SHEILA APARECIDA COELHO SIQUEIRA

(Fonte: Lattes)
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Lattes
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina

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Assunto: Oncology ×

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  • conferenceObject
    Expression of ERCC1 protein (excision repair cross complementing group 1) in patients with invasive carcinoma of the uterine cervix (CC) undergoing definitive chemoradiation (CR)
    (2012) CAIRES, Inacelli Queiroz de Souza; CAIRES-LIMA, Rafael; COLOMBO, Renata; RAMOS, Clarissa C. A.; MACHADO, Karime Kalil; SIQUEIRA, Sheila Aparecida Coelho; CARVALHO, Heloisa de Andrade; FUKUSHIMA, Julia Tizue; ADRA, Thais Rodrigues; HOFF, Paulo M.; ESTEVEZ-DIZ, Maria Del Pilar
    Background: CC is the leading cause of cancer death among women in developing countries. ERCC1 protein participates in DNA repair through the nucleotide excision repair pathway, involved in resistance to platinum-based chemotherapy. Its value as a predictive marker of tumor response to treatment, progression or death is still unknown. We evaluated ERCC1 protein expression and clinical variables as a predictive marker of progression-free survival (PFS) and overall survival (OS) in patients (pts) with CC submitted to CR. Methods: Retrospective data analysis of pts with histological diagnosis of CC, treated with CR between 2004-2009. Platinum-based chemotherapy was administered weekly (x6) concurrent to external beam radiotherapy (EBRT) to the pelvis (39.6 – 45.0 Gy), parametrial boost (14.0 – 20.0 Gy) when indicated and high-dose rate brachytherapy (HDR) (28.0 – 30.0 Gy). ERCC1 expression was assessed by immunohistochemistry (IHC). Results: We analyzed 75 pts, median age was 55 years (range 24-76), the performance status (PS) was 0 or 1 at baseline in 50 pts (66%) and 63 had squamous histology (84%). Thirty-two were stage IIB (43%) and 19 were IIIB (25%). Sixty-five patients received cisplatin 40mg/m2/w (87%) and 9, carboplatin AUC2/w (12%), median of 6 cycles (range 2-9). Median RT and HDR doses were 59.4 Gy (range 40.4 to 60.3) and 28.0 Gy (range 14.0 – 37.5), respectively. Thirty-two pts were available by ERCC1 IHC and all expressed the marker. Median PFS and OS were 35.5 (95% CI – 13.8 - 57.6) and 81 (95% CI- 21.2 - 140.8) months, respectively. In multivariate analysis, receiving < 6 chemotherapy cycles and baseline Hb <10.0 were correlated with disease progression and death, HR 0.302; p 0.011 (95% CI- 0.012-0.762) and HR 0.6; p 0.00 (95% CI- 0.474 – 0.760), respectively. PS at baseline did not correlate with PFS or OS, HR 0.985; p 0.614 (95% CI 0.930 – 1.044). Conclusions: In this population, since all pts expressed the protein, ERCC1 expression couldn't discriminate patients who most benefit from CR. Interestingly, a minimum of 6 chemotherapy cycles and a baseline Hb ≥ 10.0 seem to have a prognostic value.
