Displaying publications 41 - 60 of 90 in total

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  1. Fulltext Field trials on the management of scabies in Jengka Triangle, Pahang
    Kaur GA, Nadeswary K
    Med J Malaysia, 1980 Sep;35(1):14-21.
    PMID: 6166839
    A study was carried out in theJengka Triangle in Pahang to find out the prevalence and a practical cum effective method of treatment and control of scabies. Scabies was the commonest skin lesion among the 5590 people examined. its prevalence being 11.6%. Both sexes were equally affected. Prevalence was high among children and teenagers, the worst affected being the 10 to 14. 2 to 4, 15 to 19 and 5 to 9 year olds. The problem of scabies in Jengka could be due to inadequate and irregular water supply, plus lack of mothers' supervision of the personal hygiene of their children aged > 2 years. The persistence of scabies since 1976 is very likely due to the people's non-compliance with standing instructions on treatment with Benzyl benzoate emulsion A comparative study of treatment of scabies with Gamma Benzene Hexachloride [GBH] and with Benzyl benzoate emulsion [BBE] showed GBH to be the medication of choice. It was more effective and convenient, giving 97.9% cure rate with one application. A hot bath was not necessary. The patients preferred GBH to BBE since it was painless and without side-effects. The cost of treatment with GBH [1 application] was also much less than that with BBE [2 applications]. Only 28.7% of the cases and contacts complied with instructions to do 2nd application of the medication on their own, making it imperative that application be done by the health Staff or under their direct supervision. The majority [87.2%] complied with instructions to place their used clothes in large polythene bags and air these in the sun for two days. This procedure should replace the instructions to boil personal clothes as it is just as effective. yet more convenient and economical. A regular, biannual screening of all kindergarten and primary school children is recommended. Application of GBH to all scabies cases and all close contacts should be done by the health worker. The whole body from neck to soles of feet should have the application, and the people should be instructed to bathe only after 24 hours. They are to go to the nearest clinic or hospital on the 7th day for second application of GBH, if the itchness or lesions persist or reappear. Such supervised medication is possible and will minimise misuse of GBH.
  2. Prevalence and correlates of depression among adolescents in Malaysia
    Kaur J, Cheong SM, Mahadir Naidu B, Kaur G, Manickam MA, Mat Noor M, et al.
    Asia Pac J Public Health, 2014 Sep;26(5 Suppl):53S-62S.
    PMID: 25070697 DOI: 10.1177/1010539514544356
    Depression among adolescents has been recognized as a major public health issue. The objective of this study was to determine the prevalence and correlates of depression among school-going adolescents in Malaysia. Data from the Malaysia Global School-based Health Survey (GSHS) 2012 were analyzed with additional data from the validated DASS21 (Depression, Anxiety, and Stress) questionnaire. The study revealed that 17.7% of respondents had depressive symptoms. Multivariate analysis further showed that feeling lonely (adjusted odds ratio [aOR] = 2.99; 95% CI = 2.57-3.47), Indian ethnicity (aOR = 2.00; 95% CI = 1.63-2.44), using drugs (aOR = 1.85; 95% CI = 1.21-2.82), and being bullied (aOR = 1.79; 95% CI = 1.60-1.99) were significantly associated with depressive symptoms. Lack of parental supervision, alcohol use, and tobacco use were also significant risk factors. Addressing depressive symptoms among adolescents may have implications for managing their risks of being bullied and substance use. This study also highlights the need to further investigate depressive symptoms among adolescents of Indian ethnicity.
    Study name: Global School-Based Student Health Survey (GSHS)
  3. Predictors of physical inactivity among elderly malaysians: recommendations for policy planning
    Kaur J, Kaur G, Ho BK, Yao WK, Salleh M, Lim KH
    Asia Pac J Public Health, 2015 Apr;27(3):314-22.
    PMID: 24425796 DOI: 10.1177/1010539513517257
    Physical inactivity is the fourth leading risk factor for global mortality. Regular moderate-intensity physical activity has significant benefits for health. To determine the socioeconomic predictors of physical inactivity among elderly Malaysian population. A nationwide community-based survey was conducted among 4831 respondents aged ≥60 years with a face-to-face questionnaire. The prevalence of physical inactivity among the elderly was 88.0%, highest in respondents aged older than 80 years (95.4%), females (90.1%), other Bumiputra (92.2%), earning household income less than RM1000 (87.9%), and residing in urban locality (88.4%). In the multivariate model, the predictors of physical inactivity were only sex, ethnicity, locality, and age group (adjusted odds ratio = 1.3-3.6). The predictors of physical inactivity can identify the risk factors to develop policies that will reduce the public health burden of noncommunicable diseases.
