In vitro evaluation of the efficacy of photodynamic therapy using 5-ALA on homologous feline mammary tumors in 2D and 3D culture conditions and a mouse subcutaneous model with 3D cultured cells.

BACKGROUND: Numerous studies have shown that photodynamic therapy (PDT) has a therapeutic effect on mammary tumor cells, with 5-aminolevulinic acid (5-ALA-HCL) being a commonly used photosensitizer for PDT. Feline mammary tumors (FMTs) are relatively common. However, the cytotoxic and antitumor effects of 5-ALA-PDT on FMTs have not been clarified. To this end, we evaluated the therapeutic effect of 5-ALA-PDT on FMTs through in vitro experiments using an FMT FKR cell line established for this study. METHODS: We performed 5-ALA-PDT in 2D-cultured FKR-A (adherent cells) and 3D-cultured FKR-S (spheroid cells) cells and performed a series of studies to evaluate the cell viability and determine the protoporphyrin IX (PpIX) content in the cells as well as the expression levels of mRNAs associated with PpIX production and release. An in vivo study was performed to assess the effectiveness of 5-ALA-PDT. RESULTS: There was a significant difference in the concentration of PpIX in FMT cells under different incubation culture modes (2D versus 3D culture). The concentration of PpIX in FMT cells was correlated with the differences in cell culture (2D and 3D) as well as the expression levels of genes such as PEPT1, PEPT2, FECH, and HO-1. CONCLUSIONS: In the in vitro study, 5-ALA-PDT had a stronger inhibitory effect on 3D-cultured FKR-S cells, which resemble the internal environment of organisms more closely. We also observed a significant inhibitory effect of 5-ALA-PDT on FMT cells in vivo. To our knowledge, this is the first study on 5-ALA-PDT for FMTs under both 2D and 3D conditions.

Immunotherapy and Antivascular Targeted Therapy in Patients' Treatment with Concurrent Malignant Tumors after Organ Transplantation: Opportunity or Challenge.

Objective: To analyze the therapeutic effects and organ rejection of anti-PD-1 immunotherapy or antivascular targeting therapy on patients with combined malignancies after organ transplantation. Methods: We collected retrospective studies on "post-transplantation, cancer, immunotherapy, and vascular targeting therapy" in Embase, Wanfang database, Cochrane Library, VIP databases, CNKI, and PubMed, and the case data were organized and analyzed. Results: Data from only 40 papers met our requirements, which included 2 literature reviews, 4 original researches, and 34 case reports from 2016 to 2020. A total of 40 studies involving 66 patients were included, who were divided into 3 groups (patients using CTLA-4 inhibitors, group 1; patients who received sequential or concurrent anti-PD-1 and anti-CTLA-4 therapy, group 2; and patients using PD-1/PD-L1 inhibitors, group 3). There was no statistical difference in patients' DCR between the three groups (P > 0.05). Also, compared with group 2, there was no statistically significant difference in recipient organ rejection in group 1 and group 3 (P > 0.05). The DCR rate for antivascular targeted therapy is approximately 60%. Conclusions: Immunotherapy should be carefully selected for patients with combined malignancies after organ transplantation. Antivascular targeted therapy is one of the options worth considering; the risk of side effects of drug therapy is something that needs to be closely monitored when combined with immunotherapy.

miR-26b regulates cell proliferation and apoptosis of CD117+CD44+ ovarian cancer stem cells by targeting PTEN.

Ovarian cancer (OC) is the one of the most common cancer in women globally. However, it still represents the most dangerous gynecologic malignancy even with the advances in detection and therapeutics. Thus, there is an urgent need in finding more effective therapeutic options for OC patients including cancer stem cells (CSC). MicroRNAs (miRNAs) are small, endogenous, and non-coding RNAs that play critical roles in the progression of various types of tumor. Our aim of this study was to find the regulatory function of microRNA-26 (miRNA-26b) on the cell proliferation and apoptosis of ovarian CSCs. Our studies show that miR-26b is under-regulated in human CD117+CD44+ ovarian CSCs. The miR-26b overexpression inhibits the cell proliferation and promotes cell apoptosis. Moreover, phosphatase and tensin homolog (PTEN) is found to be a functional target of miR-26b. Moreover, PTEN overexpression reversed the effects of miR-26b on the cell proliferation and apoptosis. PTEN overexpression remarkably accelerated the cell proliferation, and inhibited cell apoptosis. These results indicate that miR-26b regulates cell proliferation and apoptosis of CD117+CD44+ ovarian CSCs by targeting PTEN.>.