41 results on '"Kuasne, Hellen"'
Search Results
2. The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer
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Taifour, Tarek, Attalla, Sherif Samer, Zuo, Dongmei, Gu, Yu, Sanguin-Gendreau, Virginie, Proud, Hailey, Solymoss, Emilie, Bui, Tung, Kuasne, Hellen, Papavasiliou, Vasilios, Lee, Chun Geun, Kamle, Suchitra, Siegel, Peter M., Elias, Jack A., Park, Morag, and Muller, William J.
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- 2023
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3. DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas
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Calanca, Naiade, Francisco, Ana Lucia Noronha, Bizinelli, Daniela, Kuasne, Hellen, Barros Filho, Mateus Camargo, Flores, Bianca Campos Troncarelli, Pinto, Clóvis Antonio Lopes, Rainho, Claudia Aparecida, Soares, Milena Botelho Pereira, Marchi, Fabio Albuquerque, Kowalski, Luiz Paulo, and Rogatto, Silvia Regina
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- 2023
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4. Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α levels
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Goyette, Marie-Anne, Elkholi, Islam E., Apcher, Chloé, Kuasne, Hellen, Rothlin, Carla V., Muller, William J., Richard, Darren E., Park, Morag, Gratton, Jean-Philippe, and Côté, Jean-François
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- 2021
5. Coordinated activation of c-Src and FOXM1 drives tumor cell proliferation and breast cancer progression
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Nandi, Ipshita, Smith, Harvey W., Sanguin-Gendreau, Virginie, Ji, Linjia, Pacis, Alain, Papavasiliou, Vasilios, Zuo, Dongmei, Nam, Stella, Attalla, Sherif S., Kim, Sung Hoon, Lusson, Sierra, Kuasne, Hellen, Fortier, Anne-Marie, Savage, Paul, Ramirez, Constanza Martinez, Park, Morag, Katzenellenbogen, John A., Katzenellenbogen, Benita S., and Muller, William J.
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Gene expression -- Analysis ,Breast cancer -- Diagnosis -- Development and progression ,Health care industry - Abstract
Activation of the tyrosine kinase c-Src promotes breast cancer progression and poor outcomes, yet the underlying mechanisms are incompletely understood. Here, we have shown that deletion of c-Src in a genetically engineered model mimicking the luminal B molecular subtype of breast cancer abrogated the activity of forkhead box M1 (FOXM1), a master transcriptional regulator of the cell cycle. We determined that c-Src phosphorylated FOXM1 on 2 tyrosine residues to stimulate its nuclear localization and target gene expression. These included key regulators of [G.sub.2]/M cell-cycle progression as well as c-Src itself, forming a positive feedback loop that drove proliferation in genetically engineered and patient-derived models of luminal B-like breast cancer. Using genetic approaches and small molecules that destabilize the FOXM1 protein, we found that targeting this mechanism induced [G.sub.2]/M cell-cycle arrest and apoptosis, blocked tumor progression, and impaired metastasis. We identified a positive correlation between FOXM1 and c-Src expression in human breast cancer and show that the expression of FOXM1 target genes predicts poor outcomes and associates with the luminal B subtype, which responds poorly to currently approved therapies. These findings revealed a regulatory network centered on c-Src and FOXM1 that is a targetable vulnerability in aggressive luminal breast cancers., Introduction Breast cancer comprises a range of histopathological and molecular subtypes differing in metastatic capacity, response to therapies, and clinical outcomes (1). Transcriptomic profiling has identified at least 5 breast [...]
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- 2023
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6. Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression
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Maller, Ori, Drain, Allison P., Barrett, Alexander S., Borgquist, Signe, Ruffell, Brian, Zakharevich, Igor, Pham, Thanh T., Gruosso, Tina, Kuasne, Hellen, Lakins, Johnathon N., Acerbi, Irene, Barnes, J. Matthew, Nemkov, Travis, Chauhan, Aastha, Gruenberg, Jessica, Nasir, Aqsa, Bjarnadottir, Olof, Werb, Zena, Kabos, Peter, Chen, Yunn-Yi, Hwang, E. Shelley, Park, Morag, Coussens, Lisa M., Nelson, Andrew C., Hansen, Kirk C., and Weaver, Valerie M.
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- 2021
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7. STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer
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Totten, Stephanie P., Im, Young Kyuen, Cepeda Cañedo, Eduardo, Najyb, Ouafa, Nguyen, Alice, Hébert, Steven, Ahn, Ryuhjin, Lewis, Kyle, Lebeau, Benjamin, La Selva, Rachel, Sabourin, Valérie, Martínez, Constanza, Savage, Paul, Kuasne, Hellen, Avizonis, Daina, Santos Martínez, Nancy, Chabot, Catherine, Aguilar-Mahecha, Adriana, Goulet, Marie-Line, Dankner, Matthew, Witcher, Michael, Petrecca, Kevin, Basik, Mark, Pollak, Michael, Topisirovic, Ivan, Lin, Rongtuan, Siegel, Peter M., Kleinman, Claudia L., Park, Morag, St-Pierre, Julie, and Ursini-Siegel, Josie
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- 2021
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8. Deregulation of E-cadherin, β-catenin, APC and Caveolin-1 expression occurs in canine prostate cancer and metastatic processes
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Kobayashi, Priscila E., Fonseca-Alves, Carlos E., Rivera-Calderón, Luis G., Carvalho, Márcio, Kuasne, Hellen, Rogatto, Silvia R., and Laufer-Amorim, Renée
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- 2018
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9. Nuclear loss and cytoplasmic expression of androgen receptor in penile carcinomas: role as a driver event and as a prognosis factor
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Kuasne, Hellen, Barros-Filho, Mateus C., Marchi, Fábio A., Drigo, Sandra A., Scapulatempo-Neto, Cristovam, Faria, Eliney F., and Rogatto, Silvia R.
