Tumor suppressive function of Matrin 3 in the basal-like breast cancer

BACKGROUND: Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized. METHODS: We analyzed in vitro tumorigenecity by cell proliferation and soft agar colony formation assays, apoptotic cell death by flow cytometry and Poly (ADP-ribose) polymerase (PARP) cleavage, epithelial-mesenchymal transition (EMT) by checking specific EMT markers with real-time quantitative PCR and in vitro migration and invasion by Boyden Chamber assays. To elucidate the underlying mechanism by which MATR3 functions as a tumor suppressor, we performed Tandem affinity purification followed by mass spectrometry (TAP-MS) and pathway analysis. We also scrutinized MATR3 expression levels in the different subtypes of human breast cancer and the correlation between MATR3 expression and patient survival by bioinformatic analyses of publicly available transcriptome datasets. RESULTS: MATR3 suppressed in vitro tumorigenecity, promoted apoptotic cell death and inhibited EMT, migration, and invasion in BLBC/TNBC cells. Various proteins regulating apoptosis were identified as MATR3-binding proteins, and YAP/TAZ pathway was suppressed by MATR3. MATR3 expression was inversely correlated with the aggressive and metastatic nature of breast cancer. Moreover, high expression levels of MATR3 were associated with a good prognosis of breast cancer patients. CONCLUSIONS: Our data demonstrate that MATR3 functions as a putative tumor suppressor in BLBC/TNBC cells. Also, MATR3 potentially plays a role as a biomarker in predicting chemotherapy-sensitivity and patient survival in breast cancer patients.

Learning curves for strabismus surgery in two ophthalmologists.

Purpose: To identify the average turning point by comparing the learning curves of two surgeons learning to perform strabismus surgery. Materials and Methods: Patients who underwent procedures to correct exotropia between January 2010 and December 2014 followed for at least 3 months were retrospectively assessed. The first 70 patients on whom each of two ophthalmologists (A and B) performed surgery to treat strabismus were divided into 7 cohorts comprising 10 patients each based on the chronological order of the surgery. Factors, including patient age, preoperative angle of deviation, operative time, and success or failure of the operation, were compared between the two surgeons. Learning curves were calculated based on changes in operative time and operation success rate. Operation success was determined by measuring the angle of deviation at a distance of 5 m 3 months after the operation. Results: A turning point was observed after 40 cases for Surgeon A and 50 cases for Surgeon B based on the operative time learning curve. No turning point was observed in the operation success rate learning curve based on the absence of a specific trend. Success rate by cohort was not significantly different between the two surgeons (P > 0.05). Surgeon B had a significantly longer mean operative time than Surgeon A (P = 0.045). Conclusions: Approximately 50 cases are required for an ophthalmologist to reach a turning point in strabismus surgery. This outcome can be used as a guideline when training surgeons to perform strabismus surgery.

Comparison of aqueous concentrations of angiogenic and inflammatory cytokines based on optical coherence tomography patterns of diabetic macular edema.

Purpose: The purpose was to compare aqueous inflammatory and angiogenic cytokine levels in diabetic macular edema (DME). Materials and Methods: Aqueous samples were obtained from 50 eyes with DME and 12 normal eyes (control group). DME was classified according to the morphologic pattern based on optical coherence tomography: Diffuse retinal thickening (DRT; n = 19), cystoid macular edema (CME; n = 17), or serous retinal detachment (SRD; n = 14). Aqueous samples were collected just before intravitreal injection and at the beginning of cataract surgery in the control group. Interleukin (IL)‑6, IL‑8, interferon‑induced protein (IP)‑10, monocyte chemotactic protein (MCP)‑1, platelet‑derived growth factor (PDGF)‑AA, and vascular endothelial growth factor (VEGF) levels were measured by multiplex bead assay. Results: The IL‑6, IL‑8, IP‑10, and PDGF‑AA levels differed significantly among the three groups of DME (P = 0.014, P = 0.038, P = 0.021, and P = 0.041, respectively). However, there were no differences between groups in aqueous concentration levels of MCP‑1 and VEGF (P = 0.205 and P = 0.062, respectively). IL‑6 (P = 0.026) and IL‑8 (P = 0.023) correlated positively with central foveal thickness (CFT) in the CME group. None of the cytokine levels correlated significantly with CFT in any of the DRT and SRD groups. Conclusions: Aqueous concentrations of cytokines varied according to the morphologic pattern of DME, which might explain the variable response to treatments such as intravitreal bevacizumab or triamcinolone injection.

Segmentation error and macular thickness measurements obtained with spectral-domain optical coherence tomography devices in neovascular age-related macular degeneration.

Purpose: To evaluate frequency and severity of segmentation errors of two spectral-domain optical coherence tomography (SD-OCT) devices and error effect on central macular thickness (CMT) measurements. Materials and Methods: Twenty-seven eyes of 25 patients with neovascular age-related macular degeneration, examined using the Cirrus HD-OCT and Spectralis HRA + OCT, were retrospectively reviewed. Macular cube 512 × 128 and 5-line raster scans were performed with the Cirrus and 512 × 25 volume scans with the Spectralis. Frequency and severity of segmentation errors were compared between scans. Results: Segmentation error frequency was 47.4% (baseline), 40.7% (1 month), 40.7% (2 months), and 48.1% (6 months) for the Cirrus, and 59.3%, 62.2%, 57.8%, and 63.7%, respectively, for the Spectralis, differing significantly between devices at all examinations (P < 0.05), except at baseline. Average error score was 1.21 ± 1.65 (baseline), 0.79 ± 1.18 (1 month), 0.74 ± 1.12 (2 months), and 0.96 ± 1.11 (6 months) for the Cirrus, and 1.73 ± 1.50, 1.54 ± 1.35, 1.38 ± 1.40, and 1.49 ± 1.30, respectively, for the Spectralis, differing significantly at 1 month and 2 months (P < 0.02). Automated and manual CMT measurements by the Spectralis were larger than those by the Cirrus. Conclusions: The Cirrus HD-OCT had a lower frequency and severity of segmentation error than the Spectralis HRA + OCT. SD-OCT error should be considered when evaluating retinal thickness.