ALOISIO SOUZA FELIPE DA SILVA

(Fonte: Lattes)
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Departamento de Patologia, Faculdade de Medicina - Docente
SVANPA-62, Hospital Universitário
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 25
  • bookPart
    Neoplasias do apêndice
    (2014) SILVA, Aloísio Souza Felipe da; PEREIRA, Emílio Marcelo
  • article 12 Citação(ões) na Scopus
    Immunohistochemical Assessment of the Expression of Biliary Transportation Proteins MRP2 and MRP3 in Hepatocellular Carcinoma and in Cholangiocarcinoma
    (2019) CIRQUEIRA, Cinthya Santos; FELIPE-SILVA, Aloisio Sousa; WAKAMATSU, Alda; MARINS, Lidiane Vieira; ROCHA, Eziel Cavalcanti; MELLO, Evandro Sobroza de; ALVES, Venancio Avancini Ferreira
    Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic anion transporter predominantly expressed in the canalicular membrane of hepatocytes, epithelial cells from gallbladder and apical membranes of proximal tubular kidney epithelium whereas multidrug resistance-associated protein 3 (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes. This study aims to detect the expression of these transporters in hepatocellular carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for future studies on differential diagnosis and on clinical essays. The immunohistochemical reactivity (IHC) of these transporters was assessed in tissue microarrays of 80 HCC and 56 CC cases using monoclonal antibodies and compared with anatomopathological (AP) variables. The positivity of MRP2 was observed in 92.3% of HCC and in 96.3% of CC. The detection of high MRP2 expression in HCC was not significantly different (p > 0.05) according to the size, number of nodules architectural pattern and growth pattern of HCC and CC. Regarding histological grades, 22/22 well moderately differentiated HCC versus 50/56 poorly differentiated HCC were positive for MRP2. A trend for lower expression in poor differentiation HCC was found. And 50/50 well/moderately differentiated CC versus 2/4 poorly/undifferentiated CC were positive for MRP2. This result showed a reduced expression (p = 0,0004) in poorly differentiated CC. MRP3 positivity was observed in 18.8% of HCC and was not significantly different according to AP parameters. MRP3 was expressed in 44.5% CC, with a trend for lower expression in less differentiated CC and significantly lower rates in the ductular histological subtype (p = 0.023). The high expression of MRP2 in HCC and in CC is conserved regardless most of the anatomopathological parameters, except for a trend of lower expression in less differentiated HCC and CC. The observation of lower MRP3 expression in less differentiated CC and, especially, in the histological subtype with expression of hepatic progenitor cell phenotypes leads to future opportunities to evaluate the expression of this marker in cholangiocarcinomas.
  • conferenceObject
    The impact of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): A retrospective study of 828 aspirates with emphasis on the prior ""indeterminate"" category
    (2012) FERREIRA, C.; LIMA, P.; MENTEM, M.; ESPOSITO, J.; WASSERSTEIN, L.; FELIPE-SILVA, A.
    Objective: We evaluated the impact of implementing TBSRTC in an academic community hospital. Method: FNAs from Jan/2004 to Dec/2010 were reclassified in TBSRTC: nondiagnostic (ND), benign (B), atypia or follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm (FN), suspicious for malignancy (S) and malignant (M). FLUS and FN were classified according to presence of Hürthle cells as HCLUS and FN-HC. Results: A total of 828 FNAs (480 patients) were obtained: 46 ND (5.55 %), 682 B (82.4 %), 9 S (1.1 %) and 25 M (3.0 %). The 66 (8.0 %) indeterminate categories were reclassified: 1 ND (1.5 %), 8 B (12.1 %), 5 AUS (7.6 %), 34 FLUS (51.5 %), 5 HCLUS (7.6 %), 3 FN (4.5 %), 9 FN-HC (13.6 %) and 1 S (1.5 %). Thyroidectomies were performed in 125 patients (26 %): benign lesions in 83 (66.4 %), 7 (5.6 %) follicular adenoma and 2 (1.6 %) follicular carcinomas, 1 (0.8 %) medullary carcinoma, 21 (16.8 %) papillary carcinomas and 16 (12.8 %) papillary microcarcinomas (PMC). Risk of malignancy (RM) excluding PMC: B 1.4 %, AUS/FLUS/HCLUS 5 %, FN/FN-HC 11.1 %, SM 50 % and M 77.8 %. Conclusion: TBSRTC criteria led to more specific diagnosis. FN/FN-HC category has a two-fold RM when compared to AUS/FLUS/HCLUS.
  • conferenceObject
    IDENTIFICATION OF O-LINKED N-ACETYLGLUCOSAMINE TRANSFERASE (OGT) EXPRESSION IN HUMAN PLACENTAS AS A POTENTIAL BIOMARKER OF PRENATAL STRESS EXPOSURE
    (2022) CAMILO, Caroline; VIEIRA, Luana Martos; TORREZAN, Arleti Caramori; SOUSA, Antonia Beatriz; GOUVEIA, Gisele Rodrigues; EUCLYDES, Veronica Luiza Vale; SILVA, Aloisio Souza Felipe da; BRENTANI, Alexandra; BRENTANI, Helena
  • conferenceObject
    The Value of Repeated Fine-Needle Aspiration Biopsy in an Academic Community Hospital after the Bethesda System
    (2012) FERREIRA, C. R.; LIMA, P. P.; MENTEM, M. S.; ESPOSITO, J. P.; WASSERSTEIN, L. H.; FELIPE-SILVA, A.
    Background: Follow-up of thyroid nodules with repeated fine-needle aspiration biopsies (rFNA) is recommended in nondiagnostic (ND) samples and in cases of atypia of unknown significance (AUS)/follicular lesions of uncertain significance (FLUS), however, the impact of this approach is generally unexplored. We evaluated the risk of neoplasia (RN) and malignancy (RM) in rFNA. Design: All FNA from Jan/04 to Dec/10 were reclassified according to Bethesda System: ND, benign (B), AUS/FLUS, suspicious for follicular neoplasm (FN), suspicious for malignancy (SM) and malignant (M). Patients with one FNA (1FNA) and with rFNA were compared according to the worst diagnosis in the first FNA (fFNA) or in the rFNA. Surgical pathology (SP) and clinical follow-up were retrieved Results: In 480 patients (F:M=7:1, average age 53), 70 (14.6%) had rFNA. Average number of rFNA was 1.3±0.8. A total of 125 (26%) had a thyroidectomy (21.4% in the rFNA and 26.8% in 1FNA - p=0.3). Diagnoses upon fFNA in rFNA group were ND in 10 (14.3%), B in 49 (70%), AUS/FLUS in 8 (11.4%) and FN/SM in 3 (4.3%). In B group rFNA changed in 3 patients (6.1%) (2 AUS/FLUS, 1 FN) and 11 patients (22.4%) had SP follow-up: 1 follicular adenoma (FA) and 10 benign non-neoplastic lesion (BN), including 1 patient with AUS/FLUS at rFNA. In ND group rFNA changed in all patients: 9 (90%) to B and 1 (10%) to M – SP confirmed papillary carcinoma (PC). In AUS/FLUS group rFNA changed to B in 3 (37.5%) and ND in 1 (12.5%), none with SP. AUS/FLUS rFNA was unchanged in 4 (50%) – SP available in 3: 1 PC, 1 papillary microcarcinoma (PMC) and 1 BN. rFNA changed to B in the 3 patients of FN/MS group, one with BN at SP. Diagnoses in 1FNA group with SP follow-up were ND in 1 (0.9%), B in 60 (54.5%), AUS/FLUS in 15 (13.6%) and FN/SM/M in 34 (30.9%). The 1 ND was BN at SP. In 1FNA B group SP confirmed 7 incidental PMC (11.7%) and 1 FA (1.7%). In 1FNA AUS/FLUS group SP showed 1 FA (6.7%), 1 PC (6.7%) and 1 PMC (6.7%). In 1FNA FN/SFN/M group SP showed 18 PC (52.9%), 6 PMC (17.6%), 1 follicular and 1 medullary carcinoma. RM was 9.1% for all ND FNA. General RN was 9.1% in rFNA B group, 15% in the 1FNA B, 66% in rFNA AUS/FLUS, 20% in 1FNA AUS/FLUS and 82.4% in 1FNA FN/SM/M. Conclusions: Our data support the recommendation of rFNA in ND category. A repeated diagnosis of AUS/FLUS increased the general RN from 20% to 66% (p=0.1). A B fFNA diagnosis had a 4% chance of changing upon rFNA, and a virtually null RM.
