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Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.
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BACKGROUND: Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. METHODS: This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student's t-test. RESULTS: The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. CONCLUSIONS: This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.
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Neoplasias da Mama , Neoplasias Inflamatórias Mamárias , Adipocinas/genética , Tecido Adiposo/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Caderinas , Linhagem Celular Tumoral , Citocinas/genética , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/metabolismo , Neoplasias Inflamatórias Mamárias/patologia , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8 , Obesidade/complicações , Obesidade/genéticaRESUMO
BACKGROUND: Workplace violence (WPV) has been recognized as a major occupational hazard worldwide. Healthcare professions are particularly at a higher risk of WPV. Patients and their relatives are commonly the most common perpetrators for WPV against physicians. Trainings on the universal precautions of violence, how to effectively anticipate, recognize and manage potentially violent situation is recommended by OSHA as a part of a written, effective, comprehensive, and interactive WPV prevention program. OBJECTIVE: To implement and evaluate the effectiveness of a training session delivered to nurses. The training session aimed to increase nurses' ability to identify potentially violent situations and to effectively manage these situations in a teaching hospital in Egypt. METHODOLOGY: A total of 99 nurses attended the training sessions. Confidence in coping with aggressive patient scale, along with nurses' attitudes toward WPV, were used to assess the effectiveness of the training sessions. RESULTS: Nurses' perceived confidence to deal with aggression increased after attending the training sessions. Nurses' attitudes toward WPV positively changed after attending the training session. CONCLUSION AND RECOMMENDATIONS: Increasing awareness of the problem among healthcare professions as well as the public is warranted. Violence prevention program with a zero-tolerance policy is warranted.
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Inflammatory breast cancer (IBC) is a highly metastatic and lethal breast cancer. As many as 25-30% of IBCs are triple negative (TN) and associated with low survival rates and poor prognosis. We found that the microenvironment of IBC is characterized by high infiltration of tumor associated macrophages (TAMs) and by over-expression of the cysteine protease cathepsin B (CTSB). TAMs in IBC secrete high levels of the cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared to non-IBC patients. Herein, we tested the roles of IL-8 and MCP-1/CCL2 in modulating proteolytic activity and invasiveness of TN-non-IBC as compared to TN-IBC and addressed the underlying molecular mechanism(s) for both cytokines. Quantitative real time PCR results showed that IL-8 and MCP-1/CCL2 were significantly overexpressed in tissues of TN-IBCs. IL-8 and MCP-1/CCL2 induced CTSB expression and activity of the p-Src and p-Erk1/2 signaling pathways relevant for invasion and metastasis in TN-non-IBC, HCC70 cells and TN-IBC, SUM149 cells. Dasatinib, an inhibitor of p-Src, and U0126, an inhibitor of p-Erk1/2, down-regulated invasion and expression of CTSB by HCC70 and SUM149 cells, a mechanism that is reversed by IL-8 and MCP-1/CCL2. Our study shows that targeting the cytokines IL-8 and MCP-1/CCL2 and associated signaling molecules may represent a promising therapeutic strategy in TN-IBC patients.
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Quimiocina CCL2/biossíntese , Genes src/fisiologia , Neoplasias Inflamatórias Mamárias/metabolismo , Interleucina-8/biossíntese , Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Feminino , Genes src/efeitos dos fármacos , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pessoa de Meia-Idade , Proteólise/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND: Breast cancer treatment is an established cause of financial toxicity, and associated costs may contribute to higher mortality and morbidity rates. In Egypt, breast cancer incidence and mortality rates are among the highest in the Middle East. Late-stage diagnosis is common, and disease occurs at an earlier age than in Europe and North America. Out-of-pocket payments are the primary means of financing healthcare in Egypt, and socioeconomic factors have been shown to significantly impact access to cancer screening and treatment. METHODS: An observational cross-sectional study was conducted among breast cancer patients at Ain Shams University Hospitals in Cairo from 2013 to 2015. RESULTS: One hundred women with breast cancer participated. There was a high need for financial assistance (66.0%) and patients with financial needs had great difficulty affording medications (80.0%). A number of patients had lost their jobs following diagnosis, with 32.7% employed prior to diagnosis and 15.3% afterwards. Nearly one-half of participants were classified as food insecure, and nearly one-third reported difficulty affording transportation costs. CONCLUSIONS: This is the first study to describe socioeconomic needs and financial impact among a cohort of Egyptian women undergoing breast cancer treatment. The findings highlight the financial impact of breast cancer treatment on a cohort of Egyptian breast cancer patients and the need for a multidisciplinary approach to help them access and mitigate the costs of treatment. Recommendations include implementing patient financial navigation services and producing printed materials to inform patients of resources to help mitigate the treatment's financial impact.
