Pilot study of the Korean national breast implant registry: Experiences and lessons learned.

BACKGROUND: To improve the safety and early detection of unexpected breast implant-related complications, the Korean Breast Implant Registry (K-BIR) was launched in 2020 in cooperation with the Korean Society of Plastic and Reconstructive Surgeons and the Korean Ministry of Food and Drug Safety, and a pilot study was conducted. OBJECTIVE: This article provides an overview of our pilot study and experiences of the K-BIR. METHODS: The dataset to be used in the pilot form of K-BIR was constructed by holding online surveys and meetings focusing on the global breast device registry's minimum dataset. A pilot study was implemented from April 1, 2020, to July 31, 2020, with six university teaching hospitals and four private clinics. RESULTS: During the pilot study period, 325 patients, 451 procedures, and 366 implants were entered into the K-BIR. The most common procedure registered was augmentation mammaplasty (30%) for cosmetic indications, followed by direct-to-implant breast reconstruction (27%). Smooth silicone implant was the most common type (73%) of implant used. A feedback survey after the pilot study included questions about the registration rate compared with an actual procedure, entry time, reasons for difficulty in entry, and additional data needed. CONCLUSIONS: The continuous maintenance and development of K-BIR will require an effective dataset, a strengthened legal system for an opt-out registry and personal data protection, various incentives for increasing participation rates, and an electronic platform that patients, manufacturers, and clinicians can easily access. K-BIR has the potential to provide quality assurance and outcomes for research and post-market surveillance systems for breast implants as well as methods for enhancing patient safety.

The Effects of N-terminal Mutations on ß-amyloid Peptide Aggregation and Toxicity.

Human amyloid ß1-42 (hAß1-42) peptides are known to self-aggregate into oligomers that contribute to the degeneration of neurons and development of Alzheimer's disease (AD) pathology. Unlike humans, rodents do not develop AD, possibly due to differences in three amino acids (R5G, Y10F and H13R) within the hydrophilic N-terminal domain of Aß1-42. This is partly supported by evidence that hAß1-42 is more prone to fibrillization and has a higher cellular toxicity than rodent Aß1-42 (rAß1-42). Mutagenesis studies, however, have shown that correlation between fibrillization potential and toxicity is not always direct. Thus, to understand better how N-terminal mutations can affect hAß1-42 toxicity through oligomerization, we evaluated fibrillization kinetics, oligomer sizes and toxicity profiles of double mutant (human toward rodent) Aß1-42. Additionally, we tested the mutant peptides in combination with hAß1-42, to assess effects on hAß1-42 aggregation/toxicity. Our results clearly show that double mutations to humanize rAß1-42 result in a significantly reduced efficiency of fibril formation, as determined by Thioflavin-T aggregation assays and confirmed with electron micrographic studies. Interestingly, the mutants are still able to aggregate into oligomers, which are predominantly larger than those comprised of hAß1-42. Our cell viability experiments further showed a rank order of oligomer toxicity of hAß1-42 > rAß1-42 ≫ mutant Aß1-42, suggesting that toxicity can be influenced by N-terminal Aß1-42 mutations via reduction of fibril formation and/or alteration of oligomer size. These results, taken together, confirm that N-terminal mutations can affect Aß fibril and oligomer formation with reduced toxicity despite lying outside the core amyloid region of Aß peptide.

Whole-Tumor Histogram and Texture Analyses of DTI for Evaluation of IDH1-Mutation and 1p/19q-Codeletion Status in World Health Organization Grade II Gliomas.

BACKGROUND AND PURPOSE: Prediction of the isocitrate dehydrogenase 1 (IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine IDH1-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas. MATERIALS AND METHODS: Ninety-three patients with World Health Organization grade II gliomas with known IDH1-mutation and 1p/19q-codeletion status (18 IDH1 wild-type, 45 IDH1 mutant and no 1p/19q codeletion, 30 IDH1-mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the IDH1-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for IDH1 wild-type tumors and 1p/19q-codeletion status in IDH1-mutant subgroups were evaluated using the least absolute shrinkage and selection operator. RESULTS: Various histogram and texture parameters differed significantly according to IDH1-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an IDH1 wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in IDH1-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807. CONCLUSIONS: Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the IDH1-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.

