BRCA1: linking HOX to breast cancer suppression

Homeobox (HOX) genes play key roles in embryogenesis and tissue differentiation. Recently, a number of groups have reported altered HOX gene expression in breast cancer. However, the mechanism of HOX gene regulation and the search for direct targets of its transcriptional regulatory function have been minimally fruitful. Recently, Gilbert and colleagues reported that HOXA9 restrains breast cancer progression by upregulation of BRCA1, a tumor suppressor. This finding raises our hope that more, rather elusive targets of HOX genes important in tumor progression or suppression will be found in the future

Effective treatment of ductal carcinoma in situ with a HER-2-targeted alpha-particle emitting radionuclide in a preclinical model of human breast cancer

The standard treatment for ductal carcinoma in situ (DCIS) of the breast is surgical resection, followed by radiation. Here, we tested localized therapy of DCIS in mice using the immunoconjugate 225Ac linked-trastuzumab delivered through the intraductal (i.duc) route. Trastuzumab targets HER-2/neu, while the alpha-emitter 225Ac (half-life, 10 days) delivers highly cytotoxic, focused doses of radiation to tumors. Systemic 225Ac, however, elicits hematologic toxicity and at high doses free 213Bi, generated by its decay, causes renal toxicity. I.duc delivery of the radioimmunoconjugate could bypass its systemic toxicity. Bioluminescent imaging showed that the therapeutic efficacy of intraductal 225Ac-trastuzumab (10-40 nCi per mammary gland; 30-120 nCi per mouse) in a DCIS model of human SUM225 cancer cells in NSG mice was significantly higher (p<0.0003) than intravenous (120 nCi per mouse) administration, with no kidney toxicity or loss of body weight. Our findings suggest that i.duc radioimmunotherapy using 225Ac-trastuzumab deserves greater attention for future clinical development as a treatment modality for early breast cancer

Current status of groundwater monitoring networks in Korea

Korea has been operating groundwater monitoring systems since 1996 as the Groundwater Act enacted in 1994 enforces nationwide monitoring. Currently, there are six main groundwater monitoring networks operated by different government ministries with different purposes: National Groundwater Monitoring Network (NGMN), Groundwater Quality Monitoring Network (GQMN), Seawater Intrusion Monitoring Network (SIMN), Rural Groundwater Monitoring Network (RGMN), Subsidiary Groundwater Monitoring Network (SGMN), and Drinking Water Monitoring Network (DWMN). The Networks have a total of over 3500 monitoring wells and the majority of them are now equipped with automatic data loggers and remote terminal units. Most of the monitoring data are available to the public through internet websites. These Networks have provided scientific data for designing groundwater management plans and contributed to securing the groundwater resource particularly for recent prolonged drought seasons. Each Network, however, utilizes its own well-specifications, probes, and telecommunication protocols with minimal communication with other Networks, and thus duplicate installations of monitoring wells are not uncommon among different Networks. This mini-review introduces the current regulations and the Groundwater Monitoring Networks operated in Korea and provides some suggestions to improve the sustainability of the current groundwater monitoring system in Korea

Sensitivity Analysis of Event-Specific Calibration Data and Its Application to Modeling of Subaerial Storm Erosion under Complex Bathymetry

Key parameters in a process-based model depicting the morphological changes during storm events should be adjusted to simulate the hydro- and morphodynamics, leading to site-, profile-, and event-specific calibration. Although area models eliminate variability in calibrated parameters along with each profile in complex bathymetry, the amount of influence datasets with different wave conditions have on model performance is still unclear in an area model in a given parameter space. This study collected hydrodynamic and bathymetric field data over four different storm conditions (two single and two cluster storms) at Maengbang Beach, South Korea. The numerical model XBeach was adopted using four storm datasets with four key parameters to examine the influence of event-specific calibration data on subaerial storm erosion. When using clustered storm data, a relatively limited number of parameter combinations showed higher model sensitivity to different parameter sets as opposed to single storm data with the same parameter sets. Model sensitivity to different storm events was correlated with cumulative storm power and resultant erosion volume in comparison with other features in the datasets. The results are expected to guide the selection of an event-specific dataset with various morphological and hydrodynamic factors in an area model under complex bathymetry

Process-Based Model Prediction of Coastal Dune Erosion through Parametric Calibration

Coastal dunes are important morphological features for both ecosystems and coastal hazard mitigation. Because understanding and predicting dune erosion phenomena is very important, various numerical models have been developed to improve the accuracy. In the present study, a process-based model (XBeachX) was tested and calibrated to improve the accuracy of the simulation of dune erosion from a storm event by adjusting the coefficients in the model and comparing it with the large-scale experimental data. The breaker slope coefficient was calibrated to predict cross-shore wave transformation more accurately. To improve the prediction of the dune erosion profile, the coefficients related to skewness and asymmetry were adjusted. Moreover, the bermslope coefficient was calibrated to improve the simulation performance of the bermslope near the dune face. Model performance was assessed based on the model-data comparisons. The calibrated XBeachX successfully predicted wave transformation and dune erosion phenomena. In addition, the results obtained from other two similar experiments on dune erosion with the same calibrated set matched well with the observed wave and profile data. However, the prediction of underwater sand bar evolution remains a challenge

