Displaying publications 41 - 60 of 210 in total

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  1. Jee YH, Ho WK, Park S, Easton DF, Teo SH, Jung KJ, et al.
    Int J Epidemiol, 2023 Jun 06;52(3):796-805.
    PMID: 36343017 DOI: 10.1093/ije/dyac206
    BACKGROUND: Polygenic risk scores (PRSs) for breast cancer, developed using European and Asian genome-wide association studies (GWAS), have been shown to have good discrimination in Asian women. However, prospective calibration of absolute risk prediction models, based on a PRS or PRS combined with lifestyle, clinical and environmental factors, in Asian women is limited.

    METHODS: We consider several PRSs trained using European and/or Asian GWAS. For each PRS, we evaluate the discrimination and calibration of three absolute risk models among 41 031 women from the Korean Cancer Prevention Study (KCPS)-II Biobank: (i) a model using incidence, mortality and risk factor distributions (reference inputs) among US women and European relative risks; (ii) a recalibrated model, using Korean reference but European relative risks; and (iii) a fully Korean-based model using Korean reference and relative risk estimates from KCPS.

    RESULTS: All Asian and European PRS improved discrimination over lifestyle, clinical and environmental (Qx) factors in Korean women. US-based absolute risk models overestimated the risks for women aged ≥50 years, and this overestimation was larger for models that only included PRS (expected-to-observed ratio E/O = 1.2 for women <50, E/O = 2.7 for women ≥50). Recalibrated and Korean-based risk models had better calibration in the large, although the risk in the highest decile was consistently overestimated. Absolute risk projections suggest that risk-reducing lifestyle changes would lead to larger absolute risk reductions among women at higher PRS.

    CONCLUSIONS: Absolute risk models incorporating PRS trained in European and Asian GWAS and population-appropriate average age-specific incidences may be useful for risk-stratified interventions in Korean women.

