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Objective This study aims to evaluate the correlation between electrolytes and serial miRNAs from our previous study. We want to prove that there is the molecular basis that underlying electrolytes disturbances as the predictive indicator to the outcome in NSCLC patients. Results There were positive correlation between potassium level with miR-34 (p = 0.008, r = 0.366), miR-148 (p = 0.004, r = 0.394) and miR-155 (p = 0.031, r = 0.300).

Background: Epithelial ovarian cancer (EOC) is a lethal disease due to late diagnosis and lack of effective screening methods. MicroRNA (miR/miRNA) plays an important role in ovarian carcinogenesis and may serve as a non-invasive biomarker for EOC. This study aimed to assess miR-141 expression in the blood plasma of patients with EOC and healthy subjects and determine its association with the clinical stage of EOC. Methods: This cross-sectional study used blood plasma from 30 newly diagnosed untreated patients with EOC and 25 healthy subjects. The mean age was 47.73 (SD = 10.29) years for EOC and 44.48 (SD = 16.14) years for healthy subject. The total RNA was isolated from blood plasma and reversed transcribed to obtain cDNA. The expression of miR-141 was measured by real- time quantitative polymerase chain reaction (qRT-PCR), and calculated using 2-∆∆Ct methods. The data were analysed using Mann-Whitney test. Results: The expression of miR-141 was upregulated 8.41 fold in the blood plasma of EOC patients compared to healthy controls (P < 0.001). Expression of miR-141 in the advanced stage was upregulated 4.2 fold compared to the early stage (P < 0.001). Conclusion: The miR-141 was upregulated in the blood plasma of EOC and associated with an advanced stage of disease, suggesting it has potential as a biomarker for EOC detection.

Latar belakang: Angka kekambuhan dan resistensi pasien kanker rektum mencapai 40 persen. Kondisi tersebut bisa disebabkan karena peningkatan ekspresi GLUT-1 dan VEGF-A, serta mempengaruhi prognosis pasien. Tujuan penelitian ini adalah untuk mengetahui korelasi ekspresi mRNA GLUT-1 dan VEGF-A, serta hubungannya dengan prognosis pasien kanker rektum yang menjalani kemoradiasi. Metode: Penelitian Kohor ini melibatkan 16 orang pasien kanker rektum lokal stadium II atau III yang menjalani kemoradiasi di RSUP Kariadi Semarang. Sampel darah intravena diambil 5 mL pada saat sebelum dan sesudah kemoradiasi. Total RNA diisolasi dari 200 μl serum, kemudian dilakukan sintesis cDNA. Ekspresi mRNA GLUT-1 dan VEGF-A dikuantifikasi dengan metode Livak menggunakan reference gene β-actin. Hasil: Rata-rata ekspresi mRNA GLUT-1 menurun signifikan 2,14 kali (P=0,044) dan mRNA VEGF-A menurun 1,9 kali (P = 0,03). Ekspresi mRNA GLUT-1 dan VEGF-A berkorelasi positif kuat dan signifikan pada saat sebelum (r = 0,6; R2 = 0,455; P = 0,013) dan sesudah kemoradiasi (r = 0,8; R2 = 0,598; P < 0,001). Peningkatan ekspresi mRNA GLUT-1 berhubungan dengan prognosis buruk pasien, dengan resiko 18 kali lebih tinggi (P=0,036; OR=18, 95% CI=1,2 – 261). Peningkatan ekspresi mRNA VEGF-A tidak berhubungan signifikan dengan prognosis pasien (P=0,12; OR=9; 95%CI=0,6-123). Kesimpulan: Ekspresi mRNA GLUT-1 dan VEGF-A berkorelasi positif dan saling mempengaruhi satu dengan lainnya. Peningkatan ekspresi mRNA GLUT-1 berhubungan dengan prognosis buruk pasien. Hasil penelitian ini mengindikasikan bahwa ekspresi mRNA GLUT-1 dari sampel darah berpotensi sebagai biomarker prognosis pada pasien kanker rektum yang menjalani kemoradiasi. Kata kunci: kanker rektum, kemoradiasi, GLUT-1, VEGF-A, prognosis Abstract Background: Rectal cancer patients have 40 percent risk of recurrence and resistance, which is triggered by increasing in GLUT-1 and VEGF-A mRNA expression. This condition associate with the patients prognosis. This study aimed to determine the correlation between GLUT-1 and VEGF-A mRNA expression, and analyze its association with the rectal cancer patients prognosis who received chemoradiation. Methods: This was a Cohort study involving 16 rectal cancer patients with stage II or III undergoing chemoradiation at Kariadi Hospital Semarang. Five milliliters of intravenous blood samples were taken before and after chemoradiation. Total RNA was isolated from 200 μl of blood serum, followed by cDNA synthesis. GLUT-1 and VEGF-A mRNA expression was quantified by the Livak method using β-actin as a reference gene. Results: GLUT-1 and VEGF-A mRNA expression decreased significantly 2.14 times (P=0,044) and 1,9 times (P=0,03), respectively. Expression of GLUT-1 and VEGF-A mRNA have a significant and strong positive correlation at before (r=0,6; R2=0,455; P=0,013) and after chemoradiation (r=0,8; R2=0,598; P

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogenous disease which differ in characteristic, treatment response and prognosis. We aim to perform in-depth analysis on the clinicopathologic feature and the prognostic value of basal-like and non-basal-like TNBC patients in an Indonesian tertiary hospital.METHODS: We retrospectively included patients diagnosed with TNBC between 2014-2017. Clinical variables were collected from medical record. Expression of epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), p53 mutant and androgen receptor (AR) were examined by using immunohistochemistry (IHC).RESULTS: We included 67 subjects, 67.1% were basal-like and the remaining 32.9% were non-basal-like, with mean age of 51 years old, 59.7% subjects had BMI

Latar Belakang: Gangguan regulasi mikroRNA(miR) dan inflamasi kronik dapat mengubah tumor menjadi karsinoma dan kanker dengan metastasis melalui perubahan seluler dan genomik. Lesi prekanker memiliki peluang 33,3 persen menjadi kanker. Penelitian ini bertujuan untuk mengkaji peran miR-155-5p terhadap mRNA SOCS1 dan populasi makrofag terhadap progresivitas penyakit yang berhubungan dengan Benign Prostate Hyperplasia (BPH), High Grade Prostatic Intraepithelial Neoplasia (HGPIN), dan Prostate Adenocarcinoma (PRAD). Metode: Penelitian ini merupakan penelitian potong lintang dengan 3 kelompok, yaitu BPH,HGPIN, dan PRAD. Sampel jaringan didapatkan dari Tindakan TURP. Ekspresi miR-155 dianalisis menggunakan qPCR dan dikalkulasi menggunakan metode Livak. Ekspresi mRNA SOCS-1 dianalisis menggunakan reverse transcriptase PCR. Penanda pan makrofag, anti CD-68 monoclonal antibody(MoAb) digunakan untuk mendeteksi populasi makrofag pada jaringan dengan imunohistokimia. Hasil: Ekspresi miR-155 lebih tinggi pada HGPIN dibandingkan BPH dan PRAD (p=0,14). Ekspresi mRNA SOCS1 pada HGPIN paling rendah diantara ketiga sampel (p=0,96). Terdapat korelasi negative antara miR-155 dan mRNA SOCS1 (p=0,02). Terdapat peningkatan persentase populasi makrofag yang signifikan pada HGPIN (6,03 persen) dibandingkan BPH (0.89 persen) dengan p=0,00. Kesimpulan: Pada penelitian ini, terdapat perubahan persentase makrofag dan miR-155 pada HGPIN. Variasi ekspresi miR-155 dan persentase populasi makrofag dapat disebabkan karena perubahan epigenetik. Oleh sebab itu, perlu penelitian lebih lanjut untuk memvalidasi hasil tersebut dan memahami kemungkinan menjadi biomarker pada penyakit prekanker pada prostat. Kata Kunci: Prostatic Intaepithelial Neoplasia, miR-155, Makrofag Abstract Background: Impaired microRNA(miR) regulation and chronic inflammation could transform tumors into carcinoma and cancer by metastasis through cellular and genomic changes. Precancerous lesions have a 33.3 percent chance of becoming cancerous. This study investigated the role of miR-155 related to SOCS1 mRNA and macrophage population in disease progression associated with Benign Prostate Hyperplasia (BPH), High-Grade Prostatic Intraepithelial Neoplasia (HGPIN), and Prostate Adenocarcinoma (PRAD). Methods: This was a cross-sectional study using three groups of samples, namely BPH, HGPIN, and PRAD. Tissue samples were obtained from TURP Action. The expression of miR-155 was analyzed using real-time qPCR and calculated using the Livak method. The expression of SOCS1 mRNA was analyzed using reverse transcriptase PCR. The macrophage pan-marker, anti-CD68 monoclonal antibody (MoAb), was used to detect macrophage population in tissues by immunohistochemistry. Results: The expression of miR-155 was higher in HGPIN than BPH and PRAD (p=0.14). The expression of SOCS1 mRNA in HGPIN was the lowest among the three samples (p=0.96). There was a negative correlation between miR-155 and SOCS1 mRNA (p=0.02). There was a significant increase in the percentage of the macrophage population in HGPIN (6.03 percent) compared to BPH (0.89 percent) with p=0.00. Conclusion: In this study, there were changes in the percentage of macrophage and miR-155 in HGPIN. The variation in miR-155 expression and the percentage of the macrophage may be caused by epigenetic changes. Therefore, further research is needed to validate these results and understand the possibility of being a biomarker in precancerous disease of the prostate. Keywords: Prostatic Intraepithelial Neoplasia, miR-155, Macrophage

