Mochtar Riady Institute for Nanotechnology

Tangerang, Indonesia

Mochtar Riady Institute for Nanotechnology

Tangerang, Indonesia
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Wang W.-W.,National Cancer Center Singapore | Ang S.F.,National Cancer Center Singapore | Kumar R.,Singapore General Hospital | Heah C.,National University of Singapore | And 10 more authors.
PLoS ONE | Year: 2013

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential biomarker on a larger scale in patients at-risk of HCC. © 2013 Wang et al.


Suriapranata I.M.,Mochtar Riady Institute for Nanotechnology | Sudania W.M.,Mochtar Riady Institute for Nanotechnology | Tjong W.Y.,Mochtar Riady Institute for Nanotechnology | Suciptan A.A.,Mochtar Riady Institute for Nanotechnology | And 12 more authors.
Clinica Chimica Acta | Year: 2010

Background: Elevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians. Methods: Direct DNA sequencing was carried out to sequence AFP promoter, exons, and 3′ untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. Results: In this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3′UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis. Conclusion: Genetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians. © 2009 Elsevier B.V. All rights reserved.


Bachtiar I.,Mochtar Riady Institute for Nanotechnology | Kheng V.,Mochtar Riady Institute for Nanotechnology | Wibowo G.A.,Mochtar Riady Institute for Nanotechnology | Gani R.A.,University of Indonesia | And 10 more authors.
BMC Research Notes | Year: 2010

Background. The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We determined the performances of α-1-acid glycoprotein (AAG) and des-γ-carboxy prothrombin (DCP) for the diagnosis of HCC, especially for α-fetoprotein (AFP)-low HCC. Methods. Of the 220 patients included in this retrospective study, 124 had HCC, and 61 (49%) of these were AFP-low HCC (AFP ≤ 20 ng/mL). The remaining 96 patients, including 49 with chronic hepatitis B or C and 47 with cirrhosis, were considered as control. Plasma AAG was analyzed using high performance liquid chromatography (HPLC) and confirmed using Western blot technique. Results. When all patients with HCC were evaluated, the area under receiver operating characteristic (ROC) curves for AAG (0.94, 95% CI: 0.91-0.97) and DCP (0.92, 95% CI: 0.88-0.95) were similar (P = 0.40). AAG had better area under ROC curve (0.96, 95% CI: 0.94-0.99) than DCP (0.87, 95% CI: 0.81-0.93) for AFP-low HCC (P < 0.05). At the specificity 95%, the sensitivity of AAG was higher in AFP-low HCC than in AFP-high HCC (82% and 62%, respectively). In contrast, higher sensitivity was obtained from DCP in discriminating HCC patients with low AFP than that in high AFP (57% and 90%, respectively). Conclusion. Our cross-sectional study showed that AAG was better performance in diagnosing HCC patients with low AFP, while DCP did better in those with high AFP. © 2010 Bachtiar et al; licensee BioMed Central Ltd.


Salim M.I.M.,University of Technology Malaysia | Supriyanto E.,University of Technology Malaysia | Haueisen J.,TU Ilmenau | Ariffin I.,University of Technology Malaysia | And 2 more authors.
Medical and Biological Engineering and Computing | Year: 2013

This paper proposes a novel hybrid magnetoacoustic measurement (HMM) system aiming at breast cancer detection. HMM combines ultrasound and magnetism for the simultaneous assessment of bioelectric and acoustic profiles of breast tissue. HMM is demonstrated on breast tissue samples, which are exposed to 9.8 MHz ultrasound wave with the presence of a 0.25 Tesla static magnetic field. The interaction between the ultrasound wave and the magnetic field in the breast tissue results in Lorentz Force that produces a magnetoacoustic voltage output, proportional to breast tissue conductivity. Simultaneously, the ultrasound wave is sensed back by the ultrasound receiver for tissue acoustic evaluation. Experiments are performed on gel phantoms and real breast tissue samples harvested from laboratory mice. Ultrasound wave characterization results show that normal breast tissue experiences higher attenuation compared with cancerous tissue. The mean magnetoacoustic voltage results for normal tissue are lower than that for the cancerous tissue group. In conclusion, the combination of acoustic and bioelectric measurements is a promising approach for breast cancer diagnosis. © 2012 International Federation for Medical and Biological Engineering.


Utama A.,Mochtar Riady Institute for Nanotechnology | Tania N.P.,Mochtar Riady Institute for Nanotechnology | Dhenni R.,Mochtar Riady Institute for Nanotechnology | Gani R.A.,University of Indonesia | And 7 more authors.
Liver International | Year: 2010