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- 2018
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10. Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumors
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Savage, Paul, Pacis, Alain, Kuasne, Hellen, Liu, Leah, Lai, Daniel, Wan, Adrian, Dankner, Matthew, Martinez, Constanza, Muñoz-Ramos, Valentina, Pilon, Virginie, Monast, Anie, Zhao, Hong, Souleimanova, Margarita, Annis, Matthew G., Aguilar-Mahecha, Adriana, Lafleur, Josiane, Bertos, Nicholas R., Asselah, Jamil, Bouganim, Nathaniel, Petrecca, Kevin, Siegel, Peter M., Omeroglu, Atilla, Shah, Sohrab P., Aparicio, Samuel, Basik, Mark, Meterissian, Sarkis, and Park, Morag
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- 2020
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11. GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer
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Wu, Qin, ba-alawi, Wail, Deblois, Genevieve, Cruickshank, Jennifer, Duan, Shili, Lima-Fernandes, Evelyne, Haight, Jillian, Tonekaboni, Seyed Ali Madani, Fortier, Anne-Marie, Kuasne, Hellen, McKee, Trevor D., Mahmoud, Hassan, Kushida, Michelle, Cameron, Sarina, Dogan-Artun, Nergiz, Chen, WenJun, Nie, Yan, Zhang, Lan Xin, Vellanki, Ravi N., Zhou, Stanley, Prinos, Panagiotis, Wouters, Bradly G., Dirks, Peter B., Done, Susan J., Park, Morag, Cescon, David W., Haibe-Kains, Benjamin, Lupien, Mathieu, and Arrowsmith, Cheryl H.
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- 2020
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12. Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma
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Ortiz, Isabella Maria Dias Payão, Barros-Filho, Mateus Camargo, dos Reis, Mariana Bisarro, Beltrami, Caroline Moraes, Marchi, Fabio Albuquerque, Kuasne, Hellen, do Canto, Luísa Matos, de Mello, Julia Bette Homem, Abildgaard, Cecilie, Pinto, Clóvis Antônio Lopes, Kowalski, Luiz Paulo, and Rogatto, Silvia Regina
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- 2018
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13. Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations
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de Araújo, Érica Sara Souza, Marchi, Fabio Albuquerque, Rodrigues, Tatiane Cristina, Vieira, Henrique Cursino, Kuasne, Hellen, Achatz, Maria Isabel Waddington, Moredo, Luciana Facure, de Sá, Bianca Costa Soares, Duprat, João Pereira, Brentani, Helena Paula, Rosenberg, Carla, Carraro, Dirce Maria, and Krepischi, Ana Cristina Victorino
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- 2014
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14. Bioprinted Multicomponent Hydrogel Co-culture Tumor-Immune Model for Assessing and Simulating Tumor-Infiltrated Lymphocyte Migration and Functional Activation.
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Flores-Torres, Salvador, Dimitriou, Nikolaos M., Pardo, Lucas Antonio, Kort-Mascort, Jacqueline, Pal, Sanjima, Peza-Chavez, Omar, Kuasne, Hellen, Berube, Julie, Bertos, Nicholas, Park, Morag, Mitsis, Georgios D., Ferri, Lorenzo, Sangwan, Veena, and Kinsella, Joseph M.
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- 2023
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15. Evaluation of the influence of polymorphic variants CYP1A1*2B, CYP1B1*2, CYP3A4*1B, GSTM1*0, and GSTT1*0 in prostate cancer
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Rodrigues, Iara S., Kuasne, Hellen, Losi-Guembarovski, Roberta, Fuganti, Paulo E., Gregório, Émerson P., Kishima, Marina O., Ito, Kazuhiro, de Freitas Rodrigues, Marco A., and de Syllos Cólus, Ilce M.
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- 2011
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16. PHF21B as a candidate tumor suppressor gene in head and neck squamous cell carcinomas
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Bertonha, Fernanda Bernardi, Barros Filho, Mateus de Camargo, Kuasne, Hellen, dos Reis, Patricia Pintor, da Costa Prando, Erika, Muñoz, Juan José Augusto Moyano, Roffé, Martín, Hajj, Glaucia Noeli Maroso, Kowalski, Luiz Paulo, Rainho, Claudia Aparecida, and Rogatto, Silvia Regina
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- 2015
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17. Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer
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Grando, João Paulo Souto, Kuasne, Hellen, Losi-Guembarovski, Roberta, Sant’Ana Rodrigues, Iara, Matsuda, Henrique Mitsu, Fuganti, Paulo Emílio, Gregório, Émerson Pereira, Júnior, Farid Libos, de Menezes, Rodrigo Paes, de Freitas Rodrigues, Marco Aurélio, and de Syllos Cólus, Ilce Mara
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- 2009
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18. Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer.