  • article 2 Citação(ões) na Scopus
    Angioimmunoblastic T-cell lymphoma and correlated neoplasms with T-cell follicular helper phenotype: from molecular mechanisms to therapeutic advances
    (2023) LAGE, Luis Alberto de Padua Covas; CULLER, Hebert Fabricio; REICHERT, Cadiele Oliana; SIQUEIRA, Sheila Aparecida Coelho da; PEREIRA, Juliana
    Angioimmunoblastic T-cell lymphoma (AITL) is the second most frequent subtype of mature T-cell lymphoma (MTCL) in the Western world. It derives from the monoclonal proliferation of T-follicular helper (TFH) cells and is characterized by an exacerbated inflammatory response and immune dysregulation, with predisposition to autoimmunity phenomena and recurrent infections. Its genesis is based on a multistep integrative model, where age-related and initiator mutations involve epigenetic regulatory genes, such as TET-2 and DNMT3A. Subsequently, driver-mutations, such as RhoA G17V and IDH-2 R172K/S promote the expansion of clonal TFH-cells (""second-hit""), that finally begin to secrete cytokines and chemokines, such as IL-6, IL-21, CXCL-13 and VEGF, modulating a network of complex relationships between TFH-cells and a defective tumor microenvironment (TME), characterized by expansion of follicular dendritic cells (FDC), vessels and EBV-positive immunoblasts. This unique pathogenesis leads to peculiar clinical manifestations, generating the so-called ""immunodysplastic syndrome"", typical of AITL. Its differential diagnosis is broad, involving viral infections, collagenosis and adverse drug reactions, which led many authors to use the term ""many-faced lymphoma"" when referring to AITL. Although great advances in its biological knowledge have been obtained in the last two decades, its treatment is still an unmet medical need, with highly reserved clinical outcomes. Outside the setting of clinical trials, AITL patients are still treated with multidrug therapy based on anthracyclines (CHOP-like), followed by up-front consolidation with autologous stem cell transplantation (ASCT). In this setting, the estimated 5-year overall survival (OS) is around 30-40%. New drugs, such as hypomethylating agents (HMAs) and histone deacetylase inhibitors (HDAi), have been used for relapsed/refractory (R/R) disease with promising results. Such agents have their use based on a biological rationale, have significant potential to improve the outcomes of patients with AITL and may represent a paradigm shift in the therapeutic approach to this lymphoma in the near future.
  • article 5 Citação(ões) na Scopus
    Cardiac Tamponade as the First Manifestation of Erdheim-Chester Disease
    (2020) COSTA, Isabela B. S. da S.; COSTA, Fernanda A. de S.; BITTAR, Cristina S.; RIZK, Stephanie I.; ABDO, Andre N. R.; SIQUEIRA, Sheila A. C.; ROCHA, Vanderson; PEREIRA, Juliana; KY, Bonnie; HAJJAR, Ludhmila A.
  • article 3 Citação(ões) na Scopus
    Dealing with bone marrow biopsies in the staging of classical Hodgkin lymphoma: an old issue revisited in the F-18-fluorodeoxyglucose-positron emission tomography era
    (2015) GONCALVES, Marianne de Castro; PAULA, Henrique Moura de; LINARDI, Camila da Cruz Gouveia; CERCI, Juliano J.; ALDRED, Vera Lucia; SIQUEIRA, Sheila Aparecida Coelho; BUCCHERI, Valeria; ZERBINI, Maria Claudia Nogueira
    Bone marrow biopsy is recommended for staging of classical Hodgkin lymphoma. The aim of this study was to compare bone marrow evaluation by histology with that obtained by F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET). One hundred and three cases of Classical Hodgkin Lymphoma were reviewed. All patients were submitted to FDG-PET evaluation. Bone marrow biopsy results were compared with clinical data and FDG-PET results. Ninety-one cases had available bone marrow biopsies. Overall, there were 16 positive and one suspect case. In five cases, the FDG-PET scan was positive and biopsy was negative: 1/5 was found to correspond to a bone fracture, 3/5 showed marked reactive bone marrow changes and in 1/5 no explanation for the discrepancy was found. FDG-PET showed high sensitivity, supporting the idea that when it is negative, biopsy could be avoided. Care should be taken in patients with a positive FDG-PET, where confirmation by bone marrow biopsy should be recommended.
  • conferenceObject
    ERCC1 AND BETA-TUBULIN III IN ADVANCED NSCLC PATIENTS TREATED WITH CISPLATIN-VINORELBINE
    (2012) CASTRO JR., G. de; VICTOR, C. R.; BIGATON, F. J.; TAKAHASHI, T. K.; FEHER, O.; SABER, A. M. Ab'; TAKAGAKI, T. Y.; SIQUEIRA, S. A. C.; CHAMMAS, R.; HOFF, P. M. G.
    Background: Platinum-containing chemotherapy remains as the standard treatment in advanced/metastatic non-small-cell lung cancer (NSC LC) patients (pts). Increased ERCC 1 expression has been associated with resistance to platinum-based therapies, and beta-tubulin III (TUBB 3) was shown to be involved in resistance to antimicrotubule agents. Here we studied these tumor markers in NSC LC pts treated with cisplatin-vinorelbine and correlated their expression with survival. Methods: It is a retrospective study on pts diagnosed with advanced/metastatic NSC LC (TNM 6th ed), consecutively identified. All pts were treated with cisplatin 80 mg/m2 d1 and vinorelbine 30 mg/m2 d1, d8, d15, every 21 days, 4–6 cycles, in our Institution, between Sep/2002 and Oct/2008. ERCC 1 (clone 8F1) and TUBB 3 (clone TUJ1) expression were evaluated by immunohistochemistry, and biomarker expression was considered as high when more than 10% of tumor cells presented moderate to strong staining, nuclear or cytoplasmic, respectively. Overall survival (OS) was estimated by the Kaplan-Meier method and curves were compared with log-rank. Results: 142 pts were studied; median age 63 y (34-87), 67% male and 86% current smokers. Adenocarcinoma (ADC, 58 pts, 43%), followed by squamous cell carcinoma (SCC , 50 pts, 37%) were the most frequent histologic types. 100 pts (71%) were staged as IV and 34 pts (24%) as IIIB. The median number of cycles was 4 (1-7). Median OS was 7.9 mo. Overall, high ERCC 1 expression was observed in 61/104 pts (59%) and high TUBB 3 expression in 55/109 pts (51%). According to histologic types, low ERCC 1 expression was observed in 7/42 SCC pts (16%) and in 35/63 ADC pts (56%) (p=0.0004). Among ADC pts, 1-y OS rate was 28% and 47% in pts which tumors presented with high and low ERCC 1 expression, respectively (HR 1.57, 95% CI 0.9-2.7, p=0.08). TUBB 3 expression neither presented any difference between SCC and ADC types, nor any prognostic impact in terms of OS. Conclusions: Low ERCC 1 expression was observed more frequently in pts with advanced lung ADC and it was a favorable prognostic factor in ADC pts treated with cisplatin-vinorelbine.
  • article 33 Citação(ões) na Scopus
    ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation
    (2011) CASTRO JR., Gilberto De; PASINI, Fatima Solange; SIQUEIRA, Sheila Aparecida Coelho; FERRAZ, Alberto Rossetti; VILLAR, Rosangela Correa; SNITCOVSKY, Igor Moyses Longo; FEDERICO, Miriam Hatsue Honda
    Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T 19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T 19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.
  • conferenceObject
    EGFR GENOTYPING AND EPIDEMIOLOGY, CLINICAL AND PATHOLOGICAL FEATURES IN 191 PATIENTS WITH METASTATIC PULMONARY ADENOCARCINOMA IN SAO PAULO - BRAZIL.
    (2013) CASTRO JR., Gilberto; TAKAHASHI, Tiago K.; CAIRES-LIMA, Rafael; PROTASIO, Bruno M.; MAIA, Manuel C. D. F.; SOARES, Ibere C.; ROITBERG, Felipe S. R.; MARINI, Andrea M.; MARTINS, Renata E.; TAKAGAKI, Teresa Y.; ARAUJO, Pedro H. X. N.; TERRA, Ricardo M.; SHIANG, Christina; SIQUEIRA, Sheila A. C.; MELLO, Evandro S.; ALVES, Venancio A.; HOFF, Paulo M.
  • article 5 Citação(ões) na Scopus
    High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on TP53
    (2020) BRONDANI, Vania Balderrama; MONTENEGRO, Luciana; LACOMBE, Amanda Meneses Ferreira; MAGALHAES, Breno Marchiori; NISHI, Mirian Yumie; FUNARI, Mariana Ferreira de Assis; NARCIZO, Amanda de Moraes; CARDOSO, Lais Cavalca; SIQUEIRA, Sheila Aparecida Coelho; ZERBINI, Maria Claudia Nogueira; DENES, Francisco Tibor; LATRONICO, Ana Claudia; MENDONCA, Berenice Bilharinho; ALMEIDA, Madson Queiroz; LERARIO, Antonio Marcondes; SOARES, Ibere Cauduro; FRAGOSO, Maria Candida Barisson Villares
    Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific TP53 germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for theMMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the TP53 p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the MMR genes (two in MLH1 and one in MSH6). The prevalence of alteredMMR genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome.
