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Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer
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Ibrahim, Sherif. Evaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer. Retrieved from https://doi.org/doi:10.7282/T35T3NCV

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TitleEvaluation of a camptothecin/sodium-R-alpha lipoate combination for the treatment of non-small cell lung cancer
NameIbrahim, Sherif (author); Sinko, Patrick (chair); Colaizzi, John L. (internal member); Suh, Nanjoo (internal member); Prud'homme, Robert (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2015
Other Date2015-01 (degree)
SubjectPharmaceutical Science, Lungs--Cancer--Treatment, Camptothecin
Extent1 online resource (x, 111 p. : ill.)
DescriptionLung 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.
NotePh.D.
NoteIncludes bibliographical references
Noteby Sherif Ibrahim
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T35T3NCV
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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