Orientation of imaging and histology of radical prostatectomy specimen in prostate cancer using 3D modelling and fabricated molds

BackgroundTo develop patient-specific 3T MRI data based rapid prototyping molds for sectioning prostatectomy specimens that would facilitate comparison between histopathology, in vivo MRI and Shear Wave Elastography (SWE).MethodPost-radical prostatectomy specimens were fixed in formalin and sectioned in similar orientation to T2-weighted MR scanning. This was facilitated by the use of mold prepared in biomedical software Mimics (Materialise, Belgium) and CAD software Solidworkds (Dassault Systèmes SolidWorks Corp., USA) through 3-D segmentation, reconstruction and rapid prototyping. The specimens were sliced with a single blade and the resultant MRI images defined tissue blocks were used for histopathology analysis. The multi-parametric MRI data, SWE and histological sectioning were compared to assess prostate cancer characteristics.ResultsThe prostatectomy specimen slices were very uniform in thickness with good quality histological sectioning. A number of cancer foci were picked up with some of them significant disease (Gleason grade 7 and more). Multiparametric MRI (mp-MRI), quantitative SWE data as measured in kilopascals and histopathology comparison showed good correspondence between the three images.ConclusionThe method described here allows a reliable orientation and comparison between imaging (mp-MRI, SWE) and histology of prostatectomy specimens and paves the way for the translation of imaging biomarkers, especially detection of significant cancers.</p

Measurement of enhancement kinetics using heuristic parameters in multiparametric MRI as markers of prostate cancer aggressiveness.

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been used as a diagnostic modality with known added value in multi-parametric MRI (mp-MRI) characterisation of prostate cancers (PCa). Several methods have been applied to analyse DCE MRI data. The purpose of this study is to assess the ability of mp-MRI for detecting grade of prostate carcinomas in comparison to pathology using heuristic model-free parametric evaluation (wash-in and wash-out slope, etc.) provided by Tissue 4D (Siemens Multi-Modality Work Platform).Method21 patients with histologically proven prostate cancer who were scanned at 3T mp-MRI and opted for laparoscopic radical prostatectomy were recruited in this study. Post-prostatectomy pathology reports were considered as reference standard. The pathology specimens were processed by a special method to ensure exact orientation between imaging and slices of section during histopathology. Multi-parametric MRI data including conventional T1 and T2 weighted imaging (T1WI and T2WI), DWI and DCE-MRI was recorded. DCE-MRI was analysed in Tissue 4D using the two different methods: tofts model (Ktrans, kep values and the colour-distribution map for the perfusion parameters); wash-in and –out rates, which were calculated according to the parametric time-concentration curves.ResultsThere are 46 lesions detected in pathology of 21 prostatectomy specimen and mp-MRI correctly picked up 33 of them. Smaller lesions (2mm and less) with Gleason grade 3+4 were not identified by DCE-MRI. There was a strong trend towards a positive correlation between grade of cancer and enhancement rate as assessed by toft model.ConclusionDCE-MRI with the two difference methods could predict aggressiveness of prostate cancers more than 2mm in size. Smaller lesions and those with Gleason score 7 and less could still be a challenge for multiparamteric MRI detection method.</p

Computer aided image analysis and rapid prototyping molds using patient-specific MRI data for reliable comparison between imaging and histopathology of radical prostatectomy specimens

Legacy description not available</p

Anti-proliferative and pro-apoptotic effects of cinobufagin on human breast cancer MCF-7 cells and its molecular mechanism

<p>Cinobufagin (CBF) is an active ingredient isolated from Venenum Bufonis extracted and dried from the secretory glands of <i>Bufo gargarizans Cantor</i>. The purpose of the study was to investigate the effects and underlying mechanisms of CBF on human breast cancer MCF-7 cells <i>in vitro</i>. Our results showed that CBF exhibited obvious cytotoxicity on MCF-7 cells in a dose- and time-dependent manner, as indicated by CCK-8 assays. Also, Hoechst 33258 staining and flow cytometry assays showed that CBF strongly induced MCF-7 cell apoptosis and G1 phase arrest. In addition, further molecular mechanistic investigation demonstrated that cinobufagin significantly increased Bax expression, decreased Bcl-2 expression level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays. Taken together, our data confirm that CBF inhibits growth and triggers apoptosis of MCF-7 cells by affecting the expression of Bax and Bcl-2 <i>in vitro</i>.</p

Simple Preparation of Carbon Nanofibers with Graphene Layers Perpendicular to the Length Direction and the Excellent Li-Ion Storage Performance

Sulfur-containing carbon nanofibers with the graphene layers approximately vertical to the fiber axis were prepared by a simple reaction between thiophene and sulfur at 550 °C in stainless steel autoclaves without using any templates. The formation mechanism was discussed briefly, and the potential application as anode material for lithium-ion batteries was tentatively investigated. The carbon nanofibers exhibit a stable reversible capacity of 676.8 mAh/g after cycling 50 times at 0.1 C, as well as the capacities of 623.5, 463.2, and 365.8 mAh/g at 0.1, 0.5, and 1.0 C, respectively. The excellent electrochemical performance could be attributed to the effect of sulfur. On one hand, sulfur could improve the reversible capacity of carbon materials due to its high theoretical capacity; on the other hand, sulfur could promote the formation of the unique carbon nanofibers with the graphene layers perpendicular to the axis direction, favorable to shortening the Li-ion diffusion path

