Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Monitoring Preparation of Derivative Protein Crystals via Raman Microscopy

This chapter deals with the application of Raman confocal microscopy to monitor the preparation of chemically modified protein crystals. We first introduce the peculiar properties of protein single crystals and related crystallization techniques. Then we move to present experimental sampling and theoretical background of Raman microscopy. Finally we show some examples of applications of Raman microscopy to protein derivative crystal

Utilizzo di una Superossidodismutasi modificata ottenuta in forma ricombinante (rMnSod) come agente antineoplastico e marker tumorale per neoplasie mammarie canine estrogeno-positive

Nel presente lavoro viene studiato l'utilizzo diagnostico di un’isoforma ricombinante di una superossidodismutasi isolata da liposarcoma umano (rMnSod) utilizzabile come marker tumorale per neoplasie mammarie canine sovraesprimenti recettori per estrogeni. Le capacità citostatiche e selettive Er+ di tale proteina sono state valutate in esperimenti “in vitro” prima su colture cellulari “MCF-7”e “in vivo” poi. In questo lavoro vengono descritte le pratiche diagnostiche e l’utilizzo della proteina marcata con Gallio 68 in cinque cagne sottoposte ad indagine PET di cui si è voluto dimostrare la captazione neoplastica della molecola

High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation

POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the diseaserelated symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation at 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial response in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analysed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome

O conhecimento e a importância das métricas de marketing para gestores de médias e grandes empresas brasileiras

Um dos principais desafios do marketing é possibilitar a identificação dos resultados gerados a partir da realização de ações na área. Os indicadores de marketing surgem como uma ferramenta que auxilia na mensuração e avaliação do desempenho. Este trabalho tem como foco a identificação do conhecimento, utilização e importância atribuída aos indicadores de marketing por profissionais de médias e grandes empresas brasileiras. Através de um estudo qualitativo com 11 gerentes ou diretores responsáveis pela área de marketing, identificou-se os principais indicadores de marketing utilizados no país e, através de uma survey realizada pelo telefone com 234 gestores de marketing de médias e grandes empresas do país, constatou-se que os profissionais brasileiros têm alto grau de conhecimento dos indicadores, porém, que a utilização dos mesmos no Brasil é menor do que em países como Reino Unido e China, embora os profissionais atribuam uma maior importância aos indicadores do que os destes países. O estudo verifica relações entre características das empresas, a utilização e o grau de importância que atribuem aos indicadores. Por fim, são apresentadas as considerações finais, limitações da pesquisa e sugestões para estudos futuros.One of the main marketing challenges is making the identification of the results generated from the actions made on this area. The marketing metrics come as one tool to assist measuring and availing the performance. This work has a focus the identification of the knowledge, use and importance attributed to the marketing metrics by professionals of medium and big Brazilian companies. Through a qualitative study with 11 marketing managers or directors where identified the main marketing metrics used in the country and, beyond a survey realized by the phone with 234 marketing executives of medium and big companies from Brazil, where identified that the Brazilian professionals have high degree of metrics knowledge, however the usage of these on Brazil still is lesser than countries like United Kingdom and China, even so the professionals attribute a bigger importance to the metrics than the professionals of this countries. The study verifies relations between characteristics of the companies and the usage and degree of importance that they attribute to the metrics. Finally the final considerations, limitations of the research and suggestions for future studies are presented

Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia. A patient-based survey on 1133 patients

Therapeutic approach for chronic myeloid leukemia (CML) patients has undergone a revolutionary change with the introduction of tyrosine kinase inhibitors, which improved overall survival and quality of life. Optimal therapy adherence has become of paramount importance to maximize the benefits in the long-term outcome. Several evidences have been reported that personal factors, such as social support, psychological and subjective perceptions about the drug used and the future, could influence adherence. We here report the results of a questionnaire specifically designed to evaluate factors influencing adherence and perceptions about the future, distributed to patients during regional Italian meetings. Overall, 1133 patients compiled the questionnaire: median age was 57 years. High rate of adherence was reported, but 42% of interviewed patients admitted that they had occasionally postponed a dose and 58% had discontinued therapy mainly for forgetfulness. The majority of patients discussed with personal physician about the importance of adherence and received sufficient information about illness and treatment, but would like to have discussed more about discomfort, anxiety and fear of the future. Summarizing personal drug compliance and estimating how many days a month, on average, the patients did not take the drug, the majority answered that it was less than 3 days (55%) and only a minority (4%) admitted that it was more than 7 days. Interviewed about discontinuation, 49% of patients answered that wouldn't interrupt because of fear of losing all the results achieved so far. This study suggests a higher level of satisfaction with more information received but the need of improving communication about possible future treatment free remission

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Exploring the relationships between dominance behavioral system, mentalization, theory of mind and assertiveness: analysis in a non-clinical sample

Introduction: The dominance behavioral system, a fundamental aspect of human behavior, orchestrates the drive for dominance, regulates dominant-subordinate dynamics, and shapes responses to perceived power dynamics. While the existing literature extensively delves into the components of this system, scant attention is paid to its interplay with mentalization, theory of mind, and assertiveness. Moreover, gender disparities in dominance behaviors are largely studied in terms of biological variables (levels of testosterone) and clinical populations. This study aims to understand the relationships between activation strategies of the dominance behavioral system, mentalization processes, theory of mind abilities, and levels of social discomfort in assertive communication. Moreover, to identify gender differences in the dominance behavioral system in a non-clinical sample. Methods: Our sample was composed of 67 students from a non-clinical population. They claimed the absence of any psychological, neurological, or developmental disorders. Results: A regression analysis was performed, and we found that levels of mentalization predict levels of hyperactivation of dominance behavioral system, but no significant results for the deactivation levels of the system were found. Moreover, no gender differences were found in levels of activations of the dominance behavioral system. Conclusion: These findings underscore the pivotal role of mentalization abilities in interpersonal dynamics, emphasizing the need for individuals to navigate social interactions adeptly. Furthermore, our research unveils implications for individual well-being and psychopathology, urging further investigation into how these dimensions intersect with various psychological disorders. By discerning the intricate mechanisms at play, we can develop targeted therapeutic interventions tailored to specific behavioral patterns, ultimately enhancing psychological resilience and fostering healthier social relationships in a non-clinical population

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment