CARVAJAL HAUSDORF, DANIEL EDUARDO
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CARVAJAL HAUSDORF, DANIEL EDUARDO
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dcarvajal@udd.cl
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56274228900

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2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 2017 2017 2016 2016 2015 2015 2014 2014 0.0 0.0 1.0 1.0 2.0 2.0 3.0 3.0 4.0 4.0 5.0 5.0

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Dataset - Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression

2021 , CARVAJAL HAUSDORF, DANIEL EDUARDO

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Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry

2019 , CARVAJAL HAUSDORF, DANIEL EDUARDO , Jonathan Patsenker , Kelly P. Stanton , Franz Villarroel-Espindola , Amanda Esch , Ruth R. Montgomery , Amanda Psyrri , Konstantine T. Kalogeras , Vassiliki Kotoula , George Foutzilas , Kurt A. Schalper , Yuval Kluger , David L. Rimm

Abstract Purpose: Imaging mass cytometry (IMC) uses metal-conjugated antibodies to provide multidimensional, objective measurement of protein targets. We used this high-throughput platform to perform an 18-plex assessment of HER2 ICD/ECD, cytotoxic T-cell infiltration and other structural and signaling proteins in a cohort of patients treated with trastuzumab to discover associations with trastuzumab benefit. Experimental Design: An antibody panel for detection of 18 targets (pan-cytokeratin, HER2 ICD, HER2 ECD, CD8, vimentin, cytokeratin 7, β-catenin, HER3, MET, EGFR, ERK 1–2, MEK 1–2, PTEN, PI3K p110 α, Akt, mTOR, Ki67, and Histone H3) was used with a selection of trastuzumab-treated patients from the Hellenic Cooperative Oncology Group 10/05 trial (n = 180), and identified a case–control series. Results: Patients that recurred after adjuvant treatment with trastuzumab trended toward a decreased fraction of HER2 ECD pixels over threshold compared with cases without recurrence (P = 0.057). After exclusion of the lowest HER2 expressers, 5-year recurrence events were associated with reduced total extracellular domain (ECD)/intracellular domain (ICD) ratio intensity in tumor (P = 0.044). These observations are consistent with our previous work using quantitative immunofluorescence, but represent the proof on identical cell content. We also describe the association of the ECD of HER2 with CD8 T-cell infiltration on the same slide. Conclusions: The proximity of CD8 cells as a function of the expression of the ECD of HER2 provides further evidence for the role of the immune system in the mechanism of action of trastuzumab.

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Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high‐incidence country

2023 , Felix Boekstegers , Dominique Scherer , Carol Barahona Ponce , Katherine Marcelain , Valentina Gárate‐Calderón , Melanie Waldenberger , Erik Morales , Armando Rojas , César Munoz , Javier Retamales , Gonzalo de Toro , Olga Barajas , María Teresa Rivera , Analía Cortés , Denisse Loader , Javiera Saavedra , Lorena Gutiérrez , Alejandro Ortega , Maria Enriqueta Bertrán , Leonardo Bartolotti , Fernando Gabler , Mónica Campos , Juan Alvarado , Fabricio Moisán , Loreto Spencer , Bruno Nervi , CARVAJAL HAUSDORF, DANIEL EDUARDO , Héctor Losada , Mauricio Almau , Plinio Fernández , Jordi Olloquequi , Macarena Fuentes‐Guajardo , Rolando Gonzalez‐Jose , Maria Cátira Bortolini , Victor Acuña‐Alonzo , Carla Gallo , Andres Ruiz Linares , Francisco Rothhammer , Justo Lorenzo Bermejo

AbstractSince 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population‐based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non‐genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision‐recall curve (AUC‐PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC‐PRC for the Baseline Model (0.44%, 95%CI 0.42‐0.46) increased by 0.22 (95%CI 0.15‐0.29) when non‐genetic factors were included, and by 0.25 (95%CI 0.20‐0.30) when incorporating non‐genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104‐131) decreased to 92 (95%CI 60‐128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59‐110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non‐genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

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Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC)

2019 , CARVAJAL HAUSDORF, DANIEL EDUARDO , Mehmet Altan , Vamsidhar Velcheti , Scott N. Gettinger , Roy S. Herbst , David L. Rimm , Kurt A. Schalper

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Implementation of a platform for objective immunohistochemistry analysis in a tertiary hospital from Chile: a pilot study

2018 , MARCELA GALLEGOS ANGULO , MARCELA SCHULTZ HARAMOTO , CARVAJAL HAUSDORF, DANIEL EDUARDO , Viviana Ahumada

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Dataset - BioStudies ArrayExpress - Functional Genomics Data

2021 , CARVAJAL HAUSDORF, DANIEL EDUARDO

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Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer

2017 , CARVAJAL HAUSDORF, DANIEL EDUARDO , Nikita Mani , Vamsidhar Velcheti , Kurt A. Schalper , David L. Rimm

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Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers

2023 , Linda Zollner , Felix Boekstegers , Carol Barahona Ponce , Dominique Scherer , Katherine Marcelain , Valentina Gárate-Calderón , Melanie Waldenberger , Erik Morales , Armando Rojas , César Munoz , Javier Retamales , Gonzalo De Toro , Allan Vera Kortmann , Olga Barajas , María Teresa Rivera , Analía Cortés , Denisse Loader , Javiera Saavedra , Lorena Gutiérrez , Alejandro Ortega , Maria Enriqueta Bertrán , Leonardo Bartolotti , Fernando Gabler , Mónica Campos , Juan Alvarado , Fabricio Moisán , Loreto Spencer , Bruno Nervi , CARVAJAL HAUSDORF, DANIEL EDUARDO , Héctor Losada , Mauricio Almau , Plinio Fernández , Jordi Olloquequi , Alice R. Carter , Juan Francisco Miquel Poblete , Bernabe Ignacio Bustos , Macarena Fuentes Guajardo , Rolando Gonzalez-Jose , Maria Cátira Bortolini , Victor Acuña-Alonzo , Carla Gallo , Andres Ruiz Linares , Francisco Rothhammer , Justo Lorenzo Bermejo

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10−5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m2, 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

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Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression

2022 , Alice Blandino , Dominique Scherer , Trine B. Rounge , Sinan U. Umu , Felix Boekstegers , Carol Barahona Ponce , Katherine Marcelain , Valentina Gárate-Calderón , Melanie Waldenberger , Erik Morales , Armando Rojas , César Munoz , Javier Retamales , Gonzalo de Toro , Olga Barajas , María Teresa Rivera , Analía Cortés , Denisse Loader , Javiera Saavedra , Lorena Gutiérrez , Alejandro Ortega , Maria Enriqueta Bertrán , Fernando Gabler , Mónica Campos , Juan Alvarado , Fabrizio Moisán , Loreto Spencer , Bruno Nervi , CARVAJAL HAUSDORF, DANIEL EDUARDO , Héctor Losada , Mauricio Almau , Plinio Fernández , Ivan Gallegos , Jordi Olloquequi , Macarena Fuentes-Guajardo , Rolando Gonzalez-Jose , Maria Cátira Bortolini , Carla Gallo , Andres Ruiz Linares , Francisco Rothhammer , Justo Lorenzo Bermejo

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04–1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.

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Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer

2018 , Mehmet Altan , Kelley M. Kidwell , Vasiliki Pelekanou , CARVAJAL HAUSDORF, DANIEL EDUARDO , Kurt A. Schalper , Maria I. Toki , Dafydd G. Thomas , Michael S. Sabel , Daniel F. Hayes , David L. Rimm

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