9 results on '"Brunaldi, Mariângela Ottoboni"'
Search Results
2. mRNA Expression and Methylation of the RAD51 , ATM , ATR , BRCA1 , and BRCA2 Genes in Gastric Adenocarcinoma.
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Pádua, Joel Del Bel, Mariano, Carolline Fontes Alves, Fabro, Alexandre Todorovic, Lizarte Neto, Fermino Sanches, Zuliani, Rogério Lenotti, Sares, Cláudia Tarcila Gomes, Santos, José Sebastião dos, Sankarankutty, Ajith Kumar, Tirapelli, Daniela Pretti da Cunha, Silveira, Vanessa da Silva, Molfetta, Greice Andreotti de, Júnior, Wilson Araújo da Silva, and Brunaldi, Mariângela Ottoboni
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GENE expression ,BRCA genes ,METHYLATION ,AUTOMATED teller machines ,NEOADJUVANT chemotherapy ,P16 gene - Abstract
Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. Objective and design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm. Methods: We evaluated mRNA expression and methylation of RAD51, ATM, ATR, BRCA1, and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features. Results: RAD51, ATR, BRCA1, BRCA2, and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR (P =.027), BRCA1 (P <.001), and BRCA2 (P <.001); ATR with BRCA1 (P =.007), and ATM (P =.001); BRCA1 with BRCA2 (P = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P =.015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P =.035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P =.010) and death (1.664 vs 0.929, P =.036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P =.032), and no significant correlation for the other markers. Conclusions: Our results suggest RAD51, BRCA1, and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Lipometaplasia in fibrous hyperplasia and inflammatory fibrous hyperplasia of the oral cavity.
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Silveira, Heitor Albergoni, Javaroni, Julia Biliato, da Silva, Anderson Tangerino Ferreira, Reyes, Magdalena Raquel Torres, Hashimoto, Jennifer Mayumi, Cuadra‐Zelaya, Florence Juana Maria, Dominguete, Matheus Henrique Lopes, Mesquita, Ana Terezinha Marques, Brunaldi, Mariângela Ottoboni, Bufalino, Andreia, and León, Jorge Esquiche
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HYPERPLASIA ,CELL analysis ,HEMATOXYLIN & eosin staining - Abstract
Fibrous hyperplasia (FH) is a reactive hyperplastic lesion of the connective tissue, being considered the most common intraoral lesion. The microscopical differential diagnosis of FH/IFH presenting lipometaplasia includes lipoma, notably low-fat/fat-free spindle cell lipoma (SCL), fibrolipoma, and sclerotic (fibroma-like) lipoma, mesenchymal non-lipogenic neoplasms, such as liponeurofibroma and lipomatous perineurioma, and rare disorders such as benign symmetrical lipomatosis (BSL)[[7], [9], [11], [13]] (Figure 2B,C). Only those FH/IFH cases presenting lipometaplasia supported by typical reactive connective tissue stroma were selected. [Extracted from the article]
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- 2023
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4. Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma.
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Pádua, Joel Del Bel, Mariano, Carolline Fontes Alves, Fabro, Alexandre Todorovic, Tirapelli, Daniela Pretti da Cunha, Sankarankutty, Ajith Kumar, dos Santos, José Sebastião, and Brunaldi, Mariângela Ottoboni
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CANCER prognosis ,PROGNOSIS ,BRCA genes ,BREAST cancer prognosis ,SCIENTIFIC literature ,PROGRESSION-free survival ,ADENOCARCINOMA - Abstract
Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Endoscopic Ultrasound–Guided Fine-Needle Aspiration Microhistology in Asymptomatic and Symptomatic Pancreatic Cystic Lesions.
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Vaiciunas, Spencer, Taglieri, Eloy, Micelli-Neto, Otávio, Brunaldi, Mariângela Ottoboni, Venco, Filadélfio, Goldman, Suzan Menasce, Kemp, Rafael, dos Santos, José Sebastião, and Ardengh, José Celso
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- 2020
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6. Yellow Fever-induced Acute Lung Injury.
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Fabro, Alexandre Todorovic, Engelman, Gustavo Gonçalves, Ferreira, Natasha Nicos, Velloni, Júlia Maranhão Fagundes, Espósito, Danillo Lucas Alves, da Fonseca, Benedito Antônio Lopes, and Brunaldi, Mariângela Ottoboni
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- 2019
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7. Trypanosomiasis-Induced Megacolon Illustrates How Myenteric Neurons Modulate the Risk for Colon Cancer in Rats and Humans.
