20 results on '"Lopez RVM"'
Search Results
2. Prevalence of germline variants in Brazilian pancreatic carcinoma patients.
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Rodrigues LM, Maistro S, Katayama MLH, Rocha VM, Lopez RVM, Lopes EFDT, Gonçalves FT, Fridman C, Serio PAMP, Barros LRC, Leite LAS, Segatelli V, Estevez-Diz MDP, Guindalini RSC, Ribeiro Junior U, and Folgueira MAAK
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- Humans, Brazil epidemiology, Male, Middle Aged, Female, Aged, Cross-Sectional Studies, Adult, Prevalence, Aged, 80 and over, Adenocarcinoma genetics, Pancreatic Neoplasms genetics, Pancreatic Neoplasms epidemiology, Germ-Line Mutation, Genetic Predisposition to Disease
- Abstract
We evaluated the prevalence of pathogenic/likely pathogenic germline variants (PGV) in Brazilian pancreatic adenocarcinoma (PC) patients, that represent a multiethnic population, in a cross-sectional study. We included 192 PC patients unselected for family history of cancer. We evaluated a panel of 113 cancer genes, through genomic DNA sequencing and 46 ancestry-informative markers, through multiplex PCR. The median age was 61 years; 63.5% of the patients presented disease clinical stages III or IV; 8.3% reported personal history of cancer; 4.7% and 16.1% reported first-degree relatives with PC or breast and/or prostate cancer, respectively. Although the main ancestry was European, there was considerable genetic composition admixture. Twelve patients (6.25%) were PGV carriers in PC predisposition genes (ATM, BRCA1, BRCA2, CDKN2A, MSH2, PALB2) and another 25 (13.0%) were PGV carriers in genes with a limited association or not previously associated with PC (ACD, BLM, BRIP1, CHEK2, ERCC4, FANCA, FANCE, FANCM, GALNT12, MITF, MRE11, MUTYH, POLE, RAD51B, RAD51C, RECQL4, SDHA, TERF2IP). The most frequently affected genes were CHEK2, ATM and FANC. In tumor samples from PGV carriers in ACD, BRIP1, MRE11, POLE, SDHA, TERF2IP, which were examined through exome sequencing, the main single base substitutions (SBS) mutational signature was SBS1+5+18, probably associated with age, tobacco smoking and reactive oxygen species. SBS3 associated with homologous repair deficiency was also represented, but on a lower scale. There was no difference in the frequency of PGV carriers between: (a) patients with or without first-degree relatives with cancer; and (b) patients with admixed ancestry versus those with predominantly European ancestry. Furthermore, there was no difference in overall survival between PGV carriers and non-carriers. Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk., (© 2024. The Author(s).)
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- 2024
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3. Prospective Randomized Phase 2 Trial of Hypofractionated Stereotactic Radiation Therapy of 25 Gy in 5 Fractions Compared With 35 Gy in 5 Fractions in the Reirradiation of Recurrent Glioblastoma.
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Chen ATC, Serante AR, Ayres AS, Tonaki JO, Moreno RA, Shih H, Gattás GS, Lopez RVM, Dos Santos de Jesus GR, de Carvalho IT, Marotta RC, Marta GN, Feher O, Neto HS, Ribeiro ISN, Vasconcelos KGMDC, Figueiredo EG, and Weltman E
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- Humans, Middle Aged, Aged, Male, Female, Adult, Prospective Studies, Dose Fractionation, Radiation, Necrosis, Glioblastoma radiotherapy, Glioblastoma mortality, Glioblastoma surgery, Glioblastoma pathology, Radiation Dose Hypofractionation, Re-Irradiation adverse effects, Radiosurgery adverse effects, Radiosurgery methods, Neoplasm Recurrence, Local radiotherapy, Progression-Free Survival, Brain Neoplasms radiotherapy, Brain Neoplasms mortality, Brain Neoplasms pathology, Brain Neoplasms surgery
- Abstract
Purpose: The aim of this work was to investigate whether reirradiation of recurrent glioblastoma with hypofractionated stereotactic radiation therapy (HSRT) consisting of 35 Gy in 5 fractions (35 Gy/5 fx) compared with 25 Gy in 5 fractions (25 Gy/5 fx) improves outcomes while maintaining acceptable toxicity., Methods and Materials: We conducted a prospective randomized phase 2 trial involving patients with recurrent glioblastoma (per the 2007 and 2016 World Health Organization classification). A minimum interval from first radiation therapy of 5 months and gross tumor volume of 150 cc were required. Patients were randomized 1:1 to receive HSRT alone in 25 Gy/5 fx or 35 Gy/5 fx. The primary endpoint was progression-free survival (PFS). We used a