Prediction of IDH1-Mutation and 1p/19q-Codeletion Status Using Preoperative MR Imaging Phenotypes in Lower Grade Gliomas.

BACKGROUND AND PURPOSE: WHO grade II gliomas are divided into three classes: isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant and no 1p/19q codeletion, and IDH-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas. MATERIALS AND METHODS: MR imaging scans of 175 patients with lower grade gliomas with known IDH1 mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set. MR imaging features were reviewed by using Visually AcceSAble Rembrandt Images (VASARI); their associations with molecular markers were assessed. The predictive power of imaging features for IDH1-wild type tumors was evaluated using the Least Absolute Shrinkage and Selection Operator. We tested the model in a validation set (40 subjects). RESULTS: Various imaging features were significantly different according to IDH1 mutation. Nonlobar location, larger proportion of enhancing tumors, multifocal/multicentric distribution, and poor definition of nonenhancing margins were independent predictors of an IDH1 wild type according to the Least Absolute Shrinkage and Selection Operator. The areas under the curve for the prediction model were 0.859 and 0.778 in the discovery and validation sets, respectively. The IDH1-mutant, 1p/19q-codeleted group frequently had mixed/restricted diffusion characteristics and showed more pial invasion compared with the IDH1-mutant, no codeletion group. CONCLUSIONS: Preoperative MR imaging phenotypes are different according to the molecular markers of lower grade gliomas, and they may be helpful in predicting the IDH1-mutation status.

The Initial Area Under the Curve Derived from Dynamic Contrast-Enhanced MRI Improves Prognosis Prediction in Glioblastoma with Unmethylated MGMT Promoter.

BACKGROUND AND PURPOSE: Although perfusion and permeability MR parameters have known to have prognostic value, they have reproducibility issues. Our aim was to evaluate whether the initial area under the time-to-signal intensity curve (IAUC) derived from dynamic contrast-enhanced MR imaging can improve prognosis prediction in patients with glioblastoma with known MGMT status. MATERIALS AND METHODS: We retrospectively examined 88 patients with glioblastoma who underwent preoperative dynamic contrast-enhanced MR imaging. The means of IAUC values at 30 and 60 seconds (IAUC30mean and IAUC60mean) were extracted from enhancing tumors. The prognostic values of IAUC parameters for overall survival and progression-free survival were assessed with log-rank tests, according to the MGMT status. Multivariate overall survival and progression-free survival models before and after adding the IAUC parameters as covariates were explored by net reclassification improvement after receiver operating characteristic analysis for 1.5-year overall survival and 1-year progression-free survival and by random survival forest. RESULTS: High IAUC parameters were associated with worse overall survival and progression-free survival in the unmethylated MGMT group, but not in the methylated group. In the unmethylated MGMT group, 1.5-year overall survival and 1-year progression-free survival prediction improved significantly after adding IAUC parameters (overall survival area under the receiver operating characteristic curve, 0.86; progression-free survival area under the receiver operating characteristic curve, 0.74-0.76) to the model with other prognostic factors (overall survival area under the receiver operating characteristic curve, 0.81; progression-free survival area under the receiver operating characteristic curve, 0.69; P < .05 for all) except in the case of IAUC60mean for 1-year progression-free survival prediction (P = .059). Random survival forest models indicated that the IAUC parameters were the second or most important predictors in the unmethylated MGMT group, except in the case of the IAUC60mean for progression-free survival. CONCLUSIONS: IAUC can be a useful prognostic imaging biomarker in patients with glioblastoma with known MGMT status, improving prediction of glioblastoma prognosis with the unmethylated MGMT promoter status.

Acute toxicity of organic antifouling biocides to phytoplankton Nitzschia pungens and zooplankton Artemia larvae.

