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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)

Articles 35 Documents

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Search results for , issue "Vol 48, No 4 (2016): SUPPLEMENT" : 35 Documents clear

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.

Expression of Circulating microRNA-141 and mRNA of PTEN (Phosphatase and Tensin Homolog) in Blood Plasma of Ovarian Tumor and Epithelial Ovarian Cancer Patient AS. Fitriawan; SN Chasanah; FK Pakun; AI Kartika; R. Oktriani; A. Trirahmanto; H. Prajatmo; A. Ghozali; T. Aryandono; SM. Harjana
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Epithelial Ovarian Cancer (EOC) is the most lethal gynecological malignancies among woman. The majority of this disease is diagnosed at the advanced stage due to lack of specific symptoms and effective screening methods. Therefore, an adequate biomarker for early detection is needed and may improve patient survival. microRNA is a small non-coding RNA that regulates gene expression in post-transcriptional level. Several studies have shown the ability to detect microRNA in blood circulation so microRNA may be used as a minimally invasive biomarker for EOC. microRNA-141 (miR-141) plays a major role in EOC by regulating expression of several tumor suppressor gene. Previous study have confirmed that miR-141 regulated PTEN gene directly by interacting with 3’UTR sequence of PTEN mRNA, and upregulation of miR-141 caused downregulation of PTEN expression in vivo. PTEN is important tumor suppressor gene that its inactivation found in various human cancer. PTEN is protein with lipid phosphatase activity that negatively regulate PI3K-AKT signaling pathway, thus playing a important role in various cellular process such as proliferation, growth, cell survival, EMT, cell motility, and angiogenesis. When various studies found that PTEN mRNA and protein expression is significantly downregulated in EOC tissue, little is known about the expression of PTEN mRNA in blood circulation of EOC patient, especially in Yogyakarta population.The aims of this study is to measure and to investigate the correlation of miR-141 and mRNA PTEN expression in plasma of ovarian tumor patient and EOC patient.This study used cross-sectional design. 25 blood plasma of ovarian tumor and 25 blood plasma of EOC were collected. Total RNA was isolated and reverse transcribed to obtain cDNA. The expression of miR-141 and mRNA PTEN were measured by quantitative real-time polymerase chain reaction assay (qPCR). The 2^(-∆∆cq) method was used to calculate relative quantification of miR-141 and mRNA PTEN using miR-16 as reference gene for microRNA and beta-actin mRNA as reference genes for PTEN mRNA. Expression of miR-141 is significantly elevated in blood plasma of epithelial ovarian cancer patient compared to the ovarian tumor (p=0,001, fold change=7,59). Expression of PTEN mRNA significantly downregulated in blood plasma of epithelial ovarian cancer patient compared to the ovarian tumor (p=0,001, fold change=11,63). There was a significant negative correlation between miR-141 expression and mRNA PTEN expression in blood plasma of epithelial ovarian cancer patient (p=0,033; r=-0,428).miR-141 and mRNA PTEN differentially expressed in blood plasma of ovarian tumor and epithelial ovarian cancer patient. There was a negative correlation between miR-141 and mRNA PTEN expression in blood plasma of epithelial ovarian cancer patient. Keywords: Epithelial ovarian cancer, circulating microRNA, miR-141, PTEN mRNA

A Comprehensive Exploration of Java Man: Bio-Cultural Evolution from Homo erectus to Homo sapiens Samuel J Haryono; Sri Utami; Restu Ambar Rahayuningsih
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

ABSTRACTAn overlap of time period between Homo erectus and Homo sapiens has not been confirmed. In the history of man, there have been two missing links: one between man and ape, and one between progressive Homo erectus and archaic Homo sapiens. Specimen dating on Java Man has been discrepant among research groups, and the use of molecular biology in ancient specimens has been a novelty. This study intends to use fossilised specimens, to harvest DNA to be sequenced for ribosomal DNA analysis for comparative phylogeny among ancient and modern man and other hominids. Dental calculus will be analysed to identify starch, carbohydrate, and protein to illustrate paleo dietary pattern. Soil samples will be examined for pollen and phytoliths to elaborate on ancient ecosystem. Blood samples will be procured from indigenous people along the riverflow region of Bengawan Solo to analyse modern human DNA. We hope that we may reconstruct the evolution pathway, construct the phylogenetic tree between ancient and modern hominids, and discover the uniqueness of Homo sapiens sapiens.Keywords: Java Man, Ribosomal DNA, Hominid Phylogenetic,

BRCA1 and BRCA2 Germline Mutations in Asian and European Populations Ute Hamann
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Women who carry a pathogenic mutation in the breast cancer susceptibility genes BRCA1 or BRCA2 (BRCA) have markedly increased risks of developing breast and ovarian cancers during their lifetime. It has been estimated that their breast and ovarian cancer risks are in the range of 46-87% and 15-68%, respectively. Therefore it is of utmost clinical importance to identify BRCA mutation carriers in order to target unaffected women for prevention and/or close surveillance and to help affected women choose the best chemotherapy regimen.Genetic testing for BRCA germline mutations is expanding in clinical oncology centers worldwide. Given the high costs of complete BRCA gene screens, a lot of effort has been expended on deciding upon whom to test. Relevant issues involved in decision making include the prior probability of a woman having a BRCA mutation, which is a function of her age and her disease status, her ethnic group, and her family history of breast or ovarian cancer.The frequency and spectrum of mutations in these genes show considerable variation by ethnic groups and by geographic regions. Most studies have been conducted in European and North American populations, while studies in Asian, Hispanic, and African populations are fewer. In most populations, many BRCA mutations were identified, which were distributed all over the genes. However, in some populations, a relatively small number of specific BRCA mutations are recurrent and account for the majority of all mutations in that population. Many of the recurrent mutations are founder mutations, which were derived from a common ancestor. Founder mutations are present in Ashkenazi Jewish, European, and Islander (Faroe, Easter, and Pitcairn) populations. Such mutations have also been identified in patients from several Asian, South American, and African countries. Population-specific genetic risk assessment and genetic mutation screening have been facilitated at low costs. Given that mutations in the BRCA genes are distributed in populations throughout the world, it is important that the benefits of genetic testing and of targeted therapies be made available not only to women from developed countries in Europe and North America, but also to those from less developed countries in Asia, Africa and South America.

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https://jurnal.ugm.ac.id/bik/about/editorialTeam

Location
Kab. sleman,

Daerah istimewa yogyakarta

INDONESIA