randomized phase 2 screening design with a 2-sided α of 0.15 for the primary endpoint., Results: From 2011 to 2019, 40 patients were randomized and received HSRT, with 20 patients in each group. The median age was 50 years (range, 27-71); a new resection before HSRT was performed in 75% of patients. The median PFS was 4.9 months in the 25 Gy/5 fx group and 5.2 months in the 35 Gy/5 fx group (P = .23). Six-month PFS was similar at 40% (85% CI, 24%-55%) for both groups. The median overall survival (OS) was 9.2 months in the 25 Gy/5 fx group and 10 months in the 35 Gy/5 fx group (P = .201). Grade ≥3 necrosis was numerically higher in the 35 Gy/5 fx group (3 [16%] vs 1 [5%]), but the difference was not statistically significant (P = .267). In an exploratory analysis, median OS of patients who developed treatment-related necrosis was 14.1 months, and that of patients who did not was 8.7 months (P = .003)., Conclusions: HSRT alone with 35 Gy/5 fx was not superior to 25 Gy/5 fx in terms of PFS or OS. Due to a potential increase in the rate of clinically meaningful treatment-related necrosis, we suggest 25 Gy/5 fx as the standard dose in HSRT alone. During follow-up, attention should be given to differentiating tumor progression from potentially manageable complications., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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4. Loss of Caveolin-1 Expression in Tumor Cells is Associated with Increased Aggressiveness and Cell Invasion in Oral Squamous Cell Carcinoma.
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Nascimento RB, Paiva KBS, Risteli M, Silva LHS, Rodini CO, Rodrigues MFSD, De Cicco R, Lopez RVM, Salo TA, Nunes FD, and Xavier FCA
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- Humans, Squamous Cell Carcinoma of Head and Neck, Caveolin 1 genetics, Caveolin 1 metabolism, Epithelial-Mesenchymal Transition, RNA, Messenger, Cell Line, Tumor, Tumor Microenvironment, Mouth Neoplasms pathology, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms
- Abstract
Background: Changes in Caveolin-1 (CAV-1) expression are related to tumorigenesis. The aim of this study was to evaluate the role of CAV-1 in tumor progression in oral squamous cell carcinoma (SCC) tissue samples and the effect of CAV-1 silencing on two oral tongue SCC (OTSCC) cell lines (SCC-25, from a primary tumor, and HSC-3 from lymph node metastases)., Methods: Mycroarray hybridization, mRNA expression, and immunohistochemistry were performed on OSCC tissue samples and corresponding non-tumoral margin tissues. The effects of CAV-1 silencing (siCAV-1) on cell viability, membrane fluidity, on the expression of epithelial to mesenchymal transition (EMT) markers and on cell migration and invasion capacity of OTSCC cell lines were evaluated., Results: Microarray showed a greater CAV-1 expression (1.77-fold) in OSCC tumors than in non-tumoral tissues and 2.0-fold more in less aggressive OSCCs. However, significant differences in CAV-1 gene expression were not seen between tumors and non-tumoral margins nor CAV-1 with any clinicopathological parameters. CAV-1 protein was localized both in carcinoma and in spindle cells of the tumor microenvironment (TME), and CAV-1 positive TME cells were associated with smaller/more aggressive tumors, independent of the carcinoma cells' expression. Silencing of CAV-1 increased cell viability only in SCC-25 cells. It also stimulated the invasion of HSC-3 cells and increased ECAD and BCAT mRNA in these cells; however, the protein levels of the EMT markers were not affected., Conclusion: Decreased expression of CAV-1 by tumor cells in OSCC and an increase in the TME were associated with increased cell invasiveness and tumor aggressiveness., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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5. Erratum: METNET: a phase II trial of metformin in patients with well-differentiated neuroendocrine tumours.
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Glasberg J, Talans A, Giollo TR, Recchimuzzi DZ, Neto JEB, Lopez RVM, Hoff PMG, and Riechelmann RP
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[This corrects the article on p. 1 in vol. 16.]., (© the authors; licensee ecancermedicalscience.)
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- 2022
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6. ASO Author Reflections: Oncological Surgery during the COVID-19 Pandemic: Effectiveness of Preoperative Screening and Factors Associated with Postoperative SARS-CoV-2 Infection.
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Lopes A, Pastore CBP, Deckers P, Halla IKMW, Dias ALR, da Mata MVM, do Nascimento Martins A, Viu MM, Lopez RVM, and Yamada AD
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- Humans, Infection Control, Mass Screening, Pandemics prevention & control, SARS-CoV-2, COVID-19
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- 2022
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7. Oncological Surgery During the COVID-19 Pandemic: Effectiveness of Preoperative Screening and Factors Associated with Postoperative SARS-CoV-2 Infection.
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Lopes A, Pastore CBP, Deckers P, Halla IKMW, Dias ALR, da Mata MVM, do Nascimento Martins A, Viu MM, Lopez RVM, and Yamada AD
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- Cohort Studies, Humans, Pandemics, Prospective Studies, SARS-CoV-2, COVID-19 epidemiology
- Abstract
Background: Routine preoperative screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with reverse transcriptase-polymerase chain reaction (RT-PCR) may reduce in-hospital SARS-CoV-2 transmission., Methods: This was a prospective, observational, cohort study. The endpoints were the incidence of asymptomatic patients with positive preoperative RT-PCR results and the incidence and factors associated with postoperative SARS-CoV-2 infection in patients with cancer referred for elective surgery. Patients with elective surgery between May and October 2020 were included. RT-PCR of nasopharyngeal swabs was performed preoperatively for all patients. Postoperative SARS-CoV-2 infection was assessed within 30 postoperative days., Results: A total of 1636 preoperative screening RT-PCR tests were performed. Of these, 102 (6.2%) cases were positive, and 1,298 surgical procedures were analyzed. The postoperative SARS-CoV-2 infection rate was 0.9%. The length of stay (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.04-1.11; p < 0.001), surgical time (OR 1.004; 95% CI 1.001-1.008; p = 0.023), intensive care unit admission (OR 7.7; 95% CI 2.03-29.28; p = 0.003), and hospital readmissions (OR 9.56; 95% CI 2.50-36.56; p = 0.001) were associated with postoperative coronavirus disease (COVID-19). Using unadjusted and adjusted logistic regression, length of stay (OR 1.08; 95% CI 1.04-1.11; p < 0.001), and readmission (OR 9.02; 95% CI 2.30-35.48; p = 0.002) were independent factors of postoperative COVID-19., Conclusions: Screening patients preoperatively may reduce in-hospital SARS-CoV-2 transmission. Length of stay and readmission were independently correlated with postoperative COVID-19., (© 2021. Society of Surgical Oncology.)
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- 2022
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8. METNET: a phase II trial of metformin in patients with well-differentiated neuroendocrine tumours.
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Glasberg J, Talans A, Giollo TR, Recchimuzzi DZ, Neto JEB, Lopez RVM, Hoff PMG, and Riechelmann RP
- Abstract
Background: Preclinical studies have suggested that metformin has anti-tumour effects, likely due to blockage of mammalian target of rapamycin pathway through adenosine monophosphate-activated protein kinase and decreased insulin levels. A retrospective study showed that metformin added to everolimus to treat type 2 diabetes mellitus offered longer progression-free survival (PFS) in patients with pancreatic neuroendocrine tumours (NET)., Aims: To evaluate the efficacy and safety of metformin monotherapy in patients with advanced/metastatic well-differentiated NET (WD-NET) of gastroenteropancreatic (GEP) or pulmonary origin., Patients and Methods: Single-arm phase II trial of metformin 850 mg PO twice daily until progression or intolerance for patients with progressive metastatic well-differentiated GEP or pulmonary NET. The primary endpoint was disease control rate (DCR) by RECIST 1.1 at 6 months. Secondary endpoints were response rate, PFS, toxicity and variations in glycaemic profiles (glycaemia, glycated haemoglobin and peptide C and insulin) at baseline, at 30 and 90 days., Results: From 2014 to 2019, 28 patients were enrolled: median age was 50 years; 84% had non-functional NET, 86% were of GEP origin and 62% had G2 NET. At the time of last follow-up, 26 patients had progression, with 13 (46%) presenting DCR at 6 months and a median PFS of 6.3 months (95% confidence interval: 3.2-9.3). There was no objective response, but one patient with refractory carcinoid syndrome had complete symptom relief, lasting for more than 5 years. Variations in glycaemic profiles were not associated with DCR at 6 months. Diarrhoea was the most common adverse event, being grade 3 or 4 in 10% of the cases., Conclusion: Metformin monotherapy offers modest anti-tumour activity in well-differentiated GEP or lung NET., Competing Interests: R P Riechelmann: honoraria for lectures from Novartis. J Glasberg, A Talans, T Rivelli Giollo, D Zachello Recchimuzzi, J E Bezerra Neto, R V Mendonza Lopez and P M Gehm Hoff: none., (© the authors; licensee ecancermedicalscience.)
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- 2022
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9. Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs.
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de Paula Silva E, Marti LC, Andreghetto FM, de Sales RO, Hoberman M, Dos Santos Dias B, Diniz LFA, Dos Santos AM, Moyses RA, Curioni OA, Lopez RVM, Nunes FD, Tajara EH, and Severino P
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- Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms blood, Humans, MicroRNAs blood, Transcriptome, Dendritic Cells metabolism, Extracellular Vesicles genetics, Head and Neck Neoplasms genetics, MicroRNAs genetics
- Abstract
Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients' plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck., (© 2021. The Author(s).)
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- 2021
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10. Survival analysis of young adults from a Brazilian cohort of non-small cell lung cancer patients.
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Nicolau JS, Lopez RVM, de Moraes Luizaga CT, Ribeiro KB, Roela RA, Maistro S, Katayama MLH, Natalino RJM, de Castro G Jr, Neto JE, and Folgueira MAAK
- Abstract
Background: The influence of age at diagnosis in non-small cell lung cancer (NSCLC) prognosis is unclear., Objectives: To compare in a Brazilian cohort of NSCLC patients of different age groups: 1) The overall survival; 2) Clinical features and treatment options., Methods: This is a retrospective cohort study using a hospital-based registry, for NSCLC patients registered in years 2000-2009. Patients were grouped into three age groups: Young adults (YA: < 40 years), middle-aged (MA: 40-64 years) and elderly (E: ≥ 65 years). Kaplan-Meier was used to estimate overall survival and Cox regression for hazard ratios (HRs) and 95% confidence intervals., Results: 17,422 NSCLC patients were included: 370 YA (2.1%), 8,697 MA (49.9%) and 8,355 E (48.0%). Compared with older age groups, the YA group had a higher proportion of females, patients diagnosed with adenocarcinoma and metastatic disease (63.2%). Overall survival was longer in YA in the entire cohort and in all clinical stages (CSs) (p < 0.001). For YA, higher education level was a good prognosis factor (compared with illiterate and incomplete elementary); advanced or metastatic disease (compared with early-stage disease) and treatment based in radiotherapy or chemotherapy (CT) (without surgery), compared with treatment combinations with surgery, were poor prognostic factors. Young men (but not women) had lower HR of death compared with older groups; YA had lower HR of death in all CSs compared with patients from older groups. A higher percentage of YA were treated with surgery or CT in early-stage disease compared with older groups. Besides that, YA and MA patients treated with surgery or CT had a better prognosis than elderlies. Conclusions: In this Brazilian cohort of NSCLC patients, most young individuals were diagnosed with metastatic disease. YA presented longer survival than older age groups in all CSs, but mainly in CS I/II and III, where some patients may achieve long remissions or cure., Competing Interests: The authors declare no conflicts of interest., (© the authors; licensee ecancermedicalscience.)
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- 2021
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11. Role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high-grade serous ovarian carcinoma.
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Lopes A, Genta MLND, da Costa Miranda V, Aranha A, Lopez RVM, Piato DSAM, Anton C, Carvalho FM, Del Pilar Esteves Diz M, and Carvalho JP
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- Chemotherapy, Adjuvant, Cytoreduction Surgical Procedures, Female, Humans, Lymph Node Excision, Neoplasm Recurrence, Local, Neoplasm Staging, Retrospective Studies, Neoadjuvant Therapy, Ovarian Neoplasms drug therapy, Ovarian Neoplasms surgery
- Abstract
Introduction: We analyzed the role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high-grade serous ovarian carcinoma., Materials and Methods: We retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin-paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC-IVB high-grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin-paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression-free and overall survivals were analyzed using the Kaplan-Meier method., Results: Totally, 132 patients with FIGO IIIC-IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4-70.1) and 61.2 (21.4-101.0) months (p = 0.934); the corresponding disease-free survival was 8.1 (6.2-10.1) and 8.3 (5.1-11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence., Conclusions: Systematic lymphadenectomy after six NACT cycles may have no influence on survival., (© 2021 Japan Society of Obstetrics and Gynecology.)
