ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
76 resultados
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- Historical Analysis of the Brazilian Cervical Cancer Screening Program from 2006 to 2013: A Time for Reflection(2015) COSTA, Ricardo Filipe Alves; LONGATTO-FILHO, Adhemar; PINHEIRO, Celine; ZEFERINO, Luiz Carlos; FREGNANI, Jose HumbertoBackground The Cervical Cancer Database of the Brazilian National Health Service (SISCOLO) contains information regarding all cervical cytological tests and, if properly explored, can be used as a tool for monitoring and managing the cervical cancer screening program. The aim of this study was to perform a historical analysis of the cervical cancer screening program in Brazil from 2006 to 2013. Material and Methods The data necessary to calculate quality indicators were obtained from the SISCOLO, a Brazilian health system tool. Joinpoint analysis was used to calculate the annual percentage change. Results We observed important trends showing decreased rates of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and an increased rate of rejected exams from 2009 to 2013. The index of positivity was maintained at levels below those indicated by international standards; very low frequencies of unsatisfactory cases were observed over the study period, which partially contradicts the low rate of positive cases. The number of positive cytological diagnoses was below that expected, considering that developed countries with low frequencies of cervical cancer detect more lesions annually. Conclusions The evolution of indicators from 2006 to 2013 suggests that actions must be taken to improve the effectiveness of cervical cancer control in Brazil.
- Characterization of PAR1 and FGFR1 expression in invasive breast carcinomas: Prognostic significance(2012) TIBURCIO, Marta; COSTA, Sandra M. A.; DUARTE, Maria De Fatima; SCHMITT, Fernando C.; LONGATTO FILHO, AdhemarBreast cancer is the most common cause of cancer mortality among women worldwide. Among the several factors associated with breast cancer development, angiogenesis plays an essential role and has currently emerged as a potential diagnostic, prognostic and therapeutic target. Protease-activated receptor 1 (PAR1) and fibroblast growth factor receptor 1 (FGFR1) have important activities in tumor angiogenesis and progression. The aim of this study was to investigate the prognostic significance of these two receptors, hypothesising significant correlations between receptor expression in tumor angiogenesis and clinicopathological parameters customarily used in breast cancer prognosis and prediction. Formalin-fixed and paraffin-embedded samples of ductal invasive breast carcinomas were used to analyze the expression of PAR1 and FGFR1, in the tumor cells as well as in the tumor stroma, and further determine intratumoral microvessel density (iMVD) to quantify intratumoral angiogenesis. Correlations between PAR1 and FGFR1 expression in tumor cells and stroma, iMVD and several clinicopathological parameters and molecular markers used in breast cancer diagnosis have been addressed. The correlation between PAR1 and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression. The results reported in the present study also emphasize the importance of microenvironmental factors in tumor progression, while precluding the positive association between iMVD and breast cancer aggressiveness.
