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Conductive metal-organic frameworks (cMOFs) manifest great potential in modern electrical devices due to their porous nature and the ability to conduct charges in a regular network. cMOFs applied in electrical devices normally hybridize with other materials, especially a substrate. Therefore, the precise control of the interface between cMOF and a substrate is particularly crucial. However, the unexplored interface chemistry of cMOFs makes the controlled synthesis and advanced characterization of high-quality thin films, particularly challenging. Herein, we report the development of a simplified synthesis method to grow "face-on" and "edge-on" cMOF nanofilms on substrates, and the establishment of operando characterization methodology using atomic force microscopy and X-ray, thereby demonstrating the relationship between the soft structure of surface-mounted oriented networks and their characteristic conductive functions. As a result, crystallinity of cMOF nanofilms with a thickness down to a few nanometers is obtained, the possible growth mechanisms are proposed, and the interesting anisotropic softness-dependent conducting properties (over 2 orders of magnitude change) of the cMOF are also illustrated.
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BACKGROUND: Pathologists commonly employ the Ki67 immunohistochemistry labelling index (LI) when deciding appropriate therapeutic strategies for patients with breast cancer. However, despite several attempts at standardizing the Ki67 LI, inter-observer and inter-laboratory bias remain problematic. We developed a flow cytometric assay that employed tissue dissociation, enzymatic treatment and a gating process to analyse Ki67 in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue. RESULTS: We demonstrated that mechanical homogenizations combined with thrombin treatment can be used to recover efficiently intact single-cell nuclei from FFPE breast cancer tissue. Ki67 in the recovered cell nuclei retained reactivity against the MIB-1 antibody, which has been widely used in clinical settings. Additionally, since the method did not alter the nucleoskeletal structure of tissues, the nuclei of cancer cells can be enriched in data analysis based on differences in size and complexity of nuclei of lymphocytes and normal mammary cells. In a clinical study using the developed protocol, Ki67 positivity was correlated with the Ki67 LI obtained by hot spot analysis by a pathologist in Japan (rho = 0.756, P < 0.0001). The number of cancer cell nuclei subjected to the analysis in our assay was more than twice the number routinely checked by pathologists in clinical settings. CONCLUSIONS: The findings of this study showed the application of this new flow cytometry method could potentially be used to standardize Ki67 assessments in breast cancer.
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Neoplasias da Mama , Citometria de Fluxo , Antígeno Ki-67 , Inclusão em Parafina , Antígeno Ki-67/metabolismo , Antígeno Ki-67/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Humanos , Citometria de Fluxo/métodos , Feminino , Inclusão em Parafina/métodos , Formaldeído , Fixação de Tecidos/métodosRESUMO
Crystal-to-glass transformation is a powerful approach to modulating the chemical and physical properties of crystals. Here we demonstrate that the glass transformation of cobalt hexacyanoferrate crystals, one of the Prussian blue analogues, increased the concentration of open metal sites and altered the electronic state while maintaining coordination geometries and short-range ordering in the structure. The compositional and structural changes were characterized by X-ray absorption fine structure, energy dispersive X-ray spectroscopy, and X-ray total scattering. The changes contribute to the flat band potential of the glass becoming closer to the redox potential of CO2 reduction. The valence band energy of the glass also shifts, resulting in lower band gap energy. Both the increased open metal sites and the optimal electronic structure upon vitrification enhance photocatalytic activity toward CO2-to-CO conversions (9.9 µmol h-1 CO production) and selectivity (72.4%) in comparison with the crystalline counterpart (3.9 µmol h-1 and 42.8%).
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Crystalline triazine-based covalent organic frameworks (COFs) are aromatic nitrogen-rich porous materials. COFs typically show high thermal/chemical stability, and are promising for energy applications, but often require harsh synthesis conditions and suffer from low crystallinity. In this work, we propose an environmentally friendly route for the synthesis of crystalline COFs from CO2 molecules as a precursor. The mass ratio of CO2 conversion into COFs formula unit reaches 46.3 %. The synthesis consists of two steps; preparation of 1,4-piperazinedicarboxaldehyde from CO2 and piperazine, and condensation of the dicarboxaldehyde and melamine to construct the framework. The CO2 -derived COF has a 3-fold interpenetrated structure of 2D layers determined by powder X-ray diffraction, high-resolution transmission electron microscopy, and select-area electron diffraction. The structure shows a high Brunauer-Emmett-Teller surface area of 945â m2 g-1 and high stability against strong acid (6â M HCl), base (6â M NaOH), and boiling water over 24â hours. Post-modification of the framework with oxone has been demonstrated to modulate hydrophilicity, and it exhibits proton conductivity of 2.5×10-2 â S cm-1 at 85 °C, 95 % of relative humidity.
