RESUMEN
BACKGROUND: The diagnostic value of six tumor markers was investigated and the appropriate combinations of those tumor markers to discriminate small cell lung cancer was explored. METHODS: Patients suspected with lung cancer (1938) were retrospectively analyzed. Candidate tumor markers from carcinoembryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), cytokeratin 19 fragment 21-1 (CYFRA 21-1), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and progastrin releasing peptide (ProGRP) were selected to construct a logistic regression model. The receiver operating characteristic curve was used for evaluating the diagnostic value of the tumor markers and the predictive model. RESULTS: ProGRP had the highest positive rate (72.3%) in diagnosed small cell lung cancer, followed by neuron-specific enolase (68.3%), CYFRA21-1 (50.5%), carcinoembryonic antigen (45.5%), tissue polypeptide antigen (30.7%), and squamous cell carcinoma-related antigen (5.9%). The predictive model for small cell lung cancer discrimination was established, which yielded the highest area under the curve (0.888; 95% confidence interval: 0.846-0.929), with a sensitivity of 71.3%, a specificity of 95.0%, a positive predictive value of 49.0%, and a negative predictive value of 98.0%. CONCLUSIONS: Combining tumor markers can improve the efficacy for small cell lung cancer discrimination. A predictive model has been established in small cell lung cancer differential diagnosis with preferable efficacy.
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Neoplasias Pulmonares , Serpinas , Carcinoma Pulmonar de Células Pequeñas , Antígenos de Neoplasias , Biomarcadores de Tumor , Antígeno Carcinoembrionario , Gastrinas , Humanos , Queratina-19 , Neoplasias Pulmonares/diagnóstico , Fosfopiruvato Hidratasa , Precursores de Proteínas , Estudios Retrospectivos , Sensibilidad y Especificidad , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Antígeno Polipéptido de TejidoRESUMEN
This study tested the hypothesis that MMP-9-/-tPA-/- double knock out (i.e., MTDKO) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MTDKO mouse. Animals were categorized into sham-operated controls in MTDKO animals (group 1) and in wild type (B6: group 2), AMI-MTDKO (group 3) and AMI-B6 (group 4) animals. They were euthanized, and the ischemic myocardium was harvested, by day 60 post AMI. The mortality rate was significantly higher in group 3 than in other groups and significantly higher in group 4 than in groups 1/2, but it showed no difference in the latter two groups (all p < 0.01). By day 28, the left-ventricular (LV) ejection fraction displayed an opposite pattern, whereas by day 60, the gross anatomic infarct size displayed an identical pattern of mortality among the four groups (all p < 0.001). The ratio of heart weight to tibial length and the lung injury score exhibited an identical pattern of mortality (p < 0.01). The protein expressions of apoptosis (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP), fibrosis (Smad3/T-GF-ß), oxidative stress (NOX-1/NOX-2/oxidized-protein), inflammation (MMPs2,9/TNF-α/p-NF-κB), heart failure/pressure overload (BNP/ß-MHC) and mitochondrial/DNA damage (cytosolic-cytochrome-C/γ-H2AX) biomarkers displayed identical patterns, whereas the angiogenesis markers (small vessel number/CD31+cells in LV myocardium) displayed opposite patterns of mortality among the groups (all p < 0.0001). The microscopic findings of fibrotic/collagen deposition/infarct areas and inflammatory cell infiltration of LV myocardium were similar to the mortality among the four groups (all p < 0.0001). MTDKO strongly predicted unfavorable prognostic outcome after AMI.
