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Objectives:Osteoporosis is a metabolic bone disease of reduced bone mass density (BMD) and elevated risk of fracture due to an imbalance in bone formation and resorption. The risk and incidence of osteoporosis increase towards advanced age, particularly in postmenopausal women, and the risk is known to be affected by the variation in the expression of the associated regulatory genes. This work aimed to clarify the impact of variation in RUNX2 (runt domain transcription factor 2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding single-nucleotide polymorphism within RUNX2 promoter (P1) and risk of osteoporosis in postmenopausal Indonesian women.Methods:Using DNA sampling from blood, the variation at the single-nucleotide polymorphism (-330, G→T, rs59983488) at the RUNX2 P1 promoter was investigated using polymerase chain reaction–restriction fragment length polymorphism for 180 consenting postmenopausal Indonesian women. The subjects were examined for bone mass density and classification to normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Chi-square testing and logistic regression were mainly used for statistical assessment.Results:The results showed a general trend with increased risk of osteoporosis associated with the genotype TT (mutant type) and the corresponding T allele of the tested polymorphism of RUNX2 promoter P1. The trend was, however, not significant in multivariate testing adjusted for age and time after menopause.Conclusion:To confirm the potential risk with TT genotype would require testing of a much larger sample of subjects. As the tested single-nucleotide polymorphism only represents one of the relevant candidate locations of RUNX2, the results are taken nevertheless to suggest an impact by overall RUNX2 variation in the risk of osteoporosis in Indonesian postmenopausal women.

Context: Polycystic ovarian syndrome (PCOS) is a common endocrine system disorder among the women of reproductive age, yet the etiology of PCOS remains unclear. Infertility in females with PCOS can be caused by anovulation, high luteinizing hormone levels, and hyperandrogenism. Aims: This research analyzed the role of the aromatase gene (CYP19A1) in PCOS pathogenesis. Settings and Design: This study used an observational, cross-sectional design. Subjects and Methods: A total of 110 research participants (55 PCOS patients and 55 non-PCOS patients) were included in the study. Statistical Analysis Used: A real-time quantitative polymerase chain reaction was used to analyze the mRNA expression for aromatase in granulosa cells. Results: The relative expression of aromatase mRNA is lower in women with PCOS compared to those without PCOS ( P < 0.05). Relative expression of CYP19A1 (aromatase) mRNA in PCOS group was 0.38 ± 0.25, whereas in non-PCOS group was 1.00 ± 0.00. The decline in aromatase activity contributes to an increase in testosterone level. This condition has a role in hyperandrogenism which is a typical characteristic of PCOS women. Granulosa cells in polycystic ovary undergo disturbance in the development and cannot respond to follicle-stimulating hormone (FSH) stimulation. Lack of stimulation of FSH causes induction inadequacy to aromatase enzyme activity in the aromatization process. The decline in FSH activity is caused by various factors that are associated with typical characteristics of PCOS. Conclusions: There is a decrease in the relative expression rate of granulosa cells’ aromatase mRNA in women with PCOS compared to the non-PCOS.

Background Agriculture is a major economic sector in Indonesia. Chemical pesticides are widely being used in agriculture for controlling pest. There is a growing concern that pesticide exposure, particularly chlorpyrifos (CPF) exposure, combined with other occupational characteristics that determine the level of exposure, can lead to further health impacts for farmers. Our objective was to evaluate the cumulative exposure characteristics among farmers exposed to CPF by using a validated algorithm. Methods We conducted a cross-sectional study of 152 vegetable farmers aged 18–65 who actively used CPF for at least 1 year in Central Java, Indonesia. Subject characteristics were obtained using a structured interviewer-administered questionnaire, addressed for sociodemographic and work-related characteristics. The cumulative exposure level (CEL) was estimated as a function of the intensity level of pesticide exposure (IL), lifetime years of pesticide use and the number of days spraying per year. CEL was subsequently classified into two groups, high and low exposure groups. The difference in characteristics of the study population was measured using Chi-square, independent-t or Mann-Whitney test. Association between CEL and its characteristics variables were performed by multiple linear regression. Results Seventy-one subjects (46.7%) were classified as the high exposure group. The use of multiple pesticide mixtures was common among our study population, with 94% of them using 2 or more pesticides. 73% reported direct contact with concentrated pesticides product, and over 80% reported being splashed or spilt during preparation or spraying activity. However, we found that the proportion of proper personal protective equipment (PPE) use in our subjects was low. Higher volume of mixture applied (p <  0.001) and broader acres of land (p = 0.001) were associated with higher cumulative exposure level, while using long-sleeved clothes and long pants (p <  0.05) during pesticide spraying were associated with lower cumulative exposure after adjusted for age and gender. Conclusions These findings indicate an inadequate knowledge of using pesticides properly. Thus, we recommend comprehensive training on pesticide usage and encourage proper PPE to reduce the exposure level.

