There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016-2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all-186/197 (99.45%)-MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as "Probable Lynch" (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both "Probable Lynch" and non-LS (sporadic) groups (n = 227) was comparable (p = 0.59), with follow up period of 0-1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72-11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.
Hepatitis B virus (HBV) infection is still a global health problem and a major precipitation factor for hepatocellular carcinoma (HCC).MicroRNAs (miRNAs) consist of small non-coding RNAs that regulate gene expression at the post-transcriptional level, thus involving in primary biological processes, including proliferation, differentiation, and apoptosis of cells.MicroRNA-155 is known as an oncogene in some cancer cells and has a relationship with the severity of cancer cells.Here, we investigated the level of microRNA-155 expression in hepatocellular carcinoma patients associated with HBV infection.It was found that the expression of microRNA-155 in the blood plasma of HBV-related to HCC patients was higher and up-regulated by 2.33-fold compared to the blood plasma of HCC patients without HBV infection.This result suggests that microRNA-155 may have a major regulatory role in hepatocarcinogenesis associated with hepatitis B infection and potentially be a therapeutic target for HBV patients developing HCC treatment.
AbstractBackground: Breast cancer (BC) is a global health concern with significant mortality rates, necessitating a deep understanding of its molecular landscape. Objective: This study focuses on the prevalence of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations in Luminal A and B BC within the Indonesian population. Luminal A and B BC, characterized by estrogen receptor (ER) and/or progesterone receptor (PR) positivity, face challenges in endocrine therapy due to acquired resistance, often mediated by PI3K/Akt/mTOR pathway activation. Methods: The study, conducted from 2019 to 2022, collected samples from diverse Indonesian regions, representing various islands. Histopathological analysis and immunohistochemistry classified samples into molecular subtypes. Results: Genetic analysis using PIK3CA mutation detection kits revealed a mutation frequency of 36.2%, with Luminal A BC exhibiting the highest mutation rate (46.1%). Notably, Luminal B HER-2 (positive) BC demonstrated a lower mutation frequency (19%). Statistical analyses highlighted correlations between PIK3CA mutations and molecular subtypes (p=0.01), with Luminal A and Luminal B HER-2 (negative) BC showing higher mutation frequencies. No significant associations were observed with age, tumor location, or histopathology diagnosis. Luminal A BC demonstrated a higher prevalence of PIK3CA mutations in patients over 50 years old (68.1%). Comparisons with existing literature and inconsistencies in PIK3CA mutation prevalence across different BC subtypes underline the need for population-specific research. Conclusion: The study emphasizes the importance of assessing PIK3CA mutations in BC management, offering insights for personalized therapies and potential advancements in understanding this complex disease within the Indonesian context.
Thyroid cancer incidence has steadily increased in Indonesia. However, data on Kirsten rat sarcoma virus (KRAS) and EGFR mutations in thyroid cancer in Indonesia remain unavailable, except for BRAF-V600E, the most common BRAF gene mutation. This study aimed to analyze KRAS and EGFR mutation profiles in BRAF-V600E negative thyroid cancer samples.BRAF-V600E mutations were found in papillary thyroid carcinomas in 40.3% patients with mean age of 53 years old. In BRAF-V600E-negative samples, 41.3% had KRAS mutations with mean age of 55.5 years old. KRAS mutation was found in 52.6% of follicular carcinomas and 47.4% of papillary thyroid carcinomas. Additionally, 45.7% had EGFR mutations in patients with mean age of 50.5 years old. EGFR mutation was found in 71.4% of papillary thyroid carcinoma and 28.6% of follicular carcinoma. Nearly half of the BRAF-V600E negative thyroid carcinoma samples harbored either KRAS or EGFR mutations. This finding suggests that in BRAF-V600E negative thyroid carcinoma samples, testing for RAS and EGFR mutation may be warranted for further therapeutic consideration.
