Pharmacology Commons^™

The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified …

Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal

Wayne State University Dissertations

Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for

treatment of several indications including endobronchial and esophageal cancers that are

accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)

are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal

lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients

have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is

underexplored for breast cancers but has been proposed for treatment of subtypes for which a

targeted therapy is unavailable. …

Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh

Wayne State University Dissertations

AMPK activation and Ubiquitin Proteasome System (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. Although the crosstalk between them is suggested, the relationship between these two important pathways is not very clear. We observed that proteasome inhibition leads to AMPK activation in human breast cancer cells. We report that a variety of proteasome inhibitors activate AMPK in all of the tested cancer cell lines. Our data using Liver Kinase B1 (LKB1)-deficient cancer cells suggests that proteasome inhibitor-induced …

Novel Protein Phosphatase 2a Complexes In Skeletal Muscle From Obese Insulin Resistant Human Participants, Divyasri Damacharla

Wayne State University Theses

Type 2 Diabetes is a metabolic disorder associated with insulin resistance and consequent high blood glucose levels. Maximum glucose disposal takes place in skeletal muscle and studying skeletal muscle insulin resistance is crucial. Protein Phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases belonging to PhosphoProteinPhosphatase (PPP) family. It constitutes about 80% of all serine/threonine phosphatases. It is regulated by numerous regulatory subunits as well as other substrate molecules and post translational modifications. This alters their localization, activity and also its target molecules. Many evidences show the effect of insulin on PP2Ac and its abnormal regulation in conditions of …

The Role Of E3 Ligase Parkin In Trafficking Of Monoamine Storage Vesicles In Rat Model Of Methamphetamine Neurotoxicity, Heli Dineshchandra Chauhan

Wayne State University Theses

Methamphetamine (METH), a psychostimulant, is a widely used drug of abuse. METH is toxic to dopaminergic (DAergic) and serotonergic (5-HT) nerve terminals in the striatum when administered at high doses. METH releases Dopamine (DA) from vesicular monoamine transporter 2 (VMAT2) containing synaptic vesicles and induces oxidative stress by auto-oxidation of DA. The VMAT2 plays a neurprotective role by sequestering cytoplasmic DA into vesicles for storage and protection from auto-oxidation. It has previously been shown that METH toxicity is associated with impaired VMAT2 trafficking and oxidative damage to the E3 ligase parkin. CDCrel1, a protein found to inhibit exocytosis, is regulated …

Effect Of Metformin On Global Phosphorylation Profiles Of Primary Skeletal Muscle Cells Derived From Overweight/Obese Insulin Resistant Human Participants, Nishit Shah

Wayne State University Theses

Metformin is a drug from the biguanide class and it has been in use for the treatment of type 2 diabetes for a long time, and it can improve insulin sensitivity in skeletal muscle. However, the mechanism for metformin’s action is unclear. Phosphatases and kinases, and their subunits are the proteins required for dephosphorylation and phosphorylation of proteins in cells during various signaling pathways. Phosphorylation studies of proteins from primary cell culture derived from skeletal muscle tissue from obese/overweight insulin resistant participants will help to understand the regulation of phosphorylation in phosphatases and kinases by metformin.

In the current research, …

Therapeutic Targeting Of Bmp2 In Nf1-Deficient Malignant Peripheral Nerve Sheath Tumors (Mpnsts), Sidra Ahsan

Wayne State University Dissertations

Neurofibromatosis type I (NF1)-deficient malignant peripheral nerve sheath tumor (MPNST) is an aggressive tumor for which the standard treatment is surgical removal with wide margins, often leaving behind cancer cells needing chemotherapy. RAS-GRD is the most widely studied functional target of NF1 implicated in tumorigenesis, however, therapeutic interventions targeting RAS activity have met with limited success. Using gene expression profiling, our lab identified BMP2-SMAD1/5/8 signaling pathway as a therapeutic target in MPNSTs, independent of the NRAS and MEK1/2 regulation. The overall goal of my research was to validate the significance of BMP2 in MPNSTs in novel cellular models, study the …

Cross-Talk Between The Tumor Suppressors Par-4 And P53, Tripti Shrestha Bhattarai

Theses and Dissertations--Toxicology and Cancer Biology

This work describes the fascinating interplay between two tumor suppressors Prostate apoptosis response-4 (Par-4) and p53. The guardian of the genome, p53, is frequently mutated in human cancers, and may contribute to therapeutic resistance. However, p53 is intact and functional in normal tissues, and we observed that specific activation of p53 in normal fibroblasts could induce apoptosis selectively in p53-deficient cancer cells. This paracrine apoptotic effect was executed by Par-4 secreted in response to p53 activation. Accordingly, activation of p53 in wild-type mice, but not in p53^-/- or Par-4^-/- mice, caused systemic elevation of Par-4 that induced apoptosis …

Evaluation Of The Methanol Whole Root Extract Of Securidaca Longipedunculata For Antitrypanosomal Activity In Vitro And In Vivo, Eke Ifeanyi Gabriel, Ihedioha Thelma Ebere, Ezeh Ikenna Onyema, Ezeudu Terry Adaku, Eze Ukamaka Uchenna, Okoye Chidozie Nwabuisi, Anaga Aruh Otah

The Thai Journal of Pharmaceutical Sciences

Securidaca longipedunculata is a medicinal plant used in different parts of Africa for treatment of various ailments including sleeping sickness in Northern Nigeria. On this basis, the methanol root extract of S. longipedunculata was investigated for ant...