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Biomarcadores/metabolismo , Matriz Extracelular/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Infarto del Miocardio/fisiopatología , Antígeno Polipéptido de Tejido/genética , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Ventrículos Cardíacos/fisiopatología , Masculino , Ratones , Ratones Noqueados , Mortalidad , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/mortalidad , Tamaño de los Órganos , Pronóstico , Volumen SistólicoRESUMEN
Objective: To investigate the expressional levels and diagnostic values of miR-18a and miR-21 in esophageal carcinoma. Methods: The expressions of miR-18a and miR-21 in esophageal cancer tissues and adjacent tissues from 45 esophageal cancer patients, peripheral blood from 45 esophageal cancer patients and 50 healthy donors respectively were detected by RT-PCR. The expressions of miR-18a and miR-21 in normal esophageal epithelial cell HET-1A, esophageal cancer cell lines including ECA109, KYSE150 and TE1 were also detected. Chemiluminescence immunoassay was used to quantitatively detect the concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYRFA21-1 and TPA (tissue polypeptide antigen) in peripheral blood serum from esophageal cancer patients and healthy controls. Meanwhile, the diagnostic effects of miR-18a and miR-21 on esophageal cancer were compared with those of tumor markers in serum. Results: The expression levels of miR-18a and miR-21 in esophageal cancer cells ECA109, KYSE150 and TE1 were 1.64±0.17, 1.62±0.19, 1.46±0.12 and 20.52±1.48, 6.73±0.73, 1.43±0.19, respectively, higher than those in normal esophageal epithelial cells (both P<0.01). The expressions of miR-18a and miR-21 in esophageal cancer tissues were 32.48±28.62 and 8.67±11.98, respectively, significantly higher than those in adjacent tissues (all P<0.001). The expression levels of miR-18a and miR-21 in peripheral blood of patients with esophageal cancer were 12.66±11.92 and 9.15±8.14, respectively, significantly higher than those in the normal control group (both P<0.001). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-18a and miR-21 for diagnosis of esophageal cancer were 0.948 and 0.913 5, respectively. Compared with traditional esophageal tumor markers, the expressions of miR-18a and miR-21 were more sensitive in the diagnosis of esophageal cancer. The sensitivity and accuracy of the expressions of miR-18a and miR-21 combined with traditional esophageal tumor markers in diagnosis of esophageal cancer can be further improved to 97.8% and 68.4%, respectively. Conclusion: Our study reveals that the expressions of miR-18a and miR-21 play important roles in the diagnosis of esophageal cancer and may be potentially novel biomarkers.
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Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , MicroARNs/metabolismo , Antígenos de Neoplasias/análisis , Área Bajo la Curva , Biomarcadores de Tumor , Antígeno Carcinoembrionario/análisis , Carcinoma de Células Escamosas/química , Estudios de Casos y Controles , Línea Celular Tumoral , Neoplasias Esofágicas/química , Esófago/química , Esófago/metabolismo , Humanos , Curva ROC , Serpinas/análisis , Antígeno Polipéptido de Tejido/análisisRESUMEN
TPA is considered to be a tumor promoting molecule that induces the expression of COX-2 protein. However, it is contradictory to find that TPA can induce tumor cell apoptosis and exert antitumor activity. Therefore, the role of TPA in tumorigenesis and development has not yet been elucidated. Here we show that TPA can promote the apoptosis of breast cancer cells and increase the ratio of Bax/Bcl-2. It is suggested that TPA may induce apoptosis of breast cancer cells through mitochondrial apoptosis pathway. Further studies showed that TPA could cause mitochondrial dysfunction and trigger mitochondrial apoptotic pathway. In mechanism, the mitochondrial targeting of TR3 is involved in TPA induced apoptosis in breast cancer cells. In conclusion, our findings suggest that TPA can play a role in inhibiting cancer by inducing apoptosis and TR3 is expected to be a new target for cancer treatment.
