Person:
Juárez Martín-Delgado, Ignacio

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First Name
Ignacio
Last Name
Juárez Martín-Delgado
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Inmunología
Identifiers
UCM identifierORCIDScopus Author IDDialnet ID

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Now showing 1 - 6 of 6
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Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer

2022-10-28, Aguinaga Barrilero, Ana, Juárez Martín-Delgado, Ignacio, Vaquero Yuste, Christian, Molina Alejandre, Marta, Gutiérrez Calvo, Alberto, Lasa, Inmaculada, López, Adela, Gómez, Remedios, Molanes López, Elisa M., Martin Villa, Jose Manuel

The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory Tcell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67–6.64]*; AGC 2.90 % [1.37–4.44]; TF 3.14 % [2.33–4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30–0.45]*, AGC 0.12 [0.07–0.14]; TF 0.12 [0.09–0.31]; *p < 0.05 vs AGC). Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.

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A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer

2021-06-10, Juárez Martín-Delgado, Ignacio, Toro Fernandez, Juan Francisco, Vaquero Yuste, Christian, Molina Alejandre, Marta, Lasa, Inmaculada, Gomez, Remedios, Lopez, Adela, Martín Villa, José Manuel, Gutierrez, Alberto

We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification.

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A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer

2021-06-10, Juárez Martín-Delgado, Ignacio, Toro Fernandez, Juan Francisco, Vaquero Yuste, Christian, Molina Alejandre, Marta, Lasa, Inmaculada, Gomez, Remedios, Lopez, Adela, Martin Villa, Jose Manuel, Gutierrez, Alberto

We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification.

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Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer

2022-12, Aguinaga Barrilero, Ana, Juárez Martín-Delgado, Ignacio, Vaquero Yuste, Christian, Molina Alejandre, Marta, Gutiérrez Calvo, Alberto, Lasa, Inmaculada, López, Adela, Gómez, Remedios, Molanes López, Elisa María, Martín Villa, José Manuel

The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory T-cell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67-6.64]*; AGC 2.90 % [1.37-4.44]; TF 3.14 % [2.33-4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30-0.45]*, AGC 0.12 [0.07-0.14]; TF 0.12 [0.09-0.31]; *p < 0.05 vs AGC).Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.

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HLA study in Mexico Nahua/Aztec Amerindians: Close relatedness to the ancient Central America ethnic groups

2023-05, Suarez Trujillo, Fabio, Vargas Alarcon, Gilberto, Juárez Martín-Delgado, Ignacio, Gil Martin, Roberto, Granados, Julio, Vaquero Yuste, Christian, Martín Villa, José Manuel, Arnaiz Villena, Antonio

Nahua population (also named Aztec or Mexica) was studied for HLA class II genes in a Mexican rural city (Santo Domingo Ocotitlan, Morelos State) belonging to the nowadays Náhuatl speaking areas in Mexico. The most frequent HLA class II alleles were typical Amerindian (HLA-DRB1*04:07, DQB1*03:01 DRB1*04:03 or DRB1*04:04) and also were some calculated extended haplotypes (HLA-DRB1*04:07-DQB1*03:02,DRB1*08:02-DQB1*04:02, or DRB1*10:01-DQB1*05:01 among others). When using HLA-DRB1 Neís genetic distances, our isolated Nahua population was found to be close to other Central America Amerindians like the ancient-established Mayans or Mixe. This may suggest that Nahuas origin was also from Central America. It contrasts to legend that assumes they came from the North, and they built the Aztec Empire after submitting Central America neighbouring ethnic groups before 1519 CE when Spaniards led by Hernán Cortés arrived to Mexico

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HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients

2021-09-07, Vaquero Yuste, Christian, Juárez Martín-Delgado, Ignacio, Molina Alejandre, Marta, Molanes López, Elisa María, López Nares, Adrián, Suárez Trujillo, Fabio, Gutiérrez Calvo, Alberto, Fernández-Cruz Pérez, Eduardo, Rodríguez Sainz, Carmen, Martín Villa, José Manuel, Arnaiz Villena, Antonio

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.