This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Background: s/Aims: While large-for-size syndrome is uncommon in liver transplantation (LT), it can result in fatal outcome. To prevent such fatality, we manufactured 3D-printed intra-abdominal cavity replicas to provide intuitive understanding of the sizes of the graft and the patient’s abdomen in patients with small body size between July 2020 and February 2022. Methods: Clinical outcomes were compared between patients using our 3D model during LT, and patients who underwent LT without 3D model by using 1 : 5 ratio propensity score-matched analysis. Results: After matching, a total of 20 patients using 3D-printed abdominal cavity model and 100 patients of the control group were included in this study. There were no significant differences in 30-day postoperative complication (50.0% vs. 64.0%, p = 0.356) and the incidence of large-for-size syndrome (0% vs. 7%, p = 0.599). Overall survival of the 3D-printed group was similar to that of the control group (p = 0.665), but graft survival was significantly superior in the 3D-printed group, compared to the control group (p = 0.034). Conclusions Since it showed better graft survival, as well as low cost and short production time, our 3D-printing protocol can be a feasible option for patients with small abdominal cavity to prevent large-for-size syndrome after LT.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44–1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67–1.14; p=0.310). Conclusions Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

Aortic regurgitation (AR) in children is usually caused by congenital valve anomalies, and Behçet syndrome (BS) can be suspected in cases of isolated AR. Patients with BS undergoing aortic valve surgery due to aortic valve invasion have a high risk of complications, such as leakage around the valve and dehiscence. Cardiovascular involvement occurs in 7%–46% of adult patients with BS and is the main cause of mortality; however, its prevalence is unclear and rare in children. A 12-year-old boy was diagnosed with severe AR associated with BS. A progressive subaortic pseudoaneurysm was observed after aortic valve replacement. The periaortic intracardiac pouch was at risk of rupture; therefore, the patient underwent a Bentall operation. After the Bentall procedure, a newly developed subaortic pseudoaneurysm was detected below the prosthetic valve. However, the risk of rupture reduced as the subaortic pseudoaneurysm regressed with anti-inflammatory drugs alone without reoperation. Repeated surgery is inevitable in patients with BS undergoing aortic valve surgery due to the progressive chronic inflammatory reactions that present with a pseudoaneurysm. Here, we report an 8-year follow-up of a pediatric case of BS with subaortic pseudoaneurysm, highlighting the importance of close follow-up, medical management, and early diagnosis in treating this condition.

Purpose: Adjuvant treatment for craniopharyngioma after surgery is controversial. Adjuvant external beam radiation therapy (EBRT) can increase the risk of long-term sequelae. Stereotactic radiosurgery (SRS) is used to reduce treatment-related toxicity.In this study, we compared the treatment outcomes and toxicities of adjuvant therapies for craniopharyngioma. Materials and Methods: We analyzed patients who underwent craniopharyngioma tumor removal between 2000 and 2017. Of the 153 patients, 27 and 20 received adjuvant fractionated EBRT and SRS, respectively. We compared the local control (LC), progression-free survival (PFS), and overall survival between groups that received adjuvant fractionated EBRT, SRS, and surveillance. Results: The median follow-up period was 77.7 months. For SRS and surveillance, the 10-year LC was 57.2% and 57.4%, respectively. No local progression was observed after adjuvant fractionated EBRT. One patient in the adjuvant fractionated EBRT group died owing to glioma 94 months after receiving radiotherapy (10-year PFS: 80%). The 10-year PFS was 43.6% and 50.7% in the SRS and surveillance groups, respectively. The treatment outcomes significantly differed according to adjuvant treatment in nongross total resection (GTR) patients. Additional treatment-related toxicity was comparable in the adjuvant fractionated EBRT and other groups. Conclusion Adjuvant fractionated EBRT could be effective in controlling local failure, especially in patients with non-GTR, while maintaining acceptable treatment-related toxicity.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.