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Cury, Sarah Santiloni, Kuasne, Hellen, dos Santos Souza, Jeferson, Moyano Muñoz, Juan Jose, Pereira da Silva, Jeyson, Lopes, Ademar, Scapulatempo-Neto, Cristovam, Ferreira Faria, Eliney, Delaissé, Jean-Marie, Albuquerque Marchi, Fabio, and Regina Rogatto, Silvia
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PENILE cancer ,FIBROBLASTS ,EXTRACELLULAR matrix ,METALLOPROTEINASES ,CELL populations - Abstract
Extracellular matrix (ECM) remodeling and inflammation have been reported in penile carcinomas (PeCa). However, the cell types and cellular crosstalk involved in PeCa are unexplored. We aimed to characterize the complexity of cells and pathways involved in the tumor microenvironment (TME) in PeCa and propose target molecules associated with the TME. We first investigated the prognostic impact of cell types with a secretory profile to identify drug targets that modulate TME-enriched cells. The secretome analysis using the PeCa transcriptome revealed the enrichment of inflammation and extracellular matrix pathways. Twenty-three secreted factors were upregulated, mainly collagens and matrix metalloproteinases (MMPs). The deregulation of collagens and MMPs was confirmed by Quantitative reverse transcription - polymerase chain reaction (RT-qPCR). Further, the deconvolution method (digital cytometry) of the bulk samples revealed a high proportion of macrophages and dendritic cells (DCs) and B cells. Increased DCs and B cells were associated with better survival. A high proportion of cancer-associated fibroblasts (CAFs) was observed in low-survival patients. Patients with increased CAFs had decreased immune cell proportions. The treatment with the MMP inhibitor GM6001 in CAF cells derived from PeCa resulted in altered cell viability. We reported a crosstalk between immune cells and CAFs, and the proportion of these cell populations was associated with prognosis. We demonstrate that a drug targeting MMPs modulates CAFs, expanding the therapeutic options of PeCa. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Multi-omics data integration analysis identifies the spliceosome as a key regulator of DNA double-strand break repair.
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Sherill-Rofe, Dana, Raban, Oded, Findlay, Steven, Rahat, Dolev, Unterman, Irene, Samiei, Arash, Yasmeen, Amber, Kaiser, Zafir, Kuasne, Hellen, Park, Morag, Foulkes, William D., Bloch, Idit, Zick, Aviad, Gotlieb, Walter H., Tabach, Yuval, and Orthwein, Alexandre
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- 2022
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20. miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands.
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Naakka, Erika, Barros-Filho, Mateus Camargo, Adnan-Awad, Shady, Al-Samadi, Ahmed, Marchi, Fábio Albuquerque, Kuasne, Hellen, Korelin, Katja, Suleymanova, Ilida, Brown, Amy Louise, Scapulatempo-Neto, Cristovam, Lourenço, Silvia Vanessa, Castilho, Rogério Moraes, Kowalski, Luiz Paulo, Mäkitie, Antti, Araújo, Vera Cavalcanti, Leivo, Ilmo, Rogatto, Silvia Regina, Salo, Tuula, and Passador-Santos, Fabricio
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MICRORNA ,SALIVARY glands ,HIERARCHICAL clustering (Cluster analysis) ,CARCINOMA ,CELL migration - Abstract
Objectives: To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers. Material and Methods: Gene and miRNA expression arrays were performed in 35 MECs and six NSGs. Results: We found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT. Conclusion: The in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Alginate–gelatin–Matrigel hydrogels enable the development and multigenerational passaging of patient-derived 3D bioprinted cancer spheroid models.
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Flores-Torres, Salvador, Peza-Chavez, Omar, Kuasne, Hellen, Munguia-Lopez, Jose G, Kort-Mascort, Jacqueline, Ferri, Lorenzo, Jiang, Tao, Rajadurai, Charles V, Park, Morag, Sangwan, Veena, and Kinsella, Joseph M
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- 2021
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22. Circulating mRNA signature as a marker for high-risk prostate cancer.
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Souza, Marilesia Ferreira De, Kuasne, Hellen, Barros-Filho, Mateus De Camargo, Cilião, Heloísa Lizotti, Marchi, Fabio Albuquerque, Fuganti, Paulo Emilio, Rogatto, Silvia Regina, and Cólus, Ilce Mara De Syllos
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Prostate cancer (PCa) is the second most common cancer in men. The indolent course of the disease makes the treatment choice a challenge for physicians and patients. In this study, a minimally invasive method was used to evaluate the potential of molecular markers in identifying patients with aggressive disease. Cell-free plasma samples from 60 PCa patients collected before radical prostatectomy were used to evaluate the levels of expression of eight genes (AMACR , BCL2 , NKX3-1 , GOLM1 , OR51E2 , PCA3 , SIM2 and TRPM8) by quantitative real-time PCR. Overexpression of A MACR , GOLM1 , TRPM8 and NKX3-1 genes was significantly associated with aggressive disease characteristics, including extracapsular extension, tumor stage and vesicular seminal invasion. A trio of genes (GOLM1 , NKX3-1 and TRPM8) was able to identify high-risk PCa cases (85% of sensitivity and 58% of specificity), yielding a better overall performance compared with the biopsy Gleason score and prostate-specific antigen, routinely used in the clinical practice. Although more studies are required, these circulating markers have the potential to be used as an additional test to improve the diagnosis and treatment decision of high-risk PCa patients. [ABSTRACT FROM AUTHOR]
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- 2020
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23. E-Cadherin Downregulation is Mediated by Promoter Methylation in Canine Prostate Cancer.
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Fonseca-Alves, Carlos Eduardo, Kobayashi, Priscila Emiko, Leis-Filho, Antonio Fernando, Lainetti, Patricia de Faria, Grieco, Valeria, Kuasne, Hellen, Rogatto, Silvia Regina, and Laufer-Amorim, Renee
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PROSTATE cancer ,METHYLATION ,P16 gene ,DOWNREGULATION ,DNA methylation ,GENE expression - Abstract
E-cadherin is a transmembrane glycoprotein responsible for cell-to-cell adhesion, and its loss has been associated with metastasis development. Although E-cadherin downregulation was previously reported in canine prostate cancer (PC), the mechanism involved in this process is unclear. It is well established that dogs, besides humans, spontaneously develop PC with high frequency; therefore, canine PC is an interesting model to study human PC. In human PC, CDH1 methylation has been associated with E-cadherin downregulation. However, no previous studies have described the methylation pattern of CDH1 promoter in canine PC. Herein, we evaluated the E-cadherin protein and gene expression in canine PC compared to normal tissues. DNA methylation pattern was investigated as a regulatory mechanism of CDH1 silencing. Our cohort is composed of 20 normal prostates, 20 proliferative inflammatory atrophy (PIA) lesions, 20 PC, and 11 metastases from 60 dogs. The E-cadherin protein expression was assessed by immunohistochemistry and western blotting and gene expression by qPCR. Bisulfite- pyrosequencing assay was performed to investigate the CDH1 promoter methylation pattern. Membranous E-cadherin expression was observed in all prostatic tissues. A higher number of E-cadherin negative cells was detected more frequently in PC compared to normal and PIA samples. High-grade PC showed a diffuse membranous positive immunostaining. Furthermore, PC patients with a higher number of E-cadherin negative cells presented shorter survival time and higher Gleason scores. Western blotting and qPCR assays confirmed the immunohistochemical results, showing lower E-cadherin protein and gene expression levels in PC compared to normal samples. We identified CDH1 promoter hypermethylation in PIA and PC samples. An in vitro assay with two canine prostate cancer cells (PC1 and PC2 cell lines) was performed to confirm the methylation as a regulatory mechanism of E-cadherin expression. PC1 cell line presented CDH1 hypermethylation and after 5-Aza-dC treatment, a decreased CDH1 methylation and increased gene expression levels were observed. Positive E-cadherin cells were massively found in metastases (mean of 90.6%). In conclusion, low levels of E-cadherin protein, gene downregulation and CDH1 hypermethylation was detected in canine PC. However, in metastatic foci occur E-cadherin re-expression confirming its relevance in these processes. [ABSTRACT FROM AUTHOR]
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- 2019
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24. DNA Methylation-Based Method to Differentiate Malignant from Benign Thyroid Lesions.
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Barros-Filho, Mateus Camargo, dos Reis, Mariana Bisarro, Beltrami, Caroline Moraes, de Mello, Julia Bette Homem, Marchi, Fábio Albuquerque, Kuasne, Hellen, Drigo, Sandra Aparecida, de Andrade, Victor Piana, Saieg, Mauro Ajaj, Pinto, Clóvis Antonio Lopes, Kowalski, Luiz Paulo, and Rogatto, Silvia Regina
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PYROSEQUENCING ,RECEIVER operating characteristic curves ,NEEDLE biopsy ,DNA methylation ,THYROID cancer ,DNA - Abstract
Background: The differential diagnosis of thyroid nodules using fine-needle aspiration biopsy (FNAB) is challenging due to the inherent limitation of the cytology tests. The use of molecular markers has potential to complement the FNAB-based diagnosis and avoid unnecessary surgeries. In this study, we aimed to identify DNA methylation biomarkers and to develop a diagnostic tool useful for thyroid lesions. Methods: Genome-wide DNA methylation profiles (Illumina 450K) of papillary thyroid carcinoma (PTC = 60) and follicular thyroid carcinoma (FTC = 10) were compared with non-neoplastic thyroid tissue samples (NT = 50) and benign thyroid lesions (BTL = 17). The results were confirmed in publicly available databases from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) using the same DNA methylation platform. Two classifiers were trained to discriminate FTC and PTC from BTL. To increase the applicability of the method, six differentially methylated CpGs were selected and evaluated in 161 thyroid tumors and 69 BTL postsurgical specimens and 55 prospectively collected FNAB using bisulfite-pyrosequencing. Results: DNA methylation analysis revealed 2130 and 19 differentially methylated CpGs in PTC and FTC, respectively. The CpGs confirmed by GEO and TCGA databases showing high areas under the receiver operating characteristic curve in all sample sets were used to train our diagnostic classifier. The model based on six CpGs was able to differentiate benign from malignant thyroid lesions with 94.3% sensitivity and 82.4% specificity. A similar performance was found applying the algorithm to TCGA and GEO external data sets (91.3–97.4% sensitivity and 87.5% specificity). We successfully evaluated the classifiers using a bisulfite-pyrosequencing technique, achieving 90.7% sensitivity and 75.4% specificity in surgical specimens (five of six CpGs). The study comprising FNAB cytology materials corroborated the applicability and performance of the methodology, demonstrating 86.7% sensitivity and 89.5% specificity in confirmed malignant tumors, and 100% sensitivity and 89% specificity in cases with indeterminate cytology. Conclusions: A novel diagnostic tool with potential application in preoperative screening of thyroid nodules is reported here. The proposed protocol has the potential to avoid unnecessary thyroidectomies. [ABSTRACT FROM AUTHOR]
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- 2019
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25. SHLD2/FAM35A co‐operates with REV7 to coordinate DNA double‐strand break repair pathway choice.
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Findlay, Steven, Heath, John, Luo, Vincent M., Malina, Abba, Morin, Théo, Coulombe, Yan, Djerir, Billel, Li, Zhigang, Samiei, Arash, Simo‐Cheyou, Estelle, Karam, Martin, Bagci, Halil, Rahat, Dolev, Grapton, Damien, Lavoie, Elise G., Dove, Christian, Khaled, Husam, Kuasne, Hellen, Mann, Koren K., and Klein, Kathleen Oros
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DNA ,DNA repair ,CELL cycle ,DEOXYRIBOSE ,BIOCHEMICAL genetics - Abstract
Abstract: DNA double‐strand breaks (DSBs) can be repaired by two major pathways: non‐homologous end‐joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle. Using a mass spectrometry (MS)‐based approach, we identify 11 high‐confidence REV7 interactors and elucidate the role of SHLD2 (previously annotated as FAM35A and RINN2) as an effector of REV7 in the NHEJ pathway. FAM35A depletion impairs NHEJ‐mediated DNA repair and compromises antibody diversification by class switch recombination (CSR) in B cells. FAM35A accumulates at DSBs in a 53BP1‐, RIF1‐, and REV7‐dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM35A is part of a larger complex composed of REV7 and SHLD1 (previously annotated as C20orf196 and RINN3), which promotes NHEJ and limits HR. Together, these results establish SHLD2 as a novel effector of REV7 in controlling the decision‐making process during DSB repair. [ABSTRACT FROM AUTHOR]
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- 2018
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26. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.
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Filho, Paulo Roberto Stevanato, Júnior, Samuel Aguiar, Begnami, Maria Dirlei, Kuasne, Hellen, Spencer, Ranyell Matheus, Nakagawa, Wilson Toshihiko, Bezerra, Tiago Santoro, Kupper, Bruna Catin, Takahashi, Renata Maymi, Filho, Mateus Barros, Rogatto, Silvia Regina, Lopes, Ademar, Stevanato Filho, Paulo Roberto, Aguiar Júnior, Samuel, and Barros Filho, Mateus
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ESTROGEN receptors ,COLON cancer ,ADENOMATOUS polyposis coli ,PROTEIN expression ,PROGRESSION-free survival ,COLON tumors ,DATABASES ,GENES ,PROGNOSIS ,PROTEINS ,RECTUM tumors ,RESEARCH funding ,RNA ,TUMOR classification ,SEQUENCE analysis ,TUMOR grading - Abstract
Background: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described.Methods: This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas.Results: Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERβ1 and ERβ5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002).Conclusion: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome. [ABSTRACT FROM AUTHOR]- Published
- 2017
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27. Circulating mRNAs and miRNAs as candidate markers for the diagnosis and prognosis of prostate cancer.
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Souza, Marilesia Ferreira de, Kuasne, Hellen, Barros-Filho, Mateus de Camargo, Cilião, Heloísa Lizotti, Marchi, Fabio Albuquerque, Fuganti, Paulo Emilio, Paschoal, Alexandre Rossi, Rogatto, Silvia Regina, and Cólus, Ilce Mara de Syllos
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BODY fluids , *NUCLEIC acids , *MESSENGER RNA , *MICRORNA , *PROSTATE cancer , *DIAGNOSIS , *GENETIC markers - Abstract
Circulating nucleic acids are found in free form in body fluids and may serve as minimally invasive tools for cancer diagnosis and prognosis. Only a few studies have investigated the potential application of circulating mRNAs and microRNAs (miRNAs) in prostate cancer (PCa). The Cancer Genome Atlas (TCGA) database was used for an in silico analysis to identify circulating mRNA and miRNA as potential markers of PCa. A total of 2,267 genes and 49 miRNAs were differentially expressed between normal and tumor samples. The prediction analyses of target genes and integrative analysis of mRNA and miRNA expression revealed eleven genes and eight miRNAs which were validated by RT-qPCR in plasma samples from 102 untreated PCa patients and 50 cancer-free individuals. Two genes, OR51E2 and SIM2, and two miRNAs, miR-200c and miR-200b, showed significant association with PCa. Expression levels of these transcripts distinguished PCa patients from controls (67% sensitivity and 75% specificity). PCa patients and controls with prostate-specific antigen (PSA) ≤ 4.0 ng/mL were discriminated based on OR51E2 and SIM2 expression levels. The miR-200c expression showed association with Gleason score and miR-200b, with bone metastasis, bilateral tumor, and PSA > 10.0 ng/mL. The combination of circulating mRNA and miRNA was useful for the diagnosis and prognosis of PCa. [ABSTRACT FROM AUTHOR]
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- 2017
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28. Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas.
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Beltrami, Caroline Moraes, dos Reis, Mariana Bisarro, Barros-Filho, Mateus Camargo, Marchi, Fabio Albuquerque, Kuasne, Hellen, Lopes Pinto, Clóvis Antônio, Ambatipudi, Srikant, Herceg, Zdenko, Paulo Kowalski, Luiz, and Regina Rogatto, Silvia
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- 2017
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29. A comprehensive characterization of cell cultures and xenografts derived from a human verrucous penile carcinoma.
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Muñoz, Juan, Drigo, Sandra, Kuasne, Hellen, Villacis, Rolando, Marchi, Fabio, Domingues, Maria, Lopes, Ademar, Santos, Tiago, and Rogatto, Silvia
- Abstract
This study aimed to establish and characterize primary cell cultures and xenografts derived from penile carcinoma (PeCa) in order to provide experimental models for cellular processes and efficacy of new treatments. A verrucous squamous cell carcinoma (VSCC) was macrodissected, dissociated, and cultivated in KSFM/DF12 medium. Cell cultures were evaluated at passage 5 (P5) using migration and invasion assays and were serially propagated, in vivo, in BALB/c nude mice until passage 3 (X1-X3). Immunophenotypic characterization of cultures and xenografts was performed. Genomic (CytoScan HD, Affymetrix) and transcriptomic profiles (HTA 2.0 platform, Affymetrix) for VSCC, cell cultures, and xenografts were assessed. P5 cells were able to migrate, invade the Matrigel, and produce tumors in immunodeficient mice, demonstrating their malignant potential. The xenografts unexpectedly presented a sarcomatoid-like carcinoma phenotype. Genomic analysis revealed a high similarity between the VSCC and tumor-derived xenograft, confirming its xenograft origin. Interestingly, a subpopulation of P5 cells presented stem cell-related markers (CD44CD24 and ALDH1) and sphere-forming capacity, suggesting their potential xenograft origin. Cell cultures and xenografts retained the genomic alterations present in the parental tumor. Compared to VSCC, differentially expressed transcripts detected in all experimental conditions were associated with cellular morphology, movement, and metabolism and organization pathways. Malignant cell cultures and xenografts derived from a verrucous penile carcinoma were established and fully characterized. Nevertheless, xenograft PeCa models must be used with caution, taking into consideration the selection of specific cell populations and anatomical sites for cell/tumor implantation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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30. Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers.
- Author
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Kuasne, Hellen, de Syllos Cólus, Ilce Mara, Busso, Ariane Fidelis, Hernandez-Vargas, Hector, Barros-Filho, Mateus Camargo, Marchi, Fabio Albuquerque, Scapulatempo-Neto, Cristovam, Faria, Eliney Ferreira, Ademar Lopes, Ademar, Guimarães, Gustavo Cardoso, Herceg, Zdenko, and Rogatto, Silvia Regina
- Published
- 2015
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31. Epigenetic Mechanisms in Penile Carcinoma.
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Kuasne, Hellen, Marchi, Fabio Albuquerque, Rogatto, Silvia Regina, and de Syllos Cólus, Ilce Mara
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EPIGENETICS , *CHROMATIN , *DNA methylation , *HISTONE acetylation , *MICRORNA , *TUMOR markers - Abstract
Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations in specific genes in a limited number of cases. This review aims to provide an overview of the current knowledge of the epigenetic alterations in PeCa and the promising results in this field. The identification of epigenetically altered genes in PeCa is an important step in understanding the mechanisms involved in this unexplored disease. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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32. Polymorphisms in the AR and PSA Genes as Markers of Susceptibility and Aggressiveness in Prostate Cancer.
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Kuasne, Hellen, Rodrigues, Iara Sant'Ana, Fuganti, Paulo Emílio, Losi-Guembarovski, Roberta, Ito, Kazuhiro, Kishima, Marina O., Rodrigues, Marco Aurélio de Freitas, Rogatto, Silvia Regina, Santos, Rodrigo Mattos dos, and Cólus, Ilce Mara de Syllos
- Subjects
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GENETIC polymorphisms , *ANDROGENS , *PROSTATE cancer , *PROSTATE-specific antigen , *TUMOR markers - Abstract
The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06-2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21-2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability. In conclusion, polymorphisms in these genes may be indicated as potential biomarkers for prostate cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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33. Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer.