  2. Mohamad S, Isa NM, Muhammad R, Emran NA, Kitan NM, Kang P, et al.
    PLoS One, 2015;10(1):e0117104.
    PMID: 25629968 DOI: 10.1371/journal.pone.0117104
    CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population.
  3. Lim KP, Chun NA, Gan CP, Teo SH, Rahman ZA, Abraham MT, et al.
    Hum Vaccin Immunother, 2014;10(11):3214-23.
    PMID: 25483651 DOI: 10.4161/hv.29226
    The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic. Further, T cells stimulated with peptide-pulsed dendritic cells showed enhanced T-cell cytotoxic activity against MAGED4B-overexpressing OSCC cell lines. In summary, we have identified MAGED4B peptides that induce anti-tumor immune responses advocating that they could be further developed as vaccine candidates for the treatment of OSCC.
  4. Gan CP, Hamid S, Hor SY, Zain RB, Ismail SM, Wan Mustafa WM, et al.
    Head Neck, 2012 Mar;34(3):344-53.
    PMID: 21438066 DOI: 10.1002/hed.21734
    There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC.
  5. Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, et al.
    Oral Oncol, 2010 May;46(5):379-86.
    PMID: 20371203 DOI: 10.1016/j.oraloncology.2010.02.022
    Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.
  6. Ong CY, Ling SK, Ali RM, Chee CF, Samah ZA, Ho AS, et al.
    J. Photochem. Photobiol. B, Biol., 2009 Sep 4;96(3):216-22.
    PMID: 19647445 DOI: 10.1016/j.jphotobiol.2009.06.009
    One hundred and fifty-five extracts from 93 terrestrial species of plants in Peninsula Malaysia were screened for in vitro photo-cytotoxic activity by means of a cell viability test using a human leukaemia cell-line HL60. These plants which can be classified into 43 plant families are diverse in their type of vegetation and their natural habitat in the wild, and may therefore harbour equally diverse metabolites with potential pharmaceutical properties. Of these, 29 plants, namely three from each of the Clusiaceae, Leguminosae, Rutaceae and Verbenaceae families, two from the Piperaceae family and the remaining 15 are from Acanthaceae, Apocynaceae, Bignoniaceae, Celastraceae, Chrysobalanaceae, Irvingiaceae, Lauraceae, Lythraceae, Malvaceae, Meliaceae, Moraceae, Myristicaceae, Myrsinaceae, Olacaceae and Sapindaceae. Hibiscus cannabinus (Malvaceae), Ficus deltoidea (Moraceae), Maranthes corymbosa (Chrysobalanaceae), Micromelum sp., Micromelum minutum and Citrus hystrix (Rutaceae), Cryptocarya griffithiana (Lauraceae), Litchi chinensis (Sapindaceae), Scorodocarpus bornensis (Olacaceae), Kokoona reflexa (Celastraceae), Irvingia malayana (Irvingiaceae), Knema curtisii (Myristicaceae), Dysoxylum sericeum (Meliaceae), Garcinia atroviridis, Garcinia mangostana and Calophyllum inophyllum (Clusiaceae), Ervatamia hirta (Apocynaceae), Cassia alata, Entada phaseoloides and Leucaena leucocephala (Leguminosae), Oroxylum indicum (Bignoniaceae), Peronema canescens,Vitex pubescens and Premna odorata (Verbenaceae), Piper mucronatum and Piper sp. (Piperaceae), Ardisia crenata (Myrsinaceae), Lawsonia inermis (Lythraceae), Strobilanthes sp. (Acanthaceae) were able to reduce the in vitro cell viability by more than 50% when exposed to 9.6J/cm(2) of a broad spectrum light when tested at a concentration of 20 microg/mL. Six of these active extracts were further fractionated and bio-assayed to yield four photosensitisers, all of which are based on the pheophorbide-a and -b core structures. Our results suggest that the main photosensitisers from terrestrial plants are likely based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in minor amounts or are not as active as those with the cyclic tetrapyrrole structure.
  7. Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, et al.
    Oral Oncol, 2009 Aug;45(8):712-9.
    PMID: 19147396 DOI: 10.1016/j.oraloncology.2008.11.002
    Oral squamous cell carcinoma (OSCC) is a world health problem and is associated with exposure to different risk factors. In the west, smoking and alcohol consumption are considered to be the main risk factors whilst in India and southeast Asia, betel quid (BQ) chewing is predominant. In this study, we compared the gene expression patterns of oral cancers associated with BQ chewing to those caused by smoking using Affymetrix microarrays. We found that 281 genes were differentially expressed between OSCC and normal oral mucosa regardless of aetiological factors including MMP1, PLAU, MAGE-D4, GNA12, IFITM3 and NMU. Further, we identified 168 genes that were differentially expressed between the BQ and smoking groups including CXCL-9, TMPRSS2, CA12 and RNF24. The expression of these genes was validated using qPCR using independent tissue samples. The results demonstrate that whilst common genes/pathways contribute to the development of oral cancer, there are also other gene expression changes that are specific to certain risk factors. The findings suggest that different carcinogens activate or inhibit specific pathways during cancer development and progression. These unique gene expression profiles should be taken into consideration when developing biomarkers for future use in prognostic or therapeutic applications.
  8. Chai SJ, Yap YY, Foo YC, Yap LF, Ponniah S, Teo SH, et al.
    PLoS One, 2015;10(11):e0130464.
    PMID: 26536470 DOI: 10.1371/journal.pone.0130464
    Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9-20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.
  9. Lim KK, Yoon SY, Mohd Taib NA, Shabaruddin FH, Dahlui M, Woo YL, et al.
    Appl Health Econ Health Policy, 2018 06;16(3):395-406.
    PMID: 29572724 DOI: 10.1007/s40258-018-0384-8
    OBJECTIVE: Previous studies showed that offering BRCA mutation testing to population subgroups at high risk of harbouring the mutation may be cost effective, yet no evidence is available for low- or middle-income countries (LMIC) and in Asia. We estimated the cost effectiveness of BRCA mutation testing in early-stage breast cancer patients with high pre-test probability of harbouring the mutation in Malaysia, an LMIC in Asia.

    METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.

    RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.

    CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.

  10. Ariffin H, Chan AS, Oh L, Abd-Ghafar S, Ong GB, Mohamed M, et al.
    Clin Genet, 2015 Nov;88(5):450-5.
    PMID: 25318593 DOI: 10.1111/cge.12525
    Type of cancer and age of onset in individuals with inherited aberrations in the tumour suppressor gene TP53 are variable, possibly influenced by genetic modifiers and different environmental exposure. Since 2009, the modified Chompret criteria (MCC) have been used to identify individuals for TP53 mutation screening. Using the TP53 mutation database maintained by the International Agency for Research on Cancer (IARC), we investigated if the MCC, mainly developed for a Caucasian population, was also applicable in Asia. We identified several differences in Asian families compared with similar Caucasian cohorts, suggesting that identification and management of Li-Fraumeni syndrome in Asia do not completely mirror that of North America and Western Europe. Early gastric cancer (<40 years) may be considered a new addition to the MCC especially for Asian families.
  11. Balakrishnan N, Teo SH, Sinnadurai S, Bhoo Pathy NT, See MH, Taib NA, et al.
    World J Surg, 2017 11;41(11):2735-2745.
    PMID: 28653143 DOI: 10.1007/s00268-017-4081-9
    BACKGROUND: Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia.

    METHOD: A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics.

    RESULTS: Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5-year overall survival (OS) (66.9; 95% CI 60.2-73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36-0.77), 0.49 (95% CI 0.33-0.75), 0.61 (95% CI 0.43-0.85), and 0.64 (95% CI 0.44-0.93), respectively; P trend = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment.

    CONCLUSION: Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.

  12. Ng PS, Wen WX, Fadlullah MZ, Yoon SY, Lee SY, Thong MK, et al.
    Clin Genet, 2016 10;90(4):315-23.
    PMID: 26757417 DOI: 10.1111/cge.12735
    Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
  13. Soh WH, Rajaram N, Mariapun S, Eriksson M, Fadzli F, Ho WK, et al.
    Cancer Causes Control, 2018 Sep;29(9):883-894.
    PMID: 30062608 DOI: 10.1007/s10552-018-1064-6
    BACKGROUND: Physical activity is a modifiable lifestyle factor associated with reduced breast cancer risk. Mammographic density is a strong, independent risk factor for breast cancer, and some breast cancer risk factors have been shown to modify mammographic density. However, the effect of physical activity on mammographic density, studied predominantly among Caucasians, has yielded conflicting results. In this study, we examined, in an Asian population, the association between physical activity and mammographic density.

    METHODS: We conducted a cross-sectional study of 2,377 Malaysian women aged 40-74 years. Physical activity information was obtained at screening mammogram and mammographic density was measured from mammograms by the area-based STRATUS method (n = 1,522) and the volumetric Volpara™ (n = 1,200) method. Linear regression analyses were performed to evaluate the association between physical activity and mammographic density, adjusting for potential confounders.

    RESULTS: We observed that recent physical activity was associated with area-based mammographic density measures among postmenopausal women, but not premenopausal women. In the fully adjusted model, postmenopausal women with the highest level of recent physical activity had 8.0 cm2 [95% confidence interval: 1.3, 14.3 cm2] lower non-dense area and 3.1% [0.1, 6.3%] higher area-based percent density, compared to women with the lowest level of recent physical activity. Physical activity was not associated to volumetric mammographic density.

    CONCLUSIONS: Our findings suggest that the beneficial effects of physical activity on breast cancer risk may not be measurable through mammographic density. Future research is needed to identify appropriate biomarkers to assess the effect of physical activity on breast cancer risk.

