AIMS: To determine the usefulness of immunohistochemical techniques and FISH of the tumour suppressor TP 53 gene to identify microinvasion in marginal tissue sections and to relate the possible correlation between protein expression and genetic aberrations in OSCC cases in Malaysia.
METHODS: Immunohistochemistry and FISH of TP 53 genes were applied on 26 OSCC formalin fixed paraffin embed (FFEP) blocks selected from two oral cancer referral centers in Malaysia.
RESULTS: For p53 protein immunohistochemistry, 96% of the 26 OSCC studied showed positive immunostaining at the excision margins. In FISH assay, 48.9±9.7% of the cancerous cells were monoploid for p53 probe signals, 41.0±9.5 % were diploid, and 10.2±7.8 % were polyploid. A correlation between p53 immunostaining and TP53 gene aberrations was noted (p< 0.05).
CONCLUSIONS: Immunohistochemical analysis of p53 protein expression and FISH of TP53 gene could be applied as screening tool for microinvasion of OSCC.
MATERIALS AND METHODS: miR-205 expression was investigated in 48 cases of inflammatory, benign and malignant tumor tissue array of the neck, oronasopharynx, larynx and salivary glands by Locked Nucleic Acid in situ hybridization (LNA-ISH) technology.
RESULTS: miR-205 expression was significantly differentially expressed across all of the inflammatory, benign and malignant tumor tissues of the neck. A significant increase in miR-205 staining intensity (p<0.05) was observed from inflammation to benign and malignant tumors in head and neck tissue array, suggesting that miR-205 could be a biomarker to differentiate between cancer and non-cancer tissues.
CONCLUSIONS: LNA-ISH revealed that miR-205 exhibited significant differential cytoplasmic and nuclear staining among inflammation, benign and malignant tumors of head and neck. miR-205 was not only exclusively expressed in squamous epithelial malignancy. This study offers information and a basis for a comprehensive study of the role of miR-205 that may be useful as a biomarker and/or therapeutic target in head and neck tumors.
METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.
RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
OBJECTIVE: This study aimed to determine the survival rate of breast cancer among the women of Malaysia and characteristics of the survivors.
METHOD: A retrospective cohort study was conducted on secondary data obtained from the Breast Cancer Registry and medical records of breast cancer patients admitted to Hospital Kuala Lumpur from 2005 to 2009. Survival data were validated with National Birth and Death Registry. Statistical analysis applied logistic regression, the Cox proportional hazard model, the Kaplan-Meier method and log rank test.
RESULTS: A total of 868 women were diagnosed with breast cancer between January 2005 and December 2009, comprising 58%, 25% and 17% Malays, Chinese and Indians, respectively. The overall survival rate was 43.5% (CI 0.573-0.597), with Chinese, Indians and Malays having 5 year survival rates of 48.2% (CI 0.444-0.520), 47.2% (CI 0.432-0.512) and 39.7% (CI 0.373-0.421), respectively (p<0.05). The survival rate was lower as the stages increased, with the late stages were mostly seen among the Malays (46%), followed by Chinese (36%) and Indians (34%). Size of tumor>3.0cm; lymph node involvement, ERPR, and HER 2 status, delayed presentation and involvement of both breasts were among other factors that were associated with poor survival.
CONCLUSIONS: The overall survival rate of Malaysian women with breast cancer was lower than the western figures with Malays having the lowest because they presented at late stage, after a long duration of symptoms, had larger tumor size, and had more lymph nodes affected. There is an urgent need to conduct studies on why there is delay in diagnosis and treatment of breast cancer women in Malaysia.
METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.
RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of Bax and down-regulation of Bcl-2 protein. Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
OBJECTIVE: Hence, this study aimed to determine the effects of bedak sejuk made from Oryza sativa ssp. indica (Indica) and Oryza sativa ssp. japonica (Japonica) on UVB-induced B164A5 melanoma cells, and also identify the antioxidant capacities of both types of bedak sejuk.
METHODS: The optimum dose of Indica and Japonica bedak sejuk to treat the cells was determined via the MTT assay. Then, the antioxidant capacities of both types of bedak sejuk were determined using the FRAP assay.
RESULTS: From the MTT assay, it was found that Indica and Japonica bedak sejuk showed no cytotoxic effects towards the cells. Hence, no IC50 can be obtained and two of the higher doses, 50 and 100 g/L were chosen for treatment. In the FRAP assay, Indica bedak sejuk at 50 and 100 g/L showed FRAP values of 0.003 ± 0.001 μg AA (ascorbic acid)/g of bedak sejuk and 0.004 ± 0.0003 μg AA/g of bedak sejuk. Whereas Japonica bedak sejuk at 50 g/L had the same FRAP value as Indica bedak sejuk at 100 g/L. As for Japonica bedak sejuk at 100 g/L, it showed the highest antioxidant capacity with the FRAP value of 0.01 ± 0.0007 μg AA/g of bedak sejuk which was statistically significant (p < 0.05) when compared to other tested concentrations.
CONCLUSION: In conclusion, Japonica bedak sejuk has a higher antioxidant capacity compared to Indica bedak sejuk despite both being not cytotoxic towards the cells. Regardless, further investigations need to be done before bedak sejuk could be developed as potential melanoma chemoprevention agents.
METHODS: Blood from 30 patients with primary OSCC and 1:1 age-sex-matched controls was subjected to qPCR and ELISA to detect VEGF-A gene expression and serum level. Tumors of the 30 patients were investigated for VEGF Receptor-2 (VEGFR-2) expression and were analyzed using Image J software version 1.52 for DAB percentage (DAB-P) area and optical density (OD).
RESULTS: VEGF-A relative gene expression among patients was 2.43-fold higher compared to the healthy control group. Well-differentiated had a 1.98-fold increment, while poorly differentiated had a 3.58-fold increment. Serum VEGF-A was significantly elevated among the patients compared to controls (458.7 vs 253.2, p=0.0225). Poorly differentiated had a higher serum VEGF concentration (1262.0±354.7pg/ml) compared with other two. Mean VEGFR-2 DAB-P level in OSCC was 42.41±5.61(p=0.15). Well-differentiated had a DAB-P of 41.20±5.32 while poorly differentiated had DAB-P 46.21±3.78. The mean OD in OSCC was 0.54±0.16. VEGFR-2 OD in well and poorly differentiated OSCC were 0.48±0.12 and 0.68±0.17, respectively.
CONCLUSIONS: VEGF-A gene expression, serum levels, and tissue VEGFR-2 levels correlated linearly with the stage and grade of the tumor. This study justifies the value of VEGF-A as a potential biomarker in OSCC in early detection of OSCC. More studies are needed to accept the use of VEGF-A.
MATERIALS AND METHODS: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction- restriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing.
RESULTS: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ≥50 years and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC.
CONCLUSIONS: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.
OBJECTIVE: This study aims to evaluate the efficacy of the M2PK Quick Stool Test (ScheBo®) in detecting colorectal adenoma and adenocarcinoma in high-risk Malaysian populations using colonoscopy as the comparison.
METHODS: A prospective, cross-sectional, multicenter study was conducted from December 2017 to December 2019 in four hospitals in Malaysia. Participants were eligible if they met any of the following criteria: personal or family history of colorectal polyps or cancer, inherited syndromes, altered bowel habits, rectal bleeding, unintended weight loss, loss of appetite, abdominal pain or cramps, or unexplained iron deficiency, or an Asia-Pacific Colorectal Screening score of 4-7. Participants provided a stool sample that was tested for M2PK using the M2PK Quick Test. Participants then underwent a colonoscopy, and any lesions found were biopsied and sent for histopathological examination.
RESULTS: A total of 562 participants were included in the study, of whom 89 had a positive M2PK test. Presence of adenoma and/or dysplastic lesions were confirmed in 14.4% and adenocarcinoma in 3.0% of the participants. The M2PK Quick Stool Test showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 58.8%, 85.5%, 11.2% and 98.5%, respectively in detecting colorectal adenocarcinoma. For detection of colorectal adenoma, this test yielded a sensitivity, specificity, PPV and NPV of 27.3%, 86.3%, 27.0% and 86.5%, respectively.
CONCLUSIONS: The M2PK Quick Stool Test showed a moderate accuracy in detecting colorectal adenocarcinoma and adenomas in the studied population.
MATERIALS AND METHODS: A data set of 91 patients with high-risk acute lymphoblastic leukemia (ALL) followed for five years from 1982 to 1987 was chosen for fitting the mixture cure model. We used the maximum likelihood estimation technique via R software 3.6.2 to obtain the estimates for parameters of the proposed model in the existence of cure rate, censored data, and covariates. For the best model choice, the Akaike information criterion (AIC) was implemented.
RESULTS: After comparing different parametric models fitted to the data, including or excluding cure fraction, without covariates, the smallest AIC values were obtained by the EW and the GMW distributions, (953.31/969.35) and (955.84/975.99), respectively. Besides, assuming a mixture cure model based on GMW with covariates, an estimated ratio between cure fractions for allogeneic and autologous bone marrow transplant groups (and its 95% confidence intervals) were 1.42972 (95% CI: 1.18614 - 1.72955).
CONCLUSION: The results of this study reveal that the EW and the GMW distributions are the best choices for the survival times of Leukemia patients.