Browsing by Author "Araujo, JM"

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Adjuvant chemotherapy after curative D2 gastrectomy in Latin American patients with gastric cancer
(ecancer Global Foundation, 2022) Serrano, M; Araujo, JM; Pacheco-Román, C; Macetas, J; Blum, MA; Carrato, A; Ruiz-Figueroa, E; Berrospi-Espinoza, F; Luque Vasquez, C; Chavez-Pasiuri, IK; Payet-Meza, ET; Taxa-Rojas, L; Montenegro, P
Background: Gastric cancer (GC) is the fourth most common cause of cancer deaths around the world and the first cause of cancer deaths in Peru
Chip-based digital Polymerase Chain Reaction as quantitative technique for the detection of PIK3CA mutations in breast cancer patients
(Elsevier Ltd, 2022) Giannoni-Luza, S; Acosta, O; Murillo Carrasco, AG; Danos, P; Cotrina Concha, JM; Guerra Miller, H; Pinto, JA; Aguilar, A; Araujo, JM; Fujita, R; Buleje, J
Background: PIK3CA is a gene frequently mutated in breast cancer. With the FDA approval of alpelisib, the evaluation of PIK3CA for activating mutations is becoming routinely. Novel platforms for gene analysis as digital PCR (dPCR) are emerging as a potential replacement for the traditional Sanger sequencing. However, there are still few studies on chip-based dPCR to detect mutations in tumor samples. Thus, this cross-sectional study aimed to assess the sensibility of a chip-based dPCR to detect and quantify PIK3CA mutations and compare its performance with Sanger sequencing. Materials and Methods: Tumor samples from 57 breast cancer patients (22 pre-treatment samples, 32 tumors after neoadjuvant chemotherapy, and three lymph nodes) were collected and analyzed by Sanger sequencing and dPCR for the three PIK3CA most relevant mutations (p.E545K, p. H1047R, and p. H1047L). Digital PCR sensitivity, specificity, and overall performance were estimated by contingency tables, receptor operator characteristic (ROC), and area under the curve (AUC). Association of PIK3CA mutations with clinicopathological variables was conducted. Results: Sanger sequencing identified PIK3CA mutations in six patients (10.5%), two with p. H1047R, and four with p. E545K. Digital PCR confirmed those mutations and identified 19 additional patients with at least one mutation. Comparison between dPCR and Sanger sequencing showed a sensitivity of 100% (95% CI 53–100%), and a specificity of 84.2% (95% CI 83–84.2%). Besides, p. H1047R mutation detected by dPCR showed a significant association with breast cancer phenotype (p = 0.019) and lymphatic nodes infiltration (p = 0.046). Conclusions: Digital PCR showed a high sensitivity to detect mutations in tumor samples and it might be capable to detect low-rate mutations and tumor subpopulations not detected by Sanger sequencing. © 2022 The Author(s)
Effect of CCL5 expression in the recruitment of immune cells in triple negative breast cancer
(Nature Publishing Group, 2018) Araujo, JM; Gomez, AC; Aguilar, A; Salgado, R; Balko, JM; Bravo, L; Doimi, F; Bretel, D; Morante, Z; Flores, C; Gomez, HL; Pinto, JA
Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine's expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150-0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.
PIK3CA mutation in non-metastatic triple-negative breast cancer as a potential biomarker of early relapse: A case report
(Baishideng Publishing Group, 2021) Valencia, GA; Rioja, P; Morante, Z; Araujo, JM; Vallejos, HD; Guerra, H; Gomez, Henry L
Background: Currently, the detection of PIK3CA mutations is of special interest in personalized medicine because it is frequently found in triple-negative breast cancer (TNBC). The PI3KCA mutation is an independent negative prognostic factor for survival in metastatic breast cancer, and its prognostic value in liquid biopsy as a biomarker of treatment and early relapse is under investigation, both for metastatic disease and neoadjuvant scenario with curative intent. Case summary: A 54-year-old female patient with TNBC clinical stage IIIA, who, after receiving neoadjuvant chemotherapy (based on anthracyclines and taxanes), surgery, radiotherapy, and adjuvant capecitabine, was detected with a PI3KCA mutation in tissue and peripheral blood (ctDNA in liquid biopsy). After 10 mo, the patient had disease relapse of left cervical node disease. Conclusion: The detection of PIK3CA mutation in TNBC after neoadjuvant treatment might be associated with early relapse or rapid disease progression.
Promoter hypermethylation of RARB and GSTP1 genes in plasma cell-free DNA as breast cancer biomarkers in Peruvian women
(John Wiley and Sons Inc, 2023) Danos, P; Giannoni-Luza, S; Murillo-Carrasco, AG; Acosta, O; Guevara-Fujita, ML; Cotrina-Concha, JM; Guerra-Miller, H; Pinto-Oblitas, J; Aguilar-Cartagena, A; Araujo, JM; Fujita, R; Buleje-Sono, JL
Background: Promoter hypermethylation is one of the enabling mechanisms of hallmarks of cancer. Tumor suppressor genes like RARB and GSTP1 have been reported as hypermethylated in breast cancer tumors compared with normal tissues in several populations. This case–control study aimed to determine the association between the promoter methylation ratio (PMR) of RARB and GSTP1 genes (separately and as a group) with breast cancer and its clinical-pathological variables in Peruvian patients, using a liquid biopsy approach. Methods: A total of 58 breast cancer patients and 58 healthy controls, matched by age, participated in the study. We exacted cell-free DNA (cfDNA) from blood plasma and converted it by bisulfite salts. Methylight PCR was performed to obtain the PMR value of the studied genes. We determined the association between PMR and breast cancer, in addition to other clinicopathological variables. The sensitivity and specificity of the PMR of these genes were obtained. Results: A significant association was not found between breast cancer and the RARB PMR (OR = 1.90; 95% CI [0.62–6.18]; p = 0.210) or the GSTP1 PMR (OR = 6.57; 95% CI [0.75–307.66]; p = 0.114). The combination of the RARB + GSTP1 PMR was associated with breast cancer (OR = 2.81; 95% CI [1.02–8.22]; p = 0.026), controls under 50 years old (p = 0.048), patients older than 50 (p = 0.007), and postmenopausal (p = 0.034). The PMR of both genes showed a specificity of 86.21% and a sensitivity of 31.03%. Conclusion: Promoter hypermethylation of RARB + GSTP1 genes is associated with breast cancer, older age, and postmenopausal Peruvian patients. The methylated promoter of the RARB + GSTP1 genes needs further validation to be used as a biomarker for liquid biopsy and as a recommendation criterion for additional tests in asymptomatic women younger than 50 years.
Sex, immunity, and cancer
(Elsevier B.V., 2022) Pinto, JA; Araujo, JM; Gómez, HL
The composition of the tumor microenvironment is the complex result of the interaction between tumoral and host factors. Since there are several differences in the regulation of gene circuits between sexes, mainly influenced by sex hormones, the tumor-host interaction presents some differences, leading tumors to evolve under different conditions. Nowadays, it is well known the existence of sexual dimorphism in the regulation of the immune system, where women present an improved immunity to various infectious agents and, on the other hand, a higher incidence of autoimmune diseases than men. In oncology, differences in cancer susceptibility, response to treatment, and clinical outcomes between men and women patients are well known. Recently, sex-specific differences have also been reported in mutations in driver genes and the prognostic value of several biomarkers. Sex has been a widely forgotten biomarker in cancer therapy, but it has recently acquired great relevance due to the different results seen in immunotherapy treatment. © 2021 Elsevier B.V.