- Peri-Carotid Adipose Tissue and Atherosclerosis at Carotid Bifurcation(2024) FERREIRA, Joana; LONGATTO-FILHO, Adhemar; DIONISIO, Ana; CORREIA-NEVES, Margarida; CUNHA, Pedro; MANSILHA, ArmandoVulnerable carotid plaques are responsible for 20% of the ischemic strokes. The identification of these asymptomatic carotid plaques that will become symptomatic is essential but remains unclear. Our main goal was to investigate whether the amount of the peri-carotid adipose tissue, estimated by the extra-media thickness (EMT), is associated with the atherosclerotic characteristics at the carotid bifurcation in patients with PAD. An observational, prospective, single-center, longitudinal study was conducted. Overall, 177 patients were subjected to carotid Doppler ultrasound at the study admission. The following data were collected: EMT, intima-media thickness (IMT), the presence of carotid plaques, the area of the highest plaque, the presence of ""acute culprit"" carotid stenosis, and the grade of internal carotid stenosis. ""Acute culprit"" carotid stenosis was defined as a significant atherosclerotic plaque that leads to a neurologic event within 15 days. From each carotid bifurcation, a right and a left EMT were determined. We analyzed both the mean EMTs (calculated as the mean between the right and the left EMT) and the EMT ipsilateral to the carotid bifurcation. The presence of carotid plaques was associated with a higher mean EMT [Median = 1.14; IQR = 0.66 versus Median = 0.97; IQR = 0.40; p = 0.001]. A positive correlation was found between the mean EMT and IMT (right: rho = 0.20; p = 0.010; left: rho = 0.21; p = 0.007) and between the mean EMT and the area of the largest carotid plaque (right: rho = 0.17; p = 0.036; left: rho = 0.22; p = 0.004). Left carotid stenosis >= 70% was associated with higher ipsilateral EMT [Median = 1.56; IQR = 0.70 versus Median = 0.94; IQR = 0.42; p = 0.009]. Patients with ""acute culprit"" carotid stenosis had a higher ipsilateral EMT [left ipsilateral EMT: Median = 1.46; IQR = 0.63; ""non-acute"": Median = 0.94; IQR = 0.43; p = 0.009; right ipsilateral EMT: Median = 2.25; IQR = 0.62; ""non-acute"": Median = 1.00; IQR = 0.51; p = 0.015]. This difference was not found in the contra-lateral EMT. Six months after the neurologic event, EMT ipsilateral to an ""acute culprit"" carotid stenosis decreased (p = 0.036). The amount of peri-carotid adipose tissue, estimated with EMT, was associated with atherosclerosis at the carotid arteries. The mean EMT was associated with the features of chronic atherosclerosis lesions: the presence of carotid plaques, IMT, and the area of the highest plaque. Ipsilateral EMT was linked with ""acute culprit"" atherosclerotic plaque.
- Increased CD3(+), CD8(+), or FoxP3(+) T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients(2021) BARBOSA, Ana Margarida; MARTINHO, Olga; NOGUEIRA, Rosete; CAMPOS, Juliana; LOBO, Liliana; PINTO, Henrique; LONGATTO-FILHO, Adhemar; CASTRO, Antonio G.; MARTINS, Sandra F.; TORRADO, EgidioSimple Summary Colorectal cancer (CRC) is amongst the deadliest cancers. Surgical excision of the primary tumor is the curative intent treatment; however, recurrence occurs in approximately 20% of patients. Therefore, novel staging protocols are crucial to inform clinicians which patients will recur. In this study, we explored the prognostic potential of tumor-infiltrating lymphocytes. Our data did not reveal any association between intratumor lymphocyte infiltrations with clinical or pathological data. On the other hand, the presence of CD3(+), CD8(+), or FoxP3(+) lymphocyte infiltration in the tumor invasive margins were associated with markers of good prognosis. Despite this, we were not able to find any statistically significant alterations in the overall survival of patients, even though high infiltrations of FoxP3(+) T lymphocytes in the tumor margin resulted in an increased overall survival of 14 months. Taken together, our data show that the location and type of tumor-infiltrating lymphocytes are associated with the pathogenesis of CRC; however, only high FoxP3(+) T lymphocyte infiltrations are inclined to indicate favorable prognosis. Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3(+), CD8(+), and FoxP3(+) T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3(+), CD8(+), or FoxP3(+) T lymphocytes were associated with TNM stages I-II (p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases (p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3(+) T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3(+), CD8(+), or FoxP3(+)T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3(+) T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.
