Notes

Repeat associated with Primary Busts Lymphoma Showing as Bilateral Vitreoretinal Lymphoma.
Emerging evidence has shown that SKP1-cullin-1-F-box-protein (SCF) E3 ligases contribute to the pathogenesis of different cancers by mediating the ubiquitination and degradation of tumor suppressors. However, the functions of SCF E3 ligases in the pathogenesis of colorectal cancer (CRC) remain obscure.

The cancerous and adjacent noncancerous tissues from CRC patients were collected, and protein levels were analyzed. Lentiviral short hairpin RNA (shRNA) and plasmid transfection were used to knock down and overexpress gene expression in CRC cell lines. Immunoprecipitation (IP), mass spectrometry, and co-IP analyses were used to determine protein interactions and the assembly of the SCF complex. Cell proliferation, migration, and tumor xenograft assays were performed to examine the effects of SCF members on CRC cell growth in vitro and in vivo.

Hypoxia activated the docking of HIF1a onto the CUL1 promoter and induced CUL1 expression in CRC cells. CUL1 coupled with RBX1, SKP1, and FBXL1 to assemble the SCFFBXL1 complex in CRC biopsies and cells. The SCFFBXL1 E3 ligase specifically ubiquitinated and degraded the MEN1 tumor suppressor. Knockdown of HIF1a or SCFFBXL1 members, or blockage of SCFFBXL1 by two inhibitors (DT204 and SZLP1-41) caused the accumulation of MEN1 protein and led to a significant decrease in cell proliferation and migration in vitro and tumor growth in vivo.

The SCFFBXL1 E3 ligase is required for the ubiquitination of MEN1, and disruption of this complex may represent a new therapeutic strategy for the treatment of CRC.
The SCFFBXL1 E3 ligase is required for the ubiquitination of MEN1, and disruption of this complex may represent a new therapeutic strategy for the treatment of CRC.
The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).

In this randomized, open-label, phase II trial, 90 patients with WHO grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to CCRT with temozolomide followed by 6 cycles of adjuvant temozolomide (Arm A) and radiotherapy (RT) alone (Arm B).

Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizolomide.
For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of PD-L1.

We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS.

The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (HR=0.38), abdomen-pelvis origin (HR=2.43), tumor size larger than 5cm (HR=1.83), positive resection margin (HR=2.58), and postoperative radiotherapy (HR=0.36) were significantly related differentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non-small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.

This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. PD-L1 protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString® nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.

Eleven (36.7%) patients showed a durable clinical benefit (DCB), whereas nineteen (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044, 0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (Area under the curve [AUC]=0.794), followed by TMB (AUC=0.679) and PD-L1 (AUC=0.622). TMB and ES showed the highest AUC (0.8373) among other combinations (AUC, TMB and PD-L1=0.7775; AUC, PD-L1 and ES=0.7632) and was similar to that of all biomarkers used together (0.8325).

The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.
To evaluate the compatibility of corneal curvature and astigmatism, and higher-order aberrations (HOAs) measured by the Scheimpflug camera Pentacam HR and the swept-source optical coherence tomography ANTERION.

This prospective study included normal subjects with no ophthalmic history. Steep keratometry (K), flat K, astigmatism and its axis of the anterior and posterior surfaces, total corneal power, and HOAs using the two instruments were compared. To compare the mean values of the measurements, a paired t-test was used. Bland-Altman analysis was applied to assess the agreement between the two devices.

Fifty-three eyes of 53 subjects were evaluated. There were statistically significant differences for steep K, astigmatism, and vector J0, J45 in the anterior surface and total corneal power between the two devices (p<0.05). There were also significant differences in the most of the keratometric values of the posterior corneal surface (p<0.05) except J0 (p=0.410). Both devices showed strong positive HOAs showed acceptable agreements, except for the horizontal trefoil.
Most of the keratometric values cannot be used interchangeably. However, the vectoral component of astigmatism showed clinically good agreement. Several HOAs have statistically significant differences; however, almost all HOAs showed acceptable agreements, except for the horizontal trefoil.
This study aimed to analyze the common causes of epiphora in Korean patients and their response to subsequent management.