Synthetic Cannabinoids Versus Delta-9-Tetrahydrocannabinol: Abuse-Related Consequences Of Enhanced Efficacy At The Cannabinoid 1 Receptor, Travis Grim

Theses and Dissertations

In the past ten years, synthetic cannabinoids (SC) have emerged as drugs of abuse. Unlike D⁹-tetrahydrocannabinol (THC), many SCs are associated with serious health complications and death. One way in which THC and SCs differ lies with their enhanced potency and efficacy at the CB₁ receptor. No current methods exist to measure efficacy at the CB₁ receptor in vivo, and the abuse-related properties of SC cannabinoids are not well explored. Here, we utilized CB₁ wild type (WT), heterozygous (HET), and knockout (KO) mice. By employing CB₁ ligands which differ in efficacy we have …

Relationship Between Autophagy, Senescence, And Dna Damage In Radiation Sensitization By Parp Inhibition, Moureq Alotaibi

Theses and Dissertations

Radiotherapy continues to be a primary modality in the treatment of cancer. DNA damage induced by radiation can promote apoptosis as well as both autophagy and senescence, where autophagy and senescence can theoretically function to prolong tumor survival. A primary aim of this work was to investigate the hypothesis that autophagy and/or senescence could be permissive for DNA repair, thereby facilitating tumor cell recovery from radiation-induced growth arrest and/or cell death. In addition, studies were designed to elucidate the involvement of autophagy and senescence in radiation sensitization by PARP inhibitors and the re-emergence of a proliferating tumor cell population. In …

Effect Of Vitamin E Supplementation On Inflammatory Markers And Nutrition Status In Thalassemia Intermedia Patients, Watcharee Prapawatwech, Bunchoo Pongtanakul, Kulwara Meksawan

The Thai Journal of Pharmaceutical Sciences

Inflammation is a complication found in thalassemic patients. It may be diminished by supplementation of vitamin E. The purpose of this study was to investigate the effects of 12-week vitamin E supplementation on inflammatory markers in patients with tha...

Short Native Α-Helical Cationic Antimicrobial Peptides: Promising Alternative Antibiotics, Jiraphun Jittikoon

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Synthesis And Characterization Of Sodium Alginate Conjugate: Preparation And Evaluation Of Transdermal Patches Of Losartan Potassium Using Sodium Alginate Conjugate, Satheesha Babu Bk, Srinivasa Rao K

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Relationship Between Carbamazepine Concentrations In Serum And Saliva Of Thai Epileptic Patients, Piyaporn Kaewdoung, Chartchai Puripokai, Chartchai Puripokai, Mayuree H. Tantisira, Somsong Laanwprasert

The Thai Journal of Pharmaceutical Sciences

This study aims to examine and verify the correlation between serum and saliva carbamazepine concentrations in Thai epileptic patients. The subjects were patients aged 15-60 years old who were under treatment with carbamazepine. Carbamazepine concentrati...

Development And Validation Of A Stability-Indicating Ultra-Performance Liquid Chromatographic Method For The Determination Of Rifampicin In Bulk Drug And Capsules, N. Swamy, K. Basavaiah, P. Vamsikrishna, G. Krishnamurthy

The Thai Journal of Pharmaceutical Sciences

A rapid method based on ultra-performance liquid chromatography (UPLC) was developed and validated for the specific determination of anti-tuberculosis drug rifampicin (RIF) in bulk form and capsules. The UPLC determination was carried out on a reversed-p...

Synthesis Of Novel Fused Heterocyclic Pyrazolo-Pyridazine Derivatives As Antimicrobial Agents, M. Alam, M. S. Zaman, K. Arora, A. Ahmad, S. A. Khan, A. Husain

The Thai Journal of Pharmaceutical Sciences

A series of pyrazolo-pyridazine derivatives (4a-j) were synthesized and evaluated for their antimicrobial activities with an aim to obtain promising antimicrobial agents. In the first step, 6-substituted phenyl-2,3,4,5- tetrahydropyridazin-3-one (2a,b) w...

Application Of Proteoglycans From Fish Cartilage For The Acceleration Of Burn Wound Healing, Sitthiphon Bunman, Pornanong Aramwit, Noppadol Larbcharoensub, Pasarapa Towiwat

The Thai Journal of Pharmaceutical Sciences

Cartilage contains a variety of proteoglycans (PGs) that can accelerate wound healing. The aim of this study was to evaluate the efficacy of proteoglycans extracted from fish cartilage for the acceleration of burn wound healing. Second degree burn wounds...

Evaluation Of Anti-Anxiety Activity Of Melissa Parviflora (Benth.) In Rats, Kundan Singh Bora, Aruna Dubey

The Thai Journal of Pharmaceutical Sciences

Melissa parviflora Benth. (Family: Lamiaceae) has been traditionally used as a tranquillizer, relaxants, nervine and sleeping aids throughout the world. The plant is reported to relieve tension and stress reactions, and widely valued for its calming prop...

In Vitro Biological Activities Of Black Pepper Essential Oil And Its Major Components Relevant To The Prevention Of Alzheimer’S Disease, Pattamapan Lomarat, Kittisak Sripha, Phanida Phanthong, Worawan Kitphati, Krit Thirapanmethee, Nuntavan Bunyapraphatsara

The Thai Journal of Pharmaceutical Sciences

Black pepper oil and its major components were investigated for the biological activities related to the prevention of AD. The inhibition of acetylcholinesterase (AChE) and β-amyloid aggregation, anti-inflammatory and antioxidant activities were examine...