Ke Li

Red blood cell–hitchhiking fluorescent probe to promote intraoperative diagnosis of human ovarian tumor

Ovarian cancer is the deadliest gynecological malignancy. The fluorescence-guided surgery technique provides a real-time visualization of the desired regions to guide the tumor resection. However, the fluorescent probes used in clinics suffer from the limited selectivity of ovarian tumors and short blood circulation half-lives. Here, we design an activatable trident-like fluorescent peptide probe (RMN) to bind with the ovarian tumor-overexpressed N-cadherin and respond to the matrix metalloproteinases (MMPs). Upon intravenous administration, the RMN initially hitchhikes on the red blood cell (RBC) surface with prolonged circulation half-lives. When arriving at the tumor regions, the peptide sequence is cleaved by the tumor-secreted MMPs to recover the fluorescent signals. The released “spears” containing N-cadherin–targeting moiety and fluorophore can specifically recognize the ovarian tumor cells, thereby facilitating the visualization of primary or metastatic tumor regions. Overall, this study highlights the potential of RBC-hitchhiking fluorescent probes in advancing the intraoperative diagnosis of human ovarian tumor tissues during the fluorescence-guided surgery process in clinics.

Establishment and characterization of a novel cell line (SCCOHT-CH-1) and PDX models derived from Chinese patients of small cell ovarian carcinoma of the hypercalcemic type

AbstractSmall cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.