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(Bi0.5Na0.5)1-xBaxTiO3 (BNBT), which exhibits compositions for the morphotropic phase boundary (MPB) where exist an intimate coexistence of the rhombohedral and tetragonal structures, is being considered as promising lead-free alternative to the well known Pb(Zrx,Ti1-x)O3 (PZT). In this work, BNBT thin films were fabricated by chemical solution deposition (CSD) with a wide range of compositions(x~0.050-0.150) onto Pt/TiO2/SiO2/(100)Si substrates. Structural studies by X-ray diffraction (λCu~1.5406 Å) using a four-circle goniometer were carried out to determine the crystalline structure of the films. Rietveld analysis of the experimental X-ray patterns showed different volume fractions of the rhombohedral and tetragonal phases as a function of the Ba2+) content and the coexistence of both phases, characteristic of a MPB region, for x∼0.055-0.080. Finally, Rutherford backscattering experiments (RBS) were performed to determine the compositional profile of the films. This study revealed a homogenous composition of the BNBT films with abrupt film/substrate interfaces.El (Bi0.5Na0.5)1-xBaxTiO3 (BNBT), considerado un posible candidato sin plomo para substituir al Pb(Zrx,Ti1-x)O3 (PZT), presenta una frontera de fase morfotrópica donde se da la coexistencia de las estructuras tetragonal y romboédrica. En este trabajo, se han fabricado láminas delgadas de BNBT por depósito químico de disoluciones (CSD) con composiciones comprendidas entre x~ 0.050 y x~ 0.150 sobre substratos de Pt/TiO2/SiO2/(100)Si. En dichas láminas se ha llevado a cabo un estudio estructural empleando difracción de rayos X (DRX) (λCu~1.5406 Å) y un goniómetro de cuatro círculos. El análisis Rietveld de los patrones experimentales de DRX mostró: i) diferentes fracciones volumétricas para las fases romboédrica y tetragonal, en función del contenido de Ba2+ ii) la coexistencia de ambas estructuras, característico de una región MPB, para composiciones con x∼0.055-0.080. Finalmente, se determinó el perfil composicional de las láminas de BNBT por espectroscopía de retrodispersión Rutherford (RBS). Este estudio demostró que las láminas de BNBT presentan una composición homogénea e intercaras abruptas lámina/substrato.

Patients with lung cancer are especially vulnerable to coronavirus disease 2019 (COVID-19) with a greater than sevenfold higher rate of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19, a greater than threefold higher hospitalization rate with high complication rates, and an estimated case fatality rate of more than 30%. The reasons for the increased vulnerability are not known. In addition, beyond the direct impact of the pandemic on morbidity and mortality among patients with lung cancer, COVID-19, with its disruption of patient care, has also resulted in substantial impact on lung cancer screening and treatment/management.COVID-19 vaccines are safe and effective in people with lung cancer. On the basis of the available data, patients with lung cancer should continue their course of cancer treatment and get vaccinated against the SARS-CoV-2 virus. For unknown reasons, some patients with lung cancer mount poor antibody responses to vaccination. Thus, boosting vaccination seems urgently indicated in this subgroup of vulnerable patients with lung cancer. Nevertheless, many unanswered questions regarding vaccination in this population remain, including the magnitude, quality, and duration of antibody response and the role of innate and acquired cellular immunities for clinical protection. Additional important knowledge gaps also remain, including the following: how can we best protect patients with lung cancer from developing COVID-19, including managing care in patient with lung cancer and the home environment of patients with lung cancer; are there clinical/treatment demographics and tumor molecular demographics that affect severity of COVID-19 disease in patients with lung cancer; does anticancer treatment affect antibody production and protection; does SARS-CoV-2 infection affect the development/progression of lung cancer; and are special measures and vaccine strategies needed for patients with lung cancer as viral variants of concern