Medicine and Health Sciences Commons^™

Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu

University of the Pacific Theses and Dissertations

Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling.

We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 …

Design And In Vitro Characterization Of Lipids With A Ph-Sensitive Conformational Switch And Their Liposomes For Anticancer Drug Delivery, Shen Zhao

University of the Pacific Theses and Dissertations

The traditional anticancer drugs are distributed in vivo through systemic blood circulation with a very small portion reaching the tumor site. Targeted drug delivery systems are developed in efforts to concentrate the drug molecules in the tissue of interest while reducing the drug distribution to healthy tissues to reduce the side effects. Liposomes are colloidal systems composed of amphiphilic molecules that assemble into vesicle structures in aqueous media. They are common carriers for targeted drug delivery with the advantages of low toxicity, low immunogenicity and the ability of encapsulating both lipophilic and hydrophilic drugs.

Prior research indicated the advantages of …

An Evaluation Of Mobile Apps For The Collation Of Materials To Propose An App For Type-2 Diabetes Self-Management, Sydney Watson

Honors Theses

This study is an evaluation of mobile application (apps) with the intention to collate materials appropriate for the proposal of a mobile app for type 2 diabetes self-management. In order to decipher the most vital aspects to be included in the app, an evaluation of mobile apps pertaining to nutrition and diabetes management were investigated. It was found that there is a lack of mobile apps that have all-encompassing features regarding the management of the disease. Future app developers looking to develop a mobile app that is efficient in type 2 diabetes self-management should include each feature as follows: blood …

A Blueprint For Knowledge Management In The Biopharmaceutical Sector, Paige Kane

Doctoral

This research examined current industry Knowledge Management (KM) methodologies and capabilities in order to gain insights into the level of maturity and understanding of KM within the biopharmaceutical sector. In addition, the researcher has developed models, tools and processes that can assist the sector to gain greater clarity of the value and merits that KM can offer to organizations. The researcher proposes that a systematic KM program can be used to “unlock” the knowledge and organizational capabilities necessary to convey real competitive advantage, but more importantly for the patient, to enable organizations to successfully develop and deliver the next generation …

Synthesis Of (2r,6r)-Hydroxy-Norketamine For Evaluation Of Antidepressant Effects, Savannah Fairley

Honors Theses

Major Depressive Disorder, colloquially known as depression, is a devastating mental illness that affects a large portion of today's population. Following a drug side-effect that caused depression, the monoamine theory of depression was created, stating that depressive symptoms were caused by a decrease in concentrations of vital monoamine neurotransmitters at the synaptic cleft. Pharmaceutical remedies to combat depression were first introduced in the 1950s and to this date, most available drugs follow the monoamine theory. These drugs have a large loading dose lag time, numerous negative side effects, and still many patients do not experience relief from symptoms. In 2000, …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …

Discovery Of Natural Product Analogs Against Ethanol-Induced Cytotoxicity In Hippocampal Slice Cultures, Meredith A. Saunders-Mattingly

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol (ethanol; EtOH) use disorder (AUD). While there are 4 medications approved by the Food and Drug Administration (FDA) to treat AUD, these treatments have demonstrated poor clinical efficacy. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about the mechanisms underlying EtOH-induced changes in neurobiology and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for AUD in a rodent organotypic hippocampal slice culture model. Initial screens of several natural product compounds identified …

Mechanisms Of Rad51d-Dependent Repair Of Dna And Telomere Damage Induced By Interstrand Crosslinking Agents And Thiopurines, Nicole M. Reilly

Theses and Dissertations

Mutations in homologous recombination (HR) genes increase genomic instability, an enabling characteristic of cancer. However, the status of these same genes can also determine chemotherapy outcomes. RAD51D is a breast and ovarian cancer susceptibility gene that is an important component of HR. Mammalian cells defective for RAD51D have extensive chromosomal aberrations and are more sensitive to the interstrand crosslink-inducing agent mitomycin C (MMC) and the thiopurine 6-thioguanine (6TG). Previously, the RNF138 E3 ubiquitin ligase was identified to promote RAD51D ubiquitination, and loss of RNF138 also increased cellular sensitivity to MMC. Ubiquitination assays were used to show that a 3-ubiquitin modification …

Mechanistic Study Of P23-Mediated Aryl Hydrocarbon Receptor Expression, Beverly Pappas

