Heavy alloy based on tungsten and bismuth: fabrication, crystal structure, morphology, and shielding efficiency against gamma-radiation.

W-Bi2O3 composites were fabricated using the hot isostatic pressing technique for the first time. The duration of the samples sintering was 3 minutes under conditions of high pressure and temperature. The study of microstructural features and chemical composition of sintered samples was carried out using scanning electron microscopy and energy-dispersive X-ray spectroscopy, respectively. The effect of temperature on the quality of the obtained W-Bi2O3 composites is determined. The densest samples were obtained at a pressure of 5 GPa and temperatures of 25 °C and 500 °C, the densities of which were 18.10 and 17.85 g cm-3, respectively. It is presented that high temperature exposure during sintering adversely affects both the composite density and microstructure due to the redox reaction accompanied by the reduction of Bi and the oxidation of W. The results of the W-Bi2O3 structure study using X-ray diffraction analysis showed that all samples included the main bulk-centered cubic W phase. The presence of the WO2 phase is noted only when the sintering temperature is increased up to 850 °C, which is confirmed by the appearance of diffraction peaks that correspond to 111 and 22-2 crystallographic planes. The shielding efficiency of the W-Bi2O3 composite against gamma radiation using the Phy-X/PSD software was evaluated. A Co60 isotope with an energy of 0.826-2.506 MeV was used as a source of gamma radiation. The calculation results were compared with those for Pb and Bi. Key shielding parameters such as the linear attenuation coefficient, half-value layer, tenth-value layer, mean free path, and effective atomic number are determined. The calculation results revealed that the W-Bi2O3 composite surpasses Pb and Bi in its shielding properties, which makes it promising for use as a prospective material for radiation shielding applications.

Methodologyfor Molecular Dynamics Simulation of Plastic Deformation of a Nickel/Graphene Composite.

In this study, some features of molecular dynamics simulation for evaluating the mechanical properties of a Ni/graphene composite and analyzing the effect of incremental and dynamic tensile loading on its deformation are discussed. A new structural type of the composites is considered: graphene network (matrix) with metal nanoparticles inside. Two important factors affecting the process of uniaxial tension are studied: tension strain rate (5 ×10-3 ps-1 and 5 ×10-4 ps-1) and simulation temperature (0 and 300 K). The results show that the strain rate affects the ultimate tensile strength under tension: the lower the strain rate, the lower the critical values of strain. Tension at room temperature results in lower ultimate tensile strength in comparison with simulation at a temperature close to 0 K, at which ultimate tensile strength is closer to theoretical strength. Both simulation techniques (dynamic and incremental) can be effectively used for such a study and result in almost similar behavior. Fabrication technique plays a key role in the formation of the composite with low anisotropy. In the present work, uniaxial tension along three directions shows a big difference in the composite strength. It is shown that the ultimate tensile strength of the Ni/graphene composite is close to that of pure crumpled graphene, while the ductility of crumpled graphene with metal nanoparticles inside is two times higher. The obtained results shed the light on the simulation methodology which should be used for the study of the deformation behavior of carbon/metal nanostructures.

Investigation of cytotoxic and antioxidative activity of 1,2,3-triazolyl-modified furocoumarins and 2,3-dihydrofurocoumarins.

High biological activity of natural furocoumarins is often linked to a series of adverse side effects, e.g., genotoxicity. This makes it desirable to develop semi-synthetic derivatives with reduced negative activity while retaining or even enhancing the positive properties. Previously, we have studied the genotoxic activity of a library of twenty-one 1,2,3-triazolyl-modified furocoumarins and 2,3-dihydrofurocoumarins and identified modifications that minimize the negative properties. In the current article, we report on an investigation into the cytotoxic activity of the same library. We have aimed to rank the substances in order of the severity of their cytotoxicity and therefore to predict, with the use of statistical processing, the most promising substituents for the furocoumarin scaffold.

Fra-2 overexpression upregulates pro-metastatic cell-adhesion molecules, promotes pulmonary metastasis, and reduces survival in a spontaneous xenograft model of human breast cancer.

