Controlling the Phase Transformation of Alumina for Enhanced Stability and Catalytic Properties.

Current transition alumina catalysts require the presence of significant amounts of toxic, environmentally deleterious dopants for their stabilization. Herein, we report a simple and novel strategy to engineer transition aluminas to withstand aging temperatures up to 1200 °C without inducing the transformation to low-surface-area α-Al2O3 and without requiring dopants. By judiciously optimizing the abundance of dominant facets and the interparticle distance, we can control the temperature of the phase transformation from θ-Al2O3 to α-Al2O3 and the specific surface sites on the latter. These specific surface sites provide favorable interactions with supported metal catalysts, leading to improved metal dispersion and greatly enhanced catalytic activity for hydrocarbon oxidation. The results presented herein not only provide molecular-level insights into the critical factors causing deactivation and phase transformation of aluminas but also pave the way for the development of catalysts with improved activity for catalytic hydrocarbon oxidation.

Correction to: A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL.

The blots of control and docetaxel for caspase-9, caspase-3, caspase-8, Bcl-XL, and tubulin in the Figure 4f were reused from Figure 4 of our previous paper published in Journal of Urology in 2010 ( https://doi.org/10.1016/j.juro.2010.07.035 ).

Reappraisal of hMLH1 promoter methylation and protein expression status in the serrated neoplasia pathway.

AIMS: The aim of this study was to determine whether human mutL homologue 1 (hMLH1) inactivation precedes the progression of sessile serrated lesion (SSL) into SSL with cytological dysplasia (SSL/D) and to define the histological stage at which promoter methylation and inactivation of hMLH1 occur. METHODS AND RESULTS: Using the MassARRAY EpiTYPER assay and immunohistochemistry, we examined methylation levels and the protein expression status of hMLH1 in 33 SSL/Ds with conventional epithelial dysplasia and compared the results with those of control hyperplastic polyps (HPs) and SSLs. The methylation level of hMLH1 was higher in the dysplastic component than in the non-dysplastic component of SSL/Ds (P = 0.005), and differed significantly with regard to the degree of dysplasia (P = 0.002). The methylation levels of hMLH1 in the dysplastic component of SSL/Ds tended to be higher than those of control SSLs and HPs (P = 0.063 and P = 0.017, respectively). The loss of hMLH1 protein expression was identified in only 13 of 33 (39.39%) dysplastic components of SSL/Ds. CONCLUSION: Promoter methylation and loss of protein expression of hMLH1 are not parallel processes that occur concurrently. hMLH1 methylation is an early molecular event which occurs even in HP. However, the loss of hMLH1 expression is a much later step, found in approximately 40% of SSL/Ds at various histological stages. Notably, the loss of hMLH1 protein expression does not necessarily precede the development of cytological dysplasia in SSL.

Humidifier disinfectant-associated children's interstitial lung disease: Computed tomographic features, histopathologic correlation and comparison between survivors and non-survivors.

OBJECTIVES: To report radiologic findings with histopathologic correlations of humidifier disinfectant-associated children's interstitial lung disease (HD-chILD) and to compare computed tomography (CT) findings between survivors and non-survivors. METHODS: Forty-seven children with HD-chILD (27.4 ± 12.4 months old) were categorized as survivors (n = 25) and non-survivors (n = 22). The patterns, distributions, and chronological changes in lung lesions at follow-up CT were investigated. Histopathologic correlations were performed in 23 patients. RESULTS: CT features were characterized by chronological changes, from consolidation to centrilobular opacities, and lesions eventually became faint centrilobular nodules. Histopathologic features were bronchocentric-distributed fibro-inflammatory lesions, which were more profound in the advanced stage than the early stage. Consolidation ≥ 30 % [hazard ratio (HR), 2.932], centrilobular opacities ≥ 60 % of the total lung volume (TLV; HR, 0.206) and spontaneous air leaks (HR, 3.457) were significant factors associated with patient survival, as per univariate analysis. Consolidation ≥ 30 % (HR, 3.519), centrilobular opacities ≥ 60 % (HR, 0.205) and diffuse ground glass opacity (GGO) ≥ 70 % of the TLV (HR, 3.521) were significant factors associated with patient survival, as determined via multivariate analysis. CONCLUSION: Distinctive chronological CT features were observed in the HD-chILD images. Spontaneous air leaks, consolidation, GGO, and centrilobular opacities were prognostic factors. KEY POINTS: Chemical disinfectants can induce severe inhalation lung injury. Lung injury caused by inhaled disinfectants demonstrates chronologic changes in radiologic findings. Understanding of radiological characteristics is important to predict outcomes in chemical pneumonitis. Physicians should be aware of the potential risk of environmental chemicals.

