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Published by Universitas Gadjah Mada

ISSN : 01261312 EISSN : 23563931 DOI : http://dx.doi.org/10.19106/JMedSci005303202101

Core Subject : Science,

Immunology & microbiology Neuroscience

Journal of the Medical Sciences (JMedSci) or Berkala Ilmu Kedokteran (BIK) is an international, open-access, and double-blind peer-reviewed journal, published by Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada Yogyakarta Indonesia. JMedSci aiming to communicate high-quality articles in the areas of biomedical science from basic to clinical sciences.The journal welcomes papers from original articles, case reports, reviews, and book reviews. All papers published in JMedSci are freely available as downloadable pdf files. The journal began its publication on March 1973 and published quarterly (January, April, July, and October). JMedSci is abstracted and indexed in DOAJ, Crossref, Google Scholar, Sinta, Indonesia One Search. JMedSci is accredited by Directorate of General Higher Education, the Ministry of Research, Technology, and Higher Education, Indonesia

Arjuna Subject : Kedokteran - Kedokteran (Lain-Lain)

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Search results for , issue "Vol 48, No 4 (2016)" : 41 Documents clear

miR-21, miR-29c, and miR-155 as Biomarker to Develop Minimal Invasive Diagnostic in Hepatocellular Carcinoma Patient P Lestari; N Qoriansas; D.S Tanjung; M.S. Fitria; A.I. Kartika; T. Wardana; N. Ratnasari; S.M. Harjana; T. Aryandono
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and the third leading cause of cancer-related deaths worldwide. Incidence and mortality of HCC increase annually because of its poor prognosis. The most common cause of this condition is its characteristics with high metastasis and high recurrence after surgical treatment. So, it is become important to find new serological biomarkers for early stage detection of HCC. Plasma microRNA are being actively investigated as minimal invasive biomarkers in human cancers, including HCC.Objective: The aim of this study is to investigate the level expression of miR-21, miR-29c, and miR-155 as novel serological biomarkers for hepatocellular carcinoma.Methods: This study is quasi experimental and remain as preliminary study. Collecting for more samples is currently underway. HCC patient blood samples obtained from RSUP dr. Sardjito Yogyakarta based on specific inclusion and exclusion criteria. Blood samples were collected from 8 patients and 8 healthy controls. The collected blood samples were treated as follows: plasma isolation, RNA total isolation, cDNA synthesis, quantification by qRT-PCR, data analysis with Biorad CFX ManagerTM Softwere to determine Cq, followed by the calculation of expression levels using Livax Methods.Result: The result showed that miR-21 and miR-155 were upregulated 1.68 fold and 2.38 fold respectively compared with healthy control, while miR-29c was downregulated 3,45 fold compared with healthy control.Conclusion: Based on the result of preliminary study, it can be concluded that miR-21 act as oncomiR, while miR-29c and miR-155 act as tumor supressor miR in HCC. The three microRNAs can be detected in HCC and can be used as minimal invasive biomarkers to detect HCC.Keywords: HCC, miR-21, miR-29c, miR-155, minimal invasive, biomarker

Over- and down-expression mir-29c and mir-21 after chemotherapy and radio-therapy in nasopharyngeal carcinomas and the down-regulating proteins encoding eipstein barr virus and c-Myc. Tirta wardana; Cita Herawati; Risky Oktriani; Sumadi Lukman Anwar; Indwiani Astuti; Teguh Aryandono; Sofia Mubarika Haryana
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

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 <0.1). The parameters tend to increase in patients with partial response (PR) (3.00 ± 5, 86 compared to 8.77 ± 8.43; p <0.5), while no significant difference in expression of miR-29c in patients with CR and PR was detected. We concluded that miRNA might be detected in the plasma of NPC patients, and miR-21 might become a useful biomarker to determine therapeutic outcome in NPC patients.Keywords: nasopharyngeal cancer; miRNA; biomarker

Long Non-Coding RNA (lncRNA) and MicroRNA ( miRNA) in Cancer Management Sofia Mubarika Haryana
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

