LUISA LINA VILLA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
9 resultados
Resultados de Busca
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- Correlation of a microRNA expression profile and the prognosis of penile cancer: A prospective study using microarray data analysis(2018) FURUYA, Tatiane K.; MURTA, Claudio B.; PONTES JR., Jose; UNO, Miyuki; CARRASCO, Alexis; SICHERO, Laura C.; VILLA, Luisa L.; COELHO, Rafael F.; GUGLIELMETTI, Giuliano B.; CORDEIRO, Mauricio D.; LEITE, Katia R.; SROUGI, Miguel; CHAMMAS, Roger; NAHAS, William C.
conferenceObject CORRELATION BETWEEN MICRORNAS AND MRNA EXPRESSION PROFILES WITH THE PROGNOSIS OF CLINICALLY LOCALIZED PENILE CANCER(2019) MURTA, Claudio; PONTES JR., Jose; FURUYA, Tatiane; UNO, Miyuki; CARRASCO, Alexis; COELHO, Rafael; GUGLIELMETTI, Giuliano; CORDEIRO, Mauricio; FARAJ, Sheila; LEITE, Katia; SICHERO, Laura; VILLA, Luisa; SROUGI, Miguel; CHAMMAS, Roger; NAHAS, William- miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma(2022) MURTA, Claudio B.; FURUYA, Tatiane K.; CARRASCO, Alexis G. M.; UNO, Miyuki; SICHERO, Laura; VILLA, Luisa L.; FARAJ, Sheila F.; COELHO, Rafael F.; GUGLIELMETTI, Giuliano B.; CORDEIRO, Mauricio D.; LEITE, Katia R. M.; NAHAS, William C.; CHAMMAS, Roger; PONTES JR., JosePenile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.
- Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer(2022) BUSSO-LOPES, Ariane F.; NEVES, Leandro X.; CAMARA, Guilherme A.; GRANATO, Daniela C.; PRETTI, Marco Antonio M.; HEBERLE, Henry; PATRONI, Fabio M. S.; SA, Jamile; YOKOO, Sami; RIVERA, Cesar; DOMINGUES, Romenia R.; NORMANDO, Ana Gabriela C.; ROSSI, Tatiane De; MELLO, Barbara P.; GALDINO, Nayane A. L.; PAULETTI, Bianca A.; LACERDA, Pammela A.; RODRIGUES, Andre Afonso N.; CASARIM, Andre Luis M.; LIMA-SOUZA, Reydson A. De; DAMAS, Ingrid I.; V, Fernanda Mariano; GOLLOB, Kenneth J.; MEDINA, Tiago S.; CERVIGNE, Nilva K.; PRADO-RIBEIRO, Ana Carolina; BRANDAO, Thais Bianca; VILLA, Luisa L.; UNO, Miyuki; BORONI, Mariana; KOWALSKI, Luiz Paulo; GONZALEZ-ARRIAGADA, Wilfredo Alejandro; LEME, Adriana F. PaesThe poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures. The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures.
- Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis(2021) FURUYA, Tatiane Katsue; MURTA, Claudio Bovolenta; CARRASCO, Alexis German Murillo; UNO, Miyuki; SICHERO, Laura; VILLA, Luisa Lina; CARDILLI, Leonardo; COELHO, Rafael Ferreira; GUGLIELMETTI, Giuliano Betoni; CORDEIRO, Mauricio Dener; LEITE, Katia Ramos Moreira; NAHAS, William Carlos; CHAMMAS, Roger; JR, Jose PontesSimple Summary: As there are still no biomarkers reported in clinical practice in penile cancer (PeC), we aimed to investigate and validate molecular signatures based on miRNA and mRNA profiles to identify molecular drivers and pathways involved in PeC tumorigenesis. We found eight DEmiRs and 37 DEGs comparing tumoral tissues (TT) paired with non-neoplastic tissues (NNT) of PeC patients. Four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) were identified as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. Furthermore, we performed an analysis of miRNA-mRNA interaction and found disruption in the dynamics of the regulation of eight pairs during tumor development that have never been described in PeC. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis. Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.
- Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer(2020) ROSSETTI, Renata A. M.; SILVA-JUNIOR, Ildefonso A. da; RODRIGUEZ, Gretel R; ALVAREZ, Karla L. F.; STONE, Simone C.; CIPELLI, Marcella; SILVEIRA, Caio R. F.; BELDI, Mariana Carmezim; MOTA, Giana R.; MARGARIDO, Paulo F. R.; BARACAT, Edmund C.; UNO, Miyuki; VILLA, Luisa L.; CARVALHO, Jesus P.; YOKOCHI, Kaori; ROSA, Maria Beatriz S. F.; LORENZI, Noely P.; LEPIQUE, Ana PaulaCervical cancer, which main etiologic factor is Human Papillomavirus (HPV) infection, continues to be a burden for public health systems in developing countries. Our laboratory has been working with the hypothesis that signals generated in the tumor microenvironment can modulate local and systemic immune responses. In this context, it would be reasonable to think that tumors create pro-tumoral bias in immune cells, even before they are recruited to the tumor microenvironment. To understand if and how signaling started in the tumor microenvironment can influence cells within the tumor and systemically, we investigated the expression of key proteins in signaling pathways important for cell proliferation, viability, immune responses and tolerance. Besides, we used detection of specific phosphorylated residues, which are indicative of activation for Akt, CREB, p65 NF kappa B, and STAT3. Our findings included the observation of a significant STAT3 expression increase and p65 NF kappa B decrease in circulating leukocytes in correlation with lesion grade. In light of those observations, we started investigating the result of the inhibition of STAT3 in a tumor experimental model. STAT3 inhibition impaired tumor growth, increased anti-tumor T cell responses and decreased the accumulation of myeloid cells in the spleen. The concomitant inhibition of NF kappa B partially reversed these effects. This study indicates that STAT3 and NF kappa B are involved in immunomodulatory tumor effects and STAT3 inhibition could be considered as therapy for patients with cervical cancer.
conferenceObject Correlation of the expression of microRNA and their predicted targets with prognosis and mortality of penile squamous cell carcinoma(2022) MURTA, C. B.; FURUYA, T. K.; UNO, M.; CARRASCO, A. G. M.; SICHERO, L.; VILLA, L. L.; FARAJ, S. F.; COELHO, R. F.; GUGLIELMETTI, G. B.; CORDEIRO, M. D.; LEITE, K. R. M.; NAHAS, W. C.; CHAMMAS, R.; PONTES, Jr J.- Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil(2024) SICHERO, Laura; GONCALVES, Milena Giulia; BETTONI, Fabiana; COSER, Elisangela Monteiro; MOTA, Giana; NUNES, Rafaella A. L.; MERCANTE, Ana Maria da Cunha; NATALINO, Renato; UNO, Miyuki; ALVES, Maria Jose Ferreira; MATOS, Leandro Luongo; KOWALSKI, Luiz Paulo; KULCSAR, Marco Aurelio Vamondes; ALVARENGA, Gustavo Fernandes de; HOEFLER, Daniela; SCHROEDER, Lea; WATERBOER, Tim; TOMMASINO, Massimo; VILLA, Luisa LinaBackground: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16(INK4a) status was also accessed. Methods: HPV was genotyped by PCR-hybridization. All HPV DNA positive and similar to 10 % HPV DNA negative cases underwent p16(INK4a) immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. Results: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16(INK4) (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. Conclusions: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.
- Correlation of microRNA expression profile and prognosis of penile cancer: A prospective study using microarray data analysis(2018) MURTA, Claudio Bovolenta; PONTES JR., Jose; FURUYA, Tatiane Katsue; UNO, Miyuki; CARRASCO, Alexis; SICHERO, Laura; VILLA, Luisa Lina; CORDEIRO, Mauricio; GUGLIELMETTI, Giuliano; COELHO, Rafael; LEITE, Katia Ramos Moreira; SROUGI, Miguel; CHAMMAS, Roger; NAHAS, William Carlos