ADHEMAR LONGATTO FILHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- 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
- High-Risk HPV Testing in Primary Screening for Cervical Cancer in the Public Health System, Sao Paulo, Brazil(2019) LEVI, Jose Eduardo; MARTINS, Toni Ricardo; LONGATTO-FILHO, Adhemar; COHEN, Diane Dede; CURY, Use; FUZA, Luiz Mario; VILLA, Luisa L.; ELUF-NETO, JoseEvery year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of Sao Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to I IPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class >= ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papillomavirus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7,2% of the women. Per protocol, 1,592 Hr-HPV+ women, in addition to 72 patients with cytologic classification > low-grade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2(+)) cases were diagnosed, 79 were Hr-HPV DNA(+) and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3(+) cases were Hr-HPV DNA(+). HPV genotyping may be useful in the management of Hr-HPV+ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3(+). Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.
- 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.
- Impact of Brush Cytology Analysis for the Diagnosis of Esophageal Squamous Cell Carcinoma: The Quality of Liquid-Based Preparation of Cytological Slides(2019) MARIANO, Vania S.; PASTREZ, Paula R. A.; COSTA, Allini Mafra; GUIMARAES, Denise P.; CUNHA, Thiago R.; NETO, Said A. Z.; SCAPULATEMPO-NETO, Christovam; SYRJANEN, Kari J.; LONGATTO-FILHO, AdhemarObjectives: The diagnostic performance of cytology in esophageal squamous cell carcinoma (ESCC) is meticulously described. Methods: Cytological and biopsy specimens were prospectively taken during esophagogastroduodenoscopy of 123 individuals in 2013 and 2014. Cytology samples were maintained in preservative fluid until processing and biopsies were formalin-fixed and paraffin-embedded. Results: Based on endoscopic biopsy results, 70 cases were positive for ESCC whilst 53 were negative for cancer. In addition, brush cytology showed high sensitivity and specificity (98.57 and 96.23%, respectively) in detecting the disease, and high accuracy (97.5%) comparable to that provided by histopathology which is the accepted gold standard. Conclusion: Brush cytology specimens preserved in liquid medium may be a good alternative for ESCC diagnosis. (C) 2019 S. Karger AG, Basel
- Human papillomavirus is not associated to non-small cell lung cancer: data from a prospective cross-sectional study(2019) SILVA, Estela Maria; MARIANO, Vania Sammartino; PASTREZ, Paula Roberta Aguiar; PINTO, Miguel Cordoba; NUNES, Emily Montosa; SICHERO, Laura; VILLA, Luisa Lina; SCAPULATEMPO-NETO, Cristovam; SYRJANEN, Kari Juhani; LONGATTO-FILHO, AdhemarBackground The pathogenesis of lung cancer is triggered by a combination of genetic and environmental factors, being the tobacco smoke the most important risk factor. Nevertheless, the incidence of lung cancer in non-smokers is gradually increasing, which demands the search for different other etiological factors such as occupational exposure, previous lung disease, diet among others. In the early 80's a theory linked specific types of human papillomavirus (HPV) to lung cancer due to morphological similarities of a subset of bronchial squamous cell carcinomas with other HPV-induced cancers. Since then, several studies revealed variable rates of HPV DNA detection. The current study aimed to provide accurate information on the prevalence of HPV DNA in lung cancer. Methods Biopsies were collected from 77 newly diagnosed non-small cell lung cancer (NSCLC) patients treated at the Thoracic Oncology Department at Barretos Cancer Hospital. The samples were formalin fixed and paraffin embedded (FFPE), histologic analysis was performed by an experienced pathologist. DNA was extracted from FFPE material using a commercial extraction kit and HPV DNA detection was evaluated by multiplex PCR and HPV16 specific real-time PCR. Results HPV was not identified in any of the samples analysed (69). Conclusions Our data demonstrated a lack of HPV DNA in a series of NSCL cancers.
- Clinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma-MCT1 as potential target in diffuse large B cell lymphoma(2019) AFONSO, Julieta; PINTO, Tatiana; SIMOES-SOUSA, Susana; SCHMITT, Fernando; LONGATTO-FILHO, Adhemar; PINHEIRO, Celine; MARQUES, Herlander; BALTAZAR, FatimaPurposeIncreased glycolytic activity with accumulation of extracellular lactate is regarded as a hallmark of cancer. In lymphomas, FDG-PET has undeniable diagnostic and prognostic value, corroborating that these tumours are avid for glucose. However, the role of glycolytic metabolism-related molecules in lymphoma is not well known. Here, we aimed to evaluate the clinical and prognostic significance of a panel of glycolytic metabolism-related molecules in primary non-Hodgkin lymphomas (NHL) and to test in vitro the putative therapeutic impact of lactate transport inhibition.MethodsWe assessed, by immunohistochemistry, the expression of the metabolism-related molecules MCT1, MCT2, MCT4, CD147, GLUT1, LDHA and CAIX in both tumour and stroma compartments of tissue sections obtained from 104 NHL patients. In addition, the lymphoma-derived cell lines OZ and DOHH-2 were used to evaluate the effect of AZD3965 on their viability and on apoptosis induction, as well as on extracellular lactate accumulation.ResultsWe found that expression of MCT1 in the NHL tumour compartment was significantly associated with a poor clinicopathological profile. We also found that MCT4 and CAIX were present in the stromal compartment and correlated with an aggressive phenotype, while MCT1 was absent in this compartment. In addition, we found that AZD3965-mediated disruption of MCT1 activity led to inhibited NHL cell viability and extracellular lactate accumulation, while increasing apoptotic cell death.ConclusionsOur results indicate that elevated glycolytic activity is associated with NHL aggressiveness, pointing at metabolic cooperation, mediated by MCT1 and MCT4, between tumour cells and their surrounding stroma. MCT1 may serve as a target to treat NHL (diffuse large B cell lymphoma) patients with high MCT1/low MCT4 expressing tumours. Further (pre-)clinical studies are required to allow the design of novel therapeutic strategies aimed at e.g. reprogramming the tumour microenvironment.