  • article 10 Citação(ões) na Scopus
    Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance
    (2020) SANDRI, Silvana; WATANABE, Luis R. M.; OLIVEIRA, Erica Aparecida de; FAIAO-FLORES, Fernanda; MIGLIORINI, Silene; TIAGO, Manoela; FELIPE-SILVA, Aloisio; VAZQUEZ, Vinicius de Lima; SOUZA, Paola da Costa; CONSOLARO, Marcia Edilaine Lopes; CAMPA, Ana; MARIA-ENGLER, Silvya Stuchi
    Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFN gamma) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant.
  • conferenceObject
    Performance and validation of a tumor mutation profiling, based on artificial intelligence annotation, to assist oncology decision making.
    (2019) MITNE NETO, Miguel; FORNARI, Alexandre Ricardo; MOREIRA, Luciana Peniche; BURGER, Matheus; OKU, Andre; PEREIRA, Luciana Guilhermino; STABELLINI, Raquel; VALIM, Gabriela Rampazzo; EULALIO, Otavio Jose; COLLEONI, Gisele Wally; SANTORO, Ilka Lopes; PINTAO, Maria Carolina; STIEPCICH, Monica Maria Agata; FELIPE-SILVA, Aloisio Souza; RAMALHO, Rodrigo Fernandes; ANTONIO, David Santos Marco; FRAGA, Ana Maria; FERREIRA, Elisa Napolitano
  • article 6 Citação(ões) na Scopus
    Academic autopsies in Brazil - a national survey
    (2014) FELIPE-SILVA, Aloisio; ISHIGAI, Marcia; MAUAD, Thais
    Objective: To investigate the number and rate of academic autopsies, general organization, educational and research in Brazilian academic services. Methods: Standardized questionnaires were sent to Brazilian medical schools (n=177) and active pathology residency programs (n=53) from March to June 2009. Data were collected for years 2003 to 2008. Results: Thirty-two academic services in 11 Brazilian states answered the survey. Twenty-one (65.6%) perform less than a hundred autopsies for natural causes and less than fifty pediatric or fetal autopsies/year. Twenty-four (75%) perform less than a hundred adult autopsies/year. Many institutions (46.9%) reported a drop in the number of autopsies in a six-year period. The total autopsy count and autopsy rate in 2008 ranged 1-632 (median = 80), and 0-66% (mean = 10.6%), respectively. A steady decrease in the total count of autopsies in a pool of 19 institutions was observed (p < 0.01). Median autopsy rates have fallen from 19.3%, in 2003, to 10.6%, in 2008 (p=0.07). Significant discrepancies at autopsies led to changes in institutional healthcare practice in 37.5% of the services. The low number of autopsies was a limiting factor in undergraduate education for 25% of respondents. A minimum number of autopsies is required to complete the pathology residency program in 34.6% of the services. Conclusion: The total number and the rate of academic autopsies have decreased in Brazil between 2003 and 2008. The number of autopsies and the general organization of academic services must be enhanced to improve medical education, research, and the quality control of patient care.
  • article 2 Citação(ões) na Scopus
    In vivo antitumoral effect of 4-nerolidylcatechol (4-NC) in NRAS-mutant human melanoma
    (2020) ALVES-FERNANDES, Debora Kristina; OLIVEIRA, Erica Aparecida de; HASTREITER, Araceli Aparecida; FAIAO-FLORES, Fernanda; FELIPE-SILVA, Aloisio Souza; TURATO, Walter; FOCK, Ricardo Ambrosio; MARIA-ENGLER, Silvya Stuchi; BARROS, Silvia Berlanga de Moraes
    NRAS-mutations arise in 15-20% of all melanomas and are associated with aggressive disease and poor prognosis. Besides, the treatment for NRAS-mutant melanoma are not very efficient and is currently limited to immune checkpoints inhibitors or aggressive chemotherapy. 4-nerolidylcathecol (4-NC), a natural product extracted from Pothomorphe umbellata, induces apoptosis in melanoma cells by ROS production, DNA damage and increased p53 expression, in addition to inhibiting invasion in reconstructed skin. Moreover, 4-NC showed cytotoxicity in BRAF/MEKi-resistant and naive melanoma cells by Endoplasmic Reticulum (ER) stress induction in vitro. We evaluated the in vivo efficacy and the systemic toxicity of 4-NC in a NRAS-mutant melanoma model. 4-NC was able to significantly suppress tumor growth 4-fold compared to controls. Cleaved PARP and p53 expression were increased indicating cell death. As a proof of concept, MMP-2 and MMP-14 gene expression were decreased, demonstrating a possible role of 4-NC in melanoma invasion inhibition. Toxicological analysis indicated minor changes in the liver and bone marrow, but this toxicity was very mild when compared to other proteasome inhibitors and ER stress inductors already described. Our data indicate that 4-NC can counteract melanoma growth in vivo with minor adverse effects, suggesting further investigation as a potential NRAS-mutant melanoma treatment.
  • article 5 Citação(ões) na Scopus
    TOP1 modulation during melanoma progression and in adaptative resistance to BRAF and MEK inhibitors
    (2021) OLIVEIRA, Erica Aparecida de; CHAUHAN, Jagat; SILVA, Julia Rezende da; CARVALHO, Larissa Anastacio da Costa; DIAS, Diogo; CARVALHO, Danielle Goncalves de; WATANABE, Luis Roberto Masao; REBECCA, Vito W.; MILLS, Gordon; LU, Yiling; SILVA, Aloisio Souza Felipe da; CONSOLARO, Marcia Edilaine Lopes; HERLYN, Meenhard; POSSIK, Patricia A.; GODING, Colin R.; MARIA-ENGLER, Silvya Stuchi
    In melanomas, therapy resistance can arise due to a combination of genetic, epigenetic and phenotypic mechanisms. Due to its crucial role in DNA supercoil relaxation, TOP1 is often considered an essential chemotherapeutic target in cancer. However, how TOP1 expression and activity might differ in therapy sensitive versus resistant cell types is unknown. Here we show that TOP1 expression is increased in metastatic melanoma and correlates with an invasive gene expression signature. More specifically, TOP1 expression is highest in cells with the lowest expression of MITF, a key regulator of melanoma biology. Notably, TOP1 and DNA Single-Strand Break Repair genes are downregulated in BRAFi- and BRAFi/MEKi-resistant cells and TOP1 inhibition decreases invasion markers only in BRAFi/MEKi-resistant cells. Thus, we show three different phenotypes related to TOP1 levels: i) non-malignant cells with low TOP1 levels; ii) metastatic cells with high TOP1 levels and high invasiveness; and iii) BRAFi- and BRAFi/MEKi-resistant cells with low TOP1 levels and high invasiveness. Together, these results highlight the potential role of TOP1 in melanoma progression and resistance.