Objective. Early diagnosis of contrast-induced nephropathy (CIN) remains crucial for successful treatment; unfortunately, the widely used serum creatinine is elevated only in the late stage of CIN. The circulating microRNAs (miRNAs) are stable biomarker that might be useful. The aim of this scoping review and meta-analysis is to assess the role of miRNAs in CIN. Methods. We performed a systematic literature search on topics that assess the role of miRNAs in CIN from several electronic databases. Results. There were 6 preclinical studies and 2 of them validated their findings in human. Only miR-30a, miR-30c, miR-30e, and miR-188 have been validated in human models. Meta-analysis showed that increase in miR-30a expression was associated with higher incidence of CIN (OR 4.48 [1.52, 13.26], p=0.007; I2: 94%, p<0.001). An increase in miR-30e expression was associated with higher incidence of CIN (OR 2.34 [1.70, 3.20], p<0.001; I2: 0%, p=0.76). There is an indication that miR-188 is associated with contrast-induced apoptosis and might potentially be a drug target in the future. Conclusion. This study highlighted the importance of certain miRNAs in CIN pathophysiology. Future researches should explore on the prognostic and therapeutic implication of miRNA in CIN.

Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner.Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma.Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (−139 to 160) vs.−136 (−237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: −171(-844 to +1,166) vs. −517(−1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2–6.4) to 5.9 (4.8–6.4), p < 0.001] and sham [5.2 (4.1–9.4) to 5.6 (4.8–6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3–36.5) vs. sham 2.8 (0–15), p = 0.33)].Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).

BACKGROUND: The diagnosis of tuberculosis (TB) in children is challenging by the absence of a practical gold standard. Interferon (IFN)-ginducible protein 10 (IP-10) is a chemokine that may serve as the leading candidate marker in child TB diagnosis. The aim of this study is to assess the diagnostic value of IP-10 in the diagnosis of TB in children. METHODS: We recruited eligible symptomatic and asymptomatic children aged

Objective To evaluate the miR-21-5p and miR-200c-3p expressions in the urine of patients with prostate cancer (PCa) and to investigate their potential as biomarkers. Material and methods The urine samples collected from 80 patients, including 20 patients diagnosed with benign prostate hyperplasia (BPH) and 60 patients diagnosed with PCa, were examined. The exosome isolation was performed using the miRCURY exosome isolation kit (Exiqon, Denmark), total RNA was extracted using the miRCURY RNA Isolation Kit-Biofluid kit (Exiqon, Denmark), and complementary DNA (cDNA) was synthesized using the Universal cDNA Synthesis kit (Exiqon, Denmark). A quantitative polymerase chain reaction (qPCR) analysis of gene expression was performed using the qPCR CFX 96 Thermocycler (Bio-Rad). All the procedures followed the manufacturer's recommendations. Results The overexpressions of miR-21 in the non-metastatic PCa and metastatic PCa group compared to the BPH group were statistically significant with a p-value of 0.001 and 0.018, respectively. The non-metastatic PCa compared to the metastatic PCa group was also statistically significant with a p-value of 0.037. The under expressions of miR-200c in the non-metastatic PCa and metastatic PCa group compared to the BPH group are statistically significant with a p-value of 0.001 and 0.001, respectively. Conclusion The overexpressions of miR-21 found in this study could be a potential non-invasive diagnostic tool for patients with PCa. Despite the significant results in our study, the use of micro-RNA in urine samples may vary due to epigenetic variation. Further studies with larger populations are required to investigate the role of miR-21 and miR-200c as biomarkers in PCa.

Background: Most of breast cancer patients are estrogen receptor alpha-positive and have high resistance and side effect of chemotherapeutic drug. Therefore, discovering an effective anticancer agent is needed. This research explored the effect of (E)-1-(4’-aminophenyl)-3-phenylprop-2-en-1-one (APE) on miR-18a, Dicer1, and MMP-9 expressions. Methods: Twenty four female Sprague-Dawley rats were invetigated in this study. The rats were divided into 6 groups of 4. G1 was considered as normal rat. G2, G3, T1, T2, and T3 were given DMBA 20 mg/kgBW twice a week for 5 weeks to induce mammary cancer. After being affiliated with cancer, G2 was given vehicle and G3 was treated with tamoxifen. T1, T2, and T3 were treated with APE intraperitoneally everyday for 21 days at doses of 5, 15, and 45 mg/kgBW/day, respectively. Blood plasma was collected to measure miR-18a expression using qRT-PCR. Mammary tissues were also collected to determine Dicer1 and MMP-9 expressions by using immunohistochemistry. Results: The results showed significant down-regulation of miR-18a relative expression and up-regulation of Dicer1 expression in G3 and T1 compared to G2 (P

Background: Breast cancer incidence rates have been continuously increasing in majority nations with significant higher portion of cancer-related mortality in low- and middle-income countries. Developing new biomarker is an emerging field in the breast cancer research. Application of a promising minimally invasive biomarker, circulating microRNA, for additional improvement of diagnosis, prognosis, and therapeutic monitoring in breast cancer is not well corroborated. Materials and Methods: To uncover the potential use of circulating miR-155 expression as a clinical biomarker in breast cancer, we analyzed 102 breast cancer patients at diagnosis and after treatment as well as 15 healthy women. Total RNA was isolated from patient’s plasma and expression of circulating miR-155 was measured with quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of circulating miR-155 were compared according to the effect of treatment, clinicopathological variables, and progression-free survival. Results: In comparison to the healthy women, expression of circulating miR-155 levels were significantly higher (medians were 18.49±19 and 1.28±0.18, respectively; p

Background: Triple negative breast cancer (TNBC) (represents roughly 25% of all breast cancers in Yogyakarta) still has the worst survival compared to other breast cancer subtypes. Results from recent studies have shown that inhibition of programmed death-ligand 1 receptor (PD-L1) in TNBC patients is associated with better prognosis. Currently, data on PD-L1 expression and its prognostic value in Indonesian TNBC patients are still relatively unknown. This study aimed to investigate the expression of PD-L1 in Indonesian TNBC patients as preliminary proof to support PD-L1 inhibitor as a possible treatment option near in the future. Methods: We retrospectively included stage I-III TNBC patients diagnosed between 2014 and 2017 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Clinical variables were collected from medical record. Paraffin blocks of biopsy specimen were retrieved to examine mRNA level of PD-L1. Results: We included 48 subjects with mean age of 51.09 years and mean body mass index (BMI) of 24.58. The 3-year overall survival (OS) was 58.3%. Overexpression of PD-L1 mRNA in TNBC patients is associated with worse prognosis (P < 0.01). There were no statistically significant associations between PD-L1 mRNA expression and any of the clinicopathologic variables examined. Conclusions: In summary, PD-L1 mRNA overexpression is associated with worse survival in Indonesian TNBC patients, independent of other established risk factors. PD-L1 mRNA is expressed in all of our samples, presenting as a feasible alternative or complementary method in deciding which patient might benefit from receiving PD-L1 inhibitor. World J Oncol. 2020;11(5):216-222 doi: https://doi.org/10.14740/wjon1302