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Neoplasias de la Mama/metabolismo , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Antígeno Polipéptido de Tejido/metabolismo , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Transformación Celular Neoplásica/metabolismo , Femenino , Humanos , Mitocondrias/genética , Mitocondrias/metabolismo , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Proteínas Proto-Oncogénicas c-bcl-2 , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Proteína X Asociada a bcl-2RESUMEN
Serum biomarkers provide valuable information about the diagnosis and prognosis of a wide variety of malignant tumors. Despite the identification of several useful serum biomarkers in lung cancer, consensus on their utility has not yet been reached. Furthermore, guidelines and standard protocols to implement their use for patients with lung cancer are lacking, despite the accumulation of much data on the efficacy of several serum biomarkers over recent decades. In this review, we discuss the molecular features, functions, and clinical relevance of the conventional serum biomarkers for lung cancer, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA 21-1), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), sialyl Lewisx (sLex), carbohydrate antigen 125 (CA-125), squamous cell carcinoma-related antigen (SCC-Ag), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (proGRP), aiming to provide a snapshot of the current landscape and their potential combined utility in the diagnosis and prognosis of lung cancer.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/análisis , Tumor Carcinoide/diagnóstico , Carcinoma Neuroendocrino/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Queratina-19/sangre , Neoplasias Pulmonares/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Antígeno Polipéptido de Tejido/sangre , Antígeno Ca-125/sangre , Humanos , Oligosacáridos/sangre , Fragmentos de Péptidos , Fosfopiruvato Hidratasa/sangre , Proteínas Recombinantes , Antígeno Sialil Lewis XRESUMEN
BACKGROUND: The aim of the present study was to investigate the predictive performance of serial tissue polypeptide antigen (TPA) testing after curative intent resection for detection of recurrence of colorectal malignancy. METHODS: Serum samples were obtained in 572 patients from three different hospitals during follow-up after surgery. Test characteristics of serial TPA testing were assessed using a cut-off value of 75 U/L. The relation with American Joint Committee on Cancer stage and the potential additive value of tissue polypeptide antigen testing upon standard carcinoembryonic antigen (CEA) testing were investigated. RESULTS: The area under the receiver operating characteristic curve of TPA for recurrent disease was 0.70, indicating marginal usefulness as a predictive test. Forty percent of cases that were detected by CEA testing would have been missed by TPA testing alone, whilst most cases missed by CEA were also not detected by TPA testing. In the subpopulation of patients with stage III disease predictive performance was good (area under the curve 0.92 within 30 days of diagnosing recurrent disease). In this group of patients, 86% of cases that were detected by CEA were also detected by TPA. CONCLUSIONS: Overall, TPA is a relatively poor predictor for recurrent disease during follow-up. When looking at the specific subpopulation of patients with stage III disease predictive performance of TPA was good. However, TPA testing was not found to be superior to CEA testing in this specific subpopulation.
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Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/cirugía , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Antígeno Polipéptido de Tejido/sangre , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugíaRESUMEN
So far, a number of tumour-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, carcino-embryonic antigen and others have been identified in a variety of malignant tumours. Differences in the expression levels of TAAs in cancers compared with normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers or exciting targets in cancer treatment. Here, we systematically list the current representative TAAs to shed some light on current approaches and challenges for their anti-cancer application in cancer therapy. In this review, we discuss the ongoing pre-clinical studies and clinical development of TAAs in human cancers, and the potential application of these TAAs in the diagnosis and prognosis for cancer treatment.
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Antígenos de Neoplasias/inmunología , Proteínas de Choque Térmico/inmunología , Neoplasias/inmunología , alfa-Fetoproteínas/inmunología , Antígenos de Carbohidratos Asociados a Tumores/inmunología , Antígeno Carcinoembrionario/inmunología , Glipicanos/inmunología , Humanos , Neoplasias/diagnóstico , Pronóstico , Antígeno Prostático Específico/inmunología , Serpinas/inmunología , Antígeno Polipéptido de Tejido/inmunologíaRESUMEN
AIM: to evaluate an association between fibrinolysis defect and glycemic status in prediabetic population by assessing the levels of t-PA antigen and PAI-1 activity. METHODS: it was an observational study with cross-sectional approach. There were 72 subjects aged 30-50 years who had met the inclusion criteria. The diagnosis of diabetes mellitus (DM) and glycemic index were determined based on the American Diabetes Association (ADA) criteria. The PAI-1 and t-PA antigen levels were measured quantitatively using enzyme-linked immunosorbent assay (ELISA). Analysis between the levels of t-PA antigen and PAI-1 activity was performed using ANOVA. RESULTS: the t-PA antigen level was significantly higher in subjects with impaired glucose tolerance (IGT) and impaired fasting blood glucose (IFBG) as well as subject with impaired fasting blood glucose (IFBG) than those with normal glucose tolerance (NGT) (p=0.047). The PAI-1 activity was significantly higher in subjects with IGT, IFBG and subjects with IFBG than NGT (p=0.024). There was a significant association between glycemic status in prediabetic subjects and PAI-1 activity (p=0.04). CONCLUSION: the level of t-PA antigen and PAI-1 activity were significantly higher in prediabetic subjects than those with NGT; and there was a significant association between glycemic status in prediabetic subjects and PAI-1 activity.
