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Subject: search.filters.subject.carcinoma, squamous cell

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    Mitochondria in oral cancer stem cells: Unraveling the potential drug targets for new and old drugs
    (2023)
    Ivonne Olmedo
    ;
    Daniela Martínez
    ;
    Javiera Carrasco-Rojas
    ;
    José A. Jara
      1Scopus© Citations 19
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      10Scopus© Citations 1
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    SPINK7 expression changes accompanied by HER2, P53 and RB1 can be relevant in predicting oral squamous cell carcinoma at a molecular level
    (2021)
    Gina Pennacchiotti
    ;
    Fabio Valdés-Gutiérrez
    ;
    Wilfredo Alejandro González-Arriagada
    ;
    Héctor Federico Montes
    ;
    Judith Maria Roxana Parra
    <jats:title>Abstract</jats:title><jats:p>The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of <jats:italic>SPINK7, P53, RB, NFKB</jats:italic> and <jats:italic>CYP4B1</jats:italic> were quantified by qPCR. <jats:italic>SPINK7</jats:italic> levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal–Wallis test and Dunn's <jats:italic>post-hoc</jats:italic> with a <jats:italic>p</jats:italic> &lt; 0.05 significance was used to analyze data. In OSCC, the <jats:italic>SPINK7</jats:italic> expression had down regulated while <jats:italic>P53, RB, NFKB</jats:italic> and <jats:italic>CYP4B1</jats:italic> had up regulated (<jats:italic>p</jats:italic> &lt; 0.001). <jats:italic>SPINK7</jats:italic> had also diminished in TCGA patients (<jats:italic>p</jats:italic> = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (<jats:italic>p</jats:italic> &lt; 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels. </jats:p>
    Scopus© Citations 16  1
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    Scopus© Citations 18  5
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    Total mutational load and clinical features as predictors of the metastatic status in lung adenocarcinoma and squamous cell carcinoma patients
    (2022)
    Karen Y. Oróstica
    ;
    Juan Saez-Hidalgo
    ;
    Pamela R. de Santiago
    ;
    RIVAS VERA, SOLANGE VERÓNICA  
    ;
    Sebastian Contreras
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Recently, extensive cancer genomic studies have revealed mutational and clinical data of large cohorts of cancer patients. For example, the Pan-Lung Cancer 2016 dataset (part of The Cancer Genome Atlas project), summarises the mutational and clinical profiles of different subtypes of Lung Cancer (LC). Mutational and clinical signatures have been used independently for tumour typification and prediction of metastasis in LC patients. Is it then possible to achieve better typifications and predictions when combining both data streams?</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>In a cohort of 1144 Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LSCC) patients, we studied the number of missense mutations (hereafter, the Total Mutational Load TML) and distribution of clinical variables, for different classes of patients. Using the TML and different sets of clinical variables (tumour stage, age, sex, smoking status, and packs of cigarettes smoked per year), we built Random Forest classification models that calculate the likelihood of developing metastasis.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We found that LC patients different in age, smoking status, and tumour type had significantly different mean TMLs. Although TML was an informative feature, its effect was secondary to the "tumour stage" feature. However, its contribution to the classification is not redundant with the latter; models trained using both TML and tumour stage performed better than models trained using only one of these variables. We found that models trained in the entire dataset (i.e., without using dimensionality reduction techniques) and without resampling achieved the highest performance, with an F1 score of 0.64 (95%CrI [0.62, 0.66]).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Clinical variables and TML should be considered together when assessing the likelihood of LC patients progressing to metastatic states, as the information these encode is not redundant. Altogether, we provide new evidence of the need for comprehensive diagnostic tools for metastasis.</jats:p> </jats:sec>
      2  1Scopus© Citations 3
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      1Scopus© Citations 2  10
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    Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma
    (2019)
    Leonie Rosenberger
    ;
    EZQUER, EDUARDO MARCELO  
    ;
    Fernando Lillo-Vera
    ;
    Paulina L. Pedraza
    ;
    María Ignacia Ortúzar
      12Scopus© Citations 125
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    Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma
    (2019)
    Velina S. Atanasova
    ;
    Celine Pourreyron
    ;
    Mehdi Farshchian
    ;
    Michael Lawler
    ;
    Christian A. Brown
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need.</jats:p> <jats:p>Experimental Design: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>These data support a "first in RDEB" phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC.</jats:p> </jats:sec>
      24Scopus© Citations 32