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Neoplasias da Mama/terapia , Segurança Alimentar/métodos , Fatores Socioeconômicos , Neoplasias da Mama/epidemiologia , Estudos Transversais , Egito , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Childhood injuries are a significant and growing global public health problem, often with high morbidity and, at times, mortality. A large proportion of injuries in preschool children occur in or around the home. We aimed to identify socioeconomic and demographic factors associated with preschool children injuries in Egypt. METHODS: Secondary data analysis were done for the Egyptian Demographic and Health Surveys (EDHS), 2014. Potential associated factors were measured from data on child welfare and questions on the prevalence of accidents and injuries of preschool children. These data were linked to the children demographic data, maternal age at marriage, working status of the mother, and questions on childcare arrangements. RESULTS: Out of the 634 injured children, 520 (83.4%) children required medical care for their injuries. The most common reported injury was an open wound 288 (45.5%), followed by fractures 237 (35.7%), burns 124 (19.7%), electrical shock 12 (1.9%) and other unknown types of injury 15 (2.4%). There was a positive correlation between injury and child's age, household wealth, mother's age at marriage, and unsupervised children or children left in the care of a minor. CONCLUSION: Leaving children unsupervised or in the presence of other young children is significantly associated with the occurrence of child injuries.
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Acidentes/estatística & dados numéricos , Saúde da Criança/estatística & dados numéricos , Inquéritos Epidemiológicos/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Fatores Etários , Pré-Escolar , Egito/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Fatores de Risco , Fatores Sexuais , Fatores SocioeconômicosRESUMO
BACKGROUND: More than half of deaths in low- and middle-income countries (LMICs) result from conditions that could be treated with emergency care - an integral component of universal health coverage (UHC) - through timely access to lifesaving interventions. METHODS: The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings. RESULTS: The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care - all within LMICs. CONCLUSIONS: Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities.
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Países em Desenvolvimento , Serviços Médicos de Emergência/normas , Relações Interprofissionais , Melhoria de Qualidade , Pesquisa , Humanos , Organização Mundial da SaúdeRESUMO
PURPOSE: Plasmacytoid dendritic cells (PDCs) infiltration into breast cancer tissues is associated with poor prognosis. Also, CXCR4 shows compelling evidences to be exploited by cancer cells to migrate to distant sites. The present study investigated lymph node metastasis in the light of PDCs infiltration and the potential cross talk with CXCR4/SDF-1 chemokine axis. METHODS: We assessed circulating PDCs proportions drained from the axillary tributaries, and the in situ expression of both CD303 and CXCR4 in breast cancer patients with positive lymph nodes (pLN) and negative lymph nodes (nLN) using immunohistochemistry and flow cytometry. We also analyzed the expression of SDF-1 in lymph nodes of pLN and nLN patients. We studied the effect of the secretome of PDCs of pLN and nLN patients on the expression of CXCR4 and activation of NF-κB in human breast cancer cell lines SKBR3 and MCF-7. TNF-α mRNA expression level in PDCs from both groups was determined by qPCR. RESULTS: Our findings indicate increased infiltration of PDCs in breast cancer tissues of pLN patients than nLN patients, which correlates with CXCR4+ cells percentage. Interestingly, SDF-1 is highly immunostained in lymph nodes of pLN patients compared to nLN patients. Our in vitro experiments demonstrate an upregulation of NF-κB expression and CXCR4 cells upon stimulation with PDCs secretome of pLN patients than those of nLN patients. Also, PDCs isolated from pLN patients exhibited a higher TNF-α mRNA expression than nLN patients. Treatment of MCF-7 cell lines with TNF-α significantly upregulates CXCR4 expression. CONCLUSIONS: Our findings suggest a potential role for microenvironmental PDCs in breast cancer lymph node metastasis via CXCR4/SDF-1 axis.
