The current investigation is a part of project concerning microstructure and texture in a series of ferrite-austenite stainless steels after deformation and annealing. The present paper focuses on ...deformation behavior of constituent phases in a metastable duplex type steel subjected to cold-rolling in the range of high reductions. Optical microscopy was used to examine changes in the morphology and the formation of ferrite-austenite band-like structure. Transmission electron microscopy was applied to analyze the microstructure and deformation mechanisms within the bands of austenite and ferrite. Additional research included the examination of texture changes in both constituent phases. Special attention was paid to deformation mechanisms operating within ferrite-austenite banded structure at high rolling reductions, including the formation of micro-shear bands, the occurrence of micro-twinning as well as deformation induced martensitic transformation. Transmission electron microscopy analysis indicates that the phase transformation occurred most likely through direct (γ→α') mechanism and obeyed predominantly Kurdjumov-Sachs orientation relationship. Within strongly fragmented two-phase microstructure at high strains the formation of α'-martensite proceeded in most cases at internal interfaces in micro-bands from the operating deformation systems.
Preferentially expressed antigen in melanoma (PRAME) is considered a useful marker in the differential diagnosis between malignant melanoma and its melanocytic mimics. Recently PRAME expression was ...documented in nonmelanocytic tumors, but much of the data are based on mRNA studies. This investigation evaluated PRAME expression in the spectrum of normal tissues and >5800 human tumors using immunohistochemistry and EP461 monoclonal antibody. In normal tissues, PRAME was expressed in the testis and proliferative endometrium. In tumors, PRAME was variably expressed in malignancies of different lineages. Among epithelial tumors, >50% of PRAME-positive lesions were found among endometrial carcinomas (82%), uterine serous carcinomas (82%), uterine carcinosarcomas (60%), ovarian clear cell carcinomas (90%), ovarian serous carcinomas (63%), adenoid cystic carcinomas (81%), seminomas (78%), thymic carcinomas (75%), and basal cell carcinomas (62%). In mesenchymal and neuroectodermal malignancies, PRAME was frequently expressed in synovial sarcoma (71%), myxoid liposarcoma (76%), neuroblastoma (61%) and metastatic melanoma (87%). Also, PRAME was consistently expressed in 4 melanomas that lacked all melanoma markers including S100 protein and SOX10 but harbored typical for melanoma BRAF or NRAS driver mutations. However, strong and diffuse PRAME immunoreactivity was seen in many types of nonmelanocytic poorly differentiated carcinomas and sarcomas. Based on this study, PRAME is a relatively unspecific immunohistochemical marker, which limits its use in diagnostic surgical pathology. However, immunohistochemistry is a reliable and unexpensive method useful in detecting PRAME-positive malignancies for potential immunotherapy.
The present research is part of a project that includes several grades of high‑manganese steels with different chemical compositions and various pre-treatment parameters. The main objective of this ...work was to determine favourable conditions for the occurrence of strain-induced phase transitions in unstable Fe-20Mn-3Al-3Si steel. After preliminary treatment the steel showed a two-phase microstructure consisting of austenite matrix and 29% of ferrite volume fraction. The deformation process of the examined steel was strongly influenced by the low stacking fault energy value of austenite matrix. Initially, the slip of dissociated dislocations led to the formation of numerous bands of stacking faults. Then, the phase transformations induced by plastic deformation took place, i.e., γ (fcc) → ε (hcp) and subsequently ε (hcp) → α’ (bcc). The beginning and further progress of these phase transitions depended primarily on the crystallographic orientations of the austenite grains. The more favourable the orientation of the grains with respect to external stresses, the more effective was the activation of dislocation slip and the greater number of deformation bands was formed. These processes directly resulted in a locally induced phase transition γ → ε. Simultaneously, in grains showing the formation of ε-bands in at least two intersecting systems, the transformation ε → α’ gradually occurred.
•Unstable austenite microstructure in two-phase Fe-Mn-Si-Al steel subjected to cold rolling.•Appearance of deformation induced transformations γ(FCC) → ε(HCP) and γ(FCC) → ε(HCP) → α’(BCC).•Occurrence of phase transformations in grains with the most favourable orientations for slip activation.•Development of preferential Shoji-Nishiyama and Kurdjumov-Sachs relationships between the phases.
The current research is part of a project covering several grades of high-manganese steels (20–26 wt% Mn) with different chemical compositions, which were deformed at room and reduced temperatures. ...In the present paper, the microstructure development is analyzed at the onset of plastic deformation in Fe–Mn–Al–Si steel containing 21.2 wt% Mn. The examination was conducted under conditions of lowering the deformation temperature and aimed to show the influence of reduced temperatures on the occurrence of strain induced phase (martensitic) transformation.
The steel samples were subjected to uniaxial deformation in a tensile test at gradually reduced temperatures, starting from 20 °C and then applying the temperatures 0 °C, −50 °C and −150 °C. The present paper includes the analysis of microstructure development and orientation relationships as well as determination of operating deformation mechanisms for samples after 10% of tensile strain. The main part of the research was carried out by means of scanning electron microscopy (SEM), using the method of electron back-scatter diffraction (EBSD).