- Author
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Souto Grando, João Paulo, Kuasne, Hellen, Losi-Guembarovski, Roberta, Rodrigues, Iara Sant'Ana, Matsuda, Henrique Mitsu, Fuganti, Paulo Emílio, Gregório, Émerson Pereira, Júnior, Farid Libos, De Menezes, Rodrigo Paes, De Freitas Rodrigues, Marco Aurélio, and Cólus, Ilce Mara de Syllos
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- *
CYTOCHROME P-450 , *ENZYMES , *GLUTATHIONE transferase , *METABOLIC detoxification , *CARCINOGENS , *BLADDER cancer - Abstract
Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione- S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case–control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 ( A2455→ G), and GSTP1 ( A313→ G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case–controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76–2.41 and OR = 0.75; 95% CI = 0.41–1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01–3.12 and OR = 1.99; 95% CI = 1.07–3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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34. Oral carcinoma epidemiology in Paraná State, Southern Brazil.
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Losi-Guembarovski, Roberta, de Menezes, Rodrigo Paes, Poliseli, Fernando, Chaves, Vivian Nappi, Kuasne, Hellen, Leichsenring, Andrei, Maciel, Marcos Euzébio, Guembarovski, Alda Losi, Oliveira, Benedito W., Ramos, Gyl, Mizuno, Lauro Toyshi, Cavalli, Iglenir João, Ribeiro, Enilze Maria de Souza Fonseca, and Cólus, Ilce Mara de Syllos
- Abstract
Copyright of Cadernos de Saude Publica is the property of Escola Nacional de Saude Publica Sergio Arouca and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2009
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35. DNA methylation patterns of the CDH1, RARB, and SFN genes in choroid plexus tumors
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Losi-Guembarovski, Roberta, Kuasne, Hellen, Guembarovski, Alda L., Rainho, Cláudia A., and Cólus, Ilce M.S.
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TUMORS , *HEREDITY , *ONCOLOGY , *CELLS - Abstract
Abstract: Genetic and epigenetic alterations in choroid plexus tumors, a rare neuroepithelial neoplasm most frequently detected in children, are poorly characterized. Epigenetic silencing associated with aberrant CpG island methylation is one mechanism leading to the loss of tumor suppressor functions in cancer cells. Using methylation-specific polymerase chain reaction, the methylation patterns of the genes CDH1 (E-cadherin), RARB (retinoic acid receptor, beta), and SFN (stratifin; 14-3-3σ) were retrospectively investigated in eight choroid plexus tumors (five papillomas, two atypical papillomas, and one carcinoma), as well as in two normal cortexes obtained after autopsy from male individuals aged 6 months and 64 years. Among the six pediatric tumors, the mean age at diagnosis was 1.8 years old (range, 0.2–6) and the two adult tumors were detected in a 66-year-old man and a 45-year-old woman. A high frequency of hypermethylation was detected in CDH1 and SFN genes in tumoral and normal cortex tissues. Tumor-specific RARB hypermethylation was observed in four papillomas. Further studies are required to evaluate the role of aberrant methylation in choroid plexus tumor progression. [Copyright &y& Elsevier]
- Published
- 2007
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36. Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx ® Digital Spatial Profiler.
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Bergholtz, Helga, Carter, Jodi M., Cesano, Alessandra, Cheang, Maggie Chon U, Church, Sarah E., Divakar, Prajan, Fuhrman, Christopher A., Goel, Shom, Gong, Jingjing, Guerriero, Jennifer L., Hoang, Margaret L., Hwang, E. Shelley, Kuasne, Hellen, Lee, Jinho, Liang, Yan, Mittendorf, Elizabeth A., Perez, Jessica, Prat, Aleix, Pusztai, Lajos, and Reeves, Jason W.
- Subjects
HIGH throughput screening (Drug development) ,IMMUNOHISTOCHEMISTRY ,FORMALDEHYDE ,CELL physiology ,MEDICAL protocols ,CANCER patients ,GENE expression profiling ,HISTOLOGICAL techniques ,DATA analysis ,BREAST tumors ,MEDICAL research - Abstract
Simple Summary: In breast cancer, there is a high degree of variability in tumors and the surrounding tissue called the tumor microenvironment (TME). To better understand tumor biology and metastasis, as well as to predict response to cancer treatments or the course of the disease, it is important to characterize molecular diversity in the breast TME. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially analyze proteins and RNA transcripts in tumors and surrounding tissues from patients or preclinical models. Using the GeoMx DSP, protein expression and RNA transcripts in the distinct regions of a tumor can be quantified up to and including the whole transcriptome level. Herein, the GeoMx Breast Cancer Consortium presents best practices for GeoMx spatial profiling of tumors to promote the collection of high-quality data, optimization of data analysis and integration of datasets to accelerate biomarker discovery. These best practices can also be applied to any tumor type to provide information about the tumor and the TME. Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
37. Penile Cancer-Derived Cells Molecularly Characterized as Models to Guide Targeted Therapies.
- Author
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Kuasne, Hellen, Canto, Luisa Matos do, Aagaard, Mads Malik, Muñoz, Juan Jose Moyano, Jamblinne, Camille De, Marchi, Fabio Albuquerque, Scapulatempo-Neto, Cristovam, Faria, Eliney Ferreira, Lopes, Ademar, Carréno, Sébastien, Rogatto, Silvia Regina, and Ear, Jason
- Subjects
- *
EPIDERMAL growth factor receptors , *PENILE cancer , *CELL morphology , *PENIS , *CISPLATIN , *CELL culture , *ANTINEOPLASTIC agents - Abstract
Penile cancer (PeCa) is a common disease in poor and developing countries, showing high morbidity rates. Despite the recent progress in understanding the molecular events involved in PeCa, the lack of well-characterized in vitro models precludes new advances in anticancer drug development. Here we describe the establishment of five human primary penile cancer-derived cell cultures, including two epithelial and three cancer-associated fibroblast (CAF) cells. Using high-throughput genomic approaches, we found that the epithelial PeCa derived- cells recapitulate the molecular alterations of their primary tumors and present the same deregulated signaling pathways. The differentially expressed genes and proteins identified are components of key oncogenic pathways, including EGFR and PI3K/AKT/mTOR. We showed that epithelial PeCa derived cells presented a good response to cisplatin, a common therapeutic approach used in PeCa patients. The growth of a PeCa-derived cell overexpressing EGFR was inhibited by EGFR inhibitors (cetuximab, gefitinib, and erlotinib). We also identified CAF signature markers in three PeCa-derived cells with fibroblast-like morphology, indicating that those cells are suitable models for PeCa microenvironment studies. We thus demonstrate the utility of PeCa cell models to dissect mechanisms that promote penile carcinogenesis, which are useful models to evaluate therapeutic approaches for the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
38. Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer.
- Author
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Silva, Camila Meirelles S., Barros-Filho, Mateus C., Wong, Deysi Viviana T., Mello, Julia Bette H., Nobre, Livia Maria S., Wanderley, Carlos Wagner S., Lucetti, Larisse T., Muniz, Heitor A., Paiva, Igor Kenned D., Kuasne, Hellen, Ferreira, Daniel Paula P., Cunha, Maria Perpétuo S. S., Hirth, Carlos G., Silva, Paulo Goberlânio B., Sant'Ana, Rosane O., Souza, Marcellus Henrique L. P., Quetz, Josiane S., Rogatto, Silvia R., Lima-Junior, Roberto César P., and García-Olmo, Damián
- Subjects
COLON tumors ,COLONOSCOPY ,RECTUM tumors ,MICRORNA ,EARLY detection of cancer ,ADENOMA ,DESCRIPTIVE statistics ,ALGORITHMS ,LONGITUDINAL method - Abstract
Simple Summary: The detection of early-stage colorectal cancer increases the chance to prevent tumor progression and death by the disease. Colonoscopy is one sensitive screening test to detect malignant or potentially malignant lesions in the intestines. However, it has some disadvantages, including sedation requirements, increased risk of colon perforation, and bleeding. Circulating microRNAs (miRNAs) in plasma or serum from cancer patients have been investigated and described as potential diagnostic or prognostic markers. We conducted an miRNAs screening test in plasma samples from colorectal cancer patients and subjects without cancer, aiming to identify markers for the early detection of the disease. We identified and validated four miRNAs capable of distinguishing cancer from non-cancer cases. Our non-invasive diagnostic biomarkers presented high performance and are easily applicable to clinical practice. Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model's performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
39. Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity.
- Author
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Lupinacci, Fernanda Cristina Sulla, Kuasne, Hellen, Roffé, Martin, Vassalakis, Julia Avian, da Silva, Fernanda Ferreira, Santos, Tiago Góss, Andrade, Victor Piana, Sanematsu, Paulo, Martins, Vilma Regina, Rogatto, Silvia Regina, and Hajj, Glaucia Noeli Maroso
- Subjects
- *
GLIOBLASTOMA multiforme , *EXTRACELLULAR matrix , *MESSENGER RNA , *PROTEOMICS , *HISTOLOGY , *GENE expression - Abstract
Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
40. Gene Expression Profile of Mucoepidermoid Carcinoma of the Salivary Gland.
- Author
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PASSADOR-SANTOS, FABRICIO, BROWN, AMY, KUASNE, HELLEN, SOARES, L ANDRESA, LOURENÇO, SILVIA, KOWALSKI, LUIZ, ROGATTO, SILVIA, and ARAUJO, VERA
- Published
- 2015
- Full Text
- View/download PDF
41. Methylation profile in penile carcinoma reveals unique signature relative to surround tissue and HPV status.
- Author
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Kuasne, Hellen, Cólus, Ilce M. S., Hernandez-Vargas, Hector, Busso, Ariane F., Barros-Filho, Mateus C., Marchi, Fábio A., Rainho, Cláudia A., Guimarães, Gustavo C., Carvalho, André L., Neto, Cristovam Scapulatempo, Lengert, André, Soares, Fernando A., Vassallo, José, Herceg, Zdengo, and Rogatto, Silvia R.
- Subjects
- *
PENILE cancer , *PAPILLOMAVIRUSES , *METHYLATION , *VIRUS diseases , *STEM cells - Abstract
The article presents information on a study related to methylation profile of penile carcinoma (PeCa) and its relation with surround tissue and papillomavirus status. The method includes collection of paired PeCa and surrounding tissue samples from 16 patients. The results conclude that differential methylation profile indicate two disrupted pathways including one related to viral infection and the other related to transcriptional regulation of stem cells.
- Published
- 2013
- Full Text
- View/download PDF
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