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Intracrine Dynamics of Luminal Breast Cancer: Correlating Intratumoral Estradiol with Estrogen Receptor Alpha Overexpression in an Advanced-Stage Cohort Erdiansyah Reza Lesmana; Widyanti Soewoto; Brian Wasita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 3 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i3.1542

Background: In postmenopausal breast cancer, systemic serum estradiol levels often fail to reflect the biologically active concentrations within the tumor microenvironment, a phenomenon known as intracrineology. While the roles of estrogen receptor alpha (ERα) and beta (ERβ) are well-characterized, the specific relationship between local ligand concentration and receptor expression in advanced-stage malignancies remains under-investigated. This study investigates the correlation between intratumoral estradiol (E2) concentration and the expression of ER isoforms in Luminal A and Luminal B subtypes. Methods: A retrospective cross-sectional study was conducted on 56 tissue samples (38 Luminal A, 18 Luminal B) from patients at Dr. Moewardi Regional General Hospital, Indonesia. Pre-analytical variables were strictly controlled, ensuring cold ischemia time was less than one hour. Expressions of E2, ERα, and ERβ were quantified using immunohistochemistry and assessed via H-Scores. Due to non-normal data distribution, associations were analyzed using Spearman’s Rho and Generalized Linear Models (GLM) with a Gamma distribution and log-link function, coupled with bootstrapping to generate robust confidence intervals. Results: The cohort was characterized by advanced disease, with 85.7% of patients presenting with Stage III or IV breast cancer. Luminal A tumors exhibited significantly higher mean intratumoral E2 (91.58 versus 56.67; p = 0.038) and ERα expression (122.23 versus 109.72; p = 0.045) compared to Luminal B. A significant positive correlation was observed between tissue E2 and ERα (Rho = 0.347; p = 0.009). GLM analysis confirmed E2 as a significant predictor of ERα expression (p = 0.015), independent of age and stage. No significant correlation was found between E2 and ERβ (p = 0.113). Conclusion: Intratumoral estradiol is a significant positive correlate of ERα expression in luminal breast cancer, supporting the existence of a ligand-driven autocrine maintenance loop even in advanced stages. The lack of correlation with ERβ suggests divergent regulatory mechanisms. These findings reinforce the rationale for therapies targeting local aromatase activity.

Thresholds of Cytoprotection: Ethanolic Propolis Extract Mitigates Ischemia-Reperfusion Injury via the MDA/IL-6 Axis in a Graded Rat Skin Flap Model Dinar Kukuh Prasetyo; Amru Sungkar; Brian Wasita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 3 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i3.1546

Background: Distal necrosis in reconstructive skin flaps results from ischemia-reperfusion (I/R) injury, driven by reactive oxygen species (ROS) and pro-inflammatory cytokines. While Propolis exhibits antioxidant properties, its efficacy limit relative to the severity of ischemic challenge remains undefined. Methods: A randomized, controlled experimental study was conducted using 36 male Wistar rats. A graded ischemia model was engineered using modified McFarlane flaps with increasing length-to-width ratios: Mild (2:1), moderate (3:1), and severe (4:1). Subjects were stratified into vehicle (Control) and treatment (Propolis 800 mg/kg/day, oral) groups across all dimensions. The primary endpoint was the percentage of viable flap area on Day 7. Secondary endpoints included serum Malondialdehyde (MDA), Interleukin-6 (IL-6), and histological scoring of inflammation. Results: All animals survived the procedure. Propolis significantly increased viable tissue area in the moderate ischemia group (76.4 ± 4.2%) compared to Vehicle (52.1 ± 5.8%; p < 0.001). In Mild ischemia, survival was near-maximal in both groups (>92%). However, in Severe ischemia, Propolis failed to prevent significant necrosis (34.2 ± 6.1% survival vs. 28.5 ± 5.4% in Vehicle; p = 0.092), indicating a therapeutic ceiling. Biochemically, Propolis suppressed MDA (11.92 ± 0.45 nmol/mL) and IL-6 (121.0 ± 4.71 pg/mL) significantly in moderate challenges but was overwhelmed by the oxidative surge in severe ischemia (MDA > 12.0 nmol/mL). Conclusion: Propolis confers significant protection against I/R injury by dampening lipid peroxidation and systemic inflammation, but this effect exhibits a distinct threshold. It is highly effective in moderate ischemic challenges but insufficient for severe vascular compromise.

Intracrine Dynamics of Luminal Breast Cancer: Correlating Intratumoral Estradiol with Estrogen Receptor Alpha Overexpression in an Advanced-Stage Cohort Erdiansyah Reza Lesmana; Widyanti Soewoto; Brian Wasita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 3 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i3.1542

Background: In postmenopausal breast cancer, systemic serum estradiol levels often fail to reflect the biologically active concentrations within the tumor microenvironment, a phenomenon known as intracrineology. While the roles of estrogen receptor alpha (ERα) and beta (ERβ) are well-characterized, the specific relationship between local ligand concentration and receptor expression in advanced-stage malignancies remains under-investigated. This study investigates the correlation between intratumoral estradiol (E2) concentration and the expression of ER isoforms in Luminal A and Luminal B subtypes. Methods: A retrospective cross-sectional study was conducted on 56 tissue samples (38 Luminal A, 18 Luminal B) from patients at Dr. Moewardi Regional General Hospital, Indonesia. Pre-analytical variables were strictly controlled, ensuring cold ischemia time was less than one hour. Expressions of E2, ERα, and ERβ were quantified using immunohistochemistry and assessed via H-Scores. Due to non-normal data distribution, associations were analyzed using Spearman’s Rho and Generalized Linear Models (GLM) with a Gamma distribution and log-link function, coupled with bootstrapping to generate robust confidence intervals. Results: The cohort was characterized by advanced disease, with 85.7% of patients presenting with Stage III or IV breast cancer. Luminal A tumors exhibited significantly higher mean intratumoral E2 (91.58 versus 56.67; p = 0.038) and ERα expression (122.23 versus 109.72; p = 0.045) compared to Luminal B. A significant positive correlation was observed between tissue E2 and ERα (Rho = 0.347; p = 0.009). GLM analysis confirmed E2 as a significant predictor of ERα expression (p = 0.015), independent of age and stage. No significant correlation was found between E2 and ERβ (p = 0.113). Conclusion: Intratumoral estradiol is a significant positive correlate of ERα expression in luminal breast cancer, supporting the existence of a ligand-driven autocrine maintenance loop even in advanced stages. The lack of correlation with ERβ suggests divergent regulatory mechanisms. These findings reinforce the rationale for therapies targeting local aromatase activity.

Thresholds of Cytoprotection: Ethanolic Propolis Extract Mitigates Ischemia-Reperfusion Injury via the MDA/IL-6 Axis in a Graded Rat Skin Flap Model Dinar Kukuh Prasetyo; Amru Sungkar; Brian Wasita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 3 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i3.1546

Background: Distal necrosis in reconstructive skin flaps results from ischemia-reperfusion (I/R) injury, driven by reactive oxygen species (ROS) and pro-inflammatory cytokines. While Propolis exhibits antioxidant properties, its efficacy limit relative to the severity of ischemic challenge remains undefined. Methods: A randomized, controlled experimental study was conducted using 36 male Wistar rats. A graded ischemia model was engineered using modified McFarlane flaps with increasing length-to-width ratios: Mild (2:1), moderate (3:1), and severe (4:1). Subjects were stratified into vehicle (Control) and treatment (Propolis 800 mg/kg/day, oral) groups across all dimensions. The primary endpoint was the percentage of viable flap area on Day 7. Secondary endpoints included serum Malondialdehyde (MDA), Interleukin-6 (IL-6), and histological scoring of inflammation. Results: All animals survived the procedure. Propolis significantly increased viable tissue area in the moderate ischemia group (76.4 ± 4.2%) compared to Vehicle (52.1 ± 5.8%; p < 0.001). In Mild ischemia, survival was near-maximal in both groups (>92%). However, in Severe ischemia, Propolis failed to prevent significant necrosis (34.2 ± 6.1% survival vs. 28.5 ± 5.4% in Vehicle; p = 0.092), indicating a therapeutic ceiling. Biochemically, Propolis suppressed MDA (11.92 ± 0.45 nmol/mL) and IL-6 (121.0 ± 4.71 pg/mL) significantly in moderate challenges but was overwhelmed by the oxidative surge in severe ischemia (MDA > 12.0 nmol/mL). Conclusion: Propolis confers significant protection against I/R injury by dampening lipid peroxidation and systemic inflammation, but this effect exhibits a distinct threshold. It is highly effective in moderate ischemic challenges but insufficient for severe vascular compromise.

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