LIM/14 - Laboratório de Investigação em Patologia Hepática

URI Permanente desta comunidade

https://observatorio.fm.usp.br/handle/OPI/3650
O Laboratório de Investigação em Patologia Hepática é ligado ao Departamento de Patologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP).

Linhas de pesquisa: patologia hepática, com ênfase na patogênese da evolução para formas mais graves de cirrose e para carcinoma hepatocelular; caracterização de anticorpos para estudos imuno-histoquímicos com ênfase em neoplasias digestivas, ginecológicas e condições obstétricas, neuropatologia.

Site oficial: http://limhc.fm.usp.br/portal/lim14-laboratorio-de-investigacao-em-patologia-hepatica/

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article 2 Citação(ões) na Scopus
Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
(2022) GRANJA, S. C.; LONGATTO-FILHO, A.; CAMPOS, P. B. De; OLIVEIRA, C. P.; STEFANO, J. T.; MARTINS-FILHO, S. N.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; ALVARES-DA-SILVA, M. Reis; CARRILHO, F. J.; BALTAZAR, F.; ALVES, V. A. F.
Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.
article 1 Citação(ões) na Scopus
Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma
(2022) MUNARI, F. F.; SICHERO, L.; CARLONI, A. C.; LACERDA, C. F.; NUNES, E. M.; OLIVEIRA, A. T. T. De; SCAPULATEMPO-NETO, C.; SILVA, S. R. M. Da; CREMA, E.; ADAD, S. J.; RODRIGUES, M. A. M.; HENRY, M. A. C. A.; GUIMARãES, D. P.; REIS, R. M.; VILLA, L. L.; LONGATTO-FILHO, A.
Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC). Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals. Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology. Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics. Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
article 0 Citação(ões) na Scopus
Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review
(2023) BOVO, Adriane Cristina; PEDRAO, Priscila Grecca; GUIMARAES, Yasmin Medeiros; GODOY, Luani Rezende; RESENDE, Julio Cesar Possati; LONGATTO-FILHO, Adhemar; REIS, Ricardo dos
Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of similar to 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.
article 0 Citação(ões) na Scopus
Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer
(2023) SILVA, Ana; FELIX, Ana; CERQUEIRA, Monica; GONCALVES, Celine S.; SAMPAIO-MARQUES, Belem; LONGATTO-FILHO, Adhemar; BALTAZAR, Fatima; AFONSO, Julieta
The Warburg Effect is characterized by high rates of glucose uptake and lactate production. Monocarboxylate transporters (MCTs) are crucial to avoid cellular acidosis by internal lactate accumulation, being largely overexpressed by cancer cells and associated with cancer aggressiveness. The MCT1-specific inhibitor AZD3965 has shown encouraging results in different cancer models. However, it has not been tested in urothelial bladder cancer (UBC), a neoplasm where rates of recurrence, progression and platinum-based resistance are generally elevated. We used two muscle-invasive UBC cell lines to study AZD3965 activity regarding lactate production, UBC cells' viability and proliferation, cell cycle profile, and migration and invasion properties. An ""in vivo"" assay with the chick chorioallantoic membrane model was additionally performed, as well as the combination of the compound with cisplatin. AZD3965 demonstrated anticancer activity upon low levels of MCT4, while a general lack of sensitivity was observed under MCT4 high expression. Cell viability, proliferation and migration were reduced, cell cycle was arrested, and tumor growth ""in vivo"" was inhibited. The compound sensitized these MCT4-low-expressing cells to cisplatin. Thus, AZD3965 seems to display anticancer properties in UBC under a low MCT4-expression setting, but additional studies are necessary to confirm AZD3965 activity in this cancer model.
article 0 Citação(ões) na Scopus
Low EGFL7 expression is associated with high lymph node spread and invasion of lymphatic vessels in colorectal cancer
(2023) OLIVEIRA, Cristiane de; MARTINS, Sandra Fatima Fernandes; GONCALVES, Paola Gyuliane; LIMONE, Gabriel Augusto; LONGATTO-FILHO, Adhemar; REIS, Rui Manuel; BIDINOTTO, Lucas Tadeu
Studies indicate EGFL7 as an important gene in controlling angiogenesis and cancer growth, including in colorectal cancer (CRC). Anti-EGFL7 agents are being explored, yet without promising results. Therefore, the role of EGFL7 in CRC carcinogenesis should be investigated. This study aimed to evaluate the prognostic value of EGFL7 expression in CRC and the signaling pathways influenced by this gene. EGFL7 expression was evaluated through immunohistochemistry in 463 patients diagnosed with CRC and further associated with clinicopathological data, angiogenesis markers and survival. In silico analyzes were performed with colon adenocarcinoma data from The Cancer Genome Atlas. Analysis of enriched gene ontology and pathways were performed using the differentially expressed genes. 77.7% of patients presented low EGFL7 expression, which was associated with higher lymph node spread and invasion of lymphatic vessels, with no impact on survival. Additionally, low EGFL7 expression was associated with high VEGFR2 expression. Finally, we found in silico that EGFL7 expression was associated with cell growth, angiogenesis, and important pathways such as VEGF, Rap-1, MAPK and PI3K/Akt. Expression of EGFL7 in tumor cells may be associated with important pathways that can alter functions related to tumor invasive processes, preventing recurrence and metastatic process.
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