AbstractThe discovery of microRNA, a small non coding RNA, has shed light to the dark matters (98%) of the genome. This finding resulted in a Nobel Prize awarded to Fire and Mello in 2006. miRNA a small non coding RNA which played a very important role in regulating protein expression through 3”UTR or other binding places to mRNA target. miRNA have been considered as negative regulators of protein coding gene expression that may impact in cell differentiation, proliferation, survival and all fundamental cellular processes, also implicated in carcinogenesis. miRNA can be grouped into tumor suppressor miRNA (miRSuppressor) and oncogenic miRNA (OncomiR). miRSuppressor regulates protein expression through targeting oncogenic mRNA, meanwhile OncomiR target mRNA Tumor Suppressor. Evidence indicates that deregulation in genetic and epigenetic may cause overexpression of oncomiR and loss of expression of Tumor Suppressor miR. In addition to that, in recent years, evidences showed that cell-to-cell communication conducted via exosome, which is released from every cell in physiological and pathological conditions andconsidered as fingerprints of cell and its status. This is a paramount biomarker discovery in cancer. In subsequent years, a lot of research further performed for the development of new cancer therapy. Our team GenomiR present our preliminary data on several miRNA in cancers aimed to develop minimal invasive biomarkers in cancer. Recently, the long non coding (lnc) RNA, another class of non-coding RNA have also attracted interest from many scientists in the world. lncRNA have emerged as an essential regulator in almost all aspect of biology included carcinogenesis. lncRNA considered as emerging key player in non-coding world.nCRNA (miRNA and lncRNA) in the context of cancer management will be discussed in this presentation

HBOC in Europe Hanne Meijers Heijboer
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

AbstractEurope has contributed to the majority of high-impact papers on genes and risk alleles in breast cancer and ovarian cancer susceptibility. Consortia like the Breast Cancer Linkage Consortium, Breast Cancer Association Consortium, and the Consortium of Investigators on Modifying genes in BRCA1/2, started from the nineties of the last century on. Many highly motivated participants throughout Europe, the US, Australia and elsewhere contributed to the formation of huge datasets. Instrumental of the success of the consortia was also the leadership and knowledge of Dough Easton, UK, on the statistics of cancer genetics. The consortia papers have produced the data on which national guidelines in HBOC were formulated in West-Europe, the US and worldwide. Genetic testing for HBOC is in most Western-European countries accepted and funded. Two decades after the identification of BRCA1 and BRCA2, attitudes towards genetic testing for HBOC are changing and becoming more ‘common’ practice. This offers opportunities to organize cancer genetic care more efficiently and at lower costs while informed decision making and consent of the patients remain in place.

CLINICOPATHOLOGICAL FEATURES OF YOUNG AGE BREAST CANCER PATIENTS IN BALI I Wayan Sudarsa
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

AbstractBreast cancer is, in general, a heterogeneous disease with diverse biological characteristics, histopathological types, subtypes and clinical behavior. Breast cancer in young age, although rare, is usually a unique and more aggressive cancer associated with poorer prognosis. The combination of young age and advanced stages of breast cancer would make this particular breast cancer more difficult to manage. Therefore, individually tailored therapies have been the subject of many studies for these patients. The purpose of this study was to determine clinicopathological features of young age breast cancer patients in Bali from 2014-2016. This was a descriptive study of young age (≤40 years) breast cancer patients in Bali from January 2014 until June 2016. The samples were taken from the Perhimpunan Ahli Bedah Onkologi Indonesia Cancer registry in Sanglah General Hospital Bali. There were 90 samples gathered from the cancer registry and 56 samples (62,2%) had complete clinicopathological records. Clinicopathological features included in this study were age group, histopathological type, primary tumor size, regional lymph node involvement, presence of distant metastasis, stage regrouping, tumor grade, hormonal receptor status, Her2 overexpression status, and breast cancer subtype. There were 56 young age breast cancer patients, with a mean age of 33,86±4,193 years old, the youngest patient was 22 years old, and the majority of the samples were in the 31-35 years age group (26 samples, 46,4%). Only 2 samples (3,6%) had special type carcinoma, both of them were invasive lobular carcinoma, the rest of the samples were invasive carcinoma of no special type. The 2 samples with invasive lobular carcinoma were in 31-35 years age group, had stage II (T2N0M0) and III (T4N1M0) breast cancer, both with grade II tumor and Luminal A subtype. The majority of primary tumor size was T4 (30 samples, 53,6%), nodal status was N1 (29 samples, 51,8%), and only 10 samples (17,9%) had distant metastasis. The majority of the stage regrouping was in stage III (35 samples, 62,5%) and had grade III tumor (33 samples, 58,9%). There were 10 samples (17,9%) with Luminal A subtype, 19 samples (33,9%) with Luminal B subtype, 16 samples (28,6%) with Her2 type subtype, and 11 samples (19,6%) with triple negative breast cancer subtype. We concluded that the majority of young age breast cancer patients in Bali were invasive carcinoma of no special type in advanced stage, with high grade tumor, and within Luminal B subtype.