Air pollution has been linked to respiratory diseases, and urban air pollution can be attributed to a number of emission sources. The emitted particles and gases are the primary components of air pollution that enter the lungs during respiration. Particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) can deposit deep into the respiratory tract via inhalation and has been proposed as a causative agent for adverse respiratory health. In addition, the lung contains a diverse microbial community (microbiome) that maintains normal homeostasis and is significantly altered in a variety of pulmonary disorders. Air pollution, specifically PM2.5, has previously been shown to significantly alter the composition of the lower airway microbiome, which has been linked to decreased lung function in chronic obstructive pulmonary disease (COPD) patients. Surprisingly, the intestinal microbiome has also been implicated in the modulation of pulmonary inflammatory diseases. Therefore, dysbiosis of the lung and intestinal microbiomes pose significant negative effects on human health. This dataset describes the microbial community profiles of the lungs and intestines of ageing rats exposed to ambient unconcentrated traffic-related air pollution for three months. The whole-body exposure system was equipped with and without high efficiency particulate air (HEPA) filtration (gaseous vs. PM2.5 pollution). The data can provide valuable information on lung and intestinal microbiome changes, including that which was only found after traffic-related air pollution exposure.
Traditional prognostic tools for non-muscle invasive bladder cancer (NMIBC) often overestimate progression and recurrence risks, underscoring the need for more precise biomarkers. While long non-coding ribonucleic acids (lncRNAs) have been reviewed in bladder cancer, no review has focused on NMIBC. The aim of this study was to address this gap by investigating the role of lncRNAs in predicting NMIBC survival and progression. A systematic review was conducted using PubMed, Scopus, and Cochrane databases as of July 31, 2024. Prognostic studies investigating the association between lncRNA expression and survival outcomes, such as cancer-specific survival, disease-free survival, recurrence-free survival, or overall survival, using Kaplan-Meier curves or hazard ratios, were included. A total of three studies were analyzed, involving 279 NMIBC patients and focusing on three lncRNAs: urothelial cancer associated 1 (UCA1), growth arrest-specific 5 (GAS5), and up-regulated in non-muscle invasive bladder cancer (UNMIBC). Increased UCA1 expression was strongly associated with poor disease-free survival (hazard ratio (HR): 1.974; 95%CI: 1.061–3.673; p=0.032) and progression-free survival (HR: 3.476; 95%CI: 1.187–10.18; p=0.023). Reduced GAS5 expression was significantly associated with poor disease-free survival (HR: 2.659; 95%CI: 1.348–5.576; p=0.005) and progression-free survival (HR: 6.628; 95%CI: 1.494–29.40; p=0.013). Higher level of UNMIBC was strongly associated with poor recurrence-free survival (HR: 2.362; 95%CI: 1.504–4.837; p=0.007). In conclusion, lncRNAs have potential as prognostic biomarkers in NMIBC, with UCA1 and UNMIBC overexpression and GAS5 underexpression being significant in predicting disease recurrence and progression, highlighting the clinical relevance of monitoring these lncRNAs to improve prognosis and guide treatment decisions.
Delay in type II alveolar epithelial cell (AECII) regeneration has been linked to higher mortality in patients with acute respiratory distress syndrome (ARDS). However, the interaction between Doublecortin-like kinase 1 (DCLK1) and the Hippo signaling pathway in ARDS-associated AECII differentiation remains unclear. Therefore, the objective of this study was to understand the role of the DCLK1/Hippo pathway in mediating AECII differentiation in ARDS.AECII MLE-12 cells were exposed to 0, 0.1, or 1 μg/mL of lipopolysaccharide (LPS) for 6 and 12 h. In the mouse model, C57BL/6JNarl mice were intratracheally (i.t.) injected with 0 (control) or 5 mg/kg LPS and were euthanized for lung collection on days 3 and 7.We found that LPS induced AECII markers of differentiation by reducing surfactant protein C (SPC) and p53 while increasing T1α (podoplanin) and E-cadherin at 12 h. Concurrently, nuclear YAP dynamic regulation and increased TAZ levels were observed in LPS-exposed AECII within 12 h. Inhibition of YAP consistently decreased cell levels of SPC, claudin 4 (CLDN-4), galectin 3 (LGALS-3), and p53 while increasing transepithelial electrical resistance (TEER) at 6 h. Furthermore, DCLK1 expression was reduced in isolated human AECII of ARDS, consistent with the results in LPS-exposed AECII at 6 h and mouse SPC-positive (SPC+) cells after 3-day LPS exposure. We observed that downregulated DCLK1 increased p-YAP/YAP, while DCLK1 overexpression slightly reduced p-YAP/YAP, indicating an association between DCLK1 and Hippo-YAP pathway.We conclude that DCLK1-mediated Hippo signaling components of YAP/TAZ regulated markers of AECII-to-AECI differentiation in an LPS-induced ARDS model.