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which is involved in diverse biological functions ranging from cancer metastasis to immune regulation. This receptor forms a cytoplasmic complex with Hsp90, p23, and XAP2. We have previously reported that down-regulation of p23 triggers degradation of the AHR protein, uncovering a potentially dynamic event which controls the cellular AHR levels without ligand treatment. Here we investigate the underlying mechanisms for this p23 effect using wild-type HeLa and the p23 knockdown HeLa cells. Reduction of the Hsp90 and XAP2 contents, however, did not affect the AHR protein levels, implying that this …

The Molecular Pathophysiology Of Sepsis-Associated Disseminated Intravascular Coagulation And Its Pharmacologic Modulation, Amanda Temple Walborn

Dissertations

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection. Sepsis patients are at risk of disseminated intravascular coagulation (DIC), a severe blood coagulation disorder. In DIC, inappropriate coagulation leads to the deposition of fibrin in the microvasculature and subsequent organ failure. This consumes platelets and coagulation factors, leaving patients at risk of severe or fatal bleeding. No treatments are approved for DIC in the United States.

In order to test the hypothesis that DIC would be best described by a combination of biomarkers representative of multiple physiological processes, an array of biomarkers, representative of hemostasis, inflammation, …

Mechanistic Study Of Potential Herbal Extracts For Development Into Hair Growth-Promoting Product, Woraanong Prugsakij

Chulalongkorn University Theses and Dissertations (Chula ETD)

Androgenic alopecia (AGA) is a major type of hair loss found in both males and females, caused by the overproduction of 5 alpha-dihydrotestosterone (DHT) which is formed from testosterone (T) by the enzymes 5 alpha-reductase (5α-R). In this study, the main focus was on cytokine factors evaluation of Avicennia marina (AM extract) in primary dermal papilla cells (DPCs) from AGA patients and the efficacy in vivo. The present study has revealed that AM extract and its active constituent, avicequinone C (AC) significantly inhibit the enzyme activity of 5α-R on cell-based assay combined with a non-radioactive thin layer chromatography (TLC) using …

Chemosensitizing Effect Of Peptides From Lentinus Squarrosulus On Cisplatin-Induced Apoptosis In Human Lung Cancer Cells, Hnin Ei Ei Khine -

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cisplatin, platinum-based chemotherapy, is one of the standard chemotherapies for the treatment of lung cancer. However, its usefulness is limited due to the adverse effects and susceptibility to chemoresistance which lead to therapeutic failure. Nowadays, natural chemosensitizers, which can enhance the efficacy and decrease the effective dose of chemo-drugs, have been found to be interested in novel therapeutic. Recently, the anticancer activity of peptides extracted from Lentinus squarrosulus Mont. in human lung cancer cells has been reported. The novel potential of L. squarrosulus peptides as a chemotherapeutic adjuvant to increase cisplatin-induced apoptosis was uncovered in this study. Crude peptides extracted …

Effects Of 4,5,4'-Trihydroxy-3,3'-Dimethoxybibenzyl From Dendrobium Ellipsophyllum On Induction Of Apoptosis And Inhibition Of Cancer Stem-Like Cells In Human Lung Cancer H460 Cells, Anirut Hlosrichok

Chulalongkorn University Theses and Dissertations (Chula ETD)

Failure of current chemotherapeutic drugs leads to the recurrence of tumors and increased mortality in lung cancer patients. This study investigated 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang as a novel anticancer agent for lung cancer. Selective anticancer activity of TDB against human lung cancer cells was demonstrated with a high half maximal inhibitory concentration (IC50) approximately > 300 µM in dermal papilla cells, while IC50 in human lung cancer H460 cells was approximately 100 ± 5.18 µM. Flow cytometry confirmed that TDB (50 µM) treatment for 24 h, caused significant early and late apoptosis but not …

Effect Of Major Triterpenoids Of Centella Asiatica On Neurite Outgrowth In Neuro-2a Cells, Nonthaneth Nalinratana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Centella asiatica has been reported to demonstrate neuroprotection and memory improvement in various animal models. Triterpenoid glycosides, madecassoside (MS), asiaticoside (AS), and their aglycones, madecassic acid (MA) and asiatic acid (AA) are considered as major neuroactive constituents in C. asiatica. In this study we aimed to compared MS, AS, MA and AA for their neurite outgrowth activities and mechanisms in Neuro-2a cells. Immunofluorescent staining against ßIII-tubulin showed that MS and AS significantly increased the percentage of neurite-bearing cells and neurite length with higher potency than MA and AA. Our mechanistic studies revealed the differences in signal activation between glycosides and …

