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Articles 1 - 18 of 18
Full-Text Articles in Pharmacology
Anticancer Efficacy Of Methyl-Cantharidimide (Mca) In Liver Cancer, Yidong Li
Anticancer Efficacy Of Methyl-Cantharidimide (Mca) In Liver Cancer, Yidong Li
Theses and Dissertations
Cancer is still one of the major public health challenges worldwide to the present day. Multi-drug resistance (MDR) that occurs in cancer chemotherapies is a non-negligible cause of cancer treatment failure and tumor recurrence. Overexpression of ATP-binding cassette (ABC) transporters is one of the most frequent mechanisms of MDR occurrence. Therefore, the establishment of a chemotherapy agent whose anticancer efficacy would not be affected by the overexpression of ABC transporters is in demand. Methyl-cantharidimide (MCA), a cantharidin (CTD) analog, has been approved in China for clinical liver cancer treatment. This study revealed that MCA was efficacious in the ABCB1-, ABCG2-mediated …
Umbralisib Antagonizes Multidrug Resistance In Abcb1- Overexpressing Cancer Cells, Letao Bo
Umbralisib Antagonizes Multidrug Resistance In Abcb1- Overexpressing Cancer Cells, Letao Bo
Theses and Dissertations
Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, is a major mechanism of multidrug resistance (MDR) and contributes to chemotherapy failure by reducing intracellular drug accumulation. Umbralisib is a dual inhibitor of phosphoinositide 3-kinase delta (PI3Kδ) and casein kinase 1 epsilon (CK1ε) that was developed for the treatment of hematologic malignancies; however, it was later withdrawn due to safety concerns. In the present study, we found that umbralisib has the potential to reverse ABCB1-mediated MDR. The MTT assay demonstrated that umbralisib significantly sensitized ABCB1-overexpressing KB-C2 and SW620/Ad300 cells, as well as ABCB1-transfected HEK293 cells. Mechanistic assays revealed that umbralisib enhanced …
Improving The Safety Of N,N-Dimethylacetamide As A Potential Treatment For Preterm Birth Using A Vaginal Nanoformulation, Asad Mir
Theses and Dissertations
With no available treatment for preterm birth, the field of reproductive medicine has been repurposing small molecule candidates into vaginal nanoformulations as potential treatments for the condition. The commercial solvent N,N-Dimethylacetamide (DMA) has previously been shown to delay and prevent inflammation-induced preterm birth in a mouse model. A vaginal nanoformulation of DMA loaded into a self-nanoemulsifying drug delivery system (SNEEDS) was studied to see if it can also be efficacious. A side by-side histological comparison was done in the more pertinent tissues of the reproductive tract between the traditional formulation of DMA given intraperitoneally (IP) and the vaginal nanoformulation of …
Developing Stiripentol Analogs As Potential Ldh Inhibitors For The Treatment Of Glioblastoma, Anshika Y. Jain
Developing Stiripentol Analogs As Potential Ldh Inhibitors For The Treatment Of Glioblastoma, Anshika Y. Jain
Theses and Dissertations
Glioblastoma multiforme (GBM) is a highly proliferative brain tumor that has a 5-year survival rate of ~7 %. Temozolomide (TMZ) is the current standard of care therapeutic for GBM. However, 50% of patients develop resistance to TMZ. Therefore, further investigation for new GBM therapeutics is necessary to overcome this issue of drug resistance. GBM patients are known to overexpress lactate dehydrogenase (LDH), which is inversely correlated with their survival. This key glycolytic enzyme catalyzes the interconversion of pyruvate and lactate and plays an important role in cancer proliferation and invasion. Therefore, we aimed to inhibit LDH for developing therapeutics for …
Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart
Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart
Theses and Dissertations
Bone morphogenetic proteins (BMPs) are the largest subfamily of the Transforming Growth Factor (TGF)-ß superfamily. BMPs are renowned for their pivotal role in cellular functions such as cell growth, apoptosis, and differentiation. Yet, BMPs have also been attributed to the maintenance of adult tissue homeostasis. BMPs elicit physiological function at the cell membrane via a heterotetrameric complex composed of two Type I and two Type II serine-threonine kinase BMP receptors. Activation of BMP transmembrane receptors results in activation of either canonical (Smad-dependent) and/or non-canonical (Smad-independent) signaling. Given the physiological importance of this intricate communication between receptor activation and induction of …
Production Of Vp3-Only Aav2 Vlp In E. Coli, Chengyu Fu
Production Of Vp3-Only Aav2 Vlp In E. Coli, Chengyu Fu
Theses and Dissertations