  14. Malekbala MR, Soltani S, Abdul Rashid S, Abdullah LC, Rashid U, Nehdi IA, et al.
    Materials (Basel), 2020 Apr 10;13(7).
    PMID: 32290065 DOI: 10.3390/ma13071775
    In the present study, a sequence of experiments was performed to assess the influence of the key process parameters on the formation of a carbon nanofiber-coated monolith (CNFCM), using a four-level factorial design in response surface methodology (RSM). The effect of reaction temperature, hydrocarbon flow rate, catalyst and catalyst promoter were examined using RSM to enhance the formation yield of CNFs on a monolith substrate. To calculate carbon yield, a quadratic polynomial model was modified through multiple regression analysis and the best possible reaction conditions were found as follows: a reaction temperature of 800 °C, furfuryl alcohol flow of 0.08525 mL/min, ferrocene catalyst concentration of 2.21 g. According to the characterization study, the synthesized CNFs showed a high graphitization which were uniformly distributed on a monolith substrate. Besides this, the feasibility of carbon dioxide (CO2) adsorption from the gaseous mixture (N2/CO2) under a range of experimental conditions was investigated at monolithic column. To get the most out of the CO2 capture, an as-prepared sample was post-modified using ammonia. Furthermore, a deactivation model (DM) was introduced for the purpose of studying the breakthrough curves. The CO2 adsorption onto CNFCM was experimentally examined under following operating conditions: a temperature of 30-50 °C, pressure of 1-2 bar, flow rate of 50-90 mL/min, and CO2 feed amount of 10-40 vol.%. A lower adsorption capacity and shorter breakthrough time were detected by escalating the temperature. On the other hand, the capacity for CO2 adsorption increased by raising the CO2 feed amount, feed flow rate, and operating pressure. The comparative evaluation of CO2 uptake over unmodified and modified CNFCM adsorbents confirmed that the introduced modification procedure caused a substantial improvement in CO2 adsorption.
  15. Lai KN, Ho WK, Kang IN, Kang PC, Phuah SY, Mariapun S, et al.
    BMC Cancer, 2017 02 22;17(1):149.
    PMID: 28222693 DOI: 10.1186/s12885-017-3099-6
    BACKGROUND: Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach.

    METHODS: The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history.

    RESULTS: Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06).

    CONCLUSIONS: Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

  16. Lee DS, Meiser B, Mariapun S, Hassan T, Yip CH, Mohd Taib NA, et al.
    J Genet Couns, 2021 Jun;30(3):720-729.
    PMID: 33245177 DOI: 10.1002/jgc4.1360
    The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty-seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi-structured interview guide. Fifty-six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first- and second-degree relatives were informed by the proband about the testing result and that 11.5% of eligible first- and second-degree relatives had genetic testing. First-degree relatives were more likely to have been informed and tested compared to second-degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second-degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes.
  17. Teo SH, Ong TK, Merican AM, Hashim MS, Ng WM, Al-Fayyadh MZM, et al.
    Indian J Orthop, 2023 Jun;57(6):847-855.
    PMID: 37214363 DOI: 10.1007/s43465-023-00874-x
    BACKGROUND: Accurate planning for patellar instability correction is important in obtaining good post-operative outcome. The main challenge in the current two-dimensional (2-D) computed tomographic (CT) scans method is the difficulty in choosing reliable bony landmarks. This study aimed to compare the reliabilities between the 2-D and three-dimensional (3-D) methods of measuring tibial tubercle-trochlear groove (TT-TG) distance. We hypothesize that the proposed 3-D method will result in measurements with narrower error margin, providing higher reliability and accuracy.

    MATERIALS AND METHODS: We traced CT scans of 106 knees with no patellofemoral pathology from 59 subjects from the database system and converted all 2-D images into 3-D models to determine the values for each parameter. We compared the intra- and interobserver reliability of each method using intraclass correlation (ICC) and Bland-Altman method.

