ABSTRACT
High-temperature requirement A1 (HtrA1) has been identified as a disease-susceptibility gene for age-related macular degeneration (AMD) including polypoidal choroidal neovasculopathy (PCV). We characterized the underlying phenotypic changes of transgenic (Tg) mice expressing ubiquitous CAG promoter (CAG-HtrA1 Tg). In vivo imaging modalities and histopathology were performed to investigate the possible neovascularization, drusen formation, and infiltration of macrophages. Subretinal white material deposition and scattered white-yellowish retinal foci were detected on CFP [(Tg33% (20/60) and wild-type (WT)7% (1/15), p < 0.05]. In 40% (4/10) of the CAG-HtrA1 Tg retina, ICGA showed punctate hyperfluorescent spots. There was no leakage on FFA and OCTA failed to confirm vascular flow signals from the subretinal materials. Increased macrophages and RPE cell migrations were noted from histopathological sections. Monocyte subpopulations were increased in peripheral blood in the CAG-HtrA1 Tg mice (p < 0.05). Laser induced CNV in the CAG-HtrA1 Tg mice and showed increased leakage from CNV compared to WT mice (p < 0.05). Finally, choroidal explants of the old CAG-HtrA1 Tg mice demonstrated an increased area of sprouting (p < 0.05). Signs of subclinical inflammation was observed in CAG-HtrA1 Tg mice. Such subclinical inflammation may have resulted in increased RPE cell activation and angiogenic potential.
Subject(s)
Choroidal Neovascularization , Macular Degeneration , Animals , Choroid/blood supply , Choroidal Neovascularization/genetics , Choroidal Neovascularization/pathology , High-Temperature Requirement A Serine Peptidase 1/genetics , Inflammation/genetics , Inflammation/pathology , Macular Degeneration/genetics , Macular Degeneration/pathology , Mice , Mice, Transgenic , Retina/pathologyABSTRACT
Gold-based anticancer compounds have been attracting increasing research interest due to their ability to kill cancer cells resistant to platinum-based compounds. Gold I- and gold III-based complexes have shown satisfactory anticancer activities. In this study, two new fluorine-incorporated gold (I) compounds such as Ph3PAu[SC(OMe)=NC6H4F-3] and DPPFeAu2[(SC(OMe)=NC6H4F-3)]2 were evaluated for their in vitro activities against human breast cancer cell lines, primary breast cancer cells, and breast cancer stem cells (parental breast cancer stem cells, BCSC-P, and breast cancer stem cells, BCSC). Assays for growth inhibition and cytotoxicity, including real-time cell analysis, were carried out to screen effective antibreast cancer compounds. In addition, further in vitro assays such as apoptosis, caspase 3/7 activity, and cell cycle analysis were performed to observe the action and mechanism of killing breast cancer cells by the selected gold I compound, Ph3PAu[SC(OMe)=NC6H4F-3]. The gold (I) compound, Ph3PAu[SC(OMe)=NC6H4F-3], showed low toxicity to H9c2 normal cells and significant growth inhibition in MDA-MB-231 and MCF-7 cells, primary breast cancer cells, and breast cancer stem cells (BCSC-P and BCSC). The IC50 doses of the gold (I) compound Ph3PAu[SC(OMe)=NC6H4F-3] against the breast cancer cell lines MDA-MB-231 and MCF-7 were approximately 6-fold lower than that of cisplatin (cis-diamineplatinum (II) dichloride, CDDP). Moreover, the compound Ph3PAu[SC(OMe)=NC6H4F-3] induced caspase 3/7-dependent apoptosis and cell cycle arrest at S and G2/M phases. Ph3PAu[SC(OMe)=NC6H4F-3], a gold (I) compound incorporated with fluorine, is a potential candidate for the treatment of breast cancer.
ABSTRACT
MicroRNAs have become a hot topic in cancer research nowadays due to their important role not only on cancer development, progression, invasion but also on repression of cancer related genes. With advanced technologies, these microRNAs can easily be detected from biopsy samples and blood for early diagnosis, prognosis and treatment. Due to increasing demand of research in exploring expression profile of microRNAs with respect to different subtypes of breast cancer, this review aimed to provide an update on microRNA database available resources, canine breast cancer models, the role of microRNA as oncomir or oncosupressor, detection of microRNAs and potential of miRNAs for breast cancer treatment (AU)