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- 2021
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12. Survival trends of patients with oral and oropharyngeal cancer treated at a cancer center in São Paulo, Brazil.
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Kowalski LP, Oliveira MM, Lopez RVM, Silva DRME, Ikeda MK, and Curado MP
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- Adult, Aged, Aged, 80 and over, Brazil epidemiology, Carcinoma, Squamous Cell pathology, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mouth Neoplasms pathology, Neoplasm Staging, Oropharyngeal Neoplasms pathology, Prognosis, Proportional Hazards Models, Retrospective Studies, Survival Analysis, Carcinoma, Squamous Cell mortality, Mouth Neoplasms mortality, Oropharyngeal Neoplasms mortality
- Abstract
Objective: We aimed to estimate the overall survival (OS) and conditional survival (CS) in patients diagnosed with oral and oropharyngeal squamous cell carcinoma (SCC) and to determine their survival trends., Methods: The study included all consecutive patients treated at the A.C. Camargo Cancer Center for oral or oropharyngeal SCC between 2001 and 2012. Data were obtained from the Hospital Cancer Registry. OS and CS were analyzed using the Kaplan-Meier method to evaluate the probability of survival with Cox predictor models., Results: Data of 505 oral and 380 oropharyngeal SCC patients obtained in 2001-2006 and 2007-2012 were analyzed. Most of the oral SCC (59%) and oropharyngeal SCC (90%) patients had stages III-IV SCC. The 5-year OS for patients with oral SCC was 51.7%, with no significant difference between the first and second periods. The CS rates in 2007-2012 were 65% after the first year and 86% up to the fifth year. For oropharyngeal SCC, the 5-year OS rate was 45.0% in the first period. The survival rate increased to 49.1% from 2007 to 2012, with a reduction in the risk of death (HR=0.69;0.52-09.2). The CS estimates from 2007 to 2012 were 59% after the first year and 75% up to the fifth year., Conclusion: Survival across the two time periods remained stable for oral SCC but showed a significant increase for oropharyngeal SCC, possibly because of improvements in the patients' response to radiotherapy, such as intensity-modulated radiation therapy, and the use of more accurate diagnostic imaging approaches.
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- 2020
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13. The prognostic role of microRNA in epithelial ovarian cancer: a systematic review of literature with an overall survival meta-analysis.
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Ferreira P, Roela RA, Lopez RVM, and Del Pilar Estevez-Diz M
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Objective: To accomplish a systematic review of literature with overall survival meta-analysis about the role of microRNA in epithelial ovarian cancer as prognostic and predictive factor to chemotherapy response. Methods: A search was conducted in the PubMed database, using the keywords "microRNA" and "ovarian cancer" or "miRNA" and "ovarian cancer". Original articles published before 02/02/2019 that had as main subject microRNA (miRNA) and ovarian cancer were included. We considered for inclusion only studies that associated microRNA to chemotherapy-related diagnosis, prognosis, or response in ovarian cancer. Results: The literature search returned 1,482 articles, 497 of which fulfilled inclusion criteria, yielding 350 miRNAs. The status of each miRNA was assessed in serum and tissue of ovarian cancer, benign tumors, and healthy tissue. The status of up-/downregulation of miRNAs was related to prognostic features (overall survival and disease-free survival) and response predictive features such as platinum and paclitaxel sensitivity/resistance. The miRNAs that had been cited three or more times were selected for prognostic and response predictive features analysis. Twelve miRNAs fulfilled all these criteria and were included in the overall survival meta-analysis. Conclusions: miRNAs affect virtually all mechanisms of carcinogenesis, working as either oncogenes or tumor suppressor genes. In this systematic review we identified miRNAs that may be related to prognosis, diagnosis, and chemotherapy sensitivity. The 12 miRNAs identified here should be included in future studies for validation., Competing Interests: CONFLICTS OF INTEREST All the authors declare no conflicts of interest., (Copyright: © 2020 Ferreira et al.)
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- 2020
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14. Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes.
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Anton C, Kleine RT, Mayerhoff E, Diz MDPE, Freitas D, Carvalho HA, Carvalho JPM, Silva ASE, Genta MLND, Silva ALFE, Salim RC, Aranha A, Lopez RVM, Carvalho FM, Baracat EC, and Carvalho JP
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- Adult, Aged, Aged, 80 and over, Body Mass Index, Brazil, CA-125 Antigen blood, Carcinoma, Endometrioid blood, Carcinoma, Endometrioid pathology, Endometrial Neoplasms blood, Female, Humans, Lymphatic Metastasis pathology, Lymphatic Vessels pathology, Middle Aged, Neoplasm Staging methods, Prognosis, Proportional Hazards Models, Retrospective Studies, Endometrial Neoplasms pathology, Endometrium pathology
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Few reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian institution over a 10-year period.This retrospective study included 703 patients diagnosed with endometrial cancer who were treated at a public academic tertiary hospital between 2008 and 2018. The following parameters were analyzed: age at diagnosis, race, body mass index, serum CA125 level before treatment; histological type and grade, and surgical stage. Outcomes were reported relative to histological type, surgical staging, serum CA125, lymph-vascular space involvement (LVSI), and lymph-node metastasis. The median patient age at diagnosis was 63 (range, 27-93) years (6.4% were <50 years). Minimally invasive surgeries were performed in 523 patients (74.4%). Regarding histological grade, 468 patients (66.5%) had low-grade endometrioid histology and 449 patients (63.9%) had stage I tumors. Tumors exceeded 2.0 cm in 601 patients (85.5%). Lymphadenectomy was performed in 551 cases (78.4%). LVSI was present in 208 of the patients' tumors (29.5%). Ninety-three patients (13.2%) had recurrent tumors and 97 (13.7%) died from their malignant disease. The robust prognostic value of FIGO stage and lymph node status were confirmed. Other important survival predictors were histological grade and LVSI [overall survival: hazard ratio (HR) = 3.75, p < 0.001 and HR = 2.01, p = 0.001; recurrence: HR = 2.49, p = 0.004 and HR = 3.22, p = 0.001, respectively). Disease-free (p = 0.087) and overall survival (p = 0.368) did not differ significantly between patients with stage II and III disease. These results indicate that prognostic role of cervical involvement should be explored further. This study reports the characteristics and outcomes of endometrial cancer in a large population from a single institution, with systematic surgical staging, a predominance of minimally invasive procedures, and well-documented outcomes. Prognostic factors in the present study population were generally similar to those in other countries, though our patients' tumors were larger than in studies elsewhere due to later diagnosis. Our unexpected finding of similar prognoses of stage II and III patients raises questions about the prognostic value of cervical involvement and possible differences between carcinomas originating in the lower uterine segment versus those originating in the body and fundus. The present findings can be used to guide public policies aimed at improving the diagnosis and treatment of endometrial cancer in Brazil and other similar countries., Competing Interests: The authors have declared that no competing interests exist.
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- 2020
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15. Occupational exposure to organophosphate pesticides and hematologic neoplasms: a systematic review.
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Moura LTR, Bedor CNG, Lopez RVM, Santana VS, Rocha TMBDSD, Wünsch Filho V, and Curado MP
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- Humans, Risk Assessment, Risk Factors, Time Factors, Hematologic Neoplasms chemically induced, Occupational Exposure adverse effects, Organophosphate Poisoning complications, Pesticides poisoning
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Objective: To update findings of observational analytical studies on the association between occupational exposure to organophosphates and hematologic malignancies., Methodology: Systematic literature review, including cohort and case-control studies, without limitation of publication time, in Portuguese and English. The articles were traced from June 2017 to July 2019 in PubMed, MEDLINE, LILACS, Web of Science, and Scopus databases. The qualitative bias risk assessment was performed using the Newcastle-Ottawa Scale and the Downs and Black Checklist. Results were presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)., Results: Seventeen studies evaluated as good/high methodological quality were eligible. Exposure to diazinon (1 cohort), phonophos (1 cohort), dichlorvos, crotoxiphos and famphur (1 case control) was associated with leukemia, while exposure to organophosphate was associated to lymphomas (6 case control); the risk of non-Hodgkin's lymphoma was higher in those exposed to diazinon (1 control case) and malathion (3 control case) than non-exposed ones. Multiple myeloma occurred more commonly in organophosphate exposed than in non-exposed individuals (1 case-control)., Conclusion: Occupational exposure to organophosphates increases the risk of hematologic malignancies, especially among individuals with longer exposure periods. Worker monitoring and exposure control measures are recommended.
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- 2020
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16. The impact of the time to start radiation therapy on overall survival in newly diagnosed glioblastoma.
