Visual Prognosis of Retinoblastoma in the Posterior Pole Treated with Primary Chemotherapy Plus Local Treatments

Purpose: To evaluate the visual outcomes of retinoblastoma in the posterior pole (RBPP) treated with chemotherapy plus local treatments and to address the prognostic factors that influence such outcomes. Methods: The medical records of patients with RBPP diagnosed at the Department of Pediatric Ophthalmology, Seoul National University Children’s Hospital between August 1987 and September 2007 were reviewed retrospectively. Only those patients treated via primary chemotherapy plus local treatments were included. The presence of foveal involvement and tumors in the posterior pole before and after treatment, the type of regression pattern and the best corrected visual acuity (BCVA) of each patient were evaluated. Results: A total of 13 eyes in 12 patients were included. The mean final BCVA for treated RBPP was 20/210 (range, hand motion to 20/16). However, eight eyes (61.5%) had an acuity of 20/200 or better and seven eyes (53.8%) had an acuity of 20/50 or better. The mean final BCVA was significantly better in cases with negative foveal involvement; however, four eyes (37.5%) with positive foveal involvement had an acuity of 20/200 or better. Tumors area in the posterior pole and the type of regression pattern were not significantly related to final BCVA. Conclusions: Over one half of the studied RBPP patients had working vision. Although the eyes had RBPP with positive foveal involvement, about one‐third of the patients had working vision. Vision preservation should b

Endoscopist Specialty Is Associated with High-Quality Endoscopy in Korea

Purpose: The present study was aimed to determine whether endoscopist specialty is associated with high-quality endoscopy. Materials and Methods: We prospectively collected endoscopy quality related data based on the Endoscopy Quality Rating Scale (EQRS) of 277 endoscopy units in a hospital setting from the National Cancer Screening Program of Korea in 2009. Gastroenterology medical professors (n=154) from university hospitals visited each endoscopy unit and graded the unit according to the EQRS. The scores from the EQRS were analyzed and compared in relation to endoscopy training during residency and endoscopy subspecialist certification. Results: After excluding data from 3 endoscopy units, EQRS data from 274 endoscopy units were analyzed: 263 esophagogastroduodenoscopy (EGD) screening units and 90 colonoscopy screening units. There were no significant differences in the scores of EQRS with respect to endoscopy training during residency (p=no significance), except for scores of EGDs for "Facility and Equipment" (p=0.030). However, EQRS scores were significantly higher in the endoscopy units where endoscopy subspecialists performed the endoscopies than those where Endoscopy Subspecialists did not perform the endoscopies (p<0.05, except p=0.08 for the "Process" criteria of EGD). Conclusion: Endoscopist specialty is an important determinant of high-quality endoscopy in Korea.This study was supported by a Grant-in-Aid for Cancer Research and Control from the National Cancer Center of Korea (#0960400-1)

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis

Long-Term Echocardiographic Follow-up after Posterior Mitral Annuloplasty Using a Vascular Strip for Ischemic Mitral Regurgitation: Ten-Years of Experience at a Single Center

Management of ischemic mitral regurgitation (MR) is challenging. The aim of this study was to investigate long-term clinical and echocardiographic results of restrictive mitral annuloplasty for ischemic MR. From 2001 through 2010, 96 patients who underwent myocardial revascularization with restrictive mitral annuloplasty using a vascular strip for ischemic MR were analyzed. Patients were stratified into two groups based on left ventricular ejection fraction (LVEF): group I, n = 50, with LVEF > 35% and group II, n = 46, with LVEF ≤ 35%. The early mortality rate was 2.1% (2/96) and the late cardiac mortality rate was 11.5% (11/96). MR grade was reduced at discharge (0.8 ± 0.7) but increased during follow-up (1.1 ± 0.8, P = 0.001). There was no intergroup difference in terms of freedom from recurrent MR ≥ moderate eight years after surgery (94.1% ± 5.7%, group I vs 87.8% ± 7.2%, group II; P = 0.575). NYHA functional class (odds ratio [OR], 2.2; P = 0.044) and early postoperative residual MR ≥ mild (OR, 25.4; P < 0.001) were independent predictors of recurrent MR. Restrictive mitral annuloplasty using a vascular strip is effective in ischemic MR. It is important to avoid early postoperative residual MR

Combined inhibition of Bcl-2 family members and YAP induces synthetic lethality in metastatic gastric cancer with RASA1 and NF2 deficiency

Background Targetable molecular drivers of gastric cancer (GC) metastasis remain largely unidentified, leading to limited targeted therapy options for advanced GC. We aimed to identify molecular drivers for metastasis and devise corresponding therapeutic strategies. Methods We performed an unbiased in vivo genome-wide CRISPR/Cas9 knockout (KO) screening in peritoneal dissemination using genetically engineered GC mouse models. Candidate genes were validated through in vivo transplantation assays using KO cells. We analyzed target expression patterns in GC clinical samples using immunohistochemistry. The functional contributions of target genes were studied through knockdown, KO, and overexpression approaches in tumorsphere and organoid assays. Small chemical inhibitors against Bcl-2 members and YAP were tested in vitro and in vivo. Results We identified Nf2 and Rasa1 as metastasis-suppressing genes through the screening. Clinically, RASA1 mutations along with low NF2 expression define a distinct molecular subtype of metastatic GC exhibiting aggressive traits. NF2 and RASA1 deficiency increased in vivo metastasis and in vitro tumorsphere formation by synergistically amplifying Wnt and YAP signaling in cancer stem cells (CSCs). NF2 deficiency enhanced Bcl-2-mediated Wnt signaling, conferring resistance to YAP inhibition in CSCs. This resistance was counteracted via synthetic lethality achieved by simultaneous inhibition of YAP and Bcl-2. RASA1 deficiency amplified the Wnt pathway via Bcl-xL, contributing to cancer stemness. RASA1 mutation created vulnerability to Bcl-xL inhibition, but the additional NF2 deletion conferred resistance to Bcl-xL inhibition due to YAP activation. The combined inhibition of Bcl-xL and YAP synergistically suppressed cancer stemness and in vivo metastasis in RASA1 and NF2 co-deficiency. Conclusion Our research unveils the intricate interplay between YAP and Bcl-2 family members, which can lead to synthetic lethality, offering a potential strategy to overcome drug resistance. Importantly, our findings support a personalized medicine approach where combined therapy targeting YAP and Bcl-2, tailored to NF2 and RASA1 status, could effectively manage metastatic GC.This research was supported by grants of the National Research Foundation (NRF) funded by the Korean government (NRF-RS-2023–00208984, NRF-2021M3H9A1030260, NRF-2021R1F1A1051220, NRF-2016M3A9D5A01952416)

Latent semantic kernels for WordNet: Transforming a tree-like structure into a matrix

WordNet is one of the most widely used linguistic resources in the computational linguistics society. However, many applications using the WordNet hierarchical structure are suffering from the word sense disambiguation (WSD) caused by its polysemy. In order to solve the problem, we propose a matrix representing the WordNet hierarchical structure. Firstly, we transform a term as a vector with elements of each corresponding to a synset of WordNet. Then, with singular value decomposition (SVD), we reduce the dimension size of the vector to represent the latent semantic structure. For evaluation, we implement an automatic assessment system for short essays and acquire reliable accuracy. As a result, the scores which are assessed by the automatic assessment system are signi£cantly correlated with those of human assessors. The new WordNet is expected to be easily combined with other matrix-based approaches.