Humidifier disinfectant-associated children's interstitial lung disease.

RATIONALE: Beginning in 2006, epidemics of a fatal lung injury of unknown cause in children were observed in Korea every spring. A recent study demonstrated that this type of children's interstitial lung disease (chILD) is associated with humidifier disinfectant use. OBJECTIVES: To determine the clinical characteristics of this type of chILD and to assess whether the nationwide suspension of humidifier disinfectant sales in the autumn of 2011 affected its incidence. METHODS: The clinical characteristics of suspected cases between 2006 and 2011 were determined by a nationwide retrospective study. The potential causal relationship with humidifier disinfectants was examined by a prospective surveillance study after humidifier disinfectant sales were suspended. MEASUREMENTS AND MAIN RESULTS: In total, 138 children were diagnosed with this type of chILD, which was characterized by rapid progression, high mortality, predominance in the spring season, and a familial tendency. The annual incidence increased in 2011 and then dropped to zero in 2012. The children were on average 30.4 months old. The most frequent symptoms at admission were cough and dyspnea. As the disease progressed, the typical complication was spontaneous air leak. Eighty children (58%) died. Two years after humidifier disinfectant-sale suspension, no more new cases were found. CONCLUSIONS: This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.

High throughput molecular profiling reveals differential mutation patterns in intrahepatic cholangiocarcinomas arising in chronic advanced liver diseases.

Intrahepatic cholangiocarcinomas occur mostly in the normal liver but they also arise in chronic advanced liver diseases. However, genetic differences between two groups have yet to be examined. High throughput mass spectrometry-based platform was used to interrogate mutations in intrahepatic cholangiocarcinomas and to compare the mutation profiles between 43 intrahepatic cholangiocarcinomas with normal liver and 38 with chronic advanced liver diseases. Forty seven mutations in 11 genes were identified in 38 of 81 cases (46.9%). The most commonly mutated gene was KRAS (11/81, 13.6%), followed by MLH1 (7/81, 8.6%), NRAS (7/81, 8.6%), GNAS (6/81, 7.4%), and EGFR (6/81, 7.4%). BRAF, APC, PIK3CA, CDKN2A, PTEN, and TP53 mutations were found with less than 5%. Overall mutation rate of intrahepatic cholangiocarcinomas with chronic advanced liver disease (15/38, 39.5%, 95% confidence interval: 23.9-55.0) was lower than that of intrahepatic cholangiocarcinomas with normal liver (23/43, 53.5%, 95% confidence interval: 38.5-68.3). Intrahepatic cholangiocarcinomas with chronic advanced liver disease showed higher EGFR mutation rate (5/38, 13.2% vs 1/43, 2.3%) and lower mutation rates of KRAS (3/38, 7.9% vs 8/43, 18.6%), MLH1 (2/38, 5.3% vs 5/43, 11.6%), and GNAS (1/38, 2.6% vs 5/43, 11.6%), compared with those in intrahepatic cholangiocarcinomas with normal liver. Mutations in PIK3CA, PTEN, CDKN2A, and TP53 were harbored only in intrahepatic cholangiocarcinomas with normal liver. KRAS (P=0.0075) or GNAS mutations (P=0.0256) were associated with poor overall survival in all patients with intrahepatic cholangiocarcinoma. Differential mutation patterns of intrahepatic cholangiocarcinomas with chronic advanced liver disease suggest different cholangiocarcinogenesis depending upon the predisposing factors, and support that different strategy for targeted therapy should be applied in intrahepatic cholangiocarcinoma subtypes.