Simultaneous blockade of IL-6 and CCL5 signaling for synergistic inhibition of triple-negative breast cancer growth and metastasis

Abstract Background Metastatic triple-negative breast cancer (TNBC) is a heterogeneous and incurable disease. Numerous studies have been conducted to seek molecular targets to treat TNBC effectively, but chemotherapy is still the main choice for patients with TNBC. We have previously presented evidence of the important roles of interleukin-6 (IL-6) and chemokine (C-C motif) ligand 5 (CCL5) in TNBC tumor growth and metastasis. These experiments highlighted the importance of the crosstalk between cancer cells and stromal lymphatic endothelial cells (LECs) in tumor growth and metastasis. Methods We examined the viability and migration of MDA-MB-231-LN, SUM149, and SUM159 cells co-cultured with LECs when treated with maraviroc (CCR5 inhibitor) and tocilizumab (anti-IL-6 receptor antibody). To assess the anti-tumor effects of the combination of these two drugs in an athymic nude mouse model, MDA-MB-231-LN cells were implanted in the mammary fat pad and maraviroc (8 mg/kg, orally daily) and cMR16-1 (murine surrogate of the anti-IL-6R antibody, 10 mg/kg, IP, 3 days a week) were administrated for 5 weeks and effects on tumor growth and thoracic metastasis were measured. Results In this study, we used maraviroc and tocilizumab to confirm that IL-6 and CCL5 signaling are key pathways promoting TNBC cell proliferation and migration. Further, in a xenograft mouse model, we showed that tumor growth was dramatically inhibited by cMR16-1, the mouse version of the anti-IL6R antibody. The combination of maraviroc and cMR16-1 caused significant reduction of TNBC tumor growth compared to the single agents. Significantly, the combination of maraviroc and cMR16-1 abrogated thoracic metastasis. Conclusion Taken together, these findings show that IL-6 and CCL5 signaling, which promote crosstalk between TNBC and lymphatic vessels, are key enhancers of TNBC tumor growth and metastasis. Furthermore, these results demonstrate that a drug combination inhibiting these pathways may be a promising therapy for TNBC patients

Sensitivity Analysis of Event-Specific Calibration Data and Its Application to Modeling of Subaerial Storm Erosion under Complex Bathymetry

Key parameters in a process-based model depicting the morphological changes during storm events should be adjusted to simulate the hydro- and morphodynamics, leading to site-, profile-, and event-specific calibration. Although area models eliminate variability in calibrated parameters along with each profile in complex bathymetry, the amount of influence datasets with different wave conditions have on model performance is still unclear in an area model in a given parameter space. This study collected hydrodynamic and bathymetric field data over four different storm conditions (two single and two cluster storms) at Maengbang Beach, South Korea. The numerical model XBeach was adopted using four storm datasets with four key parameters to examine the influence of event-specific calibration data on subaerial storm erosion. When using clustered storm data, a relatively limited number of parameter combinations showed higher model sensitivity to different parameter sets as opposed to single storm data with the same parameter sets. Model sensitivity to different storm events was correlated with cumulative storm power and resultant erosion volume in comparison with other features in the datasets. The results are expected to guide the selection of an event-specific dataset with various morphological and hydrodynamic factors in an area model under complex bathymetry

Additional file 1: of Simultaneous blockade of IL-6 and CCL5 signaling for synergistic inhibition of triple-negative breast cancer growth and metastasis

Figure S1. Cellular viability assays of co-cultured SUM149 (A) and SUM159 (B) cells on the bottom chambers with LECs on the top chamber in treatment with various concentration of maraviroc and d tocilizumab (transwell plates). The cellular viability was measured for 72 h by MTT assay (*P < 0.001, n = 3). C Crystal violet staining assay was performed in treatment with maraviroc (2 uM), tocilizumab (200 μg/ml), and the combination of maraviroc and tocilizumab. Figure S2. Migration assay of SUM149 (A) and SUM159 (B) cells (top chamber) in CM (bottom chamber) from LECs co-cultured with two TNBC cells with treatment with maraviroc, tocilizumab, and the combination of both. The migrated cells were counted for 24 h by the crystal violet staining. The representative migration is shown. (**P < 0.001, n = 3). C Migration assay of TNBC cells in CM from LECs co-cultured with TNBC cells with tocilizumab pre-treatment. The cells were pre-labeled with Cell Tracker Green and the migration was measured using the Oris cell migration kit. ELISA of human CCL5 (Quantikine ELISA, R&D System) in the CM of LECs co-cultured with SUM149 (D) and SUM159 (E) cells pre-treated tocilizumab (*P < 0.001, n = 3). (PDF 271 kb