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Proteome Heterogeneity in Colorectal Cancer

Lim LC, Lim YM

Proteomics, 2018 02;18(3-4).
PMID: 29316255 DOI: 10.1002/pmic.201700169

Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.
Ethnic differences in quality of life in adolescents among Chinese, Malay and Indians in Singapore

Ng TP, Lim LC, Jin A, Shinfuku N

Qual Life Res, 2005 Sep;14(7):1755-68.
PMID: 16119186

BACKGROUND: Health-related quality of life in adolescents and ethnic and cultural differences are not well characterized. We used the Quality of Life Questionnaire for Adolescents (QOLQA) to examine ethnic differences in reported QOL scores among Chinese, Malay and Indian ethnicities in Singapore.
METHODS: The 70-item QOLQA measuring five QOL domains (physical, psychological, independence, social and environmental) was administered to a random sample of 1363 school-children aged 10-15 years, representative of the ethnic composition of Singapore adolescents (Chinese 72%, Malays 20% and Indians 8%).
RESULTS: Indians reported the highest overall QOL (mean 3.71 +/- SD 0.54) compared to Chinese (3.59 +/- 0.43), p < 0.05, and Malays (3.58 +/- 0.44), p < 0.05. In particular, Indians had significantly higher psychological QOL scores (3.73 +/- 0.61) compared to Chinese (3.55 +/- 0.54), p < 0.01. On the other hand, Chinese scored highest on physical and independence domains (3.97 +/- 0.54), p < 0.01 compared to Malays (3.82 +/- 0.55). There were no statistically significant gender differences in QOL scores. QOL declined significantly from age 10 to 15 for overall score, psychological, physical (p < 0.01) and environmental (p < 0.05). Lower socio-economic status and the self-report of a significant health problem were significantly associated with lower overall QOL and most domains. These ethnic differences persisted after adjusting for differences in socio-economic and health status. Psychometric properties and known group construct validity appeared to be similar across different ethnic groups, but compared to Chinese (r = 0.39) or Malays (r = 0.39), Indians showed a higher correlation of psychological scores with physical score (r = 0.59) and with other domain scores.
CONCLUSION: Significant ethnic differences in reported adolescent quality of life among Chinese, Malays and Indians in Singapore that are independent of socioeconomic and health status suggest important cultural differences.
Activated protein C resistance: a study among 60 thromboembolic patients in the Singapore population

Lim LC, Tan HH, Lee LH, Tien SL, Abdul Ghafar A

Ann Acad Med Singap, 1999 Mar;28(2):252-5.
PMID: 10497677

Resistance to activated protein C (APC-R) is the commonest inherited cause of thrombosis among Caucasians. Few studies have been carried out on its prevalence in Asians. We conducted a prospective study on 60 patients with thromboembolism to determine its prevalence in our local population. The Factor V Leiden (VaQ506) mutation associated with this condition was detected by amplification of the Factor V gene by polymerase chain reaction (PCR) and digestion of the fragment with Mnl I. Three patients were found to be heterozygous for this mutation. None of the 3 patients had other concomitant hypercoagulable states. In addition, we studied the prevalence of this condition in Malays which was found to be 0.5%. Our study suggests that the incidence of APC-R is much lower here compared to the West.
Molecular tissue profiling by MALDI imaging: recent progress and applications in cancer research

Lee PY, Yeoh Y, Omar N, Pung YF, Lim LC, Low TY

Crit Rev Clin Lab Sci, 2021 11;58(7):513-529.
PMID: 34615421 DOI: 10.1080/10408363.2021.1942781

