EXPLORING WNT REGULATION IN GLIOMA-PROPAGATING CELLS, AND WNT INHIBITION AS A THERAPEUTIC STRATEGY

Ph.DDOCTOR OF PHILOSOPH

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Cryopreservation of Neurospheres Derived from Human Glioblastoma Multiforme

Cancer stem cells have been shown to initiate and sustain tumor growth. In many instances, clinical material is limited, compounded by a lack of methods to preserve such cells at convenient time points. Although brain tumor-initiating cells grown in a spheroid manner have been shown to maintain their integrity through serial transplantation in immune-compromised animals, practically, it is not always possible to have access to animals of suitable ages to continuously maintain these cells. We therefore explored vitrification as a cryopreservation technique for brain tumor-initiating cells. Tumor neurospheres were derived from five patients with glioblastoma multiforme (GBM). Cryopreservation in 90% serum and 10% dimethyl sulfoxide yielded greatest viability and could be explored in future studies. Vitrification yielded cells that maintained self-renewal and multipotentiality properties. Karyotypic analyses confirmed the presence of GBM hallmarks. Upon implantation into NOD/SCID mice, our vitrified cells reformed glioma masses that could be serially transplanted. Transcriptome analysis showed that the vitrified and nonvitrified samples in either the stem-like or differentiated states clustered together, providing evidence that vitrification does not change the genotype of frozen cells. Upon induction of differentiation, the transcriptomes of vitrified cells associated with the original primary tumors, indicating that tumor stem-like cells are a genetically distinct population from the differentiated mass, underscoring the importance of working with the relevant tumor-initiating population. Our results demonstrate that vitrification of brain tumor-initiating cells preserves the biological phenotype and genetic profiles of the cells. This should facilitate the establishment of a repository of tumor-initiating cells for subsequent experimental designs

The development and validation of the Satisfaction Questionnaire for Osteoporosis Prevention in Malaysia

Purpose: To develop and validate the English version of the Satisfaction Questionnaire for Osteoporosis Prevention (SQOP) in Malaysia.Methods: The SQOP was modified from the Osteoporosis Patient Satisfaction Questionnaire and developed based on literature review and patient interviews. Face and content validity were established via an expert panel. The SQOP consists of two sections: clinical services and types of counseling. There were 23 items in total, each with a five-point Likert-type response. Satisfaction score was calculated by converting the total score to a percentage. A higher score indicates higher satisfaction. English speaking, non-osteoporotic, postmenopausal women aged ≥50 years were included in the study. Participants were randomized to either the control or intervention group. Intervention participants were provided counseling, whereas control participants received none. Participants answered the SQOP at baseline and 2 weeks later.Results: A total of 140 participants were recruited (control group: n=70; intervention group: n=70). No significant differences were found in any demographic aspects. Exploratory factor analysis extracted seven domains. Cronbach’s a for the domains ranged from 0.531–0.812. All 23 items were highly correlated using Spearman’s correlation coefficient 0.469–0.996 (

Entrepreneur : a study of personality in the local context

The main objective of this paper is to determine whether entrepreneurs exhibit a common set of personalities. In that sense, we are attempting to determine, via controlled questionnaires, if entrepreneurs in general are similar in terms of personality traits. The traits that we are particularly interested in are locus of control, independence, risk-taking, Machiavellianism, need for achievement, and assertiveness.ACCOUNTANC

Quality management : does it really pay?

This is an empirical study on publicly available data that sought to investigate the possible existence of relationship between Quality Management (TQM) and common stock performance. The earlier part of the text describes how and why much emphasis has been placed on the Quality Management, as well as providing a probable explanation for such a phenomenon. The latter half of the report records the detailed statistical test methods, where the realised residuals of the sample stock returns are regressed against the SESALL share index over a period of 24 months. The final portion of the text summarizes the findings of the Chi-Square as well as the Student T tests conducted, before concluding that there exists a positive relationship between TQM and common stock performance.BUSINES

EPIGENETICS OF HEPATOCELLULAR CARCINOMA.

10.1186/s40169-019-0230-08113

A multiple case study of homegrown franchising in Singapore from the franchisors' perspective

The purpose of this project is to appraise the procedures involved in setting up homegrown franchises. Factors necessary to the success of a franchise are looked into. Problems encountered by the franchisors are also discussed and plausible reasons for their existence are dealt with. Specifically, the aim is to understand the entrepreneurial process and to analyse the problems, pros and cons and the elements of success of homegrown franchising.ACCOUNTANC

Capitalizing on Synthetic Lethality of MYC to Treat Cancer in the Digital Age

10.1016/j.tips.2020.11.014Trends in Pharmacological Sciences423166-18