function. The reviews of liposomal anticancer drugs, HDAC inhibitors and cardiac glycosides all showed that to fulfill the high expectations of all these formulations and new drugs and to overcome the existing problems much research is still necessary
Subjects/Keywords: Liposomal drug formulations; Camptothecin glycoconjugate; Histone deacetylase inhibitors; Cardiac glycosides; Liposomal drug formulations; Camptothecin glycoconjugate; Histone deacetylase inhibitors; Cardiac glycosides
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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APA (6th Edition):
Slingerland, M. (2014). Exploring novel formulations and new classes of anticancer drugs in solid tumors. (Doctoral Dissertation). Department of Clinical Oncology and Clincal Pharmacy and Toxicology, Faculty of medicine / Leiden University Medical Center (LUMC), Leiden University. Retrieved from http://hdl.handle.net/1887/28692
Chicago Manual of Style (16th Edition):
Slingerland, Marije. “Exploring novel formulations and new classes of anticancer drugs in solid tumors.” 2014. Doctoral Dissertation, Department of Clinical Oncology and Clincal Pharmacy and Toxicology, Faculty of medicine / Leiden University Medical Center (LUMC), Leiden University. Accessed April 13, 2021.
http://hdl.handle.net/1887/28692.
MLA Handbook (7th Edition):
Slingerland, Marije. “Exploring novel formulations and new classes of anticancer drugs in solid tumors.” 2014. Web. 13 Apr 2021.
Vancouver:
Slingerland M. Exploring novel formulations and new classes of anticancer drugs in solid tumors. [Internet] [Doctoral dissertation]. Department of Clinical Oncology and Clincal Pharmacy and Toxicology, Faculty of medicine / Leiden University Medical Center (LUMC), Leiden University; 2014. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1887/28692.
Council of Science Editors:
Slingerland M. Exploring novel formulations and new classes of anticancer drugs in solid tumors. [Doctoral Dissertation]. Department of Clinical Oncology and Clincal Pharmacy and Toxicology, Faculty of medicine / Leiden University Medical Center (LUMC), Leiden University; 2014. Available from: http://hdl.handle.net/1887/28692
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Open Access Theses and Dissertations