ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis(2019) LIN, Chunqing; SLAMA, Jiri; GONZALEZ, Paula; GOODMAN, Marc T.; XIA, Ningshao; KREIMER, Aimee R.; WU, Ting; HESSOL, Nancy A.; SHVETSOV, Yurii; ORTIZ, Ana P.; GRINSZTEJN, Beatriz; MOSCICKI, Anna-Barbara; HEARD, Isabelle; LOSA, Maria del Refugio Gonzalez; KOJIC, Erna M.; LOEFF, Maarten F. Schim van der; WEI, Feixue; LONGATTO-FILHO, Adhemar; MBULAWA, Zizipho A.; PALEFSKY, Joel M.; SOHN, Annette H.; HERNANDEZ, Brenda Y.; ROBISON, Katina; SIMPSON JR., Steve; CONLEY, Lois J.; POKOMANDY, Alexandra de; SANDE, Marianne A. B. van der; MANDISHORA, Racheal S. Dube; VOLPINI, Lays P. B.; PIERANGELI, Alessandra; ROMERO, Byron; WILKIN, Timothy; FRANCESCHI, Silvia; HIDALGO-TENORIO, Carmen; RAMAUTARSING, Reshmie A.; PARK, Ina U.; TSO, Fernanda K.; GODBOLE, Sheela; D'HAUWERS, Kathleen W. M.; SEHNAL, Borek; MENEZES, Lynette J.; HERACLIO, Sandra A.; CLIFFORD, Gary M.Background Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. Methods We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. Findings Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16.5, 95% CI 14.2-19.2, p<0.0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4.4, 3.7-5.3, p<0.0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14.1, 11.1-17.9, p<0.0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12.9, 95% CI 6.7-24.8, p<0.0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2.3, 1.6-3.4, p<0.0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23.1, 9.4-57.0, p<0.0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3.6, 2.5-5.3, p<0.0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). Interpretation HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. Copyright
- Is Proflavine Exposure Associated with Disease Progression in Women with Cervical Dysplasia? A Brief Report(2018) PANTANO, Naitielle; HUNT, Brady; SCHWARZ, Richard A.; PARRA, Sonia; CHERRY, Katelin; POSSATI-RESENDE, Julio Cesar; LONGATTO-FILHO, Adhemar; FREGNANI, Jose Humberto Tavares Guerreiro; CASTLE, Philip E.; SCHMELER, Kathleen; RICHARDS-KORTUM, RebeccaProflavine is an acridine dye used with high-resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short-term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow-up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow-up visits. Mean duration of follow-up was 18.7 and 20.1 months for the proflavine-exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.
- Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells(2023) FERREIRA, Debora; SANTOS-PEREIRA, Catia; COSTA, Marta; AFONSO, Julieta; YANG, Sujuan; HENSEL, Janine; MCANDREWS, Kathleen M.; LONGATTO-FILHO, Adhemar; FERNANDES, Rui; MELO, Joana B.; BALTAZAR, Fatima; MOREIRA, Joao N.; KALLURI, Raghu; RODRIGUES, Ligia R.Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an exosome-based system was successfully generated for the siRNA loading (iExoMEK1). Our data suggested absence of modification of the physical properties and general integrity of the iExoMEK1 comparatively to the unmodified counterparts. Such exosome-mediated down-regulation of MEK1 led to a tumor regression accompanied by a decrease of angiogenesis using the chick chorioallantoic-membrane model. Our results highlight the potential of the targeting of MAPK/ERK cascade as a promising therapeutic approach against TNBC.
- RKIP Inhibition in Cervical Cancer Is Associated with Higher Tumor Aggressive Behavior and Resistance to Cisplatin Therapy(2013) MARTINHO, Olga; PINTO, Filipe; GRANJA, Sara; MIRANDA-GONCALVES, Vera; MOREIRA, Marise A. R.; RIBEIRO, Luis F. J.; LORETO, Celso di; ROSNER, Marsha R.; LONGATTO-FILHO, Adhemar; REIS, Rui ManuelCervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (similar to 15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.