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Neoplasias da Mama/patologia , Quimiocina CXCL12/metabolismo , Células Dendríticas/patologia , Metástase Linfática/patologia , NF-kappa B/metabolismo , Receptores CXCR4/metabolismo , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Feminino , Humanos , Metástase Linfática/genética , Células MCF-7 , Pessoa de Meia-Idade , Transdução de Sinais , Microambiente TumoralRESUMO
We aimed to explore the efficacy of active caspase-3 and X-chromosome linked inhibitor of apoptosis protein (XIAP) as diagnostic markers for breast cancer. Furthermore, we examined the relationship between the examined parameters and clinicopathological factors. The current study involved 96 patients diagnosed with breast cancer and 40 patients had benign breast diseases. The expression of active caspase-3 was analyzed by both ELISA and Western blot, whereas the expression of XIAP was determined by ELISA in cell lysates. Active caspase-3 was significantly downregulated, while XIAP was markedly upregulated in patients with breast cancer in comparison to benign group. A significant negative correlation was observed between active caspase-3 and XIAP in breast cancer patients. Low active caspase-3 expression was associated with high grade, whereas, the high XIAP level was correlated with poorly differentiated tumors and late tumor stages. The sensitivity and specificity were 73.96% and 80.0% for active caspase-3, and, 70.83% and 82.5% for XIAP. A combination of active caspase-3 and XIAP provided a promising sensitivity of 88.54% and specificity of 90.0%. Our data indicate that active caspase-3 and XIAP could be substantial diagnostic markers for breast cancer patients.
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Biomarcadores Tumorais/biossíntese , Neoplasias da Mama , Caspase 3/biossíntese , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Regulação para Cima , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/biossíntese , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Inflammatory breast cancer (IBC) has a poor prognosis because of the lack of specific biomarkers and its late diagnosis. An accurate and rapid diagnosis implemented early enough can significantly improve the disease outcome. Vibrational spectroscopy has proven to be useful for cell and tissue characterization based on the intrinsic molecular information. Here, we have applied infrared and Raman microspectroscopy and imaging to differentiate between non-IBC and IBC at both cell and tissue levels. Two human breast cancer cell lines (MDA-MB-231 and SUM-149), 20 breast cancer patients (10 non-IBC and 10 IBC), and 4 healthy volunteer biopsies were investigated. Fixed cells and tissues were analyzed by FTIR microspectroscopy and imaging, while live cells were studied by Raman microspectroscopy. Spectra were analyzed by hierarchical cluster analysis (HCA) and images by common k-means clustering algorithms. For both cell suspensions and single cells, FTIR spectroscopy showed sufficient high inter-group variability to delineate MDA-MB-231 and SUM-149 cell lines. Most significant differences were observed in the spectral regions of 1096-1108 and 1672-1692 cm-1. Analysis of live cells by Raman microspectroscopy gave also a good discrimination of these cell types. The most discriminant regions were 688-992, 1019-1114, 1217-1375 and 1516-1625 cm-1. Finally, k-means cluster analysis of FTIR images allowed delineating non-IBC from IBC tissues. This study demonstrates the potential of vibrational spectroscopy and imaging to discriminate between non-IBC and IBC at both cell and tissue levels.
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Neoplasias Inflamatórias Mamárias/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodos , Adulto , Idoso , Algoritmos , Linhagem Celular Tumoral , Análise por Conglomerados , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/química , Pessoa de Meia-Idade , Análise de Célula Única/métodos , VibraçãoRESUMO
BACKGROUND: Inflammatory breast cancer (IBC), a particularly aggressive form of breast cancer, is characterized by cancer stem cell (CSC) phenotype. Due to a lack of targeted therapies, the identification of molecular markers of IBC is of major importance. The heparan sulfate proteoglycan Syndecan-1 acts as a coreceptor for growth factors and chemokines, modulating inflammation, tumor progression, and cancer stemness, thus it may emerge as a molecular marker for IBC. METHODS: We characterized expression of Syndecan-1 and the CSC marker CD44, Notch-1 & -3 and EGFR in carcinoma tissues of triple negative IBC (n = 13) and non-IBC (n = 17) patients using qPCR and immunohistochemistry. Impact of siRNA-mediated Syndecan-1 knockdown on the CSC phenotype of the human triple negative IBC cell line SUM-149 and HER-2-overexpressing non-IBC SKBR3 cells employing qPCR, flow cytometry, Western blotting, secretome profiling and Notch pharmacological inhibition experiments. Data were statistically analyzed using Student's t-test/Mann-Whitney U-test or one-way ANOVA followed by Tukey's multiple comparison tests. RESULTS: Our data indicate upregulation and a significant positive correlation of Syndecan-1 with CD44 protein, and Notch-1 & -3 and EGFR mRNA in IBC vs non-IBC. ALDH1 activity and the CD44(+)CD24(-/low) subset as readout of a CSC phenotype were reduced upon Syndecan-1 knockdown. Functionally, Syndecan-1 silencing significantly reduced 3D spheroid and colony formation. Intriguingly, qPCR results indicate downregulation of the IL-6, IL-8, CCL20, gp130 and EGFR mRNA upon Syndecan-1 suppression in both cell lines. Moreover, Syndecan-1 silencing significantly downregulated Notch-1, -3, -4 and Hey-1 in SUM-149 cells, and downregulated only Notch-3 and Gli-1 mRNA in SKBR3 cells. Secretome profiling unveiled reduced IL-6, IL-8, GRO-alpha and GRO a/b/g cytokines in conditioned media of Syndecan-1 knockdown SUM-149 cells compared to controls. The constitutively activated STAT3 and NFκB, and expression of gp130, Notch-1 & -2, and EGFR proteins were suppressed upon Syndecan-1 ablation. Mechanistically, gamma-secretase inhibition experiments suggested that Syndecan-1 may regulate the expression of IL-6, IL-8, gp130, Hey-1, EGFR and p-Akt via Notch signaling. CONCLUSIONS: Syndecan-1 acts as a novel tissue biomarker and a modulator of CSC phenotype of triple negative IBC via the IL-6/STAT3, Notch and EGFR signaling pathways, thus emerging as a promising therapeutic target for IBC.
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Neoplasias Inflamatórias Mamárias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais , Sindecana-1/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Biomarcadores , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/patologia , Interleucina-6/metabolismo , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Gradação de Tumores , Metástase Neoplásica , Células-Tronco Neoplásicas/patologia , Fenótipo , Proteoma , Proteômica/métodos , Receptores Notch/metabolismo , Fator de Transcrição STAT3/metabolismo , Sindecana-1/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Interleukin-10 is involved in carcinogenesis by supporting tumor escape from the immune response. The aim of this study was to assess the single nucleotide polymorphisms, -1082A/G, -819T/C and -592A/C, in interleukin-10 gene promoter in inflammatory breast cancer compared to non-inflammatory breast cancer and association of these polymorphisms with interleukin-10 gene expression. We enrolled 105 breast cancer tissue (72 non-inflammatory breast cancer and 33 inflammatory breast cancer) patients and we determined the three studied single nucleotide polymorphisms in all samples by polymerase chain reaction restriction fragment length polymorphism and investigated their association with the disease and with various prognostic factors. In addition, we assessed the expression of interleukin-10 gene by real-time quantitative reverse transcription polymerase chain reaction and the correlation between studied single nucleotide polymorphisms and interleukin-10 messenger RNA expression. We found co-dominant effect as the best inheritance model (in the three studied single nucleotide polymorphisms in non-inflammatory breast cancer and inflammatory breast cancer samples), and we didn't identify any association between single nucleotide polymorphisms genotypes and breast cancer prognostic factors. However, GCC haplotype was found highly associated with inflammatory breast cancer risk (p < 0.001, odds ratio = 43.05). Moreover, the expression of interleukin-10 messenger RNA was significantly higher (p < 0.001) by 5.28-fold and 8.95-fold than non-inflammatory breast cancer and healthy control, respectively, where GCC haplotype significantly increased interleukin-10 gene expression (r = 0.9, p < 0.001).