PURPOSE: The transcription factor Fra-2 affects the invasive potential of breast cancer cells by dysregulating adhesion molecules in vitro. Previous results suggested that it upregulates the expression of E- and P-selectin ligands. Such selectin ligands are important members of the leukocyte adhesion cascade, which govern the adhesion and transmigration of cancer cells into the stroma of the host organ of metastasis. As so far, no in vivo data are available, this study was designed to elucidate the role of Fra-2 expression in a spontaneous breast cancer metastasis xenograft model. METHODS: The effect of Fra-2 overexpression in two stable Fra-2 overexpressing clones of the human breast cancer cell line MDA MB231 on survival and metastatic load was studied after subcutaneous injection into scid and E- and P-selectin-deficient scid mice. RESULTS: Fra-2 overexpression leads to a significantly shorter overall survival and a higher amount of spontaneous lung metastases not only in scid mice, but also in E- and P-deficient mice, indicating that it regulates not only selectin ligands, but also selectin-independent adhesion processes. CONCLUSION: Thus, Fra-2 expression influences the metastatic potential of breast cancer cells by changing the expression of adhesion molecules, resulting in increased adherence to endothelial cells in a breast cancer xenograft model.

Linear/Ladder-Like Polysiloxane Block Copolymers with Methyl-, Trifluoropropyl- and Phenyl- Siloxane Units for Surface Modification.

Multiblock copolymers containing linear polydimethylsiloxane or polymethyltrifluoropropylsiloxane and ladder-like polyphenylsiloxane were synthesized in a one-step pathway. The functional homopolymer blocks and final multiblock copolymers were characterized using solution and solid-state multinuclear 1H, 13C, 19F, and 29Si NMR spectroscopy. It was shown that the ladder-like block contains silanol units, which influence the adhesion properties of multiblock copolymers and morphology of their casted films. The adhesion to metals and mechanical properties of multiblock copolymers were tested. The SEM study of casted films of multiblock copolymers shows the variety of formed morphologies, including long-strip-like or globular.

Snail and E-Cadherin Immunoexpression in Clear Cell Renal Cell Carcinoma.

Renal cell clear cell carcinomas (ccRCC) represent 75% of the malignant renal neoplasias. A critical molecular characteristic in the epithelial-mesenchymal transition (EMT) is the loss of E-cadherin expression, as well as the epithelial-mesenchymal transcription factors, one of the most important of which is Snail. In the current study, we analyzed the immunoexpression of the two markers in 46 cases of clear cell renal cell carcinomas, with reference to the most important prognosis histopathological factors. Our results indicated significant associations between the overexpression of Snail, under expression of E-cadherin and high Fuhrman grade. E-cadherin immunoexpression was high in incipient tumoral stages, and Snail was overexpressed in advanced tumoral stages of ccRCC. Our study supports the importance of this antibody panel in the prognosis of ccRCC.

E-cadherin and Snail Immunoexpression in Colorectal Adenocarcinomas.

Epithelial-mesenchymal transition (EMT) is a fundamental process which governs invasiveness. E-cadherin plays a major role in development, organogenesis and tissue formation, but also in tumor progression. Snail is a transcription factor described as a direct repressor of E-cadherin during development and in carcinogenesis. In this study we analyzed E-cadherin and Snail immunoexpression in 47 cases of colorectal adenocarcinoma (CRC) in comparison with some histopathological prognostic factors. The majority of cases were G2 tumors in stages II and III, with vascular and perineural invasion. All cases showed positive cytoplasmic signal for E-cadherin and Snail. E-cadherin reactions were intense with the highest composite score (CS) values in CRC G1. CS values of E-cadherin decreased with the advancement in tumor stage and the association with vascular and perineural invasion was statistically significant. Snail immunoreaction was intense with the highest values of CS in CRC G3, being more evident with the increase of tumor staging, aspect which was statistically significant. CS and Snail association demonstrated a statistically significant aspect related to vascular invasion. We found a negative linear correlation of E-cadherin and Snail expression. The obtained results indicate the implication of Snail and E-cadherin in EMT of CRC, aspect which is useful in the evaluation and stratification of patients with CRC for the targeted specific therapy.

Low Grade Ovarian Serous Carcinoma - A Clinical-Morphologic Study.

Low grade ovarian serous carcinomas (LGSC) are rare tumors, representing only a small part of all ovarian carcinomas. The study included six LGSC cases for which we followed the clinical-epidemiological and morphological parameters depending on the tumoral stages. The tumors corresponded to stage I in four cases, in one case to stage II and in another case to stage III. The majority of the analyzed histopathological parameters were present in all tumoral stages. The accuracy of the diagnostic and the correct staging of the LGSC affected patients is very important, because the grade and stage of the serous ovarian tumors impose the therapy and the prognosis.