Latar Belakang: Kanker kolorektal menempati urutan ketiga penyebab kanker di dunia, dengan prevalensi kanker rektum sebanyak 30% dari total kasus. Saat ini belum ada biomarker yang efektif untuk memprediksi respon pasien terhadap terapi yang diberikan. Beberapa penelitian menggunakan potensi miRNA sebagai biomarker untuk melihat respon terapi. Salah satunya yaitu MiR-124-3p berperan sebagai tumor supresor yang mengalami penurunan ekspresi pada berbagi jenis kanker. Tujuan dari penelitian ini adalah untuk meneliti ekspresi miR-124-3p dari pasien kanker rektum yang menerima nCRT, dan menganalisis hubungannya dengan kelangsungan hidup pasien dan parameter klinis lainnya. Metode: Penelitian ini melibatkan 15 orang pasien yang didiagnosis menderita kanker rektum lokal dan menjalani kemoradioterapi neoajuvan (radioterapi 45-50 Gy dengan fraksi 1,8-2 Gy selama 1-3 bulan, dan kemoterapi 5-fluororacil secara oral). Sampel penelitian berupa darah intravena sebanyak 5 ml diambil saat sebelum dan sesudah kemoradioterapi. Selanjutnya ekspresi miR-124-3p dianalisis menggunakan qRT-PCR dan dikalkulasi menggunakan metode Livak. Hasil: Terdapat hubungan signifikan antara peningkatan ekspresi miR-124-3p dengan sintasan hidup pasien (P=0,003; OR =30, 95% CI = 1,41 – 638,15), serta adanya peningkatan ekspresi miR-124-3p yang signifikan (P

AIM: To investigate neurofibromatosis type 2 (NF2) gene mutation at mRNA levels in sporadic orbitocranial meningioma and its association with progesterone receptor (PR) mRNA expression. METHODS: This was a case-control study. Thirty-four sporadic meningioma patients with no familial NF2-related meningioma history were recruited. They were interviewed for their obstetric, gynecologic, and contraception history. PR investigation was performed with real-time polymerase chain reaction (PCR). NF2 mutation was investigated using Qbiomarker Somatic Mutation PCR Assay at NF2 mRNA level after its cDNA extraction (four mRNA mutation cytoband coordinates for nucleotide change: c.634C>T/p.Q212, c.655G>A/p.V219M, c.784C>T/p.R262 and c.1228C>T/p. Q410). RESULTS: After mutation analysis at mRNA level, NF2 gene mutation was found in 35.29% patients. Non-mutation group was strongly associated with exogenous hormonal exposure (non-mutation vs mutation: 95.5% vs 83.3%, P

Objective: We determine the utility of Prostate Specific Antigen (PSA) for predicting the presence of skeletal metastasis on Bone Scan (BS) in prostate cancer patients. Material & Methods: Retrospective analysis of medical records of 70 consecutive prostate cancer patients subjected to bone scan during the last 2 years was done. 5 cases were excluded due to the following reasons: Serum PSA not available, hormonal or other therapy given prior to serum PSA measurement, and/or Bone Scan, and symptomatic for bone metastasis. In remaining 65 cases, PSA value and bone scan were evaluated. Results: BS was found to be positive in 20/65 (31%) and negative in 45(69%) patients. 24 (37%) had serum PSA > 100 ng/ml, 25 (38.5%) had PSA of 20‐100 ng/ml and only 16 (24.5%) had PSA < 20 ng/ml. Conclusion: Serum PSA < 20 ng/ml have high predictive value in ruling out skeletal metastasis. Our data are in corroboration with results from previous studies that BS should be performed only if PSA > 20 ng/ml. Using this cut‐off, unnecessary investigation can be avoided. Avoiding BS asymptomatic in this group of patients would translate into a significant cost‐saving and reduction in their psychological and physical burden.

Ibnu Purwanto,1 Didik Setyo Heriyanto,2 Irianiwati Widodo,2 Mohammad Hakimi,3 Mardiah Suci Hardianti,1 Teguh Aryandono,4 Sofia Mubarika Haryana5 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 3Department of Clinical Epidemiology and Biostatistics Unit, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 4Department of Surgical Oncology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, Indonesia; 5Department of Histology and Cell Biology, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Yogyakarta, IndonesiaCorrespondence: Ibnu PurwantoDivision of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University/Dr Sardjito Hospital, Jalan Farmako, Sekip Utara, Yogyakarta 55281, IndonesiaTel/Fax (+62 274) 560300Email ibnupurwanto@ugm.ac.idPurpose: Determining the optimal strategy to implement systemic treatment modalities has been challenging in triple-negative breast cancer (TNBC). We aim to investigate the role of microRNA-223 (miR-223) as prognostic factor and predictor of response toward chemotherapy in TNBC.Patients and Methods: We retrospectively analyzed the association of pretreatment miR-223 expression with clinicopathologic characteristics and 36-month overall survival (OS) of 53 all stages TNBC patients. Tumor level of miR-223 was measured using real-time quantitative polymerase chain reaction (expressed in fold change). Cutoff value for miR-223 was determined by using receiver operating curve (ROC). Kaplan–Meier curve was used to perform survival analysis.Results: The optimum cutoff value for miR-223 was 23.435 (AUC: 0.706, 95%CI: 0.565– 0.848; p:0.01; sensitivity: 78.6%; specificity: 56%) and was used to categorize mir-223 expression into over- and underexpressed group. Overexpression of miR-223 was associated with increased expression of EGFR (69.7% vs 35%, p: 0.022) and lower 36-month OS (33.3% vs 70%; median OS±SE (months): 25.66± 1.58 vs 30.23± 1.99; log rank p< 0.05). Worse survival is observed in miR-223 overexpressed group receiving platinum-based chemotherapy compared to miR-223 underexpressed group (mean OS (95%CI) months: 24.7 (20.3– 29.1) vs 34.3 (31.2– 37.4); p< 0.01), while no significant difference observed in non-platinum containing regimen. No significant association was observed between miR-223 expression with other clinicopathologic characteristics.Conclusion: Overexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.Keywords: miR-223, chemotherapy, prognosis, EGFR, TNBC

Purpose This study aims to explore the potential of hsa-mir-106b-5p as a new liquid biomarker for prostate cancer sufferers in Indonesia. Methods Analysis of hsa-mir-106b-5p expression of two tissue samples from BPH patients and two PCa patients used NanoString nCounter Expression Assay then validated by qRT-PCR using 10 patient urine samples for prostate cancer and BPH. Furthermore, analysis of the role of hsa-mir-106b-5p in prostate cancer was carried out bioinformatically. Results The results of this study indicated that the expression of hsa-mir-106b-5p in prostate cancer tissue was 1.23 times higher than that of BPH and urine of Indonesian patients (1.72 times). Moreover, this miRNA was upregulated in prostate cancer cells compared to normal cells 1.37 times. The hsa-mir-106b-5p appeared to be involved in the development of prostate cancer through the binding of genes involved in endoplasmic reticulum stress pathways and tumor suppressor genes. Conclusion hsa-mir-106b-5p could modulate prostate cancer by interfering with the endoplasmic reticulum stress repair pathways and decreasing the expression of tumor suppressor genes involved in many biological processes. These updates our understanding of the role of hsa-mir-106b-5p in cancer and its potential as a candidate of a biomarker for clinical diagnosis of prostate cancer.