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Santos VM, Marta GN, Mesquita MC, Lopez RVM, Cavalcante ER, and Feher O
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- Adult, Aged, Brain Neoplasms diagnosis, Brain Neoplasms surgery, Chemoradiotherapy, Female, Follow-Up Studies, Glioblastoma diagnosis, Glioblastoma surgery, Humans, Male, Middle Aged, Retrospective Studies, Survival Analysis, Time-to-Treatment, Treatment Outcome, Young Adult, Brain Neoplasms mortality, Brain Neoplasms radiotherapy, Glioblastoma mortality, Glioblastoma radiotherapy
- Abstract
Purpose: The standard treatment for newly diagnosed glioblastoma includes maximal safe surgical resection followed by concurrent radiation therapy and temozolomide (TMZ) and maintenance TMZ. The impact of time to start radiation therapy (TRT) on overall survival (OS) in glioblastoma patients is controversial. The study aimed to evaluate the impact of TRT on OS in patients diagnosed with glioblastoma who received standard treatment., Methods: In this retrospective study, we included patients with confirmed diagnosis of glioblastoma treated from 2011 to 2016. TRT was defined as the time between surgery (biopsy or resection) and the first day of radiation therapy. The endpoint was OS. The patients were divided according to the TRT in three categories: < 30 days, 30-60 days and ≥ 60 days., Results: A total of 134 patients were included with a mean age of 51.82 years (range 19-78 years). Median TRT was 80 days. On univariate and multivariable analysis, we identified age as the only significant independent predictor for OS. There was no statistically significant negative impact of TRT on OS (p = 0.47)., Conclusions: There was no clear evidence that delaying post-operative combined chemoradiotherapy negatively impacts OS, not even for TRT longer than 60 days.
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- 2019
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17. Comparison of 68Ga PET/CT to Other Imaging Studies in Medullary Thyroid Cancer: Superiority in Detecting Bone Metastases.
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Castroneves LA, Coura Filho G, de Freitas RMC, Salles R, Moyses RA, Lopez RVM, Pereira MAA, Tavares MR, Jorge AAL, Buchpiguel CA, and Hoff AO
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- Adult, Aged, Female, Gallium Radioisotopes, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organometallic Compounds, Positron Emission Tomography Computed Tomography methods, Prospective Studies, Sensitivity and Specificity, Ultrasonography, Young Adult, Bone Neoplasms diagnostic imaging, Bone Neoplasms secondary, Carcinoma, Neuroendocrine diagnostic imaging, Carcinoma, Neuroendocrine secondary, Thyroid Neoplasms diagnostic imaging, Thyroid Neoplasms secondary
- Abstract
Context: Persistent disease after surgery is common in medullary thyroid cancer (MTC), requiring lifelong radiological surveillance. Staging workup includes imaging of neck, chest, abdomen, and bones. A study integrating all sites would be ideal. Despite the established use of gallium-68 (68Ga) positron emission tomography (PET)/CT with somatostatin analogues in most neuroendocrine tumors, its efficacy is controversial in MTC., Objective: Evaluate the efficacy of 68Ga PET/CT in detecting MTC lesions and evaluate tumor expression of somatostatin receptors (SSTRs) associated with 68Ga PET/CT findings., Methods: Prospective study evaluating 30 patients with MTC [group 1 (n = 16), biochemical disease; group 2 (n = 14), metastatic disease]. Patients underwent 68Ga PET/CT, bone scan, CT and ultrasound of the neck, CT of the chest, CT/MRI of the abdomen, and MRI of the spine. 68Ga PET/CT findings were analyzed by disease site as positive or negative and as concordant or discordant with conventional studies. Sensitivity and specificity were calculated using pathological or cytological analysis or unequivocal identification by standard imaging studies. Immunohistochemical analysis of SSTRs was compared with 68Ga PET/CT findings., Results: In both groups, 68Ga PET/CT was inferior to currently used imaging studies except for bone scan. In group 2, 68Ga PET/CT sensitivities were 56%, 57%, and 9% for detecting neck lymph nodes, lung metastases, and liver metastases, respectively, and 100% for bone metastases, superior to the bone scan (44%). Expression of SSTRs, observed in 44% of tumors, was not associated with 68Ga-DOTATATE uptake., Conclusions: 68Ga PET/CT does not provide optimal whole-body imaging as a single procedure in patients with MTC. However, it is highly sensitive in detecting bone lesions and could be a substitute for a bone scan and MRI.
- Published
- 2018
- Full Text
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18. JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and oropharyngeal squamous cell carcinoma.
