Publisher：Scientific Reports  

Androgen deprivation therapy is given to suppress prostate cancer growth; however, some cells continue to grow hormone-independently as castration-resistant prostate cancer (CRPC). Sulfated glycosaminoglycans promote ligand binding to receptors as co-receptors, but their role in CRPC remains unknown. Using the human prostate cancer cell line C4-2, which can proliferate in hormone-dependent and hormone-independent conditions, we found that epidermal growth factor (EGF)-activated EGFR–ERK1/2 signaling via 3-O-sulfated heparan sulfate (HS) produced by HS 3-O-sulfotransferase 1 (HS3ST1) is activated in C4-2 cells under hormone depletion. Knockdown of HS3ST1 in C4-2 cells suppressed hormone-independent growth, and inhibited both EGF binding to the cell surface and activation of EGFR–ERK1/2 signaling. Gefitinib, an EGFR inhibitor, significantly suppressed C4-2 cell proliferation and growth of a xenografted C4-2 tumor in castrated mouse. Collectively, our study has revealed a mechanism by which cancer cells switch to hormone-independent growth and identified the key regulator as 3-O-sulfated HS.

DOI： 10.1038/s41598-023-38746-x

Scopus

Language：English   Publisher：Graefe's Archive for Clinical and Experimental Ophthalmology  

Purpose: To assess the effects of half-dose photodynamic therapy (PDT) combined with an intravitreous aflibercept (IVA) injection for pachychoroid neovasculopathy (PNV) and its predictive factors. Methods: Clinical information of 43 patients (43 eyes) with PNV obtained before and 6 months after treatment with half-dose PDT combined with IVA was retrospectively analyzed. Patients were categorized into the sufficient (25 eyes, 58.1%) or insufficient (18 eyes, 41.9%) group based on resolution or persistence/recurrence of subretinal fluid (SRF), respectively, and clinical data were compared. Macular neovascularization (MNV) change was studied in 30 cases with available pre- and post-treatment optical coherence tomography angiography images. Results: The sufficient group included younger patients with better baseline best-corrected visual acuity (BCVA), more treatment-naïve eyes, and smaller MNV lesions at baseline than the insufficient group (all, P < 0.047). Complete SRF resolution was 81.8% in treatment-naïve eyes and only 33.3% in previously treated eyes. MNV expanded after half-dose PDT was combined with IVA regardless of the treatment outcome (P = 0.003). Conclusion: Half-dose PDT combined with IVA was effective for PNV treatment, especially for younger patients with good baseline BCVA, treatment-naïve eyes, and small MNV sizes at baseline. MNV expanded after treatment regardless of the treatment outcomes.

DOI： 10.1007/s00417-023-06030-3

Web of Science

Scopus

PubMed

Language：English   Publisher：Retina  

Purpose:To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&E) regimen.Methods:This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment.Results:The mean MNV area increased significantly from 0.65 ± 0.42 mm2 at baseline to 0.78 ± 0.45 mm2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline (R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels.Conclusion:Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.

DOI： 10.1097/IAE.0000000000003676

Web of Science

Scopus

PubMed

Language：English   Publisher：Japanese Journal of Ophthalmology  

Purpose: We investigated the differences in displacement of the outer and inner macular retina toward the optic disc after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). Foveal avascular zone (FAZ) area changes were also investigated. Study design: Retrospective observational study Methods: This retrospective observational case series included 45 eyes of 43 patients that underwent vitrectomy with ERM and ILM peeling for ERM and 38 normal eyes. The locations of the centroid of the FAZ (C-FAZ, center of the foveal inner retina) and foveal bulge (center of the foveal outer retina) were determined using 3×3mm superficial optical coherence tomography angiography. C-FAZ and foveal bulge displacements, and the pre- and postoperative FAZ areas and their associated factors, were investigated. Results: Postoperative C-FAZ dislocated significantly more toward the optic disc than in pre-operative or normal eyes (P<0.001). C-FAZ and foveal bulge displaced toward the optic disc after surgery; C-FAZ showed significantly greater displacement than foveal bulge (P<0.001). The pre- and postoperative FAZ areas were correlated (P=0.01). Preoperative FAZ areas ≧0.10mm2 were reduced after surgery, and FAZ areas < 0.10mm2 were increased, independent of foveal displacement. Conclusion: ILM peeling during vitrectomy for ERM caused larger displacement of the inner and smaller displacement of the outer retinas, towards the optic disc. Postoperative changes in the FAZ area were dependent on the baseline FAZ area, but not on the foveal displacement. ILM may physiologically exert centrifugal tractional forces on the fovea.

DOI： 10.1007/s10384-022-00964-7

Web of Science

Scopus

PubMed