Diabetes mellitus type 2 is the most common type of diabetes. This study was conducted to determine the effect of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in Homeostatic Model Assessment of β-cell function (HOMA-β) value, normal Langerhans cells, and Transcription Factor 7-Like 2 (TCF7L2) gene expression in type 2 diabetic rats model. As many as 27 male Sprague Dawley rats were divided into 3 study research groups: normal control (9 normal rats), diabetic control (9 type 2 diabetic rats, induced by 60 mg/kg BW Streptozotocin and 120 mg/kg BW Nicotinamide i.p.), and treatment (9 type 2 diabetic rats treatment with 0.1 ml/200g BW MSC-CM i.p.). On day 30 after therapy, the expression of TCF7L2 gene was performed with real time-quantitative PCR (RT-qPCR). The HOMA-β value were calculated based on Fasting Insulins (FINs) levels and Fasting Blood Glucose (FBG) levels data from other research team members. Based on results, MSC-CM increases the HOMA-β value and amount of normal Langerhans cells of treatment group that indicates amelioration effect of MSC-CM, but there was no significant difference in TCF7L2 gene expression level between diabetic control and treatment group.

The outcome of inoperable rectal cancer treatment by chemotherapy, radiotherapy, and targeted therapy are still unfavorable. Carbogen is a combination of 98% oxygen and 2% carbon dioxide proven effective as chemoradiosensitizer. The aim of this study is to know the effect of concurrent carbogen and chemoradiotherapy in locally advanced rectal cancer by measuring the shrinkage of the tumor volume. The design of this study was randomized true experimental 2 groups pre and post-test-controlled design. Samples were patients with locally advanced rectal cancer. MRI of the pelvis before and 4-8 weeks after the chemoradiation were examined. A total of 28 subjects were randomized to 14 patients who received concurrent chemoradiation with carbogen (treatment group) and 14 patients chemoradiation (control) The tumor shrinkage in the treatment group (13.08 to 6.08 cm3 ) was significantly higher compared to the control group (18.00 to 12.83 cm3 ). Supplementation of carbogen to standard treatment chemoradiation for locally advanced rectal cancer significantly shrinkage the tumor volume.

Background: Aberrant patterns of microRNA expression have been highlighted as a potential clinical biomarker in breast cancer as the most frequent cancer among women that contributes nearly a quarter of total cancer incidence in 2018. Upregulation of microRNA-21 (miR-21) is associated with adverse clinical outcomes in breast cancer. However, the use of circulating free miR-21 as a non-invasive biomarker for diagnosis and therapeutic monitoring in breast cancer is not well established. We quantified the levels of circulating miR-21 expression and analyzed their correlation with clinicopathological variables and progression-free survival. Materials and Methods: This initial study included a cohort of 102 breast cancer patients of different subtypes and clinicat stages. We also included 15 unrelated healthy women. Venous blood from patients was collected at diagnosis and after treatment of surgery and chemotherapy. MiR-21 expression was quantified from total RNA fraction isolated from patient’s plasma. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyzed miR-21 expression. Results: Expression of circulating miR-21 was significantly elevated in breast cancer patients compared to healthy women (median miR-21 expression levels were 7.67±2.2 and 1.28±0.16, respectively; p

Preeclampsia is one of the main causes of maternal and perinatal mortality and morbidity. The pathogenesis of preeclampsia remains unclear until now. It is believed that regulation of apoptosis in trophoblast cells plays an important role in the pathophysiology of preeclampsia. Failure of spiral arteries remodeling will eventually lead to placental hypoxia lead to excessive trophoblast apoptosis. The molecular mechanism of apoptosis is very complicated involving many signaling molecules included Bcl-2 proteins. The Bcl- 2 protein group consists of proapoptosis proteins (Bax) and apoptosis inhibitor proteins (Bcl-2 and Bcl-xL). The aimed of this stuty was to compare the expression of Bcl-xL protein in placental trophoblast cells of pregnancy complicated by severe preeclampsia with that normotensive pregnancy. This study was an observational study with cross sectional design involving 43 pregnancy patients with severe preeclampsia and 38 normotensive pregnancy who treated in Dr. Sardjito General Hospital, Yogyakarta from October 2011 until March 2012. Placenta samples were obtained from all subjects for Bcl-xL protein expression analysis using immunohistochemistry technique. Data were analyzed using independent t-test, chi-square test, and logistic regression. A p value

Background Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment. It is thought that neoadjuvant chemotherapy (NC) in locally advanced OSCC is able to shrink tumor size. Chemoresistancy is a problem due to hypoxic microenvironment characterized by increased expression of HIF-1α. It is also regulated by miR-210 as well as increased expression of CD44 and CD133. Melatonin has a powerful antioxidant and oncostatic effects that are expected to improve tumor hypoxia and clinical response. Fifty patients with OSCC were included and randomized. miR-210 and CD44 expression were measured before and after intervention using qRT-PCR absolute quantification, and clinical response was evaluated according to RECIST 1.1 criteria. This study aims to determine the effect of melatonin in improving the clinical response of patients with locally advanced oral squamous cell carcinoma (OSCC) after neoadjuvant chemotherapy to miR-210 and CD44 expression. Results Melatonin administration reduced miR-210 levels but not significant (p = 0.767). CD44 expression also decreased in the melatonin group compared with placebo yet was not significant (p = 0.103). There was a decrease in the expression of miR-210 and CD44 followed by a decrease in the percentage of residual tumor but not significant (p = 0.114). Conclusion In OSCC, the addition of 20-mg melatonin to neoadjuvant chemotherapy (NC) reduced the expression of miR-210 and CD44 and decreased the percentage of tumor residue; however, no statistically significant result was observed. Trial registration This study is registered to ClinicalTrials.gov under trial registration number: NCT04137627 with date of registration on October 22, 2019—retrospectively registered, accessible from: https://clinicaltrials.gov/ct2/show/NCT04137627

Highlights • This study investigated the potency of a xanthone derivative when used incombination with doxorubicin on a cancer cell line. • The xanthone-doxorubicin combination showed promising in vitro activity againstlymphoma cells. • Potential mechanisms of action responsible for the ability of this xanthone derivative to reduce doxorubicin resistance were investigated., Background The increasing rate of cancer chemoresistance and adverse side effects of therapy have led to the wide use of various chemotherapeutic combinations in cancer management, including lymphoid malignancy. Objective We investigated the effects of a combination of 1,3,6-trihydroxy-4,5,7-trichloroxanthone (TTX) and doxorubicin on the Raji lymphoma cell line. Methods Raji cells were treated with different concentrations of TTX, doxorubicin, or combinations thereof. Cancer cell growth inhibition was evaluated using 3-(4,5-dimethyltiazol-2-yl)-2,5- diphenyltetrazolium bromide/MTT assay to determine the half-maximal inhibitory concentration. Combination index values were calculated using CompuSyn (ComboSyn, Inc, Paramus, NJ). Molecular docking was conducted using a Protein-Ligand ANT System. Results The mean (SD) half-maximal inhibitory concentration values of TTX and doxorubicin were 15.948 (3.101) µM and 25.432 (1.417) µM, respectively. The combination index values of the different combinations ranged from 0.057 to 0.285, indicating strong to very strong synergistic effects. The docking study results reveal that TTX docks at the active site of Raf-1 and c-Jun N-kinase receptors with predicted free energies of binding of −79.37 and −75.42 kcal/mol, respectively. Conclusions The xanthone-doxorubicin combination showed promising in vitro activity against lymphoma cells. The results also indicate that the TTX and doxorubicin combination's effect was due to the interaction between TTX with Raf-1 and c-Jun N-kinase receptors, 2 determinants of doxorubicin resistance progression.

MiR-21 has been linked to tumorigenesis, development, and metastasis in tumor pathogenesis. All human cancers, including breast cancer, have increased expression of MiR-21, which is the only miRNA that has increased expression. PTEN expression was found to be reduced in the majority of solid tumors, including breast cancer. Since lymph node metastatic factors, estrogen receptor status, tumor grade, and tumor node metastasis (TNM) all decreased PTEN expression, the PTEN expression profile may be a very useful prognostic marker in breast cancer. PTEN inhibits PIP3 (phosphatidylinositol 3,4,5-triphosphate) activity by having protein phosphatase and lipid phosphatase activity that is the polar opposite of PI3K (Phosphatidyl Inositol 3-Kinase). The aim of this research was to see how often miR-21 and mRNA PTEN were expressed at different stages of breast cancer and whether they could be used as prognostic markers. This type of research is an observational study with a cross-sectional design. The sample size of 43 people came from breast cancer patients. Analysis of miR-21 expression and mRNA PTEN using Real-Time qPCR. The results showed that miR-21 expression increased 1.32 times at an advanced stage compared to an early stage, while mRNA PTEN expression decreased 1.33 fold at an advanced stage compared to an early stage. According to the findings, miR-21 expression in the blood plasma of breast cancer patients was upregulated at an advanced stage compared to an early stage and downregulated mRNA PTEN expression. MiR-21 which is increased at an advanced stage has the potential to be a poor prognostic marker at the stage of breast cancer. The change in miR-21 expression can be a good candidate as a molecular prognostic marker and for future research the role of miR-21 in breast cancer progression will further enrich the scientific repertoire, especially in the health and clinical fields.

Objective The identification of new genetic-associated risk factor of ischemic stroke could improves strategies for stroke prevention. This study aims to identify insulin receptor substrate 1 (IRS-1) gene polymorphism Gly972Arg as the risk factor for ischemic stroke among Indonesian subjects. The case–control study was conducted by matching the gender and race on 85 cases of patients with ischemic stroke and 86 healthy non-stroke control subjects. Ischemic stroke was established by the complete neurology examination and brain computed tomography scan or magnetic resonance imaging. Polymerase chain reaction–Restriction Fragment Length Polymorphism was performed to analyze IRS-1 gene Gly972Arg genotype. Results There were 85 ischemic stroke cases and 86 control subjects. The distribution of nucleotide IRS-1 gene polymorphism Gly972Arg in the ischemic stroke vs health controls for GG were 32.2% vs 41.5%, for GR were 16% vs 7.6%, and for RR were 0.5% vs 1.9%. IRS-1 gene polymorphism Gly972Arg was found as significant risk factor for ischemic stroke [odds ratio of 2.6 (1.27–5.27); CI 95%, p = 0.008]. Conclusively, the IRS-1 gene polymorphism Gly972Arg should be considered as an important factor in the prevention and treatment of ischemic stroke. Electronic supplementary material The online version of this article (10.1186/s13104-018-3823-6) contains supplementary material, which is available to authorized users.

Background: The pathogenesis of meningioma in females and its association with exogenous progesterone is remained unclear. This study was aimed to examine expression of Progesterone receptor (PR) and Neurofibromatosis-2 (NF2) and assess their relationships to history of exogenous progesterone use and risk of meningioma.Methods: Our study was a case-control study that involves 115 females, 40 cases who diagnosed with orbito-cranial meningioma and 75 controls of healthy, that has been presented in previous study. The demographic characteristics, reproductive factors, and history of progesterone use were obtained in–depth face-to-face interviews. PR and NF2 mRNA were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) on serum specimens.Results: The mean age of participants in cases vs. controls were 46.6 ± 6.2 vs. 46.5 ± 7.45 (P = 0.969). The expression of PR and NF2 in cases was significantly lower than in controls. The longer duration of progesterone exposure was significantly associated with lower expression of PR and NF2. Significant association between lower expression of PR (OR 11.7; 95% CI 4.17–32.9; P < 0.001 comparing the lowest quartile vs. 3 highest quartile of PR) and NF2 (OR 4.23; 95% CI 1.85–9.67; P = 0.001 comparing the 2 lowest quartiles vs. 2 highest quartiles) with increased risk of meningioma were also reported.Conclusion: In this study we showed that the longer the exposure to exogenous progesterone, the lower the expression of PR and NF2 mRNA in the serum. Low expression of PR and NF2 were associated with higher risk of meningioma, suggesting that low PR expression and inactivation of NF2 might play a key role in progesterone-associated meningioma tumorigenesis and may be potential clinical marker for females at higher risk of meningioma.

Background Incidence rates of breast cancer have been increasing in every country with significant higher proportion of cancer-related mortality particularly in low- and middle-income countries including in Indonesia. Developing novel biomarker is an emerging field in the breast cancer study. Application of a promising minimally-invasive biomarker, circulating microRNA, for additional improvement of diagnosis and therapeutic monitoring in breast cancer is not fully understood. Methods We analysed expression of circulating miR-155 in 102 breast cancer patients at diagnosis and after treatment as well as 15 healthy women. Total RNA was extracted from patient’s plasma and microRNA expression was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of circulating miR-155 were compared according to the effect of treatment, clinicopathological variables, and progression-free survival. Results In comparison to the healthy women, expression of circulating miR-155 levels were significantly higher (medians were 18.49±19 and 1.28±0.18, respectively; p Conclusions Expression of circulating miR-155 expression was significantly elevated in breast cancer patients and was decreased after treatment. Therefore, circulating miR-155 was potentially applicable as diagnostic and therapeutic monitoring marker in breast cancer. Legal entity responsible for the study Universities Gadjah Mada. Funding The Ministry of Research and Higher Education - Republic of Indonesia (PTUPT 1818/UNI/DITLIT/LT/2018 and PPUPT 1987/UNI/DITLIT/LT/2018). Disclosure All authors have declared no conflicts of interest.

Background: With an estimated 13,000 newly diagnosed patients per year, nasopharyngeal carcinoma (NPC) is one of the most common types of cancer in males in Indonesia. Moreover, most patients are diagnosed at an advanced stage of the disease. This study aimed to explore the health behaviors of patients diagnosed with NPC and the possible causes of patient delay in NPC diagnosis.Methods: A qualitative research method was used to gain better insight into patient behaviors. Twelve patients were interviewed using semi-structured interview guidelines. All interviews were recorded, transcribed verbatim and analyzed according to a standard content analysis framework.Results: Most patients had limited knowledge regarding NPC and its causes. Fifty percent of the patients had a delay of six months from the onset of symptoms to diagnosis. The main reason for this delay was the lack of awareness among the patients, which was influenced by their environment, economic status, family, culture, and religion. The perceived barriers to seeking medical help included direct non-medical costs not covered by health insurance, complex and time-consuming insurance and referral systems, and negative experiences in the past. Health insurance did motivate people to seek medical help.Conclusion: This study provides additional insight into patients' motivations to delay seeking medical help and can facilitate the design of NPC education programs. To improve awareness of the abovementioned causes for delay, community-based education programs are highly warranted and should focus on the recognition of NPC symptoms and possible solutions to overcome the main barriers at an earlier disease stage.

Objective: Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen receptors (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Only 30% of TNBC patients show a pathologic complete response, and the other 70% of patients exhibit a less pronounced response followed by relapse and metastasis to distant organs after neoadjuvant chemotherapy. Achievements of immunotherapy targeting programmed cell death 1 ligand 1 (PD-L1) in clinical trials for treating melanoma, nonsmall-cell lung cancer, renal cell carcinoma, and TNBC suggest that targeting the interaction of tumor cells with tumor microenvironment is highly beneficial for cancer treatment. Finding a novel dual-targeting therapy against tumor cells and the tumor microenvironment (TME) may provide options for improved responses in TNBC patients. Data Sources: We searched the potential targeted therapy candidates that regulate tumor cells as well as the TME of cancer diseases, including TNBC, based on our previous and recent other publications. Study Selection: We selected the potential targeted therapies supported by relevance clinical data, in vitro and in vivo studies. Results: In this review, we found the KDM5B, Cadherin 11, β-catenin, CDK2, signal peptide CUB-EGF domain-containing protein 2, and PDL1 regulate the tumor cells and TME of TNBC cells. In addition, we also highlighted the Antrocin, Ovatodiolide, and Pterostilbene as natural small compound possess anti-cancer through the disruption of tumor cell–TME interactions. Conclusion: The new therapy approach targeting tumor cells-TME interaction may improve the response and survival rate of TNBC patients. Later, natural small compounds could provide alternative therapy options for TNBC patients.

Disease progression in Tuberculosis (TB) is dependent on host’s immune system. Phyllanthus niruri, a traditional herb, has long been used to boost immune system in Indonesian society. This study aimed to observe the potential role of P. niruri in inducing immune cells activity in TB patients by in vitro approach. Peripheral blood mononuclear cells (PBMCs) and macrophages were collected from active pulmonary TB patients. After stimulation with graded doses of P. niruri aqueous extract, cell proliferation, phagocytic activity and nitric oxide (NO) release were analysed. P. niruri aqueous extract induced proliferation of PBMCs, increased NO release, and improved macrophages phagocytic activity. These effects were observed in a dose-dependent manner. This may lead to further research for the potential role of P. niruri as immunomodulatory adjuvant therapy for TB patients.

Background: Cancer stem cells (CSCs) promote tumor progression and distant metastasis in breast cancer. Cadherin 11 (CDH11) is overexpressed in invasive breast cancer cells and implicated in distant bone metastases in several cancers. The WNT signalling pathway regulates CSC activity. Growing evidence suggest that cadherins play critical roles in WNT signalling pathway. However, CDH11 role in canonical WNT signalling and CSCs in breast cancer is poorly understood. Methods: We investigated the functional association between CDH11 and WNT signalling pathway in triple negative breast cancer (TNBC), by analyzing their expression profile in the TCGA Breast Cancer (BRCA) cohort and immunohistochemical (IHC) staining of TNBC samples. Results: We observed a significant correlation between high CDH11 expression and poor prognosis in the basal and TNBC subtypes. Also, CDH11 expression positively correlated with β-catenin, wingless type MMTV integration site (WNT)2, and transcription factor (TCF)12 expression. IHC results showed CDH11 and β-catenin expression significantly correlated in TNBC patients (p < 0.05). We also showed that siRNA-mediated loss-of-CDH11 (siCDH11) function decreases β-catenin, Met, c-Myc, and matrix metalloproteinase (MMP)7 expression level in MDA-MB-231 and Hs578t. Interestingly, immunofluorescence staining showed that siCDH11 reduced β-catenin nuclear localization and attenuated TNBC cell migration, invasion and tumorsphere-formation. Of translational relevance, siCDH11 exhibited significant anticancer efficacy in murine tumor xenograft models, as demonstrated by reduced tumor-size, inhibited tumor growth and longer survival time. Conclusions: Our findings indicate that by modulating β-catenin, CDH11 regulates the canonical WNT signalling pathway. CDH11 inhibition suppresses the CSC-like phenotypes and tumor growth of TNBC cells and represents a novel therapeutic approach in TNBC treatment.

Ovarian cancer is a lethal disease. One of the problems faced by patients with ovarian cancer is the lack of symptoms in its early stages, which results in it only being detected when it is at an advanced stage. Therefore, there is an urgent need for biomarkers that can predict ovarian cancer precisely. The purpose of this study was to determine the expression of microRNA-21 as a predictive biomarker candidate in both early- and advanced-stage ovarian cancer. This was a cross-sectional study using the blood plasma of 21 healthy control subjects and 37 blood plasma samples from patients with ovarian cancer. Blood plasmas were collected, from which the RNA was isolated. Based on the RNA, the cDNA was synthesized and run through qPCR, the results of which were analyzed using the Livak method. The results showed an upregulation of microRNA-21 in the advanced stage by 2.14 fold compared with the early stage, and 6.13 fold compared with the healthy controls (p < 0.05). The upregulation of microRNA-21 in early-stage ovarian cancer was 2.86 fold compared with the healthy control subjects (p < 0.05). In addition, there was an increase in the expression of microRNA-21 in ovarian cancer by 4.14 fold compared with the healthy controls (p < 0.05). Based on these results, it can be concluded that the expression of microRNA 21 upregulated with the severity of the disease.

PurposeIn Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored.MethodsIn this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS).ResultsThe median WT was 117 days (range 12–581) and OTT was 58 days (43–142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log- WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09–2.61), LRC (HR 1.66; 95% ci: 1.15–2.39), and DFS (HR 1.4; 95% ci: 1.09–1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn’t received concurrent chemotherapy.ConclusionNot receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient’s physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors.

Objective: To evaluate the effectiveness of a nasopharyngeal carcinoma (NPC) awareness programme on the short-term and long-term improvement of knowledge and referral of patients with NPC by primary healthcare centres (PHCCs) staff in Indonesia. Design: The NPC awareness programme consisted of 12 symposia including a Train-The-Trainer component, containing lectures about early symptoms and risk factors of NPC, practical examination and the referral system for NPC suspects. Before and after training participants completed a questionnaire. The Indonesian Doctors Association accredited all activities. Participants: 1 representative general practitioner (GP) from each PHCC attended an NPC awareness symposium. On the basis of the Train-The-Trainer principle, GPs received training material and were obligated to train their colleagues in the PHCC. Results: 703 GPs attended the symposia and trained 1349 staff members: 314 other GPs, 685 nurses and 350 midwives. After the training, respondents’ average score regarding the knowledge of NPC symptoms increased from 47 points (of the 100) to 74 points (p

Aim: The exact immunopathogenesis of Epstein-Barr virus (EBV)- associated nasopharyngeal carcinoma (NPC) remains unclear. The aim of the present study was to assess the expression of CD4, CD8, and MHC class I molecules in NPC. Method: Biopsies were obtained from patients with NPC as well as the Epstein Barr virus (EBV)-seronegative patients as a control. Nasopharyngeal carcinoma patients were classified using the World Health Organization (WHO) pathological assessment and clinical stag- ing of NPC. The expression of CD4, CD8, and MHC class I in the biop- sies were assessed immunohistochemically. Result: The results showed that the number of CD4 positive, CD8 pos- itive, and MHC class I positive cells in NPC patients were higher than those in EBV-negative subjects (p0.05). No statistical differences between the number of CD4 positive and CD8 positive cells in NPC patients could be found (p>0.05). Conclusion: The results of the present study suggest, therefore, that the expression of CD4, CD8 and MHC class I molecules may not be as- sociated with the pathologic classification and clinical staging of NPC and that the CD4:CD8 ratio in nasopharyngeal carcinoma may indicate decreased functions of these infiltrating T cell subsets. Key words: CD4; CD8; MHC class I; NPC

Nasopharyngeal carcinoma (NPC) is the type of cancer related to multiple risk factors, including infection by Epstein Barr Virus (EBV). Standard treatment of NPC involves radiotherapy and chemotherapy in local and advanced tumors, while metastatic cases are treated with systemic chemotherapy. However, there is limited data on the causes of tumor recurrence, resistance, and progression. Moreover, the initial symptoms of NPC were often neglected until later enlarged, thus making it difficult to manage. MicroRNA (miRNA) is short molecule with 18-24 nucleotides and functions as protein-expression regulator protein in post-transcription. This study was aimed to determine miRNA expression and its relationship with the incidence of NPC. miR-21 and miR-29c were known to be involved in the development of NPC and resistance. A total of 51 plasma samples and 17 tissue samples were collected from Dharmais Hospital. The samples were taken from 17 untreated patients, 17 treated patients, and 17 healthy participants as control. We examined miRNA, protein of protein EBV (EBNA), and c-Myc expression using immunohistochemistry and quantitative polymerase chain reaction (qPCR). Our study revealed an increased expression of miR-21 and decreased expression of miR-29c in patients with NPC. There was also a correlation between the regulation of expression of miR-21 and c-Myc in the treated group of patients, and decreased expression in patients with complete response (CR) (4.13 ± 3.65: 2.74 ± 3.23; p

INTRODUCTION:Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia. METHODS:All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment. RESULTS:In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18-35) from day of diagnosis. CONCLUSION:The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.

