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1.
Medicine (Baltimore) ; 100(11): e25104, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33725987

RESUMEN

ABSTRACT: Our aim in this study was to investigate the relationship between serum ischemia modified albumin (IMA) levels with oxidative stress parameters [protein carbonyl (PCO), advanced protein oxidation products (AOPPs), malondialdehyde (MDA), total nitric oxide (NOx), prooxidant-antioxidant balance (PAB), and ferric reducing of antioxidant power (FRAP)] in breast cancer (BC) and colon cancer (CC).In total, 90 patients undergoing surgical treatment for BC (n = 45) or CC (n = 45) and 35 healthy controls were included in this cross-sectional study.The serum PCO, AOPPs, MDA, NOx, PAB, and IMA levels were all statistically significantly higher in the cancer patients than in the control group. MDA, NOx, and PAB levels were significantly lower in the BC group than in the CC group. FRAP values were statistically significantly lower in both the CC group and the BC group compared to the control. IMA showed a weak positive correlation with CA-19.9 (r = 0.423 P = .007) but a moderate positive correlation with tumor size in the CC group. IMA showed a positive correlation with metastasis, grade, and HER2 and a negative correlation with ER and PR in the BC group.Oxidative stress is a key player in the development of solid malignancies. Cancer development is a multistage process, and oxidative stress caused by the production of ROS/RNS in the breast and colon may predispose individuals to BC and CC. Patients with BC and CC had an impaired oxidative/antioxidant condition that favored oxidative stress. The ROC analysis indicated that IMA sensitivity above 80% could be used as a secondary biomarker in diagnosis.


Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias del Colon/sangre , Estrés Oxidativo , Especies de Nitrógeno Reactivo/sangre , Especies Reactivas de Oxígeno/sangre , Productos Avanzados de Oxidación de Proteínas/sangre , Antioxidantes/metabolismo , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Neoplasias del Colon/patología , Estudios Transversales , Femenino , Compuestos Férricos/sangre , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Clasificación del Tumor/métodos , Estadificación de Neoplasias/métodos , Óxido Nítrico/sangre , Oxidación-Reducción , Carbonilación Proteica , Curva ROC , Albúmina Sérica/análisis
2.
Medicine (Baltimore) ; 100(12): e24765, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761638

RESUMEN

ABSTRACT: MicroRNA (miR)-26a-5p is an oncogene significantly associated with osteosarcoma. We try to evaluate expression of circulating miR-26a-5p in osteosarcoma patients and evaluate its significance.A total of 243 consecutive osteosarcoma patients and 96 healthy participates were enrolled. Circulating miR-26a-5p levels were evaluated by using real-time quantitative reverse transcription polymerase chain reactions (RT-PCR). The association between circulating miR-26a-5p level and survival outcomes was evaluated by univariate and multivariate analysis.Circulating miR-26a-5p levels in osteosarcoma patients was significantly higher than that of healthy volunteers (P < .05). Upregulated miR-26a-5p was significantly related to advanced cancer and metastasis (both P < .05). Moreover, patients with a high serum miR-26a-5p had a poorer overall survival than those with a low serum miR-26a-5p levels (P < .05). Circulating miR-26a-5p level also been showed as independent risk factor for osteosarcoma in multivariate analysis (hazard ratio [HR], 0.38; 95% confidence interval [CI]: 0.11-0.98; P < .01).Circulating miR-26a-5p was significantly upregulated in osteosarcoma patients and remarkably associated with poor prognosis, indicating that circulating miR-26a-5p might serve as a useful diagnostic and prognostic biomarker for osteosarcoma.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/mortalidad , MicroARN Circulante/metabolismo , MicroARNs/metabolismo , Recurrencia Local de Neoplasia/epidemiología , Osteosarcoma/mortalidad , Adulto , Biomarcadores de Tumor/sangre , Neoplasias Óseas/sangre , Neoplasias Óseas/genética , Neoplasias Óseas/cirugía , MicroARN Circulante/sangre , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Biopsia Líquida , Masculino , MicroARNs/sangre , Recurrencia Local de Neoplasia/genética , Osteosarcoma/sangre , Osteosarcoma/genética , Osteosarcoma/cirugía , Estudios Retrospectivos , Medición de Riesgo/métodos , Regulación hacia Arriba , Adulto Joven
3.
Nat Commun ; 12(1): 1851, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33767170