Background: Hepatitis C virus (HCV) genotype distribution in Indonesia has been reported. However, the identification of HCV genotype was based on 5'-UTR or NS5B sequence. Aims: This study was aimed to observe HCV core sequence variation among HCV-associated liver disease patients in Jakarta, and to analyse the HCV genotype diversity based on the core sequence. Methods: Sixty-eight chronic hepatitis (CH), 48 liver cirrhosis (LC) and 34 hepatocellular carcinoma (HCC) were included in this study. HCV core variation was analysed by direct sequencing. Results: Alignment of HCV core sequences demonstrated that the core sequence was relatively varied among the genotype. Indeed, 237 bases of the core sequence could classify the HCV subtype; however, 236 bases failed to differentiate several subtypes. Based on 237 bases of the core sequences, the HCV strains were classified into genotypes 1 (subtypes 1a, 1b and 1c), 2 (subtypes 2a, 2e and 2f) and 3 (subtypes 3a and 3k). The HCV 1b (47.3%) was the most prevalent, followed by subtypes 1c (18.7%), 3k (10.7%), 2a (10.0%), 1a (6.7%), 2e (5.3%), 2f (0.7%) and 3a (0.7%). HCV 1b was the most common in all patients, and the prevalence increased with the severity of liver disease (36.8% in CH, 54.2% in LC and 58.8%in HCC). These results were similar to a previous report based on NS5B sequence analysis. Conclusion: Hepatitis C virus core sequence (237 bases) could identify the HCV subtype and the prevalence of HCV subtype based on core sequence was similar to those based on the NS5B region. © 2010 John Wiley & Sons A/S.


Awad H.M.,National Research Center of Egypt | El-Enshasy H.A.,University of Technology Malaysia | El-Enshasy H.A.,Genetic Engineering and Biotechnology Research Institute | Hanapi S.Z.,University of Technology Malaysia | And 2 more authors.
Natural Product Research | Year: 2014

This study discusses the isolation and identification of a new Streptomycetes highly active chitinase producer. Fifteen strains were isolated from Malaysian soil samples. The isolate WICC-A03 was found to be the most active chitinase producer. Its antifungal activity was evaluated against many phytopathogens. The identification of WICC-A03 using phenotypic and genotypic methods strongly indicated that strain WICC-A03 belonged to the genus Streptomyces and displayed similarity (91%) with Streptomyces glauciniger. Thus, it was given the suggested name S. glauciniger WICC-A03 with accession number: JX139754. WICC-A03 produces extracellular chitinase in a medium containing 1.5% colloidal chitin in submerged culture on 144 h. The produced enzyme was partially characterised and its molecular weight of 50 kDa was determined by using SDS-PAGE. This study indicates that WICC-A03 is a potential chitinase producer for biocontrol of plant pathogens. Further experiments are being carried out to optimise medium composition and cultivation conditions under lab and bioreactor scale. © 2014 Taylor & Francis.


Suriapranata I.M.,Mochtar Riady Institute for Nanotechnology | Tjong W.Y.,Mochtar Riady Institute for Nanotechnology | Wang T.,Mochtar Riady Institute for Nanotechnology | Utama A.,Mochtar Riady Institute for Nanotechnology | And 3 more authors.
BMC Medical Genetics | Year: 2011

Background: CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs) in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients.Methods: Direct sequencing method was used to identify SNPs in CYP2C9, VKORC1, CYP4F2, EPHX1, PROC and GGCX genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing.Results: From the 40 SNPs analyzed, CYP2C9 rs17847036 and VKORC1 rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between CYP2C9*3, CYP2C9C-65 (rs9332127), CYP4F2 rs2108622, GGCX rs12714145, EPHX1 rs4653436 and PROC rs1799809 with warfarin sensitivity.Conclusions: VKORC1 rs9923231 AA and CYP2C9 rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively). CYP2C9 and VKORC1 genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians. © 2011 Suriapranata et al; licensee BioMed Central Ltd.


PubMed | Mochtar Riady Institute for Nanotechnology
Type: | Journal: BMC research notes | Year: 2010

The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We determined the performances of -1-acid glycoprotein (AAG) and des--carboxy prothrombin (DCP) for the diagnosis of HCC, especially for -fetoprotein (AFP)-low HCC.Of the 220 patients included in this retrospective study, 124 had HCC, and 61 (49%) of these were AFP-low HCC (AFP 20 ng/mL). The remaining 96 patients, including 49 with chronic hepatitis B or C and 47 with cirrhosis, were considered as control. Plasma AAG was analyzed using high performance liquid chromatography (HPLC) and confirmed using Western blot technique.When all patients with HCC were evaluated, the area under receiver operating characteristic (ROC) curves for AAG (0.94, 95% CI: 0.91-0.97) and DCP (0.92, 95% CI: 0.88-0.95) were similar (P = 0.40). AAG had better area under ROC curve (0.96, 95% CI: 0.94-0.99) than DCP (0.87, 95% CI: 0.81-0.93) for AFP-low HCC (P < 0.05). At the specificity 95%, the sensitivity of AAG was higher in AFP-low HCC than in AFP-high HCC (82% and 62%, respectively). In contrast, higher sensitivity was obtained from DCP in discriminating HCC patients with low AFP than that in high AFP (57% and 90%, respectively).Our cross-sectional study showed that AAG was better performance in diagnosing HCC patients with low AFP, while DCP did better in those with high AFP.


PubMed | Mochtar Riady Institute for Nanotechnology
Type: | Journal: BMC immunology | Year: 2011

Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function.As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DR high/CD11c high and CD80+/CD86 high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70).D2- and D3- but not D1-AFP extensively suppresses the MDDC function. All the recombinant AFP proteins impaired the ability of MDDC to secrete IL-12.


PubMed | Mochtar Riady Institute for Nanotechnology
Type: Journal Article | Journal: Clinica chimica acta; international journal of clinical chemistry | Year: 2010

Elevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians.Direct DNA sequencing was carried out to sequence AFP promoter, exons, and 3 untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed.In this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis.Genetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians.

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