    RESULTS: The values of TT-TG measured by 2-D and 3-D methods were 16.1 ± 4.6 mm and 16.2 ± 4.2 mm, respectively. The ICC values of both methods were comparable (95% limits of agreement between the same observer: - 3.3 to 3.8 mm versus - 2.4 to 2.7 mm and different observers: - 4.3 to 4.9 mm versus - 3.9 to 2.7 mm), with 3-D method results in narrower limits of agreement.

    CONCLUSION: TT-TG measurement is reliable using the 2-D method without using advanced radiographic software. The 3-D method of measuring TT-TG provides measurement with narrower variation when compared with the 2-D method. However, both TT-TG distances' measurement methods in the current study were comparable as the variations are not significant.

  18. Islam A, Teo SH, Ahmed MT, Khandaker S, Ibrahim ML, Vo DN, et al.
    Chemosphere, 2021 Jun;272:129653.
    PMID: 33486455 DOI: 10.1016/j.chemosphere.2021.129653
    The contamination of groundwater by arsenic (As) in Bangladesh is the biggest impairing of a population, with a large number of peoples affected. Specifically, groundwater of Gangetic Delta is alarmingly contaminated with arsenic. Similar, perilous circumstances exist in many other countries and consequently, there is a dire need to develop cost-effective decentralized filtration unit utilizing low-cost adsorbents for eliminating arsenic from water. Morphological synthesis of carbon with unique spherical, nanorod, and massive nanostructures were achieved by solvothermal method. Owing to their intrinsic adsorption properties and different nanostructures, these nanostructures were employed as adsorption of arsenic in aqueous solution, with the purpose to better understanding the morphological effect in adsorption. It clearly demonstrated that carbon with nanorods morphology exhibited an excellent adsorption activity of arsenite (about 82%) at pH 3, remarkably superior to the two with solid sphere and massive microstructures, because of its larger specific surface area, enhanced acid strength and improved adsorption capacity. Furthermore, we discovered that iron hydroxide radicals and energy-induced contact point formation in nanorods are the responsible for the high adsorption of As in aqueous solution. Thus, our work provides insides into the microstructure-dependent capability of different carbon for As adsorption applications.
  19. Gan CP, Patel V, Mikelis CM, Zain RB, Molinolo AA, Abraham MT, et al.
    Oncotarget, 2014 Oct 30;5(20):9626-40.
    PMID: 25275299
    Oral squamous cell carcinoma (OSCC) has a propensity to spread to the cervical lymph nodes (LN). The presence of cervical LN metastases severely impacts patient survival, whereby the two-year survival for oral cancer patients with involved LN is ~30% compared to over 80% in patients with non-involved LN. Elucidation of key molecular mechanisms underlying OSCC metastasis may afford an opportunity to target specific genes, to prevent the spread of OSCC and to improve patient survival. In this study, we demonstrated that expression of the heterotrimeric G-protein alpha-12 (Gα12) is highly up-regulated in primary tumors and LN of OSCC patients, as assessed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). We also found that exogenous expression of the constitutively activated-form of Gα12 promoted cell migration and invasion in OSCC cell lines. Correspondingly, inhibition of Gα12 expression by shRNA consistently inhibited OSCC cell migration and invasion in vitro. Further, the inhibition of G12 signaling by regulator of G-protein signaling (RGS) inhibited Gα12-mediated RhoA activation, which in turn resulted in reduced LN metastases in a tongue-orthotopic xenograft mouse model of oral cancer. This study provides a rationale for future development and evaluation of drug candidates targeting Gα12-related pathways for metastasis prevention.
  20. Phuah SY, Lee SY, Kang P, Kang IN, Yoon SY, Thong MK, et al.
    PLoS One, 2013;8(8):e73638.
    PMID: 23977390 DOI: 10.1371/journal.pone.0073638
    The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.
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