RESUMEN

Radiographic imaging is routinely used to evaluate treatment response in solid tumors. Current imaging response metrics do not reliably predict the underlying biological response. Here, we present a multi-task deep learning approach that allows simultaneous tumor segmentation and response prediction. We design two Siamese subnetworks that are joined at multiple layers, which enables integration of multi-scale feature representations and in-depth comparison of pre-treatment and post-treatment images. The network is trained using 2568 magnetic resonance imaging scans of 321 rectal cancer patients for predicting pathologic complete response after neoadjuvant chemoradiotherapy. In multi-institution validation, the imaging-based model achieves AUC of 0.95 (95% confidence interval: 0.91-0.98) and 0.92 (0.87-0.96) in two independent cohorts of 160 and 141 patients, respectively. When combined with blood-based tumor markers, the integrated model further improves prediction accuracy with AUC 0.97 (0.93-0.99). Our approach to capturing dynamic information in longitudinal images may be broadly used for screening, treatment response evaluation, disease monitoring, and surveillance.


Asunto(s)
Quimioradioterapia Adyuvante/métodos , Aprendizaje Profundo , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Neoplasias del Recto/diagnóstico por imagen , Biomarcadores de Tumor/sangre , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Recto/diagnóstico por imagen , Recto/patología , Resultado del Tratamiento
5.
Methods Mol Biol ; 2265: 305-321, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33704724

RESUMEN

Tumor-derived exosomes (TEX), a subset of small extracellular vesicles (EVs) which originate from the endocytic compartment of tumor cells, are emerging as key players in cancer progression. TEX circulate freely in patients' body fluids and transfer bioactive cargos from tumor to various recipient cells. The molecular cargo of melanoma cell-derived exosomes (MTEX) mimics that of the tumor, and MTEX serve as a liquid biopsy that provides potentially useful information for cancer diagnosis, prognosis, or responses to therapy. Plasma of melanoma patients contains a mix of MTEX and exosomes produced by nonmalignant cells (NMTEX). Isolation of these exosome subtypes from the bulk of plasma exosomes is necessary to evaluate contributions of each as potential biomarkers of melanoma progression and outcome. Here, methods for separation of MTEX from T cell-derived exosomes from a single small volume of plasma and their subsequent molecular and functional characterization are described. Following size exclusion chromatography (SEC) to isolate total plasma exosomes, immune affinity-based capture of MTEX with anti-CSPG4 antibody and then of exosomes produced by T cells with anti-CD3 antibody is used to sequentially isolate the two subsets. This immune capture method enables the recovery of MTEX and CD3+ exosomes in quantities sufficient both for molecular profiling by flow cytometry or western blotting and for functional analyses.


Asunto(s)
Biomarcadores de Tumor/sangre , Western Blotting , Exosomas/metabolismo , Citometría de Flujo , Melanoma/sangre , Linfocitos T/metabolismo , Cromatografía en Gel , Exosomas/patología , Humanos , Biopsia Líquida , Plasma/metabolismo , Linfocitos T/patología
6.
Methods Mol Biol ; 2265: 447-459, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33704733

RESUMEN

Multiplex immunoassays simultaneously measure multiple analytes in a single sample providing quantitative data via parallel analyses, which is especially suitable for serum biomarker verification and validation. Multiplex immunoassays demonstrate several advantages over traditional enzyme-linked immunosorbent assays such as increasing productivity, conserving critical reagents and samples, and delivering results quickly. Here we describe the detection of uveal melanoma by magnetic bead-based multiplex immunoassays of serum biomarkers. The biomarker panels evaluated by multiplex immunoassays with high analytical performance demonstrated potential complementary values in detection of uveal melanoma.


