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Burian, Rosemarie Anne, Tobias Appenzeller, Philipp Oertle, Christian Raez, Roderick Y. H. Lim, Serafino Forte, Sophie Dellas, Ellen Obermann, and Marija Plodinec. "Nanomechanical profiling of human breast tumors as prognostic marker for breast cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 11618. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11618.
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11618 Background: Assessment of tumor aggressiveness is crucial when making treatment decisions. Established prognostic markers may be insufficient to stratify cancer patients into treatment relevant risk groups. Emerging evidence indicates mechanical properties of cancer cells and their microenvironment play a vital role in cancer invasion and metastases. Detecting and measuring these nanomechanical changes could be a marker of cancer aggressiveness. Methods: We developed an atomic force microscope (AFM) based method: ARTIDIS (Automated and Reliable Tissue Diagnostics) for measuring nanomechanical properties of human tissue biopsies. These were performed on fresh, non-fixed tissue under physiological conditions. This novel method uses a micro-fabricated 20nm tip indenting and measuring stiffness of thousands of locations within 60-180minutes. This quantitative, biopsy-wide, nanomechanical profile strongly correlates to the tissue's biological composition. Post-AFM this biopsy is analyzed by pathology. We sought to differentiate benign from cancerous lesions based on nanomechanical properties; then link the cancerous nanomechanical profiles prospectively to the clinical outcomes. Results: Our results demonstrate the first AFM based nanomechanical profiling to detect aggressive breast cancer subtypes using fresh tissue in a clinical setting. We have shown that nanomechanical profiles of human breast cancer biopsies display stiffness profiles distinct from surrounding normal tissue. Breast cancer subtypes were distinguishable by their nanomechanical properties only. We have discovered specific nanomechanical profiles of tumor subtypes likely to metastasize. When the primary tumor displayed the same soft nanomechanical profile as adjacent tissue, this was associated with positive nodal status. Conclusions: Our results demontrate nanomechanical profiling is a fast and sensitive method to stratify malignant biopsies into relevant subgroups in a clinical setting. Relative stiffness and distribution values provide a nanomechanical profile indicating cancer aggressiveness. This will help optimize specific cancer diagnosis, orientate therapy choice and support patient follow up.
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Rasskazova, E. "Latent personality profiles in mental illnesses: analysis of restructured clinical scales of MMPI-2." V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY, no. 1 (May 15, 2019): 52–60. http://dx.doi.org/10.31363/2313-7053-2019-1-52-60.
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On a sample of 262 patients with mental illnesses based on restructured clinical scales of MMPI-2 six latent personality profiles were identified. A “suppressive” profile is characterized by a tendency toward self-presentation, suppression, and is more common with adaptation disorder and schizophrenia. The “normative” profile can be combined with aggressiveness, difficulties of behavior control and is typical for every second patient with addictions. The “psychopathized” profile is haracterized by a nonspecific increase in psychopathological complaints and is common in depressions. The “neurotic” profile is typical for patients with affective and schizotypal disorders. The “schizoid” profile is associated with signs of bizarre mantations, psychotic symptoms and fears, while the profile of decompensation reflects a general acute condition or responses invalidity.
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Giusca, Simona Eliza, Elena Corina Andriescu, Irina Draga Caruntu, and Delia Ciobanu. "Clinicopathological Profile of Medullary Thyroid Carcinoma—Could We Predict Aggressive Behavior?" Biomedicines 11, no. 1 (January 3, 2023): 116. http://dx.doi.org/10.3390/biomedicines11010116.
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Medullary thyroid carcinoma (MTC) accounts for only 2–5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims to identify criteria that could predict increased aggressiveness. We analyzed 59 consecutive MTC cases. We focused on the relationships among clinicopathological characteristics, parameters of aggressiveness (extrathyroidal extension, lymphovascular invasion, and lymph node metastasis), and parameters for MTC grading. Statistically significant correlations were found for tumor size, lymphovascular invasion, and lymph node metastasis and tumor focality and lymph node metastasis. Our results showed, in tumors larger than 40 mm, odds ratios (ODs) of 13.695 and 6 for lymphovascular invasion and lymph node metastasis, respectively; in multifocal tumors, we registered an OD of 9.42 for lymph node metastasis. No significant correlation was found for the parameters of the MTC grading system when assessed individually and integrated by reporting low-grade and high-grade risk groups. Although our data indicate that lymphovascular invasion and lymph node metastasis remain significant markers for aggressiveness, studies on larger series of cases are mandatory to detect and validate new factors responsible for the variable course of MTC.
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Escalante, Hugo Jair, Esaú Villatoro-Tello, Sara E. Garza, A. Pastor López-Monroy, Manuel Montes-y-Gómez, and Luis Villaseñor-Pineda. "Early detection of deception and aggressiveness using profile-based representations." Expert Systems with Applications 89 (December 2017): 99–111. http://dx.doi.org/10.1016/j.eswa.2017.07.040.
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Boussaidi, Ahmed, and Mounira Sidhom Hamed. "The Impact of Governance Mechanisms on Tax Aggressiveness: Empirical Evidence from Tunisian Context." Journal of Asian Business Strategy 5, no. 1 (February 19, 2015): 1–12. http://dx.doi.org/10.18488/journal.1006/2015.5.1/1006.1.1.12.
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Research on the tax side occupied the stage center during the last decade. Several researchers have attempted to study the different effects of some options such as tax aggressiveness on firms and individuals. Overall, tax aggressiveness affects negatively the longevity of companies but what remains unanswered is by what specific means corporate governance decreases tax aggressiveness activities. In this paper, we examine the effect of some governance mechanisms on corporate tax aggressiveness. The study is based on the analysis of a sample of Tunisian listed firms over the 2006-2012 periods. Our regression results indicate that diversity in gender on corporate board, managerial and concentration ownership has significant effects on firms` tax aggressiveness activities. Board`s diversity and managerial ownership exhibit a positive association with the effective tax rate while increases in concentration ownership tend to affect it negatively. However, findings don`t show any significant effects of corporate board size and external auditor`s profile on the tax aggressiveness.
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Sobchik, L. N., B. A. Spasennikov, and S. V. Kulakova. "Criminological Aspects of Aggression." Psychology and Law 12, no. 1 (2022): 209–25. http://dx.doi.org/10.17759/psylaw.2022120116.
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The results of a retrospective study of groups of convicts with varying degrees of aggressive behavior show the possibilities of the Standardized Multifactorial Personality Research Method (SMIL, the Russian version of MMPI), the interpretive approach of which is based on the one created by L.N. Sobchik theory of leading trends in assessing the degree of aggressiveness corresponding to the severity of the committed act. The leading tendencies, according to the average profiles of SMIL, are determined: among "hooligans" impulsivity with weakly expressed aggressiveness and unformed self-control; the "robbers" have rigidity, readiness for illegal behavior; in "killers" the severity of aggressiveness (in the hyperthymic type, explosive features and properties of expansive-schizoid accentuation; in the hypersthenic type, exaltation, overestimated self-esteem, an outwardly blaming type of response; in persons with impulse pathology, a partial violation in the sexual sphere with preserved intelligence); for “corrupt officials”: the profile is in the corridor of normative dispersion, but self-esteem and ideas about their own material well-being are directly proportional; in minors, aggression acts as a hypercompensation of an insecure personality with pseudo-aggressive actions.
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Obminski, Zbigniew, Helena Mroczkowska, Marina Jagiello, and Artur Litwiniuk. "Sex-and sport related differences in the personality traits students in volleyball, basketball and judo athletes." Physical education of students 24, no. 6 (December 30, 2020): 304–11. http://dx.doi.org/10.15561/20755279.2020.0601.
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Background and Study Aim. Psychology is a very important field of knowledge in every area of human life, and personality and temperament have a large impact on the quality of human life, including mental and physical health, and indirectly on the results achieved in elite sport. The purpose of the study was to verify the assumption that there are differences in the psychological profile of professional sportsman students depending on the gender and type of sports discipline.
Material and methods. The research covered athletes of both sexes belonging to academic sports clubs practicing volleyball, basketball and judo. The size of each of the six groups was 24 people. Standardized psychological tests were used to determine the levels of selected personality and temperamental traits: trait anxiety, neuroticism, extraversion, briskness, perseveration, sensory sensitivity, emotional reactivity, endurance, activity, and six components of aggressiveness: physical aggressiveness, verbal aggressiveness, indirect aggressiveness, negativism, suspiciousness, resentment, irritability, overall and guilty sense. Two-way analysis of variance (sex * sport) was used to assess the differences between the groups.
Results. Women showed higher trait anxiety, extraversion, perseveration, emotional reactivity results and lower physical aggressiveness levels compared to men. Basketball practitioners had the lowest levels of aggressiveness components, and the highest levels of briskness.
Conclusions. The results suggest that the psychological profile of women participating in competitive sports may account for a higher emotional cost than men in terms of competition and failure. This fact should be taken into account by the coaches of female sports teams. The differences between sports may be due to the different structure of the task.