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Carcinogênese/genética , Carcinoma/genética , Neoplasias Inflamatórias Mamárias/genética , Interleucina-10/genética , Adulto , Idoso , Carcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Genótipo , Haplótipos/genética , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Interleucina-10/biossíntese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/biossínteseRESUMO
BACKGROUND: Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. Multiple viral infections in IBC tissues were found to be associated with disease pathogenesis. OBJECTIVE: The aim of the present study was to correlate the incidence of viral DNA with breast cancer progression. MATERIALS AND METHODS: Overall, 135 women diagnosed with breast cancer were enrolled in this study. Using polymerase chain reaction and sequencing assays, we determined the incidence of human papillomavirus types 16 and 18 (HPV-16 and -18), human cytomegalovirus (HCMV), Epstein-Barr virus, human herpes simplex virus type 1 and 2, and human herpes virus type 8 (HHV-8) in breast carcinoma tissue biopsies. We also assessed the expression of the cell proliferation marker Ki-67 by immunohistochemistry in association with the incidence of viral DNA. RESULTS: HCMV and HPV-16 were the most detected viral DNAs in breast carcinoma tissues; however, the frequency of HCMV and HHV-8 DNA were significantly higher in IBC than non-IBC tissues. Moreover, the prevalence of multiple viral DNAs was higher in IBC than non-IBC tissues. The incidence of multiple viral DNAs positively correlates with tumor size and number of metastatic lymph nodes in both non-IBC and IBC patients. The expression of Ki-67 was found to be significantly higher in both non-IBC and IBC tissues in which multiple viral DNAs were detected. CONCLUSIONS: The incidence of multiple viral DNAs in IBC tissues was higher compared with non-IBC tissues. The present results suggest the possibility of a functional relationship between the presence of multiple viral DNAs and disease pathogenesis.
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Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Lobular/epidemiologia , DNA Viral/genética , Neoplasias Inflamatórias Mamárias/epidemiologia , Viroses/complicações , Vírus/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/virologia , Carcinoma Lobular/genética , Carcinoma Lobular/secundário , Carcinoma Lobular/virologia , Progressão da Doença , Egito/epidemiologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/patologia , Neoplasias Inflamatórias Mamárias/virologia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Viroses/virologia , Vírus/genética , Vírus/patogenicidadeRESUMO
Epithelial-mesenchymal transition (EMT) is an essential process in breast cancer metastasis. The aim of the present study was to determine the role of secretions of tumor-associated leukocytes (TALs) isolated from negative and positive lymph nodes (nLNs and pLNs, respectively) breast cancer patients in regulating EMT mechanism and the associated signaling pathways. We found an increased infiltration of TALs, which was associated with downregulation of E-cadherin and over-expression of vimentin in the breast carcinoma tissues of pLNs as compared to nLNs patients and normal breast tissues obtained from healthy volunteers during mammoplasty. Furthermore, TALs isolated from pLNs breast cancer patients secreted an elevated panel of cytokines by up to 2-5-fold when compared with those isolated from nLNs patients. Secretome of TALs of pLNs possessed higher TARC, IGF-1, IL-3, TNF-ß, IL-5, G-CSF, IL-4, and IL-1α with more than a fivefold compared to those of nLNs. Using the human breast cancer cell lines MCF-7 and MDA-MB-231, we found that cytokines secreted by TALs isolated from nLNs and pLNs breast cancer patients promoted EMT via upregulation of TGF-ß and vimentin and downregulation of E-cadherin at messenger RNA (mRNA) levels in both cell lines and at protein level in MCF-7. While TGF-ß is over-expressed by MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. The downstream TGF-ß signaling transcription factors, Snail, Slug, and Twist, known to be associated with EMT mechanism were over-expressed by MCF-7 and MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. Acquisition of EMT in MCF-7 cells is mechanistically attributed to the activation of EGFR(Tyr845) and NF-κB/p65(Ser276) signaling which are significantly highly expressed by MCF-7 cells seeded in media conditioned by secretome of TALs isolated from pLNs compared to nLNs patients. Overall, this study provides implications of secretome of TALs and activated EGFR(Tyr845) and NF-κB/p65(Ser276) in EMT process that may be considered a therapeutic strategy to inhibit lymph node metastasis in breast cancer patients.