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A one-stone, two-bird method to integrate the soft porosity and electrical properties of distinct metal-organic frameworks (MOFs) into a single material involves the design of conductive-on-insulating MOF (cMOF-on-iMOF) heterostructures that allow for direct electrical control. Herein, we report the synthesis of cMOF-on-iMOF heterostructures using a seeded layer-by-layer method, in which the sorptive iMOF core is combined with chemiresistive cMOF shells. The resulting cMOF-on-iMOF heterostructures exhibit enhanced selective sorption of CO2 compared to the pristine iMOF (298â K, 1â bar, S CO 2 / H 2 ${{_{{\rm CO}{_{2}}/{\rm H}{_{2}}}}}$ from 15.4 of ZIF-7 to 43.2-152.8). This enhancement is attributed to the porous interface formed by the hybridization of both frameworks at the molecular level. Furthermore, owing to the flexible structure of the iMOF core, the cMOF-on-iMOF heterostructures with semiconductive soft porous interfaces demonstrated high flexibility in sensing and electrical "shape memory" toward acetone and CO2 . This behavior was observed through the guest-induced structural changes of the iMOF core, as revealed by the operando synchrotron grazing incidence wide-angle X-ray scattering measurements.
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BACKGROUND: The one-step nucleic acid amplification (OSNA) assay can quantify the cytokeratin 19 messenger RNA copy number as a proxy for sentinel lymph node (SN) metastasis in breast cancer. A large-scale, multicenter cohort study was performed to determine the prognostic value of the SN tumor burden based on a molecular readout and to establish a model for the prediction of early systemic recurrence in patients using the OSNA assay. METHODS: SN biopsies from 4757 patients with breast cancer were analyzed with the OSNA assay. The patients were randomly assigned to the training or validation cohort at a ratio of 2:1. On the basis of the training cohort, the threshold SN tumor burden value for stratifying distant recurrence was determined with Youden's index; predictors of distant recurrence were investigated via multivariable analyses. Based on the selected predictors, a model for estimating 5-year distant recurrence-free survival was constructed, and predictive performance was measured with the validation cohort. RESULTS: The prognostic cutoff value for the SN tumor burden was 1100 copies/µL. The following variables were significantly associated with distant recurrence and were used to construct the prediction model: SN tumor burden, age, pT classification, grade, progesterone receptor, adjuvant cytotoxic chemotherapy, and adjuvant anti-human epidermal growth factor receptor 2 therapy. The values for the area under the curve, sensitivity, specificity, and accuracy of the prediction model were 0.83, 63.4%, 81.7%, and 81.1%, respectively. CONCLUSIONS: Using the OSNA assay, the molecular readout-based SN tumor burden is an independent prognostic factor for early breast cancer. This model accurately predicts early systemic recurrence and may facilitate decision-making related to treatment.
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Neoplasias da Mama , Linfonodo Sentinela , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Estudos de Coortes , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Patologia Molecular , Linfonodo Sentinela/patologiaRESUMO
Single-ligand-based electronically conductive porous coordination polymers/metal-organic frameworks (EC-PCPs/MOFs) fail to meet the requirements of numerous electronic applications owing to their limited tunability in terms of both conductivity and topology. In this study, a new 2D π-conjugated EC-MOF containing copper units with mixed trigonal ligands was developed: Cu3 (HHTP)(THQ) (HHTP=2,3,6,7,10,11-hexahydrotriphenylene, THQ=tetrahydroxy-1,4-quinone). The modulated conductivity (σ≈2.53×10-5 â S cm-1 with an activation energy of 0.30â eV) and high porosity (ca. 441.2â m2 g-1 ) of the Cu3 (HHTP)(THQ) semiconductive nanowires provided an appropriate resistance baseline and highly accessible areas for the development of an excellent chemiresistive gas sensor.
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Covalent organic frameworks (COFs) represent an emerging class of crystalline porous materials that are constructed by the assembly of organic building blocks linked via covalent bonds. Several strategies have been developed for the construction of new COF structures; however, a facile approach to fabricate hierarchical COF architectures with controlled domain structures remains a significant challenge, and has not yet been achieved. In this study, a dynamic covalent chemistry (DCC)-based postsynthetic approach was employed at the solid-liquid interface to construct such structures. Two-dimensional imine-bonded COFs having different aromatic groups were prepared, and a homogeneously mixed-linker structure and a heterogeneously core-shell hollow structure were fabricated by controlling the reactivity of the postsynthetic reactions. Solid-state nuclear magnetic resonance (NMR) spectroscopy and transmission electron microscopy (TEM) confirmed the structures. COFs prepared by a postsynthetic approach exhibit several functional advantages compared with their parent phases. Their Brunauer-Emmett-Teller (BET) surface areas are 2-fold greater than those of their parent phases because of the higher crystallinity. In addition, the hydrophilicity of the material and the stepwise adsorption isotherms of H2O vapor in the hierarchical frameworks were precisely controlled, which was feasible because of the distribution of various domains of the two COFs by controlling the postsynthetic reaction. The approach opens new routes for constructing COF architectures with functionalities that are not possible in a single phase.