Li-Ion Storage Performance of Carbon-Coated Mn–Al–O Composite Oxides

The composites of manganese oxide and alumina (Mn–Al–O) with varied Mn/Al molar ratios were fabricated by a simple coprecipitation method and subsequently sintered at different temperatures. Carbon-coated oxides were prepared at 550 °C using pyrrole as the carbon source. Compared with the carbon-coated MnO prepared under the same conditions, the carbon-coated Mn–Al–O exhibits greatly enhanced electrochemical performance which is associated with both the Mn/Al molar ratio and sintering temperature. The carbon-coated composites with a ratio of 2:1 sintered at 600 °C could deliver a stable reversible capacity of 450 mAh g^–1 after 100 cycles at a current density of 100 mA g^–1 and the capacities of 373, 309, 245, and 175 mAh g^–1 at the densities of 200, 400, 800, and 1600 mA g^–1, respectively. The enhanced cycling and rate performance is attributed to the improved Li-ion conductivity owing to the formation of LiAlO₂ and the smaller particle size of MnO due to the dispersion effect of Al₂O₃

Table_6_Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.xlsx

BackgroundTumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.MethodsPublic databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro.ResultsPLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to “immune response”, “cell cycle”, “DNA replication”, and “mismatch repair” in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.ConclusionsPLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma. </p

DataSheet_1_Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.zip

BackgroundTumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.MethodsPublic databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro.ResultsPLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to “immune response”, “cell cycle”, “DNA replication”, and “mismatch repair” in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.ConclusionsPLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma. </p

Table_3_Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.xlsx

BackgroundTumor immune microenvironment (TIM) plays a critical role in tumorigenesis and progression. Recently, therapies based on modulating TIM have made great breakthroughs in cancer treatment. Polo-like kinase 1 (PLK1) is a crucial regulatory factor of the cell cycle process and its dysregulations often cause various pathological processes including tumorigenesis. However, the detailed mechanisms surrounding the regulation of PLK1 on glioma immune microenvironment remain undefined.MethodsPublic databases and online datasets were used to extract data of PLK1 expression, clinical features, genetic alterations, and biological functions. The EdU, flow cytometry, and macrophage infiltration assays as well as xenograft animal experiments were performed to determine the relationship between PLK1 and glioma immune microenvironment in vivo and in vitro.ResultsPLK1 is always highly expressed in multiple cancers especially in glioma. Univariable and Multivariate proportional hazard Cox analysis showed that PLK1 was a prognostic biomarker for glioma. Simultaneously, highly expressed PLK1 is significantly related to prognosis, histological and genetic features in glioma by analyzing public databases. In addition, the enrichment analysis suggested that PLK1 might related to “immune response”, “cell cycle”, “DNA replication”, and “mismatch repair” in glioma. Immune infiltration analysis demonstrated that highly expressed PLK1 inhibited M1 macrophages infiltration to glioblastoma immune microenvironment by Quantiseq and Xcell databases and negatively related to some chemokines and marker genes of M1 macrophages in glioblastoma. Subsequent experiments confirmed that PLK1 knockdown inhibited the proliferation of glioma cells but increased the M1 macrophages infiltration and polarization. Furthermore, in glioma xenograft mouse models, we showed that inhibiting PLK1 blocked tumor proliferation and increased the M1 macrophages infiltration. Finally, PLK1 methylation analysis and lncRNA-miRNA network revealed the potential mechanism of abnormal PLK1 expression in glioma.ConclusionsPLK1 inhibits M1 macrophages infiltration into glioma immune microenvironment and is a potential biomarker for glioma. </p

Table_3_IL-12p40 deletion aggravates lipopolysaccharide-induced cardiac dysfunction in mice.XLSX

BackgroundCardiac dysfunction is one of the most common complications of sepsis and is associated with the adverse outcomes and high mortality of sepsis patients. IL-12p40, the common subunit of IL-12 and IL-23, has been shown to be involved in a variety of inflammation-related diseases, such as psoriasis and inflammatory bowel disease. However, the role of IL-12p40 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains obscure. This study aimed to explore the role of IL-12p40 in LPS-induced cardiac dysfunction and its potential mechanisms.MethodsIn this study, mice were treated with LPS and the cardiac expression of IL-12p40 was determined. Then, IL-12p40–/– mice were used to detect the role and mechanisms of IL-12p40 in LPS-induced cardiac injury. In addition, monocytes were adoptively transferred to IL-12p40–/– mice to explore their effects on LPS-induced cardiac dysfunction.ResultsThe results showed that cardiac IL-12p40 expression was significantly increased after treated with LPS. In addition, IL-12p40 deletion significantly aggravated LPS-induced cardiac dysfunction, evidenced by the increased serum levels of cardiomyocyte injury markers and heart injury scores, as well as by the deteriorated cardiac function. Moreover, IL-12p40 deletion increased LPS-induced monocyte accumulation and cardiac expression of inflammatory cytokines, as well as enhanced the activation of the NF-κB and MAPK pathways. Furthermore, adoptive transfer WT mouse monocytes to IL-12p40−/− mice alleviated LPS-induced cardiac dysfunction and decreased the phosphorylation of p65.ConclusionIL-12p40 deletion significantly aggravated LPS-induced cardiac injury and cardiac dysfunction in mice by regulating the NF-κB and MAPK signaling pathways, and this process was related to monocytes. Therefore, IL-12p40 show a protective role in SIC, and IL-12p40 deficiency or anti-IL-12p40 monoclonal antibodies may be detrimental to patients with SIC.</p