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    Animal-type melanoma/pigmented epithelioid melanocytoma: three clinical cases of a rare and controversial entity
    (2023)
    Vittorio Gedda
    ;
    Francisco González-Coloma
    ;
    Alejandro Jeldres
    ;
    Carolyn Rodríguez
    ;
    Gabriela Coulon
      3  1
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    Therapeutic vaccines for advanced non-small cell lung cancer
    (2019)
    Marcela Cortés-Jofré
    ;
    Rolando Uranga
    ;
    Ania Torres Pombert
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    Maria del Carmen Arango Prado
    ;
    Iraida Caballero Aguirrechu
    Scopus© Citations 6  3
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    CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review
    (2021)
    Benjamín Durán-Vinet
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    Karla Araya-Castro
    ;
    ;
    Luis Vergara
    ;
    Helga Weber
    <jats:p>Colorectal cancer (CRC) is the third most prevalent cancer with the second highest mortality rate worldwide. CRC is a heterogenous disease with multiple risk factors associated, including obesity, smoking, and use of alcohol. Of total CRC cases, 60% are diagnosed in late stages, where survival can drop to about 10%. CRC screening programs are based primarily on colonoscopy, yet this approach is invasive and has low patient adherence. Therefore, there is a strong incentive for developing molecular-based methods that are minimally invasive and have higher patient adherence. Recent reports have highlighted the importance of extracellular vesicles (EVs), specifically exosomes, as intercellular communication vehicles with a broad cargo, including micro-RNAs (miRNAs). These have been syndicated as robust candidates for diagnosis, primarily for their known activities in cancer cells, including immunoevasion, tumor progression, and angiogenesis, whereas miRNAs are dysregulated by cancer cells and delivered by cancer-derived exosomes (CEx). Quantitative polymerase chain reaction (qPCR) has shown good results detecting specific cancer-derived exosome micro-RNAs (CEx-miRNAs) associated with CRC, but qPCR also has several challenges, including portability and sensitivity/specificity issues regarding experiment design and sample quality. CRISPR/Cas-based platforms have been presented as cost-effective, ultrasensitive, specific, and robust clinical detection tools in the presence of potential inhibitors and capable of delivering quantitative and qualitative real-time data for enhanced decision-making to healthcare teams. Thereby, CRISPR/Cas13-based technologies have become a potential strategy for early CRC diagnosis detecting CEx-miRNAs. Moreover, CRISPR/Cas13-based platforms’ ease of use, scalability, and portability also showcase them as a potential point-of-care (POC) technology for CRC early diagnosis. This study presents two potential CRISPR/Cas13-based methodologies with a proposed panel consisting of four CEx-miRNAs, including miR-126, miR-1290, miR-23a, and miR-940, to streamline novel applications which may deliver a potential early diagnosis and prognosis of CRC.</jats:p>
      7Scopus© Citations 22
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      7Scopus© Citations 8
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    Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort
    (2020)
    Claudia Maccali
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    Aline L. Chagas
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    Ilka Boin
    ;
    Emilio Quiñonez
    ;
    Sebastián Marciano
      13Scopus© Citations 18
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    Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors
    (2022)
    Cristina Royo-Cebrecos
    ;
    Julia Laporte-Amargós
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    Marta Peña
    ;
    Isabel Ruiz-Camps
    ;
    Pedro Puerta-Alcalde
    <jats:p>Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p &lt; 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p &lt; 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p &lt; 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p &lt; 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p &lt; 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p &lt; 0.001) and 30-day (49% vs. 37.3%; p &lt; 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.</jats:p>
      1Scopus© Citations 25
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    MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies
    (2022) ;
    Arnaldo Marín
    ;
    Suraj Samtani
    ;
    Evelin González-Feliú
    ;
    <jats:p>The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and β-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient’s mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.</jats:p>
    Scopus© Citations 15  16
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    Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence
    (2020)
    Federico Piñero
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    Ilka Boin
    ;
    Aline Chagas
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    Emilio Quiñonez
    ;
    Sebastián Marciano
      7Scopus© Citations 15
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    Survival of Critically Ill Oncologic Patients Requiring Invasive Ventilatory Support: A Prospective Comparative Cohort Study With Nononcologic Patients
    (2019) ;
    Suraj Rajesh Samtani
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    Jose Miguel Montes
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    ;
    Maria Jose Martin
    <jats:sec><jats:title>PURPOSE</jats:title><jats:p> Cancer is in the process of changing to become a chronic disease; therefore, an increasing number of oncologic patients (OPs) are being admitted to intensive care units (ICUs) for supportive care of disease or therapy-related complications. We compare the short- and long-term outcomes of critically ill mechanically ventilated OPs with those of their nononcologic counterparts. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> We performed a prospective study of patients admitted to our ICU between October 2017 and February 2019. Demographic, physiologic, laboratory, clinical, and treatment data were obtained. The primary outcome was survival at 28 days and at the end of the follow-up period. Secondary outcomes were survival according to acute severity scoring (Acute Physiology and Chronic Health Evaluation II score), Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson comorbidity index. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> A total of 1,490 patients were admitted during the study period; 358 patients (24%) were OPs, and 100 of these OPs were supported with mechanical ventilation. Seventy-three percent of OPs had an ECOG performances status of 0 or 1, and 90% had solid tumors. Reason for admission to the ICU was postoperative admission in 44 patients and neutropenic infection in 10 patients. The follow-up period was 148 days (range, 42 to 363 days). Survival at 28 days was similar between OPs and nononcologic patients and associated with the Acute Physiology and Chronic Health Evaluation II score. However, long-term survival was lower in OPs compared with nononcologic patients (52% v 76%, respectively; P &lt; .001) and associated with poor ECOG performance status. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Short-term survival of critically ill, mechanically ventilated OPs is similar to that of their nononcologic counterparts and is determined by the severity of the critical illness. </jats:p></jats:sec>
      2Scopus© Citations 2
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      8