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Tributyltin distribution in the coastal environment of Peninsular Malaysia

Tong SL, Pang FY, Phang SM, Lai HC

Environ Pollut, 1996;91(2):209-16.
PMID: 15091442

The occurrence of tributyltin (TBT) is reported in the coastal waters of a few selected sites in Peninsular Malaysia. Water, bivalves and sediment samples collected were analysed specifically for TBT using sensitive analytical methods which involved a solvent extraction procedure with appropriate clean-up followed by graphite furnace atomic absorption spectrometric measurements. The levels of TBT in the seawater in unexposed areas were found in the range from <3.4 to 20 ng litre(-1) as compared to coastal areas with high boat and ship activities where TBT levels in seawater were generally above 30 ng litre(-1), with the highest level found at 281.8 ng litre(-1). TBT levels in the tissues of random cockle and soft-shell clam samples from local markets were found in the range from <0.5 to 3.7 ng g(-1) wet weight. The levels of TBT found in green mussel samples both from the market (23.5 ng g(-1) wet weight) and those from a mussel farm (14.2 ng g(-1) wet weight) indicate slight accumulation of TBT. In sediments, TBT levels were found ranging from <0.7 ng g(-1) dry weight in unexposed coastal sites to as high as 216.5 ng g(-1) dry weight for a site within a port area.
Fulltext COVID-19 pandemic and unemployment rate: A hybrid unemployment rate prediction approach for developed and developing countries of Asia

Lai H, Khan YA, Thaljaoui A, Chammam W, Abbas SZ

Soft comput, 2021 May 19.
PMID: 34025212 DOI: 10.1007/s00500-021-05871-6

Unemployment remains a serious issue for both developed and developing countries and a driving force to lose their monetary and financial impact. The estimation of the unemployment rate has drawn researchers' attention in recent years. This investigation's key objective is to inquire about the impact of COVID-19 on the unemployment rate in selected, developed and developing countries of Asia. For experts and policymakers, effective prediction of the unemployment rate is an influential test that assumes an important role in planning the monetary and financial development of a country. Numerous researchers have recently utilized conventional analysis tools for unemployment rate prediction. Notably, unemployment data sets are nonstationary. Therefore, modeling these time series by conventional methods can produce an arbitrary mistake. To overcome the accuracy problem associated with conventional approaches, this investigation assumes intelligent-based prediction approaches to deal with the unemployment data and to predict the unemployment rate for the upcoming years more precisely. These intelligent-based unemployment rate strategies will force their implications by repeating diversity in the unemployment rate. For illustration purposes, unemployment data sets of five advanced and five developing countries of Asia, essentially Japan, South Korea, Malaysia, Singapore, Hong Kong, and five agricultural countries (i.e., Pakistan, China, India, Bangladesh and Indonesia) are selected. The hybrid ARIMA-ARNN model performed well among all hybrid models for advanced countries of Asia, while the hybrid ARIMA-ANN outperformed for developing countries aside from China, and hybrid ARIMA-SVM performed well for China. Furthermore, for future unemployment rate prediction, these selected models are utilized. The result displays that in developing countries of Asia, the unemployment rate will be three times higher as compared to advanced countries in the coming years, and it will take double the time to address the impacts of Coronavirus in developing countries than in developed countries of Asia.
Asian venous thromboembolism guidelines: updated recommendations for the prevention of venous thromboembolism

Liew NC, Alemany GV, Angchaisuksiri P, Bang SM, Choi G, DE Silva DA, et al.

Int Angiol, 2017 Feb;36(1):1-20.
PMID: 27606807 DOI: 10.23736/S0392-9590.16.03765-2

The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.
Knockdown of c-MET induced apoptosis in ABCB1-overexpressed multidrug-resistance cancer cell lines

Hung TH, Li YH, Tseng CP, Lan YW, Hsu SC, Chen YH, et al.

Cancer Gene Ther, 2015 May;22(5):262-70.
PMID: 25908454 DOI: 10.1038/cgt.2015.15

Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells. Moreover, leukemia cell lines overexpressing ABCB1 have also been shown to be more resistant to the tyrosine kinase inhibitor imatinib mesylate. These findings suggest that chemoresistant cancer cells may also develop a similar mechanism against chemotherapy agents. To circumvent clinical complications arising from drug resistance during cancer therapy, the present study was designed to investigate apoptosis induction in ABCB1-overexpressed cancer cells using c-MET-targeted RNA interference technology in vitro and in vivo. The results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner. In vivo reduction of tumor volume in mice harboring c-MET shRNA-knockdown MES-SA/Dx5 cells was clearly demonstrated. Our study demonstrated that downregulation of c-MET by shRNA-induced apoptosis in a multidrug resistance cell line.
Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma

Jeon AJ, Teo YY, Sekar K, Chong SL, Wu L, Chew SC, et al.

BMC Cancer, 2023 Feb 03;23(1):118.
PMID: 36737737 DOI: 10.1186/s12885-022-10444-3

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).
METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples.
RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.
DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.
Fulltext A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory

Chen J, Kaya NA, Zhang Y, Kendarsari RI, Sekar K, Lee Chong S, et al.

J Hepatol, 2024 May 21.
PMID: 38782118 DOI: 10.1016/j.jhep.2024.05.017

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies.
METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients.
RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival.
CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories.
IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making.
CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).