A Novel TFG Mutation in a Korean Family with α-Synucleinopathy and Amyotrophic Lateral Sclerosis.

BACKGROUND: Tropomyosin-receptor kinase fused gene (TFG) functions as a regulator of intracellular protein packaging and trafficking at the endoplasmic reticulum exit sites. TFG has recently been proposed as a cause of multisystem proteinopathy. OBJECTIVES: Here, we describe a Korean family presenting with Parkinson's disease or amyotrophic lateral sclerosis caused by a novel variant of TFG (c.1148 G > A, p.Arg383His). METHODS: We collected clinical, genetic, dopamine transporter imaging, nerve conduction, and electromyography data from the seven subjects. To verify the pathogenicity of the R383H variant, we studied cell viability and the abnormal aggregation of α-synuclein and TAR DNA-binding protein 43 (TDP-43) in HeLa cells expressing R383H-TFG. RESULTS: The clinical phenotypes of the R383H-TFG mutation varied; of the five family members, one had Parkinson's disease, three had subclinical parkinsonism, and one (the proband) had amyotrophic lateral sclerosis. The individual with multiple system atrophy was the proband's paternal cousin, but the TFG genotype was not confirmed due to unavailability of samples. Our in vitro studies showed that R383H-TFG overexpression impaired cell viability. In cells co-expressing R383H-TFG and α-synuclein, insoluble α-synuclein aggregates increased in concentration and were secreted from the cells and co-localized with R383H-TFG. The levels of cytoplasmic insoluble aggregates of TDP-43 increased in HeLa cells expressing R383H-TFG and co-localized with R383H-TFG. CONCLUSIONS: Clinical and in vitro studies have supported the pathogenic role of the novel TFG mutation in α-synucleinopathy and TDP-43 proteinopathy. These findings expand the phenotypic spectrum of TFG and suggest a pivotal role of endoplasmic reticulum dysfunction during neurodegeneration. © 2021 International Parkinson and Movement Disorder Society.

Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma.

BACKGROUND & GOALS: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. METHODS: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (612 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. CONCLUSIONS: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Kinetic Mechanism of Formation of Hyperactive Embryonic Ras in Cells.

Embryonic Ras (ERas)--a new subset of Ras proteins--are characterized by a unique p-loop residue, unique Switch II residues, and an unusual extended N-terminus. When expressed, both murine and human ERas are highly populated in their GTP-bound forms. The expression of murine ERas is linked to the development of murine embryonic cells, and the expression of human ERas is correlated to certain human cancers. Mutation-based kinetic analyses, in combination with assessments of the kinetic parameter-based calculation of the fraction of the GTP-bound active form of ERas proteins, explain the kinetic mechanism that produces the unprecedented hyperactive ERas. The ERas-specific p-loop residue contributes ERas proteins to intrinsically populate their GTP-bound form in cells. Furthermore, the ERas-specific Switch II residues block the catalytic action of p120GAP on ERas proteins. This blockage sustains the previously mentioned GTP-bound ERas proteins. In essence, the combined work of the ERas-specific p-loop and Switch II residues populates the exceedingly high GTP-bound form of ERas in cells. This study also rules out any kinetic function of the unique ERas-specific N-terminus in the production of the hyperactive GTP-bound ERas in cells. The biological role of this N-terminus remains uninvestigated. Intriguingly, the ERas-specific p-loop residue matches the mutated Ser residue of the Costello Syndrome G12S HRas mutant that also intrinsically populates its GTP-bound form in cells. However, because the effector protein of ERas differs from that of G12S HRas, this kinetic similarity does not confer on ERas biological and/or pathophysiological similarity to G12S HRas.

Portal hypertensive gastropathy as a prognostic index in patients with liver cirrhosis.

BACKGROUND: Portal hypertensive gastropathy (PHG) is a frequently overlooked complication of liver cirrhosis (LC). The clinical implications of PHG as a prognostic factor of LC or a predictive factor for the development of hepatocellular carcinoma (HCC) have not been established. The aim of this study was to assess the clinical significance of PHG in patients with LC. METHODS: Patients with LC were prospectively enrolled and followed in a single tertiary hospital in the Republic of Korea. Baseline hepatic vein pressure gradient (HVPG) was measured, and esophagogastroduodenoscopy (EGD) was performed. The associations of PHG with HVPG, survival and the development of HCC were evaluated. RESULTS: A total of 587 patients were enrolled. The mortality rate was 20.3 % (n = 119), and HCC developed in 9.2 % (n = 54) during the follow-up period (32.6 ± 27.8 months). The grade of PHG was well correlated with HVPG (no PGH: median 9.2 [IQR: 7.2-16.7], mild PHG: 14.6 [10.1-19.3], and severe PHG: 17.3 [12.3-21.5], P < 0.001), as well as with Child-Pugh class, MELD score or survival. However, it was not associated with the development of HCC. The grade of PHG (HR 3.29, 95 % CI: 1.12-9.63, severe vs. no PHG) and Child-Pugh class (HR 3.53, 95 % CI: 1.79-6.97, Child C vs A) showed significant associations with mortality. CONCLUSION: PHG was well correlated with portal hypertension and could be used as a prognostic factor for LC but not for the prediction of HCC.

Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey.

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.

Favorable outcome of alternate systemic and intra-arterial chemotherapy for retinoblastoma.

The recent trend of treatment for retinoblastoma is to salvage the eye globes as well as achieving patients' survival. Intra-arterial chemotherapy (IAC) is one of the current standard treatment; however, it cannot exclude the risk of occult micrometastases in the central nervous system in advanced-stage retinoblastoma. Alternate fashion of intravenous chemotherapy (IVC) and IAC strategy was developed to increase the eye salvage rate and to reduce the metastatic risk. Between January 2012 and December 2014, 13 eyes of 12 patients with newly diagnosed retinoblastoma received alternate chemotherapy using IVC and IAC in Yonsei Cancer Center. Eye salvage rate was assessed by the eye preservation time, which was defined as the duration from the diagnosis to the time of enucleation. Total 13 eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group B (n = 1, 7.7%), group C (n = 2, 15.4%), group D (n = 5, 38.5%), or group E (n = 5, 38.5%). IAC was performed, 3 to 5 times (median: 4 times) for each eye, total 54 times. Five to 15 courses (median: 8 courses) of systemic chemotherapy were performed in the patients. During the median follow-up period of 30.4 months, overall eye salvage rate was 63.9 ± 14.7%. All patients survived. The treatment was tolerable without significant complications. These results showed that primary alternate IVC-IAC was tolerable and effective for retinoblastoma.

Poor bone health at the end of puberty in childhood cancer survivors.

BACKGROUND: Although the survival rate following childhood cancer is >80%, late effects are a major concern. We aimed to determine the clinical factors affecting bone health after puberty in childhood cancer survivors at risk for low bone mineral density (BMD). PROCEDURES: We performed dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, and total hip regions for survivors with the following bone densitometry indications (BDIXs): brain or nasopharyngeal cancer, head or neck area radiotherapy, or corticosteroid treatment (N = 92). Additionally, we evaluated 16 survivors without these BDIXs but with other clinical factors that could affect bone health. We assessed the effects of these factors on BMD using univariate and logistic regression analyses. Moderate BMD deficit was defined as a Z-score of <-1.0 and ≥-2.0, and severe BMD deficit was defined as <-2.0. RESULTS: Severe BMD deficits were found in 18 survivors (16.7%) and moderate BMD deficits were in 39 (36.1%) in at least one bone region. BMD deficits tended to increase as the number of BDIXs increased (P < 0.010). There were no severe BMD deficits in survivors without BDIXs. The duration since cancer treatment completion was correlated with higher BMD (P < 0.05). Endocrine dysfunction was a significant risk factor for decreased BMD in univariate and multivariate analyses (P < 0.05 for both). CONCLUSIONS: Decreased BMD was prevalent in our study cohort. Endocrine dysfunction was found to be a significant risk factor, and it should be managed in survivors to ensure future bone health.

Long-term stability of CdSe/CdZnS quantum dot encapsulated in a multi-lamellar microcapsule.

We developed a novel and easy encapsulation method for quantum dots (QDs) using a partially oxidized semi-crystalline polymeric material which forms a micron-sized granule with a multi-lamellar structure from a dilute solution. The QDs were highly dispersed in the granule in such a way that they were adsorbed on the lamella with ∼12 nm spacing followed by lamellar stacking. The QDs were heavily loaded into the granule to 16.7 wt% without aggregation, a process which took only a few minutes. We found that the quantum yield of the QDs was not degraded after the encapsulation. The encapsulated QD-silicone composite exhibited excellent long-term photo- and thermal stability with its initial photoluminescence intensity maintained after blue LED light radiation for 67 days and storage at 85 °C and 85% relative humidity for 119 days.

Mosapride treatment for functional dyspepsia: a meta-analysis.