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Inhibidor 1 de Activador Plasminogénico/metabolismo , Estado Prediabético/metabolismo , Antígeno Polipéptido de Tejido/metabolismo , Adulto , Glucemia/análisis , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Retinol and its derivatives play an important role in epidermal growth and differentiation and represent chemopreventive agents in nonmelanoma skin cancer. Retinoic acid binding protein II (CRABP-II) is a cytoplasmic receptor that critically regulates all-trans-retinoic acid (ATRA) trafficking. We documented the marked reduced expression of CRABP-II and its promoter methylation in human poorly differentiated squamous cell carcinomas. To investigate the role of CRABP-II in skin carcinogenesis we used skin lesion induction by dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate in CRABP-II-knockout C57BL/6 mice. We observed earlier and more diffuse epidermal dysplasia, greater incidence and severity of tumors, reduced expression of cytokeratin 1/cytokeratin 10 and involucrin, increased proliferation, and impaired ATRA inhibition of tumor promotion compared with wild-type animals. CRABP-II-transfected HaCaT, FaDu, and A431 cells showed expression of differentiation markers, retinoic acid receptor-ß/-γ signaling, ATRA sensitivity, and suppression of EGFR/v-akt murine thymoma viral oncogene homolog 1 (AKT) pathways in a fatty acid binding protein 5/peroxisome proliferator-activated receptor-ß/-δ-independent manner. The opposite was true in keratinocytes isolated from CRABP-II-knockout mice. Finally, CRABP-II accumulation induced ubiquitination-associated reduction of EGFR. Our results showed reduced CRABP-II expression in human poorly differentiated squamous cell carcinomas, and its gene deletion favored experimental skin carcinogenesis and impaired ATRA antitumor efficacy, likely modulating EGFR/AKT pathways and retinoic acid receptor-ß/-γ signaling. Therapeutic interventions aimed at restoring CRABP-II-mediated signaling may amplify therapeutic retinoid efficacy in nonmelanoma skin cancer.
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Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica , Receptores de Ácido Retinoico/genética , Neoplasias Cutáneas/genética , 9,10-Dimetil-1,2-benzantraceno/metabolismo , Animales , Biopsia con Aguja , Carcinogénesis/genética , Carcinoma de Células Escamosas/patología , Células Cultivadas , Metilación de ADN , Modelos Animales de Enfermedad , Regulación hacia Abajo , Humanos , Inmunohistoquímica , Queratinocitos/citología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Regiones Promotoras Genéticas , Neoplasias Cutáneas/patología , Antígeno Polipéptido de Tejido/metabolismo , TransfecciónRESUMEN
AIM: The aim of the study was to assess the degree to which tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), as well as carcinoembryonic antigen (CEA), can assist in the detection of distant metastases. PATIENTS AND METHODS: We assessed 157 patients with colorectal and breast cancer divided into two groups. The first was a group of patients with cancer at stages 1, 2 and 3; the second was a group of patients with cancer at stage 4 with metastasis. RESULTS: We found significantly higher levels of all biomarkers in the metastatic group compared to the group with cancer at stages 1-3 (p<0.0001). The calculated area under the receiver operating characteristic (ROC) curve was 0.9929 for TPS, 0.9337 for TPA and 0.7234 for CEA. The cut-off was calculated for each biomarker at 95% specificity, TPS cut-off=255 IU/l (sensitivity 95%), TPA cut-off=200 IU/l (sensitivity 70%) and CEA cut-off=18 µg/l (sensitivity 37%). CONCLUSION: We suggest combining CEA with TPS or TPA in the detection of distant metastases or using only cytokeratins. This approach can significantly increase the quality of detection of the metastatic process.