Molecular Genetics, Genetic Testing, Novel Genome Sequencing Technologies Gerard Pals
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

AbstractWith the advance of genomic technologies, we are now able to detect genetic variations in patients with high accuracy, whole genome scale and relatively cost-effective. This offers an opportunity for altering medical practice fundamentally as well as insurance policy. Although clinicians, scientists, and health policy makers still have to deal how to interpret and handle the results that sometimes come with ambiguity and uncertainty, recent advances especially in the western world have integrated genetic tests and molecular genetic analysis for clinical management of patients. In this session, we will discuss and review the range of methods currently used in clinical setting as well as potential emerging methods in clinical molecular genetic diagnostics. Advantages and disadvantages of each methods will be carefully discussed especially application in regions of the world that have more limited access for molecular genetic tests including next generation sequencing. Outline of implementation challenges for molecular genetic tests both in term of health economics and clinical management will also be discussed.

Mitochondrial Genetics and Cancer Safarina G. Malik
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

The first modern human, the Mitochondrial Eve, was traced back to Africa about 200,000 years ago, based on the variation in the mitochondrial DNA (mtDNA). An eruption of a super volcano, Mount Toba, in Sumatra 70,000 years ago may have led to a 'nuclear winter', followed by a 1,000-year ice age. This cold snap would have made life difficult; genetic evidence indicated a sharp reduction in population size around this time, reaching approximately 10,000 individuals. Once the climate started to improve, our ancestors recovered from this near-extinction event. The population expanded, and some courageous explorers ventured beyond Africa. Around 50,000 years ago some of these brave ancestors had successfully crossed the globe to South East Asia and Australia. Some of them settled in the Indonesian archipelago, forming the first settlement of prehistoric Indonesia. The second migration happened around 10,000 years ago, where a group of hunter-gatherers followed the now-submerged river systems that once ran from mainland Asia between the modern islands of Sumatera, Java, and Borneo. Then, around 4,000 years ago the third group of ancestors arrived. This agricultural community brought along their culture of pottery, plant cultivation, and animal domestication, co-inciding with the vast spread of Austronesian languages. Therefore, it is likely that the Indonesian archipelago hosts a wide range of linguistic, ethnic and genetic diversity.1 Nowadays, the modern Indonesia is home to around 700 ethnic populations, each with distinct cultural and linguistic characteristics, representing vast genome diversity.Our ancestors’ decision to embark on a sea travel and take on its related lifestyle has influenced the development of susceptibility and resistance to various diseases observed today. During the prolonged travel, our ancestors were subjected to changes in global climate and geographic dynamic, which strongly influenced and shaped the genetic background of modern humans, including the mtDNA genome. Mitochondria, a well-adapted endosymbiotic intracellular organelles, became efficient for energy production through-out the course of evolution. They are critical for survival and proliferation of living organisms under aerobic conditions and produce ATP through oxidative phosphorylation (OXPHOS). Adaptation to new environments that favor beneficial traits may have caused genetic risk differences that influence the crucial function of the mitochondria, consequently affecting many function in the cell.2 The altered function of the mitochondria might act as an important factor for disease susceptibility across many human populations, i.e. mtDNA variation that grouped together forming a certain type/group (the mtDNA haplogroup) was reported to modulate cancer susceptibility3-5 and resistance6 in Chinese population.Cancer cells are characterized in general by a decrease of mitochondrial respiration and OXPHOS, a consequence of disruptive mtDNA mutations commonly found in cancer cells, and thus one could say that the growth of cancer cells is directly limited by energetics.7 In order to survive, cancer cells must modify their mitochondrial physiology to optimize energy production to their changing environments. There are two types of advantageous mtDNA mutation in cancer cells: mutations that impair OXPHOS and serve to stimulate neoplastic transformation, and those that facilitate cancer cell adaption to changing bioenergetics environments.8 These mtDNA mutations would eventually lead to an enhanced generation of reactive oxygen species (ROS), which can act both as mutagens and cellular mitogens, and contribute directly to cancer progression.7 Therefore, it can be concluded that mitochondrial alterations are critical for cancer initiation, promotion, and metastasis (Fig 1). Figure 1. Integrated mitochondrial paradigm to explain genetic and phenotypic complexities of metabolic and degenerative disease, aging, and cancer.Top three arrows: factors that have impact on mitochondrial OXPHOS robustness, risk for developing disease symptoms. Central oval arrows: pathophysiological basis of disease processes and the basis of disease progression. Lower five arrows: summarized disease categories and phenotypic outcomes of disturbed mitochondrial energy transformation. Bottom arrow: effect of the problematic accumulation of somatic mtDNA mutations resulting in delayed onset and a progressive course of diseases and aging. Right arrow: clinical problems that can result from reduced energy production in the most energetic tissues: the brain, heart, muscle, and kidney. Left arrow: indicates the metabolic effects of mitochondrial dysfunction, which result in the perturbation of the body’s energy balance. Lower right arrow: mitochondrial alterations are critical for cancer initiation, promotion, and metastasis. Lower left arrow: the hypothesized inflammatory and autoimmune responses that may result from chronic introduction of mitochondria’s bacteria-like DNA and N-formylmethionine proteins into the bloodstream.9

Management of Hereditary Breast and Ovarian Cancer. The Asian Experience Ava Kwong
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

BRCA1/BRCA2 mutations are the most common high penetrant genes associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Although genetic testing is standard of care in Western developed countries, there are still variations in availability of genetic testing and risk assessment for HBOC in Asia. Depending on the countries, there are variations in the clinical strategies and cancer management. The Asian BRCA Consortium has grouped together 14 Asian countries and reviewed genetic counselling/testing uptake rates and clinical management options in these countries. Moreover economic factors, healthcare and legal frameworks, and cultural issues affecting the genetic service availability in Asia were discussed. Mutation spectrum, and VUS rates and the increase use of NGS gene panel testing poses more decisional issues in the clinical management of Hereditary Breast cancer in Asia. These will be discussed.Keywords: BRCA1/BRCA2, germline, HBOC, Asia BRCA Consortium, NGS

Proposed Organization of Family Cancer Clinics in Indonesia Kunta Setiaji
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

AbstractAround 10-15% of breast cancers are associated hereditary and/or familial predisposition. By definition familial breast occurs in two or more first degree relatives within a nuclear pedigree (first or second degree relatives). Hereditary and familial cancer displays different characteristics in the pathological features, clinical course, response to treatment, and outcomes. Therefore, specific consultation and treatment need to be addressed to patients with hereditary or familial predisposition for example the need for rigorous surveillance and preventive treatment including options for preventive surgery. Cancer clinical genetic service is not yet formally available in daily clinical practice in Indonesia. Surgeons usually become the first medical specialist to see cancer patients with familial predisposition, therefore they have to elaborate clinical cancer genetic service under Family Cancer Clinic (FCC). Clinical genetic service within FCC consists of several step-wise tasks including assessment of personal and family history of cancer, personalized cancer risk assessment, review of medical and family history, individual cancer screening and surveillance recommendations, genetic testing if necessary, discussion of benefits and limitations of genetic test, cancer risk reduction options and preventive strategies, and opportunity to participate in research as well as clinical trial. Nation-wide network for FCC is of importance to share knowledge and skill to perform cancer genetic service. Ability to perform genetic test including the interpretation in Indonesia has also been required.

Addition of conjugated linoleic acid in whole milk improves lipid profile in high fat diet induced hypercholesterolemia of rats Arta Farmawati; Rio Jati Kusuma; Bayu Sigha Iswara; . Wulandari; Kurniati Dwi Utami; Istiti Kandarina
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Conjugated linoleic acid (CLA) is an isomer of linoleic acid that has been shown to havemany beneficial effects in prevention of atherosclerosis, hypertension, cardiovasculardiseases and improve immune function. Although majority of CLA in the diet are derivedfrom dairy product such as milk, however, the content of CLA in milk is affected by cow’sdiet. The aim of this study was to investigate the beneficial effect of CLA supplementationin milk for improving lipid profile in high fat diet of rats. Twenty four male Sprague Dawleyrats aged 8 weeks were given high fat diet for 3 weeks to induce hypercholesterolemia.Six rats were maintained in standard diet as control. Rats then were divided into 4 groupsi.e. normal control, negative control, high fat diet+CLA 0.5%, high fat diet + CLA 0.5%supplemented skim milk, and high fat diet + CLA 0.5% supplemented whole milk. Bloodsample was drawn after high fat diet induced hypercholesterolemia and after 4 weeksof treatment for total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDLcholesterol), and high density lipoprotein cholesterol (HDL cholesterol) analysis. Bodyweight was measured each week. Results showed that body weight was significantlyincrease in all groups received high fat diet (p<0.05). There was no significant differencein body weight between treatment group (p>0.05). Total cholesterol, triglyceride, andLDL cholesterol was significantly decrease in whole milk followed by significant increasein HDL cholesterol level. Skim milk supplemented with CLA had only modest effect ontriglyceride and HDL cholesterol level. In conclusion, CLA supplementation in whole milkimproves lipid profile in high fat diet.

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