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BACKGROUND: Embolism during percutaneous coronary intervention (PCI) causes microcirculation impairment. The aim of this study was to clarify the relationship between the pathological characteristics of tissue captured by distal protection device (DPD) and amount of tissue accumulated in DPD. MethodsâandâResults: A total of 671 consecutive lesions in PCI using DPD were examined. The amount of necrotic debris, fibrous tissue, calcified particle, platelet thrombus and organized thrombus in the DPD baskets was histologically evaluated. The DPD tissue amount was assessed semi-quantitatively, and the relationship between the captured DPD tissue characteristics and tissue amount was investigated. On pathology, 40.7% of the lesions had necrotic debris, 41.4% had fibrous tissue, and 18.0% had calcified particle. The prevalence of lesions in patients with acute coronary syndrome (ACS) was 62.1%. Tissue amount score distribution was as follows: score 1 (tissue invisible), 3.9%; score 2 (tissue clinging to the basket), 52.0%; score 3 (tissue accumulated at the bottom of the basket), 38.5%; and score 4 (tissue accumulated in more than half of the basket), 5.7%. On multivariate analysis, necrotic debris and fibrous tissue were associated with greater tissue amount as well as clinical presentation of ACS. CONCLUSIONS: The presence of atherosclerotic plaque component, such as necrotic debris and fibrous tissue, might be a risk for distal embolism during PCI.
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Dispositivos de Proteção Embólica , Embolia/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Placa Aterosclerótica/patologia , Síndrome Coronariana Aguda/complicações , Idoso , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ativação Plaquetária , Estudos Retrospectivos , Fatores de Risco , Trombose/fisiopatologiaRESUMO
The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare morphologic entity in which metastasis rarely occurs. Until now, only three cases of metastasis by CMV-PTC have been reported. We present a rare sporadic case of CMV-PTC with multiple lung metastases in a 28-year-old female, 3 years after total thyroidectomy. The lung tumor was not encapsulated but well-circumscribed and showed a mixture of cribriform, papillary, and solid patterns of growth with necrosis. The tall columnar carcinoma cells did not display the typical nuclear features of PTC. Carcinoma cells were positive for thyroid transcription factor 1, paired-box gene 8, estrogen receptor, progesterone receptor, and adenomatous polyposis coli, and showed positive nuclear and cytoplasmic staining for ß-catenin. Carcinoma cells were negative for thyroglobulin and CDX-2, and the Ki-67 labeling index was 22.1%. This immunoprofile suggests a pathological diagnosis of metastasis by a CMV-PTC displaying poorly differentiated features. To the best of our knowledge, our case is the first report of CMV-PTC with pulmonary metastasis that was confirmed by histological and immunohistochemical examinations. The present case suggests that CMV-PTC with a high Ki-67 labeling index may cause visceral metastasis.
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Neoplasias Pulmonares/secundário , Câncer Papilífero da Tireoide/secundário , Neoplasias da Glândula Tireoide/patologia , Adulto , Feminino , HumanosRESUMO
A rare case of a metastatic ectopic papillary thyroid carcinoma (PTC) of the lung that transformed into a squamous cell carcinoma (SCC) that resembles pulmonary SCC is reported. A subcutaneous ectopic PTC in the left anterior neck area, together with a normal thyroid gland, were excised. The ectopic PTC showed thyroglobulin, TTF-1 and PAX-8 immunoreactivity and a BRAF V600E mutation. During the post-operative follow-up period, a rapidly growing 2 cm nodular lesion in the lower left lobe of the lung was detected. The lung tumor consisted of solid sheets and nests of squamous cells but without the nuclear features of PTC. Neither papillary nor follicular structures of cancer cells were identified. Carcinoma cells were positive for TTF-1, PAX-8, p40, CK14, and p63, while showing a high Ki-67 labeling index and a BRAF V600E mutation. These results support our interpretation of a PTC that originated from ectopic thyroid tissue in the left anterior neck and that developed a lung metastasis showing squamous cell differentiation.
