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1.
Mol Cancer ; 20(1): 57, 2021 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-33781255

RESUMEN

Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.


Asunto(s)
Biomarcadores de Tumor , MicroARN Circulante , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Exosomas/metabolismo , MicroARNs/genética , Biomarcadores de Tumor/genética , Femenino , Humanos , MicroARNs/metabolismo , Pronóstico , Curva ROC
2.
Anticancer Drugs ; 32(10): 1123-1126, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34261916

RESUMEN

Cetuximab is an IgG1 chimeric mAb against epidermal growth factor receptor, which can be used for chemotherapy failure or tolerance in patients with epidermal growth factor receptor expressed RAS wild-type metastatic colorectal cancer. We report on a patient who developed rapid-onset interstitial pneumonia while being treated with cetuximab plus XELOX (oxaliplatin, capecitabine) for metastatic colorectal cancer. A 75-year-old man patient was administered cetuximab plus XELOX regularly. After his cetuximab schedule was adjusted from 1 to 2 weeks, he rapidly developed interstitial pneumonia which led to acute respiratory distress syndrome. Our literature review indicated that, for patients with risk factors, a 2-week regimen of cetuximab might lead to interstitial pneumonia. Clinicians should closely monitor patients for adverse drug reactions to improve drug safety.


Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Cetuximab/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Humanos , Masculino , Metástasis de la Neoplasia , Oxaloacetatos
3.
Mol Cancer ; 18(1): 76, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30940131

RESUMEN

Cervical cancer screening through detection and treatment of high-grade cervical intraepithelial neoplasia (CIN) is most successful in cancer prevention. However, the accuracy of the current cervical cancer screening tests is still low. The aim of this study was to develop a more accurate method based on circulating exosomal miRNAs. The miRNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 121 plasma samples from healthy volunteers, cervical carcinoma patients, and CIN patients. A panel with eight differentially expressed exosomal miRNAs was identified to distinguish patients in the CIN II+ group (including advanced CIN II patients) from those in the CIN I- group (including CIN I patients and healthy volunteers). Let-7d-3p and miR-30d-5p showed significant difference between cervical tumors and adjacent normal tissues (P < 0.005), exhibited a consistent trend in plasma samples, and were further validated in 203 independent plasma samples. Integrating these two miRNAs yielded an AUC value of 0.828 to distinguish patients in CIN II+ group from those in CIN I- group. Further integrating them into a cytological test-based model resulted in a higher AUC of 0.887, while the AUC value based on the cytological test alone was 0.766. In summary, plasma exosomal miR-30d-5p and let-7d-3p are valuable diagnostic biomarkers for non-invasive screening of cervical cancer and its precursors. Further validation using large sample sizes is required for clinical diagnosis.


Asunto(s)
Biomarcadores de Tumor/genética , MicroARNs/sangre , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de Secuencia de ARN , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/genética , Displasia del Cuello del Útero/genética
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120355, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34530200

RESUMEN

The mortality of ovarian cancer is closely related to its poor rate of early detection. In the search of an efficient diagnosis method, Raman spectroscopy of blood features as a promising technique allowing simple, rapid, minimally-invasive and cost-effective detection of cancers, in particular ovarian cancer. Although Raman spectroscopy has been demonstrated to be effective to detect ovarian cancers with respect to normal controls, a binary classification remains idealized with respect to the real clinical practice. This work considered a population of 95 woman patients initially suspected of an ovarian cancer and finally fixed with a cancer or a cyst. Additionally, 79 normal controls completed the ensemble of samples. Such sample collection proposed us a study case where a ternary classification should be realized with Raman spectroscopy of the collected blood samples coupled with suitable spectroscopic data treatment algorithms. In the medical as well as data points of view, the appearance of the cyst case considerably reduces the distances among the different populations and makes their distinction much more difficult, since the intermediate cyst case can share the specific features of the both cancer and normal cases. After a proper spectrum pretreatment, we first demonstrated the evidence of different behaviors among the Raman spectra of the 3 types of samples. Such difference was further visualized in a high dimensional space, where the data points of the cancer and the normal cases are separately clustered, whereas the data of the cyst case were scattered into the areas respectively occupied by the cancer and normal cases. We finally developed and tested an ensemble of models for a ternary classification with 2 consequent steps of binary classifications, based on machine learning algorithms, allowing identification with sensitivity and specificity of 81.0% and 97.3% for cancer samples, 63.6% and 91.5% for cyst samples, 100% and 90.6% for normal samples.


Asunto(s)
Neoplasias Ováricas , Espectrometría Raman , Detección Precoz del Cáncer , Femenino , Humanos , Aprendizaje Automático , Neoplasias Ováricas/diagnóstico , Plasma , Análisis de Componente Principal
5.
Biomed Opt Express ; 12(5): 2559-2574, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-34123488

RESUMEN

Early-stage screening and diagnosis of ovarian cancer represent an urgent need in medicine. Usual ultrasound imaging and cancer antigen CA-125 test when prescribed to a suspicious population still require reconfirmations. Spectroscopic analyses of blood, at the molecular and atomic levels, provide useful supplementary tests when coupled with effective information extraction methods. Laser-induced breakdown spectroscopy (LIBS) was employed in this work to record the elemental fingerprint of human blood plasma. A machine learning data treatment process was developed combining feature selection and regression with a back-propagation neural network, resulting in classification models for cancer detection among 176 blood plasma samples collected from patients, including also ovarian cyst and normal cases. Cancer diagnosis sensitivity and specificity of respectively 71.4% and 86.5% were obtained for randomly selected validation samples.

6.
PLoS One ; 12(2): e0172211, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28222154

RESUMEN

The hypoxia adaptation to high altitudes is of considerable interest in the biological sciences. As a breed with adaptability to highland environments, the Tibetan chicken (Gallus gallus domestics), provides a biological model to search for genetic differences between high and lowland chickens. To address mechanisms of hypoxia adaptability at high altitudes for the Tibetan chicken, we focused on the Endothelial PAS domain protein 1 (EPAS1), a key regulatory factor in hypoxia responses. Detected were polymorphisms of EPAS1 exons in 157 Tibetan chickens from 8 populations and 139 lowland chickens from 7 breeds. We then designed 15 pairs of primers to amplify exon sequences by Sanger sequencing methods. Six single nucleotide polymorphisms (SNPs) were detected, including 2 missense mutations (SNP3 rs316126786 and SNP5 rs740389732) and 4 synonymous mutations (SNP1 rs315040213, SNP4 rs739281102, SNP6 rs739010166, and SNP2 rs14330062). There were negative correlations between altitude and mutant allele frequencies for both SNP6 (rs739010166, r = 0.758, p<0.001) and SNP3 (rs316126786, r = 0.844, P<0.001). We also aligned the EPAS1 protein with ortholog proteins from diverse vertebrates and focused that SNP3 (Y333C) was a conserved site among species. Also, SNP3 (Y333C) occurred in a well-defined protein domain Per-AhR-Arnt-Sim (PAS domain). These results imply that SNP3 (Y333C) is the most likely casual mutation for the high-altitude adaption in Tibetan chicken. These variations of EPAS1 provide new insights into the gene's function.


Asunto(s)
Adaptación Fisiológica/genética , Mal de Altura/veterinaria , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Pollos/genética , Polimorfismo de Nucleótido Simple , Enfermedades de las Aves de Corral/genética , Alelos , Altitud , Mal de Altura/genética , Mal de Altura/fisiopatología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/química , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Cruzamiento , Pollos/fisiología , Secuencia Conservada , Frecuencia de los Genes , Estudios de Asociación Genética , Genética de Población , Enfermedades de las Aves de Corral/fisiopatología , Dominios Proteicos , Estructura Secundaria de Proteína , Alineación de Secuencia , Tibet
7.
Oncotarget ; 7(51): 84989-84998, 2016 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-27863407

RESUMEN

Aflatoxins have been shown to induce hepatotoxicity in animal models, but the effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an experimental basis for understanding the mechanism of aflatoxin-induced hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for 21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes, with increased numbers of apoptotic and autophagic hepatocytes.Poly ADP-ribose polymerase (PARP) was cleaved and caspase-3 was activated in experimental groups, showing that the apoptosis of hepatocytes was triggered by AFB2. Increased levels of the autophagy factors Beclin-1 and LC3-II/LC3-I, as well as down-regulation of p62, a marker of autophagic flux, provided additional evidence for AFB2-triggered autophagy. AFB2 induced mitochondria-mediated apoptosis via the production of reactive oxygen species (ROS) and promotion of the translocation of Bax and cytochrome c (cyt c) between mitochondria and the cytosol, triggering the formation of apoptosomes. AFB2 also inhibited the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway by activating PI3K, Akt, and mTOR and inhibiting their phosphorylation, contributing to the proautophagic activity of AFB2. These findings provide new insights into the mechanisms involved in AFB2-induced hepatotoxicity in broilers.


Asunto(s)
Aflatoxinas/metabolismo , Hepatocitos/fisiología , Mitocondrias/fisiología , Animales , Apoptosis , Autofagia , Proteínas Aviares/metabolismo , Beclina-1/metabolismo , Caspasa 3/metabolismo , Células Cultivadas , Pollos , Proteínas Asociadas a Microtúbulos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas de Unión al ARN/metabolismo , Especies Reactivas de Oxígeno , Transducción de Señal
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