- CD147 immunohistochemistry discriminates between reactive mesothelial cells and malignant mesothelioma(2012) PINHEIRO, Celine; LONGATTO-FILHO, Adhemar; SOARES, Tony R.; PEREIRA, Helena; BEDROSSIAN, Carlos; MICHAEL, Claire; SCHMITT, Fernando C.; BALTAZAR, FatimaMalignant mesothelioma (MM) is a rare form of cancer. Its histopathological diagnosis is very difficult, as it exhibits a number of different appearances that can be misinterpreted as metastatic invasion or atypical hyperplasia. Thus, there is an urgent need to identify adequate markers to distinguish between benign and malignant cells, allowing the implementation of appropriate therapies and, possibly, specific directed therapies. MM, like other tumors, show an increase in glucose uptake, due to high rates of glycolysis, inducing an intracellular overload of acids. In this context, monocarboxylate transporters (MCTs) emerge as important players, by mediating the transmembranar co-transport of lactate with a proton, thereby, regulating pH and allowing continuous glycolysis. Importantly, proper MCT expression and activity depend on its co-expression with a chaperone, CD147, which is associated with poor prognosis in cancer. Twenty-two samples including reactive mesothelial cells, MM, and atypical mesothelial hyperplasias were evaluated for immunoexpression of MCT1, MCT4, and CD147. Expression of these proteins was compared with GLUT1 as a new promising marker for MM. Although MCT isoforms were not differentially expressed in the two types of cytological specimens, CD147, as GLUT1, was almost exclusively expressed in MM. Both MCT1 and MCT4 are not able to discriminate between mesothelial reactive cells and mesothelial malignant cells, while CD147 was able to distinguish these two proliferations. If confirmed, besides being a good marker for identification of MM, CD147 may also be a target for therapeutical strategies in this rare type of tumor. Diagn. Cytopathol. 2012;40:478483. (c) 2012 Wiley Periodicals, Inc.
- Racial/Ethnic Disparities in Cervical Cancer Screening and Outcomes(2016) MUSSELWHITE, Laura W.; OLIVEIRA, Cristina M.; KWARAMBA, Tendai; PANTANO, Naitielle de Paula; SMITH, Jennifer S.; FREGNANI, Jose Humberto; REIS, Rui M.; MAUAD, Edmundo; VAZQUEZ, Fabiana de Lima; LONGATTO-FILHO, AdhemarInvasive cervical cancer disproportionately affects women without sufficient access to care, with higher rates among minority groups in higher-income countries and women in low-resource regions of the world. Many elements contribute to racial/ethnic disparities in the cervical cancer continuum -from screening and diagnosis to treatment and outcome. Sociodemographic factors, access to healthcare, income and education level, and disease stage at diagnosis are closely linked to such inequities. Despite the identification of such elements, racial/ethnic disparities persist, and are widening in several minority subgroups, particularly in older women, who are ineligible for human papillomavirus (HPV) vaccination and are underscreened. Recent studies suggest that racial/ethnic differences in HPV infection exist and may also have a role in observed differences in cervical cancer. In this review, we provide an overview of the current literature on racial disparities in cervical cancer screening, incidence, treatment and outcome to inform future strategies to reduce persistent inequities. (C) 2016 S. Karger AG, Basel.
- Detection of HPV E6 oncoprotein from urine via a novel immunochromatographic assay(2020) OLIVEIRA, Cristina Mendes de; MUSSELWHITE, Laura W.; PANTANO, Naitielle de Paula; VAZQUEZ, Fabiana Lima; SMITH, Jennifer S.; SCHWEIZER, Johannes; BELMARES, Michael; POSSATI-RESENDE, Julio Cesar; VIEIRA, Marcelo de Andrade; LONGATTO-FILHO, Adhemar; FREGNANI, Jose Humberto Tavares GuerreiroCervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6 (TM) Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (
- African genetic ancestry is associated with lower frequency of PNPLA3 G allele in non-alcoholic fatty liver in an admixed population(2022) CAVALCANTE, Lourianne Nascimento; PORTO, Jun; MAZO, Daniel; LONGATTO-FILHO, Adhemar; STEFANO, Jose Tadeu; LYRA, Andre Castro; CARRILHO, Flair Jose; REIS, Rui Manuel; ALVES, Venancio A. F.; SANYAL, Arun J.; OLIVEIRA, Claudia P.Introduction and objectives: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ances-try Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population.Methods: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplanta-tion. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyp-ing were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; a<0.05 was considered significant.Results: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerin-dian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 +/- 0.205 versus 0.105 +/- 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes.Conclusion: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.(c) 2022 Published by Elsevier Espana, S.L.U. on behalf of Fundacion Clinica Medica Sur, A.C. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- High-Risk Human Papillomavirus Detection in Urine Samples From a Referral Population With Cervical Biopsy-Proven High-Grade Lesions(2018) LORENZI, Adriana T.; FREGNANI, Jose Humberto T.; DOCKTER, Janel; FITZGERALD, Kerry; STROHECKER, Elizabeth; EATON, Barbara; VIBAT, Cecile Rose T.; ERLANDER, Mark G.; SCAPULATEMPO-NETO, Cristovam; SMITH, Jennifer S.; LONGATTO-FILHO, AdhemarObjective: The aim of the study was to evaluate the performance of the HPV-HR test to detect high-risk human papillomavirus (HPV) in urine samples in comparison with a commercial molecular HPV test. Materials and Methods: This is a prospective study, in which 350 patients diagnosed previously with cervical intraepithelial neoplasia (CIN) grade 2 or higher were enrolled. Urine and cervical specimens were collected. Urine was tested with the HPV-HR test and cervical specimens were tested with the Cobas. Results: Of the 336 evaluable patients, there were 271 cases of CIN 2+, of which 202 were CIN 3+ and the remaining 65 patients were less than CIN 2. Positivity was 77.1% (95% confidence interval [CI] = 72.5-81.5) for the urine samples and 83.6% (95% CI = 79.6-87.6) for the cervical samples. Agreement between cervical and urine samples for HPV detection was 79.8% ( = 0.363; 95% CI = 0.243-0.484). Sensitivity for CIN 2+ was 83.4% (95% CI = 78.4-87.6) for urine and 90.8% (95% CI = 86.7-92.9) for cervical samples. The sensitivity for CIN 3+ was 85.6% (95% CI = 80.0-90.2) for urine and 92.6% (95% CI = 88.0-95.8) for cervical samples. Specificity for worse than CIN 2 was 50.8% (95% CI = 33.7-59.0) and 46.2% (95% CI = 33.7-59.0) for urine and cervical samples, respectively. Conclusions: Although these results demonstrated slightly higher detection rates for HR-HPV and clinical sensitivity in cervical samples than in urine, when compared with histological diagnoses, urine sampling is a viable alternative to access women who do not participate in routine screening programs.
- Prevalence of high risk HPV DNA in esophagus is high in Brazil but not related to esophageal squamous cell carcinoma(2018) COSTA, Allini Mafra da; FREGNANI, Jose Humberto Tavares Guerreiro; PASTREZ, Paula Roberta Aguiar; MARIANO, Vania Sammartino; SCAPULATEMPO NETO, Cristovam; GUIMARAES, Denise Peixoto; OLIVEIRA, Kelly Menezio Giordina de; ZEMI NETO, Said Abdala; NUNES, Emily Montosa; FERREIRA, Silvaneide; SICHERO, Laura; VILLA, Luisa Lina; SYRJANEN, Kari Juhani; LONGATTO-FILHO, AdhemarBackground. The first publication that associated Human Papillomavirus (HPV) infection and esophageal cancer was published in 1982. However, data are still contradictory and require further investigation. The aim of this study was to identify high risk HPV DNA in esophageal tissue of patients with and without esophageal squamous cell carcinoma (ESCC) and correlate HPV presence with classical risk factors. Methods. Invited patients signed the informed consent form, and interviews were conducted in order to obtain information about sociodemographic and lifestyle behavior. During endoscopy, esophageal biopsies were collected from case and controls. Multiplex polymerase chain reaction genotyping was conducted on endoscopic biopsies to identify HPV types and HPV-16 was further evaluated by specific PCR real time. Results. Among 87 cases, 12 (13.8%) had tumors harboring high risk HPV DNA and among 87 controls, 12 (13.8%) had high risk HPV DNA (OR: 1.025 [CI: 0.405: 2.592]). Variables regarding consumption of alcohol and use of tobacco continued to characterize risk factors even after adjustments by presence or absence of high risk HPV. Conclusion. HPV was demonstrated to be frequently and similarly associated to normal and malignant esophageal tissues, but not as an independent risk factor to esophageal cancer. Impact. To contribute to the Brazilian population data on this subject, which is still contradictory.