  4. Fulltext Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression
    Kumarasamy G, Ismail MN, Tuan Sharif SE, Desire C, Mittal P, Hoffmann P, et al.
    Curr Issues Mol Biol, 2023 Apr 20;45(4):3603-3627.
    PMID: 37185759 DOI: 10.3390/cimb45040235
    Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion (SIL), and squamous cell carcinoma (SCC) were compared using liquid chromatography-mass spectrometry (LC-MS). A total of 3597 proteins were identified, with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins overlapped between the three groups. In the transition from normal cervix to SIL, all 39 differentially expressed proteins were downregulated, while all 51 proteins discovered were upregulated in SIL to SCC. The binding process was the top molecular function, while chromatin silencing in the SIL vs. normal group, and nucleosome assembly in SCC vs. SIL groups was the top biological process. The PI3 kinase pathway appears crucial in initiating neoplastic transformation, while viral carcinogenesis and necroptosis are important for cell proliferation, migration, and metastasis in cervical cancer development. Annexin A2 and cornulin were selected for validation based on LC-MS results. The former was downregulated in the SIL vs. normal cervix and upregulated in the progression from SIL to SCC. In contrast, cornulin exhibited the highest expression in the normal cervix and lowest in SCC. Although other proteins, such as histones, collagen, and vimentin, were differentially expressed, their ubiquitous expression in most cells precluded further analysis. Immunohistochemical analysis of tissue microarrays found no significant difference in Annexin A2 expression between the groups. Conversely, cornulin exhibited the strongest expression in the normal cervix and lowest in SCC, supporting its role as a tumor suppressor and potential biomarker for disease progression.
  5. Fulltext Revisiting the single cell protein application of Cupriavidus necator H16 and recovering bioplastic granules simultaneously
    Kunasundari B, Murugaiyah V, Kaur G, Maurer FH, Sudesh K
    PLoS One, 2013;8(10):e78528.
    PMID: 24205250 DOI: 10.1371/journal.pone.0078528
    Cupriavidus necator H16 (formerly known as Hydrogenomonas eutropha) was famous as a potential single cell protein (SCP) in the 1970s. The drawback however was the undesirably efficient accumulation of non-nutritive polyhydroxybutyrate (PHB) storage compound in the cytoplasm of this bacterium. Eventually, competition from soy-based protein resulted in SCP not receiving much attention. Nevertheless, C. necator H16 remained in the limelight as a producer of PHB, which is a material that resembles commodity plastics such as polypropylene. PHB is a 100% biobased and biodegradable polyester. Although tremendous achievements have been attained in the past 3 decades in the efficient production of PHB, this bioplastic is still costly. One of the main problems has been the recovery of PHB from the cell cytoplasm. In this study, we showed for the first time that kilogram quantities of PHB can be easily recovered in the laboratory without the use of any solvents and chemicals, just by using the cells as SCP. In addition, the present study also demonstrated the safety and tolerability of animal model used, Sprague Dawley given lyophilized cells of C. necator H16. The test animals readily produced fecal pellets that were whitish in color, as would be expected of PHB granules. The pellets were determined to contain about 82-97 wt% PHB and possessed molecular mass of around 930 kg/mol. The PHB granules recovered biologically possessed similar molecular mass compared to chloroform extracted PHB [950 kg/mol]. This method now allows the production and purification of substantial quantities of PHB for various experimental trials. The method reported here is easy, does not require expensive instrumentation, scalable and does not involve extensive use of solvents and strong chemicals.
  6. Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases
    Li CMY, Briggs MT, Lee YR, Tin T, Young C, Pierides J, et al.
    Clin Exp Med, 2024 Mar 16;24(1):53.
    PMID: 38492056 DOI: 10.1007/s10238-024-01311-5
    Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
  7. Fulltext Epidemiology of smoking among Malaysian adult males: prevalence and associated factors
    Lim HK, Ghazali SM, Kee CC, Lim KK, Chan YY, Teh HC, et al.
    BMC Public Health, 2013 Jan 07;13:8.
    PMID: 23294728 DOI: 10.1186/1471-2458-13-8
    BACKGROUND: Three National Health and Morbidity Surveys (NHMSs) had been conducted in Malaysia in 10-year intervals from 1986-2006. Based on the latest NHMS survey in 2006, we describe the prevalence of smoking and identify the social and demographic factors associated with smoking among adult males in Malaysia.