Asunto(s)
Biomarcadores de Tumor/sangre , Melanoma/sangre , Neoplasias de la Úvea/sangre , Humanos , Inmunoensayo
9.
Medicine (Baltimore) ; 100(6): e24651, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578593

RESUMEN

ABSTRACT: This study aimed to explore the significance and prognostic value of serum tumor-associated carbohydrate antigen 19-9 (CA19-9), D-dimer, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) in patients with pancreatic ductal adenocarcinoma (PDAC).Our study included 148 patients treated for PDAC at Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2012 to December 2016. Cutoff prognostic values were predicted using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to assess the survival rates of patients. Univariate and multivariate COX regression analyses were used to evaluate the prognostic factors.The recommended cutoff values of neutrophil-lymphocyte rate (NLR), platelet-lymphocyte rate (PLR), CA19-9, and D-dimer were 2.04 (sensitivity, 0.59; specificity, 0.9; area under the ROC curve [AUC], 0.749; P < .001), 52.94 (sensitivity, 0.73; specificity, 0.95; AUC, 0.829; P < .001), 176.66 U/mL (sensitivity, 0.7; specificity, 0.9; AUC, 0.794; P < .001), and 1.18 mg/L (sensitivity, 0.82; specificity, 0.9; AUC, 0.845; P < .001), respectively. Positive TNFAIP3/A20 expression was considered as an inclusion criterion. Serum CA19-9 expression was related with lymph node metastasis (P = .010), tumor-lymph node-metastasis (TNM) stage (P < .001), and survival rate (P < .001). D-dimer was correlated with tumor differentiation grade (P = .014), tumor size (P = .045), TNM stage (P < .001), and survival rate (P < .001). TNFAIP3/A20 was correlated with tumor differentiation grade (P < .001), body mass index (BMI) (P < .001), TNM stage (P = .014), and survival rate (P < .001). Kaplan-Meier curves showed that PDAC patients had significant differences in CA19-9, D-dimer, and TNFAIP3/A20 expressions (P < .05). CA19-9, D-dimer, TNM stage, tumor differentiation grade, and TNFAIP3/A20 were independent prognostic markers for PDAC in univariate and multivariate COX analyses.CA19-9, D-dimer, and TNFAIP3/A20 were found to be independent prognostic markers for PDAC patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Carcinoma Ductal Pancreático/mortalidad , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Plaquetas/patología , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , China/epidemiología , Femenino , Humanos , Metástasis Linfática/patología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Neutrófilos/patología , Pronóstico , Curva ROC , Sensibilidad y Especificidad , Tasa de Supervivencia
10.
Medicine (Baltimore) ; 100(6): e24700, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578606

RESUMEN

RATIONALE: Double primary lung cancer (DPLC) is a relatively rare type of lung cancers. According to whether the diagnosis interval between lesions is more than 6 months, it can be divided into synchronous DPLC (sDPLC) and metachronous DPLC (mDPLC). Here, we describe a case of sDPLC in which one of the components is a rare colloid adenocarcinoma (CA). PATIENT CONCERNS: A 69-year-old male was admitted to the hospital due to chest distress and shortness of breath for 1 year, getting worse in the last 15 days. DIAGNOSIS: Both HE staining and IHC supported the diagnosis of CA in the right lower lobe and moderately differentiated squamous cell carcinoma in the right upper lobe. INTERVENTIONS: The patient was treated with 3 cycles of adjuvant chemotherapy with pemetrexed and lobaplatin after the right upper lobectomy, wedge resection of the right lower lobe and lymph node dissection under video-assisted thoracoscope. OUTCOMES: Our plan was to follow him up with general physical examination, chest-abdomen CT and serum tumor markers every 6 months for 2 years. The patient was still alive until the last follow-up in November 2020. LESSONS: CA of the lung is a rare primary lung adenocarcinoma. The diagnosis should be based on the patient's clinical characteristics, imaging examination and pathological characteristics, and also need to be differentiated from other mucinous adenocarcinomas. Interestingly, our patient developed not only a CA in the right lower lobe, but also a moderately differentiated squamous cell carcinoma in the right upper lobe.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Neoplasias Primarias Múltiples/patología , Adenocarcinoma/terapia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/terapia , Cuidados Posteriores/métodos , Anciano , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Quimioterapia Adyuvante/métodos , Diagnóstico Diferencial , Disnea/diagnóstico , Disnea/etiología , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Escisión del Ganglio Linfático/métodos , Masculino , Estadificación de Neoplasias/métodos , Neoplasias Primarias Múltiples/terapia , Cirugía Torácica Asistida por Video/métodos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
11.
Biomed Res Int ; 2021: 3905353, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33521127