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Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Receptores ErbB/fisiologia , Leucócitos/metabolismo , Transdução de Sinais/fisiologia , Fator de Transcrição RelA/fisiologia , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/fisiologia , Microambiente TumoralRESUMO
Background: Trauma is a significant cause of mortality, especially among individuals aged between 15 and 44 years, with a substantial burden falling on economically active populations. Low- and middle-income countries (LMICs) bear the burden of trauma-related deaths, accounting for over 90 % globally. In Egypt, trauma rates are increasing, primarily due to road traffic crashes (RTC), affecting males disproportionately. Blunt abdominal trauma, often caused by RTC, can lead to missed intra-abdominal injuries (IAIs) due to atypical symptoms. Computed Tomography (CT) offers high sensitivity and specificity in detecting IAIs, but concerns about cost and radiation exposure exist. Methodology: This study investigates the roles of Focused Assessment with Sonography for Trauma (FAST) and CT in managing blunt abdominal trauma. A retrospective cohort study was conducted on hemodynamically stable patients. Data included patient demographics, trauma details, healthcare decisions, costs, and outcomes. Results: Computed tomography significantly reduced unnecessary laparotomies (12.3% vs. 24.8 %, p = 0.001), shortened hospital stays (4.83±0.71 days vs. 6.15±1.28 days, p = 0.005), and reduced ICU admissions (8 vs. 32, p = 0.023) compared to FAST alone. Overall costs were lower in the CT & FAST Group ($2055.95 vs. $3488.7, p = 0.0001), with no significant difference in missed IAIs. Conclusion: This study highlights the limitations of relying solely on FAST for IAIs and underscores the value of CT in guiding healthcare decisions. Incorporating CT led to reduced negative laparotomies, shorter hospital stays, and fewer ICU admissions. While CT incurs initial costs, its long-term benefits outweigh expenditures, particularly in LMICs. This study provides insights into optimizing diagnostic approaches for blunt abdominal trauma in low-resource settings.
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Introduction: Emergency medicine (EM) was formally recognized as a specialty in Egypt in 2002. Many institutions of higher education do not yet have an operational academic department of emergency medicine. This study attempts to quantify the awareness and attitude of Ain Shams University medical students towards emergency medicine as both a specialty and a career. Methods: A paper-based survey was delivered to undergraduate medical students at the Faculty of Medicine, Ain Shams University in Cairo, Egypt between December 2021 and April 2022. The survey was designed to assess awareness towards the scope of practice of emergency physicians as well as general attitude toward emergency medicine as a specialty and career choice. Results: A total of 391 students and interns/house officers participated in this study. 53.2% of participants were females and the mean age was 21.65 ± 2.25 years. Only 30 participants (7.7%) were classified as having "Excellent knowledge" of emergency medicine, 92 (23.5%) as "Good knowledge", 158 "40.4%" as "Fair knowledge" and 111 (28.4%) as "Poor knowledge". The difference in scores between academic years was not statistically significant (p = 0.239). 91.8% of respondents favored the creation of student interest groups in EM and 40% of respondents found it difficult to reach information regarding EM. Conclusion: Our study demonstrates a lack of awareness and knowledge towards emergency medicine as a specialty across all academic years at our institution. Formal recognition of EM as a specialty doesn't guarantee widespread knowledge among medical students, particularly at institutions without academic EM departments.
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Studies suggested that the pathogenesis of inflammatory breast cancer (IBC) is related to inflammatory manifestations accompanied by specific cellular and molecular mechanisms in the IBC tumor microenvironment (TME). IBC is characterized by significantly higher infiltration of tumor-associated macrophages (TAMs) that contribute to its metastatic process via secreting many cytokines such as TNF, IL-6, IL-8, and IL-10 that enhance invasion and angiogenesis. Thus, there is a need to first understand how IBC-TME modulates the polarization of TAMs to better understand the role of TAMs in IBC. Herein, we used gene expression signature and Synchrotron Fourier-Transform Infrared Microspectroscopy (SR-µFTIR) to study the molecular and biochemical changes, respectively of in vitro polarized TAMs stimulated by the secretome of IBC and non-IBC cells. The gene expression signature showed significant differences in the macrophage's polarization-related genes between stimulated TAMs. FTIR spectra showed absorption bands in the region of 1700-1500 cm-1 attributed to the amide I ν(C=O), & νAS (CN), δ (NH), and amide II ν(CN), δ (NH) proteins bands. Moreover, three peaks of different intensities and areas were detected in the lipid region of the νCH2 and νCH3 stretching modes positioned within the 3000-2800 cm-1 range. The PCA analysis for the second derivative spectra of the amide regions discriminates between stimulated IBC and non-IBC TAMs. This study showed that IBC and non-IBC TMEs differentially modulate the polarization of TAMs and SR-µFTIR can determine these biochemical changes which will help to better understand the potential role of TAMs in IBC.
