Unlocking Overexpressed Membrane Proteins to Guide Breast Cancer Precision Medicine.

Breast cancer (BC) is a prevalent form of cancer affecting women worldwide. However, the effectiveness of current BC drugs is limited by issues such as systemic toxicity, drug resistance, and severe side effects. Consequently, there is an urgent need for new therapeutic targets and improved tumor tracking methods. This study aims to address these challenges by proposing a strategy for identifying membrane proteins in tumors that can be targeted for specific BC therapy and diagnosis. The strategy involves the analyses of gene expressions in breast tumor and non-tumor tissues and other healthy tissues by using comprehensive bioinformatics analysis from The Cancer Genome Atlas (TCGA), UALCAN, TNM Plot, and LinkedOmics. By employing this strategy, we identified four transcripts (LRRC15, EFNA3, TSPAN13, and CA12) that encoded membrane proteins with an increased expression in BC tissue compared to healthy tissue. These four transcripts also demonstrated high accuracy, specificity, and accuracy in identifying tumor samples, as confirmed by the ROC curve. Additionally, tissue microarray (TMA) analysis revealed increased expressions of the four proteins in tumor tissues across all molecular subtypes compared to the adjacent breast tissue. Moreover, the analysis of human interactome data demonstrated the important roles of these proteins in various cancer-related pathways. Taken together, these findings suggest that LRRC15, EFNA3, TSPAN13, and CA12 can serve as potential biomarkers for improving cancer diagnosis screening and as suitable targets for therapy with reduced side effects and enhanced efficacy.

Aptamer-Based Recognition of Breast Tumor Cells: A New Era for Breast Cancer Diagnosis.

Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.

Exploring Real-World HER2-Low Data in Early-Stage Triple-Negative Breast Cancer: Insights and Implications.

Purpose: This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups. Patients and Methods: This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). Results: A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups. Conclusion: The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.

Nuclear and Cytoplasmic hTERT, Tumor-Infiltrating Lymphocytes, and Telomere Elongation Leukocytes Are Independent Factors in the Response to Neoadjuvant Treatment in HER2-Enriched Breast Cancer.

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.

Next Generation of Ovarian Cancer Detection Using Aptamers.

Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced by tumors. Here, aptamers and their potential targets in ovarian cancer cells were analyzed by in silico approaches. Specific aptamers were selected by the Cell-SELEX method using Caov-3 and OvCar-3 cells. The five most frequent aptamers obtained from the last round of selection were computationally modeled. The potential targets for those aptamers in cells were proposed by analyzing proteomic data available for the Caov-3 and OvCar-3 cell lines. Overexpressed proteins for each cell were characterized as to their three-dimensional model, cell location, and electrostatic potential. As a result, four specific aptamers for ovarian tumors were selected: AptaC2, AptaC4, AptaO1, and AptaO2. Potential targets were identified for each aptamer through Molecular Docking, and the best complexes were AptaC2-FXYD3, AptaC4-ALPP, AptaO1-TSPAN15, and AptaO2-TSPAN15. In addition, AptaC2 and AptaO1 could detect different stages and subtypes of ovarian cancer tissue samples. The application of this technology makes it possible to propose new molecular biomarkers for the differential diagnosis of epithelial ovarian cancer.

Low body mass index is associated with reduced intratumoral CD4+ T-lymphocyte infiltration in laryngeal squamous cell carcinoma patients.

Tumor size, inflammation, and nutritional status may be correlated with the immune response to cancer. Our hypothesis is that there is an interrelationship among tumor size, inflammatory response, and body mass index (BMI), and that these variables could alter T-lymphocyte infiltration in patients with laryngeal squamous cell carcinoma (LSCC). A retrospective cohort of 91 surgical LSCC patients treated at a Brazilian National Cancer Reference Center was followed for 5 years. We collected data regarding BMI, clinical factors, patients' lifestyle, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Data were obtained in the medical records within a maximum interval of 7 days before surgery. The stromal and intratumoral CD4+ and CD8+ T-cell infiltrations were obtained by immunohistochemistry. Our results demonstrated a significant correlation among tumor size and BMI, NLR, PLR, and LMR. Similarly, PLR and LMR were significantly correlated with BMI. Tumor size and inflammatory parameters were not associated with changes in T-cell infiltrations. However, patients with low BMIs had a significantly lower density of intratumoral CD4+ T lymphocytes infiltrated when compared with normal/high BMI patients (odds ratio, 0.14; 95% confidence interval, 0.03-0.58; P = .007). CD8+ T-lymphocyte infiltration did not change in low-BMI patients. In conclusion, we observed a correlation among tumor size, inflammation, and BMI. Tumor size/inflammation axis may be responsible for the change in BMI and, therefore, may have influenced the reduction of intratumoral CD4+ T-lymphocyte infiltration in LSCC patients.