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Waro, Mochammad Choirul, and Alifiati Fitrikasari. "Profile of Schizophrenia Aggressiveness with the Risk of Suicide based on the Personality and Social Performance Score." Scientia Psychiatrica 2, no. 1 (January 3, 2021): 38–41. http://dx.doi.org/10.37275/scipsy.v2i1.27.
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A B S T R A C TIntroduction. The risk of schizophrenia for suicide is 10%, of which 10% -15% ofpeople with schizophrenia die of suicide at 20 years of follow-up. Aggressiveness is afactor to be watched out. Other factors are hallucinations, suicide, early-onset,history of schizophrenia, surveillance, age, gender, education, genetics, affect ofdepression. This study aimed to describe the sociodemographic profile,aggressiveness, hallucinations of suicide in schizophrenic patients. Methods. Thedesign of this study is descriptive research. The number of samples in this study was49 schizophrenic patients at risk of suicide. The risk of aggressiveness is measuredby the Personality and Social Performance Score. Results. Of the 49 patients, it wasfound that the proportion of male patients was 31 people (63.3%) and 18 women(36.7%). Aggressive behaviour based on PSP score was divided into modestaggressiveness of 22 people (44.9%), severe 20 people (40.8%), very severe two people(4.1%). Suicidal hallucinations were also found in 11 patients (22.4%). Conclusion.There are markedly aggressive behaviour and hallucinations of suicide in the majorityof schizophrenic patients.
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Diveeva, K. A. "Sociological Analysis of the Profile of Extremist." Sociology and Law, no. 3 (October 19, 2021): 40–44. http://dx.doi.org/10.35854/2219-6242-2021-3-40-44.
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The article is devoted to the discussion of the psychological and socio-demographic characteristics of the extremist's personality. The author of the article focuses on the relevance of studying the ideas about the image of an extremist in the public consciousness. The article presents the results of a study conducted in 2021 to identify the attitude of the population of the Krasnoyarsk district to the problems of extremism and radicalism. The results of the study showed that the dominant image of an extremist among the residents of the region is negative. The respondents attributed to the main features inherent in the personality of an extremist: aggressiveness, bitterness, cruelty, intolerance to people, hostility, lack of education, selfishness.
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Deslandes, Manon, Anne Fortin, and Suzanne Landry. "Audit committee characteristics and tax aggressiveness." Managerial Auditing Journal 35, no. 2 (December 11, 2019): 272–93. http://dx.doi.org/10.1108/maj-12-2018-2109.
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Purpose This study aims to analyze the relationship between a company’s use of aggressive tax planning and several audit committee members’ characteristics, namely, independence, expertise, diligence and gender diversity. Design/methodology/approach This paper is an empirical research using archival data from 289 Canadian listed companies for the 2011-2015 period. Findings The authors find that measures of expertise and diligence are significantly related to tax aggressiveness. Financial expertise and tenure on the audit committee play an important role in constraining tax aggressiveness, as does having a larger audit committee. Research limitations/implications One limitation – and an area for future research – is that the effects of the audit committee members’ relationships with managers of the firms were not investigated. Practical implications Knowledge of audit committee characteristics may send a signal to shareholders, investors and tax agencies regarding the company’s potential risk with respect to aggressive tax planning. The analysis provides useful insights for board governance committees when determining the profile of persons to nominate for board positions and committees. In discussing tax-risk management, the study may heighten audit committee members’ awareness of their role in this respect. Originality/value This study’s results indicate that even in a setting where incentives for firms to be tax-aggressive is low compared to high-tax rate countries, there is variability in firms’ tax aggressiveness. This situation allows us to find audit committee characteristics that are effective in decreasing tax aggressiveness.
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Sekiguchi, Naohiro, Junko Nomoto, Akihisa Nagata, Masahiro Kiyota, Ichiro Fukuda, Kazuaki Yamada, Naoki Takezako, and Yukio Kobayashi. "Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion." BioMed Research International 2018 (October 4, 2018): 1–8. http://dx.doi.org/10.1155/2018/6728128.
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Background. Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoma. Clinically, chromosome 6q deletion (6q del) including loss of the B lymphocyte-induced maturation protein 1 gene (BLIMP-1) is reported to be associated with poor prognosis. However, it remains unclear how the underlying biological mechanism contributes to the aggressiveness of WM with 6q del. Methods. Here, we conducted oligonucleotide microarray analysis to clarify the differences in gene expression between WM with and without 6q del. Gene ontology (GO) analysis was performed to identify the main pathways underlying differences in gene expression. Eight bone marrow formalin-fixed paraffin-embedded samples of WM were processed for interphase fluorescence in situ hybridization analysis, and three were shown to have 6q del. Results. GO analysis revealed significant terms including “lymphocyte activation” (corrected p value=6.68E-11), which included 31 probes. Moreover, IL21R and JAK3 expression upregulation and activation of the B-cell receptor signaling (BCR) pathway including CD79a, SYK, BLNK, PLCγ2, and CARD11 were detected in WM with 6q del compared with WM without 6q del. Conclusion. The present study suggested that the BCR signaling pathway and IL21R expression are activated in WM with 6q del. Moreover, FOXP1 and CBLB appear to act as positive regulators of the BCR signaling pathway. These findings might be attributed to the aggressiveness of the WM with 6q del expression signature.
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Luna, Herdee Gloriane Cristal, Cher Alaine Cristal Luna, Gloria R. Cristal-Luna, and Cesar Vilela Luna. "Association of dyslipidemia with the aggressive molecular subtypes and pathologic profile of newly diagnosed nonmetastatic breast cancer patients." Journal of Clinical Oncology 30, no. 27_suppl (September 20, 2012): 19. http://dx.doi.org/10.1200/jco.2012.30.27_suppl.19.
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19 Background: To investigate the association of dyslipidemia with the aggressive pathologic profile and molecular subtypes among the premenopausal and postmenopausal breast cancer patients. Methods: A retrospective review of Filipino breast cancer patients from 1990 to 2010 from an oncology clinic was done. Patients were grouped to pre- and post-menopausal and each group were divided to those with and without dyslipidemia. Association of dyslipidemia with breast cancer aggressiveness, (1) by pathology (histopathologic diagnosis, grade, invasion, TNM stage) and (2) by molecular phenotype (using the hormone status: estrogen and progesterone receptor positivity) and HER-2 neu status (overexpression by immunohistochemical stain / gene amplification by fluorescent in situ hybridization), was assessed using Fisher exact test. Results: Among 728 breast cancer patients, 201 met the inclusion criteria with 103 premenopausal (36 with dyslipidemia, 67 without dyslipidemia) and 98 were postmenopausal (42 with dyslipidemia, 56 without dyslipidemia). Significant association was noted only among pre-menopausal in terms of the molecular phenotypes (p value 0.002) when compared to individual parameters: total cholesterol (p value <0.001), LDL (p value <0.001), HDL (p value 0.006), and triglyceride (p value <0.001). Conclusions: Dyslipidemia was not found to be a factor associated with aggressiveness of breast cancer in terms of the pathology for both pre-menopausal and post-menopausal groups. Only among premenopausal patients was dyslipidemia shown to be a significant marker of aggressiveness in terms of poorer molecular subset (luminal B, HER-2, basal like). This finding was not observed among post-menopausal group.
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Geffroy, Benjamin, Bastien Sadoul, and Agnès Bardonnet. "Behavioural syndrome in juvenile eels and its ecological implications." Behaviour 152, no. 2 (2015): 147–66. http://dx.doi.org/10.1163/1568539x-00003236.
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Behavioural syndrome, which refers to a suite of correlated behaviours across differing situations, has been identified in numerous animals, including fish. The presence and conservation of a behavioural syndrome throughout evolutionary times suggests it confers various advantages at a population level. In eels, such as the European eel (Anguilla anguilla), activity and aggressiveness are important factors in their life history, since both traits influence dispersal and territoriality. In the present study we investigated whether these behavioural traits were consistent at both the nychtemeral scale (24 h) and over a long time period (7 months). In addition, we investigated if aggressiveness and activity were positively correlated. Both activity and aggressiveness were significantly repeatable, indicating that both behavioural traits could be considered as personality traits. Interestingly, nocturnal activity was correlated to diurnal activity, indicating that this personality trait was highly stable at the circadian scale. Both aggressiveness and activity were correlated in the course of the experiment, underlining the presence of a behavioural syndrome. The detection of two behaviourally distinct groups in juvenile eels: aggressive and active individuals versus their counterpart have implications in the understanding of the colonization profile of the watershed. We discuss these findings in relation to the ecology of this species.
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Kocemba-Pilarczyk, Kinga A., Paulina Dudzik, and Katarzyna Leśkiewicz. "The relationship between expression of VIMENTIN and CD146 genes in breast cancer." Bio-Algorithms and Med-Systems 17, no. 1 (March 1, 2021): 1–7. http://dx.doi.org/10.1515/bams-2020-0058.
