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    Scopus© Citations 7  2
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    Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction
    (2022)
    Mojun Zhu
    ;
    Chunhua Chen
    ;
    Nathan R. Foster
    ;
    Christopher Hartley
    ;
    Taofic Mounajjed
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma.</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and Methods:</jats:title> <jats:p>Patients with GEJ adenocarcinoma (cT1–3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS &amp;lt; 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1–expressing EVs was significantly associated with higher pCR.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.</jats:p> </jats:sec>
      13Scopus© Citations 57
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      11Scopus© Citations 121
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    Scopus© Citations 113  1
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    Annona cherimola Seed Extracts Trigger an Early Apoptosis Response and Selective Anticlonogenic Activity against the Human Gastric Carcinoma Cell Line SNU-1
    (2023)
    Johan Macuer-Guzmán
    ;
    Claudia Giovagnoli-Vicuña
    ;
    Giuliano Bernal
    ;
    Lorena Lobos-González
    ;
    Erwin de la Fuente-Ortega
    <jats:p>The aim of this study was to evaluate, for the first time, the antiproliferative, apoptotic and diminishing effects of the anchored growth-independent capacity of an ethanol macerate extract from the Annona cherimola seed (EMCHS) in the human gastric cancer cell line SNU-1. The cells treated with EMCHS (20 μg/mL) significantly reduced the capacity to form clones of the tumor cell. Moreover, 50 μg/mL of EMCHS extract induced apoptosis, as was shown by the Annexin-V assay. UHPLC-MS/MS analysis detected two acetogenins (Annonacinone and Annonacin) in the EMCHS, which could be largely responsible for its selective antiproliferative effect. The identification of fatty acids by GC-FID showed the presence of eight fatty acids, among which was, oleic acid, which has recognized activity as an adjuvant in antitumor treatments. Taken together, our results indicate that the EMCHS seems promising for use as a natural therapy against gastric cancer disease.</jats:p>
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    NGF/TRKA Decrease miR-145-5p Levels in Epithelial Ovarian Cancer Cells
    (2020)
    Maritza P. Garrido
    ;
    Ignacio Torres
    ;
    Alba Avila
    ;
    Jonás Chnaiderman
    ;
    Manuel Valenzuela-Valderrama
    <jats:p>Nerve Growth Factor (NGF) and its high-affinity receptor tropomyosin receptor kinase A (TRKA) increase their expression during the progression of epithelial ovarian cancer (EOC), promoting cell proliferation and angiogenesis through several oncogenic proteins, such as c-MYC and vascular endothelial growth factor (VEGF). The expression of these proteins is controlled by microRNAs (miRs), such as miR-145, whose dysregulation has been related to cancer. The aims of this work were to evaluate in EOC cells whether NGF/TRKA decreases miR-145 levels, and the effect of miR-145 upregulation. The levels of miR-145-5p were assessed by qPCR in ovarian biopsies and ovarian cell lines (human ovarian surface epithelial cells (HOSE), A2780 and SKOV3) stimulated with NGF. Overexpression of miR-145 in ovarian cells was used to evaluate cell proliferation, migration, invasion, c-MYC and VEGF protein levels, as well as tumor formation and metastasis in vivo. In EOC samples, miR-145-5p levels were lower than in epithelial ovarian tumors. Overexpression of miR-145 decreased cell proliferation, migration and invasion of EOC cells, changes that were concomitant with the decrease in c-MYC and VEGF protein levels. We observed decreased tumor formation and suppressed metastasis behavior in mice injected with EOC cells that overexpressed miR-145. As expected, ovarian cell lines stimulated with NGF diminished miR-145-5p transcription and abundance. These results suggest that the tumoral effects of NGF/TRKA depend on the regulation of miR-145-5p levels in EOC cells, and that its upregulation could be used as a possible therapeutic strategy for EOC.</jats:p>
    Scopus© Citations 27  3
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    Scopus© Citations 18  5
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    Hematocele y hemoperitoneo como manifestación inicial de carcinoma hepatocelular: Caso clínico
    (2021)
    SCHIAPPACASSE, GIANCARLO  
    ;
    Israel Díaz-Araneda
    ;
    Patricio Vargas-Hudson
    ;
    Marcelo Vivanco-Lacalle
    ;
    Guillermo Rencoret-Palma
      17
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    Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer
    (2015)
    Iván Roa
    ;
    Gonzalo de Toro
    ;
    Fernanda Fernández
    ;
    Anakaren Game
    ;
    Sergio Muñoz
    Scopus© Citations 22  2