METHODOLOGY: MCM2, 4, 5 and 7 genes expression profiles were evaluated in three cervical tissue samples each of normal cervix, human papillomavirus (HPV)-infected low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC), using Human Transcriptome Array 2.0 and validated by nCounter® PanCancer Pathway NanoString Array. Immunohistochemical expression of MCM2 protein was semi-quantitatively assessed by histoscore in tissue microarrays containing 9 cases of normal cervix, 10 LSIL, 10 HSIL and 42 cases of SCC.
RESULTS: MCM2, 4, 5 and 7 genes expressions were upregulated with increasing fold change during the progression from LSIL to HSIL and the highest in SCC. MCM2 gene had the highest fold change in SCC compared to normal cervix. Immunohistochemically, MCM2 protein was localised in the nuclei of basal cells of normal cervical epithelium and dysplastic-neoplastic cells of CIN and SCC. There was a significant difference in MCM2 protein expression between the histological groups (P = 0.039), and histoscore was the highest in HSIL compared to normal cervix (P = 0.010).
CONCLUSION: The upregulation of MCM genes expressions in cervical carcinogenesis reaffirms MCM as a proliferative marker in DNA replication pathway, whereby proliferation of dysplastic and cancer cells become increasingly dysregulated and uncontrolled. A strong expression of MCM2 protein in HSIL may aid as a concatenated screening tool in detecting pre-cancerous cervical lesions.
METHODS: EPICOR Asia (Long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) (NCT01361386) is a prospective, multinational, observational study of patients discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to describe short- and long-term (up to 2 years post-index event) AMPs in patients hospitalized for ACS and to record clinical outcomes, healthcare resource use, and self-reported health status. Pre- and in-hospital management, AMPs, and associated outcomes, with particular focus on ischemic and bleeding events, will be recorded during the 2-year follow up.
RESULTS: Between June 2011 and May 2012, 13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616 with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from 219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea (n = 705), Thailand (n = 957), and Vietnam (n = 208).
CONCLUSIONS: EPICOR Asia will provide information regarding clinical management and AMPs for ACS patients in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self-reported health status both during hospitalization and up to 2 years after discharge will also be described.
METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).
CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
MATERIALS AND METHODS: cDNAs from 41 OSCC samples with and without risk habits were included in this study. Quantitative real-time PCR was used to analyze KRT13, FAIM2 and CYP2W1 in OSCC. The housekeeping gene (GAPDH) was used as an endogenous control.
RESULTS: Of the 41 OSCC samples, KRT13 was down-regulated in 40 samples (97.6%), while FAIM2 and CYP2W1 were down-regulated in 61.0% and 48.8%, respectively. Overall, there were no associations between KRT13, FAIM2 and CYP2W1 expression with risk habits, selected socio-demographic and clinico-pathological parameters and patient survival.
CONCLUSIONS: Although this study was unable to show significance, there were some tendencies in the associations of KRT13, FAIM2 and CYP2W1 expression in OSCC with selected clinic-pathological parameters and survival.
MATERIALS AND METHODS: This cross-sectional study was conducted on 258 community dwelling women from urban and rural settings who participated in health campaigns. In order to reduce the sampling bias, half of the study population performed the self-sampling prior to the physician sampling while the other half performed the self-sampling after the physician sampling, randomly. Acquired samples were assessed for cytological changes as well as HPV DNA detection.
RESULTS: The mean age of the subjects was 40.4±11.3 years. The prevalence of abnormal cervical changes was 2.7%. High risk and low risk HPV genotypes were found in 4.0% and 2.7% of the subjects, respectively. A substantial agreement was observed between self-sampling and the physician obtained sampling in cytological diagnosis (k=0.62, 95%CI=0.50, 0.74), micro-organism detection (k=0.77, 95%CI=0.66, 0.88) and detection of hormonal status (k=0.75, 95%CI=0.65, 0.85) as well as detection of high risk (k=0.77, 95%CI=0.4, 0.98) and low risk (K=0.77, 95%CI=0.50, 0.92) HPV. Menopausal state was found to be related with 8.39 times more adequate cell specimens for cytology but 0.13 times less adequate cell specimens for virological assessment.
CONCLUSIONS: This study revealed that self-sampling has a good agreement with physician sampling in detecting HPV genotypes. Self-sampling can serve as a tool in HPV screening while it may be useful in detecting cytological abnormalities in Malaysia.
METHODS: Predialysis CKD patients were included in this cross-sectional study. Patient demographics, medical/medication histories, and laboratory parameters (serum 25-hydroxyvitamin D (25(OH)D), creatinine, phosphate (P), calcium, albumin, and intact-PTH (i-PTH)) were collected and compared among patients with various CKD stages. The association between 25(OH)D and these parameters was determined by multiple linear regression.
RESULTS: A total of 196 patients with mean ± SD eGFR of 26.4 ± 11.2 mL/min/1.73 m2 was included. Vitamin D deficiency (25(OH)D concentration < 15 ng/mL) and insufficiency (25(OH)D concentration 16 - 30 ng/mL) was found in 29.1% and 57.7% of the patients, respectively. Mean ± SD serum 25(OH)D was 20.8 ± 9.3 ng/mL. Female patients had lower vitamin D concentrations than males (16.9 ng/mL vs. 23.9 ng/mL; p < 0.001). Vitamin D levels were also higher in Chinese (22.3 ng/mL) than Malay (17.3 ng/mL) and Indian (13.1 ng/mL) patients (p < 0.05). Nonadjusted analyses showed higher i-PTH concentration in vitamin D deficient patients (p < 0.05).
CONCLUSION: Despite being a sun-rich country all year round, the majority (86.8%) of predialysis CKD patients in Singapore have suboptimal vitamin D status. Lower vitamin D concentrations were found in females and in those with darker skin tone. Vitamin D deficient patients also tended to have higher i-PTH levels.
MATERIALS AND METHODS: This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes.
RESULTS: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese (p<0.05).
CONCLUSIONS: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.
MATERIALS AND METHODS: The clinical characteristics, presenting symptoms and survival of RCC patients (n=151) treated at UMMC from 2003-2012 were analysed. Symptoms evaluated were macrohaematuria, flank pain, palpable abdominal mass, fever, lethargy, loss of weight, anaemia, elevated ALP, hypoalbuminemia and thrombocytosis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic significance of these presenting symptoms. Kaplan Meier and log rank tests were employed for survival analysis.
RESULTS: The 2002 TNM staging was a prognostic factor (p<0.001) but Fuhrman grading was not significantly correlated with survival (p=0.088). At presentation, 76.8% of the patients were symptomatic. Generally, symptomatic tumours had a worse survival prognosis compared to asymptomatic cases (p=0.009; HR 4.74). All symptoms significantly affect disease specific survival except frank haematuria and loin pain on univariate Cox regression analysis. On multivariate analysis adjusted for stage, only clinically palpable abdominal mass remained statistically significant (p=0.027). The mean tumour size of palpable abdominal masses, 9.5±4.3cm, was larger than non palpable masses, 5.3±2.7cm (p<0.001).
CONCLUSIONS: This is the first report which includes survival information of RCC patients from Malaysia. Here the TNM stage and a palpable abdominal mass were independent predictors for survival. Further investigations using a multicentre cohort to analyse mortality and survival rates may aid in improving management of these patients.