The toxicity of the antifouling biocides Irgarol 1051, Diuron, Chlorothalonil, Dichlofluanid, Sea-nine 211, Copper pyrithione, Zinc pyrithione, Ziram and Zineb were evaluated on Nitzschia pungens and Artemia larvae. Results showed that EC50 for Irgarol 1051 was 0.586µgl-1 was the strongest effect on N. pungens following by Copper pyrithione (4.908µgl-1), Ziram (5.421µgl-1), Zinc pyrithione (5.513µgl-1), Diuron (6.640µgl-1), Zineb (232.249µgl-1), Sea-nine 211(267.368µgl-1), Chlorothalonil (360.963µgl-1) and Dichlofluanid (377.010µgl-1) in 96h. In Artemia larvae, the biocides were evaluated the LC50 for larval survivals at 48h. Sea-nine 211 and Copper pyrithione were 0.318 and 0.319mgl-1. Chlorothalonil, Zinc pyrithione and Ziram were 2.683, 3.147 and 4.778mgl-1. Irgarol 1051, Diuron, Zineb and Dichlofluanid were 9.734, 30.573, 41.170 and 154.944mgl-1. These results provide baseline data concerning the toxicity of antifouling biocides against marine environment.

Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature.

BACKGROUND: Leptomeningeal dissemination of hemangioblastomas (HB) of the central nervous system (CNS) is extremely rare. Few studies have reported leptomeningeal involvement in sporadic HB or in HB associated with von Hippel-Lindau syndrome. The clinical and radiological features of leptomeningeal involvement in HB after surgery have not been described in detail. MATERIALS AND METHODS: This retrospective case review involved patients from three different tertiary referral centers with leptomeningeal dissemination of HB after surgery for the primary mass. A literature review was also performed to describe the clinical and radiological characteristics and long-term outcomes of patients who developed leptomeningeal dissemination after initial surgical resection. RESULTS: This study included seven patients, five males and two females, ranging in age from 36 to 54 years. Incidence of leptomeningeal dissemination in patients with HB was about 4.3 % (3/69). It appeared at a mean 94.9 months (range, 39-204 months) after gross total resection of CNS HBs. Three of the seven patients died 5, 38, and 79 months, respectively, after diagnosis of leptomeningeal dissemination. Review of the literature identified 21 patients with characteristics of leptomeningeal dissemination similar to those in our series. CONCLUSIONS: Leptomeningeal dissemination of HB is a rare pattern of long-term recurrence. Long-term outcomes may be fatal. The long developmental period suggests that early detection and aggressive management may improve prognosis in patients with CNS leptomeningeal dissemination of HB.

The Added Prognostic Value of Preoperative Dynamic Contrast-Enhanced MRI Histogram Analysis in Patients with Glioblastoma: Analysis of Overall and Progression-Free Survival.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging in patients with glioblastoma is controversial. We investigated the added prognostic value of dynamic contrast-enhanced MR imaging to clinical parameters and molecular biomarkers in patients with glioblastoma by using histogram analysis. MATERIALS AND METHODS: This retrospective study consisted of 61 patients who underwent preoperative dynamic contrast-enhanced MR imaging for glioblastoma. The histogram parameters of dynamic contrast-enhanced MR imaging, including volume transfer constant, extravascular extracellular volume fraction, and plasma volume fraction, were calculated from entire enhancing tumors. Univariate analyses for overall survival and progression-free survival were performed with preoperative clinical and dynamic contrast-enhanced MR imaging parameters and postoperative molecular biomarkers. Multivariate Cox regression was performed to build pre- and postoperative models for overall survival and progression-free survival. The performance of models was assessed by calculating the Harrell concordance index. RESULTS: In univariate analysis, patients with higher volume transfer constant and extravascular extracellular volume fraction values showed worse overall survival and progression-free survival, whereas plasma volume fraction showed no significant correlation. In multivariate analyses for overall survival, the fifth percentile value of volume transfer constant and kurtosis of extravascular extracellular volume fraction were independently prognostic in the preoperative model, and kurtosis of volume transfer constant and extravascular extracellular volume fraction were independently prognostic in the postoperative model. For progression-free survival, independent prognostic factors were minimum and fifth percentile values of volume transfer constant and kurtosis of extravascular extracellular volume fraction in the preoperative model and kurtosis of extravascular extracellular volume fraction in the postoperative model. The performance of preoperative models for progression-free survival was significantly improved when minimum or fifth percentile values of volume transfer constant and kurtosis of extravascular extracellular volume fraction were added. CONCLUSIONS: Higher volume transfer constant and extravascular extracellular volume fraction values are associated with worse prognosis, and dynamic contrast-enhanced MR imaging may have added prognostic value in combination with preoperative clinical parameters, especially in predicting progression-free survival.

Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway.

Microbial metabolites, such as short-chain fatty acids (SCFAs), are highly produced in the intestine and potentially regulate the immune system. We studied the function of SCFAs in the regulation of T-cell differentiation into effector and regulatory T cells. We report that SCFAs can directly promote T-cell differentiation into T cells producing interleukin-17 (IL-17), interferon-γ, and/or IL-10 depending on cytokine milieu. This effect of SCFAs on T cells is independent of GPR41 or GPR43, but dependent on direct histone deacetylase (HDAC) inhibitor activity. Inhibition of HDACs in T cells by SCFAs increased the acetylation of p70 S6 kinase and phosphorylation rS6, regulating the mTOR pathway required for generation of Th17 (T helper type 17), Th1, and IL-10(+) T cells. Acetate (C2) administration enhanced the induction of Th1 and Th17 cells during Citrobacter rodentium infection, but decreased anti-CD3-induced inflammation in an IL-10-dependent manner. Our results indicate that SCFAs promote T-cell differentiation into both effector and regulatory T cells to promote either immunity or immune tolerance depending on immunological milieu.

Role of the superior turbinate when performing endoscopic endonasal transsphenoidal approach.

BACKGROUND: This study examined the relationship between the superior turbinate and natural ostium of the sphenoid sinus, as seen during the endoscopic endonasal transsphenoidal approach (EETSA) for sellar lesions and described how to enter the sphenoethmoid cell safely for complete exposure of the sellar floor, including adjacent vital structures such as the prominence of the optic nerve and carotid artery. MATERIALS AND METHODS: This study retrospectively reviewed the medical records and operative findings of 154 patients, who underwent EETSA between February 2009 and February 2011. We evaluated the location of the natural ostium of the sphenoid sinus relative to the superior turbinate and revealed the clinical significance of the superior turbinate as a surgical guide to enter into the sphenoethmoid cell during EETSA. RESULTS: The natural ostium of the sphenoid sinus was located medially to the posteroinferior end of the superior turbinate in 151 (98%) patients. In 1 patient, the natural ostia of the sphenoid sinus were located lateral to the superior turbinate bilaterally. Sphenoethmoid cell was encountered in 53 (34%) patients. We could easily enter the sphenoethmoid cell at the point where the superior turbinate was attached to the anterior wall of the sphenoid sinus. CONCLUSIONS: The superior turbinate is a good surgical landmark for identifying the natural ostium of the sphenoid sinus and as a guide for the surgical entrance to the sphenoethmoid cell extending to the sphenoid sinus during EETSA.

First report: Robotic pelvic exenteration for locally advanced rectal cancer.

AIM: The aim of this study was to present the feasibility and surgical outcome of robotic en bloc resection of the rectum and with prostate and seminal vesicle invaded by rectal cancer. METHOD: The details of three consecutive cases involving male patients in their forties, with locally invasive low rectal cancers are presented. The da Vinci robotic system was used by experienced colorectal and urological surgeons to perform en bloc resection of the rectum, prostate and seminal vesicles. RESULTS: In the first case, coloanal and vesico-urethral anastomoses were performed, and the second included an end colostomy and vesico-urethral anastomosis. The bladder and bulbar urethra were also removed en bloc in the third case, with robotic intracorporeal ileal conduit formation and end colostomy. There was no major complication postoperatively. In the second patient there was a minor leakage at the vesico-urethral anastomosis. The third was readmitted the following week with a urinary infection which settled with intravenous antibiotics. In the first case, the circumferential resection margin was microscopically positive but the patient is currently free of recurrence after 14 months. In the second and third cases, all margins were clear. CONCLUSION: This the first report of the use of the da Vinci robotic system for pelvic exenteration in patients with locally advanced rectal cancer invading the prostate and seminal vesicles. The robot may have a potential role in selected patients requiring exenterative pelvic surgery particularly in men.

The relaxant effect of ginseng saponin on the bladder and prostatic urethra: an in vitro and in vivo study.

AIM: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. MATERIALS AND METHODS: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10(-6)-10(-2)M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (P(ves)) and urethral perfusion pressure (UPP). RESULTS: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10(-3)M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10(-2)M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline P(ves) than the PBOO group. CONCLUSIONS: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.

c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells.

Uncovering the mechanisms that govern the maintenance of stem-like cancer cells is critical for developing therapeutic strategies for targeting these cells. Constitutive activation of c-Jun N-terminal kinase (JNK) has been reported in gliomas and correlates with histological grade. Here, we found that JNK signaling is crucial for the maintenance of 'stemness' in glioma cells. Sphere-cultured glioma cells showed more phosphorylation of JNK compared with serum-containing monolayer cultures. Importantly, blockade of JNK signaling with SP600125 or small interfering RNAs targeting JNK1 or JNK2 significantly reduced the CD133(+)/Nestin(+) population and suppressed sphere formation, colony formation in soft agar, and expression of stem cell markers in sphere-cultured glioma cells. Intriguingly, sphere-cultured glioma cells exhibited enhanced expression of Notch-2, but not Notch-1, -3 or -4, and JNK inhibition almost completely abrogated this increase. Blocking the phosphoinoside 3-kinase (PI3K)/Akt pathway with LY294002 or si-Akt also suppressed the self-renewal of sphere-cultured glioma cells. PI3K, but not Akt, had a role as an upstream kinase in JNK1/2 activation. In addition, treatment with si-JNK greatly increased etoposide- and ionizing radiation (IR)-induced cell death in glioma spheres. Consistent with glioma cell lines, glioma stem-like cells isolated from primary patient glioma cells also had a higher activity of JNK and Notch-2 expression. Importantly, inhibition of JNK2 led to a decrease of Notch-2 expression and suppressed the CD133(+)/Nestin(+) cell population in patient-derived primary glioma cells. Finally, downregulation of JNK2 almost completely suppressed intracranial tumor formation by glioma cells in nude mice. Taken together, these data demonstrate that JNK signaling is crucial for the maintenance of self-renewal and tumorigenicity of glioma stem-like cells and drug/IR resistance, and can be considered a promising target for eliminating stem-like cancer cells in gliomas.

Sports therapy for attention, cognitions and sociality.

The aim of the present study was to understand if sport improves attention symptoms, social competency, and cognitive functions in children with attention deficit and hyperactivity disorder (ADHD). The present study was designed as a 6-week, prospective trial, including 12 sessions of education/sports therapy. 13 ADHD children participated in a 90-min athletic activity (sports-cADHD) twice a week, while 15 ADHD children received education on behavior control (edu-cADHD). During the 6-week treatment period, the sports-cADHD group showed greater improvements in DuPaul's ADHD Rating Scale scores, parent and teacher version (K-ARS-PT), compared to those of the edu-sADHD group. The cognitive functions assessed with the digit symbol and Trail-Making Test part B (TMT B) were improved in the sports-cADHD group, while the cognitive functions observed in the edu-sADHD group were not significantly changed. The cooperativeness scores in the sports-cADHD group were greatly increased compared to those of the edu-sADHD group. The results demonstrated a positive correlation with sports and improvement in attention symptoms, cognitive symptoms and social skills. The results of the present study suggest that therapy in the form of athletic activity may increase social competency in children with ADHD, as demonstrated by improved cognitive functions.

Silencing of the GnRH type 1 receptor blocks the antiproliferative effect of the GnRH agonist, leuprolide, on the androgen-independent prostate cancer cell line DU145.

This study investigated the mechanism of action of a gonadotropin-releasing hormone (GnRH) agonist, leuprolide, on proliferation of the hormone-refractory prostate cancer cell line DU145, transfected with short hairpin RNA (shRNA), to reduce expression of the GNRHR1 gene (which encodes the GnRH type 1 receptor). DU145 cell proliferation in the presence of leuprolide (10(-9) and 10(-7) M) or control medium was measured before and after GnRHR1 knockdown. Reverse transcription-polymerase chain reaction and Western blot analysis were used to measure the degree of GNRHR1 silencing. DU145 cells treated with leuprolide (10(-9) and 10(-7) M) showed significant growth inhibition compared with control-treated DU145 cells. Transfection with GNRHR1 -shRNA significantly decreased GNRHR1 expression at 48 h. DU145 cells transfected with silencing GNRHR1 -shRNA showed normal growth patterns; however, there was no significant inhibition of proliferation of DU145 cells transfected with GNRHR1 -shRNA compared with cells transfected with control-shRNA in response to leuprolide. These data demonstrated that the antiproliferative effect of leuprolide was mediated by the GnRHR1.

Expression of RUNX3 in skin cancers.

BACKGROUND: Expression of Runt-related transcription factor 3 (RUNX3) is reduced in a large number of cancers. However, a few studies have reported higher expression of RUNX3 in several cancers, including basal cell carcinoma (BCC). In light of this, we explored the expression of RUNX3 in skin cancers generally, to determine whether it acts as an oncogene or a tumour-suppressor gene in skin tumours. AIM: To investigate the expression of RUNX3 in normal skin and malignant skin tumours. METHODS: RUNX3 expression was evaluated by western blotting in 24 specimens, comprising 6 malignant melanoma (MM), 6 squamous cell carcinoma (SCC), 6 BCC and 6 normal skin specimens. Immunohistochemical staining was carried out to analyse RUNX3 expression in 16 MM, 16 SCC and 16 BCC specimens. To identify where the protein was expressed, the cytoplasmic and nuclear protein expression of RUNX3 in skin cancer tissues was determined. A cell-proliferation study was performed on an MM line (G361) by small interfering (si)RNA transfection. RESULTS: The western blotting experiments showed that RUNX3 was not expressed in normal skin tissues, but it was overexpressed in all MM and SCC samples, and in five of the six BCC samples. Using immunochemistry, RUNX3 was found to be overexpressed in all cancer tissues analysed. Subcellular fraction analysis revealed that RUNX3 was expressed in the nuclei but not the cytoplasm of all the skin cancer tissues analysed, and RUNX3 silencing by siRNA in G361 cells resulted in a decrease in proliferation. CONCLUSIONS: Based on these results, we suggest that RUNX3 has an oncogenic potential and does not act as a tumour suppressor in skin cancers.

Long-term outcome of tamsulosin for patients with lower urinary tract symptoms according to the treatment response defined by lower urinary tract symptom outcomes score.

UNLABELLED: IMS: To evaluate long-term outcome of tamsuolsin 0.2 mg for benign prostatic hyperplasia (BPH) patients using a new subjective assessment of patient-reported outcomes and the lower urinary tract symptoms (LUTS) outcome score (LOS) over a 48-week period. METHODS: This study investigated the long-term outcomes of either well-responded or poorly responded patient group as defined by LOS at the period of 12 weeks after BPH treatment. Outcome parameters used in this study were the most bothersome symptoms, BPH K1-short form as well as International Prostate Symptom Score (IPSS), maximum flow rate (Qmax) and postvoiding residual urine volume at 24-, 36- and 48-week follow-up. RESULTS: Of the 414 patients recruited initially, 310 (75.2%) were defined as the responders and 39 (9.5%) as the non-responders to the treatment at 12 weeks, which was stratified by LOS. In this long-term study, the differences in improvement rates of clinical parameters between responder and non-responder groups at 12 weeks of treatment were maintained over the period of 48 weeks. Among the responder patients, most (75.6%) chose continuous administrations of tamsulosin. Improvements in clinical parameters were maintained in this subgroup. It is noteworthy that the improvements in clinical parameters of the non-responder group were dismal despite switching to the other treatment modalities. CONCLUSIONS: Long-term tamsulosin 0.2 mg for BPH patients is an effective treatment, both subjectively and objectively. Considering its integrative nature, LOS seemed to be one of the useful tools to predict the outcome after the management of LUTS.