A Study On The In Vitro Stability And Metabolism Of Curcumin Diethyl Disuccinate In Plasma, Pahweenvaj Ratnatilaka Na Bhuket

Chulalongkorn University Theses and Dissertations (Chula ETD)

Stability in aqueous media such as buffers and plasma are the one of important properties of drug candidates. Curcumin diethyl disuccinate (CDD), an ester prodrug of curcumin, has been developed to improve the chemical stability of curcumin. In this study, the in vitro stability of CDD in HCl buffer (pH 1.2), acetate buffer (pH 4.5), phosphate buffer (pH 6.8, 7.4 and 8.0) and in vitro metabolism of CDD in rat, dog and human plasma were investigated at 4, 25 and 37 °C. HPLC and nonlinear regression analyses showed that the degradation of CDD in buffers was temperature-dependent and followed pseudo-1st …

Effect Of Ercc1, Xrcc1 And Gstp1 Polymorphisms On Clinical Response And Adverse Events Of Platinum-Based Chemotherapy In Epithelial Ovarian Cancer Patients, Salisa Liblab

Chulalongkorn University Theses and Dissertations (Chula ETD)

Platinum-based chemotherapy is the first line chemotherapy regimen for epithelial ovarian cancer (EOC). Pharmacogenomics is one factor that might affect its efficacy and toxicity. This cohort study was aimed to investigate the association between ERCC1, XRCC1 and GSTP1 polymorphisms on clinical responses and adverse events related to platinum-based chemotherapy in Thai EOC patients. Fifty-two patients with advanced EOC were enrolled in this cohort study. The mean age was 55.7 years old. Genotyping analysis of ERCC1 (C>A, rs3212986), XRCC1 (A>G, rs25487) and GSTP (A>G, rs1695) were performed which allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. …

Effect Of Bitter Gourd Extracts On The Mutagenicity Of 1-Aminopyrene Reacted With Nitrite Using Ames Test, Korkiat Panpasuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

This study was conducted to investigate the mutagenic activity of raw and cooked bitter gourd (Momordica charantia) including raw fruit extract (RW), blanching water (BW), hot water extract from blanched fruit (HB), stir-fried fruit extract (SF), and stir-fried fruit (pre-squeezed with salt) extract (SS). In addition, the effects of extracts in modifying the mutagenic activity of mutagen freshly prepared by the reaction between 1-aminopyrene and sodium nitrite and the effects when adding each extract at the beginning of the same reaction using Ames test on Salmonella typhimurium strains TA98 and TA100 without enzymatic activation were also determined. The data for …

Antioxidant And Antimutagenic Activity Of Extracts From Pericarp And Seed Of Zanthoxylum Limonella Alston, Patamawan Wipoosanapan

Chulalongkorn University Theses and Dissertations (Chula ETD)

This study was conducted to investigate the antioxidant and antimutagenic activity of Zanthoxylum limonella seed extract and that of Z. limonella pericarp extract. The total phenolic contents and antioxidant activity assay including DPPH assay and FRAP assay were performed. The results showed that the antioxidant activity of pericarp extract was higher than that of the seed extract. The direct mutagenicity assay was determined, with and without nitrite treatment using the Ames test towards Salmonella typhimurium strains TA98 and TA100. The mutagenic modification assay was performed by measuring the interfering effect of the pericarp extract and the seed extract on the …

Preparation And Antimicrobial Activity Of Caprylic Acid Emulsion For Food Coating, Raweewan Bunyovimonnat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Antimicrobial food coating is the interesting method for food preservation, especially in fruits and vegetables. Previous studies have been reported that the caprylic acid had the antimicrobial activity against a variety of microorganisms. However, little research has been conducted on the use of caprylic acid in the form of food coatings. Therefore, this study aims to determine the optimum conditions for the caprylic acid emulsion preparation and to evaluate the antimicrobial activity of the emulsion, including the effect of food coatings with caprylic acid emulsion on physical properties and microbial growth inhibition. Emulsions containing 4% w/v caprylic acid (oil) and …

Carbohydrate Content Of The Medications For Epileptic Children Treated With Ketogenic Diet At King Chulalongkorn Memorial Hospital, Thanarat Sawangrit

