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Articles 1 - 10 of 10
Full-Text Articles in Entire DC Network
Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears
Characterizing The Roles Of Neutral Ceramidase In Cisplatin-Induced Kidney Injury., Sophia M. Sears
Electronic Theses and Dissertations
Cisplatin is a commonly used chemotherapeutic agent with a dose-limiting nephrotoxicity. 30% of patients given cisplatin develop acute kidney injury (AKI). AKI increases risk of chronic kidney disease (CKD) development and mortality. Patients that don’t develop clinical AKI are still at risk for long term declines in renal function. Currently, there are no FDA approved agents to treat or prevent cisplatin-induced kidney injury (CDDP-KI). In this study, we demonstrated that neutral ceramidase (nCDase) knockout provides protection from AKI in the high-dose model of CDDP-KI. However, in the repeated low dose cisplatin (RLDC) model of injury and we found nCDase knockout …
The Role Of Connexin And Pannexin Large-Pore Channels In Hearing, Julia Abitbol
The Role Of Connexin And Pannexin Large-Pore Channels In Hearing, Julia Abitbol
Electronic Thesis and Dissertation Repository
Connexin and pannexin large-pore channels allow the regulated passage of small molecules at sites of cell-cell contacts, and from the cytosol to the extracellular milieu, respectively. Since it has been known for many years that Cx26 and Cx30 gap junction proteins are crucial in hearing we propose that Cx43 might also be important in hearing. Here we used two different genetically modified mouse lines that contain systemic Cx43 gene mutations that reduces gap junctional intercellular communication (GJIC) to examine whether Cx43 is also important for proper hearing function. Furthermore, since pannexins have also been postulated to be involved in auditory …
Interaction Of A Platinum Triamine Complex Having A Seven-Membered Chelate Ring With N-Acetyl-Lmethionine And Guanosine 5'-Monophosphate, Jae Ko
Masters Theses & Specialist Projects
In the 1960s, Rosenberg and his colleagues confirmed the anti-cancer activity of cisplatin. Although cisplatin was capable of killing testicular cancer cells there were also serious side effects. It was necessary to find alternate ways of overcoming side effects, and soon many researchers have discovered novel platinum compounds that show similar reactivity. Recently, replacing one chloride group to a heterocyclic amine group showed significant cytotoxicity with a different binding activity than cisplatin. Previously in our lab, [Pt(Me5dien)(NO3)]+ and [Pt(Et2dien)Cl]+ have been synthesized and reacted with NAcetyl- L-methionine (N-AcMet) and Guanosine 5’-monophosphate (5’-GMP) showed unusual reactivity. Unlike most previously studied platinum …
Hei-Oc1 Cochlear Cells As An In Vitro Model To Study The Role Of Connexins In Ototoxicity And Hearing Loss, Rianne Beach
Hei-Oc1 Cochlear Cells As An In Vitro Model To Study The Role Of Connexins In Ototoxicity And Hearing Loss, Rianne Beach
Electronic Thesis and Dissertation Repository
Connexin 26 (Cx26) and Cx30 mediate the intercellular exchange of metabolites and ions within the cochlea in a process known as gap junctional intercellular communication (GJIC). Cochlear cell death and subsequent hearing loss can arise after treatment with ototoxic therapeutics and Cx26 mutant expression. We investigated the role of connexins and GJIC in the development of ototoxicity in HEI-OC1 cochlear-derived cells. The susceptibility of HEI-OC1 cells to aminoglycoside antibiotics and cisplatin-induced cell death was not influenced by the ablation of connexins and GJIC. However, the expression of mitochondrial apoptosis or ER stress markers was altered by the degree of GJIC. …
Non-Traditional Metallation Of Metallothioneins With Xenobiotic Therapeutic Metals, Daisy L. Wong
Non-Traditional Metallation Of Metallothioneins With Xenobiotic Therapeutic Metals, Daisy L. Wong
Electronic Thesis and Dissertation Repository
The rise of the Anthropocene has seen more global pollution than before in history. With the explosion of consumer electronics in the last half century, the rise of metal pollution from their extraction and disposal results in the unnatural introduction of heavy and rare metals into the ecosystem. Organisms have a metal defense protein, metallothionein, which has multiple roles in essential metal regulation and protection against minimal toxic metal exposure. However, these modern heavy metals prominent in electronics are not found biologically and their interactions in the body are generally unknown. Some of these metals are employed as therapeutic agents …