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Neoplasias Inflamatórias Mamárias , Macrófagos Associados a Tumor , Humanos , Síncrotrons , Secretoma , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/metabolismo , Neoplasias Inflamatórias Mamárias/patologia , Amidas , Microambiente TumoralRESUMO
Background Blunt abdominal trauma (BAT) is the most common pattern of abdominal traumas. It may be associated with intra-abdominal injuries (IAIs). Exploratory laparotomies are only needed in a minority of patients after BAT. Methodology All BAT patients who presented to the El Demerdash Hospital of Ain Shams University, Cairo, Egypt during the study period were traced. Parameters including demographic data, focused assessment with sonography for trauma (FAST) scan, CT scan results, and hematuria were collected. The cohort was divided according to the CT scan results into two groups: patients with IAIs and patients without IAIs. Results Males represented 78.2% of the patients, and the mean age of the recruited patients was 32.1 ± 18 years. Road traffic accidents represented the main cause of trauma (58%). Patients with IAIs detected by CT scan represented 1.62%, and hematuria was detected in 88.9% of them. The specificity of FAST was 97.1%, and that of hematuria was 84.1%, and for the combination of both tests, the specificity was 99.3%. Conclusion IAIs after BAT can usually be excluded if both FAST and hematuria are negative, provided that the patient is stable.
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Introduction: Chest imaging plays a prominent role in the assessment of patients with blunt trauma. Selection of the right approach at the right time is fundamental in the management of patients with blunt chest trauma.[1] A reliable, economic, bedside, and rapidly accomplished screening test can be pivotal. [2]. Objective: The aim of this study was to compare the accuracy of extended- focused assessment with sonography for trauma (E-FAST) to that of the National Emergency X-Radiography Utilisation Study (NEXUS) chest algorithm in detecting blunt chest injuries. Methods: This descriptive cross-sectional study included 50 polytrauma patients with blunt chest trauma from the emergency centre of Suez Canal University Hospital. E-FAST and computed tomography (CT) were conducted, followed by reporting of NEXUS criteria for all patients. Blinding of the E-FAST performer and CT reporter were confirmed. The results of both the NEXUS algorithm and E-FAST were compared with CT chest results. Results: The NEXUS algorithm had 100% sensitivity and 15.3% specificity, and E-FAST had 70% sensitivity and 96.7% specificity, in the detection of pneumothorax.In the detection of hemothorax, the sensitivity and specificity of the NEXUS algorithm were 90% and 7.5%, respectively, whereas E-FAST had a lower sensitivity of 80% and a higher specificity of 97.5%. Conclusion: E-FAST is highly specific for the detection of hemothorax, pneumothorax, and chest injuries compared with the NEXUS chest algorithm, which demonstrated the lowest specificity. However, the NEXUS chest algorithm showed a higher sensitivity than E-FAST and hence can be used effectively to rule out thoracic injury.
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BACKGROUND: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome. METHODS: Fifty patients (31 non-IBC and 19 IBC) were enrolled in the present study. To test their validation in clinical studies, PDEs were cultured as an ex vivo model. Gene expression and cytokine array were used to identify candidate genes and cytokines contributing to metastasis in the examined fresh tissues and PDEs. Bioinformatics analysis was applied on identified differentially expressed genes using GeneMANIA and Metascape gene annotation and analysis resource to identify pathways involved in IBC metastasis. RESULTS: Normal and cancer fresh tissues and PDEs of IBC were characterized by overexpression of CDH1 and MMP14 and downregulation of CTNNA1 and TIMP1 compared with non-IBC. The secretome of IBC cancer PDEs is characterized by significantly high expression of interleukin 6 and monocyte chemoattractant protein-1 (CCL2) compared with non-IBC. CONCLUSION: Genes expressed by adhisome and matrisome play a significant role in IBC metastasis and should be considered novel target therapy.