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Abstract Objectives CD146 is an adhesive molecule that was originally reported on malignant melanoma cells as a protein crucial for cell adhesion. It is now known that high expression of the CD146 protein is not only characteristic of melanoma, but it occurs on a number of cancers, contributing to worse prognosis and increased aggressiveness. Independent in vitro studies in breast cancer have shown that CD146 protein alone can induce a change in epithelial to mesenchymal transcriptional profile, which is the basis of the tumor aggressiveness and metastasis. Methods In the following work, the correlation coefficients were analyzed between the genes of the mesenchymal profile and the CD146 gene in 10 independent transcriptomic data of breast cancer patients. Results The analysis confirmed the relationship between CD146 expression and mesenchymal profile genes, pointing VIMENTIN as the gene which expression is most strongly correlated with the CD146, suggesting that both genes, CD146 and VIM may be directly controlled by the same mechanism or regulate one another. Conclusions The analysis points a potential route for research on the CD146 gene expression, which may lead to understanding of its regulation in breast cancer, contributing to the development of new therapeutic strategies targeting highly metastatic breast cancer cells.
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Espiau-Romera, Pilar, Sarah Courtois, Beatriz Parejo-Alonso, and Patricia Sancho. "Molecular and Metabolic Subtypes Correspondence for Pancreatic Ductal Adenocarcinoma Classification." Journal of Clinical Medicine 9, no. 12 (December 21, 2020): 4128. http://dx.doi.org/10.3390/jcm9124128.
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Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis. Interestingly, recent works have also revealed the existence of metabolic subtypes with differential prognosis within PDAC, which correlated to defined molecular subclasses in patients: lipogenic subtype correlated with a classical/progenitor signature, while glycolytic tumours associated with the highly aggressive basal/squamous profile. Bioinformatic analyses have demonstrated that the representative genes of each metabolic subtype are up-regulated in PDAC samples and predict patient survival. This suggests a relationship between the genetic signature, metabolic profile, and aggressiveness of the tumour. Considering all this, defining metabolic subtypes represents a clear opportunity for patient stratification considering tumour functional behaviour independently of their mutational background.
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Calabrese, Giovanna, Anna Dolcimascolo, Filippo Torrisi, Agata Zappalà, Rosario Gulino, and Rosalba Parenti. "MiR-19a Overexpression in FTC-133 Cell Line Induces a More De-Differentiated and Aggressive Phenotype." International Journal of Molecular Sciences 19, no. 12 (December 7, 2018): 3944. http://dx.doi.org/10.3390/ijms19123944.
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In recent years, microRNAs (miRNAs) have received increasing attention for their important role in tumor initiation and progression. MiRNAs are a class of endogenous small non-coding RNAs that negatively regulate the expression of several oncogenes or tumor suppressor genes. MiR-19a, a component of the oncogenic miR-17-92 cluster, has been reported to be highly expressed only in anaplastic thyroid cancer, the most undifferentiated, aggressive and lethal form of thyroid neoplasia. In this work, we evaluated the putative contribution of miR-19a in de-differentiation and aggressiveness of thyroid tumors. To this aim, we induced miR-19a expression in the well-differentiated follicular thyroid cancer cell line and evaluated proliferation, apoptosis and gene expression profile of cancer cells. Our results showed that miR-19a overexpression stimulates cell proliferation and alters the expression profile of genes related to thyroid cell differentiation and aggressiveness. These findings not only suggest that miR-19a has a possible involvement in de-differentiation and malignancy, but also that it could represent an important prognostic indicator and a good therapeutic target for the most aggressive thyroid cancer.
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Ben Jemaa, Awatef, Yosra Bouraoui, Sataa Sallami, Yassine Nouira, and Ridha Oueslati. "A Comparison of the Biological Features of Prostate Cancer with (PSA+, PSMA+) Profile according to RKIP." BioMed Research International 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/409179.
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Purpose. To investigate differences in the biological features of the most immunoexpressed prostate cancer (PC) profiles (PSA+, PSMA+) according to the RKIP.Methods. 19 PC with dominant Gleason grade ≥8 were studied. Expression of PSA, PSMA, RKIP, Raf-1, MEK-1, ERK-1, ERK-2, p-Akt (T308), p-Akt (S473), NF-κB p50, and NF-κBp65 were detected immunohistochemically.Results. Loss of RKIP in the most immunoexpressed PC (PSA+, PSMA+) profile was associated with increased levels of PSA and PSMA expression. Intensities of immunoreactions to PSA and PSMA were higher in cancer cells negative for RKIP (12.51 ± 1.6 and 34.95 ± 1.92) compared to those positive for RKIP (4.68 ± 1.11 and 28.56 ± 0.91). In parallel, missing RKIP expression in PC patients with PSA+, PSMA+ profile was connected with increased components of both Raf-1/MEK/ERK and NF-κB (p65/p50), whereas Akt is activated independently of RKIP.Conclusions. Although characterized by the same (PSA+, PSMA+) profile, PC phenotype missing the RKIP related to invasive potential and greater biological aggressiveness reflected in overexpression of components of Raf-1/MEK/ERK and NF-κB (p65/p50) in which Akt is activated independently of RKIP. Taking into account the PC phenotypes according to RKIP among PSA-PSMA profiles may improve distinguishing them from cancers that will become more aggressive and therefore adapt the therapeutic strategies in those patients.
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Ward, Laura Sterian, Elaine Cristina Morari, Janaina Luisa Leite, Natassia Elena Bufalo, Ana Carolina Trindade Guilhen, Priscilla Pereira C. de Araujo, Alfio J. Tincani, Ligia V. M. Assumpção, and Patricia Sabino Matos. "Identifying a risk profile for thyroid cancer." Arquivos Brasileiros de Endocrinologia & Metabologia 51, no. 5 (July 2007): 713–22. http://dx.doi.org/10.1590/s0004-27302007000500008.
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The large use of simple and effective diagnostic tools has significantly contributed to the increase in diagnosis of thyroid cancer over the past years. However, there is compelling evidence that most micropapillary carcinomas have an indolent behavior and may never evolve into clinical cancers. Therefore, there is an urgent need for new tools able to predict which thyroid cancers will remain silent, and which thyroid cancers will present an aggressive behavior. There are a number of well-established clinical predictors of malignancy and recent studies have suggested that some of the patient’s laboratory data and image methods may be useful. Molecular markers have also been increasingly tested and some of them appear to be very promising, such as BRAF, a few GST genes and p53 polymorphisms. In addition, modern tools, such as immunocytochemical markers, and the measure of the fractal nature of chromatin organization may increase the specificity of the pathological diagnosis of malignancy and help ascertain the prognosis. Guidelines designed to select nodules for further evaluation, as well as new methods aimed at distinguishing carcinomas of higher aggressiveness among the usually indolent thyroid tumors are an utmost necessity.
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Lin, Chia-Hung, Chen-Chung Liao, Shu-Ying Wang, Chia-Yi Peng, Yi-Chen Yeh, Mei-Yu Chen, and Teh-Ying Chou. "Comparative O-GlcNAc Proteomic Analysis Reveals a Role of O-GlcNAcylated SAM68 in Lung Cancer Aggressiveness." Cancers 14, no. 1 (January 4, 2022): 243. http://dx.doi.org/10.3390/cancers14010243.
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O-GlcNAcylation is a reversible and dynamic post-translational protein modification catalyzed by O-GlcNAc transferase (OGT). Despite the reported association of O-GlcNAcylation with cancer metastasis, the O-GlcNAc proteome profile for cancer aggressiveness remains largely uncharacterized. Here, we report our comparative O-GlcNAc proteome profiling of two differentially invasive lung adenocarcinoma cell lines, which identified 158 down-regulated and 106 up-regulated candidates in highly invasive cells. Among these differential proteins, a nuclear RNA-binding protein, SAM68 (SRC associated in mitosis of 68 kDa), was further investigated. Results showed that SAM68 is O-GlcNAcylated and may interact with OGT in the nucleus. Eleven O-GlcNAcylation sites were identified, and data from mutant analysis suggested that multiple serine residues in the N-terminal region are important for O-GlcNAcylation and the function of SAM68 in modulating cancer cell migration and invasion. Analysis of clinical specimens found that high SAM68 expression was associated with late cancer stages, and patients with high-OGT/high-SAM68 expression in their tumors had poorer overall survival compared to those with low-OGT/low-SAM68 expression. Our study revealed an invasiveness-associated O-GlcNAc proteome profile and connected O-GlcNAcylated SAM68 to lung cancer aggressiveness.
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Glas, Annuska M., Marie Jose Kersten, Leonie Delahaye, Robby E. Kibbelaar, Joannes H. J. M. Van Krieken, Philip M. Kluin, Laura J. van ‘t Veer, and Daphne de Jong. "Gene Expression Profiles Are Best Suited To Assess Present Though Not Future Clinical Aggressiveness in Follicular Lymphoma." Blood 104, no. 11 (November 16, 2004): 698. http://dx.doi.org/10.1182/blood.v104.11.698.698.