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Neoplasias Óseas/sangre , Neoplasias de la Mama/sangre , Neoplasias Colorrectales/sangre , Neoplasias Renales/sangre , Neoplasias Hepáticas/sangre , Neoplasias Pulmonares/sangre , Péptidos/sangre , Antígeno Polipéptido de Tejido/sangre , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales/patología , Femenino , Humanos , Neoplasias Renales/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Curva ROC , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Regulación hacia Arriba , Adulto JovenRESUMEN
OBJECTIVE: We investigated the value of the joint detection of tissue polypeptide antigen (TPA), ovarian cancer antigen X1 (OVX1), cathepsin L (CTSL) and CA125 on the early diagnosis of epithelial ovarian carcinoma (EOC). PATIENTS AND METHODS: From October 2011 to February 2015, 84 cases of patients under surgical treatment of epithelial ovarian cancer, 98 cases of patients with benign epithelial ovarian tumor and 51 subjects in healthy control group were selected to detect the level of TPA, OVX1 and CTSL in serum from the Obstetrics and Gynecology Department of the First Affiliated Hospital of Liaoning Medical University. The clinical data of patients with ovarian tumor were collected and analyzed, and the levels of CA12 were measured. RESULTS: 3 indicators in the malignant group were significantly higher than those in the benign group and healthy control group (p < 0.05). The total positive rate and the positive rate of early detection of TPA on EOC were the highest, and the total positive rate of OVX1 was lower than that of CA125. The total positive rate and the positive rate of early detection of CA125+TPA on EOC were the highest. The positive rate of early detection and the total positive rate of the pairwise combined detection of the other index and CA125 on EOC were significantly higher than those of the single detection of CA125 (p < 0.05). The joint detection of CA125+ OVX1 and the single detection of CA125 were not statistically significant. However, the remaining differences were statistically significant (p < 0.05). CONCLUSIONS: The level of TPA, OVX1 and CTSL in serum was potential detection index, the joint detection of TPA and CA125 was the ideal combination, which took into account the total positive rate, the positive rate of early detection on EOC and the improved diagnostic rate of EOC.
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Catepsina L , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Ováricas/diagnóstico , Antígeno Polipéptido de Tejido , Biomarcadores de Tumor/sangre , Antígeno Ca-125/sangre , Carcinoma Epitelial de Ovario , Detección Precoz del Cáncer , Femenino , HumanosRESUMEN
The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.
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Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Antígeno Carcinoembrionario/sangre , Metilación de ADN/genética , Mucina-1/sangre , Antígeno Polipéptido de Tejido/sangre , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Regiones Promotoras Genéticas , Proteínas Supresoras de Tumor/genéticaRESUMEN
A novel sandwich-type electrochemical immunoassay with sensitivity enhancement was developed for quantitative detection of tissue polypeptide antigen (TPA) by coupling with target-induced tyramine signal amplification on prussian blue-gold hybrid nanostructures. The immunosensor was prepared through immobilizing anti-TPA capture antibody on a cleaned screen-printed carbon electrode (SPCE). Prussian blue-gold hybrid nanostructures (PBGNS) labeled with horseradish peroxidase (HRP) and detection antibody were utilized as the signal-transduction tags. Upon target TPA introduction, the sandwiched immunocomplex was formed between capture antibody and detection antibody on the electrode. The carried HRP could trigger the formation of tyramine-HRP repeats on the PBGNS in the presence of H2O2. Using the doped prussian blue as the electron mediator, the conjugated HRP could catalyze the reduction of H2O2. Under the optimal conditions, the catalytic currents increased with the increasing target TPA in the dynamic range from 1.0 pg mL(-1) to 100 ng mL(-1) with a detection limit of 0.3 pg mL(-1). The reproducibility and specificity of the electrochemical immunoassay were acceptable. In addition, the contents of target TPA in nine human serum specimens were evaluated by using the developed electrochemical immunosensor, and the obtained results correlated well with those from commercially enzyme-linked immunosorbent assay (ELISA) method with a correlation coefficient of 0.9975.
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Técnicas Biosensibles/métodos , Técnicas para Inmunoenzimas/métodos , Antígeno Polipéptido de Tejido/sangre , Anticuerpos Inmovilizados , Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Ferrocianuros , Oro , Peroxidasa de Rábano Silvestre , Humanos , Límite de Detección , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , TiraminaRESUMEN
BACKGROUND: To determine the potential clinical utility of tumor markers CEA, TPA, and SCC-Ag for early detection of cervical precancerous lesions. MATERIALS AND METHODS: A case-control study was carried out on 120 women (46 patients with histologically confirmed cervical precancerous lesions and 74 healthy controls). The significance of serum selected tumor markers in early detection of cervical intraepithelial neoplasia (CIN) were assessed. RESULTS: Of the case group, the rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to the manufacturer's cut-off values of 2 ng/ml, 5 ng/ml, and 70 U/ml for SCC-Ag, CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA and TPA tests could not distinguish between case and control groups. The diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag, 2.6 ng/ ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%, respectively. However, the area under the receiver operating characteristic curve was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA, respectively). Moreover, there was a highly significant direct correlation between SCC-Ag concentration and the degree of cervical precancerous lesions (r=0.847, p<0.001). CONCLUSIONS: The new cutoff of 0.5 for SCC-Ag test might be useful as a tumor marker in Iranian patients with CIN and it needs to be more evaluated by studies with larger populationa.