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Carcinoma Papilar/patologia , Carcinoma de Células Escamosas/secundário , Neoplasias Pulmonares/secundário , Neoplasias da Glândula Tireoide/patologia , Idoso , Carcinoma Papilar/genética , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/patologia , Humanos , Neoplasias Pulmonares/genética , Masculino , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/genéticaRESUMO
BACKGROUND: Some poorly differentiated thyroid carcinomas (PDTC) arise from pre-existing, well-differentiated carcinomas of follicular cell origin; however, others most likely arise de novo. The case of a PDTC adjacent to a pre-existing nodular goiter is very rare. CASE PRESENTATION: A patient had a PDTC, a widely invasive, cellular tumor with cells that lacked the nuclear features of a papillary thyroid carcinoma. Carcinoma cells were arranged in trabecular, solid, and microfollicular histological patterns and displayed high mitotic activity. A nodule partially encapsulated in a thick fibrous capsule was found adjacent to the PDTC. The nodule was composed of small or dilated follicles, without papillary carcinoma-like nuclear features, that were consistent with a nodular goiter. The PDTC showed a high Ki-67 labeling index and an NRAS gene mutation (codon 61, Q61K). CONCLUSION: These results support our diagnosis of a PDTC, probably arising from a nodular goiter.
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The melting behavior of a coordination polymer (CP) crystal was utilized to achieve enhanced and optically switchable proton conductivity in the solid state. The strong acid molecules (triflic acid) were doped in one-dimensional (1D) CP, [Zn(HPO4 )(H2 PO4 )2 ](ImH2 )2 (ImH2 =monoprotonated imidazole) in the melt state, and overall enhancement in the proton conductivity was obtained. The enhanced proton conductivity is assigned to increased number of mobile protons and defects created by acid doping. Optical control over proton conductivity in the CP is achieved by doping of the photo acid molecule pyranine into the melted CP. The pyranine reversibly generates the mobile acidic protons and local defects in the glassy state of CP resulting in the bulk switchable conductivity mediated by light irradiation. Utilization of CP crystal in liquid state enables to be a novel route to incorporate functional molecules and defects, and it provides a tool to control the bulk properties of the CP material.
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The solvent-free mechanical milling process for two distinct metal-organic framework (MOF) crystals induced the formation of a solid solution, which is not feasible by conventional solution-based syntheses. X-ray and STEM-EDX studies revealed that performing mechanical milling under an Ar atmosphere promotes the high diffusivity of each metal ion in an amorphous solid matrix; the amorphous state turns into the porous crystalline structure by vapor exposure treatment to form a new phase of a MOF solid solution.
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Direct use of low pressures of CO2 as a C1 source without concentration from gas mixtures is of great interest from an energy-saving viewpoint. Porous heterogeneous catalysts containing both adsorption and catalytically active sites are promising candidates for such applications. Here, we report a porous coordination polymer (PCP)-based catalyst, PCP-Ru(II) composite, bearing a Ru(II) -CO complex active for CO2 reduction. The PCP-Ru(II) composite showed improved CO2 adsorption behavior at ambient temperature. In the photochemical reduction of CO2 the PCP-Ru(II) composite produced CO, HCOOH, and H2 . Catalytic activity was comparable with the corresponding homogeneous Ru(II) catalyst and ranks among the highest of known PCP-based catalysts. Furthermore, catalytic activity was maintained even under a 5 % CO2 /Ar gas mixture, revealing a synergistic effect between the adsorption and catalytically active sites within the PCP-Ru(II) composite.
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BACKGROUND: The estimation of recurrence risk remains a critical issue in relation to gastrointestinal stromal tumors (GISTs) treated with adjuvant therapy. The accuracy of the commonly used risk stratifications is not always adequate. METHODS: For this study, data were prospectively collected from 68 patients with GISTs who underwent R0 surgery between 2004 and 2009. The results from this analysis cohort were evaluated using the data obtained from an additional 40 patients in the validation cohort. Cyclin-dependent kinase 1 (CDK1)- and CDK2-specific activities were measured using a non-RI kinase assay system. RESULTS: The specific activities of CDK1 and CDK2, but not their expression, significantly correlated with recurrence. The specific activities of both CDK1 and CDK2 were independently correlated with mitosis and significantly correlated with recurrence-free survival (RFS). In the multivariate analysis, CDK2-specific activity (P = 0.0006), tumor size (P = 0.0347), and KIT deletion mutations (P = 0.0006) were significantly correlated with RFS in the analysis cohort. In the validation cohort, CDK2-specific activity (P = 0.0368) was identified as an independent prognostic factor for tumor recurrences with tumor location (P = 0.0442). CONCLUSION: The results suggest that the specific activities of CDK1 and CDK2 may reflect the proliferative activity of GISTs and that CDK2-specific activity is a good prognostic factor predicting recurrence after macroscopic complete resection of GISTs.