    METHODS: A cross-sectional study among 15,639 Malaysian adult males aged 18 years and above was conducted using proportional to size stratified sampling method. The socio-demographic variables examined were level of education, occupation, marital status, residential area, age group and monthly household income.

    RESULTS: The prevalence of smoking among adult males in Malaysia was 46.5% (95% CI: 45.5-47.4%), which was 3% lower than a decade ago. Mean age of smoking initiation was 18.3 years, and mean number of cigarettes smoked daily was 11.3. Prevalence of smoking was highest among the Malays (55.9%) and those aged 21-30 years (59.3%). Smoking was significantly associated with level of education (no education OR 2.09 95% CI (1.67-2.60), primary school OR 1.95, 95% CI (1.65-2.30), secondary school OR 1.88, 95% CI (1.63-2.11), with tertiary education as the reference group). Marital status (divorce OR 1.67, 95% CI (1.22-2.28), with married as the reference group), ethnicity (Malay, OR 2.29, 95% CI ( 1.98-2.66; Chinese OR 1.23 95% CI (1.05-1.91), Other Bumis OR 1.75, 95% CI (1.46-2.10, others OR 1.48 95% CI (1.15-1.91), with Indian as the reference group), age group (18-20 years OR 2.36, 95% CI (1.90-2.94); 20-29 years OR 3.31 , 95% CI 2.82-3.89; 31-40 years OR 2.85 , 95% CI ( 2.47-3.28); 41-50 years OR 1.93, 95% CI (1.69-2.20) ; 51-60 years OR 1.32, 95% CI (1.15-1.51), with 60 year-old and above as the reference group) and residential area (rural OR 1.12 , 95% CI ( 1.03-1.22)) urban as reference.

    CONCLUSION: The prevalence of smoking among Malaysian males remained high in spite of several population interventions over the past decade. Tobacco will likely remain a primary cause of premature mortality and morbidity in Malaysia. Continuous and more comprehensive anti-smoking policy measures are needed in order to further prevent the increasing prevalence of smoking among Malaysian men, particularly those who are younger, of Malay ethnicity, less educated, reside in rural residential area and with lower socio-economic status.