The carried out analysis indicates that within the range of small strains the mechanism controlling deformation behavior of high-manganese steel Fe–21Mn–3Al–3Si was slip of partial dislocations. This was immediately followed by the occurrence of strain induced phase transformation γ (fcc) → ε (hcp) and then locally ε (hcp) → α' (bcc). With decreasing deformation temperature a noticeable increase of the volume fraction of the martensitic phases was observed, first of all the ε-phase and to a much lesser extent α′-martensite. The ε-martensite appeared on the background of a deformed austenite initially in the form of relatively narrow bands. The α′-martensite was formed predominantly at the intersections of the ε-bands. An interesting result, however, is the fact that numerous places were also found where α′-martensite was formed in single set of parallel ε-phase bands. The preferential crystallographic orientation relations (ORs) between the γ-austenite and the strain induced ε- and α′- phases were successively followed, showing first of all the appearance of Shoji-Nishiyama (S–N) and Kurdjumov-Sachs (K–S) ORs respectively.
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by ...degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VE-cadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC.
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The research presented in this paper is part of a larger project concerning deformation behavior, microstructure and mechanical properties of high-manganese steels with different chemical ...compositions and processed under various conditions. The current investigation deals with the development of microstructure and crystallographic texture of Fe-21.2Mn-2.73Al-2.99Si steel deformed in tension until fracture at ambient temperature. The deformation process of the examined steel turned out to be complex and included not only dislocation slip and twinning but also strain induced phase transformations (γ → ε) and (γ → α′). The formation of ε-martensite with hexagonal structure was observed within the microstructure of the steel starting from the range of lower strains. With increasing deformation degree, the α′-martensite showing a cubic structure gradually began to form. Attempts have been made to explain the circumstances or conditions for the occurrence of the deformation mechanisms mentioned above and their impact on the mechanical properties. The obtained results indicate that the strength and plastic properties of the steel substantially exceed those of plain carbon steels. Since both, mechanical twinning and the strain-induced phase transformations took place during deformation, it seems that both types of deformation mechanisms contributed to an increase in the mechanical properties of the examined manganese steel.
Epithelial-mesenchymal transition (EMT) refers to the acquisition of mesenchymal properties in cells participating in tumor progression. One hallmark of EMT is the increased level of active ...β-catenin, which can trigger the transcription of Wnt-specific genes responsible for the control of cell fate. We investigated how Monocyte Chemotactic Protein-1-Induced Protein-1 (MCPIP1), a negative regulator of inflammatory processes, affects EMT in a clear cell renal cell carcinoma (ccRCC) cell line, patient tumor tissues and a xenotransplant model. We showed that MCPIP1 degrades miRNAs via its RNase activity and thus protects the mRNA transcripts of negative regulators of the Wnt/β-catenin pathway from degradation, which in turn prevents EMT. Mechanistically, the loss of MCPIP1 RNase activity led to the upregulation of miRNA-519a-3p, miRNA-519b-3p, and miRNA-520c-3p, which inhibited the expression of Wnt pathway inhibitors (SFRP4, KREMEN1, CXXC4, CSNK1A1 and ZNFR3). Thus, the level of active nuclear β-catenin was increased, leading to increased levels of EMT inducers (SNAI1, SNAI2, ZEB1 and TWIST) and, consequently, decreased expression of E-cadherin, increased expression of mesenchymal markers, and acquisition of the mesenchymal phenotype. This study revealed that MCPIP1 may act as a tumor suppressor that prevents EMT by stabilizing Wnt inhibitors and decreasing the levels of active β-catenin and EMT inducers.
Monocyte Chemoattractant
protein-induced protein 1 (
MCPIP1
), also known as Regnase-1, is encoded by the
ZC3H12a
gene, and it mediates inflammatory processes by regulating the stability of ...transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues. Using Caki-1 cells as a model, we analyzed the role of MCPIP1 in cancer development. We showed that MCPIP1 expression depends on the proteasome activity; however, hypoxia and hypoxia inducible factor 2 alfa (HIF2α) are key factors lowering MCPIP1 expression. Furthermore, we found that MCPIP1 negatively regulates HIF1α and HIF2α levels and in the case of the last one, the mechanism is based on the regulation of the half time of transcript coding for HIF2α. Enhanced expression of MCPIP1 in Caki-1 cells results in a downregulation of transcripts encoding VEGFA, GLUT1, and IL-6. Furthermore, MCPIP1 decreases the activity of mTOR and protein kinase B (Akt) in normoxic conditions. Taken together, MCPIP1 contributes to the ccRCC development.
The main goal of this study was to compare contrast-enhanced spectral mammography (CESM) and breast magnetic resonance imaging (MRI) with histopathological results and to compare the sensitivity, ...accuracy, and positive and negative predictive values for both imaging modalities.
After ethics approval, CESM and MRI examinations were performed in 102 patients who had suspicious lesions described in conventional mammography. All visible lesions were evaluated independently by 2 experienced radiologists using BI-RADS classifications (scale 1-5). Dimensions of lesions measured with each modality were compared to postoperative histopathology results.
There were 102 patients entered into CESM/MRI studies and 118 lesions were identified by the combination of CESM and breast MRI. Histopathology confirmed that 81 of 118 lesions were malignant and 37 were benign. Of the 81 malignant lesions, 72 were invasive cancers and 9 were in situ cancers. Sensitivity was 100% with CESM and 93% with breast MRI. Accuracy was 79% with CESM and 73% with breast MRI. ROC curve areas based on BI-RADS were 0.83 for CESM and 0.84 for breast MRI. Lesion size estimates on CESM and breast MRI were similar, both slightly larger than those from histopathology.
Our results indicate that CESM has the potential to be a valuable diagnostic method that enables accurate detection of malignant breast lesions, has high negative predictive value, and a false-positive rate similar to that of breast MRI.
The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, ...and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.
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