- Deregulated expression of superoxide dismutase-2 correlates with different stages of cervical neoplasia(2011) TERMINI, Lara; LONGATTO FILHO, Adhemar; MACIAG, Paulo Cesar; ETLINGER, Daniela; ALVES, Venancio Avancini Ferreira; NONOGAKI, Suely; SOARES, Fernando Augusto; VILLA, Luisa LinaObjective: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme may be involved in carcinogenesis, particularly in lung, gastric, colorectal and breast cancer. Methods: In the present study, we have evaluated SOD2 protein levels by immunohistochemistry (IHC) in 331 cervical histological samples including 31 low-grade cervical intraepithelial neoplasia (LSIL), 51 high-grade cervical intraepithelial neoplasia (HSIL), 197 squamous cervical carcinomas (SCC) and 52 cervical adenocarcinomas (ADENO). Results: We observed that SOD2 staining increases with cervical disease severity. Intense SOD2 staining was found in 13% of LSIL, 25.5% of HSIL and 40% of SCC. Moreover, 65.4% of ADENO exhibited intense SOD2 staining. Conclusions: Differences in the expression of SOD2 could potentially be used as a biomarker for the characterization of different stages of cervical disease.
- EARLY ORAL FEEDING POST-UPPER GASTROINTESTINAL TRACT RESECTION AND PRIMARY ANASTOMOSIS IN ONCOLOGY(2018) LOPES, Lilian Pinheiro; MENEZES, Taysa Machado; TOLEDO, Diogo Oliveira; DE-OLIVEIRA, Antonio Talvane Torres; LONGATTO-FILHO, Adhemar; NASCIMENTO, Jose Eduardo de AguilarBackground: The practice of starving patients in the immediate period after upper gastrointestinal surgery is widespread. Early oral intake has been shown to be feasible and may result in faster recovery and decrease length of hospital. Aim: To evaluate the feasibility and safety of oral nutrition on postoperative early feeding after upper gastrointestinal surgeries. Methods: Observational cohort design study with convenience retrospective data in both genders, over 18 years, undergoing to total gastrectomy and/or elective esophagectomy. They have received oral or enteral nutrition in less than 48 h after surgery, and among those who started with enteral nutrition, the oral feeding up to seven days. Results: The study was performed in 161 patients, 24 (14.9%) submitted to esophagectomy, 132 (82%) to total gastrectomy and five (3.1%) to esophagogastrectomy. Was observed good dietary acceptance and low percentage (29%) of gastrointestinal intolerances, more pronounced among those with enteral diet. Most of the patients did not present postoperative complications, 11 (6.8%) were reopened, five (3.1%) had fistulas, three (1.9%) wound dehiscence, three (1.9%) fistula more wound dehiscence and six (3.7%) other non-infectious complications. Conclusion: Early oral diet is safe and viable for patients undergoing upper gastrointestinal surgery.
- PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome(2018) MUNARI, Fernanda Franco; CRUVINEL-CARLONI, Adriana; LACERDA, Croider Franco; OLIVEIRA, Antonio Talvane Torres de; SCAPULATEMPO-NETO, Cristovam; SILVA, Sandra Regina Morini da; CREMA, Eduardo; ADAD, Sheila Jorge; RODRIGUES, Maria Aparecida Marchesan; HENRY, Maria Aparecida Coelho Arruda; GUIMARAES, Denise Peixoto; LONGATTO-FILHO, Adhemar; REIS, Rui ManuelBackgroundChronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.ObjectiveWe analyzed hotspot PIK3CA gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of PIK3CA mutations with patients' clinical and pathological features.MethodsThe study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique.ResultsPIK3CA mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, PIK3CA mutations were significantly associated with lower survival (mean 5months), when compared to wild-type patients (mean 2.0years). No other significant associations were observed between PIK3CA mutations and patients' clinical features or TP53 mutation profile.ConclusionThis is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.
- Implementation of HPV Tests in Latin America: What We Learned; What Should We Have Learned, and What Can We Do Better?(2022) GODOY, Luani Rezende; POSSATI-RESENDE, Julio Cesar; GUIMARAES, Yasmin Medeiros; PEDRAO, Priscila Grecca; REIS, Ricardo dos; LONGATTO-FILHO, AdhemarSimple Summary Cervical cancer is caused by HPV and is nearly completely preventable because of the vaccination and screening available. The present review aims to map the initiatives conducted to implement or evaluate the implementation of HPV testing in Latin American countries. We performed a review search on PubMed in the English language and on grey literature in the Spanish language. We found information concerning HPV testing as primary screening in eight countries. We learned that HPV implementation is not only feasible but a very promising tool for reducing cervical cancer morbidity and mortality. The cost for saving lives and reducing suffering due to morbidity must be pragmatically evaluated by the Latin American governments and improving outcomes must become a mandatory priority for those that are responsible for addressing an organized system of screening. Cervical cancer is caused by HPV. Although it is the fourth most common type of cancer diagnosed and the fourth cause of cancer death, cervical cancer is nearly completely preventable because of the vaccination and screening available. The present review aims to map the initiatives conducted to implement or evaluate the implementation of HPV testing in Latin American countries. We performed the review by searching on PubMed in the English language and on grey literature, as most of the information about the guidelines used was found in governmental websites in the Spanish language. We only found information in eight countries concerning HPV testing as primary screening. Only Mexico has established HPV-based screening in all territories. There are three countries with regional implementation. Two countries with pilot studies indicated results that supported implementation. Finally, there are another two countries with a national recommendation. We have learned that HPV implementation is feasible and a very promising tool for reducing cervical cancer morbidity and mortality. The costs associated with saving lives and reducing suffering due to morbidity of a preventable disease must be pragmatically evaluated by the Latin America governments, and improving outcomes must be a mandatory priority for those that are responsible for addressing an organized system of cervical cancer screening.
- Profile of esophageal squamous cell carcinoma mutations in Brazilian patients(2021) MUNARI, Fernanda Franco; SANTOS, Wellington dos; EVANGELISTA, Adriane Feijo; CARVALHO, Ana Carolina; PASTREZ, Paula Aguiar; BUGATTI, Diego; WOHNRATH, Durval R.; SCAPULATEMPO-NETO, Cristovam; GUIMARAES, Denise Peixoto; LONGATTO-FILHO, Adhemar; REIS, Rui ManuelEsophageal cancer is an aggressive tumor that has a high rate of incidence and mortality worldwide. It is the 10th most frequent type in Brazil, being squamous cell carcinoma (ESCC) the predominant subtype. There is currently an incessant search to identify the frequently altered genes associated with esophageal squamous cell carcinoma biology that could be druggable. This study aimed to analyze the somatic mutation profile of a large panel of cancer-related genes in Brazilian ESCC. In a series of 46 ESCC diagnoses at Barretos Cancer Hospital, DNA isolated from paired fresh-frozen and blood tissue, a panel of 150 cancer-related genes was analyzed by next-generation sequencing. The genes with the highest frequency of mutations were TP53 (39/46, 84.8%), followed by NOTCH1 ( 7/46, 15.2%), NFE2L2 ( 5/46, 10.8%), RB1 (3/46, 6.5%), PTEN (3/46, 6.5%), CDKN2A (3/46, 6.5%), PTCH1 (2/46, 4.3%) and PIK3CA (2/46, 4.3%). There was no significant association between molecular and patients' clinicopathological features. Applying an evolutionary action score of p53 ( EAp53), we observed that 14 (35.9%) TP53 mutations were classified as high-risk, yet no association with overall survival was observed. Concluding, this the largest mutation profile of Brazilian ESCC patients, which helps in the elucidation of the major cancer-related genes in this population.
- Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo(2019) PRATI, Bruna; ABJAUDE, Walason da Silva; TERMINI, Lara; MORALE, Mirian; HERBSTER, Suellen; LONGATTO-FILHO, Adhemar; NUNES, Rafaella Almeida Lima; CAMACHO, Lizeth Carolina Cordoba; RABELO-SANTOS, Silvia Helena; ZEFERINO, Luiz Carlos; AGUAYO, Francisco; BOCCARDO, EnriqueAlterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identified 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly affects tumor cells clonogenic and anchorage independent growth potential. We showed that this effect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression.