Patterns of Recurrence after Breast-Conserving Treatment for Early Stage Breast Cancer by Molecular Subtype

Purpose: To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer. Methods: The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive. Results: The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as th

SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion

Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4 mice (Salm3, Salm4) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion. © The Author(s) 2016110101sciescopu

Experimental Investigation on the Behavior of Bracing Damper Systems by Utilizing Metallic Yielding and Recentering Material Devices

With the aim of effectively reducing the structural damage caused by earthquake events, bracing systems equipped with retrofitting damper devices, which take advantage of the energy dissipation and impact absorption, have been widely used in practical construction sites. These bracing dampers, however, have been recognized as expendable supplies for easily replacing the damaged ones after a strong earthquake because they are commonly designed to undergo concentrated force and deformation for the purpose of protecting the main structural members such as the columns and beams. In this paper, the use of new superelastic shape memory alloy (SMA) dampers that can partially recover their original configuration is proposed to decrease the repair cost. In addition, the conventional steel dampers used for improving the energy dissipation arising due to metallic yielding are additionally integrated into the bracing member. The behaviors of such bracing systems with the damper devices were reproduced in experimental tests with the cyclic loading history, and then their strength capacity and recentering capability were estimated based on the experiment results. Finally, additional experimental tests were performed by imposing cyclic loading histories with different loading speeds on the superelastic SMA and steel plate damper specimens

No association between HLA-DRB1 alleles and susceptibility to advanced stage endometriosis in a Korean population

BACKGROUND: The aetiological factors of endometriosis still remain poorly understood. While there is growing evidence that genetic and immunological factors play important roles in the pathogenesis of the disease, HLA-DRB1 alleles have been reported to be associated with the risk of endometriosis in Japanese populations. This study was performed to determine whether susceptibility to advanced endometriosis is also associated with HLA-DRB1 alleles in a Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 100 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. HLA-DRB1 genotyping was carried out in two steps. Low to intermediate resolution typing was performed by PCR sequence-specific oligonucleotide hybridization method, followed by high resolution typing utilizing group-specific amplification and PCR-single strand conformation polymorphism method. Distribution of HLA-DRB1 alleles was compared with that of 800 unrelated ethnically matched individuals as well as 108 healthy female subjects. RESULTS: Genotyping revealed that the distribution of HLA-DRB1 alleles in patients with advanced endometriosis was not different from that in the two control groups. CONCLUSIONS: The findings of the present study suggest that susceptibility of advanced endometriosis is not associated with HLA-DRB1 alleles in a Korean population, which is apparently not the case in the Japanese population

Proton Beam Therapy versus Photon Radiotherapy for Stage I Non-Small Cell Lung Cancer

Proton beam therapy (PBT) and photon radiotherapy for stage I non-small cell lung cancer (NSCLC) were compared in terms of clinical outcomes and dosimetry. Data were obtained from patients who underwent PBT or photon radiotherapy at two institutions—the only two facilities where PBT is available in the Republic of Korea. Multivariate Cox proportional hazards models and propensity score-matched analyses were used to compare local progression-free survival (PFS) and overall survival (OS). Survival and radiation exposure to the lungs were compared in the matched population. Of 289 patients included in the analyses, 112 and 177 underwent PBT and photon radiotherapy, respectively. With a median follow-up duration of 27 months, the 2-year local PFS and OS rates were 94.0% and 83.0%, respectively. In the multivariate analysis, a biologically effective dose (BED10, using α/β = 10 Gy) of ≥125 cobalt gray equivalents was significantly associated with improved local PFS and OS. In the matched analyses, the local PFS and OS did not differ between groups. However, PBT showed significantly lower lung and heart radiation exposure in the mean dose, V5, and V10 than photon radiotherapy. PBT significantly reduced radiation exposure to the heart and lungs without worsening disease control in stage I NSCLC patients

Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

BACKGROUND: Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. METHODS: We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. RESULTS: Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. CONCLUSIONS: This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated mitochondrial alteration in a mouse model of glaucoma.

PurposeTo test whether a diet supplemented with coenzyme Q10 (CoQ10) ameliorates glutamate excitotoxicity and oxidative stress-mediated retinal ganglion cell (RGC) degeneration by preventing mitochondrial alterations in the retina of glaucomatous DBA/2J mice.MethodsPreglaucomatous DBA/2J and age-matched control DBA/2J-Gpnmb(+) mice were fed with CoQ10 (1%) or a control diet daily for 6 months. The RGC survival and axon preservation were measured by Brn3a and neurofilament immunohistochemistry and by conventional transmission electron microscopy. Glial fibrillary acidic protein (GFAP), superoxide dismutase-2 (SOD2), heme oxygenase-1 (HO1), N-methyl-d-aspartate receptor (NR) 1 and 2A, and Bax and phosphorylated Bad (pBad) protein expression was measured by Western blot analysis. Apoptotic cell death was assessed by TUNEL staining. Mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (Tfam)/oxidative phosphorylation (OXPHOS) complex IV protein expression were measured by real-time PCR and Western blot analysis.ResultsCoenzyme Q10 promoted RGC survival by approximately 29% and preserved the axons in the optic nerve head (ONH), as well as inhibited astroglial activation by decreasing GFAP expression in the retina and ONH of glaucomatous DBA/2J mice. Intriguingly, CoQ10 significantly blocked the upregulation of NR1 and NR2A, as well as of SOD2 and HO1 protein expression in the retina of glaucomatous DBA/2J mice. In addition, CoQ10 significantly prevented apoptotic cell death by decreasing Bax protein expression or by increasing pBad protein expression. More importantly, CoQ10 preserved mtDNA content and Tfam/OXPHOS complex IV protein expression in the retina of glaucomatous DBA/2J mice.ConclusionsOur findings suggest that CoQ10 may be a promising therapeutic strategy for ameliorating glutamate excitotoxicity and oxidative stress in glaucomatous neurodegeneration