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Proteína Quinase CDC2/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Tumores do Estroma Gastrointestinal/enzimologia , Neoplasias Intestinais/enzimologia , Neoplasias Hepáticas/enzimologia , Neoplasias Peritoneais/enzimologia , Neoplasias Gástricas/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Tumores do Estroma Gastrointestinal/secundário , Tumores do Estroma Gastrointestinal/cirurgia , Genótipo , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Intestino Delgado , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Mitose , Neoplasias Peritoneais/secundário , Proteínas Proto-Oncogênicas c-kit/genética , Curva ROC , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , Medição de Risco , Deleção de Sequência , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Carga Tumoral , Adulto JovemRESUMO
Protein crystals generally are stable solid protein assemblies. Certain protein crystals are suitable for use as nanovessels for immobilizing metal complexes. Here we report the preparation of ruthenium carbonyl-incorporated cross-linked hen egg white lysozyme crystals (Ru·CL-HEWL). Ru·CL-HEWL retains a Ru carbonyl moiety that can release CO, although a composite of Ru carbonyl-HEWL dissolved in buffer solution (Ru·HEWL) does not release CO. We found that treatment of cells with Ru·CL-HEWL significantly increased nuclear factor kappa B (NF-κB) activity as a cellular response to CO. These results demonstrate that Ru·CL-HEWL has potential for use as an artificial extracellular scaffold suitable for transport and release of a gas molecule.
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Monóxido de Carbono/química , Complexos de Coordenação/química , Muramidase/química , Rutênio/química , Animais , Transporte Biológico , Monóxido de Carbono/farmacologia , Galinhas , Complexos de Coordenação/farmacologia , Reagentes de Ligações Cruzadas/química , Cristalização , Cristalografia por Raios X , Clara de Ovo/química , Expressão Gênica/efeitos dos fármacos , Genes Reporter , Glutaral/química , Células HEK293 , Humanos , Luciferases/genética , Luciferases/metabolismo , Mioglobina/química , NF-kappa B/genética , NF-kappa B/metabolismo , PorosidadeRESUMO
This report describes a rare case of collagenous gastroduodenitis found in a 12-year-old Japanese girl who had recurrent hematemesis. Gastrointestinal endoscopy showed many lotus leaf-like lesions on the gastric mucosa surrounded by atrophic gastric mucosa in the antrum, with a cobblestone appearance and a scarred duodenal ulcer in the duodenal bulb. A biopsy of the gastric mucosa indicated subepithelial collagen band. The patient was treated with H2-blockers for her symptoms for 4 years following the endoscopic findings. Follow-up endoscopy showed the same appearance as before. The pathology, however, showed a more prominent subepithelial collagen deposition. To make the correct diagnosis, it is critical to know from which part the pathological biopsy specimens were taken because there were numerous collagen bands in the atrophic membrane. It is important to monitor the patient regularly for evaluation of the etiology, pathogenesis and prognosis of this rare disease.
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Colágeno/metabolismo , Duodenite/etiologia , Mucosa Gástrica/patologia , Gastrite/etiologia , Úlcera Gástrica/complicações , Biópsia , Criança , Duodenite/diagnóstico , Duodenite/metabolismo , Endoscopia Gastrointestinal , Feminino , Mucosa Gástrica/metabolismo , Gastrite/diagnóstico , Gastrite/metabolismo , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Recidiva , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/tratamento farmacológicoRESUMO
We report a case of a 62-year-old woman with a growing liver tumor that was difficult to differentiate from hepatocellular carcinoma (HCC). Abdominal CT revealed a hypervascular tumor (36 mm in diameter) in segment 3 of the liver that showed early enhancement and which had grown from 30 mm to 36 mm over the previous year. A fatty liver and gallstones were also detected. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor on both T1- and T2-weighted images, and EOB-MRI revealed a mass that showed high signal intensity in the hepatobiliary phase. The imaging findings were not typical for HCC; however, the possibility of malignancy could not be ruled out due to the enlargement of the mass. Therefore, in February 2015, we performed a laparoscopic left lateral segmentectomy with cholecystectomy. After a good postoperative course, the patient was discharged from the hospital 11 days after surgery. Histological assessment revealed the tumor was focal nodular hyperplasia (FNH).
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Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Hiperplasia Nodular Focal do Fígado/diagnóstico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Humanos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. METHODS: Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. RESULTS: H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. CONCLUSIONS: H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner.