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  1. Ulaganathan V, Kandiah M, Mohd Shariff Z
    J Gastrointest Oncol, 2018 Aug;9(4):650-663.
    PMID: 30151261 DOI: 10.21037/jgo.2018.04.01
    Background: Metabolic syndrome was linked with various chronic diseases, including cancer. The study on the effect of metabolic syndrome on colorectal cancer (CRC) was not conducted in Malaysia. Therefore, this study aims to determine the association between metabolic syndromes and its components with CRC, based on the three established definitions.

    Methods: A multi-centred matched case control study was conducted in five local hospitals. A total of 140 histologically confirmed CRC cases were matched with 280 cancer free controls. Mean value and prevalence of the components of metabolic syndrome between cases and controls were measured based on the three definitions. A multiple variable analysis using Cox regression was conducted to measure the strength of the association between the definitions of MetS, components of MetS and risk of CRC.

    Results: Multiple variable analyses showed that metabolic syndrome significantly and independently increased the risk of CRC, with an odds ratio ranging from 1.79 to 2.61. This study identified that the definition of metabolic syndrome by the International Diabetes Federation is the most sensitive in predicting the risk of CRC, compared to metabolic syndrome as defined by the World Health Organization and National Cholesterol Education Program Adults Treatment Panel III. Abdominal obesity, low HDL-cholesterol, and hypertension were identified as the three core risk factors, which promote inflammatory signals that contribute to metabolic syndrome and an increased risk of CRC.

    Conclusions: These data hypothesized that simple measurement of abdominal obesity, abnormal BP and HDL-cholesterol especially using International Diabetes Federation (IDF) definition of MetS for South Asians for to detect individuals at CRC risk may have higher clinical utility than applying other universal complex MetS definitions.

  2. Ulaganathan V, Kandiah M, Shariff ZM
    J Carcinog, 2018;17:4.
    PMID: 30294246 DOI: 10.4103/jcar.JCar_2_18
    BACKGROUND: Obesity has frequently been associated with the dyslipidemic state and with the risk of various chronic diseases.

    OBJECTIVE: The objective of this study was to determine the relationship between obesity and blood lipids with a risk of colorectal cancer (CRC).

    METHODOLOGY: Histologically confirmed CRC patients from five local hospitals were matched with cancer-free controls for age, gender, and ethnicity (n = 140: 280). The study participants underwent physical assessment for the presence of obesity and 10 mL of fasting blood was drawn for blood lipid analysis.

    RESULTS: In this study, abdominal obesity significantly doubled the risk of CRC (adjusted odds ratio [AOR] =1.69, 95% confidence interval [CI] = 1-2.83). Hypercholesterolemia and low high-density lipoprotein cholesterol (HDL) increased the risk of CRC more than twofolds (AOR = 2.6, 95% CI = 1.7-3.9 and AOR = 3.8, 95% CI = 2.3-6.3, respectively). Abdominal obesity and hypercholesterolemia synergically doubled the risk of CRC (AOR = 2.0, 95% CI = 1-4). Low-HDL has shown no synergic association with other dyslipidemic states with an increased CRC risk.

    CONCLUSION: Improving abdominal obesity, hypercholesterolemia, and low HDL may be a clinically relevant strategy to reduce the risk of CRC among Malaysians.

  3. Chowdhury PR, Salvamani S, Gunasekaran B, Peng HB, Ulaganathan V
    Yale J Biol Med, 2023 Dec;96(4):495-509.
    PMID: 38161577 DOI: 10.59249/TDBJ7410
    Colorectal cancer (CRC) has been recorded amongst the most common cancers in the world, with high morbidity and mortality rates, and relatively low survival rates. With risk factors such as chronic illness, age, and lifestyle associated with the development of CRC, the incidence of CRC is increasing each year. Thus, the discovery of novel biomarkers to improve the diagnosis and prognosis of CRC has become beneficial. Long non-coding RNAs (lncRNAs) have been emerging as potential players in several tumor types, one among them is the lncRNA H19. The paternally imprinted oncofetal gene is expressed in the embryo, downregulated at birth, and reappears in tumors. H19 aids in CRC cell growth, proliferation, invasion, and metastasis via various mechanisms of action, significantly through the lncRNA-microRNA (miRNA)-messenger RNA (mRNA)-competitive endogenous RNA (ceRNA) network, where H19 behaves as a miRNA sponge. The RNA transcript of H19 obtained from the first exon of the H19 gene, miRNA-675 also promotes CRC carcinogenesis. Overexpression of H19 in malignant tissues compared to adjacent non-malignant tissues marks H19 as an independent prognostic marker in CRC. Besides its prognostic value, H19 serves as a promising target for therapy in CRC treatment.
  4. Ulaganathan V, Kandiah M, Zalilah MS, Faizal JA, Fijeraid H, Normayah K, et al.
    Asian Pac J Cancer Prev, 2012;13(8):3873-7.
    PMID: 23098486
    OBJECTIVE: Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two.

    METHODS: Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280).

    RESULTS: MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed.

    CONCLUSION: This study provides evidence for a positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings.