  8. Proteomics of endometrial cancer diagnosis, treatment, and prognosis
    Mittal P, Klingler-Hoffmann M, Arentz G, Zhang C, Kaur G, Oehler MK, et al.
    Proteomics Clin Appl, 2016 Mar;10(3):217-29.
    PMID: 26541900 DOI: 10.1002/prca.201500055
    This review discusses the current status of proteomics technology in endometrial cancer diagnosis, treatment and prognosis. The first part of this review focuses on recently identified biomarkers for endometrial cancer, their importance in clinical use as well as the proteomic methods used in their discovery. The second part highlights some of the emerging mass spectrometry based proteomic technologies that promise to contribute to a better understanding of endometrial cancer by comparing the abundance of hundreds or thousands of proteins simultaneously.
  9. Lymph node metastasis of primary endometrial cancers: Associated proteins revealed by MALDI imaging
    Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Lokman NA, Zhang C, et al.
    Proteomics, 2016 06;16(11-12):1793-801.
    PMID: 27061135 DOI: 10.1002/pmic.201500455
    Metastasis is a crucial step of malignant progression and is the primary cause of death from endometrial cancer. However, clinicians presently face the challenge that conventional surgical-pathological variables, such as tumour size, depth of myometrial invasion, histological grade, lymphovascular space invasion or radiological imaging are unable to predict with accuracy if the primary tumour has metastasized. In the current retrospective study, we have used primary tumour samples of endometrial cancer patients diagnosed with (n = 16) and without (n = 27) lymph node metastasis to identify potential discriminators. Using peptide matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI), we have identified m/z values which can classify 88% of all tumours correctly. The top discriminative m/z values were identified using a combination of in situ sequencing and LC-MS/MS from digested tumour samples. Two of the proteins identified, plectin and α-Actin-2, were used for validation studies using LC-MS/MS data independent analysis (DIA) and immunohistochemistry. In summary, MALDI-MSI has the potential to identify discriminators of metastasis using primary tumour samples.
  10. Altered N-linked glycosylation in endometrial cancer
    Mittal P, Briggs M, Klingler-Hoffmann M, Kaur G, Packer NH, Oehler MK, et al.
    Anal Bioanal Chem, 2021 Apr;413(10):2721-2733.
    PMID: 33222001 DOI: 10.1007/s00216-020-03039-z
    It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis. Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI). This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section. Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM. By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium. Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM. Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28. A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis. In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
  11. Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer
    Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Kaur G, Anderson L, et al.
    Biochim Biophys Acta Proteins Proteom, 2017 Jul;1865(7):846-857.
    PMID: 27784647 DOI: 10.1016/j.bbapap.2016.10.010
    The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.
  12. Fulltext Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging
    Mittal P, Condina MR, Klingler-Hoffmann M, Kaur G, Oehler MK, Sieber OM, et al.
    Cancers (Basel), 2021 Oct 27;13(21).
    PMID: 34771551 DOI: 10.3390/cancers13215388
    Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.
  13. Lack of increased P15INK4B protein expression in basal cell carcinomas
    Moad AI, Tan ML, Kaur G, Mabruk M
    Asian Pac J Cancer Prev, 2012;13(12):6239-44.
    PMID: 23464438
    BACKGROUND: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. P15INK4b is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of p15INK4b protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate p15INK4b protein expression in BCCs.

    MATERIALS AND METHOD: Protein expression of p15INK4b in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach.

    RESULTS: The expression of p15INK4b was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and p15INK4b protein expression.

    CONCLUSIONS: Our finding may indicate that p15INK4b protein expression does not play a role in the genesis of BCC.

  14. Immunohistochemical determination of the P15 protein expression in cutaneous squamous cell carcinoma
    Moad AI, Lan TM, Kaur G, Hashim H, Mabruk MJ
    J Cutan Pathol, 2009 Feb;36(2):183-9.
    PMID: 18564286 DOI: 10.1111/j.1600-0560.2008.00989.x
    The tumor suppressor gene p15(INK4b) is a cyclin-dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor-derived cell lines. The precise role of p15(INK4b) protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15(INK4b) gene. This study is a continuation of our previous study and aims to determine the possible role of p15(INK4b) protein expression in the genesis of cutaneous SCC. P15(INK4b) protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15(INK4b) was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15(INK4b) protein expression. The absence of p15(INK4b) expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15(INK4b) could possibly be involved in the pathogenesis of cutaneous SCC.
  15. Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study
    Nair HK, Ahmad NW, Ismail AA, Alabed AAA, Zheming BO, Kaur G, et al.
    J Wound Care, 2021 12 01;30(Sup12):S30-S36.
    PMID: 34882006 DOI: 10.12968/jowc.2021.30.Sup12.S30
    OBJECTIVE: Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.
  16. Contribution of the MLH1 -93G>a promoter polymorphism in modulating susceptibility risk in Malaysian colorectal cancer patients
    Nizam ZM, Abdul Aziz AA, Kaur G, Abu Hassan MR, Mohd Sidek AS, Yeh LY, et al.
    Asian Pac J Cancer Prev, 2013;14(2):619-24.
    PMID: 23621208
    BACKGROUND: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable.

    AIM: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk.

    METHODS: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs).

    RESULTS: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253).

    CONCLUSION: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

  17. Fulltext Nasopharyngeal Carcinoma (NPC) Risk Factors: A Systematic Review and Meta-Analysis of the Association with Lifestyle, Diets, Socioeconomic and Sociodemographic in Asian Region
    Okekpa SI, S M N Mydin RB, Mangantig E, Azmi NSA, Zahari SNS, Kaur G, et al.
    Asian Pac J Cancer Prev, 2019 Nov 01;20(11):3505-3514.
    PMID: 31759378 DOI: 10.31557/APJCP.2019.20.11.3505
    OBJECTIVE: Risk factors of nasopharyngeal carcinoma (NPC) have been linked with diets, life style and viral
    infections. NPC is more rampant in Asian populations than non-Asian countries. Our study aims to assess the validity
    of the suggestions provided by multiple case control studies demonstrating that salted fish consumption, smoking and
    alcohol consumption are associated with the risk of NPC in Asia.

    METHODS: Search for related literature on salted fish,
    smoking and alcohol consumption were performed via Science Direct, PubMed databases and Google Scholar. Articles
    included in this study were from 2009 to 2017, with specific focus on salted fish, smoking and alcohol consumption
    as risk factors of NPC. This study excluded all articles published prior to 2009 and articles involving other cancers.
    Data were extracted independently by two different researchers and harmonized. Meta-analysis was conducted on the
    obtained data, by using R package Meta to create funnel and forest plots.

    RESULTS: The meta-analysis revealed that
    salted fish, smoking and alcohol consumption were significantly associated to NPC risk with random effect model score
    showing OR of 1.41 at 95% confidence interval (CI) of 1.13-1.75 (P<0.01), OR of 1.89 at 95 % CI of 1.49 - 2.38, and
    OR: 1.42 at 95 % CI of 1.23 - 1.65 respectively. Our results also revealed significant association of salted meat, salted
    vegetables, house type, wood dust exposure associated with NPC risk with p values less than 0.05.

    CONCLUSION: This
    study proposes that salted fish intake, smoking and alcohol consumption might be linked to NPC risk in Asians. Further
    studies are necessary to ascertain the molecular mechanisms and clarify if the associated path that could function as
    therapeutic target.

  18. Trends in food waste valorization for the production of chemicals, materials and fuels: Case study South and Southeast Asia
    Ong KL, Kaur G, Pensupa N, Uisan K, Lin CSK
    Bioresour Technol, 2018 Jan;248(Pt A):100-112.
    PMID: 28662903 DOI: 10.1016/j.biortech.2017.06.076
    Staggering amounts of food waste are being generated in Asia by means of agricultural processing, food transportation and storage, and human food consumption activities. This along with the recent sustainable development goals of food security, environmental protection, and energy efficiency are the key drivers for food waste valorization. The aim of this review is to provide an insight on the latest trends in food waste valorization in Asian countries such as India, Thailand, Singapore, Malaysia and Indonesia. Landfilling, incineration, and composting are the first-generation food waste processing technologies. The advancement of valorisation alternatives to tackle the food waste issue is the focus of this review. Furthermore, a series of examples of key food waste valorization schemes in this Asian region as case studies to demonstrate the advancement in bioconversions in these countries are described. Finally, important legislation aspects for food waste disposal in these Asian countries are also reported.
  19. Fulltext BZD9L1 benzimidazole analogue hampers colorectal tumor progression by impeding angiogenesis
    Oon CE, Subramaniam AV, Ooi LY, Yehya AHS, Lee YT, Kaur G, et al.
    World J Gastrointest Oncol, 2023 May 15;15(5):810-827.
    PMID: 37275453 DOI: 10.4251/wjgo.v15.i5.810
    BACKGROUND: The development of new vasculatures (angiogenesis) is indispensable in supplying oxygen and nutrients to fuel tumor growth. Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer (CRC) progression. Sirtuin (SIRT) enzymes are highly expressed in blood vessels. BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC. However, its role has yet to be explored in CRC tumor angiogenesis.

    AIM: To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells (EC) in vitro, ex vivo and in HCT116 CRC xenograft in vivo models.

    METHODS: EA.hy926 EC were treated with half inhibitory concentration (IC50) (2.5 μM), IC50 (5.0 μM), and double IC50 (10.0 μM) of BZD9L1 and assessed for cell proliferation, adhesion and SIRT 1 and 2 protein expression. Next, 2.5 μM and 5.0 μM of BZD9L1 were employed in downstream in vitro assays, including cell cycle, cell death and sprouting in EC. The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction (qPCR). The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array. Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC. The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids. HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis, Ki67 protein expression indicative of proliferation, cluster of differentiation 31 (CD31) and CD34 EC markers, and SIRT 1 and 2 genes via hematoxylin and eosin, immunohistochemistry and qPCR, respectively.

    RESULTS: BZD9L1 impeded EC proliferation, adhesion, and spheroid sprouting through the downregulation of intercellular adhesion molecule 1, vascular endothelial cadherin, integrin-alpha V, SIRT1 and SIRT2 genes. The compound also arrested the cells at G1 phase and induced apoptosis in the EC. In mouse choroids, BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control. Compared to the negative control, the compound also reduced the protein levels of angiogenin, basic fibroblast growth factor, platelet-derived growth factor and placental growth factor, which then inhibited HCT116 CRC spheroid invasion in co-culture. In addition, a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1 (hSIRT1), hSIRT2, CD31, and CD34 EC markers and murine SIRT2 gene, while the murine SIRT1 gene remained unaffected, compared to vehicle control. Histology analyses revealed that BZD9L1 at low (50 mg/kg) and high (250 mg/kg) doses reduced Ki-67 protein expression, while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.

    CONCLUSION: These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression. Furthermore, together with previous anticancer findings, this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.

  20. Fulltext Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues
    Othman EQ, Kaur G, Mutee AF, Muhammad TS, Tan ML
    J Clin Lab Anal, 2009;23(4):249-58.
    PMID: 19623642 DOI: 10.1002/jcla.20309
    Autophagy is a protein degradation process within the cell and its deregulation has been linked to various diseases and the formation of cancer. One of the important proteins involved in the autophagy process is microtubule-associated protein 1 light chain 3 (MAP1LC3). The aims of this study were to determine the MAP1LC3A and MAP1LC3B protein expression in both normal and cancer breast tissues and to determine the relationship between the expression of these proteins and type of tissues. Immunohistochemistry assessments were carried out on tissue microarrays consisting of breast tissues. MAP1LC3A expression was detected in 52/56 of normal breast tissue cores and 65/67 of breast cancer tissue cores. MAP1LC3B expression was detected in 55/56 of normal breast tissue cores and 67/67 of breast cancer tissue cores. MAP1LC3A and MAP1LC3B protein are expressed in the majority of normal and cancer breast tissues. A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. However, a significantly higher number of breast cancer tissues were found to express the MAP1LC3A protein with strong immunoreactivity as compared with the normal tissues, suggesting that MAP1LC3A may play a role in breast cancer development.
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