Sargassum horneri extract fermented by Lactiplantibacillus pentosus SH803 mediates adipocyte metabolism in 3T3-L1 preadipocytes by regulating oxidative damage and inflammation.

Sargassum horneri (S. horneri), a brown seaweed excessively proliferating along Asian coastlines, are damaging marine ecosystems. Thus, this study aimed to enhance nutritional value of S. horneri through lactic acid bacteria fermentation to increase S. horneri utilization as a functional food supplement, and consequently resolve coastal S. horneri accumulation. S. horneri supplemented fermentation was most effective with Lactiplantibacillus pentosus SH803, thus this product (F-SHWE) was used for further in vitro studies. F-SHWE normalized expressions of oxidative stress related genes NF-κB, p53, BAX, cytochrome C, caspase 9, and caspase 3, while non-fermented S. horneri (SHWE) did not, in a H2O2-induced HT-29 cell model. Moreover, in an LPS-induced HT-29 cell model, F-SHWE repaired expressions of inflammation marker genes ZO1, IL1ß, IFNγ more effectively than SHWE. For further functional assessment, F-SHWE was also treated in 3T3-L1 adipocytes. As a result, F-SHWE decreased lipid accumulation, along with gene expression of adipogenesis markers PPARγ, C/EBPα, C/EBPß, aP2, and Lpl; lipogenesis markers Lep, Akt, SREBP1, Acc, Fas; inflammation markers IFN-γ and NF-κB. Notably, gene expression of C/EBPß, IFN-γ and NF-κB were suppressed only by F-SHWE, suggesting the enhancing effect of fermentation on obesity-related properties. Compositional analysis attributed the protective effects of F-SHWE to acetate, an organic acid significantly higher in F-SHWE than SHWE. Therefore, F-SHWE is a novel potential anti-obesity agent, providing a strategy to reduce excess S. horneri populations along marine ecosystems.

Pulmonary metastatic nodules of uterine low-grade endometrial stromal sarcoma: histopathological and immunohistochemical analysis of 10 cases.

AIMS: To identify histopathological and immunohistochemical findings that aid diagnosis of metastatic endometrial stromal sarcoma (ESS) in small biopsy specimens of the lung. METHODS AND RESULTS: We reviewed the histology of 46 lung nodules from 10 cases of pulmonary metastatic ESS. Biopsy sections were analysed by immunohistochemistry to highlight blood and lymphatic vasculature, and for expression of CD10 and oestrogen receptor (ER). Various histological changes were identified that could mislead in making a diagnosis on small biopsy samples: haemangiopericytomatous blood vessels (39%), absence of characteristic spiral arteriole-like vasculature (26%), intratumoral cysts formed by dilatation of airways (22%) or intratumoral myxoid change (11%), prominent interstitial collagen deposits (48%), foam cell infiltration (4%) and smooth muscle differentiation (2%). Peribronchial/peribronchiolar distribution of tumour cells with juxtaepithelial growth was a frequent feature, observed in 59% of nodules. In two very small nodules the lesion was barely recognizable histologically; tumour cells were detected only by expression of ER and CD10. CONCLUSIONS: Combined staining for ER and CD10 can be helpful in avoiding an erroneous diagnosis. As lymphatics are not normally present in the juxtaepithelial bronchial/bronchiolar wall, juxtaepithelial tumour growth beneath the bronchial epithelium in early metastatic lesions indicates a haematogenous metastastic route through the bronchial artery.

Analysis of human tissue management models for medical research: preparation for implementation of the 2012 revision of the Bioethics and Safety Act of Korea.