Effects Of Ef-24 And Cisplatin On Cancer, Renal, And Auditory Cells, Denis Hodzic
Effects Of Ef-24 And Cisplatin On Cancer, Renal, And Auditory Cells, Denis Hodzic
Masters Theses & Specialist Projects
Cisplatin is a chemotherapy drug effective against several forms of cancer, but can also cause serious side-effects, including nephrotoxicity and ototoxicity. Curcumin, a natural plant compound, can increase cisplatin’s anti-cancer activity and counteract cisplatin’s deleterious effect on the auditory and renal systems. Unfortunately, curcumin exhibits poor bioavailability, which has promoted interest in the development of synthetic curcumin analogs (curcuminoids) that are soluble, target cancer, and do not cause side effects. This study investigated whether the curcuminoid (3E,5E)-3,5-bis[(2-fluorophenyl) methylene]-4-piperidinone (EF-24) increases the anti-cancer effects of cisplatin against a human ovarian cancer cell line (A2780) and its cisplatin-resistant counterpart (A2780cis), while preventing …
Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage
Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage
Wayne State University Dissertations
With the discovery of cisplatin in the 1960s, it has been widely studied as a precursor for anticancer drug development. Despite its effectiveness against certain cancers, clinical usage of cisplatin is restricted by a number of side effects and resistance. In the past decade, scientists have been exploring biologically important ligands such as sugar derivatives in the hope of overcoming such challenges. Attachment of a sugar moiety could facilitate lower accumulation of platinum drugs in the body as well as enhance cellular uptake. In this study, a carbohydrate-linked cisplatin analog, cis-dichlorido[(2-β-D-glucopyranosidyl)propane-1,3-diammine]platinum (5) has been studied. The aim was to evaluate …
Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza
Novel Insights Into The Use Of Ercc1 As A Biomarker For Response To Platinum-Based Chemotherapy In Lung Cancer, Joshua Ryan Heyza
Wayne State University Dissertations
ERCC1/XPF is a DNA endonuclease with variable expression in primary tumor specimens, and has been investigated as a predictive biomarker for efficacy of platinum-based chemotherapy in non-small cell lung cancers where up to 30-60% of tumors harbor low to undetectable ERCC1 expression. The failure of an international, randomized Phase III clinical trial utilizing ERCC1 expression to predict response to platinum-based chemotherapy suggests additional mechanisms underlying the basic biology of ERCC1 in the response to platinum-DNA damage remain unknown. In this work, we aimed to characterize a panel of ERCC1 knockout cell lines generated via CRISPR-Cas9 where we identified a synthetic …
Study Of Small Molecules With Dna Monolayers On Gold Electrodes Using Electrochemical Quartz Crystal Microbalance On The Millisecond Timescale, Sarasi Kaushalya Kumari Galagedera
Study Of Small Molecules With Dna Monolayers On Gold Electrodes Using Electrochemical Quartz Crystal Microbalance On The Millisecond Timescale, Sarasi Kaushalya Kumari Galagedera
Legacy Theses & Dissertations (2009 - 2024)
Biosensors based on DNA self-assembled monolayers (SAMs) combined with electrochemical transducers have shown great potential to serve an important role in simple, accurate and inexpensive genetic analyses relevant to many fields. The most popularly adapted method in designing biosensing platforms is the self-assembly of 5’-alkylthiol-modified single stranded or double stranded DNA on gold surfaces followed by a passivation step using a diluent like mercaptohexanol (MCH). Since analytical performance (sensitivity, selectivity and stability) of such sensors is solely related to the probe surface architecture, methods to characterize and measure the surface density has gained a lot of interest among the scientific …
The Effect Of N-Acetylcysteine On Inflammation And Oxidative Stress In Cisplatin-Induced Nephrotoxicity: A Rat Model, İnayet Güntürk, Cevat Yazici, Sema Kader Köse, Fatma Dağli, Bi̇lal Yücel, Arzu Hanim Yay
The Effect Of N-Acetylcysteine On Inflammation And Oxidative Stress In Cisplatin-Induced Nephrotoxicity: A Rat Model, İnayet Güntürk, Cevat Yazici, Sema Kader Köse, Fatma Dağli, Bi̇lal Yücel, Arzu Hanim Yay
Turkish Journal of Medical Sciences
Background/Aim: Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Materials and methods: Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental …