Journal of the Medical Sciences (Berkala ilmu Kedokteran)
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Combination treatment for type 2 diabetes mellitus (T2DM) : dipeptidyl peptidase-4 inhibitors (DPP-4) and metformin
No full textUsing the concept of inhibition of dipeptidyl peptidase-4 (DPP-4) as a new treatment for type 2 diabetes mellitus (T2DM) is based on the inhibition of bioactive peptide inactivation process. Most clinical trials on DPP-4 inhibition are based on vildagliptin, sitagliptin, saxagliptin, and linagliptin. The drugs may improve glycemic control when they are given as a combination with other oral hyperglycemic agents or when they are given to patients who received metformin and still had inadequate glycemic control. Studies showed that vildagliptin was well-tolerated if it was given as add-on treatment to metformin for 24 weeks duration. In addition, vildagliptin showed significant clinical improvement proven by the associated decrease in HbA1c and fasting glucose levels. Sitagliptin in initial combination therapy with metformin decreased HbA1c level by 2.1% after 24 weeks of treatment. It was reported that DPP-4 inhibitor saxagliptin increased glycemic control when it was added to metformin. The study included 743 patients with an average HbA1c level of 8.0% when they were treated with metformin alone. After 24 weeks of treatment, saxagliptin decreased HbA1c level by 0.7%. A multicenter, randomized, placebo-controlled, double-blind, parallel-group study examined the efficacy and tolerability of linagliptin as treatment adjunctive to metformin in patients T2DM. The primary end point was changed in HbA1c from baseline to 24 weeks of treatment. The mean adjusted change from baseline in HbA1c in the linagliptin group was 0.49% compared with an increase of 0.15% in the placebo group, with 26% and 9% of participants in the linagliptin and placebo groups, respectively, achieving an HbA1c 7.0% at 24 weeks. The combination of DPP-4 inhibitors and metformin has been shown to be well-tolerated with a very low risk of hypoglycemia. Therefore, DPP-4 inhibitors and metformin combination is an efficient, safe, and well-tolerated therapy for T2DM.
Long Non-Coding RNA (lncRNA) and MicroRNA ( miRNA) in Cancer Management
No full textAbstractThe 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 presentatio
Variation of the breast cancer susceptibility marker, rs4245739, is associated with differential miRNA binding and MDM4 expression
No full textA polymorphism, rs4245739, has been associated with susceptibility of several cancers including ER-negative breast cancer. Rs4245739 is located at the 3’UTR of MDM4 gene, an oncogene that negatively regulates p53. The polymorphism has been associated with binding changes of miR-191. We studied, the influence of SNP rs4245739 to the binding of microRNAs, expression of microRNAs and MDM4. Using FindTar software, we detected potential microRNAs affected by the SNP-flanking sequence. We then used RNA sequencing data from ER-negative breast cancer to compare expression of miR-184, miR-191, miR-193a, miR-378, and MDM4 in different genotypes. Comparison of ER-negative patients with and without expression of miR-191 as well as profile microRNAs (miR-184, miR-191, miR-193a and miR-378 altogether) can differentiate expression of MDM4between different alleles. In addition, the number of lymphatic nodes affected in the individuals was also found to be significantly reduced in the risk group obtained by the miRNA profile method. We show our methods especially miRNA profile approach, are able to obtain new molecular and clinical features related to the rs4245739 SNP, a variant located in the 3’UTR of MDM4 gene and known to appear in different types of cancer. Keywords: ER negative breast cancer, rs4245739, microRNA, MDM4, p5
Effect of Syzigium cumini (pulp) extract on malondyaldehyde and blood pressure in chronic restraint stress rat
No full textABSTRACTIntroduction. Chronic stress disturbs the equilibrium of oxidant-antioxidant redox in the human body which accelerates cellular aging. This condition promotes earlier onset of age-related diseases. Human body needs exogenous antioxidant to fight stress. Syzigium cumini has high antioxidant activity because it’s rich in anthocyanin. It has potential to become natural antioxidant source thus it needs to be developed.Aim. This study aims to investigate the effect of Syzigium cumini (Pulp) extract on the stress biomarkers which are Malondialdehyde and blood pressure in rat induced by restraint stress.Method. Chronic stress phase is conducted with male Wistar rats (n=20) which were divided into 4 groups (normal control, negative control, and two treatment groups with the ethanol extract of Syzygium cumini (Pulp) at 20 mg/200 gram and 40 mg/200 gram body weight). Restraint stress was carried out by placing the animal in narrow tube for 30 minutes daily (7 days). Blood pressure was evaluated before and after the treatment while Malondialdehyde was evaluated after the treatment. The One-way ANOVA was used to analyze the parameters.Results. Based on chronic stress phase, treatment groups show significant result in preventing the increase in blood pressure (P < 0,001). The increased levels of Malondialdehyde were prevented significantly in all treatment groups (P < 0,001)Conclusion. In chronic stress phase, Syzygium cumini (Pulp) extract can become an antihypertensive agent. Syzygium cumini (Pulp) extract shows an effect in decreasing lipid peroxidation products. This result shows that the Syzygium cumini (Pulp) extract has potent antioxidant function.Keywords. Syzigium cumini, restraint stress, malondialdehyde, MDA, blood pressur
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.
