Journal of the Medical Sciences (Berkala ilmu Kedokteran)
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HBOC in Europe
No full textAbstractEurope 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
Hospital-based Phase III Cardiac Rehabilitation Program Improves Low Density Lipoprotein, Triglyceride, and Fasting Blood Glucose Level in Coronary Artery Disease Patients : a 6-month Follow up
No full textABSTRACTBackground. Cardiac rehabilitation (CR) has been reported as effective for improving coronary risk factors and increasing exercise tolerance in patients with coronary artery disease (CAD) after cardiac events. It may be performed in 3 stages: acute (phase I), subacute (phase II), and chronic (phase III). In Indonesia, most cardiac rehabilitation programs have been phase I and some phase II, whereas phase III cardiac rehabilitation has not often been performed as it was not covered by national health insurance.Objectives. We assessed the beneficial effects of 6-month hospital-based phase III comprehensive cardiac rehabilitation on physical status and coronary risk factors among CAD patients.Methods. 74 patients were stratified as the intervention group (n=37) and the control group (n=37). In the intervention group, patients participated in hospital-based phase III CR for 6 months, whereas in the control group, they received standard care. CR program consists of warm-up (senam jantung sehat), aerobic exercise, cool-down stretching, and health education session three days a week. Blood glucose and lipid profile examination were performed at the beginning and sixth month to assess patient’s metabolic status.Results. Of 74 patients observed, most patients were male (85.1%) with mean age 54.7+3.4 years old. 57 patients had post-procedural history (77% post-PCI, 4% post-CABG), 8 patients (11%) were still active smokers, 31 patients (42%) had diabetes, and 60 patients (81%) had hypertension. Participation of hospital-based phase III CR program was significantly correlated with lower low-density lipoprotein (LDL) level (p=0.003, r=0,41), triglyceride level (p=0.001, r=0,38), and fasting blood glucose (p<0.001, r=0,46) during 6-month follow up.Conclusion. Patients with CAD who underwent hospital-based phase III CR program had significantly better fasting glucose control, LDL, and triglyceride level during 6-month follow up. These results may encourage other hospitals to perform the same program achieving better prognosis of CAD patients.Keywords: cardiac rehabilitation, high density lipoprotein, low density lipoprotein, triglyceride, blood glucos
Molecular Genetics, Genetic Testing, Novel Genome Sequencing Technologies
No full textAbstractWith 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
Bacterionomics and vironomics in carcinogenesis
No full textVirus and bacteria are microbes which are very common cause human infection. Most of the bacterial infection can be eradicated by antibiotics and infection symptoms disappear. But for virus infection, once infected, the virus will persistently stay in the host, even undergo not only a lytic cycle but also integrated into host genome. Nowadays, at least 6 virus type are consistently related to human cancer, such as EBV,HPV,HTLV,HBV,HCV,HKSV, and the new one Merkel Virus (MCV). Although not every infected people will get cancer, but around 20% of the whole cancer in human are caused by viral oncogene.Class one oncogenic bacterial is Helicobacter pylori. Infection with this bacteria can cause persistent gastro duodenal inflammation which cause some alteration in gastric cell growth into transformation. Expression of Cag gene and Vac gene and some expression of OMP protein usually link to gastric cancer.Molecular mechanisms of carcinogenesis for every virus which cause infection is a very complex , which include several processes caused by cell transformation. Besides, other host and environmental factors are also play a significant role in cancer development. Some scientist put a Hallmark analysis as a model to quickly summarize what pathobiology process will happen and what gene or protein caused the process. The Hallmark analysis comprise of several process which may happen simultaneously because some of the Hallmark is caused by the same protein. The Hallmark consists of various virus strategies in oncogenesis such as promoting angiogenesis, avoiding immune destruction, genome instability and mutation, deregulating cellular energetic, resisting cell death, sustaining proliferative signaling, evading growth suppressors, enabling cellular immortality, promoting inflammation and activation metastasis. For example, infection by HPV, will cause low grade dysplasia which can continue to invasive cervical cancer. After host cell transformation, in the long control region genes, E6 and E7 protein will cause several strategies in oncogenesis including resisting cell death and evading growth suppressors. HBV infection will end without any serious liver damage, but after cell transformation, almost all Hallmark strategies of viral oncogenesis are happening step by step in line with the severity of liver cell damage.As the onset of cancer development after infection can last years, there are an opportunity to design either vaccine or genetic therapy to minimalize further risk of cancer in human
BRCA1 and BRCA2: Lack of Certainty and Its Clinical Implications
No full textAbstractIn this time of amounting cancer incidence and mortality, genetic testing may be greatly valuable in deciding on appropriate clinical management. It is unfortunate that the test is not a practical interrogative problem. When positive, the patients can settle down with what to do next, whereas when negative, their family members may breathe out in relief from unnecessary intensive surveillance and prophylaxis, and then there is VUS (Variants of Uncertain Significance). How should a health provider deliver the elaboration and implication of VUS to a patient who had expended a lump sum of and had expected a level of certainty? Variants of UncertainSignificance have nowadays become a challenging spoiler in the setting of clinical management of cancer. How would one inform someone else on anything uninformative? BRCA1 and BRCA2 are two genes with high penetrance in breast cancer. Since their functions as tumor suppressor genes and DNA repair regulators, their mutation effects are only visible when there is Loss of Heterozygosity. Mutation of BRCA1/2 gene can be demonstrated within the tissue specimen and blood sample DNA; that would mean it has occupied all tissues and is inheritable. In the case of BRCA1 and BRCA2 mutations, 10-20% of all genetic test results will read VUS, In one previous study of sixteen Indonesian patients, 13 (81,25%) patients had VUS. There were variants that had not been found in other population. Trans-academically speaking, the reclassification of VUS in BRCA1/2 gene is not merely a challenge to clarify its clinical impacts, but also an obligation to accomplish our community contribution to science.There can be a set of factors to suggest that a VUS may be a deleterious mutation:Co-segregation: when the variant comes with multiple and multigenerational incidence of cancer, it is possible.Epidemiology: when a case control study demonstrates prevalence discrepancy, it is possible.Co-occurrence with deleterious mutation: when the variant is shared within the same gene in other individuals, it is possible.Evolutionary data: when the sequence is carried across species, it is possible.Amino acid substitution: when the substitute is structurally similar, it is impossible.Loss of heterozygosity: when there is loss of a wild type allele in tumor specimen, it is possible.Functional analysis: should an in vitro assay demonstrate a loss of protein function, it is probable.The ultimate solution is not yet available. However, there is clinical significance for families with VUSs, only if that can confidently be classified as the presence or absence of the associated disease. That condition may be achieved by increasing the availability of genetic testing so that there can be a larger, open-access repertoire of VUSs
CLINICOPATHOLOGICAL FEATURES OF YOUNG AGE BREAST CANCER PATIENTS IN BALI
No full textAbstractBreast 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.
The Expression of microRNA-155 and mRNA Hypoxia Inducible Factor Alpha (HIF1A) in the early and advanced stages of ovarian cancer patients blood plasma
No full textOvarian 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 HIF1
Expression of Circulating microRNA-141 and mRNA of PTEN (Phosphatase and Tensin Homolog) in Blood Plasma of Ovarian Tumor and Epithelial Ovarian Cancer Patient
No full textEpithelial 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 mRN
Level of Adipokines and Insulin Resistance in Obese Javanese Population
No full textIntroduction: Obesity is a condition involving low-level chronic inflammation as indicated by increased levels of C-reactive protein (CRP), TNF, interleukin and other inflammatory markers in the blood. Some endocrine mediators, such as paracrine and autocrine derived from adipose tissue play an important role in regulating the function of adipocytes, especially related to insulin sensitivity. Significant complications of obesity, including insulin resistance as a risk factor of Type 2 diabetes are associated with myocardial infarction, stroke, and peripheral vascular disease.Aim: The purpose of this study is to determine the level of C-reactive protein (CRP), TNF-alpha, interleukin, resistin and insulin resistance in the obese group compared to controls sampled from a Javanese population.Method: This study is a preliminary study of 120 people, consisting of 60 obese and 60 controls. Lipid profiles, levels of C-reactive protein (CRP), TNF-alpha, interleukin, resistin were examined with Elisa methods and insulin resistance was calculated by HOMA IR index.Results: This study found levels of glucose, insulin, CRP, and HOMA-IR were higher and significantly different in obese group than control (P 0.05)Conclusion: The study showed that there were increased levels of adipokines and insulin resistance in obese group compared with the control in the sample of Javanese population.Keywords: Obese, insulin resistance, CRP, TNF-Alpha, Interleukin, Resisti
Prognostic factors for heart valve surgery outcomes in Dr Sardjito General Hospital Yogyakarta, Indonesia
No full textHeart valve disease is a serious health probem due its significant effect on mortality.Surgical intervention plays an importan roleinthe management of moderate to the severe valvular heart disease. The evaluation of the patientoutcomes has been widely accepted as one of the important steps to improve the quality of patient care.Recognition of post operative complications might significantly affect the patient quality of life.Therefore, the identification of prognostic factors and morbidity of heart surgery patients can provide valuable insights on improving the quality of patient care.This study aimedto investigat the prognostic factors for heart valve surgery outcomes in Dr. Sardjito General Hospital, Yogyakarta, Indonesia. This study was conducted using data ofpatient’s medical records who underwent heart valve surgeryincluded morbidities and their prognostic factors.The data were analyzed using Chi-square test and logistic regression with significance level of 0.05. During 2010 to 2014, 82 patients underwent heart valve surgeries at the hospital. The kidney disorders and heart failure were significantly associated with the patient morbidity (p0.05). Multivariate analysis showed that the heart failure is the most significant factor of morbidity. The risk of New York Heart Association (NYHA) class 3 patients were 7.18 times compared with NYHA class 2 patients. In conclusion, the heart failure is the most significant factor for the morbidityof heart valve surgery followed by the kidney disorders at the Dr. Sardjito General Hospital