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Antígenos de Neoplasias/sangre , Antígeno Carcinoembrionario/sangre , Serpinas/sangre , Antígeno Polipéptido de Tejido/sangre , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Detección Precoz del Cáncer , Femenino , Humanos , Irán , Prueba de Papanicolaou , Lesiones Precancerosas/sangre , Lesiones Precancerosas/diagnóstico , Curva ROC , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/sangre , Frotis Vaginal , Displasia del Cuello del Útero/sangreRESUMEN
This study clarifies the relationship between clinical and laboratory patterns, in endocrine-responsive metastatic breast cancer patients treated with a cyclic beta-interferon and interleukin-2 sequence added to anti-estrogens. In 31 patients, a regular laboratory and immunological assessment was made. During clinical benefit, as opposed to progression, a significant increase in the total number of lymphocytes, CD4+, CD8+, NK cells, CRP and IL-12 was confirmed. Also, a significant CEA, TPA, CA15.3 decrease occurred 24-72h after interleukin-2 administration. At the progression, both basally and after interleukin-2 stimulation, the mean values of CD4+ plus CD25+ cells were more than twice higher than during clinical benefit, with a decrease of CD4+ plus CD8+ (Teffector)/CD4+CD25+ (Treg) ratio. Moreover, a significant increase for CEA and for all 3 markers (standardized values) was found 24-72h after interleukin-2 administration. In patients who survived less than 5years, the Treg cell increase occurred at a significantly shorter time interval than in those who survived longer than 5years (20 vs 45.5months, respectively; P=0.001). These data show laboratory evidence of the effect of immunotherapy as well as that of hormone resistance occuring concomitantly with a laboratory pattern compatible with immune inhibition.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Inmunidad Celular/efectos de los fármacos , Interferón beta/uso terapéutico , Interleucina-2/uso terapéutico , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Antígeno Carcinoembrionario/sangre , Citocinas/sangre , Citocinas/inmunología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoterapia , Interferón beta/administración & dosificación , Interleucina-2/administración & dosificación , Letrozol , Persona de Mediana Edad , Mucina-1/sangre , Metástasis de la Neoplasia , Neoplasias Hormono-Dependientes/inmunología , Neoplasias Hormono-Dependientes/mortalidad , Neoplasias Hormono-Dependientes/patología , Nitrilos/administración & dosificación , Nitrilos/uso terapéutico , Modelos de Riesgos Proporcionales , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Tamoxifeno/administración & dosificación , Tamoxifeno/uso terapéutico , Antígeno Polipéptido de Tejido/sangre , Toremifeno/administración & dosificación , Toremifeno/uso terapéutico , Triazoles/administración & dosificación , Triazoles/uso terapéuticoRESUMEN
BACKGROUND: Several criteria have been proposed to interpret increments in serological cancer biomarker concentrations starting from low baseline concentrations crossing the cut-off. None of the criteria have been compared for their ability to signal tumour growth when ≤2% false positive results are accepted. METHODS: The cancer biomarker Tissue Polypeptide Antigen was used as an example. Seven criteria to interpret increments in concentrations were investigated by computer simulations. Firstly, for each criterion, we identified a baseline concentration stratified for three levels of biological variation providing ≤2% false positive signals of tumour growth during one year of monitoring. Secondly, combining the steady state concentrations with rates of marker increase during tumour growth allowed calculation of the lengths of tumour detection times for each criterion. RESULTS: The number of false positive marker signals depended on the baseline concentration, the magnitude of biological variation, and the magnitude of the required increment defined in the criterion. The lengths of the tumour detection times also depended on the rates of marker increase. CONCLUSIONS: The results suggest that different types of criteria should be used within different intervals of below cut-off level concentrations if the rate of false positive signals of marker increments should be kept ≤2%.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias/diagnóstico , Algoritmos , Simulación por Computador , Progresión de la Enfermedad , Reacciones Falso Positivas , Humanos , Neoplasias/patología , Valores de Referencia , Antígeno Polipéptido de Tejido/análisisRESUMEN
A sandwich-type immunosensor was developed for the detection of human tissue polypeptide antigen (hTPA). In this work, a graphene sheet (GS) was synthesized to modify the surface of a glassy carbon electrode (GCE), and Pd-Pt bimetallic nanocrystals were used as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for catalyzing hydrogen peroxide (H2O2) was recorded. And electrochemical impedance spectroscopy was used to characterize the fabrication process of the immunosensor. The anti-human tissue polypeptide antigen primary antibody (Ab1) was immobilized onto the GS modified GCE via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). With Ab1 immobilized onto the GS modified GCE and Ab2 linked on Pd-Pt bimetallic nanocrystals, the immunosensor demonstrated a wide linear range (0.0050-15 ng ml(-1)), a low detection limit (1.2 pg ml(-1)), good reproducibility, good selectivity and acceptable stability. This design strategy may provide many potential applications in the detection of other cancer biomarkers.
