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Latin America Cutaneous Oncology Management (LACOM) I: The Role of Skin Care in Oncology Patients and Survivors
(SanovaWorks, 2025-02-01)
Daniel Alcalá Pérez
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Ana Sofia Acosta Madiedo
;
Sebastian Andreani
;
Anneke Andriessen
;
Hebert Cárdenas
2
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Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
(MDPI AG, 2025-04-03)
María José Maturana
;
Oslando Padilla
;
Pablo M. Santoro
;
Maria Alejandra Alarcón
;
Wilda Olivares
Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
1Scopus© Citations 4
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Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival
(Springer Science and Business Media LLC, 2025-01-18)
Bárbara Mora-Lagos
;
María Elena Reyes
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LOBOS GONZALEZ, LORENA DE LOURDES
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Matías del Campo
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Kurt Buchegger
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC’s most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (<jats:italic>3D</jats:italic> tumor spheroids), and animal models.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.</jats:p> </jats:sec>
3Scopus© Citations 4
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Therapeutic vaccines for advanced non-small cell lung cancer
(2019)
Marcela Cortés-Jofré
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Rolando Uranga
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Ania Torres Pombert
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Maria del Carmen Arango Prado
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Iraida Caballero Aguirrechu
Scopus© Citations 6 3
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The Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric cancer
(2021)
Lorena Ortega
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Lorena Lobos-González
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Mauricio Reyna-Jeldes
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Daniela Cerda
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Erwin De la Fuente-Ortega
Scopus© Citations 16 2
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Incidence of occult uterine sarcoma and other unexpected pathologies in patients having surgery for presumed myomas: A retrospective observational study
(2021)
Mariane Von Mühlenbrock
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Paz Navarrete-Rey
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Elias Kovoor
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Rodrigo Guzman-Rojas
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Fernando Troncoso
5Scopus© Citations 4
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A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer
(2021)
Miguel Cordova-Delgado
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María Loreto Bravo
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Elisa Cumsille
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Charlotte N. Hill
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Matías Muñoz-Medel
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in <jats:italic>GSTP1</jats:italic>, <jats:italic>ERCC2</jats:italic>, <jats:italic>ERCC1</jats:italic>, <jats:italic>TP53</jats:italic>, <jats:italic>UMPS</jats:italic>, <jats:italic>SHMT1</jats:italic>, <jats:italic>MTHFR</jats:italic>, <jats:italic>ABCC2</jats:italic> and <jats:italic>DPYD</jats:italic> were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected <jats:italic>DPYD</jats:italic> SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, <jats:italic>p</jats:italic> = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; <jats:italic>p</jats:italic> = 0.071). Combination of paired SNPs demonstrated significant associations in <jats:italic>DPYD</jats:italic> (rs1801265), <jats:italic>UMPS</jats:italic> (rs1801019), <jats:italic>ABCC2</jats:italic> (rs717620) and <jats:italic>SHMT1</jats:italic> (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs <jats:italic>DPYD</jats:italic> (rs1801265) + <jats:italic>ABCC2</jats:italic> (rs717620), and <jats:italic>DPYD</jats:italic> (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.</jats:p> </jats:sec>
Scopus© Citations 11 3
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Potential use of n-3 PUFAs to prevent oxidative stress-derived ototoxicity caused by platinum-based chemotherapy
(2020)
Ignacio A. Cortés Fuentes
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Mauricio Burotto
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Mauricio A. Retamal
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Michael Frelinghuysen
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Christian Caglevic
Scopus© Citations 4 1
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Clinical Experience With 75-mg Dose of Erlotinib for Mutated Metastatic EGFR Non-small Cell Lung Cancer
(2019)
Osvaldo Aren
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Suraj Samtani
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Micahel Frelinghuysen
;
Mauricio Burotto
2
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Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer
(2020)
Kohei Shitara
;
Eric Van Cutsem
;
Yung-Jue Bang
;
Charles Fuchs
;
Lucjan Wyrwicz
37Scopus© Citations 899

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