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Full-Text Articles in Cell Biology

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara May 2019

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari Oct 2013

Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari

Open Dartmouth: Faculty Open Access Scholarship

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using ...


Modelling Β2ar Regulation, Sharat J. Vayttaden Dec 2011

Modelling Β2ar Regulation, Sharat J. Vayttaden

UT GSBS Dissertations and Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical ...


Mechanisms Of Somatostatin-Induced Paradoxical Increase In Insulin Secretion In The Presence Of Arginine Vasopressin In Clonal [Beta]-Cell Hit-T15 , Henrique Cheng Jan 2002

Mechanisms Of Somatostatin-Induced Paradoxical Increase In Insulin Secretion In The Presence Of Arginine Vasopressin In Clonal [Beta]-Cell Hit-T15 , Henrique Cheng

Retrospective Theses and Dissertations

We investigated the mechanism underlying somatostatin-induced increase in [Ca2+]i leading to insulin release in the presence of arginine vasopressin (AVP) in clonal beta-cell HIT-T15. Somatostatin increased [Ca2+]i and insulin release in a biphasic pattern, characterized by a sharp and transient increase followed by a rapid decline to the sub-basal level. Pretreatment with pertussis toxin, which inactivates Gi/Go, abolished the effects of somatostatin. U-73122, an inhibitor of phospholipase C, antagonized somatostatin-induced increase in [Ca2+] i. In Ca2+-free environment, somatostatin still increased [Ca2+]i, whereas depletion of intracellular Ca 2+ stores with thapsigargin, a microsomal Ca2+ ATPase inhibitor ...


Comparison Of Beta-Adrenoceptor Coupled Camp Production In Cultured Human Mononuclear Leukocytes And Myometrial Cells, Yu-Li Liu Dec 1997

Comparison Of Beta-Adrenoceptor Coupled Camp Production In Cultured Human Mononuclear Leukocytes And Myometrial Cells, Yu-Li Liu

Electronic Theses and Dissertations

$\beta\sb2$-Adrenoceptor ($\beta\sb2$-AR) agonists, such as terbutaline, are used as tocolytic agents in the treatment of preterm labor. $\beta$-Adrenoceptor stimulation relaxes myometrium through specific receptors coupled through Gs to adenylyl cyclase (AC) that catalyzes the conversion of ATP to cAMP. The purpose of this study was to compare $\beta$-adrenoceptors and cAMP production in cultured human leukocytes and myometrial cells, and to determine the importance of $\beta$-adrenoceptors and cAMP production in isoproterenol-induced myometrial relaxation. $\sp{125}$I-iodopindolol was used to assess $\beta$-adrenoceptor affinity and number cAMP levels were analyzed before and after stimulation by ...


Utilization Of Fatigued And Non-Fatigued Isolated Guinea-Pig Papillary Muscles And Ventricular Myocytes On The Comparison Of Inotropic, Chronotropic And Intracellular Calcium Changes Induced By Monensin And Digoxin , Ismail Meral Jan 1996

Utilization Of Fatigued And Non-Fatigued Isolated Guinea-Pig Papillary Muscles And Ventricular Myocytes On The Comparison Of Inotropic, Chronotropic And Intracellular Calcium Changes Induced By Monensin And Digoxin , Ismail Meral

Retrospective Theses and Dissertations

Experiment 1. We investigated the effects of monensin and digoxin on contraction force (CF), initial contraction velocity (ICV), average contraction velocity (ACV), initial relaxation velocity (IRV) and stimulus to response time (ST) change in fatigued (defined as the level at which papillary muscle contraction had lost 30% of its original contraction force with the elapse of time) and non-fatigued guinea-pig papillary muscles. The five hours of measurement in Experiment 3 were divided into five periods (T0 was equilibration, T1, T2, T3, and T4 were respectively one, two, three, and four hours after drug administration). We found that both monensin and ...


Ca2+ Signaling In Porcine Myometrial Cells: Ca2+ Channels, Intracellular Ca2+ Stores And Guanine Nucleotide-Binding Protein-Coupled Receptors , Ronghua Zhuge Jan 1995

Ca2+ Signaling In Porcine Myometrial Cells: Ca2+ Channels, Intracellular Ca2+ Stores And Guanine Nucleotide-Binding Protein-Coupled Receptors , Ronghua Zhuge

Retrospective Theses and Dissertations

Fura-2 spectrofluorometry and imaging, and whole-cell patch-clamp techniques were used to characterize Ca[superscript]2+ channels and intracellular Ca[superscript]2+ stores for exploring signal transduction of the oxytocin receptor and the [alpha][subscript] 2A-adrenergic receptor in freshly dispersed porcine myometrial cells. Two types of voltage-dependent Ca[superscript]2+ channels, i.e., L-type and T-type, were found in 8% of myometrial cells while in 92% of the cells, only L-type Ca[superscript]2+ channels were detected. The analysis of occurrence, voltage dependence and kinetics of Ca[superscript]2+ channels suggested that L-type channels were responsible for the delivery of Ca ...


Characterization Of A Rat Clonal [Beta]-Cell Line, Rinm5f, In A Passage- And Morphology-Dependent Manner , Bum-Sup Lee Jan 1995

Characterization Of A Rat Clonal [Beta]-Cell Line, Rinm5f, In A Passage- And Morphology-Dependent Manner , Bum-Sup Lee

Retrospective Theses and Dissertations

A novel insulin-like immunoreactivity, adrenergic receptors (ARs) and voltage-dependent Ca[superscript]2+ channels (VDCCs) were characterized in a clonal [beta]-cell line, RINm5F, in a passage- and morphology-dependent manner. The cells exhibited two morphological features; the differentiated cells (DCs) with long neuron-like processes and the undifferentiated cells (UCs) without the processes;As morphology of the cells changed from DCs to UCs, amount of secreted insulin gradually decreased; however, insulin reacted to antiserum vs. bovine insulin (ABI) gradually increased from barely detectable amounts. Immunoblotting and immunocytochemistry showed that antiserum vs. rat insulin reacted with insulin from both cell types. ABI did ...