Chulalongkorn University Theses and Dissertations (Chula ETD)

The purposes of this study were to establish a database of the carbohydrate content of medications and investigate carbohydrate content of medications in epileptic children treated with ketogenic diet (KD) at King Chulalongkorn Memorial Hospital. One hundred sixty-nine KD order forms in 3 events (KD initiation, follow-up visit, and hospital re-admission) for epileptic children whose aged younger than 18 years old during 2009-2017 were selected. Clinical and nutritional data were obtained from medical records and KD order forms from the pediatric nutrition unit. The study showed that oral liquid dosage forms had the highest carbohydrate content in the formulations as …

Steady-State Determination Of Continuous Powder Mixing By Near Infrared Spectroscopy As Process Analytical Technology, Katesaraporn Wongves

Chulalongkorn University Theses and Dissertations (Chula ETD)

Powder mixing is one of an important unit operation in pharmaceutical manufacturing of solid dosage forms. Continuous mixing was developed as an alternative method to reduce disadvantages of traditional batch mixing processes. This process was originally developed using horizontal cylindrical mixer equipped with Process Analytical Technology (PAT) tools for real-time monitoring. In the present study, a vertical cylindrical mixer was developed and evaluated. Near Infrared (NIR) spectra obtained by monitoring the mixing process were pretreated with Multiplicative Scatter Correction (MSC), second derivative treatment and Norris-William smoothing in the 6800 - 8700 cm-1 range before a calibration model using PLS was …

Preparation And Stabilization Of Saccharide Fiber Produced By Centrifugal Spinning, Pattama Donghuntong

Chulalongkorn University Theses and Dissertations (Chula ETD)

The objectives of this study were to prepare saccharide fiber via centrifugal spinning and further investigate its stability under stress condition. Different saccharides were chosen and spun via centrifugal force to form thread like matter. The results indicated that sucrose (SC) and trehalose (TH) could be fabricated as fiber whereas other saccharides were not able to form. The formation of fiber mainly involved with glass transition temperature (Tg), molten ability including stability of saccharide after melting. High Tg saccharides were a good candidate on fiber preparation. Homogeneous melting with appreciable stability was another factor affecting on fiber preparation. Decomposing after …

Development Of A Determinant Scale Of Pharmacist’S Care For Herbal And Dietary Supplement Users, Mohd Shahezwan Abd Wahab

Chulalongkorn University Theses and Dissertations (Chula ETD)

Objective: There is a lack of instrument that is valid and reliable to measure the determinant of pharmacist's care (PCare) for herbal and dietary supplement (HDS) users. The present study aimed to develop scales to measure the determinant of PCare for HDS users and to quantify the practices. The study utilized qualitative and quantitative approaches. Methods: Three scales were developed: Direct TPB scale based on a modified Theory of Planned Behaviour (m-TPB) framework, Indirect TPB scale based on the m-TPB and beliefs elicited from community pharmacists (CPs), and PCare-HDS scale based on findings from the qualitative study. This study involved …

Taxonomy And Secondary Metabolites Of Selected Endophytic Actinomycete Strains, Nattakorn Kuncharoen

Chulalongkorn University Theses and Dissertations (Chula ETD)

A total of 50 endophytic actinomycetes isolated from fourteen plant species collected from six provinces of Thailand including Bangkok, Chachoengsao, Chiang Mai, Nakhon Pathom, Prachinburi and Suphan Buri were taxonomically studied relied on their phenotypic and chemotaxonomic characteristics, and the 16S rRNA gene sequence analysis. The isolates were identified as members of the family Streptomycetaceae involving Streptomyces (22 isolates), and the family Micromonosporaceae including Micromonospora (25 isolates), Plantactinospora (1 isolate) and Polymorphospora (1 isolate). Based on phenotypic characteristics, whole genome sequence analysis and DNA-DNA hybridization, 5 novel actinomycete species were proposed consisting of Micromonospora globbae (strain WPS1-2T), Micromonospora azadirachtae (strain …

Chemical Composition And In Vitro Anticancer Activity Of Okra (Albelmoschus Esculentus) Seed Extract To Develop Into Polymeric Micelles, Watcharaphong Chaemsawang

Chulalongkorn University Theses and Dissertations (Chula ETD)

