Person: Molanes López, Elisa María
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First Name
Elisa María
Last Name
Molanes López
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Estadística e Investigación Operativa
Area
Estadística e Investigación Operativa
Identifiers
4 results
Search Results
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Item HLA-G 3’UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients(Frontiers in Immunology, 2021) 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, AntonioHLA-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.Item Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer(Cellular Immunology, 2022) 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 ManuelThe 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.Item TGFB1 polymorphisms and TGF‐β1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease(Cellular and Molecular Life Sciences, 2020) Alberto Gutierrez; Christian Vaquero‐Yuste; Adela López; Inmaculada Lasa; Remedios Gómez; Juárez Martín-Delgado, Ignacio; Molanes López, Elisa María; Martín Villa, José ManuelAbstractTGF‐β1 is involved in tumour growth. Four TGFB1 SNPs and TGF‐β1 production by stimulated PBMC were determined in seventy‐eight gastric adenocarcinoma patients. In addition, TGF‐β1 levels were measured in the plasma of further thirty patients. rs1800471‐G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP‐G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP‐T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469‐C/rs1800470‐T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five‐year life expectancy (P = .03). TGF‐β1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF‐β1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF‐β1 levels serves to identify patients at risk of developing a more aggressive disease.Item Computer-Assisted Surgery Enables Beginner Surgeons, Under Expert Guidance, to Achieve Long-Term Clinical Results not Inferior to Those of a Skilled Surgeon in Knee Arthroplasty(Indian Journal of Orthopaedics, 2022) Larrainzar Garijo, Ricardo; Molanes López, Elisa María; Cañones Martín, Miguel; Murillo Vizuete, David; Valencia Santos, Natalia; Garcia Bogalo, Raúl; Corella Montoya, FernandoPurpose: The purpose of this study is to determine whether the use of a surgical navigation system in total knee replacement (TKR) enables beginner and intermediate surgeons to achieve clinical PROM outcomes as good as those conducted by expert surgeons in the long term. Methods: We enrolled 100 consecutive patients whose total navigated knee arthroplasty (TKA) was performed in our institution from 2008 to 2010. According to the principal surgeon's surgical experience, the patients were divided into three groups: (1) beginner surgeons, with no more than 30 previous knee replacement performances, (2) intermediate surgeons, with more than 30 but not more than 300, and (3) expert surgeons, with more than 300 knee replacements. Demographic data collected on the cohort included gender, laterality, age, and body mass index (BMI). The outcome measures assessed were Forgotten Joint Score (FJS), implant positioning, limb alignment, and prosthesis survival rate. A margin of equivalence of±18.5 points in the FJS scale was prespecifed in terms of the minimal clinically important diference (MCID) to compare the FJS results obtained in the long period between the groups of interest. Results: The mean follow-up was 11.10±0.78, 10.86±0.66, and 11.30±0.74 years, respectively, for each of the groups. The long-term FJS mean score was 80.86±21.88, 81.36±23.87, and 90.48±14.65 for each group. The statistical analysis proved noninferiority and equivalence in terms of the FJS results reported in the long term by patients in Groups 1 or 2 compared to those in Group 3. More specifcally, it has been proved that the mean diference between groups is within the interval of equivalence defned in terms of the MCID. The overall prostheses survival rate was 93.7%. Conclusion: Navigated assisted TKA, under expert guidance, can be as efective when performed by beginner or intermediate surgeons as performed by senior surgeons regarding the accuracy of implant positioning, limb alignment, and long-term clinical outcome.