emerge., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The ability of calcium aluminate cement (CAC) to encapsulate toxic metals (Pb, Zn and Cu) was assessed under two curing conditions. Changes in the consistency and in the setting time were found upon the addition of the nitrates of the target metals. Both Pb and Cu caused a delay in CAC hydration, while Zn accelerated the stiffening of the mortar. Compressive strengths of the metal-doped mortars, when initially cured at 60 °C/100% RH, were comparable with that of the free-metal mortar. Three different pore size distribution patterns were identified and related to the compounds identified by XRD and SEM. Sorbent capacities of CAC for the toxic metals were excellent: a total uptake was achieved for up to 3 wt.% loading of the three metals. In this way, CAC mortars were perfectly able to encapsulate the toxic metals, allowing the use of CAC for waste management as proved by the leaching tests., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: This study sought to determine pro-B-type natriuretic peptide (proBNP), BNP, N-terminal proBNP (NT-proBNP) and GATA-4 in the same cardiac tissue, the correlation among them, and the influence of ischemic etiology on their levels., Methods: Protein levels were analyzed by Western blot techniques and mRNA expression was quantified by quantitative real-time polymerase chain reaction (RT-PCR) in a total of 33 human samples from ischemic (ICM), and control hearts., Results: Tissue protein level of proBNP is 1.5- and 12-fold higher than BNP or NT-proBNP respectively (p<0.0001), and BNP protein level was 8-fold higher than that of NT-proBNP (p<0.0001) in ICM hearts. Furthermore, proBNP mRNA expression was also increased in ICM (4-fold) compared to control hearts (p<0.05), but there was not a significant increase in GATA-4 mRNA. Then, tissue NP forms showed a high correlation among them (proBNP vs. BNP r=0.74, p<0.0001; proBNP vs. NT-proBNP r=0.43, p=0.03; and BNP vs. NT-proBNP r=0.61, p=0.001, respectively). Furthermore, GATA-4 with proBNP (r=0.536, p=0.007) and BNP (r=0.610, p=0.001) in ischemic samples. Finally, we found that proBNP, BNP, NT-proBNP and GATA-4 were increased in our ICM hearts (by 14%, p=0.004; 46%, p=0.024, 33%, p=0.002, and 49%, p=0.026, respectively) compared with controls., Conclusions: This study shows higher protein level of proBNP in human hearts than of BNP and NT-proBNP, increased proBNP mRNA expression in ICM samples, and a good correlation among tissue natriuretic peptide and GATA-4. Finally, ICM shows a high tissue protein level of proBNP, BNP, NT-proBNP and GATA-4., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p<0.05) and DCM (141%, p<0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p<0.05) and DCM (1.70-fold, p<0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p<0.0001), and it was increased in pathological hearts (p<0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p<0.05 and 131%, p<0.001) and DCM (56%, p<0.01 and 69%, p<0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p<0.001), perinucleolar chromatin (p<0.01) and dense fibrillar components (p<0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p<0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer. A soluble fragment of the EGFR extracellular domain (sEGFR) can be detected in the blood of patients who have non-small-cell lung cancer (NSCLC), but its clinical/ prognostic role must be further elucidated., Methods: sEGFR concentration was retrospectively determined by enzyme-linked immunosorbent assay in plasma samples from 308 advanced NSCLC patients (before treatment) and 109 healthy controls and correlated with clinico-pathological variables., Results: The concentration of sEGFR was lower in NSCLC patients than in controls (P < .0001). sEGFR behaves as a sensitive but not specific screening biomarker. No significant associations were observed between sEGFR concentration and demographic/clinical characteristics such as gender, Eastern Cooperative Oncology Group performance status, stage, and number or location of the metastatic sites. sEGFR was lower in patients with progressive disease or in squamous cell carcinoma compared with adenocarcinoma, but these differences were not significant. Patients with sEGFR ≤ 34.56 ng/mL showed a shorter overall survival (median 9.1 versus 12.2 months, P = .019) than others. Moreover, in multivariate analysis, sEGFR remained a significant independent prognostic marker., Conclusion: Low baseline sEGFR is associated with reduced survival in advanced NSCLC. Therefore, our findings in this large cohort of patients suggest that the determination of sEGFR concentration provides valuable prognostic information., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Platinum doublets are standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether neutropenia is: (1) an indicator for treatment efficacy, or (2) associated with specific polymorphisms., Patients and Methods: Four hundred ninety-four patients, treated with cisplatin-docetaxel were retrospectively analyzed. Relative dose intensity (RDI) was assessed for both drugs. Neutrophil counts were assessed only on Day 21 of each cycle. Genotyping was performed for 4 different polymorphisms in ERCC1, XRCC3, XPD-23, and XPD-10., Results: The median overall survival was 9 months. The mean RDI was 0.94 for cisplatin and 0.93 for docetaxel. Four hundred three patients received ≥ 3 cycles of chemotherapy, and 239 received ≥ 6 cycles. Thirty-one percent developed neutropenia, and 19% had Grade (G)3-4 neutropenia. RDI was lower in patients with neutropenia (G1-4; 0.87-0.93) when compared with those without (G0; 0.94-0.95; P < .02). Male patients (P = .02) had inferior survival when compared with female patients, and ECOG (Eastern Cooperative Oncology Group) 1-2 patients (P < .001) had worse survival when compared with ECOG 0. There was no significant survival difference with respect to Grade of neutropenia (G0, 8.7 vs. G1-2, 11.6 vs. G3-4, 9.6 months; P = .41). In ECOG 0 patients, survival was significantly better for neutropenic G1-4 (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.31-0.96; P = .034) when compared with non-neutropenic (G0) patients. No association was observed between examined polymorphisms and neutropenia., Conclusion: RDI was significantly higher in patients who did not develop neutropenia during treatment, but as the nadir period was not explored in our study, the low occurrence of neutropenia in our cohort is considered underestimated. There was no significant survival difference with respect to grade of neutropenia. Finally, none of the examined single nucleotide polymorphisms (SNPs) were associated with the presence of neutropenia, disease characteristics, response rates, or survival., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In addition to malignant neoplastic cells, cancer tissues also include immune cells, fibroblasts, and endothelial cells, including an abundant collection of growth factors, proangiogenic mediators, cytokines, chemokines, and components of the extracellular matrix. The main physiological function of the immune cells is to monitor tissue homeostasis, to protect against invading pathogens, and to eliminate transformed or damaged cells. Between immune cells and malignant cells in the tumor stroma, there is in fact a complex interaction which has significant prognostic relevance as the immune system has both tumor-promoting and -inhibiting roles. In non-small cell lung cancer (NSCLC), there is a marked infiltration of different types of immune cells, and the distribution, tissue localization, and cell types are significantly associated with progression and survival. Cancer immunotherapy has seen a significant progress during the last decade. An increased understanding of the mechanisms by which lung cancer cells escape the immune system, and the recognition of the key tumor antigens and immune system components in tumor ignorance have led to the development of several lung cancer vaccines. As the NSCLC prognosis in general is dismal, one may hope that future immunotherapy may be an effective adjunct to standard therapy, reversing immunologic tolerance in the tumor microenvironment. This review reports on the tumor stroma and in particular tumor-suppressing and -promoting roles of the immune system. Furthermore, it presents recent literature on relevant immune cell-related research in NSCLC.

Background: Circulating DNA is observed at higher concentrations in patients with lung cancer than in controls. Qualitative and quantitative analysis of circulating DNA is a promising noninvasive tool. Our aim was to prospectively study the association between the catalytic subunit of telomerase (human telomerase reverse transcriptase [hTERT]) in plasma and clinical variables and survival in a large-scale non-small cell lung cancer (NSCLC) study., Methods: Four hundred forty-six patients with stages IIIB and IV NSCLC with a median follow-up of 9.7 months (range, 0.5-45) were analyzed. Blood samples were collected before therapy start (cisplatin/docetaxel). Quantification of baseline circulating DNA was determined as the amount of free hTERT in plasma, by using real-time quantitative polymerase chain reaction., Results: Patients with hTERT ≤ 49.8 ng/ml (median value) had a median time to progression (TTP) of 6.3 months compared with 4.9 for hTERT more than 49.8 ng/ml (p = 0.001). Overall survival (OS) was significantly higher (10.9 versus 9.3 months) at lower hTERT levels (p = 0.012). When calculations were done using hTERT as continuous variable, we did not observe independent significant differences. Thus, there is an apparent discrepancy in p values when hTERT is considered as a continuous versus dichotomized variable. There was a tendency to differentiate median hTERT levels with respect to response rates (complete response + partial response: 33.1 versus stable disease + progressive disease: 50.7 ng/ml, p = 0.12), but other clinical variables such as age, gender, performance status, stage, histology, and number of metastatic locations were not associated with hTERT. In multivariate analysis, hTERT was an independent prognostic variable for both TTP (hazard ratio: 1.44, p < 0.001) and OS (hazard ratio: 1.33, p = 0.007)., Conclusions: In advanced NSCLC, high pretreatment circulating hTERT level is an independent poor prognostic marker for TTP and OS. Circulating DNA is a noninvasive marker, which may help to improve the prognostic profile of these patients.

Maintenance of both normal epithelial tissues and their malignant counterparts is supported by the host tissue stroma. The tumor stroma mainly consists of the basement membrane, fibroblasts, extracellular matrix, immune cells, and vasculature. Although most host cells in the stroma possess certain tumor-suppressing abilities, the stroma will change during malignancy and eventually promote growth, invasion, and metastasis. Stromal changes at the invasion front include the appearance of carcinoma-associated fibroblasts (CAFs). CAFs constitute a major portion of the reactive tumor stroma and play a crucial role in tumor progression. The main precursors of CAFs are normal fibroblasts, and the transdifferentiation of fibroblasts to CAFs is driven to a great extent by cancer-derived cytokines such as transforming growth factor-β. During recent years, the crosstalk between the cancer cells and the tumor stroma, highly responsible for the progression of tumors and their metastasis, has been increasingly unveiled. A better understanding of the host stroma contribution to cancer progression will increase our knowledge about the growth promoting signaling pathways and hopefully lead to novel therapeutic interventions targeting the tumor stroma. This review reports novel data on the essential crosstalk between cancer cells and cells of the tumor stroma, with an emphasis on the role played by CAFs. Furthermore, it presents recent literature on relevant tumor stroma- and CAF-related research in non-small cell lung cancer.

The therapeutic options for patients with advanced non-small-cell lung cancer (NSCLC) are palliative. Therefore, the quality of life in oncology is considered as an endpoint in clinical trials, and several scales have been accepted for its measurement in parallel with other clinical determinations. However, its use in clinical practice is hindered by various obstacles that need to be overcome. In this article we examine the concept of the quality of life in patients with NSCLC, as well as giving an evaluation and interpretation of the results of various clinical trials. We describe the new technological methods used in daily clinical practice to measure the quality of life.

Osteonecrosis of the jaws (ONJ) is an important possible late adverse effect of bisphosphonates. Serum C-terminal cross-linking telopeptide of type I collagen (CTX) can determine bone turnover and can act as a biological marker of bone resorption. We studied this biological marker in 15 patients (Group 1) with bisphosphonate-induced ONJ comparing with a control group of 10 healthy people matched by age and gender. We found no statistically significant relationships in Group 1 either between the serum CTX and the number of areas of exposed bone nor with the size of the osteonecrotic area.

Platinum compounds play a central role in cancer chemotherapy. Although treatment is limited by side effects, they continue to have widespread application. One of the main aims of clinical or translational research in cancer is the search for genetic factors that could foresee treatment outcomes, in biologic activity and toxic effects. This genetic analysis might allow selection of patients who will have the greatest benefit from chemotherapy. Furthermore, a better knowledge of the underlying molecular profile of the host and the tumor will facilitate screening for lung cancer susceptibility and tailoring of chemotherapy in individual patients, choosing those most likely to respond, adjusting doses more precisely in order to reduce less adverse effects, and establishing safety profiles based on individual genetic analyses. Herein, we discuss current knowledge regarding gene expression and polymorphisms of DNA repair enzymes in regard to cancer susceptibility and response to chemotherapy.