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Abstract Follicular lymphoma (FL) is characterized by an indolent clinical course and frequent relapses. Transformation to more aggressive disease is common and one of the main causes of death. The time to transformation may vary widely and some patients show early transformation and a poor prognosis. Main questions in FL center on markers to predict transformation (and prognosis) at the time of diagnosis and to accurately assess the transformed phase to tailor the choice of therapy. Currently, prognostic stratification for actual aggressiveness and overall survival is based on histological grading and clinical criteria; however, in up to 30% of all cases these methods prove to be insufficient. Using 18k cDNA arrays, we analyzed gene-expression patterns of 135 cases of FL addressing both issues. 1) Using supervised classification on a training set of paired samples from the indolent and aggressive disease episodes and on an independent validation set, a 81-gene-expression profile was established that could, with an accuracy of 100% and 93% respectively distinguish indolent from aggressive disease. Importantly, in a third series of FL with ambiguous histological grade, precluding meaningful morphological guidance, the profile showed a 94% classification accuracy supporting the value of this method for practical clinical use. The profile consists of genes involved in cell cycle control, DNA synthesis and metabolism (upregulated in high-grade disease), T-cell related genes (upregulated in low-grade disease) and T-cell and macrophage activation markers, that are significantly upregulated upon transformation. This profile, however, did not predict future transformation in FL samples at diagnosis. 2) A separate analysis was performed in a selection of the biopsy samples of not previously treated patients with grade 1 and 2 FL with transformation to DLBCL within 7–22 months after diagnosis and no transformation with a minimum follow-up of 108 months. Supervised and unsupervised cluster analysis showed no differences between both groups exceeding the threshold of significance to construct a predictor profile with a validated significance, underlining the biological homogeneity of the study cohort. Direct comparison analysis on the basis of signal-to-noise ratio’s suggested a discriminative role of the immune response with enhanced cytokine- and chemokine-mediated T-cell activation and antigen-processing in the extremes of the spectrum. However, differences were slight and the immune-response seemed to play a less distinctive role in patients with transformed disease after more than 3 years. In conclusion, actual indolent and aggressive clinical behavior can be more reliably distinguished using a FL-stratification profile than the currently used histological grading and clinical criteria, and may provide an important alternative to guide the choice of therapy in FL patients both at presentation and at relapse. Although there may be subtle differences between rapidly transforming disease and long-term stable indolent disease, possible inherent variations are insufficient to reliably predict future transformation.
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Santos, Driéle B., Geysson J. Fernandez, Luciana M. C. Pardini, Maria Inês M. C. Pardini, and Adriana C. Ferrasi. "Transcriptomic Profile of Canine Mammary Ductal Carcinoma." International Journal of Molecular Sciences 24, no. 6 (March 8, 2023): 5212. http://dx.doi.org/10.3390/ijms24065212.
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Dogs can be excellent models for spontaneous studies about breast cancers, presenting similarities in clinical behavior and molecular pathways of the disease. Thus, analyses of the canine transcriptome can identify deregulated genes and pathways, contributing to the identification of biomarkers and new therapeutic targets, benefiting humans and animals. In this context, this study aimed to determine the transcriptional profile of canine mammary ductal carcinoma and contribute to the clarification of the importance of deregulated molecules in the molecular pathways involved in the disease. Therefore, we used mammary ductal carcinoma tissue samples and non-tumor mammary tissue from the radical mastectomy of six female dogs. Sequencing was performed on the NextSeq-500 System platform. A comparison of carcinoma tissue and normal tissue revealed 633 downregulated and 573 upregulated genes, which were able to differentiate the groups by principal component analysis. Gene ontology analysis indicated that inflammatory, cell differentiation and adhesion, and extracellular matrix maintenance pathways were mainly deregulated in this series. The main differentially expressed genes observed in this research can indicate greater disease aggressiveness and worse prognosis. Finally, the study of the canine transcriptome indicates that it is an excellent model to generate information relevant to oncology in both species.
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Navin Chandra, Gupta, Arora Shaweta, Kundu Aditi, Sharma Pankaj, Rao Mahesh, and Bhattacharya Ramcharan. "UPLC-Q-TOF-MS-based untargeted studies of the secondary metabolites secreted by Sclerotinia sclerotiorum under the axenic condition." Journal of Plant Science and Phytopathology 6, no. 3 (December 29, 2022): 173–82. http://dx.doi.org/10.29328/journal.jpsp.1001095.
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The stem rot disease has emerged globally as a major threat to oilseed Brassica's productivity and seed quality. The generalist causal pathogen Sclerotinia sclerotiorum (Lib.) de Bary shows large variability in their aggressiveness and pathogenicity. Revealing the pathogen's metabolic profile and signaling components in host-pathogen interaction is fundamental in understanding host resistance to the disease. In this study, the metabolites released by the pathogenic strains of S. sclerotiorum under the axenic culture have been identified using the untargeted high-resolution UPLC-QTOF-ESI-MS/MS. The analysis of the ethyl acetate extracts of the S. sclerotiorum culture revealed ten major secondary metabolites namely, sclerin, sclerotinin-B, sclerone, melanin, bostrycoidin, botcinin-D, botcinin-A, gliovirin, scleramide, and botcinic acid. The later six metabolites are being reported for the first time in the culture extract of the S. sclerotiorum pathogen. Based on the overlapping and unique informative peaks in the chromatograms, the six S. sclerotiorum strains were grouped into three major clades in the phylogenetic analysis. The clustering based on metabolic profiles does not substantiate the diversity based on morphology or virulence differences over the host. The findings of the study signified the metabolites secreted under the axenic conditions are varies based on their growth and developmental stages and may not necessarily be the determining factors for their differential aggressiveness and virulence to their host.
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Albulescu, Radu, Elena Codrici, Ionela Daniela Popescu, Simona Mihai, Laura Georgiana Necula, Daniel Petrescu, Mihaela Teodoru, and Cristiana Pistol Tanase. "Cytokine Patterns in Brain Tumour Progression." Mediators of Inflammation 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/979748.
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Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body’s response to cancer has many parallels with inflammation and repair; the inflammatory cells and cytokines present in tumours are more likely to contribute to tumour growth, progression, and immunosuppression, rather than in building an effective antitumour defence. Using new proteomic technology, we have investigated serum profile of pro- (IL-1β, IL-6, IL-8, IL-12, GM-CSF, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF) in order to assess tumoural aggressiveness. Our results indicate significant dysregulation in serum levels of cytokines and angiogenic factors, with over threefold upregulation of IL-6, IL-1β, TNF-α, and IL-10 and up to twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are involved in tumour progression and aggressiveness, and are also involved in a generation of disease associated pain.
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Yamasaki, Tomohiro, Adrian Lita, Tyrone Dowdy, Mark Gilbert, and Mioara Larion. "CBMT-07. BIOMARKERS OF AGGRESSIVENESS IN IDH MUTANT GLIOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi34. http://dx.doi.org/10.1093/neuonc/noz175.129.
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Abstract BACKGROUND Gliomas with isocitrate dehydrogenase (IDH) mutations in adults evolve from lower-grade gliomas to secondary glioblastomas (GBM), a fatal disease with fast progression. IDH mutation occurs early in tumorigenesis, and persistently contribute to the reprograming of glucose, lipid and amino acid metabolism. This offer a plethora of potential biomarkers of progression. However, because it is extremely difficult to detect the distribution and transfer of metabolites changing in every moment in a single cell, the involvement of metabolites produced by mutant IDH in malignant progression remains understudied. MATERIALS AND METHODS Raman imaging spectroscopy, which can image chemical bonds and concentration of molecules at submicron spatial resolution, enables detection of spatiotemporal changes of metabolomes in live cells. We developed the software called Biomolecular Component Analysis (BCAbox) to deconvolute the recorded raw Raman spectra, leading to detection of unique spectral features of different classes of biomolecules. RESULTS AND CONCLUSIONS We applied Raman imaging spectroscopy to GBM cell lines that were transfected with IDH1 mutant gene. Our results indicated that lipid metabolism has a unique profile in IDH1 mutant gliomas. Subsequent mass spectrometry analysis of extracted organelle revealed the exact classes of lipids altered in the IDH mutant glioma and suggested biomarkers unique to IDH1 mutant. We will report our validation studies of the biomarkers in patient-derived IDH mutant glioma cell lines and patients derived-orthotopic xenograft mouse models with different degrees of aggressiveness and in matched primary versus recurrent gliomas. The results of the present study may provide novel insights into the discovery of metabolic biomarkers for the malignant progression in IDH mutant gliomas.
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Ouldamer, Lobna, Marie-Lise Jourdan, Michelle Pinault, Flavie Arbion, and Caroline Goupille. "Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators." Biomedicines 10, no. 5 (April 26, 2022): 995. http://dx.doi.org/10.3390/biomedicines10050995.
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While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with invasive breast carcinoma were analyzed. Fatty acid profile was established by gas chromatography. For normal-weight women, major changes in fatty acid profile occurs after menopause, with the enrichment of long-chain polyunsaturated fatty acids (LC-PUFAs) of both n-6 and n-3 series enrichment, but a stable LC-PUFAs n-6/n-3 ratio across age. BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio. Regarding cancer, axillary lymph nodes (p = 0.02) and inflammatory breast cancer (p = 0.08) are more frequently involved in obese women. Increased BMI induces an LC-PUFAs n-6 accumulation, including arachidonic acid, in adipose tissue. This may participate in the development of low-grade inflammation in obese women and breast tumor progression. These results suggest the value of lifestyle and LC-PUFAs n-3 potential, in the context of obesity and breast cancer secondary/tertiary prevention.