- HPV: A Virus-Dinosaur Living among Us? Preface(2019) LONGATTO-FILHO, Adhemar; SYRJANEN, Kari
- Age-related acceptability of vaginal self-sampling in cervical cancer screening at two university hospitals: a pilot cross-sectional study(2019) LORENZ, Noely Paula Cristina; TERMINI, Lara; LONGATTO FILHO, Adhemar; TACLA, Maricy; AGUIAR, Lana Maria de; BELDI, Mariana Carmezim; FERREIRA-FILHO, Edson Santos; BARACAT, Edmund Chada; SOARES-JUNIOR, Jose MariaBackground: To determine whether age is a barrier against acceptability of cervicovaginal self-sampling in screening for cervical cancer at two gynecology outpatient clinics. Methods: This is a cross-sectional study involving 116 women over 21 years of age with an abnormal Pap smear. Clinical and laboratorial data were recorded in electronic files. Women received detailed self-collection instructions. After the self-sampling procedure (Evalyn Brush (R)), women were instructed to answer a questionnaire about vaginal self-sampling acceptability that consisted of seven multiple-choice items. The participants were divided into three age brackets: 21 to 29 years, 30 to 49 years, and 50 years and over. Chi-square, Fischer exact, Kolmogorov-Smirnov and Kruskal-Wallis tests were used. Results: The analysis of the participants' perception of the procedure stratified according to age groups showed a decline in the fear of hurting oneself during the procedure as age increased. Most participants reported that it was very easy to understand how to use the self-sampling brush and that it was easy to use it. Most of them were neither embarrassed nor afraid of getting hurt during the procedure. The majority preferred self-sampling to collection by a healthcare professional. The main reason was practicality: the possibility of choosing the place and time for sampling. Conclusions: The participating women found self-collection simple to understand and easy to accept regardless of age. The younger women indicated more fear and discomfort in self-sampling, which points to the need for attraction strategies that are more appealing to the younger generations.
- Diversity of human papillomavirus typing among women population living in rural and remote areas of Brazilian territory(2019) LORENZI, Adriana Tarla; FREGNANI, Jose Humberto; VILLA, Luisa Lina; SICHERO, Laura; NUNES, Emily Montosa; LONGATTO-FILHO, AdhemarObjectives: Genotyping HPV from samples tested positive to careHPV (TM) assay in rural and remote areas of Brazilian territory. Methods: A total of 5079 women were enrolled in an opportunistic screening from the Barretos Cancer Hospital, through mobile units or ambulatory unit. All careHPV (TM) hr-HPV positive samples were tested by a Luminex-based protocol in order to evaluate the HPV infecting types. Results: Positive hr-HPV results were obtained in 10.6% (536/5068) of women. Among these cases, HPV-56 and HPV-51 were the most common types detected in 32.3% and 31.4%, respectively. HPV-53 (20.5%), HPV-18 (18.5%), HPV-58 (17.6%), HPV-52 (16.0%) and HPV-16.6%) were the other most frequent types detected. These frequencies represent prevalences of 2.35%, 2.12%, 2.02%, 1.84% and 1.80% respectively, within the population studied. Regarding low-risk HPVs, HPV-6 was detected in 12.9% of the samples. The less frequent types (< 3%) were: HPV-70, HPV-11 and HPV-26. Conclusions: The most frequent types detected were: HPV-56, HPV-51, HPV-53, HPV-18, HPV-58, HPV-52 and HPV-16 according to decreasing rates.
- Cervical, Ovarian and Endometrial Tumor Markers: Potential Clinical Value(2019) MALHONE, Carolina; LONGATTO-FILHO, AdhemarTumors markers can be described as molecular products expressed by neoplasia tissues (immunohistochemistry), or metabolized and secreted by tumor and characterized biochemically in body fluids such as blood and urine. They may have utility as indicators of tumor stage and grade as well useful for monitoring responses to treatment and predicting recurrence, progression, development of metastases, or even patient survival. Unfortunately, in some cases they may have no identified clinical potential. Several investigations have been carried out, especially in the last decade, using biotechnological methods, in order to identify new potential tumor markers. By translating these findings into clinical use one may facilitate accurate diagnosis and prognostic prediction, and contribute to individualized treatment. The objective of this review is to describe some biomarkers with potential use in clinical settings of uterine cervix, ovary, and endometrium carcinomas.