  5. Liau XL, Salvamani S, Gunasekaran B, Chellappan DK, Rhodes A, Ulaganathan V, et al.
    Br J Biomed Sci, 2023;80:11103.
    PMID: 37025163 DOI: 10.3389/bjbs.2023.11103
    Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC tumorigenesis and treatment outcome. CCAT 1 has a high degree of specificity and sensitivity, it is readily detected in CRC tissues and is significantly overexpressed in both premalignant and malignant CRC tissues. Besides, CCAT 1 is associated with clinical manifestation and advanced features of CRC, such as lymph node metastasis, high tumor node metastasis stage, differentiation, invasion, and distant metastasis. In addition, they can upregulate oncogenic c-MYC and negatively modulate microRNAs via different mechanisms of action. Furthermore, dysregulated CCAT 1 also enhances the chemoresistance in CRC cells while downregulation of them reverses the malignant phenotypes of cancer cells. In brief, CCAT 1 serves as a potential screening, diagnostic and prognostic biomarker in CRC, it also serves as a potential therapeutic marker to treat CRC patients.
  6. Martula E, Morak-Młodawska B, Jeleń M, Okechukwu PN, Balachandran A, Tehirunavukarasu P, et al.
    Molecules, 2023 Nov 19;28(22).
    PMID: 38005384 DOI: 10.3390/molecules28227662
    Many new isomeric dipyridothiazine dimers have been presented as molecules with anticancer potential. These compounds were obtained in efficient syntheses of 1,6-, 1,8-, 2,7- and 3,6-diazaphenothiazines with selected alkylaromatic linkers. The structures of these compounds has been proven with two-dimensional spectroscopic techniques (COSY, NOESY, HSQC and HMBC) and high-resolution mass spectrometry (HRMS). In silico analyses of probable molecular targets were performed using the Way2Drug server. All new dimers were tested for anticancer activity against breast cancer line MCF7 and colon cancer line SW480. Cytotoxicity was assessed on normal L6 muscle cells. The tested dimers had high anticancer potential expressed as IC50 and the selectivity index SI. The most active derivative, 4c, showed an IC50 activity of less than 1 µM and an SI selectivity index higher than 100. Moreover, the compounds were characterized by low toxicity towards normal cells, simultaneously indicating a high cytostatic potential.
  7. Mok KT, Tung SEH, Kaur S, Chin YS, Martini MY, Ulaganathan V
    Nutr Health, 2023 Mar;29(1):9-20.
    PMID: 36330727 DOI: 10.1177/02601060221134997
    Background: One of the key importance of vegetable consumption is to obtain sufficient micronutrients, dietary fibre, and for the prevention of childhood obesity. Most Malaysian children did not meet the recommended intake of vegetable consumption, and this is especially vulnerable among the urban poor population due to food insecurity. Efforts are needed to promote vegetable consumption that fall short of the recommended intake level. Aim: This trial aims to examine the effectiveness of the "GrowEat" project, as a nutrition intervention programme integrated with home gardening activities to improve vegetable consumption among urban poor children in Kuala Lumpur, Malaysia. Methods: This is a single-blinded parallel two-arm cluster randomised controlled trial (RCT) that include 134 children. Two zones in Kuala Lumpur will be randomly selected, and three low-cost housing flats from each zone will be selected as the intervention and control groups respectively. The trial is designed based on the social cognitive theory (SCT). Children from the intervention group (n = 67) will attend a 12-week programme, which consists of home garden-based activities, gardening and nutrition education session. Assessment will be conducted for both groups at three time points: baseline, post-intervention and follow-up phase at 3 months after the intervention. Conclusion: We anticipate positive changes in vegetable consumption and its related factors after the implementation of the "GrowEat" project. The current intervention may also serve as a model and can be extended to other urban poor population for similar interventions in the future to improve vegetable consumption, agriculture and nutrition awareness.
  8. Noor KAM, Norsuddin NM, Karim MKA, Isa INC, Ulaganathan V
    Diagnostics (Basel), 2024 Nov 15;14(22).
    PMID: 39594234 DOI: 10.3390/diagnostics14222568
    BACKGROUND/OBJECTIVE: This study evaluates the mean glandular dose (MGD) in mammography screening for women aged 40-69 in Dubai, based on a retrospective analysis of a dose survey involving 2599 participants.

    METHODS: MGD was calculated using the Dance formula.

    RESULTS: The average MGD was 0.96 ± 0.39 mGy for mediolateral oblique (MLO) views and 0.81 ± 0.33 mGy for craniocaudal (CC) views. Weak inverse correlations were found between age and organ dose (OD) for both views, while a direct relationship was observed between breast thickness and entrance skin dose (ESD). In adjusted models, ESD was strongly associated with MGD (β = 1.04, 95% CI: 0.97, 1.09), while OD showed a moderate association (β = 0.44, 95% CI: 0.40, 0.49). Significant variations in ESD, OD, and MGD were noted across age groups and breast thicknesses.

    CONCLUSIONS: Lower MGD indicates reduced radiation exposure risk, while higher MGD in MLO views suggests improved imaging quality. Monitoring and optimizing MGD are essential for enhancing patient safety and screening efficacy.

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