  • article 7 Citação(ões) na Scopus
    Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers
    (2020) MAK, Milena Perez; PASINI, Fatima Solange; DIAO, Lixia; GARCIA, Fabyane O. Teixeira; TAKAHASHI, Tiago Kenji; NAKAZOTO, Denyei; MARTINS, Renata Eiras; ALMEIDA, Cristiane Maria; KULCSAR, Marco Aurelio Vamondes; LAMOUNIER, Valdelania Aparecida; NUNES, Emily Montosa; SOUZA, Isabela Cristina de; GARCIA, Marcio Ricardo Taveira; AMADIO, Alex Vieira; SIQUEIRA, Sheila Aparecida C.; SNITCOVSKY, Igor Moyses Longo; SICHERO, Laura; WANG, Jing; JR, Gilberto de Castro
    Background: Cisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) and associated biomarkers. Methods: This phase II trial included patients with unresectable locally advanced (LA) oropharynx (OP) squamous cell carcinoma. CCRT began after 2 weeks of VPA (P1). Primary goal was RR at 8 weeks after chemoradiation (CRT)+VPA (P2). Biomarkers included microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared to healthy controls by two-sample t-test. Distribution of p-values was analysed by beta-uniform mixture. Findings were validated by real-time PCR quantitative polymerase chain reaction (qPCR) for selected miRs in plasma and saliva. p16, HDAC2 and RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry were evaluated. Results: Given significant toxicities, accrual was interrupted after inclusion of ten LA p16 negative OP patients. All were male, smokers/ex-smokers, aged 41-65 and with previous moderate/high alcohol intake. Nine evaluable patients yielded a RR of 88%. At false discovery rate of 5%, 169 miRs were differentially expressed between patients and controls, including lower expression of tumour suppressors (TSs) such as miR-31, -222, -let-7a/b/e and -145. miR-let-7a/e expression was validated by qPCR using saliva. A HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease-free survival. Conclusions: VPA and CRT offered high RR; however, with prohibitive toxicities, which led to early trial termination. Patients and controls had a distinct pattern of miR expression, mainly with low levels of TS miRs targeting Tumor protein P53 (TP53). miR-let-7a/e levels were lower in patients compared to controls, which reinforces the aggressive nature of such tumours (NCT01695122).
  • article 0 Citação(ões) na Scopus
    Up-Front ASCT Overcomes the Survival Benefit Provided by HDAC-Based Induction Regimens in Mantle Cell Lymphoma: Data from a Real-Life and Long-Term Cohort
    (2023) LAGE, Luis Alberto de Padua Covas; ELIAS, Marcela do Vale; REICHERT, Cadiele Oliana; CULLER, Hebert Fabricio; FREITAS, Fabio Alessandro de; COSTA, Renata de Oliveira; ROCHA, Vanderson; SIQUEIRA, Sheila Aparecida Coelho da; PEREIRA, Juliana
    Simple Summary This study aimed to assess clinical outcomes, determine survival predictors, and compare responses between different primary therapeutic modalities in a large real-world cohort of patients with mantle cell lymphoma (MCL), with a focus on assessing the impact of intensified immunochemotherapy regimens based on high doses of cytarabine (HDAC) on outcomes in ASCT-eligible patients. A total of 165 Brazilian patients with biopsy-proven MCL were included from 2010 to 2022. After a long follow-up, our results demonstrated that patients treated with (R)-HDAC-based regimens had higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those treated with (R)-CHOP, as well as lower rates of early relapses (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, enhanced induction regimens employing (R)-HDAC were not associated with a real overall survival benefit in MCL patients undergoing ASCT (2-year OS: 88.7% for (R)-HDAC plus ASCT vs. 78.8% for (R)-CHOP plus ASCT, p = 0.289). Additionally, up-front ASCT was independently associated with improvement in OS (p < 0.001), EFS (p = 0.005), and POD-24 (p < 0.001) in MCL. In conclusion, in the largest real-world Latin American study involving MCL patients, we were able to ratify the benefit of up-front ASCT in young and physically fit patients regardless of the intensity of the induction immunochemotherapy regimen used. Although HDAC-based induction regimens were not associated with improved survival in ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses in the whole cohort. These findings can decisively impact the therapeutic management of MCL patients in different clinical settings.Abstract Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. Results: The median age at diagnosis was 65 years (38-89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky >= 7 cm, B-symptoms, ECOG >= 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.