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Biomedical subjects

Jung-Sun Kim

Publications and source records attributed to Jung-Sun Kim.

3 recordsLinked to original sources

Daratumumab monotherapy for relapsed AL amyloidosis: a single center retrospective analysis.

PURPOSE: Treatment of relapsed AL amyloidosis remains challenging as patients frequently suffer from severe organ dysfunctions. Daratumumab, a cornerstone drug in multiple myeloma and newly diagnosed AL amyloidosis, has also shown promise in relapsed AL amyloidosis. MATERIALS AND METHODS: To assess the efficacy of daratumumab, we conducted a retrospective study of 40 patients who received daratumumab monotherapy in our prospective amyloidosis cohort. RESULTS: The median age of the cohort was 67&#xa0;years, and 31 patients were classified as stage III/IV by the Mayo 2012 guidelines and 32 patients as stage IIIa/IIIb by the European staging system. The overall hematologic and cardiac response rates were 72.5% and 42.4%, respectively. With median follow-up duration of 26.9&#xa0;months, the estimated median progression-free survival was 21.9&#xa0;months. Deep hematologic (p&#x2009;<&#x2009;0.001) and cardiac response (p&#x2009;=&#x2009;0.001) were associated with prolonged progression free survival. The duration of hematologic/cardiac responses were 26.2&#xa0;months and 27.8&#xa0;months, respectively. The median overall survival was 30.9&#xa0;months. Treatment was well tolerated, as with 3 patients experiencing grade 3-4 hematologic adverse events and 8 experiencing grade 3-4 non-hematologic adverse events. DISCUSSION: Our findings suggest that daratumumab monotherapy provides rapid and durable responses and is generally well tolerated in patients with relapsed AL amyloidosis.

AL amyloidosis

MicroRNA-155 modulates STAT3 signaling by targeting KPNA1 in chronic chorioamnionitis of human placenta.

Chronic chorioamnionitis (CCA) is a placental inflammatory lesion characterized by maternal T cell infiltration and trophoblast apoptosis, resembling allograft rejection. MicroRNA-155 (miR-155) is a central regulator of immune and inflammatory pathways, but its role in CCA remains unclear. This study investigated whether miR-155 contributes to the pathogenesis of CCA by targeting karyopherin &#x3b1;1 (KPNA1) and modulating STAT3 signaling in human trophoblasts. Placental tissues from 28 CCA cases and 16 gestational age-matched controls were analyzed for miR-155 expression using quantitative RT-PCR and in situ hybridization. Functional assays were conducted in Swan 71 trophoblast cells following miR-155 overexpression and siRNA-mediated KPNA1 knockdown. Microarray and qRT-PCR analyses identified gene expression changes, while western blotting and dual-luciferase reporter assays were conducted to evaluate STAT3 activity and direct target binding. miR-155 expression was significantly elevated in CCA fetal membranes. KPNA1 was identified as a direct target of miR-155, and its suppression reduced STAT3 phosphorylation and nuclear translocation. Dual-luciferase assays confirmed that miR-155 binds to the 3' untranslated region of KPNA1 mRNA, thereby inhibiting its translation. These findings suggest that miR-155 downregulates KPNA1, leading to inhibition of STAT3 signaling in trophoblasts, which may contribute to maternal-fetal immune dysregulation and trophoblast apoptosis in CCA. The miR-155-KPNA1-STAT3 axis may represent a potential therapeutic target in pregnancy-related inflammatory disorders.

Humans

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

PURPOSE: This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. METHODS: Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. FINDINGS: At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 &#xb1; 1.0 mmHg) compared with the dual therapy group (-16.7 &#xb1; 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. IMPLICATIONS: This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. GOV IDENTIFIER: NCT07116863.

Humans