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Kannen, Vinicius, de Oliveira, Enio C., Motta, Bruno Zene, Chaguri, Annuar Jose, Brunaldi, Mariângela Ottoboni, and Garcia, Sérgio B.
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DISEASE risk factors ,COLON cancer ,SUBMUCOUS plexus ,PRECANCEROUS conditions ,CHAGAS' disease ,COLON tumors ,COLON polyps - Abstract
Background: Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods: Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results: No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas' megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2
nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance: Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research. Author Summary: The myenteric neuronal activity on colon carcinogenesis is a matter of debate. Chagas disease (a trypanosomiasis-related chronic infection) induces megacolon damaging myenteric neurons. Puzzling, tumors have been rarely reported in chagasic megacolon patients. We reveal here hyperplasia-related high-proliferation occurs in chagasic megacolon, although the risk for colon cancer is reduced. Having carcinogen-exposed rats infected with Trypanosoma cruzi reduced the numbers of myenteric neurons and colon preneoplastic lesions. An experimental model for chemical myenteric denervation was applied in carcinogen-exposed rats revealing that myenteric neurons promote the development of colon preneoplastic lesions. Yet, activity of the fecal content had to be secluded from the myenteric neuronal activity on colon carcinogenesis. Hartmann's surgical procedure enabled that. This was applied together with carcinogenic exposure and myenteric neuronal denervation ensuring that the neuronal activity is associated with enhanced development of colon carcinogenesis. Taken together, we believe colon tumors are not found within the chagasic megacolon region because the myenteric neuronal density is impaired. These observations shed lights on novel potential cell to cell interactions promoting the colon cancer development. [ABSTRACT FROM AUTHOR]- Published
- 2015
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8. Trypanosomiasis-Induced Megacolon Illustrates How Myenteric Neurons Modulate the Risk for Colon Cancer in Rats and Humans.
- Author
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Kannen, Vinicius, de Oliveira, Enio C., Motta, Bruno Zene, Chaguri, Annuar Jose, Brunaldi, Mariângela Ottoboni, and Garcia, Sérgio B.
- Subjects
TRYPANOSOMIASIS ,MEGACOLON ,COLON cancer risk factors ,CARCINOGENESIS ,TRYPANOSOMA cruzi ,BIOMARKERS ,EPITHELIAL cells - Abstract
Background: Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods: Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results: No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2
nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance: Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
9. Esophageal Ulcer in Brazilian Patients with HIV: Prevalence and Comparative Analysis Among Diagnostic Methods.
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Brunaldi, Mariângela Ottoboni, Rezende, Rosamar Eulira Fontes, Garcia, Sérgio Britto, Machado, Alcyone Artioli, Módena, José Luiz Pimenta, and Zucoloto, Sérgio
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ESOPHAGUS diseases ,HIV-positive persons ,AIDS diagnosis ,COMORBIDITY ,ENDOSCOPIC surgery ,HIV ,BIOPSY ,CYTOMEGALOVIRUS diseases - Abstract
Esophageal ulcer (EU) represents an important comorbidity in AIDS. We evaluated the prevalence of EU, the accuracy of the endoscopic and histologic methods used to investigate viral EU in HIV-positive Brazilian patients and the numerical relevance of tissue sampling. A total of 399 HIV-positive patients underwent upper gastrointestinal (UGI) endoscopy. HIV-positive patients with EU determined by UGI endoscopy followed by biopsies were analyzed by the hematoxylin-eosin (HE) and immunohistochemical (IH) methods. EU was detected in 41 patients (mean age, 39.2 years; 23 males), with a prevalence of 10.27%. The median CD4 count was 49 cells/mm
3 (range, 1–361 cells/mm3 ) and the viral load was 58,869 copies per milliliter (range, 50–77,3290 copies per milliliter). UGI endoscopy detected 29 of 41 EU suggestive of cytomegalovirus (CMV) infection and 7 of 41 indicating herpes simplex virus (HSV) infection. HE histology confirmed 4 of 29 ulcers induced by CMV, 2 of 7 induced by HSV, and 1 of 7 induced by HSV plus CMV. IH for CMV and HSV confirmed the HE findings and detected one additional CMV-induced case. UGI endoscopy showed 100% sensitivity and 15% specificity for the diagnosis of EU due to CMV or HSV compared to HE and IH. HE proved to be an adequate method for etiologic evaluation, with 87% sensitivity and 100% specificity compared to IH. The number of samples did not influence the etiologic evaluation. The data support the importance of IH as a complementary method for HE in the diagnosis of EU of viral etiology. [ABSTRACT FROM AUTHOR]- Published
- 2010
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