Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Grubbs, Clinton<br>"). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters

1. Tinsley, Heather Nicole. Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer.

Degree: PhD, 2010, University of Alabama – Birmingham

Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest that a COX-independent target may be responsible for the anticancer activity of the NSAIDs. Inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) and subsequent activation of cGMP signaling has been proposed as one COX-independent mechanism. While cGMP signaling can regulate growth in certain cell types and alterations within this pathway have been noted in human cancers, little is known about its role in human breast cells. Here we demonstrate that selective inhibition of the cGMP specific PDE5 isozyme was sufficient to selectively induce apoptosis of human breast tumor cells through a pathway involving activation of the cGMP-dependent protein kinase (PKG) and subsequent attenuation of oncogenic â-catenin transcriptional activity. Moreover, PDE5 was found to be overexpressed, while the expression of other PDE isozymes was significantly reduced in breast tumor cells when compared to normal mammary epithelial cells. The NSAID sulindac sulfide (SS) was also found to preferentially inhibit the growth of breast tumor cells through a mechanism involving selective inhibition of PDE5, activation of PKG, and attenuation of â-catenin transcriptional activity. These effects occured independently of COX inhibition, as novel sulindac derivatives that lacked COX-inhibitory activity demonstrated enhanced anticancer and PDE5-inhibitory activities. These data demonstrate that PDE5 may serve as a novel target for breast cancer chemoprevention. Furthermore, modifying the indene scaffold of sulindac to remove COX-inhibitory activity while enhancing PDE5 inhibitory activity could lead to the development of novel breast cancer chemopreventive agents that are potentially safer and more efficacious than the NSAIDs or the SERMs.

PhD

1 online resource (xiv, 148 p.) :ill., digital, PDF file.

Pharmacology and Toxicology

Joint Health Sciences

breast cancer cGMP chemoprevention NSAID PDE sulindac

UNRESTRICTED

Advisors/Committee Members: Gary A. Piazza, Bolger,Graeme Grizzle,William Grubbs,Clinton Pillion,Dennis.

Subjects/Keywords: Infant, Low Birth Weight<; br>; Oral Health<; br>; Pregnancy<; br>; Pregnancy Complications – prevention & control<; br>; Pregnancy Outcome<; br>; Premature Birth – prevention & control.<; br>; Prenatal Care – methods

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Tinsley, H. N. (2010). Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1404

Chicago Manual of Style (16th Edition):

Tinsley, Heather Nicole. “Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer.” 2010. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,1404.

MLA Handbook (7th Edition):

Tinsley, Heather Nicole. “Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer.” 2010. Web. 29 Mar 2020.

Vancouver:

Tinsley HN. Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2010. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1404.

Council of Science Editors:

Tinsley HN. Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer. [Doctoral Dissertation]. University of Alabama – Birmingham; 2010. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1404

2. Szafran, April Adams. The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer.

Degree: PhD, 2008, University of Alabama – Birmingham

The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography and SPECT-CT imaging. Through analysis of histologic sections, bioluminescent images, and markers of bone resorption, therapy studies revealed that murine death receptor 5 agonist mTRA8 and its humanized version hTRA8 significantly reduce tumor burden in mice with experimental metastatic lesions in osseous tissues when combined with zoledronic acid. In a second study, mTRA8 resulted in a significant amount of tumor regression in an in vivo model of lung metastasis. From this work we have concluded that Death Receptor 5 agonist therapy is a promising treatment for breast cancer metastasis in animal models of this human disease and should be evaluated in a clinical setting.

1 online resource (xi, 102 p. : ill., digital, PDF file)

Pathology;

Joint Health Sciences;

breast cancer apoptosis molecular imaging metastasis drug therapy

UNRESTRICTED

Advisors/Committee Members: Zinn, Kurt R., Buchsbaum, Donald J.<br>, Feng, Xu<br>, Grubbs, Clinton<br>, Lorenz, Robinna<br>, Selander, Katri.

Subjects/Keywords: Antibodies, Monoclonal  – pharmacology<; br>; Antineoplastic Combined Chemotherapy<; br>; Protocols  – pharmacology<; br>; Bone Neoplasms<; br>; Breast Neoplasms<; br>; Diphosphonates  – pharmacology<; br>; Imidazoles  – pharmacology<; br>; Mammary Neoplasms, Experimental  – pathology<; br>; Receptors, TNF-Related Apoptosis-Inducing Ligand  – agonists

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Szafran, A. A. (2008). The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,927

Chicago Manual of Style (16th Edition):

Szafran, April Adams. “The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer.” 2008. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,927.

MLA Handbook (7th Edition):

Szafran, April Adams. “The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer.” 2008. Web. 29 Mar 2020.

Vancouver:

Szafran AA. The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2008. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,927.

Council of Science Editors:

Szafran AA. The use of molecular imaging to evaluate the efficacy of treatments for metastatic breast cancer. [Doctoral Dissertation]. University of Alabama – Birmingham; 2008. Available from: http://contentdm.mhsl.uab.edu/u?/etd,927

3. Whitt, Jason Derek. Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac.

Degree: PhD, 2012, University of Alabama – Birmingham

The nonsteroidal anti-inflammatory drug (NSAID) sulindac has displayed the ability to inhibit the proliferation of colorectal cancer (CRC) cells and to increase the sensitivity of multidrug resistant (MDR) cancer cells to a wide variety of chemotherapeutic agents. The antineoplastic activity of sulindac has been attributed to inhibition of the prostaglandin producing enzyme COX-2, but the exact mechanism remains elusive and the inhibition of prostaglandin synthesis can result in gastrointestinal, hepatic, and cardiovascular toxicities. Enzymatic, cellular, and imaging assays were used to identify mechanisms that could contribute to the antiproliferative and apoptotic activity of sulindac. Screening of more than 500 sulindac derivatives revealed structural features that correlated with increased potency for growth inhibition when compared to the COX-inhibiting parent compound, sulindac sulfide (SS). An amine derivative of sulindac, sulindac benzylamine (SBA), did not inhibit prostaglandin synthesis, yet potently inhibited the growth and induced apoptosis of human colon tumor cells. This activity appeared to involve cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) inhibition, activation of cGMP-dependent protein kinase G (PKG), a decrease in β-catenin mediated transcription and caspase activation. The ability of SS to increase the sensitivity of multidrug resistant cancer cells was investigated by focusing on the two ATP-binding cassette (ABC) transport proteins that are most implicated in clinical multidrug resistant cancer, P-glycoprotein (ABCB1) and multidrug resistant protein-1(ABCC1). Cells over-expressing ABCB1 were significantly less sensitive to SS and doxorubicin in combination than ABCC1 expressing cells. SS also inhibited the efflux of LTC4, a high affinity substrate of ABCC1, from inside-out membrane vesicles, decreased levels of reduced glutathione and increased the intracellular accumulation of calcein-AM. Using SS for comparison, two classes of compounds not previously associated with MDR inhibition were identified. The two classes, 5-quinolinones and imidazopyrimidines, contained members that selectively increased the cytotoxicity of doxorubicin in ABCC1 expressing MDR cells, in some cases potentiating the antiproliferative effect of doxorubicin treatment better than SS. Overall, these studies demonstrate that SS can be used to identify COX-independent pathways involved in the antineoplastic activity of NSAIDs, leading to the development of novel targeted compounds for safer and more effective treatment of CRC and chemoresistance.

PhD

1 online resource (x, 137 p.) :ill., digital, PDF file.

Pharmacology and Toxicology

Joint Health Sciences

beta-catenin colorectal cancer multi-drug resistance NSAIDs phosphodiesterases sulindac

UNRESTRICTED

Advisors/Committee Members: Stephen Barnes, Piazza,Gary Grubbs,Clinton Johnson,Martin Pillion,Dennis Grizzle,William.

Subjects/Keywords: Bayes Theorem<; br>; Computer Simulation<; br>; Environment<; br>; Gene-Environment Interaction.<; br>; Genetic Association Studies – methods.<; br>; Haplotypes – genetics.<; br>; Models, Genetic

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Whitt, J. D. (2012). Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1413

Chicago Manual of Style (16th Edition):

Whitt, Jason Derek. “Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac.” 2012. Doctoral Dissertation, University of Alabama – Birmingham. Accessed March 29, 2020. http://contentdm.mhsl.uab.edu/u?/etd,1413.

MLA Handbook (7th Edition):

Whitt, Jason Derek. “Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac.” 2012. Web. 29 Mar 2020.

Vancouver:

Whitt JD. Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2012. [cited 2020 Mar 29]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1413.

Council of Science Editors:

Whitt JD. Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac. [Doctoral Dissertation]. University of Alabama – Birmingham; 2012. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1413

.