RESUMEN
Reproductive cancers, such as ovarian, cervical, and endometrial carcinomas, have a poor prognosis in metastatic stages. Researchers are continuously seeking improved and safer methods to target cancer-related oncoproteins, addressing the limitations of current treatments, including their limited effectiveness, drug resistance, and off-target effects. Recent advancements in understanding the molecular mechanisms involved in the progress of reproductive cancers have provided valuable insights into potential targeted therapies. By engaging with oncoproteins and co-chaperones, heat-shock protein 90 (HSP90) regulates signaling networks and fixes protein folding errors in cancer cells. The potential of HSP90 inhibition as cancer-targeted treatments is underscored by the continuous discovery and testing of novel HSP90-targeted molecules for their antitumor properties in preclinical and clinical settings. Therefore, this study aims to shed light on the mechanism and recent research breakthroughs of HSP90, as well as provide an in-depth review of their therapeutic potential in reproductive cancers.
RESUMEN
OBJECTIVE: The objective was to explore the feasibility of ultrasound-microbubble-mediated hepatocyte growth factor (HGF) gene transfer for treating rat hepatic fibrosis induced by CCl(4). METHODS: Forty-eight male SD rats were divided into ultrasound-microbubble-HGF group (U-M-HGF group), ultrasound-HGF group (U-HGF group), microbubble-HGF group (M-HGF group), HGF group (HGF group), CCl(4) group (control group), and normal group. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total protein, albumin (ALB), and globulin (GLB) and the ratio of ALB/GLB were determined after treatment. The degree of hepatic fibrosis was evaluated by histopathological numerical scores. The protein expressions of HGF, collagen I, collagen III, and α-smooth muscle antibody (α-SMA) were detected by immunohistochemistry. RESULTS: Ultrasound-microbubble-mediated HGF therapy significantly reduced the serum level of ALT and AST to 59.88% and 49.18% of the control group, respectively. Ultrasound-microbubble-mediated HGF therapy prevented liver fibrosis, with an obvious decrease in fibrosis areas and extracellular matrix production of collagen I, collagen III, and α-SMA. The gene therapy could induce HGF delivery into the fibrotic liver effectively. CONCLUSIONS: Ultrasound-microbubble-mediated HGF gene therapy can reduce liver fibrosis, which provides a novel strategy for gene therapy of chronic liver disease.