No full textNasopharyngeal 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; biomarke
Comparing P-Selectin (CD62P) expression in patients receiving non-leukodepleted vs leukodepleted thrombocyte concentrates
No full textThrombocyte concentrate (TC) transfusion is an important supportive therapy in patients with thrombocytopenia. The risks in platelet transfusions may be related to the content of TC including the contaminant leukocytes. The aim of this study was to assess the risk of increased level of P-Selectin (CD62P) expression of non-leukodepleted TC transfusions.This was a quasi-experimental study. Subjects were children patients aged 1-18 years who received a non-leukodepleted or a leukodepleted TC transfusions. Comparison of the proportion of increased expression of CD62P in both groups expressed as relative risk. The subjects consisted of 51 patients who received non-leukodepleted and 52 patients who received leukodepleted TC transfusions. The risk of increased expression of CD62P in patients receiving non-leukodepleted TC transfusions were 2.38 (95%CI:1.60-3.53) times higher than those who received leukodepleted TC. Non-leukodepleted have significant higher risks of increased CD62P expression than leukodepleted TC transfusions
Breast reconstruction
No full textBreast reconstruction is such a unique procedure that might potentially be adjustedin line with time and all advances in technology and instruments (endoscopy,silicone implants, alloderm grafting). In addition, it adapts in accordance to better,more sophisticated knowledge of breast anatomy (vascularization, perforator, andinnervation), breast subunits, and systemic changes. Surgical techniques and thecurrently available list of materials might be utilized to reconstruct the breast insuch a way to yield cosmetic satisfaction. Combination and modification of thosetechniques might be adjusted to the patients’ requests without crossing over thepaths of the disease being corrected (cancer, benign tumor, infection, or otherbreast anomalies).Breast reconstruction’s prerequisite is the absence of cancer approximately 1cm from the edge of incision, adjusted by shape and size of breasts, and sizeof cancer. Several techniques might be applied to conserve and reconstruct thebreasts when the disease has been diagnosed. Oncoplasty applies all techniquesavailable to reaffirm the principles of oncology, by increasing the distance fromthe edges of cancer and proceeding with reconstruction by reduction/mastopexy(volume displacement), or adjacent/distant flaps (volume replacement). Thedisadvantage of BCS/BCT is the short distance from the edge of incision to thetumor due to the risk of post-operative breast deformity, especially when surgeryis followed by adjuvant radiation
ROLE OF DNA METHYLATION AS A DIAGNOSTIC BIOMARKER OF SPORADIC BREAST CANCER
No full textThe initiation and progression of breast cancer have been recognized for many years to be secondary to the accumulation of genetic mutations which lead to aberrant cellular function. Genetic mutations, either inherited or sporadic, may result in the activation of oncogenes and the inactivation of tumor suppressor genes. The more recent discovery that reversible alterations in histone proteins and deoxyribonucleic acid (DNA) can also lead to tumorigenesis has introduced a novel term to the field of cancer research: epigenetics. Epigenetics refers to the study of heritable changes in gene regulation that do not involve a change in the DNA sequence. The most often studied in epigenetics of breast cancer is DNA methylation. That a promoter methylation result in transcription blockade supports the notion that cellular inhibition takes place. Compared to normal tissues, hypermethylation occurs from double to triple in cancerous ones. DNA methylation plays a crucial role in oncogenesis and is one of the hallmarks of cancer.Detection of aberrantly methylated CpG islands in promoter region of several genes in DNA sample derived from nipple aspirates, serum, or cancer tissue associated with down regulation of expression or loss of function of these genes has been associated with early stages of breast cancer, where hypermethylation of CpG island points to poorer prognosis in breast cancer. DNA methylation has been identified as signature for TNBC. Methylation of BRCA1 gene is frequently demonstrated in young, estrogen receptor-negative breast cancer patients. Methylation of specific genes is known to differ across race and socioeconomic status. BRCA1 methylation in premenopausal women with sporadic breast cancer in West Sumatra region has been higher than in Western women.DNA methylation may be used to enhance current breast cancer classification. There is such a distinction between methylation and gene expression profiles of breast cancer that not all methylation profiles fit within the same molecular subtype. Specific gene methylation profiles are identified for basal-like, luminal A and HER2-overexpressing breast cancers. A number of studies have analyzed the methylation status of BRCA1, a key player in TNBC. One study demonstrated that BRCA1 promoter was methylated in TNBC. It was discovered that the sensitivity of TNBC cell lines to PARP inhibitors was increased when BRCA1 was methylated. Concurrently, BRCA1 methylation quantity was higher in patients with complete response than in those who are non-responders of neoadjuvant chemotherapy.Epigenetics is now the cutting edge of cancer research. Advances in this field will have major implications in diagnosis, prevention, treatment of cancer, and formulation of new epigenetically targeted cancer drugs
Oncoplasty: How to start and experience from Yogyakarta
No full textAbstractReconstruction surgery after tumor removal is increasingly essential because of changes in patient expectations and demand. With the advance of early screening and detection, our ability to detect early stage cancer is significantly improved. Reconstruction is mostly suitable in patients with early stage cancer. In addition, there is growing ability that that immediate reconstruction in particular selected patients can be performed in a single time operation combining oncological and aesthetic procedures with considerably excellent result. With the implementation of full coverage insurance by BPJS, most oncological surgery including in breast cancer will be performed by general surgeon in regency hospital. Reconstruction in selected patients usually is performed as delayed procedure by plastic surgeon. With the advance in surgical oncology training, breast surgery should be performed by surgical oncologist with specific oncoplasty training that can offer immediate reconstruction with both extensive removal tumor and reconstruction. Therefore, training in oncoplasty is very important for surgical oncologist. In Yogyakarta, we performed reconstruction after surgery of breast tumor, thyroid cancer, radical neck dissection and facial basal cell carcinoma with relatively excellent results. Further training and innovation are required to improve this early stage oncoplasty practice in Yogyakarta.Keywords :
The effect of the implementation of evidence-based drug formulary on antibacterial use in a private hospital at Tanjung Enim, Sumatera Selatan, Indonesia
No full textThe increase of drug expenditure in the hospital has facilitated the implementation of an evidence-based drug formulary. The aim of this study was to assess the change in antibacterial use after the implementation of an evidence-based drug formulary in a private hospital at Tanjung Enim, Sumatera Selatan, Indonesia. This study used a pre-posttest design. Drug use data in the period before (2010-2011) and after (2012-2013) the formulary implementation were extracted from the hospital medical records. The drug use in the hospital before and after the implementation was compared using t-test and chi-square test, with the significance level of 0.05. Average number of drugs prescribed per prescription after the implementation was similar with that before the implementation (4.4 vs 4.6; p > 0.05). However, the proportion of generic drugs prescribed increased significantly after the formulary implementation (17.0% vs 52.7%; p < 0.05). Moreover, it was still significantly increased when the analysis was conducted only for antibacterial drugs (25.9% vs 72.0%; p < 0.05). Average drug cost per prescription was 34% lower after the intervention (p < 0.05), and the average cost for antibacterial drug was also decreased (26%). The use of antibacterial drugs was significantly decreased after the intervention (12.5% vs 6.9%; p < 0.05). The most often antibacterial drugs prescribed before the interventions were beta-lactams and macrolides; while quinolones were more increasingly used after the intervention. In conclusion, the implementation of evidence-based hospital drug formulary in a private hospital at Tanjung Enim, Sumatera Selatan significantly increase generic drug use and decreased antibacterial use and average drug cost per prescription. Key words : drug formulary – prescribing pattern – generic drug – antibacterial – private hospita