Undergraduate-community Engagement: Evidence from UiTM Sarawak

Undergraduate-Community engagement is a form of experiential education in which students engage in activities that address human and community needs. In Malaysia, most undergraduates have at one point or another taken part in community engagement activities. However, the outcome of participating in community engagement has not been properly measured. This study was conducted to investigate the benefits undergraduates gain as a result of community engagement experience, as there is limited studies done in the Malaysian context. This study adopted Student Community Engagement Benefits Questionnaire (SCEBQ) by Chung and Coates (2016). SCEBQ has four benefit constructs, namely career skills, diversity skills, interpersonal skills and civic skills. A total of 143 responses were analysed and results showed that female undergraduates, those who participated in voluntary projects and respondents between 21 to 23 years old reported higher mean gains across the four benefit constructs. Nevertheless, these mean gains did not show any statistically significant difference between gender, community engagement projects types, except age groups. The study is important as it lays the foundation in the process of creating a better understanding of what students learn outside the classroom and it contributes to the practical knowledge of undergraduate-community engagement experience in the context of Malaysian higher education

Undergraduate-community engagement: Evidence from UiTM Sarawak / Ellen Chung and Vloreen Nity Mathew

Undergraduate-Community engagement is a form of experiential education in which students engage in activities that address human and community needs. In Malaysia, most undergraduates have at one point or another taken part in community engagement activities. However, the outcome of participating in community engagement has not been properly measured. This study was conducted to investigate the benefits undergraduates gain as a result of community engagement experience, as there is limited studies done in the Malaysian context. This study adopted Student Community Engagement Benefits Questionnaire (SCEBQ) by Chung and Coates (2016). SCEBQ has four benefit constructs, namely career skills, diversity skills, interpersonal skills and civic skills. A total of 143 responses were analysed and results showed that female undergraduates, those who participated in voluntary projects and respondents between 21 to 23 years old reported higher mean gains across the four benefit constructs. Nevertheless, these mean gains did not show any statistically significant difference between gender, community engagement projects types, except age groups. The study is important as it lays the foundation in the process of creating a better understanding of what students learn outside the classroom and it contributes to the practical knowledge of undergraduate-community engagement experience in the context of Malaysian higher education

The random walk behaviour of Malaysian stock market : Evidence from individual stocks

This study re-examines the price behaviour of 77 individual stocks listed on Bursa Malaysia in light of the random walk hypothesis. With a new statistical tool, namely the Brock-Dechert-Scheinkman( BDS) test, it is possible to detect a more complex form of dependencies in series of financial returns that often appear completely random to standard statistical tests, such as serial correlation tests, runs test, variance ratio test and unit root tests. Our econometric results reveal that the market in general as proxied by the KLCI and all the 77 individual stocks do not follow a random walk process. This conclusion holds even when the sample period is broken down into two sub-periods with the exception of five stocks- IOICorp, KLK, MUllnd, Pos Hldgs and Tchong. The price behaviour of these five stocks in the sub-periods before and during the crisis provides empirical support to our conjecture that the Asian financial crisis in 1997 adversely affected the market's ability to price stocks efficiently, thus preventing stock prices from following a random walk process

Imaging PARP with [18F]rucaparib in pancreatic cancer models

PURPOSE: Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an 18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [18F]rucaparib in human pancreatic cancer models. METHOD: We incorporated the positron-emitting 18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models. RESULTS: Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib. In vivo studies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding. CONCLUSION: Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers

[123I]CC1:A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [ 123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer.Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [ 123I]CC1. The level and specificity of cell uptake and the therapeutic efficacy of [ 123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [ 123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG).Results: In vitro and in vivo studies showed selective uptake of [ 123I]CC1 in all models. Significantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10 Bq [ 123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [ 123I]CC1 (3 MBq) was able to significantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [ 123I]CC1 did not cause significant toxicity to normal tissues.Conclusion: Taken together, these results show the potential of [ 123I]CC1 as a radioligand therapy for PARP-expressing cancers. </p

[123I]CC1:A PARP-Targeting, Auger Electron-Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Poly(adenosine diphosphate ribose) polymerase (PARP) has emerged as an effective therapeutic strategy against cancer that targets the DNA damage repair enzyme. PARP-targeting compounds radiolabeled with an Auger electron-emitting radionuclide can be trapped close to damaged DNA in tumor tissue, where high ionizing potential and short range lead Auger electrons to kill cancer cells through the creation of complex DNA damage, with minimal damage to surrounding normal tissue. Here, we report on [ 123I]CC1, an 123I-labeled PARP inhibitor for radioligand therapy of cancer.Methods: Copper-mediated 123I iododeboronation of a boronic pinacol ester precursor afforded [ 123I]CC1. The level and specificity of cell uptake and the therapeutic efficacy of [ 123I]CC1 were determined in human breast carcinoma, pancreatic adenocarcinoma, and glioblastoma cells. Tumor uptake and tumor growth inhibition of [ 123I]CC1 were assessed in mice bearing human cancer xenografts (MDA-MB-231, PSN1, and U87MG).Results: In vitro and in vivo studies showed selective uptake of [ 123I]CC1 in all models. Significantly reduced clonogenicity, a proxy for tumor growth inhibition by ionizing radiation in vivo, was observed in vitro after treatment with as little as 10 Bq [ 123I]CC1. Biodistribution at 1 h after intravenous administration showed PSN1 tumor xenograft uptake of 0.9 ± 0.06 percentage injected dose per gram of tissue. Intravenous administration of a relatively low amount of [ 123I]CC1 (3 MBq) was able to significantly inhibit PSN1 xenograft tumor growth but was less effective in xenografts that expressed less PARP. [ 123I]CC1 did not cause significant toxicity to normal tissues.Conclusion: Taken together, these results show the potential of [ 123I]CC1 as a radioligand therapy for PARP-expressing cancers. </p

Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent

PURPOSE: Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first 18F-labelled ATM inhibitor [18F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics. METHODS: Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [18F]fluoride. Uptake of [18F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with shRNA to reduce expression of ATM. Blocking studies using several non-radioactive ATM inhibitors assessed binding specificity to ATM. In vivo biodistribution studies were performed in wild-type and ATM-knockout C57BL/6 mice using PET/CT and ex vivo analysis. Uptake of [18F]1 in H1299 tumour xenografts was assessed in BALB/c nu/nu mice. RESULTS: Nitro-precursor 2 was synthesised with an overall yield of 12%. Radiofluorination of 2 achieved radiochemically pure [18F]1 in 80 ± 13 min with a radiochemical yield of 20 ± 13% (decay-corrected) and molar activities up to 79.5 GBq/μmol (n = 11). In vitro, cell-associated activity of [18F]1 increased over 1 h, and retention of [18F]1 dropped to 50% over 2 h. [18F]1 uptake did not correlate with ATM expression, but could be reduced significantly with an excess of known ATM inhibitors, demonstrating specific binding of [18F]1 to ATM. In vivo, fast hepatobiliary clearance was observed with tumour uptake ranging 0.13-0.90%ID/g after 1 h. CONCLUSION: Here, we report the first radiofluorination of an ATM inhibitor and its in vitro and in vivo biological evaluations, revealing the benefits but also some limitations of 18F-labelled ATM inhibitors