Adeno-associated virus (AAV) is a widely used vector for gene therapy. However, few studies have focused on producing AAV-based virus-like particles (VLP) in E. coli. This project aimed to express VP3 of AAV2 or co-express VP3 of AAV2 with other proteins, such as E. coli chaperones and/or assembly-activating protein (AAP) in E. coli under different expression conditions and explore the potential to produce VP3-only VLP of AAV2 in situ in E. coli. The constructed plasmid pET15ΔHis-VP3 was used to express VP3 under different conditions. The results demonstrated that most expressed VP3 was in inclusion bodies in all tested conditions. Although …
Mobocertinib Antagonizes Multidrug Resistance In Abcb1- And Abcg2-Overexpressing Cancer Cells, Xingduo Dong
Mobocertinib Antagonizes Multidrug Resistance In Abcb1- And Abcg2-Overexpressing Cancer Cells, Xingduo Dong
Theses and Dissertations
The resistance of cancer cells to multiple drugs, known as multidrug resistance (MDR), remains a significant obstacle that leads to the ineffectiveness of cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, has been strongly correlated with MDR. There is an urgent need to explore and identify novel inhibitors targeting ABCB1 and ABCG2 to overcome the related MDR. Mobocertinib (TAK-788) is an orally administered, irreversible EGFR/HER2 inhibitor approved for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations. This study …
Therapeutic Intervention Of Neuroinflammation In Alzheimer Disease By Inhibition Of Classical Complement Pathway Using Anti-C1r Loaded Exosomes, Terjahna Richards
Therapeutic Intervention Of Neuroinflammation In Alzheimer Disease By Inhibition Of Classical Complement Pathway Using Anti-C1r Loaded Exosomes, Terjahna Richards
Theses and Dissertations
Alzheimer’s disease (AD) is a neurodegenerative disease associated with memory decline and cognitive impairment. It is a growing global health and socioeconomic concern, affecting more than 50 million people worldwide. Current therapeutics focus solely on symptomatic management instead of preventative or curative strategies. This is mainly a result of the complexity of the pathophysiological mechanism and the poor understanding of the disease progression. Recently, studies have focused on bridging knowledge gaps giving rise to substantial evidence on the vital role of neuroinflammation in the progression of AD. Neuroinflammation has been shown to be a precursor to apparent amyloid plaque accumulation …
Hjp 272, An Endothelin Receptor Antagonist, And Its Role In Cancer Cell Migration And Invasion, Nabeela Fatima Baig
Hjp 272, An Endothelin Receptor Antagonist, And Its Role In Cancer Cell Migration And Invasion, Nabeela Fatima Baig
Theses and Dissertations
Endothelins are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the Endothelin axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ETAR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first …
Characterizing The Role Of Epigenetic Regulator Menin In Pediatric Neuroblastoma Growth Using Pre-Clinical Models, Rameswari Chilamakuri
Characterizing The Role Of Epigenetic Regulator Menin In Pediatric Neuroblastoma Growth Using Pre-Clinical Models, Rameswari Chilamakuri
Theses and Dissertations
Epigenetic regulators such as Menin and MLL1 drive cancer progression, metastasis, and relapse. MLL1 forms a COMPASS complex with its binding partners, including Menin, to function as an epigenetic enzyme H3K4 methyltransferase. H3K4 methyltransferases are known to promote cancer stem cells' (CSCs) self-renewal capacity and metastasis. CSCs are one of the major causes of tumor relapse and metastasis conditions, ultimately leading to poor overall patient survival. Neuroblastoma (NB) is an extracranial solid tumor that accounts for 8-10% of all pediatric cancers, and approximately 50% of patients display metastasis at the time of diagnosis. In this study, we hypothesized and used …
Overexpression Of Abcc1 And Abcg2 Confers Resistance To Bmn-673, A Poly (Adp-Ribose) Polymerase (Parp) Inhibitors, Qiuxu Teng
Theses and Dissertations
Cancer remains a growing public health challenge worldwide. Although the development of chemotherapies has effectively reduced the cancer death rate and improved patients’ prognosis, the frequent occurrence of multi-drug resistance (MDR) in cancer has caused impairments on the efficacy of many structure-unrelated anticancer agents, leading to treatment failure and recurrence. One of the most common causes of MDR is the overexpression of ATP-binding cassette (ABC) transporters on cancer cell membranes, which transport anticancer drugs out of cancer cells, thereby reducing the intracellular drug concentration. BMN-673 (talazoparib) is a potent poly (ADP-ribose) polymerase (PARP) inhibitor that is approved for BRCA-mutated HER2-negative …
N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei
N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei
Theses and Dissertations