Matrix-assisted laser desorption/ionization (MALDI) imaging is an emergent technology that has been increasingly adopted in cancer research. MALDI imaging is capable of providing global molecular mapping of the abundance and spatial information of biomolecules directly in the tissues without labeling. It enables the characterization of a wide spectrum of analytes, including proteins, peptides, glycans, lipids, drugs, and metabolites and is well suited for both discovery and targeted analysis. An advantage of MALDI imaging is that it maintains tissue integrity, which allows correlation with histological features. It has proven to be a valuable tool for probing tumor heterogeneity and has been increasingly applied to interrogate molecular events associated with cancer. It provides unique insights into both the molecular content and spatial details that are not accessible by other techniques, and it has allowed considerable progress in the field of cancer research. In this review, we first provide an overview of the MALDI imaging workflow and approach. We then highlight some useful applications in various niches of cancer research, followed by a discussion of the challenges, recent developments and future prospect of this technique in the field.
Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics

Tan YY, Yap PK, Xin Lim GL, Mehta M, Chan Y, Ng SW, et al.

Chem Biol Interact, 2020 Sep 25;329:109221.
PMID: 32768398 DOI: 10.1016/j.cbi.2020.109221

Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy.
Results of a real-world study on vortioxetine in patients with major depressive disorder in South East Asia (REVIDA)

Chin CN, Zain A, Hemrungrojn S, Ung EK, Kwansanit P, Au Yong KC, et al.

Curr Med Res Opin, 2018 11;34(11):1975-1984.
PMID: 29768955 DOI: 10.1080/03007995.2018.1477746

OBJECTIVE: The REVIDA study aimed to assess the evolution of major depression symptoms in South East Asian (SEA) patients treated with vortioxetine for major depression in real-world clinical practice.
METHODS: This non-interventional study was conducted from August 2016 to April 2017. A total of 138 patients (aged 18-65 years) with an active episode of major depression were recruited from Malaysia, Philippines, Singapore and Thailand. Vortioxetine was initiated on the first visit and patients were followed for 3 months. Depression severity was assessed using the PHQ-9 questionnaire (patient assessed) and CGI-S scale (physician assessed); cognitive function was assessed with the PDQ-D questionnaire; work productivity and activity impairment (WPAI) was assessed with the WPAI questionnaire.
RESULTS: At baseline, 89.9% of patients were moderately to severely depressed (PHQ-9 score ≥10). During the 3 month treatment period, mean ± SD PHQ-9 score decreased from 18.7 ± 5.7 to 5.0 ± 5.3, mean ± SD CGI-S score decreased from 4.4 ± 0.7 to 2.2 ± 1.1 and mean ± SD PDQ-D score decreased from 42.1 ± 18.8 to 13.4 ± 13.0. By Month 3, response and remission rates reached 80.8% and 59.0%, respectively. Work productivity loss decreased from 73.6% to 30.5%, while activity impairment decreased from 71.5% to 24.6%. Positive correlations were observed between PHQ-9, PDQ-D, and WPAI work productivity loss and activity impairment. By Month 3, 82.0% of patients were either not depressed or only mildly depressed (PHQ-9 score ≤9).
CONCLUSION: In real-world clinical settings, vortioxetine was effective in reducing depression severity and improving cognitive function and work productivity in SEA patients with major depression.
EtOH-LN cryoembedding workflow to minimize freezing artifact in frozen tissues: A pilot study in preparing tissues compatible with mass spectrometry-based spatial proteomics application

Tan YC, Mustangin M, Rosli N, Wan Ahmad Kammal WSE, Md Isa N, Low TY, et al.

Cryobiology, 2024 Mar;114:104843.
PMID: 38158171 DOI: 10.1016/j.cryobiol.2023.104843

Coolant-assisted liquid nitrogen (LN) flash freezing of frozen tissues has been widely adopted to preserve tissue morphology for histopathological annotations in mass spectrometry-based spatial proteomics techniques. However, existing coolants pose health risks upon inhalation and are expensive. To overcome this challenge, we present our pilot study by introducing the EtOH-LN workflow, which demonstrates the feasibility of using 95 % ethanol as a safer and easily accessible alternative to existing coolants for LN-based cryoembedding of frozen tissues. Our study reveals that both the EtOH-LN and LN-only cryoembedding workflows exhibit significantly reduced freezing artifacts compared to cryoembedding in cryostat (p