Efficient management of human tissue samples is a critical issue; the supply of samples is unable to satisfy the current demands for research. Lack of informed consent is also an ethical problem. One of the goals of the 2012 revision of Korea's Bioethics and Safety Act was to implement regulations that govern the management of human tissue samples. To remain competitive, medical institutions must prepare for these future changes. In this report, we review two tissue management models that are currently in use; model 1 is the most common system utilized by hospitals in Korea and model 2 is implemented by some of the larger institutions. We also propose three alternative models that offer advantages over the systems currently in use. Model 3 is a multi-bank model that protects the independence of physicians and pathologists. Model 4 utilizes a comprehensive single bioresource bank; although in this case, the pathologists gain control of the samples, which may make it difficult to implement. Model 5, which employs a bioresource utilization steering committee (BUSC), is viable to implement and still maintains the advantages of Model 4. To comply with the upcoming law, we suggest that physicians and pathologists in an institution should collaborate to choose one of the improved models of tissue management system that best fits for their situation.

Embryonal rhabdomyosarcoma arising from a mediastinal teratoma: an unusual case report.

We report an unusual case of 9.5-cm-sized embryonal rhabdomyosarcoma arose from a mediastinal mature teratoma in a 46-yr-old man. A man presented with chest trauma as a result of an accident at 10 September 2011. On chest X-ray, an anterior mediastinal mass was detected. To obtain further information, chest computed tomography (CT) with contrast enhancement was performed, revealing an anterior mediastinal mass. Complete surgical excision was performed and entire specimen was evaluated. Pathologic diagnosis was embryonal rhabdomyosarcoma arising in mature cystic teratoma. After surgical excision, two cycles of dactinomycin-based chemotherapy were performed. Lung metastasis was detected on follow up CT in September 2012, and wedge resection was performed. Pathological finding of the lung lesion showed same feature with that of primary rhabdomyosarcoma.

Engineering Catalysis within a Saturated In(III)-Based MOF Possessing Dynamic Ligand-Metal Bonding.

Metal-organic frameworks have developed into a formidable heterogeneous catalysis platform in recent years. It is well established that thermolysis of coordinated solvents from MOF nodes can render highly reactive, coordinatively unsaturated metal complexes which are stabilized via site isolation and serve as active sites in catalysis. Such approaches are limited to frameworks featuring solvated transition-metal complexes and must be stable toward the formation of "permanent" open metal sites. Herein, we exploit the hemilability of metal-carboxylate bonds to generate transient open metal sites in an In(III) MOF, pertinent to In-centered catalysis. The transient open metal sites catalyze the Strecker reaction over multiple cycles without loss of activity or crystallinity. We employ computational and spectroscopic methods to confirm the formation of open metal sites via transient dissociation of In(III)-carboxylate bonds. Furthermore, the amount of transient open metal sites within the material and thus the catalytic performance can be temperature-modulated.

A novel histone deacetylase inhibitor, CG200745, potentiates anticancer effect of docetaxel in prostate cancer via decreasing Mcl-1 and Bcl-XL.

We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, -3 and -8 in LNCaP, DU145 and PC3 cells. These results indicate that CG200745 induces apoptosis. Next, we examined the effect of CG200745 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Compared to mono-treatment with each drug, pre-treatment of DU145 cells with docetaxel followed by CG200745 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation. Moreover, the combination treatment decreased Mcl-1 and Bcl-(XL). Docetaxel and CG200745 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that combination treatment with docetaxel and new HDACI, CG200745, potentiated anti-tumor effect in hormone-refractory prostate cancer (HRPC) cells via activation of apoptosis.

Effects of the Crystalline Properties of Hollow Ceria Nanostructures on a CuO-CeO2 Catalyst in CO Oxidation.

The development of an efficient and economic catalyst with high catalytic performance is always challenging. In this study, we report the synthesis of hollow CeO2 nanostructures and the crystallinity control of a CeO2 layer used as a support material for a CuO-CeO2 catalyst in CO oxidation. The hollow CeO2 nanostructures were synthesized using a simple hydrothermal method. The crystallinity of the hollow CeO2 shell layer was controlled through thermal treatment at various temperatures. The crystallinity of hollow CeO2 was enhanced by increasing the calcination temperature, but both porosity and surface area decreased, showing an opposite trend to that of crystallinity. The crystallinity of hollow CeO2 significantly influenced both the characteristics and the catalytic performance of the corresponding hollow CuO-CeO2 (H-Cu-CeO2) catalysts. The degree of oxygen vacancy significantly decreased with the calcination temperature. H-Cu-CeO2 (HT), which presented the lowest CeO2 crystallinity, not only had a high degree of oxygen vacancy but also showed well-dispersed CuO species, while H-Cu-CeO2 (800), with well-developed crystallinity, showed low CuO dispersion. The H-Cu-CeO2 (HT) catalyst exhibited significantly enhanced catalytic activity and stability. In this study, we systemically analyzed the characteristics and catalyst performance of hollow CeO2 samples and the corresponding hollow CuO-CeO2 catalysts.

Fabrication of Nanostructured Polycaprolactone (PCL) Film Using a Thermal Imprinting Technique and Assessment of Antibacterial Function for Its Application.

In the use of the medical devices, it is essential to prevent the attachment of bacteria to the device surface or to kill the attached bacteria. To kill bacteria, many researchers have used antibiotics or studied nanostructure-based antibacterial surfaces, which rely on mechanical antibacterial methods. Several polymers are widely used for device fabrication, one of which is polycaprolactone (PCL). PCL is biocompatible, biodegradable, easy to fabricate using 3D printing, relatively inexpensive and its quality is easily controlled; therefore, there are various approaches to its use in bio-applications. In addition, it is an FDA-approved material, so it is often used as an implantable material in the human body. However, PCL has no inherent antibacterial function, so it is necessary to develop antibacterial functions in scaffold or film-based PCL medical devices. In this study, process parameters for nanopillar fabrication were established through a simple thermal imprinting method with PCL. Finally, a PCL film with a flexible and transparent nanopillar structure was produced, and the mechano-bactericidal potential was demonstrated using only one PCL material. PCL with nanopillars showed bactericidal ability against Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) bacteria cultured on its surface that resulted in membrane damage and death due to contact with nanopillars. Additionally, bacteriostatic results were shown to inhibit bacterial growth and activity of Staphylococcus aureus (S. aureus) on PCL nanostructured columns. The fabricated nanopillar structure has confirmed that mechanically induced antibacterial function and can be applied to implantable medical devices.

Transglutaminase 2 as an independent prognostic marker for survival of patients with non-adenocarcinoma subtype of non-small cell lung cancer.

BACKGROUND: Expression of transglutaminase 2 (TGase 2) is related to invasion and resistance to chemotherapeutic agents in several cancer cells. However, there has been only limited clinical validation of TGase 2 as an independent prognostic marker in cancer. METHODS: The significance of TGase 2 expression as an invasive/migratory factor was addressed by in vitro assays employing down-regulation of TGase 2. TGase 2 expression as a prognostic indicator was assessed in 429 Korean patients with early-stage non-small cell lung cancer (NSCLC) by immunohistochemical staining. RESULTS: TGase 2 expression increased the invasive and migratory properties of NSCLC cells in vitro, which might be related to the induction of MMP-9. In the analysis of the immunohistochemical staining, TGase 2 expression in tumors was significantly correlated with recurrence in NSCLC (p = 0.005) or in the non-adenocarcinoma subtype (p = 0.031). Additionally, a multivariate analysis also showed a significant correlation between strong TGase 2 expression and shorter disease-free survival (DFS) in NSCLC (p = 0.029 and HR = 1.554) and in the non-adenocarcinoma subtype (p = 0.030 and HR = 2.184). However, the correlation in the adenocarcinoma subtype was not significant. CONCLUSIONS: TGase 2 expression was significantly correlated with recurrence and shorter DFS in NSCLC, especially in the non-adenocarcinoma subtype including squamous cell carcinoma.

Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer.

The present study investigated the association between deficient mismatch repair (dMMR) and efficacy outcomes of irinotecan-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC). Among 297 patients with sporadic mCRC receiving an irinotecan-containing regimen as first-line chemotherapy, 197 with available paraffin-embedded tissues were included in the current analysis. Tumors displaying loss of MMR protein (MLH1 or MSH2) and/or a microsatellite instability-high (MSI-H) genotype by PCR were classified as dMMR. Deficient mismatch repair was found in 23 evaluable tumors, among which eight displayed negativity for MLH1 expression, 11 for MSH2 expression, and four for both. The overall response rate was 47.2% (46.0% in proficient MMR (pMMR) and 56.5% in dMMR), with no significant difference between the two groups (P = 0.569). Median progression-free survival was 8.85 months in patients with dMMR tumors and 6.82 months in patients with pMMR tumors, but this difference did not reach statistical significance (P = 0.089). Median overall survival was not different between the two groups (P = 0.413). Efficacy outcomes of first-line irinotecan-based chemotherapy did not differ significantly between mCRC patients with pMMR and those with dMMR. Our data collectively indicate that MMR status is not effective as a single predictive marker for response to irinotecan-based chemotherapy in mCRC patients.

Direct sequencing in cytological specimens as a useful strategy for detecting EGFR mutations in non-small cell lung cancer patients.

BACKGROUND: New therapeutics targeting epidermal growth factor receptor (EGFR) have significantly improved tumor responses to therapy in non-small cell lung cancer (NSCLC) patients. Molecular testing for EGFR mutations informs important therapeutic decisions in clinical practice. In this study, we sought to validate the clinical relevance of sequencing-based EGFR mutation testing combined with cytological analysis using body fluid specimens. METHODS: Two NSCLC cell lines were used in sensitivity analyses. In addition, we performed cytological analyses and directly sequencing of exons 18-21, for 32 specimens. The absence of EGFR mutations determined by direct sequencing in 14 specimens was confirmed by real-time PCR. Changes made to patients' therapeutic strategies after reports of EGFR mutation status were investigated by querying electronic medical records. RESULTS: Sensitivity studies showed that detection of in-frame deletions in exon 19 and point mutations in exon 21 was possible in specimens containing 10% and 5% mutant DNA, respectively. In clinical practice, EGFR mutations were detected in 18 of 32 specimens (56.3%). Twelve patients with EGFR mutations detected by direct sequencing were started on treatment with EGFR tyrosine kinase inhibitor (TKI) after reports of EGFR mutation. EGFR-TKI therapy was discontinued for two patients with TKI-resistant T790M mutation. The results of real-time PCR were consistent with those of direct sequencing in 13 of 14 specimens (92.9%) in which no mutation was detected by direct sequencing. CONCLUSIONS: Combined direct sequencing and cytological analysis of body fluid specimen might be clinically useful and sensitive test for the detection of EGFR mutations in NSCLC patients.

Bead-Shaped Mesoporous Alumina Adsorbents for Adsorption of Ammonia.

It is of great importance to remove toxic gases by efficient methods for recovering the atmosphere to safe levels. The adsorption of the toxic gas molecules on solid adsorbents is one of the most useful techniques because of its simple operation and economic feasibility. Here, we report the uniform Bead-Shaped Mesoporous Alumina (BSMA) with tunable particle size for use as an adsorbent for removal of toxic ammonia. The BSMA particles with tunable diameters were synthesized by means of a sol-gel reaction of Al(NO3)3∙9H2O as an alumina precursor in the presence of chitosan as a template. When the ammonia solution is added dropwise to the prepared viscose mixture containing chitosan, acetic acid, and the alumina precursor solution, the sol-gel condensation reaction of the alumina precursor occurs in the chitosan polymer metrics, resulting in bead-shaped chitosan-aluminum hydroxide particles. Then, final Bead-Shaped Mesoporous Alumina (BSMA) particles are obtained by calcination at a high temperature. During the synthesis, changing the mole ratio of the chitosan template to the alumina precursor allowed the particle diameter of the final bead sample to be finely controlled. In addition, the prepared BSMA particles have well-developed mesoporous characteristics with relatively large surface areas, which are beneficial for adsorption of gas molecules. In an ammonia adsorption experiment, the BSMA-1.5 sample, which has the smallest particle diameter among the bead samples, was the best in terms of adsorption capacity. In this manuscript, we systemically discuss the relationship between the characteristics of BSMA samples and their adsorption of ammonia.