Talimogene laherparepvec (T-VEC) in advanced melanoma: complete response in a heart and kidney transplant patient. A case report.

Talimogene laherparepvec (T-VEC) is a intralesional oncolytic virotherapy, licensed in the European Union for locoregional advanced melanoma of American Joint Committee on Cancer stages IIIB, IIIC and IVM1a. Organ transplant recipients are currently excluded from all clinical trials dealing with immunotherapies due to the risk of transplant rejection. A 58-year-old white man with a history of heart and kidney transplantation in 2014 was diagnosed with melanoma (Breslow thickness 1·6 mm, stage pT2a) on the left arm in September 2015. In March 2016 he developed in transit metastases, and local therapy with a combination of topical imiquimod (5%) and cryotherapy of individual lesions was initiated. However, in November 2016 therapy was stopped following local progression of the metastases. An interdisciplinary decision to treat the patient with T-VEC was taken. After 11 cycles of T-VEC, the patient showed a complete response. As of June 2018, 11 months after the last treatment cycle of T-VEC, the patient continues to be tumour free. The patient tolerated the therapy well with only mild adverse events and did not show any sign of graft rejection or loss of function of the transplanted organs. We conclude that T-VEC can be a potentially effective and safe treatment in patients with a history of organ transplantation. Nevertheless, due to this special situation, the risks and benefits should always be discussed with an interdisciplinary tumour board.

Assessment of Histopathological Parameters Useful in the Diagnosis of Low Grade Non-Invasive Urothelial Carcinomas.

Urothelial papillary lesions of urinary bladder are frequent lesions in medical practice and sometimes difficult to be histopathologically classified. In this study were included 179 urothelial papillary lesions, represented by low grade non-invasive urothelial carcinomas (LGNIUC), papillary urothelial neoplasms of low malignant potential (PUNLMP) and urothelial papillomas (UP), for which the architectural and cytological histopathological parameters were analyzed in order to determine their usefulness for the classification of lesions. For each parameter, an aggressivity score was set, the sum representing the composite histological score (CHS) for each case. The increase of urothelial thickness, the papillae fusion, the loss of cellular polarity, loss of basal cell palisading and absence of umbelliform cells were commonly associated with diffuse pattern in LGNIUC, were focal/absent in PUNLMP and absent in UP. The nuclear hypertrophy and hyperchromasia, the nucleoli presence and mitotic activity were specific for LGNIUC, rarely associated with PUNLMP and absent/low in UP. CHS values for the three categories of analyzed lesions were superior statistically significant in LGNIUC compared to PUNLMP and UP. The mitotic index and the thickness of cytological atypical epithelial layers support the parameters utility as reproducible criteria for the differentiation of papillary urothelial tumors.

Histopathological Patterns of Microinvasion in Ovarian Serous Borderline Tumors.

Stromal microinvasion in ovarian serous borderline tumors can take various aspects, some of which are difficult to identify. Thus, the identification of stromal microinvasion is relatively simple for typical intracystic papillary proliferations such as serous borderline tumors, but may be difficult for tumors with glandular component. The study analyzed 14 cases of ovarian serous borderline tumors diagnosed in patients with mean age of 47,1 years. Histopathologically all tumors corresponded to typical forms in which we identified only two cases of stromal microinvasion. In one case, microinvasion was of eosinophilic type, and in the other case was observed a glandular and micropapillary pattern, being associated with the noninvasive peritoneal implants.

Proliferative Activity in Basal Cell Carcinomas.

Basal cell carcinomas (BCCs) represent one of the most common human neoplasias. The excellent prognosis of the diagnosed early lesions and the low metastasis rate are particularities that required the investigation of the mechanisms of carcinogenesis on these lesions. In this study we analyzed the proliferation rate for 53 cases of BCC in relation to the clinicopathological parameters of the lesions using Ki67, considered a true indicator of cellular proliferation. The results indicated statistically significant differences in Ki67 immunoexpression related to histological type and lesion stage. The highest Ki67 values were observed in the adenoid and morpheaform subtypes, and in advanced tumor stages. This aspects may be useful for stratification of lesions in terms of tumor aggressiveness.