Objectives Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy. Methods We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy. Results Strong expression of SOX2 ( p = 0.011, p = 0.001) and OCT4 ( p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively). Conclusions Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

Introduction: Nasopharyngeal carcinoma (NPC) is a multifactorial disease with genetic, viral, environmental and lifestyle-related risk factors. Epstein-Barr virus (EBV) can promote the oncogenic transformation of an infected cell into malignant. EBV encodes many stimulating products including Epstein-Barr virus nuclear antigen-1 (EBNA-1) which plays a key role in the regulation of gene expression and replication of the genome in the latent period of infection. EBNA-1 in serum and tumour tissue of NPC patients correlates with NPC prognosis. Moreover, the presence of EBV DNA in serum samples from NPC patients' blood circulation can be used as an early marker in the diagnosis of NPC. Objective:The objective of this study was to find effective methods for monitoring the progress of NPC patients undergoing radiotherapy and therapeutic efficacy by observing the changes in EBV DNA in serum and saliva. Methodology:The pre-experimental design compared blood and saliva taken from a pretest and post-test group of NPC patients before and after radiation therapy. The concentration of EBV DNA was measured in the serum and saliva after amplification using quantitative polymerase chain reaction (qPCR) with compatible primers for the EBNA-1 gene. The data were statistically analysed by paired T-test.Results: Highly significant (p = 0.0001) increase in cycle threshold qPCR and decrease in the mean concentration of EBV DNA (p = 0.0001) were observed in serum samples, but no significant changes were observed in saliva. Conclusions:The results suggest that EBV DNA in serum can be used as the gold standard and a marker for monitoring the response to radiation therapy in NPC patients, whereas the examination of EBV DNA from saliva samples is not accurate and thus, not appropriate.

Table of contentsA1 Hope and despair in the current treatment of nasopharyngeal cancerIB TanI1 NPC international incidence and risk factorsEllen T ChangI2 Familial nasopharyngeal carcinoma and the use of biomarkersChien-Jen Chen, Wan-Lun Hsu, Yin-Chu ChienI3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findingsAllan HildesheimI5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast AsiaJames D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena DeviI6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylationLi L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao QI7 Tumor exosomes and translational research in NPCPierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira DelhemI8 Host manipulations of the Epstein-Barr virus EBNA1 proteinSheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori FrappierI9 Somatic genetic changes in EBV-associated nasopharyngeal carcinomaLo Kwok WaiI10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern ChinaSui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei CaoI11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disordersDenise L. Doolan, Anna Coghill, Jason Mulvenna, Carla Proietti, Lea Lekieffre, Jeffrey Bethony, and Allan HildesheimI12 The nasopharyngeal carcinoma awareness program in IndonesiaRenske Fles, Sagung Rai Indrasari, Camelia Herdini, Santi Martini, Atoillah Isfandiari, Achmad Rhomdoni, Marlinda Adham, Ika Mayangsari, Erik van Werkhoven, Maarten Wildeman, Bambang Hariwiyanto, Bambang Hermani, Widodo Ario Kentjono, Sofia Mubarika Haryana, Marjanka Schmidt, IB TanI13 Current advances and future direction in nasopharyngeal cancer managementBrian O’SullivanI14 Management of juvenile nasopharyngeal cancerEnis OzyarI15 Global pattern of nasopharyngeal cancer: correlation of outcome with access to radiotherapyAnne WM LeeI16 The predictive/prognostic biomarker for nasopharyngeal carcinomaMu-Sheng ZengI17 Effect of HLA and KIR polymorphism on NPC riskXiaojiang Gao, Minzhong Tang, Pat Martin, Yi Zeng, Mary CarringtonI18 Exploring the Association between Potentially Neutralizing Antibodies against EBV Infection and Nasopharyngeal CarcinomaAnna E Coghill, Wei Bu, Hanh Nguyen, Wan-Lun Hsu, Kelly J Yu, Pei-Jen Lou, Cheng-Ping Wang, Chien-Jen Chen, Allan Hildesheim, Jeffrey I CohenI19 Advances in MR imaging in NPCAnn D KingO1 Epstein-Barr virus seromarkers and risk of nasopharyngeal carcinoma: the gene-environment interaction study on nasopharyngeal carcinoma in TaiwanYin-Chu Chien, Wan-Lun Hsu, Kelly J Yu, Tseng-Cheng Chen, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Laio, Yen-Liang Chang, Cheng-Ping Wang, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan ...

ObjectiveThis study aimed to examine the effect of vitrification on apoptosis and survival in human preantral follicles after thawing.MethodsThis experimental study was conducted at an acute tertiary care hospital from March 2012 to April 2013. Ovaries were sliced into 5×5×1-mm pieces and divided into the following three groups: preantral follicle isolation, ovarian tissue vitrification-warming followed by follicle isolation, and immunohistochemistry of fresh ovarian tissue. For statistical analyses, the Student t-test, chi-square test, Kruskal-Wallis test, and Kaplan-Meier survival analysis were used.ResultsA total of 161 preantral follicles (70% secondary) were collected from ovarian cortex tissue of six women between 30 and 37 years of age who underwent oophorectomy due to cervical cancer or breast cancer. There were no significant differences in the follicular morphology of fresh preantral follicles and vitrified follicles after thawing. The mean Fas ligand (FasL) mRNA expression level was 0.43±0.20 (relative to β-actin) in fresh preantral follicles versus 0.51±0.20 in vitrified follicles (p=0.22). The mean caspase-3 mRNA expression level in fresh preantral follicles was 0.56±0.49 vs. 0.27±0.21 in vitrified follicles (p=0.233). One vitrified-thawed secondary follicle grew and developed to an antral follicle within 6 days of culture.ConclusionVitrification did not affect preantral follicle morphology or mRNA expression of the apoptosis markers FasL and caspase-3. Further studies are required to establish whether vitrification affects the outcomes of in vitro culture and the maturation of preantral follicles.