Displaying publications 21 - 28 of 28 in total

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  1. Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA
    Asian Pac J Cancer Prev, 2010;11(3):713-6.
    PMID: 21039041
    A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.
    Matched MeSH terms: Telomerase/metabolism*
  2. Makpol S, Yaacob N, Zainuddin A, Yusof YA, Ngah WZ
    Afr J Tradit Complement Altern Med, 2009 Jul 03;6(4):560-72.
    PMID: 20606778
    The objective of this study was to investigate the modulatory effect of Chlorella vulgaris on cultured fibroblast cells derived from young and old aged individuals focusing on DNA damage, telomere length and telomerase activity. Dose-response test of the algal extract on cells in both age groups revealed that optimum viability was observed at a concentration of 50 microg/ml. Results obtained showed that Chlorella vulgaris exhibited protective effects against H(2)O(2)-induced oxidative stress as shown by the reduction in damaged DNA caused by H(2)O(2) treatment (p<0.05) in Chlorella vulgaris pre- and post-treated groups (p<0.05). Pre-treatment of Chlorella vulgaris resulted in a significant decrease in DNA damage suggesting a bioprotective effect against free radical attacks. A decline in DNA damage was observed in post-treated cells which proves Chlorella vulgaris to present bioremediative properties. In cells induced with oxidative stress, telomere length decreased significantly coupled with a concomitant decline of telomerase activity (p<0.05). However, these reductions were prevented with prior and post treatment of Chlorella vulgaris. Therefore, we concluded that Chlorella vulgaris exhibited bioprotective effects especially in cells obtained from young donor but were more bioremediative for cells obtained from old donor as indicated by DNA damage, telomere shortening and reduction in telomerase activity.
    Matched MeSH terms: Telomerase/metabolism*
  3. Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS
    Molecules, 2021 Jan 13;26(2).
    PMID: 33450878 DOI: 10.3390/molecules26020376
    Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated. Screening on HCT 116 at 48 h showed that berberine (10.30 ± 0.89 µg/mL) is the most effective (lowest IC50 value) telomerase inhibitor compared to boldine (37.87 ± 3.12 µg/mL) and silymarin (>200 µg/mL). Further analyses exhibited that berberine treatment caused G0/G1 phase arrest at 48 h due to high cyclin D1 (CCND1) and low cyclin-dependent kinase 4 (CDK4) protein and mRNA levels, simultaneous downregulation of human telomerase reverse transcriptase (TERT) mRNA and human telomerase RNA component (TERC) levels, as well as a decrease in the TERT protein level and telomerase activity. The effect of berberine treatment on the cell cycle was time dependent as it resulted in a delayed cell cycle and doubling time by 2.18-fold. Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.
    Matched MeSH terms: Telomerase/metabolism
  4. Cheah PL, Looi LM, Ng MH, Sivanesaratnam V
    J Clin Pathol, 2002 Jan;55(1):22-6.
    PMID: 11825919
    AIM: Telomerase activity was studied in invasive uterine cervical carcinoma to assess whether it was activated during cervical malignant transformation and to look for a possible association with human papillomavirus (HPV) infection in a set of Malaysian patients.

    METHODS: Histologically confirmed invasive cervical carcinoma and benign cervices were assayed for telomerase activity using a commercial telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay kit. The same cases were subjected to PCR detection of HPV using type specific (HPV types 6b, 11, 16, and 18) followed by L1 open reading frame (ORF) consensus primers.

    RESULTS: HPV was detected in 18 (13 HPV-16, one HPV-6b, four only L1 ORF) of 20 invasive cervical carcinoma and one (only L1 ORF) of 19 benign cervices. Raised telomerase activity (A(450 nm) > 0.215) was detected in 11 cervical carcinomas, with A(450 nm) ranging between 0.238 and 21.790 (mean, 3.952) in positive squamous carcinomas, whereas A(450 nm) was only 0.222 in the one positive adenosquamous carcinoma. Five of 11 cervical carcinomas in stage I, three of six in stage II, both in stage III, and the only case in stage IV showed telomerase activation. Increased telomerase activity was noted in five of the 12 lymph node negative, five of the seven lymph node status unknown cases, and the one case with presumed lymph node metastasis. Ten of 18 HPV positive and one of two HPV negative cervical carcinomas showed telomerase upregulation.

    CONCLUSIONS: Telomerase is activated in invasive cervical carcinoma. Although larger studies are needed, there seems to be no clear association between telomerase upregulation and HPV status, although there is a suggestion of increased telomerase activity in squamous carcinomas and late stage disease.

    Matched MeSH terms: Telomerase/metabolism*
  5. Shaharuddin B, Ahmad S, Md Latar N, Ali S, Meeson A
    Stem Cells Transl Med, 2017 03;6(3):761-766.
    PMID: 28297580 DOI: 10.5966/sctm.2016-0175
    Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological responses of these cells within the transplants could improve cell engraftment and survival. However, human corneal rings used as a source of LSCs are not always readily available for research purposes. As an alternative, we hypothesized that a human telomerase-immortalized corneal epithelial cell (HTCEC) line could be used as a model for studying LSC immunobiology. HTCEC constitutively expressed human leukocyte antigen (HLA) class I but not class II molecules. However, when stimulated by interferon-γ, HTCECs then expressed HLA class II antigens. Some HTCECs were also migratory in response to CXCL12 and expressed stem cell markers, Nanog, Oct4, and Sox2. In addition because both HTCECs and LECs contain side population (SP) cells, which are an enriched LSC population, we used these SP cells to show that some HTCEC SP cells coexpressed ABCG2 and ABCB5. HTCEC SP and non-side population (NSP) cells also expressed CXCR4, but the SP cells expressed higher levels. Both were capable of colony formation, but the NSP colonies were smaller and contained fewer cells. In addition, HTCECs expressed ΔNp63α. These results suggest the HTCEC line is a useful model for further understanding LSC biology by using an in vitro approach without reliance on a supply of human tissue. Stem Cells Translational Medicine 2017;6:761-766.
    Matched MeSH terms: Telomerase/metabolism
  6. Thomas G, Tr S, George S P, Somanathan T, Sarojam S, Krishnankutti N, et al.
    Asian Pac J Cancer Prev, 2020 Feb 01;21(2):309-316.
    PMID: 32102504 DOI: 10.31557/APJCP.2020.21.2.309
    BACKGROUND: Although leukoplakia shows a higher risk for malignant transformation to oral cancer, currently there are no clinically relevant biomarker which can predict the potentially high risk leukoplakia. This study aimed to investigate the genetic alterations such as DNA ploidy, telomerase expression and DNA repair capacity as predictive markers of malignant transformation risk of leukoplakia.

    METHODS: The study was initiated in September 2005 and patients were followed up to March 2014. Two hundred patients with oral leukoplakia, 100 patients with oral cancer and 100 healthy, age and sex matched adults with normal oral mucosa as controls were recruited. The DNA ploidy content was measured by high resolution flow cytometry, level of telomerase expression was identified by TRAP assay and intrinsic DNA repair capacity was measured by mutagen induced chromosome sensitivity assay of cultured peripheral blood lymphocytes. The Chi-square test or Fisher's Exact test was used for comparison of categorical variables between biomarkers. A p value less than or equal to 0.05 was considered as statistically significant. Analysis was performed with SPSS software version 16. Logistic regression was used to find the association between the dependent and three independent variables.

    RESULTS: There was significant difference in the distribution of ploidy status, telomerase activity and DNA repair capacity among control, leukoplakia and oral cancer group (p<0.001). When the molecular markers were compared with histological grading of leukoplakia, both DNA ploidy analysis and telomerase activity showed statistical significance (p<0.001). Both aneuploidy and telomerase positivity was found to coincide with high-risk sites of leukoplakia and were statistically significant (p.

    Matched MeSH terms: Telomerase/metabolism*
  7. Malek Rivan NF, Shahar S, Rajab NF, Singh DKA, Din NC, Hazlina M, et al.
    Clin Interv Aging, 2019;14:1343-1352.
    PMID: 31413555 DOI: 10.2147/CIA.S211027
    PURPOSE: This study was aimed at determining the presence of cognitive frailty and its associated factors among community-dwelling older adults from the "LRGS-Towards Useful Aging (TUA)" longitudinal study.

    PATIENTS AND METHODS: The available data related to cognitive frailty among a sub-sample of older adults aged 60 years and above (n=815) from two states in Malaysia were analysed. In the LRGS-TUA study, a comprehensive interview-based questionnaire was administered to obtain the socio-demographic information of the participants, followed by assessments to examine the cognitive function, functional status, dietary intake, lifestyle, psychosocial status and biomarkers associated with cognitive frailty. The factors associated with cognitive frailty were assessed using a bivariate logistic regression (BLR).

    RESULTS: The majority of the older adults were categorized as robust (68.4%), followed by cognitively pre-frail (37.4%) and cognitively frail (2.2%). The data on the cognitively frail and pre-frail groups were combined for comparison with the robust group. A hierarchical BLR indicated that advancing age (OR=1.04, 95% CI:1.01-1.08, p<0.05) and depression (OR=1.49, 95% CI:1.34-1.65, p<0.001) scored lower on the Activity of Daily Living (ADL) scale (OR=0.98, 95% CI:0.96-0.99, p<0.05), while low social support (OR=0.98, 95% CI:0.97-0.99, p<0.05) and low niacin intake (OR=0.94, 95% CI:0.89-0.99, p<0.05) were found to be significant factors for cognitive frailty. Higher oxidative stress (MDA) and lower telomerase activity were also associated with cognitive frailty (p<0.05).

    CONCLUSION: Older age, a lower niacin intake, lack of social support, depression and lower functional status were identified as significant factors associated with cognitive frailty among older Malaysian adults. MDA and telomerase activity can be used as potential biomarkers for the identification of cognitive frailty.

    Matched MeSH terms: Telomerase/metabolism
  8. Makpol S, Abdul Rahim N, Hui CK, Ngah WZ
    Oxid Med Cell Longev, 2012;2012:785743.
    PMID: 22919441 DOI: 10.1155/2012/785743
    In this study, we determined the molecular mechanism of γ-tocotrienol (GTT) in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs). Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal) and promoted G(0)/G(1) cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P < 0.05). GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P < 0.05). Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P < 0.05) in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.
    Matched MeSH terms: Telomerase/metabolism
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