Alzheimer’s disease (AD) is a neurodegenerative disorder with no cure, accounting for 60-80% of cases of dementia. While the two pathologic hallmarks of AD, senile plaques from extracellular deposition of amyloid β-protein (Aβ) and tau-based neurofibrillary tangles (NFT), have been known for decades, the pathogenesis of AD remains unclear. In recent years, anti-neuroinflammatory treatment has entered the spotlight in AD research. In previous studies, we have shown that N,N-dimethylacetamide (DMA), a common drug excipient, is a potent anti-inflammatory agent. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo …
Repurposing An Anti-Epileptic Drug For The Treatment Of Glioblastoma, Anjali Yadav
Repurposing An Anti-Epileptic Drug For The Treatment Of Glioblastoma, Anjali Yadav
Theses and Dissertations
Glioblastoma multiforme (GBM) is a grade IV malignant glioma. It is a highly proliferative form of brain tumor with 5-year survival rate ~ 5% indicating a high mortality rate. Current treatment strategies for GBM include surgery, radiation, and chemotherapy. Surgical resection is challenging due to vital function of brain and as GBM often metastasizes in different brain regions. Additionally, development of resistance against the standard of care drug temozolomide (TMZ) is a major challenge in GBM management. GBM is also shielded with the blood brain barrier (BBB) which prevents the entry of several drugs. Therefore, a new drug must overcome …
Evaluating The Effects Of Mechlorethamine On The Dermal-Epidermal Junction, Trishaal Janardhanam Raghavendra Rao
Evaluating The Effects Of Mechlorethamine On The Dermal-Epidermal Junction, Trishaal Janardhanam Raghavendra Rao
Theses and Dissertations
Sulfur Mustard (SM) is a chemical warfare agent first utilized on the battlefield more than 100 years ago. To the present time, no antidote to combat the dermatotoxicity of SM exists. Mechlorethamine (HN2) is a derivative of SM which is used in anticancer therapy. Dermal exposure of HN2 is associated with dermal-epidermal junction (DEJ) disruption (vesication) which limits its clinical usefulness. The primary purpose of the present study was to investigate the mechanisms of vesication caused by HN2 using an in vivo mouse ear vesicant model (MEVM). The ears of male or female C57BL/ 6J mice were exposed to a …
Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan
Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan
Theses and Dissertations
Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, irinotecan, a topoisomerase I inhibitor, is an important anticancer drug approved for patients with advanced or recurrent colorectal cancer. Considering the low response rate and the events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anticancer activity against most of the tested colon cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, …
Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot
Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot
Theses and Dissertations
Metabolic reprogramming is one of the important features of cancers, and there has been growing interest in targeting metabolic proteins to treat cancer. Glycogen is a polymer of glucose and serves as its storage unit in cells. Glycogen can provide energy to cells during the situations of high energy demand. A number of tumors are known to contain high levels of glycogen than their normal tissue counterparts. The liver plays an essential role in maintaining glucose homeostasis in the body via storing it into glycogen. The significance of glycogen metabolism in patients suffering from hepatocellular carcinoma (HCC) has not been …
Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang
Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang
Theses and Dissertations
ATP-binding cassette (ABC) transporters are responsible for the efflux of structurally distinct endo- and xenobiotics energized by ATP hydrolysis. MRP7/ABCC10 belongs to the 10th member of subfamily C and responsible for mediating MDR against a series of chemotherapeutic drugs such as taxanes, epothilones, Vinca alkaloids, anthracyclines and epipodophyllotoxins. Establishment of new in silico and in vitro models for MRP7 substrates/inhibitors prediction Considering the limited knowledge of MRP7, we established a homology model based on bovine MRP1 cryo-EM models. The final model was used for protein global motion analysis and docking analysis. Before docking, potential drug binding pockets were identified and …
Design, Synthesis And Pharmacological Evaluation Of Quinazolinamine Derivatives As Bcrp And P-Gp Inhibitors With Improved Metabolic Stability, Chao-Yun Cai
Theses and Dissertations
A series of twenty-two quinazolinamine derivatives showing potent inhibitory activities on BCRP and P-gp was synthesized. The reversal study showed that when combined with the potent dual BCRP and P-gp inhibitors 7-8, 29-31, and 34, the IC50 value of mitoxantrone was decreased from 6.50 µM to the range of 0.24 - 0.35 µM for BCRP, and IC50 value of colchicine was decreased from 7.34 μM to the range of 0.12 - 0.29 µM for P-gp. Cyclopropyl quinazolinamine 29 (VKCY-1), which was a dual BCRP and P-gp inhibitor, and azide quinazolinamine 40 (VKCY-2), which was a BCRP inhibitor, were selected for …