Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial.

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction.

OBJECTIVES: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). METHODS: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. RESULTS: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. CONCLUSION: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

Three-dimensional ultrasound appearance of pelvic floor in nulliparous women and postpartum women one week after their first delivery.

This study investigated the morphology and structure of pelvic floor in 50 nulliparous and 95 postpartum women (47 vaginal delivery, 48 Cesarean section) using translabial three-dimensional (3D) ultrasound. All the primiparae underwent ultrasound examination within one week after their first delivery. Volume datasets were acquired and analyzed to determine the alterations of levator hiatus after childbirth. Significant differences were observed in the levator hiatus of postpartum women compared with that of nullipara women. In postpartum women, the levator hiatus, with their dimensions increased, expanded into a circular shape. Puborectalis was avulsed in eight cases (accounting for 8.42% of all) and pelvic organ prolapse was found in 12 cases (accounting for 12.63%). The hiatal dimensions were larger and the incidence of pubrectalis muscle avulsion (17.02% vs. 0%) and pelvic organ prolapse (21.28% vs. 4.17%) was significantly higher in Vaginal delivery group than Cesarean section group. In summary, 3D ultrasound is an effective tool to detect the pelvic floor of postpartum women who present with morphological abnormalities, and such abnormalities are more likely to show in vaginal delivery women compared to Cesarean section.

Combined low-frequency ultrasound and microbubble contrast agent for the treatment of benign prostatic hyperplasia.

BACKGROUND AND PURPOSE: Benign prostatic hyperplasia is one of the most common conditions in middle-aged and elderly men. The aim of the study was to investigate the treatment effects of low-frequency ultrasound combined with a microbubbles agent on benign prostatic hyperplasia. METHODS: Eighteen 7-year-old male beagles with prostatic hyperplasia were randomly divided into six groups (n=3): Control group, 21 kHz ultrasound group, 21 kHz ultrasound and microbubble contrast agent group, 1 MHz ultrasound group, 1 MHz ultrasound and microbubble contrast agent group, and microbubble contrast agent group. The histopathologic damage to prostate cells was assessed via transmission electron microscopy and optical microscopy. The protein expressions of prostate-specific antigen (PSA), inducible nitric oxide synthase (iNOS), and super oxidase dimutase (SOD) were detected by enzyme-linked immunosorbent assay. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) were detected by the Biochemistry Automatic Analyzer. RESULTS: Significant tissue injury, mitochondria injury, and cell apoptosis were observed in 21 kHz ultrasound and the microbubble contrast agent group. Compared with the control and microbubbles contrast agent groups, the decrease in levels of PSA or increase in levels of iNOs and SOD in the other four groups were statistically significant (P<0.05). The lowest level of PSA and the highest levels of iNOs and SOD were observed in the 21 kHz ultrasound and microbubbles contrast agent group. No significant changes in levels of AST, ALT, BUN, and Cr were observed between the six groups. CONCLUSIONS: Our results suggest that lower frequency ultrasound may have a better effect on benign prostatic hyperplasia, and microbubble contrast agent application further strengthens this biological effect.