Complementary roles of retinoic acid and TGF-ß1 in coordinated expression of mucosal integrins by T cells.

α(4) and ß(7) integrins, such as α(4)ß(1), α(4)ß(7), and α(E)ß(7), are major integrins required for migration of leukocytes into mucosal tissues. The mechanisms responsible for coordinated expression of these three integrins have been poorly elucidated to date. We report that expression of the Itg-α(4) subunit by both CD4(+) and CD8(+) T cells requires the retinoic acid signal. In contrast, transcription of Itg-α(E) genes is induced by the transforming growth factor-ß1 (TGFß1) signal. Expression of Itg-ß(7) is constitutive but can be further increased by TGFß1. Consistently, expression of α(4)-containing integrins is severely suppressed in vitamin A deficiency with a compensatory increase of α(E)ß(7), whereas expression of Itg-α(E) and Itg-ß(7) is decreased in TGFß-signal deficiency with a compensatory increase in α(4)ß(1). The retinoic acid-mediated regulation of α(4) integrins is required for specific migration of T cells in vitro and in vivo. These results provide central regulatory mechanisms for coordinated expression of the major mucosal integrins.

Therapeutic results of intra-arterial thrombolysis after full-dose intravenous tissue plasminogen activator administration.

BACKGROUND AND PURPOSE: IV administration of tPA is accepted as a standard treatment for acute cerebral ischemia, but the clinical outcomes cannot be guaranteed in patients who are not recanalized after IV-tPA and in those who are not eligible for IV-tPA. In this study, outcomes from groups of patients treated with additional IA thrombolytic therapy with the use or omission of IV-tPA administration were compared. MATERIALS AND METHODS: IA thrombolytic therapy (thrombolytic agents combined with mechanical intervention) was attempted in those patients who were not eligible for IV-tPA and who showed continuous major vessel occlusion after IV-tPA. Sixty-three patients were divided into 2 groups: a tPA group (n = 29, IA thrombolysis after IV-tPA) and a non-tPA group (n = 34, IA thrombolysis without IV-tPA). These groups were subdivided according to match or mismatch DWI/PWI after MR imaging. Treatment results were compared by recanalization rate, clinical outcome, mortality, and ICH rate. RESULTS: The recanalization rate was 79.3% in the tPA group and 55.9% in the non-tPA group (χ(2) test, P < .05). Subgroup analysis between DWI/PWI mismatch in the tPA group and DWI/PWI mismatch in the non-tPA group also showed no statistical difference in recanalization rate, favorable clinical outcome, and mortality (χ(2) test, P > .05), but the significant ICH rate was high in the tPA group (χ(2) test, P < .05). CONCLUSIONS: Additional IA thrombolytic treatment after full-dose IV-tPA administration might be an acceptable treatment option for patients with DWI/PWI mismatch.

The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut.

Migration and trafficking receptors of Th17 cells to mucosal tissues have been unclear. We report that Th17 cells preferentially migrate to the intestine and associated lymphoid tissues, and CCR6 is the homing receptor important for Th17 cell migration to certain tissue microenvironments of the intestine such as Peyer's patches and other sites where its ligand CCL20 is expressed. We found the cytokine transforming growth factor-beta1 is required for CCR6 expression whereas IL-2 suppresses it. CCR6-deficient Th17 cells aberrantly migrate to different compartments of the intestine. Surprisingly, administration of CCR6-deficient Th17 cells into severe combined immunodeficiency (SCID) mice led to excessive intestinal inflammation with increased Th1 but decreased Th17 cells and FoxP3(+) T cells. In addition, CCR6 deficiency led to aberrantly widespread effector T cells in the inflamed intestine of the SCID mice. We conclude that CCR6 regulates Th17 cell migration to the gut and effector T-cell balance/distribution in inflamed intestine.