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1.
Medicine (Baltimore) ; 99(1): e18574, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895802

RESUMO

Progranulin (PGRN) is a secreted protein that can regulate cell cycle progression, cell motility, and tumorigenesis. The PGRN expression in hematological malignancies is limited to multiple myeloma, but its expression and survival prognostic role in acute myeloid leukemia (AML) is still controversial.To evaluate the PGRN expression and estimate its survival prognostic role in AML patients.In this study, all patients were divided into three groups, which included 38 newly diagnosed adult AML patients, 33 complete remissions (CR-AML) patients, and 60 healthy control (HC) patients. The endpoints were relapse-free survival (RFS) and overall survival (OS). We investigated plasma PGRN levels by using enzyme-linked immunosorbent assay.Plasma PGRN levels in AML patients were higher than that in CR-AML and HC groups. After two chemo cycles, 16 patients had complete remission (CR). The level of plasma PGRN in non-CR patients compared to CR patients was obviously different (median 44.19 vs 21.10 ng/mL) (P = .025). In non-M3 (French-American-British classification) patients, 70% (21/30) patients relapsed in 1 year and 80% (24/80) patients died in the observed time. Using the value (median 19.95) as a "cut-off" value, we have divided non-M3 patients into low- and high-PGRN expression groups. High-PGRN expression patients had a poorer RFS with a median of 5.4 months (95% CI 3.7-7.1) and low-PGRN expression patients had a good RFS with a median of 8.9 months (95% CI 6.3-11.5; P = .027). In the survival analyses, high-PGRN expression of AML patients had shorter OS than low-PGRN expression of AML patients (6.2 vs 20.5 months, P = .008).PGRN is overexpressed in AML, which is a convenient and independent prognostic marker that is measured easily in AML patients.


Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Progranulinas/sangue , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Quimioterapia de Indução/mortalidade , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Adulto Jovem
2.
Br J Radiol ; 93(1105): 20190719, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31670571

RESUMO

OBJECTIVE: To compare therapeutic outcomes between hepatic resection (HR) and radiofrequency ablation (RFA) for small hepatic masses diagnosed as hepatocellular carcinoma (HCC) on pre-treatment imaging study. METHODS: Our institutional review board approved this retrospective study, and informed consent was waived. Patients with a single (≤3 cm) mass diagnosed as HCC on pre-treatment imaging study between January 2008 and December 2009 who underwent HR (n = 145) or RFA (n = 178) were included. Recurrence-free survival (RFS) and overall survival (OS) were assessed. In the HR group, the false-positive rate for imaging diagnosis was calculated. For the RFA group, the local tumor progression rate was calculated. RESULTS: RFS rates at 5 years were 59.3% for the HR group and 32.2% for the RFA group. OS rates at 5 years were 85.4% for the HR group and 76.8% for the RFA group. In the RFA group, cumulative local tumor progression rates were 8.3 and 20.2% at 1 and 3 years. Treatment modality was not an independent prognostic factor for either RFS or OS on multivariate analysis. The false-positive rate for HCC diagnosis based on imaging criteria was 4.8% in the HR group. CONCLUSION: The imaging criteria for diagnosis of HCC have a high positive predictive value. Multivariate analysis showed that RFS and OS rates were not significantly different between HR and RFA for small hepatic masses diagnosed as HCC on pre-treatment imaging. ADVANCES IN KNOWLEDGE: Treatment modality (hepatic resection vs RFA) was not an independent prognostic factor for both RFS and OS for small masses (≤3 cm) diagnosed as hepatocellular carcinoma on pre-treatment imaging.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência , Biomarcadores Tumorais/sangue , Meios de Contraste , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
3.
Gut ; 69(1): 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30971436

RESUMO

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Doenças Biliares/diagnóstico , Doenças Biliares/genética , Doenças Biliares/patologia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Constrição Patológica/diagnóstico , Constrição Patológica/genética , Diagnóstico Diferencial , Feminino , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Adulto Jovem
4.
Gut ; 69(1): 103-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023832

RESUMO

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/cirurgia , Vitamina D/análogos & derivados , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptores de Calcitriol/genética , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue , Vitamina D/sangue
6.
J Urol ; 203(1): 73-82, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389764

RESUMO

PURPOSE: Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases. MATERIALS AND METHODS: We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer. RESULTS: Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p <0.0001) and clinically significant prostate cancer (p <0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629). CONCLUSIONS: Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment.


