Uptake and Cytotoxicity Characterization of Radioiodine in MCF-7 and SKBR3 Breast Cancer Cell Lines

Radioiodine is an effective and low-risk therapy modality in well-differentiated thyroid cancer patients post near-total thyroidectomy. Extra thyroidal tumors such as breast cancer are known to be able to uptake radioiodine. The aim of this study was to analyze the uptake, efflux and cytotoxicity of radioiodine for two molecular types of breast cancer cell lines. Two types of breast cancer cell lines were used in this study, MCF-7 (luminal A type) and SKBR3 (HER2 type). The HaCaT cell line was used as normal cells. Iodine-125 (I-125)was used to measured radioiodine uptake and efflux. Clonogenic assay was used to assess cytotoxicity of iodine-131 (I-131) based on the tested cell reproductive ability. The radioiodine uptake in SKBR3cells was found to be higher than that of MCF-7 and HaCaT cells atp<0.05. The reproductive ability of MCF-7 cells are lower than SKBR3 cells at p<0.05. Both breast cancer cells have lessreproduction ability than HaCaT cells at p<0.05. Both types of breast cancer cells present the ability to uptake radioiodine and show a high sensitivity to radioiodine exposure. Normal cells also demonstrate an ability to uptake radioiodine. However, they have a better tolerance to the amount of I-131 exposure. These findings could potentially lead to the use if I-131 for ablative therapy in breast cancer, similiar to its use in the treatment of thyroid cancer.Received: 4 October 2015; Revised: 14 August 2016; Accepted: 2 September 2016

ACTIVITY OF BENZOPHENONE GLUCOSIDE FROM MAHKOTA DEWA {Phaleria macrocarpa (Scheff.) Boerl.} FRUITS ON PROLIFERATION OF HUMAN CERVICAL-CANCER CELLS (HeLa and CasKi) AND HUMAN ESOPHAGEAL CANCER CELLS (TE-2, TE-8, and TE-14)

Phaleria macrocarpa, locally named mahkota dewa, is known as a medicinal plant in Indonesia. Fruits of this plant are traditionally used in treatment of cancer diseases. Several substances were isolated from mahkota dewa fruits. A benzophenone glucoside, 4,6`-dihydroxy-4`-methoxybenzophenone-2’-O-glucoside, has been isolated from an ethyl acetate fraction of mahkota dewa fruits. The structure of this compound was determined based on the analysis of UV, IR, NMR and MS spectral data. Antiproliferative activity was measured on human cervical cancer cells (HeLa and CasKi) and human esophageal cancer cells (TE-2, TE-8, and TE-14) by MTT assay. The result of this study showed that at concentration of 500 ìg/mL, benzophenone glucoside derived from mahkota dewa didn’t reach CPI50 to all tested cells. Those CPI50 were 34 ìg/mL (HeLa), 32 ìg/mL (CasKi), 33.91 ìg/mL (TE-2), 35.43 ìg/mL (TE-8), 43.04 ìg/mL (TE-14). There were no significantly differences (á=0.5) of this activity among HeLa, CasKi, TE-2, TE-8 and TE-14 cells.Key words : Benzophenone glucoside, Phaleria macrocarpa, HeLa, CasKi, TE-2, TE-8, and TE-14 cells, MTT assa

HUBUNGAN POLIMORFISME GEN ME2 DENGAN EPILEPSI IDIOPATIK UMUM DAN RESPON TERAPI VALPROAT

Penelitian ini bertujuan untuk: (1) Mendeteksipolimorfisme rs585344, rs645088 dan rs642698, genME2 pada EIU anak tanpa epilepsi untuk menentukanadanya hubungan polimorfime gen ME2 denganEIU. (2) Menentukan jumlah proporsi hilangnyabangkitan 6 bulan setelah pengobatan valproat padaEIU dengan genotipe mutan dan genotip bukanmutan polimorfisme rs585344, rs645088 dan rs642698gen ME2. Penelitian kasus-kontrol dilakukan selamaperiode Juli 2010 sampai April 2012 terhadap 92subjek EIU usia awitan anak dan remaja di RS HasanSadikin Bandung, RS Cipto Mangunkusumo Jakartadan RS St Borromeus Bandung, 336 subjek kontrol diRS Hasan Sadikin Bandung. Hasil penelitian denganuji chi-kuadrat menunjukkan perbedaan bermaknaproporsi genotip polimorfisme rs585344 gen ME2antara EIU usia awitan anak dan remaja dengankontrol (p 0,05). Didapatkan perbedaan bermakna genotipmutan polimorfisme rs585344, rs645088 dan rs642698gen ME2 EIU usia awitan anak < 11 tahun dengangenotip mutan polimorfisme rs585344, rs645088 danrs642698 gen ME2 EIU usia awitan anak ≥ 11 tahun(age-dependent penetrance)

G6PD genetic variations in neonatal Hyperbilirubinemia in Indonesian Deutromalay population

Background: Neonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations a

Uptake and Cytotoxicity Characterization of Radioiodine in MCF-7 and SKBR3 Breast Cancer Cell Lines

Radioiodine is an effective and low-risk therapy modality in well-differentiated thyroid cancer patients post near-total thyroidectomy. Extra thyroidal tumors such as breast cancer are known to be able to uptake radioiodine. The aim of this study was to analyze the uptake, efflux and cytotoxicity of radioiodine for two molecular types of breast cancer cell lines. Two types of breast cancer cell lines were used in this study, MCF-7 (luminal A type) and SKBR3 (HER2 type). The HaCaT cell line was used as normal cells. Iodine-125 (I-125)was used to measured radioiodine uptake and efflux. Clonogenic assay was used to assess cytotoxicity of iodine-131 (I-131) based on the tested cell reproductive ability. The radioiodine uptake in SKBR3cells was found to be higher than that of MCF-7 and HaCaT cells atp<0.05. The reproductive ability of MCF-7 cells are lower than SKBR3 cells at p<0.05. Both breast cancer cells have lessreproduction ability than HaCaT cells at p<0.05. Both types of breast cancer cells present the ability to uptake radioiodine and show a high sensitivity to radioiodine exposure. Normal cells also demonstrate an ability to uptake radioiodine. However, they have a better tolerance to the amount of I-131 exposure. These findings could potentially lead to the use if I-131 for ablative therapy in breast cancer, similiar to its use in the treatment of thyroid cancer

Developing a Competence-Based Addiction Medicine Curriculum in Indonesia: The Training Needs Assessment

Item does not contain fulltextIndonesia has one of the fastest growing, injecting drugs user-driven, human immunodeficiency virus (HIV) epidemics in Asia. Coverage of needle and syringe programs (NSPs), opioid substitution therapy (OST), and antiretroviral treatment (ART) is increasing, but is still low, whereas professional training in addiction medicine is not yet established. Urgent development and scaling-up of professional capacity in comprehensive, evidence-based addiction medicine is needed. In this article the results of the first step is presented, being the training needs assessment (TNA) and the process of further developing a national evidence- and competence-based addiction medicine curriculum in Indonesia

Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial.

Contains fulltext : 118671.pdf (publisher's version ) (Closed access)BACKGROUND: Intensified antibiotic treatment might improve the outcome of tuberculous meningitis. We assessed pharmacokinetics, safety, and survival benefit of several treatment regimens containing high-dose rifampicin and moxifloxacin in patients with tuberculous meningitis in a hospital setting. METHODS: In an open-label, phase 2 trial with a factorial design in one hospital in Indonesia, patients (aged >14 years) with tuberculous meningitis were randomly assigned to receive, according to a computer-generated schedule, first rifampicin standard dose (450 mg, about 10 mg/kg) orally or high dose (600 mg, about 13 mg/kg) intravenously, and second oral moxifloxacin 400 mg, moxifloxacin 800 mg, or ethambutol 750 mg once daily. All patients were given standard-dose isoniazid, pyrazinamide, and adjunctive corticosteroids. After 14 days of treatment all patients continued with standard treatment for tuberculosis. Endpoints included pharmacokinetic analyses of the blood and cerebrospinal fluid, adverse events attributable to tuberculosis treatment, and survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01158755. FINDINGS: 60 patients were randomly assigned to receive rifampicin standard dose (12 no moxifloxacin, ten moxifloxacin 400 mg, and nine moxifloxacin 800 mg) and high dose (ten no moxifloxacin, nine moxifloxacin 400 mg, and ten moxifloxacin 800 mg). A 33% higher dose of rifampicin, intravenously, led to a three times higher geometric mean area under the time-concentration curve up to 6 h after dose (AUC(0-6); 78.7 mg.h/L [95% CI 71.0-87.3] vs 26.0 mg.h/L [19.0-35.6]), maximum plasma concentrations (C(max); 22.1 mg/L [19.9-24.6] vs 6.3 mg/L [4.9-8.3]), and concentrations in cerebrospinal fluid (0.60 mg/L [0.46-0.78] vs 0.21 mg/L [0.16-0.27]). Doubling the dose of moxifloxacin resulted in a proportional increase in plasma AUC(0-6) (31.5 mg.h/L [24.1-41.1] vs 15.1 mg.h/L [12.8-17.7]), C(max) (7.4 mg/L [5.6-9.6] vs 3.9 mg/L [3.2-4.8]), and drug concentrations in the cerebrospinal fluid (2.43 mg/L [1.81-3.27] vs 1.52 mg/L [1.28-1.82]). Intensified treatment did not result in increased toxicity. 6 month mortality was substantially lower in patients given high-dose rifampicin intravenously (ten [35%] vs 20 [65%]), which could not be explained by HIV status or severity of disease at the time of presentation (adjusted HR 0.42; 95% CI 0.20-0.91; p=0.03). INTERPRETATION: These data suggest that treatment containing a higher dose of rifampicin and standard-dose or high-dose moxifloxacin during the first 2 weeks is safe in patients with tuberculous meningitis, and that high-dose intravenous rifampicin could be associated with a survival benefit in patients with severe disease. FUNDING: Royal Dutch Academy of Arts and Sciences, Netherlands Foundation for Scientific Research, and Padjadjaran University, Bandung, Indonesia.1 januari 201

Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in Indonesia

Contains fulltext : 174715.pdf (publisher's version ) (Closed access)Background: Damaging inflammation is thought to contribute to the high morbidity and mortality of tuberculous meningitis (TBM), but the link between inflammation and outcome remains unclear. Methods: We performed prospective clinical and routine laboratory analyses of a cohort of adult patients with TBM in Indonesia. We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM. Patients were followed for >1 year. Results: We included 608 patients with TBM, of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe (ie, grade II or III) disease. One-year mortality was 43.7% and strongly associated with decreased consciousness, fever, and focal neurological signs. Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was associated with higher mortality and different CSF characteristics, compared with absence of HIV infection. Among HIV-uninfected patients, mortality was associated with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95% confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16 per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI, 1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95% CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear cell count but not with mortality (P = .915). Conclusions: A strong neutrophil response and fever may contribute to or be a result of (immuno)pathology in TBM. Aggressive fever control might improve outcome, and more-precise characterization of CSF leukocytes could guide possible host-directed therapeutic strategies in TBM

Predominance of modern Mycobacterium tuberculosis strains and active transmission of Beijing sublineage in Jayapura, Indonesia Papua

Mycobacterium tuberculosis genotype distribution is different between West and Central Indonesia, but there are no data on the most Eastern part, Papua. We aimed to identify the predominant genotypes of M. tuberculosis responsible for tuberculosis in coastal Papua, their transmission, and the association with patient characteristics. A total of 199 M. tuberculosis isolates were collected. Spoligotyping was applied to describe the population structure of M. tuberculosis, lineage identification was performed using a combination of lineage-specific markers, and genotypic clusters were identified using a combination of 24-locus-MIRU-VNTR and spoligotyping. A high degree of genetic diversity was observed among isolates based on their spoligopatterns. Strains from modern lineage 4 made up almost half of strains (46.9%), being more abundant than the ancient lineage 1 (33.7%), and modern lineage 2 (19.4%). Thirty-five percent of strains belonged to genotypic clusters, especially strains in the Beijing genotype. Previous TB treatment and mutations associated with drug resistance were more common in patients infected with strains of the Beijing genotype. Papua shows a different distribution of M. tuberculosis genotypes compared to other parts of Indonesia. Clustering and drug resistance of modern strains recently introduced to Papua may contribute to the high tuberculosis burden in this region