Journal of the Medical Sciences (Berkala ilmu Kedokteran)
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miR-21, miR-29c, and miR-155 as Biomarker to Develop Minimal Invasive Diagnostic in Hepatocellular Carcinoma Patient
Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and the third leading cause of cancer-related deaths worldwide. Incidence and mortality of HCC increase annually because of its poor prognosis. The most common cause of this condition is its characteristics with high metastasis and high recurrence after surgical treatment. So, it is become important to find new serological biomarkers for early stage detection of HCC. Plasma microRNA are being actively investigated as minimal invasive biomarkers in human cancers, including HCC.Objective: The aim of this study is to investigate the level expression of miR-21, miR-29c, and miR-155 as novel serological biomarkers for hepatocellular carcinoma.Methods: This study is quasi experimental and remain as preliminary study. Collecting for more samples is currently underway. HCC patient blood samples obtained from RSUP dr. Sardjito Yogyakarta based on specific inclusion and exclusion criteria. Blood samples were collected from 8 patients and 8 healthy controls. The collected blood samples were treated as follows: plasma isolation, RNA total isolation, cDNA synthesis, quantification by qRT-PCR, data analysis with Biorad CFX ManagerTM Softwere to determine Cq, followed by the calculation of expression levels using Livax Methods.Result: The result showed that miR-21 and miR-155 were upregulated 1.68 fold and 2.38 fold respectively compared with healthy control, while miR-29c was downregulated 3,45 fold compared with healthy control.Conclusion: Based on the result of preliminary study, it can be concluded that miR-21 act as oncomiR, while miR-29c and miR-155 act as tumor supressor miR in HCC. The three microRNAs can be detected in HCC and can be used as minimal invasive biomarkers to detect HCC.Keywords: HCC, miR-21, miR-29c, miR-155, minimal invasive, biomarke
The Expression of Homo Sapiens microRNA-21 (Hsa-miR-21-5p) and mRNA Reversion Inducing Cysteine Rich Protein with Kazal Motifs (RECK) in Plasma of Epithelial Ovarian Cancer
ABSTRACT Epithelial Ovarian Cancer (EOC) is malignant cancer that caused death for most women in Indonesia. The emergence of EOC showed no specific symptoms in its early stages; that makes the screening mostly occur when patients are in advanced stage. Treatment of EOC at an advanced stage will be more challenging with poor prognosis. Therefore, minimally invasive biomarkers are needed to diagnose at the early stage. microRNA is one of the potential biomarkers which not only expressed inside the cell but also secreted outside the cell with exosome protection. This protection makes microRNA stable. Moreover, several studies have shown the ability to detect microRNA in the blood sample. microRNA-21 (miR-21) is oncomiR which targeted tumor suppressor mRNA RECK based on in silico analysis.The first aim is to determine the expression of miR-21 in plasma samples of EOC patients compared with healthy controls. The second aim is to investigate the expression correlation between miR-21 and RECK mRNA.Blood samples were collected from 30 patients and 30 healthy controls. Plasma was then obtained from centrifugated blood samples. The total RNA was isolated and reverse transcribed to produce cDNAs. cDNAs were then quantified using qPCR using specific primer for miR-21 and RECK mRNA. The expression analysis was done relative expression method by Livak. The expression of miR-21 was calculated using the miR-16 expression as the reference gene. Also, Beta-actin was used as reference gene for RECK mRNA calculation. The correlation between the expression of miR-21 and mRNA RECK was analyzed using the Spearman rho correlation analysis.In this study showed the expression of miR-21 in patients with EOC increased 4.7579-fold compared with healthy controls (p <0.05). On the other hand, the miR-21 target, RECK mRNA, decreased 4,2 times with fold change 0.237665 on plasma EOC patients compared with healthy controls (p <0.05). The statistical calculation of the expression of miR-21 and mRNA RECK was inversely proportional to mRNA RECK with a strong correlationThis study has been able to prove that the expression of miR-21 is up-regulated in EOC patients and confirmed by the down-regulation of RECK expression. The next research challenge is to make anti-miR-21 to suppress the expression of miR-21 in EOC, which can be analyzed the effect of miR-21 in the development of EOC
Hormonal Contraceptive Use as Risk Factor for Breast Cancer in Young Javanese Women
Previous study from 351 Indonesian women shown that they had breast cancers at younger age compared with western. In this study we investigate role of hormonal contraceptive as risk factor for Indonesian Javanese young breast cancer cases. However, the presence different life style between ethnic alter their risk as causal factors across populations. Diagnostic and prognostic study findings, including breast cancer prediction rules, must therefore be validated in Asian women. We undertook case-control study to determine population-based distributions of breast cancer among young Javanese people, one of the largest populations in Indonesia (Southeast Asia). A total of 500 women diagnosed with breast cancer participated in this study, divided in to two group young (less 40 years old) and mature breast cancer. Data for hormonal contraceptive, clinico-pathological characteristics and other risk factors were collected. We found that young Javanese women who use hormonal contraceptive for more than 10 years had a 4,67 fold increased risk of being diagnosed with breast cancer in young age (p<0,01). We didn’t found any differences between this two groups in menarche and parity. Interestingly for Javanese women who breast feeding more than 18 months increase 1,74 fold increased risk of being diagnosed with breast cancer in young age (p<0,01).