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Técnicas Biosensibles/instrumentación , Nanopartículas del Metal , Antígeno Polipéptido de Tejido/análisis , Anticuerpos Inmovilizados , Técnicas Electroquímicas , Grafito , Humanos , Inmunoensayo/métodos , Límite de Detección , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Nanotecnología , Paladio , Platino (Metal) , Reproducibilidad de los Resultados , Antígeno Polipéptido de Tejido/sangreRESUMEN
To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/sangre , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/sangre , Antígenos de Carbohidratos Asociados a Tumores/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Péptidos/sangre , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Serpinas/sangre , Neoplasias Gástricas/sangre , Neoplasias Gástricas/cirugía , Antígeno Polipéptido de Tejido/sangre , alfa-Fetoproteínas/metabolismoRESUMEN
The higher incidence of breast cancer in developed countries has been tempered by reductions in mortality, largely attributable to mammographic screening programmes and advances in adjuvant therapy. Optimal systemic management requires consideration of clinical, pathological and biological parameters. Oestrogen receptor alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) are established biomarkers evaluated at diagnosis, which identify cardinal subtypes of breast cancer. Their prognostic and predictive utility effectively guides systemic treatment with endocrine, anti-HER2 and chemotherapy. Hence, accurate and reliable determination remains of paramount importance. However, the goals of personalized medicine and targeted therapies demand further information regarding residual risk and potential benefit of additional treatments in specific circumstances. The need for biomarkers which are fit for purpose, and the demands placed upon them, is therefore expected to increase. Technological advances, in particular high-throughput global gene expression profiling, have generated multi-gene signatures providing further prognostic and predictive information. The rational integration of routinely evaluated clinico-pathological parameters with key indicators of biological activity, such as proliferation markers, also provides a ready opportunity to improve the information available to guide systemic therapy decisions. The additional value of such information and its proper place in patient management is currently under evaluation in prospective clinical trials. Expanding the utility of biomarkers to lower resource settings requires an emphasis on cost effectiveness, quality assurance and possible international variations in tumor biology; the potential for improved clinical outcomes should be justified against logistical and economic considerations.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Recursos en Salud/provisión & distribución , Terapia Molecular Dirigida , Antígenos de Carbohidratos Asociados a Tumores/sangre , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/epidemiología , Antígeno Carcinoembrionario/sangre , Proliferación Celular , Análisis Costo-Beneficio , Ciclina D1/metabolismo , Ciclina E/metabolismo , ADN de Neoplasias , Países Desarrollados/estadística & datos numéricos , Países en Desarrollo/estadística & datos numéricos , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Femenino , Perfilación de la Expresión Génica , Salud Global , Humanos , Antígeno Ki-67/metabolismo , Células Neoplásicas Circulantes , Inhibidor 1 de Activador Plasminogénico/metabolismo , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Garantía de la Calidad de Atención de Salud , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Antígeno Polipéptido de Tejido/sangre , Transcriptoma , Activador de Plasminógeno de Tipo Uroquinasa/metabolismoRESUMEN
BACKGROUND: To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy. MATERIAL AND METHODS: One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses. RESULTS: A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value. CONCLUSIONS: Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.