RESUMEN

Background: The objective of this study was to explore the role of preoperative fibrinogen-to-prealbumin ratio (FPR) in evaluating the prognosis of patients with stage I-III colorectal cancer (CRC). Methods: This retrospective study enrolled 584 stage I-III CRC patients undergoing surgical resection. Logistic regression analysis was used to explore the correlation between FPR and postoperative complications. The Kaplan-Meier curve and Cox proportional hazards model were used to identify the prognostic factors. The nomograms were constructed based on the prognostic factors. The concordance index and calibration curve were used to determine the accuracy of the nomograms. Time-dependent receiver operating characteristic was used to compare the predictive prognostic efficacy of nomograms and TNM stage. Results: FPR was determined to be an independent factor affecting postoperative complications. Patients with a low-FPR had a significantly better prognosis than those with a high-FPR (disease-free survival, p = 0.028; overall survival, p = 0.027), especially patients with stage I CRC (disease-free survival, p = 0.015; overall survival, p = 0.017). The Cox proportional hazards model identified FPR as an independent poor prognostic factor of disease-free survival (hazard ratio (HR) = 1.459, 95% confidence interval (CI) = 1.074-1.954, p = 0.011) and overall survival (HR = 1.405, 95% CI = 1.034-1.909, p = 0.030). The prognostic nomograms had good accuracy and were superior to the traditional TNM stage. Conclusions: FPR is a potential indicator for predicting short- and long-term prognosis of stage I-III CRC patients undergoing surgical resection.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , Fibrinógeno/análisis , Prealbúmina/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Periodo Posoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Análisis de Regresión , Estudios Retrospectivos , Adulto Joven
12.
BMJ Case Rep ; 14(2)2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33547121

RESUMEN

Renal involvement in mantle cell lymphoma (MCL) is rare. We present the case of a man followed for MCL presented with acute kidney injury and positive antineutrophil cytoplasmic antibody (ANCA) type anti proteinase 3 (PR3). He was treated as for a rapidly progressing glomerulonephritis with cyclophosphamide and methylprednisolone followed by oral prednisone. Renal biopsy revealed diffuse endocapillary proliferation and segmental extracapillary proliferation in four glomeruli. Immunohistochemistry confirmed the renal invasion of lymphomatous cells. He started improving his renal function shortly after starting treatment. The coexistence of renal MCL infiltration, extracapillary proliferation and ANCA positive is exceptional.


Asunto(s)
Glomerulonefritis/etiología , Linfoma de Células del Manto/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor/sangre , Biopsia , Ciclofosfamida , Diagnóstico Diferencial , Doxorrubicina , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/patología , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Prednisona , Rituximab , Vincristina
13.
J. obstet. gynaecol. Can ; 43(1): 91-105, Jan. 1, 2021.
Artículo en Inglés | BIGG - guías GRADE | ID: biblio-1146603

RESUMEN

This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. Women of reproductive age with gestational trophoblastic diseases. Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care.


Asunto(s)
Humanos , Femenino , Embarazo , Biomarcadores de Tumor/sangre , Enfermedad Trofoblástica Gestacional/diagnóstico , Enfermedad Trofoblástica Gestacional/terapia , Gonadotropina Coriónica/sangre , Mola Hidatiforme/terapia
14.
Methods Mol Biol ; 2261: 151-191, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33420989

RESUMEN

Cancer cells secrete membranous extracellular vesicles (EVs) which contain specific oncogenic molecular cargo (including oncoproteins, oncopeptides, and RNA) into their microenvironment and the circulation. As such, EVs including exosomes (small EVs) and microvesicles (large EVs) represent important circulating biomarkers for various diseases, including cancer and its progression. These circulating biomarkers offer a potentially minimally invasive and repeatable targets for analysis (liquid biopsy) that could aid in the diagnosis, risk stratification, and monitoring of cancer. Although their potential as cancer biomarkers has been promising, the identification and quantification of EVs in clinical samples remain challenging. Like EVs, other types of circulating biomarkers (including cell-free nucleic acids, cf-NAs; or circulating tumor cells, CTCs) may represent a complementary or alternative approach to cancer diagnosis. In the context of multiple myeloma (MM), a systemic cancer type that causes cancer cells to accumulate in the bone marrow, the specific role for EVs as biomarkers for diagnosis and monitoring remains undefined. Tumor heterogeneity along with the various subtypes of MM (such as non-secretory MM) that cannot be monitored using conventional testing (e.g. sequential serological testing and bone marrow biopsies) render liquid biopsy and circulating tumor-derived EVs a promising approach. In this protocol, we describe the isolation and purification of EVs from peripheral blood plasma (PBPL) collected from healthy donors and patients with MM for a biomarker discovery strategy. Our results demonstrate detection of circulating EVs from as little as 1 mL of MM patients' PBPL. High-resolution mass spectrometry (MS)-based proteomics promises to provide new avenues in identifying novel markers for detection, monitoring, and therapeutic intervention of disease. We describe biophysical characterization and quantitative proteomic profiling of disease-specific circulating EVs which may provide important implications for the development of cancer diagnostics in MM.


Asunto(s)
Biomarcadores de Tumor/sangre , Proteínas Sanguíneas/aislamiento & purificación , Exosomas/metabolismo , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Mieloma Múltiple/sangre , Proteómica , Espectrometría de Masas en Tándem , Métodos Analíticos de la Preparación de la Muestra , Estudios de Casos y Controles , Cromatografía Liquida , Exosomas/ultraestructura , Humanos , Biopsia Líquida , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/ultraestructura , Proteolisis
15.
Cancer Sci ; 112(3): 1275-1288, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33426736

RESUMEN

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. High recurrence rates after curative resection and the lack of specific biomarkers for intrahepatic metastases are major clinical problems. Recently, exosomal microRNAs (miRNAs) have been reported to have a role in the formation of the pre-metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. A highly intrahepatic metastatic cell line (HuH-7M) was established by in vivo selection. HuH-7M showed increased proliferative ability and suppression of apoptosis and anoikis. HuH-7M and the parental cell (HuH-7P) showed the similar expression of epithelial-mesenchymal transition markers and cancer stem cell markers. In vivo, mice treated with exosomes derived from HuH-7M showed increased tumorigenesis of liver metastases. Exosomes from HuH-7M downregulated endothelial cell expression of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 (ZO-1) in non-cancerous regions of liver and increased the permeability of FITC-dextran through the monolayer of endothelial cells. The miRNAs (miR-638, miR-663a, miR-3648, and miR-4258) could attenuate endothelial junction integrity by inhibiting VE-cadherin and ZO-1 expression. In patients with HCC, higher serum exosomal miR-638 expression was associated with tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancer cell can promote vascular permeability via downregulation of endothelial expression of VE-cadherin and ZO-1. Serum exosomal miR-638 expression holds potential for serving as a significant and independent prognostic marker in HCC.


Asunto(s)
Antígenos CD/genética , Biomarcadores de Tumor/metabolismo , Cadherinas/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , Recurrencia Local de Neoplasia/diagnóstico , Proteína de la Zonula Occludens-1/genética , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Células Endoteliales/patología , Transición Epitelial-Mesenquimal/genética , Exosomas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Hepatectomía , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hígado/citología , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Ratones , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/prevención & control , Periodo Preoperatorio
16.
JAMA Netw Open ; 4(1): e2034633, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33496795