The protein-protein interaction network of intestinal gastric cancer patients reveals hub proteins with potential prognostic value.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer worldwide. According to the Lauren classification, gastric adenocarcinoma is divided into two subtypes: diffuse and intestinal. The development of intestinal gastric cancer (IGC) can take years and involves multiple factors. OBJECTIVE: To investigate the protein profile of tumor samples from patients with IGC in comparison with adjacent nontumor tissue samples. METHODS: We used label-free nano-LC-MS/MS to identify proteins from the tissues samples. The results were analyzed using MetaCore™ software to access functional enrichment information. Protein-protein interactions (PPI) were predicted using STRING analysis. Hub proteins were determined using the Cytoscape plugin, CytoHubba. Survival analysis was performed using KM plotter. We identified 429 differentially expressed proteins whose pathways and processes were related to protein folding, apoptosis, and immune response. RESULTS: The PPI network of these proteins showed enrichment modules related to the regulation of cell death, immune system, neutrophil degranulation, metabolism of RNA and chromatin DNA binding. From the PPI network, we identified 20 differentially expressed hub proteins, and assessed the prognostic value of the expression of genes that encode them. Among them, the expression of four hub genes was significantly associated with the overall survival of IGC patients. CONCLUSIONS: This study reveals important findings that affect IGC development based on specific biological alterations in IGC patients. Bioinformatics analysis showed that the pathogenesis of IGC patients is complex and involves different interconnected biological processes. These findings may be useful in research on new targets to develop novel therapies to improve the overall survival of patients with IGC.

Prognostic Influence of Residual Tumor-Infiltrating Lymphocyte Subtype After Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

OBJECTIVE: This study aimed to examine the prevalence and prognostic role of tumor microenvironment (TME) in triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NACT) through immunohistochemical characterization. METHODS: The internal database of the Brazilian National Cancer Institute for women diagnosed with TNBC who underwent NACT and thereafter curative surgery between January 2010 and December 2014 was queried out. Core biopsy specimens and tissue microarrays containing surgical samples of TNBC from 171 and 134 women, respectively, were assessed by immunohistochemistry for CD3, CD4, CD8, CD14, CD56, CD68, CD117, FOXP3, PD-1, PD-L1, and PD-L2. Immune cell profiles were analyzed and correlated with response and survival. RESULTS: Mean age was 50.5 years, and most cases were clinical stage III [143 cases (83.6%)]. According to the multivariate analysis, only Ki67 and clinical stage significantly influenced the pattern of response to systemic treatment (p = 0.019 and p = 0.033, respectively). None of the pre-NACT IHC markers showed a significant association with event-free survival (EFS) or overall survival (OS). As for post-NACT markers, patients with high CD14 had significantly shorter EFS (p = 0.015), while patients with high CD3 (p = 0.025), CD4 (p = 0.025), CD8 (p = 0.030), CD14 (p = 0.015), FOXP3 (p = 0.005), high CD4/FOXP3 (p = 0.034), and CD8/FOXP3 (p = 0.008) showed longer EFS. Only high post-NACT CD4 showed significantly influenced OS (p = 0.038). CONCLUSION: The present study demonstrated that the post-NACT TIL subtype can be a determining factor in the prognosis of patients with TNBC.

GLIPR1 and SPARC expression profile reveals a signature associated with prostate Cancer Brain metastasis.

Despite advances in treatment of lethal prostate cancer, the incidence of prostate cancer brain metastases is increasing. In this sense, we analyzed the molecular profile, as well as the functional consequences involved in the reciprocal interactions between prostate tumor cells and human astrocytes. We observed that the DU145 cells, but not the LNCaP cells or the RWPE-1 cells, exhibited more pronounced, malignant and invasive phenotypes along their interactions with astrocytes. Moreover, global gene expression analysis revealed several genes that were differently expressed in our co-culture models with the overexpression of GLIPR1 and SPARC potentially representing a molecular signature associated with the invasion of central nervous system by prostate malignant cells. Further, these results were corroborated by immunohistochemistry and in silico analysis. Thus, we conjecture that the data here presented may increase the knowledge about the molecular mechanisms associated with the invasion of CNS by prostate malignant cells.

Secretory carcinoma of salivary glands at the National Cancer Institute: A 20-year retrospective clinical, pathological, immunohistochemical and molecular study.

OBJECTIVES: This study aim was to review cases of acinic cell carcinoma (the main differential diagnosis of secretory carcinoma) that were diagnosed and treated at the National Cancer Institute of Brazil (INCA) between 1996 and 2016. The primary objective was to identify underdiagnosed cases of secretory carcinoma via a clinical, immunopathological and molecular reassessment. MATERIALS AND METHODS: This is a cross sectional study, with retrospective data collection from medical records and histological specimen review, with staining for periodic acid-Schiff (PAS) and PAS with diastase, immunohistochemistry for S-100, mammaglobin, and DOG-1, and droplet digital RT-PCR for ETV6-NTRK3. The Research Ethics Committee approved this study, and the patients allowed their participation through informed consent. RESULTS: Eighty-three cases of acinic cell carcinoma were diagnosed and treated in the specified period at INCA, of which, seven had their diagnosis changed to secretory carcinoma. CONCLUSION: The present study adds seven cases of secretory carcinoma to the literature, contributing to a better understanding of the epidemiological, histological, immunohistochemical and molecular characteristics of this recently described tumor. Also, the use of a comprehensive diagnostic approach, including immunohistochemical and molecular methods, along with classical morphological studies, allowed the reclassification of acinic cell carcinoma to secretory carcinoma.

Triple-Negative Breast Cancer: Assessing the Role of Immunohistochemical Biomarkers on Neoadjuvant Treatment.

OBJECTIVE: This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC). MATERIALS AND METHODS: The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes. RESULTS: Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0-1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p <0.0001, respectively) and LNR (p <0.0001 and p <0.0001, respectively) showed significant association. CONCLUSION: No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.

Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes.

BACKGROUND: Colorectal cancer (CRC) is among the deadliest cancers, wherein early dissemination of tumor cells, and consequently, metastasis formation, are the main causes of mortality and poor prognosis. Cofilin-1 (CFL-1) and its modulators, LIMK1/SSH1, play key roles in mediating the invasiveness by driving actin cytoskeleton reorganization in various cancer types. However, their clinical significance and prognostic value in CRC has not been fully explored. Here, we evaluated the clinical contribution of these actin regulators according to TNM and consensus molecular subtypes (CMSs) classification. METHODS: CFL-1, LIMK1 and SSH1 mRNA/protein levels were assessed by real-time PCR and immunohistochemical analyses using normal adjacent and tumor tissues obtained from a clinical cohort of CRC patients. The expression levels of these proteins were associated with clinicopathological features by using the chi square test. In addition, using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we determine how these actin regulators are expressed and distributed according to TNM and CMSs classification. Based on gene expression profiling, Kaplan-Meier survival analysis was used to evaluated overall survival. RESULTS: Bioinformatic analysis revealed that LIMK1 expression was upregulated in all tumor stages. Patients with high levels of LIMK1 demonstrated significantly lower overall survival rates and exhibited greater lymph node metastatic potential in a clinical cohort. In contrast, CFL-1 and SSH1 have expression downregulated in all tumor stages. However, immunohistochemical analyses showed that patients with high protein levels of CFL-1 and SSH1 exhibited greater lymph node metastatic potential and greater depth of local invasion. In addition, using the CMSs classification to evaluate different biological phenotypes of CRC, we observed that LIMK1 and SSH1 genes are upregulated in immune (CMS1) and mesenchymal (CMS4) subtypes. However, patients with high levels of LIMK1 also demonstrated significantly lower overall survival rates in canonical (CMS2), and metabolic (CMS3) subtypes. CONCLUSIONS: We demonstrated that CFL-1 and its modulators, LIMK1/SSH1, are differentially expressed and associated with lymph node metastasis in CRC. Finally, this expression profile may be useful to predict patients with aggressive signatures, particularly, the immune and mesenchymal subtypes of CRC.

High infiltration of B cells in tertiary lymphoid structures, TCR oligoclonality, and neoantigens are part of esophageal squamous cell carcinoma microenvironment.

Esophageal squamous cell carcinoma (ESCA) exhibits high intratumoral molecular heterogeneity posing a challenge to cancer therapy. Immune checkpoint blockade therapy has been approved for this disease, but with modest results. RNA-Seq data from paired tumor and surrounding nonmalignant tissue from 14 patients diagnosed with ESCA without previous treatment and from The Cancer Genome Atlas-ESCA cohort were analyzed. Herein, we investigated ESCA immune landscape including mutation-derived neoantigens and immune cell subpopulations. Tumor-associated antigen expression was determined by in silico analyses and confirmed by immunohistochemistry showing that PRAME, CEACAM4, and MAGEA11 proteins are expressed on tumors. Immune checkpoint molecules gene expression was higher in the tumor compared with surrounding nonmalignant tissue, but its expression varies greatly among patients. TCR repertoire and BCR transcripts analysis evidenced low clonal diversity with one TCR clone predicted to be specific for a MAGEA11-derived peptide. A high number of B-cell clones infiltrating the tumors and the abundance of these cells in tertiary lymphoid structures observed in ESCA tumors support B cells as a potential immune modulator in this tumor.

Hpv impact on oropharyngeal cancer patients treated at the largest cancer center from Brazil.

Oropharyngeal squamous cell carcinoma (OSCC) is a fatal and highly incident disease. Although tobacco and alcohol consumption are the main risk factors associated with OSCC, a recent significant increase in OSCC HPV16 positive cases in high-income countries has been observed. However, it is not clear whether this change is also present in low- and middle-income countries. In this study, we evaluated HPV16 prevalence in 346 OSCC cases diagnosed in the largest Brazilian oncology public hospital by using the combination of two techniques, HPV16 E6 detection by qPCR and p16 immunohistochemistry. In total, 11.9% of cases were HPV16 E6 positive, 9.2% were p16 positive and 6.1% were positive in both analyses. There was a predominance of keratinizing-SCC, with only four HPV-positive cases showing basaloid-like or non-keratinizing-SCC. HPV infection had no impact on disease-free or overall survival, while alcohol use was an independent prognostic factor for overall survival. Most cases reported a high frequency of tobacco (94.6%) and alcohol consumption (88.2%), were of low education level, and typically presented at advanced clinical stages, indicating that the profile of Brazilian OSCC patients has not changed.

TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma.

PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

p53 expression and subcellular survivin localization improve the diagnosis and prognosis of patients with diffuse astrocytic tumors.

PURPOSE: Diffuse astrocytic tumors are the most frequently occurring primary central nervous system (CNS) tumors. Their histological sub-classification into diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GB) is challenging and the available prognostic factors are limited to age and tumor subtype. Biomarkers that may improve the histological sub-classification and/or serve as prognostic factors are, therefore, urgently needed. The relationship between survivin and p53 in diffuse astrocytic tumor progression and survival is currently unclear. Here, we aimed to assess the relevance of these proteins in the accuracy of the histological sub-classification of these tumors and their respective treatment responses. METHODS: One hundred and thirty-three formalin-fixed paraffin-embedded diffuse astrocytic tumor samples were included. The tumor samples were histologically reviewed and subsequently assessed for p53 and survivin expression and the presence of the IDH R132H mutation by immunohistochemistry. p53 expression levels and survivin subcellular localization patterns were correlated with histological classification and clinical outcome. RESULTS: We found that age and histological subtype were the only features with a prognostic impact. In addition, we found that high p53 expression levels and a nuclear survivin localization correlated with the AA subtype, whereas cytoplasmic survivin localization correlated with the GB subtype. We also found that patients carrying tumors with a high cytoplasmic survivin expression, a high nuclear survivin expression or a high p53 expression, and who did not receive radiotherapy, exhibited poorer short-term and long-term overall survival rates. CONCLUSIONS: Our data suggest that subcellular survivin localization and p53 expression may be employed as valuable tools to improve the accuracy of the histological sub-classification of diffuse astrocytic tumors. Patients whose tumors overexpress these proteins may benefit from radiotherapy, irrespective age and/or histological classification.

DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis.

Despite remarkable advances in diagnosis, prognosis and treatment, advanced or recurrent breast tumors have limited therapeutic approaches. Many treatment strategies try to explore the limitations of DNA damage response (DDR) in tumor cells to selectively eliminate them. BRCT (BRCA1 C-terminal) domains are present in a superfamily of proteins involved in cell cycle checkpoints and the DDR. Tandem BRCT domains (tBRCT) represent a distinct class of these domains. We investigated the expression profile of 7 tBRCT genes (BARD1, BRCA1, LIG4, ECT2, MDC1, PAXIP1/PTIP and TP53BP1) in breast cancer specimens and observed a high correlation between PAXIP1 and TP53BP1 gene expression in tumor samples. Tumors with worse prognosis (tumor grade 3 and triple negative) showed reduced expression of tBRCT genes, notably, PAXIP1 and TP53BP1. Survival analyses data indicated that tumor status of both genes may impact prognosis. PAXIP1 and 53BP1 protein levels followed gene expression results, i.e., are intrinsically correlated, and also reduced in more advanced tumors. Evaluation of both genes in triple negative breast tumor samples which were characterized for their BRCA1 status showed that PAXIP1 is overexpressed in BRCA1 mutant tumors. Taken together our findings indicate that PAXIP1 status correlates with breast cancer staging, in a manner similar to what has been characterized for TP53BP1.

Banda 6. 0: a experiência da música na terceira idade / Band 6. 0: the music experience in the third age / Banda 6. 0: la experiencia de la música en la vejez

O processo de envelhecimento é marcado pela passagem dos anos e por diversas transições biopsicossociais muito comuns. Atualmente, são verificadas formas novas de envelhecimento e garantir a qualidade de vida para idosos representa um desafio. O Centro de Convivência da Terceira Idade, serviço voltado para idosos, buscou utilizar a música como uma de suas ferramentas de trabalho. A proposta foi criar uma banda de música em que os idosos fossem participantes e coordenadores do próprio grupo. O trabalho foi realizado de forma transdisciplinar e foi considerado extremamente positivo, pois os idosos participantes trataram a banda com muito compromisso e seriedade. A banda lhes deu visibilidade social. Os idosos se dedicavam integralmente a ela de forma que cada apresentação foi satisfatória. Foram observados como resultados desse trabalho o fortalecimento da autoimagem, maior valorização do idoso de forma geral e, particularmente, o reconhecimento do idoso pela sua família e comunidade.

The process of aging is marked by the passage of years and by several very common bio psychosocial transitions. Nowadays, new forms of aging are verified and assuring the quality of life for the elderly poses a challenge. The Elderly Living Center, a service focused on the elderly, sought to use music as one of their working tools. The proposal was to create a music band in which the elderly were participants and coordinators of the group itself. The work was carried out in a transdisciplinary way and was considered extremely positive, since the elderly participants treated the band with a lot of commitment and seriousness. The band gave them social visibility. The elderly were fully dedicated to it so that each presentation was satisfactory. The results of this work were the strengthening of the self-image, greater appreciation of the elderly in general, and particularly the recognition of the elderly by their family and community.