BACKGROUND AND AIM: The aim of this study was to assess the therapeutic effect of mosapride in patients with functional dyspepsia (FD). METHODS: Randomized controlled trials (RCTs) of mosapride for the treatment of FD performed between 2002 and 2013 were identified from databases. Symptom response rates were extracted and analyzed using risk ratios (RRs). A random effect model was applied based on Higgins I(2) tests. Publication bias was evaluated using a funnel plot, Egger's test, trim and fill, and the rank correlation test. RESULTS: In total, 13 RCTs, which included 1091 mosapride-treated patients and 1129 control patients (on placebo or other drugs), were identified and analyzed. Overall, mosapride showed an RR of 0.999 (95% confidence interval [CI]: 0.869-1.150, P = 0.992) for improving global efficacy or symptom-based scores. In a sensitivity analysis of the high-quality RCTs, mosapride showed an RR of 1.114 (95% CI: 1.011-1.227, P = 0.029). However, in the studies using the Rome III criteria for the diagnosis of FD, mosapride showed an RR of 0.906 (95% CI: 0.807-1.016, P = 0.092). In the studies having funding source, mosapride showed an RR of 1.131 (95% CI: 1.028-1.244, P = 0.012), whereas an RR of 0.966 (95% CI: 0.896-1.042, P = 0.367) was observed in the studies without funding source. Publication bias was not detected. CONCLUSION: In this analysis, we could not find a significant effect of mosapride on FD. Inconsistent diagnostic criteria for FD and different assessment outcomes are causes of heterogeneity. Further studies using common validated outcomes or questionnaires and high-quality RCTs will elucidate the real effect of this medication on FD.

Impact of psychological and cancer-related factors on HRQoL for Korean childhood cancer survivors.

PURPOSE: The purposes of this study were (1) to compare health-related quality of life (HRQoL) between Korean childhood cancer survivors and healthy controls and (2) to examine the impact of demographic, diagnosis/treatment, and psychological variables on physical and psychosocial health in survivors. METHODS: The HRQoL (PedsQL), Self-Concept Inventory, and Child Behavior Checklist were administered to childhood cancer survivors, age/gender-matched healthy counterparts, and their parents. Independent-samples t tests and hierarchical multiple regression analyses were conducted. RESULTS: Compared with healthy controls, childhood cancer survivors reported significantly lower scores across physical and psychosocial HRQoL. For survivors, demographic, diagnosis/treatment, current health status, and psychological variables explained more than 50 % of the variance in both subscales of HRQoL. Especially, self-concept, a psychological variable, explained a significant portion of the variance in physical and psychosocial HRQoL after controlling for cancer-related factors. Several cancer-related factors including time since treatment completion, having a history of allogeneic hematopoietic stem cell transplantation, multiple treatment modalities, and suffering from severe late effects also associated with specific dimension of HRQoL. CONCLUSIONS: Childhood cancer survivors do experience lower level of QoL and psychological factors, especially self-concept, should be considered when supporting the well-being of childhood cancer survivors.

Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.

Targeted delivery of small-molecule drugs via covalent attachments to monoclonal antibodies has proved successful in clinic. For this purpose, full-length antibodies are mainly used as drug-carrying vehicles. Despite their flexible conjugation sites and versatile biological activities, intact immunoglobulins with conjugated drugs, which feature relatively large molecular weights, tend to have restricted tissue distribution and penetration and low fractions of payloads. Linking small-molecule therapeutics to other formats of antibody may lead to conjugates with optimal properties. Here, we designed and synthesized ADP-ribosyl cyclase-enabled fragment antigen-binding (Fab) drug conjugates (ARC-FDCs) by utilizing CD38 catalytic activity. Through rapidly forming a stable covalent bond with a nicotinamide adenine dinucleotide (NAD+ )-based drug linker at its active site, CD38 genetically fused with Fab mediates robust site-specific drug conjugations via enzymatic reactions. Generated ARC-FDCs with defined drug-to-Fab ratios display potent and antigen-dependent cytotoxicity against breast cancer cells. This work demonstrates a new strategy for developing site-specific FDCs. It may be applicable to different antibody scaffolds for therapeutic conjugations, leading to novel targeted agents.

Increasing and worsening late effects in childhood cancer survivors during follow-up.

Recent advances in childhood cancer treatment have increased survival rates to 80%. Two out of three survivors experience late effects (LEs). From a group of 241 survivors previously described, 193 were followed at the long-term follow-up clinic (LTFC) of Severance Hospital in Korea; the presence of LEs was confirmed by oncologists. We reported the change in LEs during 3 yr of follow-up. The median follow-up from diagnosis was 10.4 yr (5.1-26.2 yr). Among 193 survivors, the percentage of patients with at least one LE increased from 63.2% at the initial visit to 75.1% at the most recent visit (P = 0.011). The proportion of patients having multiple LEs and grade 2 or higher LEs increased from the initial visit (P = 0.001 respectively). Forty-eight non-responders to the LTFC were older and had less frequent and severe LEs than responders at initial visit (all P < 0.05). In multivariate analysis, younger age at diagnosis, older age at initial visit, a diagnosis of a brain tumor or lymphoma, and use of radiotherapy were significant risk factors for LEs (all P < 0.05). Adverse changes in LEs were seen among the survivors, regardless of most clinical risk factors. They need to receive comprehensive, long-term follow up.

A case of Diphyllobothrium nihonkaiense infection as confirmed by mitochondrial COX1 gene sequence analysis.

Diphyllobothrium nihonkaiense has been reported in Korea as Diphyllobothrium latum because of their close morphologic resemblance. We have identified a human case of D. nihonkaiense infection using the mitochondrial cytochrome c oxidase subunit I (cox1) gene sequence analysis. On 18 February 2012, a patient who had consumed raw fish a month earlier visited our outpatient clinic with a long tapeworm parasite excreted in the feces. The body of the segmented worm was 2 m long and divided into the scolex (head) and proglottids. It was morphologically close to D. nihonkaiense and D. latum. The cox1 gene analysis showed 99.4% (340/342 bp) homology with D. nihonkaiense but only 91.8% (314/342 bp) homology with D. latum. The present study suggested that the Diphyllobothrium spp. infection in Korea should be analyzed with specific DNA sequence for an accurate species identification.

Initial experience with dexmedetomidine for dental sedation in children.

Sedation of uncooperative children for dental treatment is difficult since treatment is mainly carried out inside the oral cavity. Dexmedetomidine (DEX), recently introduced into clinical practice, has little influence on respiratory system even at high doses. We present cases of patients who underwent dental treatment under sedation using DEX infusion. DEX at a dose of 1 microg/kg was administered over 10 min after intravenous cannulation. DEX was infused to maintain sedation level within the range of the Observer's Assessment of Alertness and Sedation (OAA/S) scale 3- 4 throughout dental treatments. They were successfully treated under DEX sedation without any complications. Their uncooperative behaviors were successfully managed under DEX sedation.

Generation of Bispecific Antibodies by Functionalized Poly-ADP-Ribose Polymers.

Bispecific antibodies have drawn considerate research interests for therapeutic development. Numerous genetic and chemical methods are established to produce bispecific antibodies with varied formats. This protocol describes a novel approach to the synthesis of bispecific antibodies by utilizing chemically functionalized poly-ADP-ribose polymers derived from post-translational poly-ADP-ribosylation. Basic Protocol 1 includes experimental procedures for expressing and purifying recombinant full-length human poly-ADP-ribose polymerase 1 (PARP1) as well as monoclonal antibodies targeting T-cell CD3 and breast cancer tumor-associated human epidermal growth factor receptor 2 (HER2) molecules. Basic Protocol 2 details methods for enzymatic preparation of functionalized poly-ADP-ribose polymers by PARP1 and chemical conjugation of antibody molecules for bispecific antibody production. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Expression and purification of PARP1 and antibodies Basic Protocol 2: PARP1 auto-modification and antibody conjugation.

The Efficacy of Alternate Systemic Intravenous Chemotherapy and Intra-arterial Chemotherapy Approach for Eye Globe Salvage in Retinoblastoma.

PURPOSE: The advances in the treatment of retinoblastoma have enabled salvaging the globe in advanced stages with intra-arterial chemotherapy (IAC). We developed a strategy of alternate application of systemic intravenous chemotherapy (IVC) and IAC (referred to as alternate systemic IVC and IAC; ASIAC) to reduce central nervous metastases during IAC and examined its efficacy and safety in eye globe salvage in this study. MATERIALS AND METHODS: Between January 2010 and February 2021, 43 eyes of 40 patients received ASIAC treatment for retinoblastoma at the Yonsei Cancer Center, Yonsei University Health System. Their medical records were reviewed retrospectively to evaluate the eye salvage rate (ESR), defined from diagnosis to enucleation. High-risk retinoblastoma was defined as group D or E by the International Classification of Retinoblastoma. RESULTS: The study enrolled 38 and five cases of high-risk and low-risk retinoblastoma, respectively. In total, 178 IAC and 410 IVC courses were administered, with a median of 4 (interquartile range [IQR], 3.0 to 5.0) IAC and 9 (IQR, 6.0 to 11) IVC courses per eye, respectively. The 5-year ESR was 60.4%±8.7% for the whole cohort, 100% for low-risk retinoblastoma, and 53.6%±9.8% for high-risk retinoblastoma. Among those diagnosed since 2015, the 5-year ESR for high-risk retinoblastoma was 63.5%±14.0%. Fifteen eyes underwent enucleation; no viable tumor was found in three enucleated eyes. There were no deaths in this cohort. CONCLUSION: Primary IAC-IVC (i.e., ASIAC) for patients with retinoblastoma was tolerable and effective in salvaging the eye and maintaining survival.

Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment.

The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.922 indicated good diagnostic accuracy for Nectin-4 expression in EC. Furthermore, Nectin-4 expression was associated with DNA mismatch repair (MMR) protein deficiency. Notably, the high Nectin-4 expression group of patients with MSH2/6-deficient EC had shorter progression-free survival than that of the low Nectin-4 expression group. The number of lymphovascular space invasion-positive patients in groups with MMR deficiency and high Nectin-4 expression was also increased compared with that in the low Nectin-4 expression group. Bioinformatics analysis revealed that alteration in Nectin-4 and MMR genes is associated with Nectin-4 expression in EC. To the best of our knowledge, this is the first study to show that Nectin-4 expression may be a potential biomarker for EC diagnosis and that high Nectin-4 expression in MMR-deficient patients with EC can predict short progression-free survival, thus providing clues to identify patients for adjuvant therapy.

Prognostic value of ß-Arrestins in combination with glucocorticoid receptor in epithelial ovarian cancer.

Hormones may be key factors driving cancer development, and epidemiological findings suggest that steroid hormones play a crucial role in ovarian tumorigenesis. We demonstrated that high glucocorticoid receptor (GR) expression is associated with a poor prognosis of epithelial ovarian cancer. Recent studies have shown that the GR affects ß-arrestin expression, and vice versa. Hence, we assessed the clinical significance of ß-arrestin expression in ovarian cancer and determined whether ß-arrestin and the GR synergistically have clinical significance and value as prognostic factors. We evaluated the expression of ß-arrestins 1 and 2 and the GR in 169 patients with primary epithelial ovarian cancer using immunohistochemistry. The staining intensity was graded on a scale of 0-4 and multiplied by the percentage of positive cells. We divided the samples into two categories based on the expression levels. ß-arrestin 1 and GR expression showed a moderate correlation, whereas ß-arrestin 2 and GR expression did not demonstrate any correlation. Patients with high ß-arrestin 1 and 2 expression exhibited improved survival rates, whereas patients with low GR expression showed a better survival rate. Patients with high ß-arrestin 1 and low GR levels had the best prognosis among all groups. ß-arrestin is highly expressed in ovarian cancer, suggesting its potential as a diagnostic and therapeutic biomarker. The combination of ß-arrestin and GR demonstrated greater predictive prognostic power than GR expression alone, implicating another possible role in prognostication.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

PURPOSE: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. MATERIALS AND METHODS: From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. RESULTS: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). CONCLUSION: The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Over-expression of rice leucine-rich repeat protein results in activation of defense response, thereby enhancing resistance to bacterial soft rot in Chinese cabbage.

Pectobacterium carotovorum subsp. carotovorum causes soft rot disease in various plants, including Chinese cabbage. The simple extracellular leucine-rich repeat (eLRR) domain proteins have been implicated in disease resistance. Rice leucine-rich repeat protein (OsLRP), a rice simple eLRR domain protein, is induced by pathogens, phytohormones, and salt. To see whether OsLRP enhances disease resistance to bacterial soft rot, OsLRP was introduced into Chinese cabbage by Agrobacterium-mediated transformation. Two independent transgenic lines over-expressing OsLRP were generated and further analyzed. Transgenic lines over-expressing OsLRP showed enhanced disease resistance to bacterial soft rot compared to non-transgenic control. Bacterial growth was retarded in transgenic lines over-expressing OsLRP compared to non-transgenic controls. We propose that OsLRP confers enhanced resistance to bacterial soft rot. Monitoring expression of defense-associated genes in transgenic lines over-expressing OsLRP, two different glucanases and Brassica rapa polygalacturonase inhibiting protein 2, PDF1 were constitutively activated in transgenic lines compared to non-transgenic control. Taken together, heterologous expression of OsLRP results in the activation of defense response and enhanced resistance to bacterial soft rot.