We retrospectively analyzed the medical records of 180 patients who visited Kim's Eye Hospital for epiphora between December 2017 and January 2019. This study included 320 eyes of 180 patients.

In the 320 eyes of 180 patients, the most common etiology of epiphora was reflex tearing due to dry eye syndrome, which occurred in 167 (52.19%) eyes. The other etiologies of epiphora included anatomical abnormality (68 [21.25%] eyes), multifactorial (60 [18.75%] eyes), functional epiphora (14 [4.38%] eyes), ocular surface disease (7 [2.19%] eyes), and eyelid abnormality (4 [1.25%] eyes).

The most common etiology of epiphora in Korean patients was reflex tearing due to dry eye syndrome, followed by lacrimal passage abnormality, multifactorial, functional epiphora, anterior segment disease, and eyelid malposition. Most patients with reflex tearing reported improvement in their symptoms after lubrication.
The most common etiology of epiphora in Korean patients was reflex tearing due to dry eye syndrome, followed by lacrimal passage abnormality, multifactorial, functional epiphora, anterior segment disease, and eyelid malposition. Most patients with reflex tearing reported improvement in their symptoms after lubrication.The Korean Intermittent Exotropia Multicenter Study (KIEMS), which was initiated by the Korean Association of Pediatric Ophthalmology and Strabismus (KAPOS), is a collaborative multicenter study on intermittent exotropia in the Republic of Korea. Selleckchem GSK503 The KIEMS was designed to provide comprehensive information, including subjective and objective findings of intermittent exotropia in a large study population. A total of 65 strabismus specialists in 53 institutions contributed to this study, which, to date, is one of the largest clinical studies on intermittent exotropia. In this article, we provide a detailed methodology of the KIEMS to help future investigations that may use the KIEMS data.C-type natriuretic peptide (CNP) is an important regulator of the male reproductive process. Our previous investigations showed that CNP can significantly stimulate the mRNA expression of androgen-binding protein (Abp) and transferrin (Trf) in the rat Sertoli cells, but the pathways responsible for this process remain to be elucidated. We predict that CNP binds the natriuretic peptide receptor B (NPR-B) to regulate expression of ABP and TRF through the intracellular cyclic guanosine monophosphate (cGMP) pathway. To address this question, in this study, we first confirmed the expression and localization of CNP and NPR-B in rat testes by immunohistochemistry and western blotting. Then, ELISA and real-time PCR were performed to investigate the signaling pathway of CNP in Sertoli cells in rat testes. Our results showed that CNP was mainly localized in the germ cells and Leydig cells, and its receptor, NPR-B, was mostly expressed in the Sertoli cells and vascular endothelial cells. CNP supplementation in the Sertoli cell medium was accompanied by an increase in the amount of intracellular cGMP and in the production of Abp and Trf mRNA, whereas inhibition of PKG with KT5823 led to a decrease in the expression of Abp and Trf mRNA. Moreover, Abp and Trf mRNA were no longer elevated when we used liposome-mediated RNA interference technology to silence the NPR-B gene in a mouse Sertoli cell line (TM4). These results suggest that CNP contributes to the regulation of ABP and TRF in the Sertoli cells through the NPR-B/cGMP/PKG signaling pathways.Recent work within early executive function (EF) seems to suggest that toddlers show distinct patterns of development, involving poorly correlated performance across EF tasks and significant improvements over relatively short periods of time. The present study sought to extend these findings by investigating evidence for these patterns in toddlers and the existence of more traditional patterns of EF (e.g., correlations between tasks, links to language) when using the same tasks in a novel Latin American sample. Eighty toddlers (18-24 months) and sixty young preschoolers (30-36) months completed a battery of EF tasks, early social communication, and receptive and expressive language measures. Results indicated that toddlers showed similar distinct patterns of development (i.e., few relations between tasks and links to responding to joint attention), but by early preschool a more cohesive EF and links to language were present. Further, work demonstrated significant age (older children outperformed younger children), gender (girls outperformed boys), and socioeconomic differences (satisfied basic needs outperformed unsatisfied basic needs, but only on the snack delay).
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