Study Background : Testicular torsion is a genitourinary emergency most common in children and emergencies requiring second surgery in adolescents after acute appendicitis1. Testicular torsion is more common on the left with a 1.2: 1 ratio, which is probably caused by a slightly longer spermatic cord on the left2. Testicular torsion can occur at any age, but the peak incidence is at age 14, with a peak of second occurrence at 1 year of age3. At 1 year of age, testicular torsion is a major cause of acute scrotum (83%). At the age of 3 - 13 years, the most frequent diagnosis is the torsion of the testicular appendix. After the age of 17 years, epididymitis is the most frequent diagnosis (75%)4. Method: This study is an experimental study, post-test only control group design, the sample was randomly divided into 4 groups, 2 intervention groups and 2 control groups. In this study the independent variables are the duration of the right torsion-detection treatment of the testes and the injection of Methylprednisolone in Wistar male rats. The dependent variables are mRNA expression in apoptosis and anti-apoptosis genes in rats’ ipsilateral and contralateral testes. . Results and Discussion: In this study, two-way ANOVA is used to analyze data between groups. Significant decrease in BAX gene mRNA expression (p <0.05) with Methylprednisolone was present when group 2 (TD) was compared with group 4 (TD-MP). Significant increase in the expression of BCL-2 anti-apoptotic gene (p <0.05) with Methylprednisolone was present when group 1 (T) was compared with group 3 (T-MP). When group 2 (TD) compared with group 4 (TD-MP) also showed a significant increase in the expression of BCL-2 anti-apoptotic gene (p <0.05). Conclusion: The administration of Methylprednisolone in the case of testicular torsion proved to be significant in increasing the expression of the BCL-2 gene that could be a protective mechanism against germ cell apoptosis in testicular tissue.
Background: Telomere length is a potential prognostic biomarker in breast cancer, but its clinical utility remains uncertain due to inconsistent findings across the literature. This systematic review and meta-analysis aims to evaluate the association between telomere length and breast cancer survival outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and recurrence-free survival (RFS). Methods: A systematic search of ten sources, including databases and publishers (JSTOR, Nature, ProQuest, PubMed, Sage Journals, ScienceDirect, Science, Scopus, Springer, and Wiley) was conducted to identify studies published up to December 31, 2023. Studies reporting associations between telomere length and survival outcomes in breast cancer patients were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) were extracted or calculated. Quality assessment was performed using the Newcastle-Ottawa Scale, and publication bias was evaluated using funnel plots, Egger’s, and Begg’s tests. Results: Nine studies involving 3,145 breast cancer patients were included. Shorter telomere length was significantly associated with increased recurrence risk (DFS/RFS) (pooled HR: 1.97; 95% CI: 1.04–3.74, P = 0.039), indicating a nearly twofold increase in risk. Trends toward worse OS (pooled HR: 1.60; 95% CI: 0.90–2.86, P = 0.110) and DSS (pooled HR: 1.09; 95% CI: 0.80–1.49, P = 0.565) were observed, but did not reach statistical significance. Additionally, shorter telomere length was significantly associated with premenopausal status (pooled OR: 1.34; 95% CI: 1.06–1.70, P = 0.01). Discussion: Shorter telomere length is associated with an increased risk of recurrence in breast cancer, highlighting its potential as a prognostic biomarker. However, further research is needed to standardize telomere length measurement methodologies and validate these findings across diverse populations and breast cancer subtypes.
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