RESUMEN

Importance: Black patients have been underrepresented in prospective clinical trials of advanced prostate cancer. This study evaluated the efficacy of enzalutamide compared with bicalutamide, with planned subset analysis of Black patients with metastatic hormone-sensitive prostate cancer (mHSPC), which is a disease state responsive to androgen deprivation therapy (ADT). Objective: To compare the efficacy of enzalutamide vs bicalutamide in combination with ADT in men with mHSPC, with a subset analysis of Black patients. Design, Setting, and Participants: In this randomized clinical trial, a phase 2 screening design enabled a nondefinitive comparison of the primary outcome by treatment. Patients were stratified by race (Black or other) and bone pain (present or absent). Accrual of at least 30% Black patients was required. This multicenter trial was conducted at 4 centers in the US. Men with mHSPC with no history of seizures and adequate marrow, renal, and liver function were eligible. Data analysis was performed from February 2019 to March 2020. Interventions: Participants were randomized 1:1 to receive oral enzalutamide (160 mg daily) or bicalutamide (50 mg daily) in addition to ADT. Main Outcomes and Measures: The primary end point was the 7-month prostate-specific antigen (PSA) response (SMPR) rate, a previously accepted surrogate for overall survival (OS) outcome. Secondary end points included adverse reactions, time to PSA progression, and OS. Results: A total of 71 men (median [range] age, 65 [51-86] years) were enrolled; 29 (41%) were Black, 41 (58%) were White, and 1 (1%) was Asian. Thirty-six patients were randomized to receive enzalutamide, and 35 were randomized to receive bicalutamide. Twenty-six patients (37%) had bone pain and 37 patients (52%) had extensive disease. SMPR was achieved in 30 of 32 patients (94%; 95% CI, 80%-98%) taking enzalutamide and 17 of 26 patients (65%; 95% CI, 46%-81%) taking bicalutamide (P = .008) (difference, 29%; 95% CI, 5%-50%). Among Black patients, the SMPR was 93% (95% CI, 69%-99%) among those taking enzalutamide and 42% (95% CI, 19%-68%) among those taking bicalutamide (P = .009); among non-Black patients, the SMPR was 94% (95% CI, 74%-99%) among those taking enzalutamide and 86% (95% CI, 60%-96%) among those taking bicalutamide. The 12-month PSA response rates were 84% with enzalutamide and 34% with bicalutamide. Conclusions and Relevance: The findings of this randomized clinical trial comparing enzalutamide with bicalutamide suggest that enzalutamide is associated with improved outcomes compared with bicalutamide, in terms of the rate and duration of PSA response, in Black patients with mHSPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02058706.


Asunto(s)
Afroamericanos , Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Nitrilos/uso terapéutico , Feniltiohidantoína/análogos & derivados , Neoplasias de la Próstata/tratamiento farmacológico , Compuestos de Tosilo/uso terapéutico , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Feniltiohidantoína/uso terapéutico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/etnología , Resultado del Tratamiento
17.
Life Sci ; 270: 119061, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33454364

RESUMEN

For patients with hepatocellular carcinoma (HCC), early detection is critical to improve survival. Secreted frizzled-related protein 2 (SFRP2) is a candidate tumor suppressor as Wnt antagonist and SFRP2 promoter has been found hypermethylated in various malignancies. This study aimed to investigate the methylation status of SFRP2 promoter in hepatitis B virus (HBV) associated HCC and estimate its diagnostic value as a non-invasive biomarker. A total of 293 patients, including 132 patients with HBV-associated HCC, 121 with chronic hepatitis B (CHB) and 40 healthy controls (HCs) were enrolled. SFRP2 methylation level in peripheral mononuclear cells (PBMCs) was quantitatively detected by MethyLight. SFRP2 methylation level was significantly higher in patients with HBV-associated HCC than in those with CHB (p < 0.001) and HCs (p < 0.001) while mRNA level of SFRP2 was significantly lower in HCC group than the other two groups (p < 0.05). In HCC subgroup, SFRP2 methylation level markedly increased in patients >50 years old, female, with negative HBeAg, negative HBV-DNA and poor differentiation compared with the remaining groups (P < 0.05). Furthermore, SFRP2 methylation level showed a significantly better diagnostic value than alpha-fetoprotein (AFP) and the combination of AFP and methylation levels of SFRP2 markedly improved the area under the receiver operating characteristic curve (p < 0.05). In conclusion, hypermethylation of SFRP2 promoter exists in HBV-associated HCC. The combination of SFRP2 methylation level in PBMCs and AFP could significantly improve the diagnostic ability of AFP in discriminating HBV-associated HCC from CHB and SFRP2 methylation level had the potential to serve as a non-invasive biomarker for HCC diagnosis.


Asunto(s)
Carcinoma Hepatocelular/genética , Proteínas de la Membrana/genética , Adulto , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Metilación de ADN/genética , Femenino , Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , ARN Mensajero/metabolismo , alfa-Fetoproteínas/genética
18.
Medicine (Baltimore) ; 100(2): e24172, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466191