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Ouldamer, Lobna, Marie-Lise Jourdan, Michelle Pinault, Flavie Arbion, and Caroline Goupille. "Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators." Biomedicines 10, no. 5 (April 26, 2022): 995. http://dx.doi.org/10.3390/biomedicines10050995.
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While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with invasive breast carcinoma were analyzed. Fatty acid profile was established by gas chromatography. For normal-weight women, major changes in fatty acid profile occurs after menopause, with the enrichment of long-chain polyunsaturated fatty acids (LC-PUFAs) of both n-6 and n-3 series enrichment, but a stable LC-PUFAs n-6/n-3 ratio across age. BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio. Regarding cancer, axillary lymph nodes (p = 0.02) and inflammatory breast cancer (p = 0.08) are more frequently involved in obese women. Increased BMI induces an LC-PUFAs n-6 accumulation, including arachidonic acid, in adipose tissue. This may participate in the development of low-grade inflammation in obese women and breast tumor progression. These results suggest the value of lifestyle and LC-PUFAs n-3 potential, in the context of obesity and breast cancer secondary/tertiary prevention.
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Dairkee, Shanaz H., Junhee Seok, Stacey Champion, Aejaz Sayeed, Michael Mindrinos, Wenzhong Xiao, Ronald W. Davis, and William H. Goodson. "Bisphenol A Induces a Profile of Tumor Aggressiveness in High-Risk Cells from Breast Cancer Patients." Cancer Research 68, no. 7 (April 1, 2008): 2076–80. http://dx.doi.org/10.1158/0008-5472.can-07-6526.
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Souza, Danival José de, Terezinha Maria Castro Della Lucia, and Luiz Cláudio de Almeida Barbosa. "Discrimination between workers of Acromyrmex subterraneus molestans from monogynous and polygynous colonies." Brazilian Archives of Biology and Technology 49, no. 2 (March 2006): 277–85. http://dx.doi.org/10.1590/s1516-89132006000300013.
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Behavioral assays were conducted with individuals from monogynous and polygynous colonies of Acromyrmex subterraneus molestans to evaluate the discriminatory ability of ant workers. These bioassays showed that this subspecies could not discriminate among non-nestmates or nestmate workers. However, nestmates of these same colonies did discriminate among workers of another subspecies Ac. subterraneus subterraneus. When discrimation occurred there were no differences in the response of workers from either monogynous or polygynous colonies. Similarities or differences in the chemical profile of both subspecies explained the absence or occurence of aggressiveness among workers. The chemical profile of colonies of the same subspecies was very similar among them, although distinct among subspecies. The number of queens did not influence the cuticular chemical composition of the workers or their behavior.
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Zanon, Maicon Fernando, Cristovam Scapulatempo-Neto, Ricardo Ribeiro Gama, Márcia Maria Chiquitelli Marques, Rui Manuel Reis, and Adriane Feijó Evangelista. "Identification of MicroRNA Expression Profiles Related to the Aggressiveness of Salivary Gland Adenoid Cystic Carcinomas." Genes 14, no. 6 (June 2, 2023): 1220. http://dx.doi.org/10.3390/genes14061220.
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Adenoid cystic carcinoma (ACC) has been reported as the second most frequent carcinoma of the salivary glands. Few studies have associated the miRNAs expression with ACC aggressiveness. In this study, we evaluated the miRNAs profile of formalin-fixed, paraffin-embedded (FFPE) samples of salivary gland ACC patients using the NanoString platform. We studied the miRNA expression levels associated with the solid growth pattern, the more aggressive histologic feature of ACCs, compared with the tubular and cribriform growth patterns. Moreover, the perineural invasion status, a common clinicopathological feature of the disease that is frequently associated with the clinical progression of ACC, was investigated. The miRNAs showing significant differences between the study groups were selected for target prediction and functional enrichment, which included associations with the disease according to dedicated databases. We observed decreased expression of miR-181d, miR-23b, miR-455, miR-154-5p, and miR-409 in the solid growth pattern compared with tubular and cribriform growth patterns. In contrast, miR-29c, miR-140, miR-195, miR-24, miR-143, and miR-21 were overexpressed in patients with perineural invasion. Several target genes of the miRNAs identified have been associated with molecular processes involved in cell proliferation, apoptosis, and tumor progression. Together, these findings allowed the characterization of miRNAs potentially associated with aggressiveness in salivary gland adenoid cystic carcinoma. Our results highlight important new miRNA expression profiles involved in ACC carcinogenesis that could be associated with the aggressive behavior of this tumor type.
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Lin, Xiaoqi, Sydney D. Finkelstein, Bing Zhu, and Jan F. Silverman. "Molecular analysis of multifocal papillary thyroid carcinoma." Journal of Molecular Endocrinology 41, no. 4 (July 15, 2008): 195–203. http://dx.doi.org/10.1677/jme-08-0063.
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Papillary thyroid carcinoma (PTC) frequently presents as a multifocal process. To study the importance of separating independent primary (IP) from intrathyroid metastatic (ITM) PTC, we examined 19 molecular markers on 42 separate tumors from 18 multifocal PTC cases. In 12 of 18 (66.7%) cases, including 6 of 12 (50%) papillary microcarcinoma cases, the same or similar profile of loss of heterozygosities (LOH) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation was demonstrated, indicating that they were from the same primary and represented ITM. Different profiles of LOHs and BRAF mutation were detected in separate tumors of 6 of 18 cases, indicating that they represented IP. Patients with ITM, including papillary microcarcinoma, had significantly increased lymph node metastasis. The frequencies of LOHs of 17q21, 17p13, 10q23, and 22q13 were higher in tumors with lymph node metastasis, suggesting that these LOHs may be important in increased lymph node metastasis. LOH of 9p21 was found at the highest frequency in PTC (53.8%), followed by 1p36 (46.2%), 10q23 (34.6%), and 22q13 (34.6%). Papillary microcarcinoma had acquired similar genomic mutations as conventional PTC, but higher frequencies of mutations of BRAF, 1p36, 18q, and 22q13 were found in the larger PTC, suggesting that they might play a role in the aggressiveness of PTC. Different profiles of mutations were observed in conventional, follicular variants, and diffuse sclerosing variant of PTC, which might influence the different morphological appearances and clinical courses. In conclusion, molecular analysis can separate multifocal IP PTC from ITM PTC, and may be more important than tumor size in predicting lymph node metastasis, aggressiveness, and prognosis of PTC.
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Bozzini, Nicolò, Sofia Avnet, Nicola Baldini, and Margherita Cortini. "Epigenetic Regulation Mediated by Sphingolipids in Cancer." International Journal of Molecular Sciences 24, no. 6 (March 10, 2023): 5294. http://dx.doi.org/10.3390/ijms24065294.
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Epigenetic changes are heritable modifications that do not directly affect the DNA sequence. In cancer cells, the maintenance of a stable epigenetic profile can be crucial to support survival and proliferation, and said profile can differ significantly from that of healthy cells. The epigenetic profile of a cancer cell can be modulated by several factors, including metabolites. Recently, sphingolipids have emerged as novel modulators of epigenetic changes. Ceramide and sphingosine 1-phosphate have become well known in cancer due to activating anti-tumour and pro-tumour signalling pathways, respectively, and they have recently been shown to also induce several epigenetic modifications connected to cancer growth. Additionally, acellular factors in the tumour microenvironment, such as hypoxia and acidosis, are now recognised as crucial in promoting aggressiveness through several mechanisms, including epigenetic modifications. Here, we review the existing literature on sphingolipids, cancer, and epigenetic changes, with a focus on the interaction between these elements and components of the chemical tumour microenvironment.
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Ortas, Eduardo, and Isabel Gallego-Álvarez. "Bridging the gap between corporate social responsibility performance and tax aggressiveness." Accounting, Auditing & Accountability Journal 33, no. 4 (March 2, 2020): 825–55. http://dx.doi.org/10.1108/aaaj-03-2017-2896.
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PurposeThis paper addresses the role of corporate social responsibility (CSR) performance as a potential mechanism for reducing firms' likelihood of engaging in tax aggressiveness (TAG). The paper also contributes to the existing literature by addressing the moderating effect of national cultures on the link between CSR performance and corporate TAG.Design/methodology/approachThe focus is placed on an unbalanced panel of 2,696 companies distributed in 30 countries and seven economic sectors over the period of 2002–2014.FindingsThe results provide support for those companies achieving high corporate social performance (CSP), corporate environmental performance (CEP) and corporate governance performance (CGP) being less likely to engage in aggressive tax practices. Finally, the results identify some national cultural dimensions moderating the link between disaggregated measures of CSR performance and firms' TAG.Research limitations/implicationsThe difficulty of accessing CSR and TAG data for non-listed companies could bias the data set towards a compliant company profile because of the higher visibility. In addition, the use of effective tax rates to examine firms' TAG should be interpreted with some caution.Practical implicationsThe paper's findings provide unique and useful information for company stakeholders and managers aiming to address the factors that enhance firms' incentives to engage in aggressive tax practices.Originality/valueThis paper addresses the multidimensional nature of CSR performance by analysing the links between CSP, CEP and CGP and corporations' TAG. Furthermore, the research addresses the way in which national culture moderates the links between disaggregated measures of CSR performance and corporate TAG.
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Kariche, Nora, Nabila Moulaï, Leila-Sarah Sellam, Samir Benyahia, Wahiba Ouahioune, Djamel Djennaoui, Chafia Touil-Boukoffa, and Mehdi Bourouba. "Expression Analysis of the Mediators of Epithelial to Mesenchymal Transition and Early Risk Assessment of Therapeutic Failure in Laryngeal Carcinoma." Journal of Oncology 2019 (December 6, 2019): 1–15. http://dx.doi.org/10.1155/2019/5649846.
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Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy which lacks early predictors of prognosis. Here, we hypothesized that expression and prognostic characterization of the critical mediators of epithelial to mesenchymal transition (EMT) may provide key information in this regard. Linear regression and multiple correspondence analyses were performed on immunohistochemical data obtained from 20 invasive tumors. Principal component and unsupervised hierarchical clustering were used to analyze the dataset patterns associating with LSCC metastatic profile. Survival and death risk assessments were performed using Kaplan–Meier and hazard ratio tests. Data mining analysis using CHAID decision tree and logistic regression analysis was applied to define the predictive value of the risk factors of tumor aggressiveness. Our analyses showed, that in invasive LSCC tumors, cells associating with a mesenchymal profile were likely to exhibit enhanced NOS2, TGF-β, and IL-17A expression levels, concomitantly to NF-κB nuclear translocation. IHC data deciphering determined that EMT induction was also linked to the enrichment of the tumors with CD68+ populations and IL-10 signal. Strikingly, dataset cluster analysis showed that these signatures could define distinct patterns of invasive tumors, where NOS2 associated with IL-10 expression, and TGF-β and IL-17A signals associated with MMP-9 activation. Decision tree analysis identified IL-17A as a possible predictor of LSCC aggressiveness. Altogether, our results show that distinct immunological patterns would support the acquisition of EMT features in invasive LSCC and suggest that IL-17A may be useful in the early identification of patients “at-risk” of therapeutic failure.
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You, Daeun, Hyungjoo Kim, Yisun Jeong, Sun Young Yoon, Eunji Lo, Sangmin Kim, and Jeong Eon Lee. "Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages." International Journal of Molecular Sciences 24, no. 2 (January 11, 2023): 1443. http://dx.doi.org/10.3390/ijms24021443.
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Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1β. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1β from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2.
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Okręglicka, Małgorzata. "ORGANIZATIONAL CULTURE SHAPED BY ENTREPRENEURIAL ORIENTATION IN FAMILY FIRMS." Zeszyty Naukowe Wyższej Szkoły Humanitas Zarządzanie 22, no. 2 (June 30, 2021): 9–21. http://dx.doi.org/10.5604/01.3001.0015.0033.
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Contemporary enterprises are still looking for ways and methods of achieving a competitive advantage, which invariably include entrepreneurship. Entrepreneurial orientation is an organizational construct consisting of five dimensions: proactivity, innovation, competitive aggressiveness, autonomy and risk taking. Family businesses show a significant specificity of functioning in many areas due to the dominant influence of the family on the management of such entities. It is not a uniform group, and individual companies may significantly differ, e.g. depending on the profile of their activity. However, in cases, organizational culture can determine the level of entrepreneurial orientation of the organization. In this article, research efforts focus on differences in the level of entrepreneurial orientation and building an entrepreneurial culture depending on the profile of the business. The conclusions were based on the results of the own questionnaire survey conducted among 118 small family businesses in Poland.
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PALAGHIA, Carmen. "THE DYNAMIC OF THE AGGRESSOR-VICTIM RELATIONSHIP SPECIFIC TO THE SCHOOL BULLYING AND CYBERBULLYING PHENOMENON." Social Research Reports 11, no. 2 (June 30, 2019): 37–48. http://dx.doi.org/10.33788/srr11.2.3.
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This study conceptually and etiologically defines the harassment among students, either face to face or virtually, the types of bullying and cyberbullying from the perspective of the dynamic of the aggressor-victim relationship. In this regard, the aggressor and the victim’s profile are outlined, as well as the fluctuations of the attitudinal-behavioral pattern within the victim-aggressor-school triad. By referring to the aggressiveness among students, we will predominantly analyse the school harassment, emphasizing both the determinant factors and the effects on the psychological plan with reference to the efficient strategies of preventing the bullying and cyberbullying from the educational environment.
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Robert, P. H., and H. Allain. "Clinical management of agitation in the elderly with tiapride." European Psychiatry 16, S1 (2001): 42s—47S. http://dx.doi.org/10.1016/s0924-9338(00)00527-7.
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SummaryAgitated behaviors such as uncooperativeness with necessary care, motor hyperactivity, and verbal or physical aggression are some of the most commonly reported complications in dementia and organic disorders in elderly subjects. These symptoms present greater clinical challenges and management issues than the cognitive deficits. Antipsychotics are the most commonly used psychotropic agents for treating these types of symptoms.The aims of this article are to review clinical studies with tiapride, a substituted benzamide, and more specifically to present recent data coming from two double-blind, randomized studies in elderly subjects.The first study versus melperone was conducted in Germany, with over 176 hospitalized demented patients, and indicated that tiapride was as effective and safe as melperone.More recently, a multicentre, international, double-blind, three-parallel group study compared a 21-day treatment of tiapride to haloperidol and placebo and included 306 demented elderly patients with agitation and aggressiveness. The results showed that tiapride and haloperidol were significantly effective in the treatment of agitation and aggressiveness compared to placebo. The tiapride safety profile was found to be better than haloperidol for clinical acceptability, particularly for significantly fewer extrapyramidal symptoms in the tiapride group.
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Alohali, Sama, Alexandra E. Payne, Marc Pusztaszeri, Mohannad Rajab, Véronique-Isabelle Forest, Michael P. Hier, Michael Tamilia, and Richard J. Payne. "Effect of Having Concurrent Mutations on the Degree of Aggressiveness in Patients with Thyroid Cancer Positive for TERT Promoter Mutations." Cancers 15, no. 2 (January 8, 2023): 413. http://dx.doi.org/10.3390/cancers15020413.
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This study aimed to examine whether concurrent mutations with a TERT promoter mutation are associated with a greater likelihood of more aggressive disease than a TERT promoter mutation alone. The medical records of 1477 patients who underwent thyroid surgery at two tertiary hospitals between 2017 and 2022 were reviewed. Twenty-four patients had TERT promoter mutations based on molecular profile testing. Clinicodemographic data, mutational profiles, and histopathological features were assessed. Descriptive analysis, Fisher’s exact test, and binary logistic regression were performed. Seven patients had single-gene TERT promoter mutations, and 17 had concurrent mutations, including BRAF V600E, HRAS, NRAS, PIK3CA, and EIF1AX. The overall prevalence of malignancy was 95.8%, of which 78.3% were aggressive thyroid cancers. There was a statistically significant association between concurrent mutations and disease aggressiveness. The odds of having aggressive disease were 10 times higher in patients with a TERT promoter mutation and a concurrent molecular alteration than in those with a TERT promoter mutation alone. This is an important finding for thyroid specialists to consider when counseling patients concerning risk stratification and management options.
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Garrote-Cámara, María Elena, Vicente Gea-Caballero, Teresa Sufrate-Sorzano, Esther Rubinat-Arnaldo, José Ángel Santos-Sánchez, Ana Cobos-Rincón, Iván Santolalla-Arnedo, and Raúl Juárez-Vela. "Clinical and Sociodemographic Profile of Psychomotor Agitation in Mental Health Hospitalisation: A Multicentre Study." International Journal of Environmental Research and Public Health 19, no. 23 (November 30, 2022): 15972. http://dx.doi.org/10.3390/ijerph192315972.
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Psychomotor agitation is characterised by an increase in psychomotor activity, restlessness and irritability. People with psychomotor agitation respond by over-reacting to both intrinsic and extrinsic stimuli, experiencing stress and/or altered cognition. The objective of this study is to assess the clinical and sociodemographic profile of psychomotor agitation in patients with severe mental disorders. The study was carried out in Spain by means of multicentre cross-sectional convenience sampling involving 140 patients who had been admitted to psychiatric hospital units and had experienced an episode of psychomotor agitation between 2018 and 2021.Corrigan’s Agitated Behaviour Scale was used to assess psychomotor agitation. The results show that the predominant characteristic in psychomotor agitation is aggressiveness, which is also the most reported factor in patients with severe mental disorder. Patients who also have anxiety develop psychomotor agitation symptoms of moderate/severe intensity. The clinical and sociodemographic profile found in our study is consistent with other studies on the prevalence of psychomotor agitation.