The effect of a-terpineol on cell cycle, apoptosis and Bcl-2 family protein expression of breast cancer cell line MCF-7
ABSTRACT The cytotoxic activity of a-terpineol on T47D and HeLa cancer cell lines have been reported. This study was conducted to evaluate the effect of a-terpineol on cell cycle, apoptosis and Bcl-2 as well as Bax expression on MCF-7 cell line. The cytotoxic activity of a-terpineol was determined using MTT cell assay. Cell cycle and apoptosis were analysed using flowcytometry, whereas Bcl-2 and Bax expression were evaluated using immunohistochemistry. The results showed that a-terpineol had cytotoxic effect on the MCF-7 cell lines with an IC50 value of 33.0 ± 5.4 μg/mL. a-Terpineol induced cell accumulation in Sub-G1 lead to apoptosis of the MCF-7 cell. Moreover, a-terpineol inhibited Bcl-2 and induced Bax expressions. In conclusion, a-terpineol has potential anticancer activity against MCF-7 cancer cell line trough through cells cycle inhibition and apoptosis stimulation
Scoring system based on electrocardiogram features to predict the type of heart failure in patients with chronic heart failure
ABSTRACT Heart failure is divided into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Additional studies are required to distinguish between these two types of HF. A previous study showed that HFrEF is less likely when ECG findings are normal. This study aims to create a scoring system based on ECG findings that will predict the type of HF. We performed a cross-sectional study analyzing ECG and echocardiographic data from 110 subjects. HFrEF was defined as an ejection fraction ≤40%. Fifty people were diagnosed with HFpEF and 60 people suffered from HFrEF. Multiple logistic regression analysis revealed certain ECG variables that were independent predictors of HFrEF i.e., LAH, QRS duration >100 ms, RBBB, ST-T segment changes and prolongation of the QT interval. Based on ROC curve analysis, we obtained a score for HFpEF of -1 to +3, while HFrEF had a score of +4 to +6 with 76% sensitivity, 96% specificity, 95% positive predictive value, an 80% negative predictive value and an accuracy of 86%. The scoring system derived from this study, including the presence or absence of LAH, QRS duration >100 ms, RBBB, ST-T segment changes and prolongation of the QT interval can be used to predict the type of HF with satisfactory sensitivity and specificit
Association between HLA-B alleles and nevirapine-induced allergies among Indonesian HIV patients
This study aimed to investigate the association between human leukocyte antigen-B(HLA-B) alleles and nevirapine allergy in HIV patients in Indonesia. A case control studywas conducted involving 147 HIV patients comprising of 50 patients with and 97patients without nevirapine allergy as control. The HLA-B allele typing was conducted byusing polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP),followed by sequencing. Bivariate analysis using Chi-square (X2) test and multivariatelogistic regression with significance level at p<0.05 were applied to analysis the data.Among 147 subjects, 34 with HLA-B alleles were identified. Bivariable analysis showedthat HLA-B*58 allele was the most significant risk factor for the nevirapine allergy (OR= 3.67; 95% CI: 1.79 to 7.54), while HLA-B*35 allele was a protective factor (OR =0.18; 95% CI: 0.08 to 0.42). Multivariate logistic regression analysis showed that youngmen and HLA-B*58 allele were the significant risk factors of nevirapine allergy (OR: 4.63;95% CI: 2.02 to 10.61), while older women with the HLA-B*35 was able to reducethe risk of nevirapine allergy approximately 81% (OR: 0.19; 95% CI: 0.08 to 0.49). Inconclusion, young male with the HLA-B*58 allele are the high risk factor for nevirapineallergy in Indonesian HIV patients
The influence of proton pump inhibitors on the effect of clopidogrel on the risk of recurrent ischemic stroke
Patients surviving with a stroke have an increased risk for recurrent stroke. Clopidogrel iswidely used to prevent recurrent stroke. However, clopidogrel may cause gastrointestinalbleeding (GIB). Therefore, proton pump inhibitors (PPIs) is recommended to reduce theside effect of clopidogrel. Unfortunately, these both drugs are metabolized in the liverby the same enzyme i.e. cytochrome P4502C19 (CYP219) that may reduce the effectof clopidogrel. The aim of this study was to evaluate the influence of PPIs on the effectof clopidogrel in the prevention of recurrent stroke. It was a hospital-based case controlstudy conducted in Bethesda Private Hospital, Yogyakarta involving 392 patients withrecurrent stroke as cases and 784 patients with first-ever stroke as controls. The exposureof PPIs during clopidogrel therapy on both cases and controls groups were recordedfrom prescription records for at least six months before index date. The duration of PPIsexposure were categorized as current expoure (less than two months before the indexdate) and recent exposure (2-6 months before the index date). The result showed therewas no influence of PPIs exposure on the effect of clopidogrel on the risk of recurrentischemic stroke (OR: 1.00; 95% CI: 0.56-1.79). Moreover, the current use of PPIs andclopidogrel could decrease the risk of recurrent ischemic stroke (OR: 0.04; 95% CI:0.01-0.41). In conclusion, there is no association between PPI exposure and the risk ofrecurrent stroke in patients receiving clopidogrel
The effect of mitomycin-c in keloid fibroblast cultures
ABSTRACTKeloid occurs due to hyperactivity of keloid fibroblast (KF) in proliferation, migration, collagen deposition, together with low rates of collagen degradation. These are under the responsibility of TGF-b. Mitomycin C (MC) is used for treating keloid by a topical application during surgery at the level of 0.02% to 0.08%. Unfortunately, the lowest effective level of MC for keloid has not been determined yet. We aimed to determine the lowest effective level of MC in the suppression of KF activities. Various levels of MC diluted in growth medium were administered on KF that were isolated from six patients. After 24 hours and 72 hours of incubation, cellular proliferation, collagen deposition, cellular migration and level of TGF-b, were analyzed. Application of 120 uM MC on KF culture for 24 hours could significantly reduce TGF-b production from 1265.74 ± 274.81 pg/mL to 265.17 ± 12.20 pg/mL; proliferation index from 100% to 84.01 ± 12.91%; inhibit cellular migration to 64.38 ± 3.66%; but reduce collagen depositions from 100% to only 91.13 ± 10.19%. The lowest MC level is on 30 uM or equal with 0.001%. In conclusion, the lowest level of MC can suppress the activities of KF is 0.001%. Moreover, due to low activity in inhibiting collagen deposition, MC would be better as an adjuvant drug for keloid surgery
Prognostic factors for constipation following primary surgery of anorectal malformations in Yogyakarta, Indonesia
ABSTRACT Anorectal Malformation (ARM) is a congenital malformation of the anorectal area, occur approximately once in every 5000 live births. There are several morbidities could occur after surgery in ARM. Constipation is the most common morbidity post-surgery in ARM. This study was conducted to evaluate the prognostic factors affecting constipation in postoperative anorectal malformation. This was a case control study involving 74 children who undergo surgery in Dr. Sardjito General Hospital, Yogyakarta from 2008 to 2012. The prognostic factors are sex, type of ARM, age, type of ostomi, type of anoplasty operation, dehiscence of anoplasty, and anal dilatation. There were 41 (55.4%) male patients and 33 (44.6%) female patients in this study. The risk of constipation in the patients with high level ARM was lower than in low level ARM with an OR of 0.150 (95% CI=0.032 - 0.711; p=0.008). Abdominoperineal pullthrough had higher risk for constipation than non abdominoperineal pullthrough (PSARP and ASA) with p = 0.003. The constipation rate was also different between patients with and without dehiscence of anoplasty with an OR of 0.139 (95% CI=0.033 - 0.584; p=0.005). The gender, types of colostomy, types of colon for colostomy, age of primary operation, and frequency of anal dilatation did not affect the constipation rate. In conclusion, postoperative constipation is still a major problem in surgical for anorectal malformations in Yogyakarta. Types of anomaly, primary operative procedures, and dehiscence of anoplasty operation are the prognostic factors that affect the constipation in anorectal malformations
Evaluation of primary health workers training program to provide psychoeducation to family caregivers of persons with psychotic disorder
ABTRACT Many persons suffering psychotic illnesses, such as schizophrenia, are largely untreated in low income countries. In these settings, most persons with severe mental illness live with their families. Thus, families play a particular critical role in determining whether a person with a psychotic illness will receive treatment and what the quality of treatment. Psychoeducation has proven to be extremely effective in helping families develop the knowledge and skills which is necessary to help their family members. Indonesia has a national policy to integrate the management of mental health problems into the primary health care system. However, in practice, such care does not implemented effectively. A preliminary study in primary health centers in two districts of Bantul and Gunung Kidul regency, Yogyakarta province, showed that there was very little or there is not any training for health care workers on diagnosis and treatment of psychotic disorder. This study was conducted to evaluate the effectiveness of the training program for health workers in three primary health centers in Yogyakarta, Indonesia, to provide psychoeducation to family caregivers for persons with psychotic disorder. A quasi-experimental study with the approach of one group pre and posttest design was performed in this study. Fortythree health workers in 3 primary health centers in Bantul and Gunung Kidul, Yogyakarta were trained every week for a month to provide psychoeducation to family caregivers who live with psychotic disorder patient. Result showed that the baseline score of knowledge of schizophrenia among health workers in 3 primary health centers in Bantul and Gunung Kidul before training were not significantly different (p=0.162). After the psychoeducation training program there were significantly different (p=0.003) of the score of knowledge of schizophrenia among health workers in 3 primary health care centers compared with before training. For conclusion, the training program to provide psychoeducation to family care providers of persons with psychotic disorder for primary health workers was effective to increase their knowledge of schizophrenia