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis. METHODS: Gene expression data of PBMC in both healthy individuals and patients with HCC were extracted from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to annotate the function of DEGs. Protein-protein interaction analysis was performed to screen the hub genes from DEGs. cBioportal database analysis was performed to assess the prognostic significance of hub genes. The Cancer Cell Line Encyclopedia (CCLE) and The Human Protein Atlas (HPA) database analyses were performed to confirm the expression levels of the hub genes in HCC cells and tissue. RESULTS: A total of 95 DEGs were screened. Results of the GO analysis revealed that DEGs were primarily involved in platelet degranulation, cytoplasm, and protein binding. Results of the KEGG analysis indicated that DEGs were primarily enriched in focal adhesion. Five genes, namely, myosin light chain kinase (MYLK), interleukin 1 beta (IL1B), phospholipase D1 (PLD1), cortactin (CTTN), and moesin (MSN), were identified as hub genes. A search in the CCLE and HPA database showed that the expression levels of these hub genes were remarkably increased in the HCC samples. Survival analysis revealed that the overexpression of MYLK, IL1B, and PLD1 may have a significant effect on HCC survival. The aberrant high expression levels of MYLK, IL1B, and PLD1 strongly indicated worse prognosis in patients with HCC. CONCLUSIONS: The identified hub genes may be closely linked with HCC tumorigenicity and may act as potentially useful biomarkers for the prognostic prediction of HCC in PBMC samples.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/sangre , Protocolos Clínicos , Biomarcadores de Tumor/sangre , Análisis por Conglomerados , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Leucocitos Mononucleares , Neoplasias Hepáticas/sangre , Metaanálisis como Asunto , Pronóstico , Mapas de Interacción de Proteínas/genética , Análisis de Supervivencia , Revisiones Sistemáticas como Asunto
19.
J Surg Oncol ; 123(4): 1134-1143, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33497476

RESUMEN

BACKGROUND AND OBJECTIVES: To construct a prediction model of solitary pulmonary nodules (SPNs), to predict the possibility of malignant SPNs in patients aged 15-85 years in northwest China for clinical diagnostic and therapeutic decision-making. METHODS: The features of SPNs were assessed by multivariate logistic regression, followed by visualization using a nomogram. Hosmer lemeshow was applied to evaluate the fitting degree of the model. The area under the receiver operating characteristic (ROC) curve was identified to determine the discriminative ability of the model. RESULTS: Lobulation, spiculation, pleural-tag, carcinoembryonic antigen, neuron-specific enolase, and total serum protein were independent predictors of malignant pulmonary nodules (p < .05). Lobulation (100 points) scored the highest in the nomogram, and the Hosmer-Lemeshow goodness-of-fit statistic was 0.805 (p > .05). The area under curve (AUC) of the modeling and validation groups using logistic regression were 0.859 (95% CI, 0.805-0.903) and 0.823 (95% CI, 0.738-0.890), respectively. Moreover, the AUC of our model was higher than that of the Mayo model, VA model, and Peking University (AUC 0.823 vs. 0.655 vs. 0.603 vs. 0.521). CONCLUSION: Our prediction model is more suitable for predicting the possibility of malignant SPNs in northwest China, and can be calculated using a nomogram to determine further treatments.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Pulmonares/diagnóstico , Modelos Estadísticos , Nomogramas , Nódulo Pulmonar Solitario/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Factores de Riesgo , Nódulo Pulmonar Solitario/sangre , Nódulo Pulmonar Solitario/cirugía , Adulto Joven
20.
Anticancer Res ; 41(2): 1021-1026, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33517310

RESUMEN

BACKGROUND/AIM: Biomarkers for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) are required. We encountered a patient whose skin irAE fluctuated in parallel with serum soluble interleukin-2 receptor (sIL-2R). PATIENTS AND METHODS: We examined 15 patients with cancer who received ICIs. Serum sIL-2R levels before and during ICI treatment were measured. The sIL-2R levels of preserved serum samples from another five patients who developed grade 3 irAEs were measured. RESULTS: Twelve patients showed no significant changes in sIL-2R levels during ICI treatment. Baseline serum sIL-2R levels in three patients increased beyond the normal range before the second cycle. These three patients had grade ≥2 irAEs at the second cycle treatment visit, supporting our hypothesis. Furthermore, at diagnosis of irAEs, the sIL-2R levels of all preserved samples from patients with grade 3 irAEs were significantly elevated. CONCLUSION: Serum sIL-2R is a promising biomarker for the diagnosis of irAEs.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias/tratamiento farmacológico , Receptores de Interleucina-2/sangre , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Humanos , Ipilimumab/efectos adversos , Ipilimumab/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Resultado del Tratamiento , Regulación hacia Arriba
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