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Kansra, S., A. Mazzei, and J. Bhatt. "Safety, Efficacy, and Patient Acceptability of Montelukast in Exercise-Induced Asthma." Clinical Medicine Insights: Therapeutics 4 (January 2012): CMT.S7389. http://dx.doi.org/10.4137/cmt.s7389.
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Exercise-induced bronchoconstriction (EIB) can be a troublesome problem in asthmatic children and in some children without asthma. Self-reported exercise related symptoms should be verified formally. EIB is mediated by changes in temperature and humidity in the airway and is secondary to release of several mediators of the bronchoconstriction including leukotrienes. Montelukast as a leukotriene receptor antagonist offers protection against but does not completely ameliorate EIB. Regular use does not appear to lead to tolerance. Nightmares, abdominal pain, fever, nausea and aggressiveness are commonly described side effects; however, the overall safety profile of montelukast is good and does not change with long term use. There are individual differences in response to montelukast for protection against EIB. Bronchoconstriction triggered by exercise responds to cessation of exercise in its natural course. Due to its pharamacokinetic profile, montelukast may be more useful as a prophylaxis than to relieve symptoms.
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Krupelnytska, Liudmyla, and Artem Baratiuk. "Personality Traits Contributing to Anxiety and Phobic Disorders in Psychology Students." Bulletin of Taras Shevchenko National University of Kyiv. Psychology, no. 2 (16) (2022): 25–32. http://dx.doi.org/10.17721/bpsy.2022.2(16).5.
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The research analyses factors of personal predisposition to anxiety and phobic disorders among psychology students. The research subject is insufficiently covered in scientific publications; therefore, it needs further study. The purpose of the research is to identify personal factors of predisposition to anxiety-phobic disorders in psychology students. The research uses Freiburg Personality Inventory, Questionnaire of the Hierarchical Structure of Actual Personal Fears; Integrative Anxiety Test; Patient Health Questionnaire (PHQ) - Panic Screening Questions. 70 students took part in the study (male/female ratio is 21/49). All of them studied at the Faculty of Psychology of Taras Shevchenko National University of Kyiv. The age of the respondents is from 18 to 22 years old, the average age is 20.00, the standard deviation is 1.47. The personal profile of psychology students is distinguished by the following characteristics. The extremes are openness (upper peak) and shyness (lower peak). The second-highest indicator is for sociability; and the third is for neuroticism. Next to the lower peak there is also an indicator of reactive aggressiveness. The research establishes gender differences in the manifestation of neuroticism and reactive aggressiveness of psychology students, the correlation of current fears, anxiety, and the tendency to panic attacks with personality characteristics. It builds prognostic models of the influence of personal traits on the tendency to manifest current fears, situational and personal anxiety, and panic attacks. In descending order of influence: phobic symptoms are influenced by anxious assessment of prospects, shyness, emotional lability; personal anxiety is influenced by depression, neuroticism, spontaneous aggressiveness; situational anxiety is influenced by depression, current fears and introversion; tendency to panic attacks is influenced by neuroticism.
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Figiel, Sandy, Michelle Pinault, Isabelle Domingo, Cyrille Guimaraes, Roseline Guibon, Pierre Besson, Elsa Tavernier, et al. "Fatty acid profile in peri-prostatic adipose tissue and prostate cancer aggressiveness in African–Caribbean and Caucasian patients." European Journal of Cancer 91 (March 2018): 107–15. http://dx.doi.org/10.1016/j.ejca.2017.12.017.
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Rodrigues, Claudia, Lidija Milkovic, Ivana Tartaro Bujak, Marko Tomljanovic, Graça Soveral, and Ana Cipak Gasparovic. "Lipid Profile and Aquaporin Expression under Oxidative Stress in Breast Cancer Cells of Different Malignancies." Oxidative Medicine and Cellular Longevity 2019 (July 11, 2019): 1–10. http://dx.doi.org/10.1155/2019/2061830.
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Breast cancer is the major cause of tumor-associated mortality in women worldwide, with prognosis depending on the early discovery of the disease and on the type of breast cancer diagnosed. Among many factors, lipids could contribute to breast cancer malignancy by participating in cellular processes. Also, aquaporins are membrane channels found aberrantly expressed in cancer tissues that were correlated with tumor aggressiveness, progression, and metastasis. However, the differences in lipid profile and aquaporin expression between cell types of different malignant potential have never been investigated. Here, we selected three breast cancer cell lines representing the three major breast cancer types (hormone positive, HER2NEU positive, and triple negative) and analyzed their lipid profile and steady state lipid hydroperoxide levels to correlate with cell sensitivity to H2O2. Additionally, the expression profiles of AQP1, AQP3, and AQP5 and the Nrf2 transcription factor were evaluated, before and after oxidative challenge. We found that the lipid profile was dependent on the cell type, with the HER2-positive cells having the lowest level PUFA, whereas the triple negative showed the highest. However, in triple-negative cancer cells, a lower level of the Nrf2 may be responsible for a higher sensitivity to H2O2 challenge. Interestingly, HER2-positive cells showed the highest increase in intracellular ROS after oxidative challenge, concomitant with a significantly higher level of AQP1, AQP3, and AQP5 expression compared to the other cell types, with AQP3 always being the most expressed isoform. The AQP3 gene expression was stimulated by H2O2 treatment in hormone-positive and HER2NEU cells, together with Nrf2 expression, but was downregulated in triple-negative cells that showed instead upregulation of AQP1 and AQP5. The lipid profile and AQP gene expression after oxidative challenge of these particularly aggressive cell types may represent metabolic reprogramming of cancer cells and reflect a role in adaptation to stress and therapy resistance.
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Koutsioumpa, Marina, Maria Hatziapostolou, Christos Polytarchou, Swapna Joshi, and Dimitrios Iliopoulos. "ING3 as a novel regulator of pancreatic cancer growth and aggressiveness." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 304. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.304.
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304 Background: Recent studies demonstrate that chromatin regulation by posttranslational means, such as histone methylation or acetylation, is an essential control mechanism in tumorigenesis and tumor progression. Accumulative findings support the notion that pancreatic cancer tumorigenesis is not only governed by genetic alterations but also aberrant epigenetic regulation. The aim of the present study was to identify and assess the role of chromatin regulators in pancreatic cancer. Methods: The gene expression profile of chromatin regulators was assessed using gene expression microarray analysis in pancreatic cancer and uninvolved human tissues. Validation of microarray findings was performed by qRT-PCR in two extended cohorts of patients and by immunohistochemistry in pancreas tumor tissue microarrays. PANC-1, MIA Paca-2, Capan-2, HPAF-II and AsPC-1 cell lines were used for in vitro assays. Efficiency of knockdown experiments, performed by RNAi interference assays and shRNA-expressing lentiviral vectors, was evidenced by qRT-PCR and Western Blot Analysis. Cell proliferation, invasion and colony formation assays were conducted in genetically modified cells. The significance of variability between the results from each group and corresponding control was determined by unpaired t-test. Results: Differential expression analysis of chromatin regulators in pancreatic cancer versus uninvolved tissues demonstrates that 27 epigenetic molecules are significantly de-regulated (>1.5 fold, P<0.05). By hierarchical clustering, the samples are classified into two major groups that reflect the normal and cancer state. The decreased expression of inhibitor of growth family member 3 (ING3), a component of the NuA4 histone acetyl-transferase complex, was further validated by qRT-PCR and immunohistochemistry analysis in tumor tissues. Transient or stable silencing of ING3 caused significant increase of viability, proliferation, colony formation and invasion in several pancreatic cell lines. Conclusions: Our data show that human pancreatic cancer is characterized by loss of ING3 expression and we defined a potential role of the latter in pancreatic cancer cell growth and invasion.
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Häggström, Christel, Oskar Hagberg, Truls Gårdmark, Firas Aljabery, Viveka Ströck, Abolfazl Hosseini, Amir Sherif, et al. "Cohort profile: Bladder Cancer Data Base Sweden (BladderBaSe) 2.0." BMJ Open 12, no. 12 (December 2022): e064898. http://dx.doi.org/10.1136/bmjopen-2022-064898.
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PurposeWe constructed Bladder Cancer Data Base Sweden (BladderBaSe) 2.0 to expand studies in BladderBaSe on incidence, treatment outcomes, side effects, survival and health economic aspects of men and women with cancer in the urinary bladder, upper tract urothelial carcinoma (UTUC) (renal pelvis and ureter) and urethral carcinoma.ParticipantsBladderBaSe 2.0 includes 53 298 patients with cancer in the urinary bladder, diagnosed from 1 January 1997 to 31 December 2019, and 961 patients with UTUC in the renal pelvis and 792 in the ureter, and 146 patients with urethral urothelial carcinoma, diagnosed from 1 January 2015 to 31 December 2019, and in total 275 816 participants in reference groups, free of cancer in the urinary tract, matched 1:5 on sex, age and county.Findings to dateTo date, 18 published studies based on data from the BladderBaSe have investigated calendar time trends in survival; impact of gender, socioeconomic factors, tumour aggressiveness and hospital volume for radical cystectomy on prognosis; survival after radical cystectomy compared with radical radiotherapy; risk factors for complications and side effects after radical cystectomy such as thromboembolism, strictures of ureteroenterostomies and incisional hernia.Future plansThe BladderBaSe initiators are currently investigating gender-dependent detection delays due to urinary tract infections; survival after non-muscle invasive bladder cancer with respect to the number of transurethral resections; short-term outcomes comparing open and robot-assisted radical cystectomy; studies on risk for intravesical recurrence after different diagnostic measures in UTUC, and suicide risk after bladder cancer diagnosis. The BladderBaSe project group is open for collaborations with national and international colleagues.
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Dias Carvalho, Patrícia, Ana Luísa Machado, Flávia Martins, Raquel Seruca, and Sérgia Velho. "Targeting the Tumor Microenvironment: An Unexplored Strategy for Mutant KRAS Tumors." Cancers 11, no. 12 (December 13, 2019): 2010. http://dx.doi.org/10.3390/cancers11122010.
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Current evidence strongly suggests that cancer cells depend on the microenvironment in order to thrive. In fact, signals from the surrounding tumor microenvironment are crucial for cancer cells´ aggressiveness, altering their expression profile and favoring their metastatic potential. As such, targeting the tumor microenvironment to impair cancer progression became an attractive therapeutic option. Interestingly, it has been shown that oncogenic KRAS signaling promotes a pro-tumorigenic microenvironment, and the associated crosstalk alters the expression profile of cancer cells. These findings award KRAS a key role in controlling the interactions between cancer cells and the microenvironment, granting cancer a poor prognosis. Given the lack of effective approaches to target KRAS itself or its downstream effectors in the clinic, exploring such interactions may open new perspectives on possible therapeutic strategies to hinder mutant KRAS tumors. This review highlights those communications and their implications for the development of effective therapies or to provide insights regarding response to existing regimens.
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Janković, Stipan, Vlasta Stivičević, Goran Dodig, Mihovil Biočić, Ivan Stajner, and Dragon Primorac. "Psychological Characteristics of Wounded and Disabled Croatian War Veterans." Military Medicine 163, no. 5 (May 1, 1998): 331–36. http://dx.doi.org/10.1093/milmed/163.5.331.
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Abstract Objective: Evaluation of the psychological state of a group of 119 Croatian disabled war veterans who suffered grave traumatic war experiences during the war in Croatia (1991–1992). Methods: Semistructured Clinical Interview, Profile Index Emotions test, and Zung's Self-Rating Depression Scale were used to assess disabled war veterans accommodated in special institutions for rehabilitation. Results: Changes in psychological functioning were established in 63.8% of disabled war veterans, the most frequent among them being indisposition, irritability, anxiety, and fear. In nearly half of the veterans there were changes in their relationships with close persons, difficulties in accepting the reality of their situations, and increased aggressiveness. Higher average values on the depression index (0.52) were also established. Conclusion: The established change in the psychological profile of disabled Croatian war veterans was lower than expected. However, because of their great vulnerability, it is necessary to increase efforts to secure their complete psychosocial recovery.
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Michelutti, Kamylla Balbuena, Nathan Rodrigues Batista, Sidnei Eduardo Lima-Junior, Claudia Andrea Lima Cardoso, and William Fernando Antonialli-Junior. "Temperature increase impairs recognition among nestmates in the social wasp Polybia paulista H. von Ihering, 1896 (Vespidae: Polistinae: Epiponini)." Papéis Avulsos de Zoologia 62 (October 4, 2022): e202262059. http://dx.doi.org/10.11606/1807-0205/2022.62.059.
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Cuticular hydrocarbons (CHCs) of most terrestrial arthropods primarily serve as a protective barrier against desiccation and infection. Throughout evolution, these compounds have acquired another fundamental function: the exchange of signals during interactions between nestmates. However, even though cuticular hydrocarbons perform a dual function in social insects, little is known about the effect(s) of one function on the other in social insects, and no study has evaluated this relationship in social wasps. Therefore, the present study tests the hypothesis that the level of aggressiveness presented during induced encounters between nestmates of Polybia paulista who were subjected to different conditions temperature is different than between nestmates who remained under the same temperature conditions. If the hypothesis is confirmed, it is likely because the cuticle of the wasps that had been exposed to temperature variation adjusted to these conditions leading them not to recognize the cuticular chemical signature of their colony. To test this hypothesis, workers were exposed to temperature variation in a BOD chamber and then subjected to encounters with workers who were maintained at a constant temperature of 24℃. We also used control groups to evaluate the effect of isolation alone among the groups. According to our results, our hypothesis was confirmed, the level of aggressiveness presented between nestmates who were exposed to temperature variation and those who remained at 24℃ was significantly higher than the levels of aggressiveness presented between nestmates who remained isolated but under constant temperature during the same period, in some cases, it was similar to the aggressiveness presented in encounters between wasps from different colonies. During these encounters, wasps performed alarm behavior, bites, and stings not seen during encounters between wasps that remained under the same temperature, but in isolated groups. The lack of aggressive behavior under isolated conditions indicates that isolation had no effect on chemical recognition signature. These results suggest that temperature variation may have caused some change in the cues that allow recognition between nestmates. On the other hand, these results were not caused by isolation or stress generated by the study design and difference in the CHC profile of workers, as described in the literature, is consistent with our results.
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Martí-Bonmatí, L. "Pancreatic Cancer, Radiomics and Artificial Intelligence: A Review." ANALES RANM 139, no. 139(01) (2022): 23–30. http://dx.doi.org/10.32440/ar.2022.139.01.rev03.
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Computed tomography (CT) scans stratified patients with pancreatic ductal adenocarcinoma (PDA) into categories based on whether the tumor is expected to be resectable, borderline resectable, initially unresectable, or metastatic. When reporting these exams, radiologists use structured templates to ensure that the generated information is complete, although the difficulty in identifying initial microscopic infiltrations of adjacent structures and small metastases is well recognized. Radiomics is seen as a potentially useful tool for determining tumor aggressiveness and building predictive clinical models. If extracted radiomic signatures are validated as prognostic and predictive biomarkers, they could be used aiding in decision-making to facilitate personalized patient management with ACDP. Models with convolutional neural networks provide estimations associated with a biological aggressiveness profile by combining clinical, semantic, and radiomic features. Despite encouraging results, the main limitations for clinical use of quantitative imaging are due to the instability of the measurements and the diversity of obtained images (different equipment and protocols), both making difficult to generalize the obtained results. The availability of large multicenter repositories with standardized and annotated images, and associated data (clinical, molecular, genetic), together with radiomics and artificial intelligence tools, will allow to predict the behavior of these tumors at the diagnosis. Its validation in totally independent cohorts and causal inference models is needed.
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Scatton, B., C. Cohen, G. Perrault, A. Oblin, Y. Claustre, H. Schoemaker, D. J. Sanger, L. Rouquier, and R. Porsolt. "The preclinical pharmacologic profile of tiapride." European Psychiatry 16, S1 (2001): 29s—34S. http://dx.doi.org/10.1016/s0924-9338(00)00526-5.
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SummaryTiapride is a benzamide derivative that has been used successfully in the clinic for a number of years for the treatment of agitation and aggressiveness in elderly patients. Like many substituted benzamides, tiapride specifically blocks dopamine receptors in the brain. It has affinity for dopamine D2 (IC50 = 110–320 nM) and D3 (IC50 = 180 nM) receptors in vitro but lacks affinity for dopamine D1 and D4 receptors and for non-dopaminergic receptors including H1, α1, α2-adrenergic and serotonergic receptors. Tiapride also shows dose-related inhibition of [3H]-raclopride binding in limbic areas and in the striatum of the rat in vivo (ED50 ∼ 20 mg/kg, ip). In microdialysis experiments, tiapride (over the range 10–30 mg/kg, ip) increased extracellular levels of dopamine in the nucleus accumbens and striatum, a reflection of its blockade of postsynaptic dopamine receptors in these brain areas.In behavioral experiments in rats, lower doses of tiapride (ED50 = 10 mg/kg, ip) antagonised dopamine agonist-induced hyperactivity while higher doses (ED50 = 60 mg/kg, ip) were required to block stereotyped movements.In addition, doses of tiapride up to 200 mg/kg, ip failed to induce catalepsy, an effect observed with many other drugs which block dopamine receptors. In tests of conditioned behavior in rats, tiapride was found to give rise to an interoceptive stimulus associated with dopamine receptor blockade at doses (ED50 = 2.2 mg/kg, ip) much lower than those producing motor disturbances or sedation (ED50 = 40 mg/kg, ip), in striking contrast to a range of conventional or atypical neuroleptics that produced interoceptive stimulus and sedation at similar doses. Furthermore, the acquisition by rats of a place-learning task in a water maze was not affected by tiapride (over the range 3–30 mg/kg, ip), whereas haloperidol (MED = 0.25 mg/kg, ip) and risperidone (MED = 0.03 mg/kg, ip) impaired performance.The preclinical pharmacologic and behavioral profile of tiapride suggests that its clinical activity may be due to a selective blockade of dopamine D2 and D3 receptors in limbic brain regions. The results are also consistent with a lack of motor or cognitive side effects.