Publications by authors named "Marcos Alves de Lima"

7 Publications

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Absolute telomere length in peripheral blood lymphocytes of workers exposed to construction environment.

Int J Environ Health Res 2022 Apr 24:1-9. Epub 2022 Apr 24.

Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil.

Construction environment is composed of various substances classified as carcinogens. Thus, workers exposed in this environment can be susceptible to genomic instability that can be evaluated by absolute telomere length (TL). In this work, we evaluated TL in construction workers compared to a non-exposed group performed by qPCR assay. The TL was evaluated in 59 men exposed to the construction environment (10 years of exposure) and 49 men non-exposed. Our data showed that individuals exposed to the construction environment exhibited a significantly lower TL in relation to non-exposed group ( = 0.009). Also, on the multiple linear regression model, we observed that TL was significantly influenced by the construction environment exposure ( ≤ 0.001). Additionally, the arsenic exposure is associated to a shortening telomere ( ≤ 0.001), and the lead exposure caused an increase in TL ( ≤ 0.001). Thus, our findings suggest a modulation in TL by construction environment exposure, mainly by arsenic and lead exposure.
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http://dx.doi.org/10.1080/09603123.2022.2066069DOI Listing
April 2022

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer.

Front Oncol 2021 17;11:729219. Epub 2021 Aug 17.

Department of Gynecologic Oncology, Barretos Cancer Hospital, Barretos, Brazil.

Background: The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer.

Methods: A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the , which contains 770 genes.

Results: The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: . The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%.

Conclusion: We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.
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http://dx.doi.org/10.3389/fonc.2021.729219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416164PMC
August 2021

Evaluation of acetylation and methylation in oral rinse of patients with head and neck cancer history exposed to valproic acid.

Sci Rep 2021 08 12;11(1):16415. Epub 2021 Aug 12.

Head and Neck Surgery Department, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Bairro Dr. Paulo Prata, Barretos, SP, 14784-400, Brazil.

Evaluate the biological action of valproic acid in the acetylation of histones and in the methylation of tumor suppressor genes via oral rinse in patients with a previous history of head and neck squamous cell carcinoma (HNSCC). Forty-two active or former smokers were included in this randomized, double-blind, placebo-controlled trial. Oral rinse samples were collected prior to treatment with valproic acid or placebo and after 90 days of treatment. The methylation status of five tumor suppressor genes and histone acetylation were evaluated by pyrosequencing and ELISA techniques, respectively. Differences between the 90-day and baseline oral rinse acetylation and methylation results were analyzed by comparing groups. Thirty-four patients were considered for analysis. The mean percentage adherence in the valproic and placebo groups was 93.4 and 93.0, respectively (p = 0.718). There was no statistically significant difference between groups when comparing the medians of the histone acetylation ratio and the methylation ratio for most of the studied genes. A significant reduction in the DCC methylation pattern was observed in the valproic group (p = 0.023). The use of valproic acid was safe and accompanied by good therapeutic adherence. DCC methylation was lower in the valproic acid group than in the placebo group.
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http://dx.doi.org/10.1038/s41598-021-95845-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361187PMC
August 2021

Squamous differentiation portends poor prognosis in low and intermediate-risk endometrioid endometrial cancer.

PLoS One 2019 10;14(10):e0220086. Epub 2019 Oct 10.

Department of Gynecologic Oncology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.

Background: Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer.

Methods: A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging.

Results: Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031).

Conclusion: Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220086PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786591PMC
March 2020

EGF+61 A>G polymorphism is not associated with lung cancer risk in the Brazilian population.

Mol Biol Rep 2019 Apr 19;46(2):2417-2425. Epub 2019 Feb 19.

Molecular Oncology Research Center, Barretos Cancer Hospital, Antenor Duarte Villela St, 1331, Barretos, SP, 14784-400, Brazil.

Epidermal growth factor (EGF) and its receptor (EGFR) play an important role in lung carcinogenesis. A functional single nucleotide polymorphism (SNP) in EGF promoter region (EGF+61 A>G-rs4444903) has been associated with cancer susceptibility. Yet, in lung cancer, the EGF+61 A>G role is unclear. The aim of this study was to evaluate the risk of lung cancer associated with EGF+61 A>G SNP in the Brazilian population. For that, 669 lung cancer patients and 1104 controls were analyzed. EGF+61 A>G genotype was assessed by PCR-RFLP and TaqMan genotyping assay. Both patients and controls were in Hardy-Weinberg equilibrium. As expected, uni- and multivariate analyses showed that tobacco consumption and age were significant risk factors for lung cancer. The genotype frequencies in lung cancer patients were 27.3% of AA, 47.4% of AG and 25.3% of GG, and for controls were 25.3% of AA, 51.6% of AG and 23.1% of GG. The allele frequencies were 51.1% of A and 48.9% of G for both cases and controls. No significant differences for the three genotypes (AA, AG and GG-codominant model) were observed between cases and controls. We then grouped AG and GG (recessive model) genotypes, as well as AA and AG (dominant model), and again, no significant differences were also found. This is the largest study to explore EGF+61 A>G polymorphism association with lung cancer risk and suggests that this SNP is not a risk factor for lung cancer in the Brazilian population.
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http://dx.doi.org/10.1007/s11033-019-04702-0DOI Listing
April 2019

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib.

Urol Oncol 2018 01 4;36(1):11.e13-11.e21. Epub 2017 Oct 4.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address:

Background: Renal cell carcinoma (RCC) represents 2%-3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib.

Objective: To study the expression of AXL in a series patients with of mRCC treated with sunitinib and to correlate it with patient's clinic-pathological features and therapeutic response.

Material And Methods: Sixty-four patients with mRCC (51 clear cell carcinomas (CCCs) and 13 non-CCCs) were evaluated for AXL expression by immunohistochemistry in the primary tumor.

Results: AXL positivity was observed in 47% (30/64) of cases, namely in 43% (22/51) of CCCs and 61% (8/13) of non-CCC. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, Karnofsky performance status, more than 1 site of metastasis and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Overall, the multivariate survival analysis showed that absence of nephrectomy (HR = 4.85, P = 0.001), more than 1 site of metastasis (HR = 2.99, P = 0.002), bone metastasis (HR = 2.95, P = 0.001), together with AXL expression (HR = 2.01, P = 0.048) were independent poor prognostic factor in patients with mRCC.

Conclusion: AXL expression was associated with worse clinical outcome and may be an important prognostic biomarker in sunitinib-treated patients with metastatic renal cell carcinoma.
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http://dx.doi.org/10.1016/j.urolonc.2017.09.003DOI Listing
January 2018

ITADE flap after mastectomy for locally advanced breast cancer: A good choice for mid-sized defects of the chest wall, based on a systematic review of thoracoabdominal flaps.

J Surg Oncol 2017 Jun 27;115(8):949-958. Epub 2017 Mar 27.

Center of Epidemiology and Statistics, Barretos Cancer Hospital, Pio XII Foundation, Barretos, São Paulo, Brazil.

Background: Locally advanced breast cancer (LABC) is still a common problem in developing countries. Extensive resections are aimed at local control and improving quality of life. Dermofat flaps are an option for medium-sized defects.

Objectives: Evaluate the results of a new thoracoabdominal flap (TAF).

Methods: We describe and evaluate an ipsilateral, thoracoabdominal horizontal, dermofat (ITADE) flap performed in patients submitted to mastectomy and immediate reconstruction. A systematic review of the flaps used in this situation was performed.

Results: A total of 23 patients underwent the ITADE flap. The average flap size was 360 cm . One (4.3%) patient presented extensive loss of the flap. In the literature review, we observed 354 patients with 159 TAFs. We added our cases to the evaluation. A significant reduction in the risk of necrosis using myocutaneous flaps versus TAFs was observed (P < 0.001). Comparing other TAFs and ITADE flaps, considering all necrosis, a significant difference was apparent (P = 0.02), which disappeared when evaluating only larger necrosis (P = 0.13). Multivariate analysis showed that the resected area was the best variable related to the presence of necrosis.

Conclusions: ITADE allows extensive coverage areas, an early start of adjuvant treatment and it can be performed without requiring a reconstructive team.
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http://dx.doi.org/10.1002/jso.24619DOI Listing
June 2017
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