Aim: To explore the potential of the circulating plasma miRNA-21 as an early detection biomarker by comparing early-stage breast cancer (BG) and healthy control (HG) in Indonesian population. Materials and methods: The enlisted patients were 26 adult female early-stage breast cancer patients (stage 1A, 1B, 2A, and 2B) of Airlangga University Hospital from August 2019 to October 2019. Sixteen volunteers were recruited as matching healthy subjects. MiRNA-21 expression was quantified by plasma qRT-PCR. Data analysis performed using IBM SPSS Statistics v.24 (IBM Corp., Armonk, NY, USA). MiRNA-21 cut-off, sensitivity, and specificity were analyzed using receiver operating characteristic (ROC) curve. Results: The study included 26 BG and 16 HG subjects. The miRNA-21 expression in BG group was 3.933 (1.181-11.794) and 0.905 (0.164-4.532) in HG group (4.34 folds; P = 0.001), with 1.66 cut-off (92.3% sensitivity; 81.2% specificity). MiRNA-21 expression separated analysis in HG showed a 0.578 times lower expression in menopause subjects [0.651 (0.164-0.414)], compared to premenopause ones [(1.123 (0.758 -4.532); P = 0.031]. Yet, in BG group, 1.729 times higher miRNA-21 expression was observed in menopause subjects (6.021 +/- 3.583), compared to premenopause ones (3.500 +/- 1.517; P = 0.022). Conclusion: Circulating miRNA-21 expression is a potential biomarker for early detection of breast cancer and might act as a breast cancer risk predictor.

BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-21

Objective: The emerging renal complications in beta-thalassemia patients have raised the global exchange of views. Despite better survival due to blood transfusion and iron chelation therapy, the previously unrecognized renal complication remain a burden of disease affecting this population —the primary concern on how iron overload and chelation therapy correlated with renal impairment is still controversial. Early detection and diagnosis is crucial in preventing further kidney damage. Therefore, a systematic review was performed to identify markers of kidney complications in beta thalassemia patients with iron overload receiving chelation therapy. Methods: Searches of PubMed, Scopus, Science Direct, and Web of Science were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify studies of literature reporting renal outcome in β-TM patients with iron overload and receiving chelation therapy. The eligible 17 studies were obtained. Results: uNGAL/NGAL, uNAG/NAG, uKIM-1 are markers that can be used as predictor of renal tubular damage in early renal complications, while Cystatin C and uβ 2MG showed further damage at the glomerular level. Discussion and Conclusion: The renal complication in beta-thalassemia patients with iron overload receiving chelating agent therapy may progress to kidney disease. Early detection using accurate biological markers is a substantial issue that deserves further evaluation to determine prevention and management.

BACKGROUND: Cancer stem cells (CSCs) eradication might serve as a robust approach for cancer eradication. MCF-7 as breast cancer continuous cell line is known to contain breast CSCs (BCSCs) for its capability to maintain its original tumor population. CSCs enriched culture is a fundamental tool for CSCs targeted therapy development. Effective and unsophisticated CSCs dedifferentiation protocol for producing CSCs enriched culture is needed.METHODS: MCF-7 cells were cultured initially in Dulbecco's Modified Eagle Medium (DMEM) low glucose medium then changed to DMEM:F12. Serum starvation was performed during each medium refreshment gradually with fetal bovine serum (FBS) concentration of 10%, 5%, 2.5% until reaching 1% FBS concentration. Stable MCF-7 culture was then adapted to serum free culture system, containing DMEM:F12, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and B27 supplement as dedifferentiation protocol for 18 days. Cluster of differentiation (CD)44 and CD24 double staining immunocytochemistry was performed to evaluate cell stemness.RESULTS: The population of cells expressing BCSCs markers (CD44+/CD24low) in non-adherent single cells subpopulation was significantly increased after the dedifferentiation procedure (70.39%) compared to control groups (0.71%) (p<0.05). In contrast, the expression of BCSCs marker in adherent single cells subpopulation and for both adherent and non-adherent mammosphere the BCSCs markers showed a stable expression.CONCLUSION: BCSCs enrichment of breast cancer cell cultures from MCF-7 breast cancer cell line can be performed. Breast cancer cell plasticity is observed during the dedifferentiation protocol. Development of dedifferentiation inducing protocols can serve as an important foundation for breast cancer therapy development through BCSCs elimination.KEYWORDS: breast neoplasms, cell line, dedifferentiation, immunohistochemistry, neoplastic stem cells

Purpose: This study aims to evaluate the role of high-sensitivity troponin T (hsTnT) as a complementary tool for determining cardiotoxicity in non-Hodgkin lymphoma (NHL) patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen chemotherapy. Methods: We included 35 patients diagnosed with NHL who received CHOP chemotherapy. Left ventricular ejection fraction (LVEF) and hsTnT were measured at two time points: before the first cycle (pre-test) and after the fourth cycle (post-test). The LVEF and hsTnT were analysed using IBM SPSS version 24 through the paired-sample T-test, Wilcoxon signed-rank test, Pearson’s correlation and Spearman’s correlation. Results: There was a significant difference in both LVEF and hsTnT between pre-chemotherapy and post-4th chemotherapy cycles (p = 0.001). However, more contrast difference from the baseline value of hsTnT compared to LVEF could be observed. LVEF did not detect any deterioration in myocardial function. However, 10 out of 35 subjects exhibit hsTnT higher than the 99th percentile of the population (>14 pg/ml), suggesting that myocardial injury (MI) could be detected. There was no correlation between LVEF and hsTnT (p > 0.05). Conclusion: HsTnT, together with LVEF, could complement each other and offer better coverage for detecting cardiotoxicity during the administration of CHOP in NHL patients. An insignificant correlation between hsTnT and LVEF showed that cardiotoxicity existed in a broad spectrum including cellular damage and functional impairment, as hsTnT represents cellular damage, and LVEF reflects heart functional capacity.

Background/Objectives: Ineffective erythropoiesis (IE) is a hallmark of β-thalassemia and contributes to major clinical complications, including severe anemia, extramedullary hematopoiesis, and progressive iron overload. Despite its central role in disease pathophysiology, there is no established biomarker for the reliable identification and monitoring of IE. This systematic review was conducted to evaluate potential serum markers that reflect IE in β-thalassemia. Methods: Across seven databases (PubMed, ScienceDirect, Web of Science, SpringerLink, Taylor & Francis, ProQuest, and SAGE), thirteen studies met the eligibility criteria and were analyzed to identify circulating biomarkers associated with IE in β-thalassemia. Results: The most consistently reported markers were growth differentiation factor-15 (GDF-15), soluble transferrin receptor (sTfR), erythropoietin (EPO), and erythroferrone (ERFE), all of which demonstrated strong correlations with the degree of IE and erythroid expansion. Additional markers, including circulating cell-free DNA (cfDNA), CA15.3, hepcidin, ferritin, and phosphatidylserine (PS)-exposed red blood cells, were also found to be elevated, reflecting increased erythroid turnover, apoptosis, and secondary iron dysregulation. These findings suggest that while individual markers capture different aspects of IE, their combined evaluation may provide a more comprehensive picture of disease burden. Conclusions: IE represents the central pathophysiological driver of β-thalassemia and is closely linked to disease complications. Early detection through circulating biomarkers offers the potential for timely identification of high-risk patients, monitoring of therapeutic responses, and prognostication. Although current evidence highlights GDF-15, sTfR, ERFE, and EPO as the most promising candidates, further validation in larger, longitudinal cohorts is required before clinical implementation.