The objective of this research was to study the phytochemical composition of the Okra seed extract and its in vitro anticancer activity for future pharmaceutical use. We detected active flavonoids compounds such as isoquercitrin, at an amount of 2.89 ± 1.64 % w/w. Furthermore, antioxidation testing by DPPH assay and ABTS assay, showed values of IC50 = 55.80 ug/ml and 49.04 ug/ml, respectively. The Okra seed extract’s anti-cancer activity was evaluated on cancer cell lines, indicating anticancer properties for certain forms of cancer such as cervical cancer (HeLa), liver cancer (HepG2), and most significantly for breast cancer (MCF-7). The mechanisms …

Alpha-Glucosidase Inhibitors From Dendrobium Scabrilingue, Chalermporn Sarakulwattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemical study of the methanol extract of the whole plant of Dendrobium scabrilingue Lindl. (Orchidaceae) resulted in the isolation of a new phenanthrene and a new bisbibenzyl namely dendroscabrols A and B, respectively, along with eight known compounds, identified as (Z)-ferulic acid tetracosyl ester, (E)-ferulic acid tetracosyl ester, gigantol, batatasin III, coelonin, aloifol I, lusianthridin and RF-3192C. The structures of these isolated compounds were determined mainly by spectroscopic data. All isolates were examined for alpha-glucosidase inhibitory activity. Dendroscabrol B and RF-3192C exhibited the most potent activity. In addition, dendroscabrol A, gigantol, coelonin and lusianthridin displayed strong activity compared with the …

Neuroprotective Effects Of The Standardized Extract Of Centella Asiatica Eca233 In Rotenone-Induced Parkinson’S Disease Model, Narudol Teerapattarakan

Chulalongkorn University Theses and Dissertations (Chula ETD)

The standardized extract of Centella asiatica ECa233 consists of asiaticoside and madecassoside. Previous studies reported various pharmacological effects of, ECa233, especially in the central nervous system disorders. The present study aimed to investigate the neuroprotective effects and protective mechanisms of ECa233 against rotenone-induced neurotoxicity in rats and in neuroblastoma SH-SY5Y cells. In animal study, male Wistar rats were divided into five experimental groups (n=10); control, PD, PD-ECa10, PD-ECa30, and PD-EC100. On days 1-20, control and PD rats received 0.5% carboxymethylcellulose (CMC) (1 mL/kg, p.o.) while ECa233 10, 30 and 100 mg/kg (p.o.) were given to PD-ECa10, PD-ECa30, and PD-EC100, respectively. …

Protective Effects Of Eriodictyol On Hydrogen Peroxide-Induced Cell Death In Sh-Sy5y Cells, Saowarose Thongin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Oxidative stress and mitochondrial dysfunction are the major causes of neuronal death in neurodegenerative disorders. Eriodictyol is a flavonoid extracted from the whole plant of Dendrobium ellipsophyllum (thai name: Ueang Thong). The antioxidant and anti-inflammatory effects of eriodictyol have been widely reported. The present study aimed to investigate the protective effect and mechanisms of eriodictyol on hydrogen peroxide (H2O2)-induced cell death in human neuroblastoma SH-SY5Y cells. The protective effect of eriodictyol on cytotoxicity induced by H2O2 was evaluated using resazurin assay. The effects on intracellular reactive oxygen species (ROS) and mitochondria membrane potential were evaluated by 2´-7’ dichlorodihydrofluorescein diacetate (DCFH-DA) …

Pharmacokinetic Study Of Cucurbitacin B From Trichosanthes Cucumerina L. In Rats, Natthaphon Hunsakunachai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cucurbitacin B is a triterpenoid, majorly found in Cucurbitaceae family, particularly in the Trichosanthes cucumerina L. fruits. The pharmacological properties of cucurbitacin B have been studied for decades, particularly an anti-tumor and anti-inflammatory activity. However, the pharmacokinetic profile of this compound is still limited and the investigation is needed for further pharmaceutical product development. This study aimed to investigate the pharmacokinetic profile of cucurbitacin B after administering the compound at different doses and routes to the rats. Male Wistar rats, weighed approximately 400-500 g, were treated with cucurbitacin B extracted from Trichosanthes cucumerina L. The cucurbitacin B was administered at …

Novel Regulatory Mechanisms Of Protein Kinase B On Apoptosis Susceptibility And Cancer Dedifferentiation, Arnatchai Maiuthed

Chulalongkorn University Theses and Dissertations (Chula ETD)

No abstract provided.