Evaluation of Gastric Carcinomas Histological Patterns in Relation to Tumors Aggressiveness Parameters.

Gastric carcinomas are frequent tumors with variable growth patterns that may interfere with the evaluation of histopathological prognostic parameters of the lesions. In this study we analyzed the incidence and statistical relation of histological growth patterns depending on the prognostic parameters of gastric carcinomas for 95 cases. Pure forms were present in 82.2% of cases, from which more frequent subtypes were low grade tubular carcinomas and poorly cohesive with signet-ring cells carcinomas. Mixed forms were present in 17.8% of cases, with the highest incidence of tumors containing well differentiated tubular carcinoma and poorly differentiated papillary carcinoma areas. Analysis of the identified types and subtypes in relation to the histological prognostic parameters indicated significant differences regarding the tumor stage, the mixed subtypes being more frequent in advanced stages. Although mixed subtypes were more commonly associated with vascular and perineural invasion, the aspects were statistically insignificant. Together with tumor stage, the lymphovascular and/or perineural invasion should be taken into consideration as prognostic indicators in the postoperative management of gastric cancer.

Architectural Histopathological Changes in Ovarian Serous Carcinomas.

Ovarian serous carcinomas have a very large spectrum of growth patterns that contrast with the most primitive ovarian carcinomas, in which the morphology varies very much less. Serous carcinomas growth patterns include papillary and glandular aspects, but also cribriform, solid, microcystic and trabecular, some being common to the both high- and low-grade types of ovarian serous carcinomas, others being distinct. The study included 45 cases of ovarian serous carcinomas out of which five cases with low grade and 40 cases with high grade. High grade serous carcinomas were associated with mixed growth patterns, with large complex papillae, glands with irregular shape lined by stratified epithelia, often with areas of extended necrosis. In the case of low grade ovarian carcinomas we observed the association with more uniform growth patterns, micropapillary or glandular, the presence of optically empty slit-like spaces, psammoma bodies, the absence of necrosis and the association with a borderline or benign component. The recognition of the common histopathological aspects, allows a more accurate diagnosis of the ovarian serous carcinoma types and subtypes, which has a great importance in the actual era of personalized therapy.

EGFR Immunoexpression in Malignant Serous and Mucinous Ovarian Tumors.

The epithelial growth factor receptor (EGFR) is involved in various stages of cancer growth such as tumor initiation, angiogenesis and metastasis, being an attractive target for oncogenic therapy. The present study aims to evaluate the EGFR expression in 54 cases of serous and mucinous ovarian borderline tumors and carcinomas. EGFR expression was present in more than half of the investigated tumors, more frequently in carcinomas than in borderline tumors, especially in the serous type. The highest values of the final staining score (FSS) were observed only in serous carcinomas in the advanced stages of the disease. As a result of frequent expression of EGFR in ovarian tumors, it is necessary to monitor EGFR inhibitors for ovarian cancer therapy, but probably after establishing more rigorous selection and stratification criteria for patients.

Immunoexpression of Transforming Growth Factor Beta 3 (TGFß3) and Its Receptor Type III (TGFßRIII) in Basal Cell Carcinomas.

Basal cell carcinomas (BCCs) are malignant tumors with particular biological prognosis and behavior, and the biomolecular investigation of these lesions can provide important therapeutic targets for epithelial neoplasia. In this study we analyzed the immunoexpression of transforming growth factor beta 3 (TGFß3) and its receptor type III (TGFßRIII) for 53 cases of BCC in relation to the main histopathological prognostic parameters. The results indicated statistically significant differences of TGFß3 and TGFßRIII expression related to histological type and lesion stage, the both proteins being higher expressed in adenoid and morpheaform advanced stage tumors. In this study, TGFß3 and TGFßRIII immunoexpression analysis indicated their utility for identifying aggressive BCCs with potential for tumor progression.

Histopathological Prognostic Factors for Colic Adenocarcinoma.