El proceso de envejecimiento está marcado por el paso de los años y por varias transiciones bio-psicosociales muy comunes. Hoy en día, se verifican nuevas formas de envejecimiento y asegurar la calidad de vida de los ancianos plantea un desafío. El Centro de Ancianos, un servicio enfocado a los ancianos, buscó utilizar la música como una de sus herramientas de trabajo. La propuesta era crear una banda de música en la que los ancianos fueran participantes y coordinadores del propio grupo. El trabajo se realizó de forma transdisciplinaria y fue considerado extremadamente positivo, ya que los participantes trataron a la banda con mucho compromiso y seriedad. La banda les dio visibilidad social. Los ancianos se dedicaron plenamente a ella para que cada presentación fuera satisfactoria. Los resultados de este trabajo fueron el fortalecimiento de la autoimagen, la mayor apreciación de los ancianos en general y particularmente el reconocimiento de los ancianos por su familia y comunidad.

Peculiaridades entre conselho tutelar e crianças encaminhadas pela escola / Particularities between tutorial council and children sent by the schools

Este artigo se propõe a considerar as peculiaridades da relação entre o Conselho Tutelar e as crianças que foram encaminhadas a este órgão pela escola no município de Cariacica-ES. A partir do método qualitativo, priorizou-se o estudo com conselheiras tutelares tentando apreender, por meio de suas experiências, como descrevem o atendimento dado às crianças que lhes são encaminhadas. O referencial teórico que sustentou o trabalho aproximou-se de autores que compartilham, juntamente com Foucault, da ideia de uma história que pode ser abordada numa perspectiva genealógica permitindo-nos a visibilidade dos mais variados saberes existentes em um determinado espaço e momento social. Foram realizadas entrevistas semiestruturadas com quatro conselheiras. Na análise, pode-se constatar processos de psicologização, a presença da formulação de um discurso competente baseado no intimismo e no familiarismo e a formação de um campo de forças entre escola e conselho, no qual a criança tem, em geral, seu comportamento tido como inaceitável.

This article aims at the particularities concerning the Tutorial Council and children that were sent by their schools from the city of Cariacica ES to this institution. From this qualitative method, the study with the tutorial counselors was prioritized in an attempt to learn, through their experiences how to describe the assistance given to the children brought to them. The theoretical reference works with authors that share the idea of a story that can be approached in a genealogical perspective, together with Foucault, that allows a vision of a wide variety of knowledge existing in a determined space and social moment. Interviews were made with four counselors. Through the analysis, it comes a relation marked by psychology, competent speech, proximity, familiarization and the formation of a strength field among the schools and the Tutorial Council, on which most of the times, the child's behavior is considered unacceptable.

Peculiaridades entre conselho tutelar e crianças encaminhadas pela escola / Particularities between tutorial council and children sent by the schools

Este artigo se propõe a considerar as peculiaridades da relação entre o Conselho Tutelar e as crianças que foram encaminhadas a este órgão pela escola no município de Cariacica-ES. A partir do método qualitativo, priorizou-se o estudo com conselheiras tutelares tentando apreender, por meio de suas experiências, como descrevem o atendimento dado às crianças que lhes são encaminhadas. O referencial teórico que sustentou o trabalho aproximou-se de autores que compartilham, juntamente com Foucault, da ideia de uma história que pode ser abordada numa perspectiva genealógica permitindo-nos a visibilidade dos mais variados saberes existentes em um determinado espaço e momento social. Foram realizadas entrevistas semiestruturadas com quatro conselheiras. Na análise, pode-se constatar processos de psicologização, a presença da formulação de um discurso competente baseado no intimismo e no familiarismo e a formação de um campo de forças entre escola e conselho, no qual a criança tem, em geral, seu comportamento tido como inaceitável.(AU)

This article aims at the particularities concerning the Tutorial Council and children that were sent by their schools from the city of Cariacica ES to this institution. From this qualitative method, the study with the tutorial counselors was prioritized in an attempt to learn, through their experiences how to describe the assistance given to the children brought to them. The theoretical reference works with authors that share the idea of a story that can be approached in a genealogical perspective, together with Foucault, that allows a vision of a wide variety of knowledge existing in a determined space and social moment. Interviews were made with four counselors. Through the analysis, it comes a relation marked by psychology, competent speech, proximity, familiarization and the formation of a strength field among the schools and the Tutorial Council, on which most of the times, the child's behavior is considered unacceptable.(AU)