A novel histone deacetylase inhibitor, CG0006, induces cell death through both extrinsic and intrinsic apoptotic pathways.

Histone deacetylase inhibitors (HDACIs) are potent anticancer drugs, and suberoylanilide hydroxamic acid is used for the treatment of cutaneous T-cell lymphoma patients. We synthesized a novel hydroxamate-based HDACI, CG0006, and assessed its antiproliferative effects on the NCI-60 cancer cell panel and cell lines from liver and stomach cancers that are common in Korea. Micromolar levels of CG0006 induced cell death in several breast, central nervous system, colon, hematopoietic, lung, melanoma, ovarian, prostatic, renal, and stomach cancer cell lines. We further analyzed cell death mechanisms activated by CG0006 in HCT116 (colon cancer) and K562 (leukemia) cells. First, to test the activity of CG0006, we analyzed acetylation of substrates of HDACs and effect on gene expression. CG0006 increased acetylation of histone 3, histone 4, and tubulin in a time-dependent and dose-dependent manner in both HCT116 and K562 cells. Moreover, CG0006 increased the mRNA level of p21 and decreased that of Bcl-xl efficiently in HCT116 cells. Cell cycle analysis showed G2-M arrest, and increased apoptosis in populations of HCT116 and K562 cells treated with CG0006. Western blot analysis showed that CG0006 increased levels of p21 in HCT116 cells and of p21 and p27 in K562 cells. In addition, CG0006 activated caspase-9, caspase-3, and caspase-8. These results indicate that CG0006 induces death in HCT116 and K562 cells through both intrinsic and extrinsic apoptotic pathways. The HDACI CG0006 may be a potent anticancer drug for solid tumors and leukemia.

Feasibility, safety, and adequacy of research biopsies for cancer clinical trials at an academic medical center.

OBJECTIVE: Research biopsies are an essential component of cancer clinical trials for studying drug efficacy and identifying biomarkers. Site-level clinical investigators, however, do not have access to results on the adequacy of research biopsies for histological or molecular assays, because samples are sent to central labs and the test results are seldom reported back to site-level investigators unless requested. We evaluated the feasibility, safety, and adequacy of research biopsies performed at an academic medical center. MATERIALS AND METHODS: We retrospectively reviewed the data on 122 research biopsy sessions conducted in 99 patients via percutaneous core needle biopsy for 39 clinical trials from January 2017 to February 2018 at a single institute. We asked the sponsors of each clinical trial for the adequacy of the biopsy samples for histological or molecular assays. RESULTS: The biopsy success rate was 93.4% (113/122), with nine samples categorized as inadequate for obtaining pathologic diagnosis. Post-biopsy complications occurred in 9.8% (12/122) of biopsies, all of which were mild and completely recovered by the day after the biopsy. The sponsors of clinical trials provided feedbacks on the adequacy of 76 biopsy samples, and noted that a total of 8 biopsy samples from 7 patients were inadequate for analysis, resulting in an adequacy rate of 89.5% (68/76): the reasons for inadequacy were insufficient tumor content for immunohistochemistry (n = 3) and low RNA yield for sequencing (n = 5). CONCLUSION: Research biopsies performed at an experienced, multidisciplinary center had acceptable safety for patients as well as practicality in terms of obtaining adequate tissue samples for molecular studies.