- Author
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Maia LL, Peterle GT, Dos Santos M, Trivilin LO, Mendes SO, de Oliveira MM, Dos Santos JG, Stur E, Agostini LP, Couto CVMDS, Dalbó J, de Assis ALEM, Archanjo AB, Mercante AMDC, Lopez RVM, Nunes FD, de Carvalho MB, Tajara EH, Louro ID, and Álvares-da-Silva AM
- Subjects
- Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell surgery, Epigenesis, Genetic, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis, Male, Middle Aged, Mouth Neoplasms metabolism, Mouth Neoplasms surgery, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Oropharyngeal Neoplasms metabolism, Oropharyngeal Neoplasms surgery, Prognosis, Survival Rate, Adrenomedullin metabolism, Biomarkers, Tumor metabolism, Carcinoma, Squamous Cell secondary, Histones metabolism, Jumonji Domain-Containing Histone Demethylases metabolism, Mouth Neoplasms pathology, Oropharyngeal Neoplasms pathology
- Abstract
Aims: Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono-methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9 (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A and ADM expression, as well as H3K9 methylation level have been related with development risk and prognosis of several tumor types., Methods and Results: We aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples through immunohistochemistry analysis. Our results showed that nuclear JMJD1A expression was related to lymph node metastasis risk. In addition, JMJD1A cytoplasmic expression was an independent risk marker for advanced tumor stages. H3K9me1 cytoplasmic expression was associated with reduced disease-specific death risk. Furthermore, high H3K9me2 nuclear expression was associated with worse specific-disease and disease-free survival. Finally, high ADM cytoplasmic expression was an independent marker of lymph node metastasis risk., Conclusion: JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and prognosis in oral and oropharynx cancer patients, as well as putative therapeutic targets.
- Published
- 2018
- Full Text
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19. Quality of life in a sample of Brazilian adults using the generic SF-12 questionnaire.
- Author
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Campolina AG, Lopez RVM, Nardi EP, and Ferraz MB
- Subjects
- Adolescent, Adult, Aged, Brazil, Female, Humans, Male, Middle Aged, Sampling Studies, Socioeconomic Factors, Urban Population statistics & numerical data, Young Adult, Health Surveys statistics & numerical data, Quality of Life
- Abstract
Objective: This study describes the summary scores of the Short Form-12 (SF-12) questionnaire, according to socio-demographic factors obtained in a probabilistic and representative sample of the Brazilian urban population., Method: Five thousand (5,000) individuals, over the age of 15, were assessed in 16 capital cities, in the five regions of the country. The selection of households was random. Face-to-face approach was applied in the household interviews. The SF-12 questionnaire was used to assess quality of life. Demographic and socioeconomic characteristics were also evaluated: gender, age, marital status, skin color, region of the country and use of the public health service., Results: The mean value (SD) of the SF-12 for the entire population was 49.3 (8.7) for the physical component (PCS-12) and 52.7 (9.7) for the mental component (MCS-12). Statistical differences were found for gender (PCS-12 and MCS-12), age (PCS-12) and working status (PCS-12 and MCS-12). Women, elderly, widowed and unemployed individuals, those with lower income and with complaints in the last seven days showed lower mean values (PCS-12 and MCS-12)., Conclusion: From this point forward, we can provide the basis for comparisons with future research that use the SF-12 for quality of life assessment in Brazil. The Brazilian population has a lower degree of quality of life related do the physical component, and the SF-12 is a useful and discriminative instrument for assessing quality of life in different socio-demographic groups.
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- 2018
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20. Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils.
- Author
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Alvarez KLF, Beldi M, Sarmanho F, Rossetti RAM, Silveira CRF, Mota GR, Andreoli MA, Caruso EDC, Kamillos MF, Souza AM, Mastrocalla H, Clavijo-Salomon MA, Barbuto JAM, Lorenzi NP, Longatto-Filho A, Baracat E, Lopez RVM, Villa LL, Tacla M, and Lepique AP
- Subjects
- Adult, Aged, Aged, 80 and over, Dendritic Cells immunology, Female, Humans, Macrophages immunology, Middle Aged, Papillomavirus Infections complications, T-Lymphocytes immunology, Young Adult, Granulocyte Colony-Stimulating Factor blood, Immune Evasion, Neutrophils immunology, Papillomaviridae immunology, Papillomavirus Infections pathology, Uterine Cervical Neoplasms pathology
- Abstract
Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.
- Published
- 2017
- Full Text
- View/download PDF
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