WorldCat Identities

Wondrak, Georg

Overview
Works: 7 works in 8 publications in 2 languages and 10 library holdings
Genres: Academic theses 
Roles: Author, Performer, Narrator
Classifications: RC268.5, 571.6
Publication Timeline
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Most widely held works by Georg Wondrak
Stress response pathways in cancer : from molecular targets to novel therapeutics by Georg T Wondrak( )

2 editions published in 2014 in English and held by 4 WorldCat member libraries worldwide

4.3.1.1 Regulation of Cell Proliferation4.3.1.2 Promotion of Normal Cell Metabolism; 4.3.2 p53 Controlling Stemness; 4.4 Deficient p53 Activity in Tumor Cells; 4.4.1 Mutant p53 in Tumors; 4.4.2 Inactivation of Wild Type p53; 4.5 p53, a Key Target for Cancer Therapy; 4.5.1 Proof-of-Principle and Strategy to Restore p53 Function; 4.5.1.1 Activating Wild Type p53; 4.5.1.2 Reactivating Mutant p53; 4.5.2 Other p53-Based Strategies; 4.5.3 Future Directions and Expectations; References; Chapter 5: Sirtuins as a Double-Edged Sword in Cancer: From Molecular Mechanisms to Therapeutic Opportunities
Peter ist der Boss( Book )

1 edition published in 2008 in German and held by 1 WorldCat member library worldwide

Targeting the Transcription of RET Oncogene in Medullary Thyroid Carcinoma Using Drug-Like Small Molecules by Vishnu Muthuraj Kumarasamy( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Dominant-activating mutations in the RET (Rearranged during transfection) proto-oncogene, which encodes a receptor tyrosine kinase, was identified as the major cause for the development of medullary thyroid carcinoma (MTC). Hence, the RET protein has been explored as an excellent molecular target for therapeutic intervention to treat progressive and advanced MTC. The main objective of this dissertation is to highlight a clinically relevant therapeutic strategy for the treatment of MTC by selectively suppressing the transcription of mutant RET oncogene. The basal transcriptional activity of the RET gene is mainly regulated by the polypurine/polypyrimidine (pPu/pPy) tract, present within the proximal promoter region of this gene ( -51 to -33 relative to transcription start site). The pPu/pPy tract is rich in guanine-repeat sequence containing five runs of consecutive guanine residues that serve as the binding site for transcriptional factors. This stretch of nucleotides in the promoter region is highly dynamic in nature and tend to adopt non-B DNA secondary structures called G-quadruplexes. As we have recently shown, the formation of G-quadruplex structures on the RET promoter region negatively regulates the transcription of this gene through sequestration of the transcription factor binding sites. Hence, we hypothesized that the stabilization of these structures using small molecules could exert transcriptional inhibitory effect on the RET gene. \nIn our study, we validated that the RET promoter G-quadruplex structure is an amenable drug target to silence RET gene expression by demonstrating the anti-RET activity of a well-characterized G-quadruplex stabilizing agent, berberine. This compound inhibits the RET gene transcription in an MTC derived TT cell line by specifically targeting its promoter G-quadruplex structure. Interestingly, the inhibitory effect of berberine on the RET expression is lost in papillary thyroid carcinoma cell line, TPC1, which lacks the G-quadruplex forming sequence on the RET promoter region due to chromosomal rearrangement. Furthermore, the RET downregulation by berberine results in the inhibition of TT-cell proliferation through cell-cycle arrest and activation of apoptosis. Overall, these data strongly suggest that the formation of G-quadruplex structure and its stabilization by small molecules is an ideal approach for the transcriptional repression of the RET oncogene. \nIn continuation of our study, we next explored for more drug-like small molecules as potential RET G-quadruplex stabilizers that could be used for MTC patients in a clinical setting. We identified the anti-cancer drug, ellipticine, and its derivatives as excellent RET G-quadruplex stabilizing agents. Circular dichroism (CD) spectroscopic studies revealed that one of the ellipticine analogs, NSC311153 that incorporates a ethylpiperidine group, showed improved binding with the G-quadruplex structure and the stability induced by this compound is more potent than ellipticine. Furthermore, this compound possessed selective inhibitory effect on RET transcription in TT cell line over the TPC1 cells. The RET downregulation by NSC311153 selectively suppresses cell proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways in the TT cells. In this study, we also showed that the systemic administration of a structural analog of NSC311153 in mice, bearing MTC xenografts, results in the inhibition of tumor growth through RET downregulation. Overall, our study supports the rationale for the development of RET G-quadruplex stabilizing-based therapeutic approaches for the treatment of progressive MTC
Die Pulvermänner( Book )

1 edition published in 2008 in German and held by 1 WorldCat member library worldwide

Molecular and Chemical Modulation of NRF2 for Disease Intervention by Bryan Harder( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Cells are frequently exposed to endogenous and environmental stressors that pose a threat to homeostatic cellular conditions. In response to such stress, the cell activates an adaptive antioxidant response, which is regulated by the transcription factor NRF2 to mitigate the harmful effects of electrophilic or oxidative species. Pharmacological activation of NRF2 has shown to be effective for preventing the initiation and promotion of cancer, neurodegenerative diseases, and other chronic illnesses, leading to the search for more specific molecules that activate this pathway. Intriguingly, because it is a pro-survival factor, NRF2 is frequently found to be deregulated in many cancer types that are resistant to chemotherapy, calling for the use of NRF2 inhibitors as an adjuvant therapy to enhance the effects of primary chemotherapeutic regimens. In this dissertation, detailed molecular studies have identified a new mechanism by which NRF2 can be aberrantly up-regulated in Type 1 endometrial carcinoma. Additionally, key mechanistic approaches were undertaken to understand the biological consequence of the first NRF2 inhibitor, brusatol. Furthermore, strategic approaches to identify novel chemical modulators of the NRF2 pathway were used, using natural products as a primary source. Assessment of the mechanism of action of biological activity for chemical modulators of the NRF2 pathway was of extreme interest, and rational approaches for the use of these compounds for disease intervention based on disease context will be discussed. Strat-MTM is a synthetic model for transdermal diffusion testing made by EMD Millipore and was marketed as a new skin mimetic membrane. It has been reported to be predictive of diffusion in human skin. Independent researchers had evaluated this membrane and compared it with animal and human skin and other polymeric membranes. Yet, there are not a published research to correlate the animal skin and Strat-MTM based on the amount of drug retained after topical application, which is one of the critical criteria for dermal drug delivery system. In this research, five compounds, with various physiochemical properties, were selected to perform this correlation. Resatorvid, Methyl Para aminobenzoate (M-PABA), Diclofenac sodium, Salicylic acid and hydrocortisone, each one was dissolved in phosphate buffer saline (pH 7.4) in concentrations of 60 ug/ml for resatorvid and 100-120 ug/ ml for others. All experiments were uniform in the setting and made in triplicate. As a conclusion from the results, the number of tested compounds were shorted to reflect the correlation in flux or permeability coefficient between murine skin and Strat-MTM membrane. With exception of M-PABA, there is a trend of correlation with the percentage of drug retained in dermis layers; however, the number of compounds still low to reflect a real correlation
MEDIOS II an der Grundschule "Am Stadion" = MEDIOS II at elementary school Grundschule "Am Stadion" by Georg Wondrak( Book )

1 edition published in 2014 in German and held by 1 WorldCat member library worldwide

Elefantenboy Hörspiel by Kurt Vethake( Recording )

1 edition published in 1974 in German and held by 1 WorldCat member library worldwide

 
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