Mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog gene) and BRAF (v‐Raf murine sarcoma viral oncogene homolog B1) gene play a significant role in primary resistance to colorectal cancer therapy. Around 85‐90% of KRAS mutations in colorectal cancer occur in exon 2 (codon 12 and 13), whereas approximately 96% of BRAF mutations occur in exon 15 codon 600 (V600E). This study aimed to determine the prevalence and mutation characteristics of the KRAS and BRAF genes in colorectal cancer patients in Bali. The DNA was isolated from 44 formalin‐fixed paraffin‐embedded colorectal cancer samples which were stored in the Department of Pathology, Sanglah General Hospital in 2017. Detection of mutation was carried out by polymerase chain reaction (PCR) and direct sequencing. Out of 44 samples, only 27 were successfully amplified and sequenced. Our findings showed six samples (22.2%) with mutated KRAS at codons 12 and 13 (including two samples with G12D, one sample with G12V, and three samples with G13D). Interestingly, we found three samples (11.1%) of BRAF mutation, including two samples with V600E mutation and one with V600L mutation. Taken together, our results showed that KRAS and BRAF mutations were identified and occurred exclusively. Further studies are essential to identify the correlation of these mutations with colorectal cancer prognosis and response to chemotherapy
Kanker kolorektal merupakan masalah kesehatan di dunia. Perkembangan kanker kolorektal memerlukan waktu panjang dan berkaitan dengan faktor lingkungan, genetik dan epigenetik. Patogenesis kanker kolorektal melibatkan tiga jalur yang seringkali tumpang tindih yaitu chromosomal instability (CIN), microsatellite instability (MSI) dan CpG island methylator phenotype (CIMP). Dalam tulisan ini dibahas mengenai kanker kolorektal herediter dan sporadik serta aspek genetiknya. Pemahaman mengenai aspek genetik kanker kolorektal sangat berperan dalam manajemen penyakit ini.
Background: Medical students are a population that is considered vulnerable to experience stress during the COVID-19 pandemic, especially with the heavy learning load and changes in the learning system that were initially carried out face-to-face. Currently, there are limited data regarding the stress of studying online in medical students and their effect on learning achievement. This study aimed to determine the stress effect of studying online in medical students on their academic achievement.Methods: This study was an analytic observational study with a cross-sectional approach. 112 samples were obtained from students of Bachelor of Medicine and Medical Doctor in one of the universities in Bali with the instruments that were distributed via Google Form. Primary data collection was carried out using the Medical Student Stressor Questionnaire (MSSQ) questionnaire, while secondary data collection was obtained from the average score of three-block exams done online during the COVID-19 pandemic.Results: The stress level of medical students in online learning was dominated by high stress (55.4%) with the majority cause due to Academic Related Stressor (ARS). There is a significant relationship (p = 0.021) between the incidence of stress and learning achievement in students (-0.217, 95% CI -0.39 to -0.03). The learning system preference that was chosen by the students is dominated by a 50% online learning system and 50% offline as much as 27.7%.Conclusion: The results indicated that there is a high level of stress among medical students. There is a correlation between stress events and medical student’s achievement during online learning.
Diabetes mellitus type 2 (T2DM) has been a global health problem. Current studies have shown that the increased mortality and morbidity in T2DM are related to vascular complications. The vascular complications were caused by increased reactive oxygen species (ROS) associated with chronic hyperglycemia and insulin resistance. The increase of ROS in T2DM was influenced by the p38 MAPK pathway which is directly related to the modulation of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) of endothelium cells. The decrease of NO by eNOS also has a connection with an event known as eNOS uncoupling. The decrease of eNOS plays a role in the pathogenesis of T2DM and its vascular complications such as increased inflammatory pro-cytokine, activation of NADPH pathway, increased of AGEs, VCAM-1, ICAM-1, and also the activation of protein kinase c and Rho-kinase pathway. Some interventions indirectly or directly have modulated NO relayed to its work targets such as oral antidiabetic drugs (metformin, sulfonylurea, and acarbose) or some polyphenol compounds such as emodin, α-Lipoic acid, curcumin, and olive oil. Modulation of NO in these interventions can be strong evidence that NO can be a target for further therapy in the management of T2DM and its complications. Keywords: eNOS, vascular complication, Type 2 Diabetes mellitus.
Triple negative breast cancer (TNBC) adalah salah stau subtipe kanker payudara yang memiliki persentase sebanyak 15% dari total kasus kanker payudara. Triple negative breast cancer memiliki karakteristik yang sangat berbeda dengan jenis kanker payudara pada umumnya karena bersifat agresif, resisten terhadap pengobatan, proliferasi yang tinggi, dan angka harapan hidup yang rendah. Pengobatan yang umum dilakukan untuk TNBC adalah pembedahan dan kemoterapi. Namun, pembedahan menimbulkan banyak efek samping, seperti bentuk payudara yang berubah, terjadinya hematoma, dan lymphedema. Begitu pula dengan kemoterapi yang tidak hanya membunuh sel kanker, tetapi juga merusak sel normal di dalam tubuh. Pemanfaatan siRNA spesifik silencing gen mutan p53 dan VEGF sebagai penatalaksanaan TNBC merupakan metode yang menjanjikan. Nantinya, siRNA akan dikonjugasi dengan aptamer dan PLEGP1800. Aptamer berfungsi untuk meningkatkan kestabilannya dan PLEGP1800 digunakan untuk meningkatkan konsentrasi dan transfeksi yang lebih efisien, serta memiliki sitotoksisitas yang rendah. siRNA-Aptamer-PLEGP1800 juga akan dienkapsulasi dengan chitosan untuk meningkatkan bioavailibilitas, melindungi senyawa di dalamnya dari degradasi serum, dan meningkatkan penyerapan ke gen target. Penulisan literature review ini bertujuan untuk mengkaji mekanisme dan efek klinis siRNA-Aptamer-PLEGP1800-Chitosan sebagai terapi TNBC berbasis teknologi nano.
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