Knockdown of apoptosis signal-regulating kinase 1 modulates basal glycogen synthase kinase-3β kinase activity and regulates cell migration

AbstractGSK-3β is a basally active kinase. Axin forms a complex with GSK-3β and β-catenin; this complex promotes the GSK-3β-dependent phosphorylation of β-catenin, thereby inducing its degradation. However, the inhibition of GSK-3β provokes cell migration via the dysregulation of β-catenin. In this study, we determined that the level of apoptosis signal-regulating kinase 1 (ASK1) was lower in a metastatic breast cancer cell line, compared to that of non-metastatic cancer cell lines and the knockdown of ASK1 not only induces β-catenin activation via the inhibition of GSK-3β and collapsing the subsequent protein complex by regulating Axin dynamics, but also stimulates cell migration. Together, the blockage of the GSK-3β–β-catenin pathway resulting from the knockdown of ASK1 modulates the migration of breast cancer cells

Carbon and nitrogen accumulation and decomposition from coarse woody debris in a naturally regenerated Korean red pine (pinus densiflora S. et Z.) forest

The contribution of coarse woody debris (CWD) to forest carbon (C) and nitrogen (N) dynamics is poorly quantified. This study quantified total C and N content in CWD and estimated the decomposition rates of CWD at different decay stages in a 70-year-old naturally regenerated Korean red pine forest (Pinus densiflora S. et Z.). The N concentration in CWD varied among species and decay classes (from 0.15% to 0.82%), and exhibited a decreasing pattern in C:N ratios with increasing decay class. Total CWD amounts of 4.84 Mg C ha−1, dominated by pine logs (45.4%) and decay class III (40.0%), contained total N of 20.48 kg N ha−1, which was approximately nine times the N input from annual tree mortality. In addition, this study demonstrated that the decay constant rate k was 0.2497 for needle litter, whereas k values were 0.0438, 0.0693, 0.1054, and 0.1947 for red pine CWD of decay class I, II, III, and IV, respectively. The decay rates were significantly related to wood density, N concentration, and C:N ratio across the decay classes of CWD. The results suggest that the C:N ratio of CWD is a key factor affecting its decomposition

Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3 beta-mediated B-cell lymphoma 2 regulation

Glycogen synthase kinase-3 beta (GSK-3 beta) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3 beta and that GSK-3 beta-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK3 beta siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3 beta, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3 beta, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal-and paclitaxel-treated cells. Furthermore, we demonstrate that GSK-3 beta-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3 beta-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy.clos

The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency

In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and anti-inflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4+/+ BMDCs was not observed in TLR4-/- BMDCs. Furthermore, FAP induced DC-mediated CD8+ T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway

Factors associated with late recurrence after completion of 5-year adjuvant tamoxifen in estrogen receptor positive breast cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Recent large trials have shown the survival benefits of 10-year use of tamoxifen by reducing late recurrence compared with 5-year therapy in estrogen receptor(ER)-positive breast cancer. We tried to identify clinical factors associated with the late recurrence. Methods We reviewed our database of ER-positive patients who had received operations between 1996 and 2006 in two institutions. We selected 444 who had completed 5-year tamoxifen and were disease-free up to 10 years after the operation. Patients who had received aromatase inhibitors with any regimens were excluded. As a late recurrence group, 139 patients were identified who had completed 5-year tamoxifen, but had recurrence afterwards. Among them, 61 had local/contralateral breast recurrence and 78 had distant metastasis. The median follow-up was 9.7 years. Clinicopathological factors at the time of initial operation, such as age, menopausal status, progesterone receptor expression, HER2 status, tumor grade and Ki-67, were compared between the disease-free group and the late recurrence group. Results In a univariate analysis, tumor size (>2 cm), lymph node metastasis and high histologic grade were significantly associated with late recurrences (p < 0.05). In a multivariate analysis, only axillary lymph node metastasis was significant (p < 0.001). Late distant metastasis was significantly associated with tumor size and axillary lymph node metastasis (p = 0.038, p < 0.001,respectively). Late local/contralateral breast recurrence was associated with axillary lymph node metastasis (p = 0.042). Conclusions Our data showed axillary lymph node metastasis at initial operation was the only risk factor of late recurrence after completion of tamoxifen for 5 years. Our results can be helpful in making decisions to use extended tamoxifen beyond 5 years

Chest Computed Tomography (CT) Immediately after CT-Guided Transthoracic Needle Aspiration Biopsy as a Predictor of Overt Pneumothorax

BACKGROUND/AIMS: This study examined the correlation between pneumothorax detected by immediate post-transthoracic needle aspiration-biopsy (TTNB) chest computed tomography (CT) and overt pneumothorax detected by chest PA, and investigated factors that might influence the correlation. METHODS: Adult patients who had undergone CT-guided TTNB for lung lesions from May 2003 to June 2007 at Seoul National University Bundang Hospital were included. Immediate post-TTNB CT and chest PA follow-up at 4 and 16 hours after CT-guided TTNB were performed in 934 patients. RESULTS: Pneumothorax detected by immediate chest CT (CT-pneumothorax) was found in 237 (25%) and overt pneumothorax was detected by chest PA follow-up in 92 (38.8%) of the 237 patients. However, overt pneumothorax was found in 18 (2.6%) of the 697 patients without CT-pneumothorax. The width and depth of CT-pneumothorax were predictive risk factors for overt pneumothorax. CONCLUSIONS: CT-pneumothorax is very sensitive for predicting overt pneumothorax, and the width and depth on CT-pneumothorax are reliable risk factors for predicting overt pneumothorax.ope