The majority of colorectal carcinomas are adenocarcinomas derived from the colic mucosae cell, more frequently moderately differentiated. The purpose of this study was to determine de incidence of CRC and the relationship between histopathological risk factors in patients with colic adenocarcinomas. The study included 144 cases of CRC diagnosed within the Pathology Laboratory of the Clinical County Hospital of Craiova in the year 2017.The biological material consisted in samples from colectomies and hemicolectomies provided from patients admitted within the surgical clinics of the same hospital, then fixed with 10% buffered formalin and afterwards processed using the classic histopathological technique of paraffin inclusion and staining with hematoxylin and eosin. We observed certain histopathological parameters such as: pattern, grading, stage, vascular invasion and neural invasion. The mean age of diagnostic was 68.6 ± 11.2, and it was predominantly male patients (64.6%). Most cases presented with mucinous pattern (31.9%) and cribriform comedocarcinoma type (29.9%). The majority were classified as stage III B (34%), being moderately differentiated (64.6%) and associated with vascular invasion (47.2%) and perineural invasion (25.7%). Statistical analysis indicated significant relationships between tumor stage and differentiation grade (p<0.01, χ²test), as well as between tumor stage and vascular invasion (p<0.05, χ²test), without including perineural invasion (p<0.05, χ²test).

Study of Histopatological Parameters of Gastric Carcinomas with Micropapillary Component.

Micropapillary carcinoma was recently identified as a carcinoma variant characterized by the presence of small clusters of tumor cells located in optically empty spaces. The study included a number of 14 cases represented by surgical excision specimens diagnosed with gastric carcinoma (tubular, papillary and signet-ring) which associated the micropapillary component in variable proportions. Regarding the low-grade tubular carcinomas, the micropapillary component represented less than 25% of the tumor, while in the high-grade tubular carcinomas and papillary carcinomas it represented 25-50%. Among signet-ring carcinomas, the micropapillary component had a percentage of over 50. The depth of invasion was frequently associated with T3 and T4 categories. Lymph nodes metastasis were found in ten cases and distant metastasis were present in three cases. Recognition of the micropapillary component associated with gastric carcinoma represents an aspect of great importance because it is frequently correlated with unfavorable prognosis parameters.

Histopathological Prognostic Factors in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (CCRCC) are the most frequent type of renal cell carcinoma. Fuhrman grade and tumor stage are prognostic factors with great importance in survival rate. This study was performed on 75 cases of CCRCC diagnosed by the Anatomical Pathology Laboratory of the County Clinical Emergency Hospital of Craiova between 2014 and 2017. The biological material was represented by pieces of nephrectomy. The cases were analyzed on two criteria: epidemiology (age, sex) and histopathology (Fuhrman grade, tumor stage, architectural pattern, sarcomatoid transformation, and necrosis). Statistical analysis was done using Chi Square tests in IBM SPSS software. Average diagnosis age of CCRCC was 58.8±10.2 years, predominantly in male patients (66.7%). Tumor sizes were between 2 and 14cm, with an average of 6.7±2.9cm. Most cases were determined to be tumor stage III (60%) and Fuhrman grade 2 (56%), followed, in order of frequency, by tumor stages I and II (28% and 10.7%) and Fuhrman grades 3 and 1 (21.3% and 20%). High Fuhrman grade CCRCC were significantly associated with advanced tumor stage (p<0.05, χ2 test). Most cases presented a mixed pattern, significantly associated with advanced tumor stages (p<0.05, χ2 test). Even though the presence of sarcomatoid transformation was more frequent in advanced tumor stages, it wasn't significantly linked to them (p<0.05, χ2 test). Conclusions: Analyzed histopathological parameters are useful for determining CCRCC aggressiveness. CCRCC in advanced tumor stages is associated with high Fuhrman grade and mixed architectural pattern.

Histopathological Aspects of the Myocardium in Dilated Cardiomyopathy.

Dilated cardiomyopathy is the most common form of cardiac muscle disease, accounting for approximately 60% of all cardiomyopathies. We proposed to identify histopathological changes of the myocardium in dilative cardiomyopathy. This study comprised a total of 19 cases, represented by myocardial fragments from deceased patients with diagnosis of dilated cardiomyopathy. Histopathological analysis allowed changes to be observed for both myocytes and myocardial interstitial components. We have found a combination of hypertrophic, atrophic and normal myocardocytes, or associated with the presence of hydropic changes. We rarely identified the aspect of myocytosis, cytoplasmic accumulation of lipofuscin pigment or mucinous material, and variable nuclear pleomorphism. At the interstitial level we noticed changes in fibrosis, lipomatosis and rarely the presence of inflammatory infiltrate. Histopathological characteristics of the myocardium in dilated cardiomyopathy are numerous but nonspecific, similar to those in the terminal stages of other cardiac diseases.