Ovarian cancer has the problem turned out to be the greatest and almost half the death rate of mortality throughout gynecological malignancy. Ovarian cancer is found in the female reproductive organs and the second most common cancer after cervical cancer. The process of carcinogenesis of ovarian cancer occurs at the molecular level, regulated by microRNA. At in silico research that has been done, it is known that microRNA-155 (miR-155) targeted mRNA HIF1A which is the regulator genes in hypoxia conditions. HIF1A involved in various cancer hallmarks, where some of them have roles in Warburg effect and also as genetical transcription factors in angiogenesis. Regulation of miR-155 and mRNA HIF1A believed to be involved in the process of ovarian cancer progression and thus potentially as minimally invasive biomarker for prognosis. The aim of this study is to determine whether there are differences in the expression of miR-155 and mRNA HIF1A in plasma ovarian cancer patients at the early stage compared with the advanced stage. The samples using blood plasma from ovarian cancer patients RSUP Dr. Sardjito with 32 ovarian cancer patients early stages and 20 ovarian cancer patients advanced stages. Total RNA was isolated from blood plasma samples of ovarian cancer patients. cDNA synthesis from total RNA was performed to obtain cDNA. The expression of miR-155 and HIF1A were calculated using qPCR. qPCR results were analyzed using Biorad CFX Manager Software. The analysis showed that the expression of miR-155 were 2,18 times lower (p-value = 0,018*) in the plasma of advanced stage ovarian cancer compared with early stage, the differences were statistically significant (p value≤ 0,05). Whereas the mRNA expression HIF1A were 2,46 times higher (p-value = 0,039*) in the plasma of advanced stage ovarian cancer compared with early stage, the differences were statistically significant (p value≤ 0,05). This study has proved that miR-155 expression is downregulated and followed by upregulation of mRNA expression HIF1A at an advanced stage ovarian cancer compared with early stage. Keywords : Plasma, stage ovarian cancer, microRNA-155, mRNA HIF1A

Breast cancer has emerged as the most common cancer-related mortality among women worldwide. Therefore, early cancer detection using biomarkers such as microRNA is needed. One of microRNAs that has an important role in breast cancer development is miR-155. Hsa-miR-155-5p is an oncomir that is commonly dysregulated in breast cancer. This study aims to determine the expression of hsa-miR-155-5p in breast cancer patient’s plasma before and after chemotherapy. We collected 64 samples from breast cancer patients admitted to Dr. Sardjito Hospital in Yogyakarta. RNA from plasma was extracted using RNA Isolation Kit miRCURY-Biofluid. cDNA synthesis was performed using cDNA Synthesis kit II and quantification of miR-155-5p using ExiLent SYBR Green master mix (Exiqon). qRT-PCR results were then analyzed with Livak's method and compared (before and after chemotherapy) with t-test. Expression of miR-155-5p in the breast cancer patients’ plasma after chemotherapy was significantly increased (10.59 times) when compared to before chemotherapy (p = 0.001). We concluded that there was upregulated expression of miR-155-5p after chemotherapy than before chemotherapy. There has not been a known, relevant pathway between hsa-miR-155-5p and chemotherapy regimens nor resistance to chemotherapy. Keywords: Breast cancer, plasma, hsa-miR-155-5p, oncomiR, chemotherapy.

Background: Osteoblast and osteoclast are the important factor in periodontal tissue remodeling for the orthodontic treatment success. Resorption process takes place in compression area by osteoclast and apposition in the tension area by osteoblast. In general hormone condition and age affect remodeling process. Estrogen has a high contribution in remodelling process and decreased in elderly individual such as menopausal women. Soybean contains isoflavone genistein which has similar structure and activity to estrogen. Many researchers indicate that isoflavone genistein not only has an inhibitor effect in osteoporosis but also has estrogenic and antiestrogenic effect as well. Purpose: The study aimed to investigate the effect of soybean isoflavone genistein administration on osteoblast and osteoclast cells number in orthodontic tooth movement of young and old guinea pigs. Method: The research was quasi-experimental study with post test only with control design. The experimental animals were 24 male guinea pigs that divided into: young guinea pigs (±4 months old) and old guinea pigs (±2.5 years old). Each group was divided into 4 subgroups for receiving the treatment namely; control, orthodontic treatment, genistein treatment and orthodontic+genistein treatment. All of the subjects were sacrificed at day 7 and the specimens were histologically analyzed using tartrate resistance acid phosphatase (TRAP) and hematoxylin eosin (HE) staining and observed using microscope that connected to obtilab and an image raster program . Result: U Mann-Whitney statistical analysis showed there were significant differences in osteoblast cell numbers; between orthodontic treatment and orthodontic+genistein treatment in the old guinea pigs (p=0.004); between orthodontic treatment in the young guinea pig and orthodontic+genistein treatment in the old guinea pig (p=0.016); between orthodontics treatment and orthodontic+genistein treatment in the young guinea pigs (p=0.025). U Mann-Whitney statistical analysis showed there were significant differences in osteoclast cell numbers: between the orthodontic treatment in the old guinea pig and orthodontics+genistein treatment in the young guinea pigs (p=0.007); between orthodontic treatment group in the young guinea pigs and orthodontics+genistein treatment in the old guinea pigs; between orthodontic treatment and orthodontic+ genistein treatment in the young guinea pigs (p=0.007). All groups administered by genistein the numbers of osteoblast in the surrounding of the tension sites increased, while in the surrounding of the compression sites had less osteoclasts; even, there were no osteoclasts found in some samples. Conclusion: Soybean isoflavone genistein administration on orthodontic tooth movement increased osteoblast numbers in the tension sides and decreased osteoclast numbers in the compression sides.

Background Nasopharyngeal carcinoma (NPC) is one of the leading causes of cancer death in Indonesia. At initial diagnosis, 80% of the patients present with advanced stage disease. In Indonesia, primary medical care is generally provided by the health care centres; named Puskesmas. The lack of knowledge of various aspects of NPC of the General practitioners (GPs) working in these centers might contribute to the diagnostic delay. The aim of this study was to assess the knowledge of these GPs on different aspects of NPC including symptoms, risk factors and incidence. Methods One hundred six GPs in the Puskesmas in the Yogyakarta province were subjected to a questionnaire on different aspects of NPC based on literature and interviews with Head and Neck Surgeons. Results All GPs approached participated and in total 106 questionnaires were filled in. All participants were aware of NPC as a disease and 89% confirmed that it is a serious problem in Indonesia. However, 50% of the participants believed NPC has a low incidence in their region. The question on early symptoms gave a mean 4.2 answers of which 50% were incorrect. The GPs provided a total of 318 answers when asked for the risk factors of NPC, 75% of which were incorrect. Fifty seven GPs (54%) stated that they did not receive sufficient education on NPC at the university and insufficient knowledge was gained during daily practice. Ninety-two percent of the GPs were interested in additional education, preferably in form of lectures, meetings or folders. Conclusion This study revealed that GPs in the Puskesmas in Yogyakarta lack knowledge on all aspects of NPC. This is an important finding as NPC is endemic in Indonesia and the Puskesmas are the institutions which provide primary medical health care in the country. Further education of the GPs in these endemic areas could be a first step to increase the rate of early detection. Therefore, we suggest 1) to conduct a medical awareness campaign for GPs on the most important subjects concerning NPC, and 2) as soon as NPC awareness among GPs has risen, provide further education on the risk factors, the early symptoms and the incidence, education to the community. We propose to extend this study to other areas in Indonesia (i.e. Jakarta, Surabaya, Central Java), using models that have been developed in Yogyakarta.

Background BamHI-A rightward frame-1 (BARF1) is a carcinoma-specific Epstein-Barr virus (EBV) encoded oncogene. Here we describe the BARF1 sequence diversity in nasopharyngeal carcinoma (NPC), other EBV-related diseases and Indonesian healthy EBV carriers in relation to EBV genotype, viral load and serology markers. Nasopharyngeal brushings from 56 NPC cases, blood or tissue from 15 other EBV-related disorders, spontaneous B cell lines (LCL) from 5 Indonesian healthy individuals and several prototype EBV isolates were analysed by PCR-direct sequencing. Results Most NPC isolates revealed specific BARF1 nucleotide changes compared to prototype B95-8 virus. At the protein level these mutations resulted in 3 main substitutions (V29A, W72G, H130R), which are not considered to cause gross tertiary structure alterations in the hexameric BARF1 protein. At least one amino acid conversion was detected in 80.3% of NPC samples compared to 33.3% of non-NPC samples (p < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence. Conclusion The sequence variation of BARF1 observed in Indonesian NPC patients and controls may reflect a natural selection of EBV strains unlikely to be predisposing to carcinogenesis. The conserved nature of BARF1 may reflect an important role in EBV (epithelial) persistence.

Latar belakang: Karsinoma nasofaring (KNF) adalah keganasan epitelial yang banyak dijumpai pada populasi Cina dan Asia Tenggara termasuk Indonesia. Virus Epstein Barr (EBV) terbukti berasosiasi kuat dengan karsinoma nasofaring. Beberapa protein virus seperti EBER, LMP1, LMP2 ditemukan pada jaringan dan darah penderita kanker nasofaring. Selain itu terjadi peningkatan kadar antibodi terhadap protein virus IgA (VCA-p18+EBNA-1) pada mayoritas pasien. Peningkatan plasma EBV DNA merupakan marker yang penting adanya penyakit dan untuk monitoring progresifitas penyakit. Parameter lain serum/ plasma yaitu kadar Interleukin-8 (IL-8) dan interleukin-10 (IL-10) juga terlibat didalam progresifitas karsinoma nasofaring. Tujuan: penelitian ini untuk melihat hubungan kadar IL-8 dan IL-10 dengan stadium dari karsinoma nasofaring. Metode: Penelitian ini bersifat potong lintang (cross sectional study) pendekatan survei eksploratif dengan 39 pasien karsinoma nasofaring dan kontrol 29 orang sehat dalam penelitian ini. Nilai kadar plasma IL-8 dan IL-10 diperiksa dengan ELISA. Hasil: menunjukkan terdapat korelasi positif antara IL-8 dan IL-10 terhadap progresifitas KNF. Kesimpulan: IL-8 berhubungan dengan progresivitas karsinoma nasofaring. Rasio IL-8 dan IL-10 dapat digunakan menilai prognosis KNF. Bila hasil rasio IL-8:IL-10>1 menunjukkan tendensi buruk, oleh karena itu mungkin dapat diusulkan sebagai faktor prediktor karsinoma nasofaring. Kata kunci: Karsinoma nasofaring, IL-8, IL-10.0 ABSTRACT Background: Nasopharyngeal cancer (NPC) is an epithelial malignancy, prevalent in Chinese populations and Southeast Asia including Indonesia. Epstein Barr Virus (EBV) has been assosiation with nasopharyngeal cancer. Viral gene products namely EBER. LMP1, LMP2 and EBNA’S have been found in nasopharyngeal cancer tissues. In addition increase of IgA (VCA-p18+EBNA-1) in the majority of patients. most often found in nasopharyngeal cancer tissues with an increase in IgA antibody titer of viral proteins (VCA-p18+EBNA -1) in the majority of patients. The increase of plasma of EBV DNA load is an important marker of disease and for monitoring its progression. Other parameters of serum/plasma is level of Interleukin-8 (IL-8) and interleukin-10 (IL-10) which also involved in nasopharyngeal cancer progression. Purpose: to find out the relationship level of interleukin-8 (IL-8) and interleukin-10 (IL-10) in relation with the stadium of nasopharyngeal cancer. Method: A cross sectional study with exploratif survey was conducted 39 patients of NPC, controls 29 healthy subjects included in this study. The value of plasma levels of IL-8 and IL-10 examined by ELISA. Result: There was a positive correlation between IL-8 and IL-10 against the progression of NPC. Conclusion: IL-8 and is a marker of NPC and the progression of the disease. The ratio of IL-8 and IL-10 can be used to assess prognosis of NPC. Ratio of IL-8:IL-10 > 1 indicates a poor prognosis. Keywords: Nasopharyngeal, cancer, IL-8, IL-10

Undifferentiated nasopharyngeal carcinoma (NPC) is strongly linked to Epstein-Barr virus (EBV) infection. The presence of aberrant antibodies against EBV and high viral DNA load can be predictive for the disease and have been proposed for screening tools. Beside the EBV-based markers, analysis of aberrant methylation in gene promoter of tumor suppressor gene (TSG) may have potential value in identifying NPC at early stage. This study determined methylation status of multiple TSGs and evaluated whether it may improve NPC early detection using EBV-based assays. Association between EBV-encoded latent membrane protein 1 (LMP1) and methylation status was also tested. Nasopharyngeal brushings and sera were obtained from 53 NPC cases, 22 high risk individuals and 25 healthy EBV carriers. In all sera the detection of antibody against EBV was performed using EBV-IgA ELISA. EBV DNA load was measured by a quantitative light-cycler PCR on nasopharyngeal brushing samples. For methylation analysis, DNA was modified using bisulfite treatment and amplified by methylation-specific PCR (MSP) or quantitative MSP to target region within promoter of eleven TSGs. The expression of LMP1 was tested using immunohistochemistry. NPC samples demonstrated frequent methylation for individual TSGs (DAPK1 79%, CDH13 77%, DLC1 77%, RASSF1A 76%, CADM1 70%, p16 66%, WIF1 61%, CHFR 59%, RIZ1 57% and RASSF2A 29%). High risk individuals showed high frequency of four methylated genes, low methylation of two TSGs and undetectable methylation of another four TSGs. Healthy subjects had similar pattern as high risk individuals. Because not all of methylated genes allowed good discrimination between NPC and healthy individuals, a panel of markers (RASSF1A, p16, WIF1, CHFR and RIZ1) was determined and combined analysis revealed a detection rate of 98%. Quantitative analysis of MAL gene, TSG that has never been tested in NPC, showed promising result for NPC marker. The expression of LMP1 was observed to associate with methylated RASSF1A. In conclusion, methylation analysis has a complementary value to EBV-based assays for NPC risk assessment. The association of EBV oncogene to methylation status underlined the role of EBV in epigenetic event during oncogenesis. Disclosure All authors have declared no conflicts of interest.

In Indonesia Gynura procumbens (Lour) Merr leaves have been long used as various cancers medication. Many in vitro and in vivo studies have demonstrated anticarcinogenesis of ethanol extract of Gynura procumbens leaves. The aim of this study was to investigate the anticarcinogenesis of the ethanol extract of Gynura procumbens leaves on 4 nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. Fifty six 4 week old male Sprague Dawley rats were used in this study and divided into 7 groups. Group 1, 2 and 3 were lingually induced by 4NQO for 8 weeks. In groups 2 and 3 the extract was given simultaneously with or after 4NQO induction finished, each for 10 weeks and 26 weeks, respectively. Groups 4, 5 and 6 were induced by 4NQO for 16 weeks. However, in groups 5 and 6 the extract was given as well simultaneously with or after the 4NQO induction, each for 18 weeks, respectively. Group 7 served as the as untreated control group. The results from microscopical assessment showed that tongue squamous cell carcinomas (SCC) developed in 100% (3/3) of group 1. However, only 33.3% (2/6) and 25% (2/8) of rats in groups 2 and 3, respectively demonstrated tongue SCC. Among groups 4, 5 and 6, no significant difference of tongue SCC incidence was observed. From these results it is apparent that the ethanol extract of Gynura procumbens leaves could inhibit the progression of 4NQOinduced rat tongue carcinogenesis in the initiation phase.

BackgroundTreating local failures of nasopharyngeal carcinoma (NPC) is a challenge. This study evaluates photodynamic therapy (PDT) in the treatment of residual and recurrent NPC.MethodIn this phase II study, patients with local recurrent or residual NPC after curative intent (chemo-) radiation could be included. Exclusion criterion was a tumour depth more than 10 mm. Foscan® 0.15 mg/kg was administered intravenously. After 96 h, the illumination was performed under local anaesthesia with a nasopharyngeal light applicator. Tumour response was measured 10 weeks after illumination by endoscopy, biopsy and CT-scan. Kaplan-Meier method was used for survival analysis.ResultsTwenty-one patients were included. Fourteen patients were treated for residual disease (67%), and two for recurrent (10%). For five patients this distinction could not be made, due to uncertainty about complete response after initial treatment. The median follow-up time was 32 months. Twenty patients (95%) had a complete response 10 weeks post-treatment. Two patients had recurrent local disease at 5 and 7 months post-PDT. They received another course of PDT, one with success. The 2-year local control rate was 75%, progression free survival was 49% and overall survival was 65%. Nine patients (43%) had no evidence of disease and were in a good clinical condition (ECOG Performance Scale 0) at the end of the study period. No serious adverse events were observed.ConclusionThis study showed that PDT is effective in treating local failures of NPC with a depth of less than 10 mm. The treatment was easy to perform under local anaesthesia. Especially in regions were other modalities like radiation and surgery are limited PDT can be a good alternative treatment.