Assuntos
Células Neoplásicas Circulantes , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biomarcadores Tumorais/sangue , Biópsia , MicroRNA Circulante/sangue , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Gradação de Tumores , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Sensibilidade e Especificidade
7.
J Urol ; 203(1): 83-91, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430244

RESUMO

PURPOSE: The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml. MATERIALS AND METHODS: Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer. RESULTS: Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy. CONCLUSIONS: Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Biópsia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Precursores de Proteínas
8.
Medicine (Baltimore) ; 98(50): e17814, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852062

RESUMO

The purpose of our research was to evaluate diagnostic performance of serum microRNA-135a (miR-135a) in non-small cell lung cancer (NSCLC).Quantitative real time-polymerase chain reaction was employed to detect the expression serum of miR-135a in NSCLC patients and controls. The influence of serum miR-135a level on clinical characteristics of NSCLC patients was explored through the Chi-square test. Serum carcinoembryonic antigen (CEA) level was estimated via enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was plotted to elucidate diagnostic roles of serum miR-135a and CEA in NSCLC.The expression level of serum miR-135a was significantly lower in NSCLC patients than in healthy controls (0.40 ±â€Š0.29 vs 1.00 ±â€Š0.40, P < .001). Moreover, miR-135a expression was related to lymph node metastasis (P = .021), tumor differentiation (P = .020), and tumor node metastasis stage (P = .031). ROC curve showed serum miR-135a level could discriminate NSCLC patients from healthy controls (P < .0001) with a corresponding cutoff value of 0.665, and a sensitivity and specificity of 81.3% and 83.1%, respectively. The area under the curve was 0.888. In diagnosis analysis on the combination of miR-135a and CEA, when its specificity was maintained at 90%, diagnosis cut-off point reached 0.678.Serum miR-135a level is significantly downregulated in NSCLC and serves as a potential diagnostic biomarker for the disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , MicroRNAs/sangue , Estadiamento de Neoplasias/métodos , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , RNA Neoplásico/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real
9.
Bratisl Lek Listy ; 120(12): 912-918, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855050

RESUMO

OBJECTIVES: The objective of this study was to evaluate the diagnostic value of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte­to­monocyte ratio (LMR), and mean platelet volume (MPV) in patients with endometriosis as compared with healthy controls. BACKGROUND: Currently, no non-invasive diagnostic test of endometriosis has been implemented in clinical practice. METHODS: A total of 121 women with endometriosis and 136 controls participated in this retrospective study. The extent of the disease in the patients with endometriosis was determined using the American Society of Reproductive Medicine revised classification. Sensitivities and specificities of NLR, LMR and MPV were evaluated by receiver-operating characteristic (ROC) analysis. RESULTS: Patients with endometriosis had higher neutrophil counts, white blood cell (WBC) levels, NLR, MPV, and lower lymphocyte count and LMR than the control group. The cut-off values were found to be 1.6 for NLR at 87.6 % sensitivity and 44.8 % specificity and 8 for MPV at 75.2 % sensitivity and 68.4 % specficity. For LMR, the cut-off value was 5.6 with 66.1 % sensitivity, 50 % specificity. Patients with stages III or IV had significantly lower MPV (p = 0.039) and LMR levels (p = 0.016) than patients with stages I or II. CONCLUSION: NLR, LMR, and MPV may be used to distinguish patients with endometriosis from controls (Tab. 4, Fig. 4, Ref. 37).


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Endometriose/diagnóstico , Contagem de Linfócitos , Volume Plaquetário Médio , Estudos de Casos e Controles , Endometriose/sangue , Endometriose/imunologia , Feminino , Humanos , Linfócitos , Neutrófilos , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
Medicine (Baltimore) ; 98(50): e18306, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852112

RESUMO

This retrospective analysis of patients aims to show the blood levels of preoperative inflammatory markers in patients with glioblastoma and brain metastasis and to provide the diagnostic accuracy of the neutrophil-lymphocyte (NLR), lymphocyte-monocyte (LMR), and platelet-lymphocyte (PLR) ratios between the 2 groups of patients.The retrospective reviews of the neutrophil, lymphocyte, monocyte, and platelet counts were analyzed in 80 patients with newly diagnosed glioblastoma and 70 patients with brain metastasis. The NLR, LMR, and PLR were calculated in each group. The differences in all the parameters were compared between the 2 groups.Although the neutrophil, monocyte, and platelet counts were higher and the lymphocyte count was lower in patients with metastasis, the difference was not significant. A significantly higher PLR (P = .004) and a lower LMR (P = .01) were found in patients with brain metastasis. Although both PLR and LMR had diagnostic accuracy in differentiating glioblastoma from brain metastasis, LMR showed the highest diagnostic accuracy. NLR showed no diagnostic accuracy.Systemic inflammation is more severe in glioblastoma than in brain metastasis, and LMR is more sensitive and/or specific than PLR in differentiating glioblastoma from brain metastasis. Therefore, LMR (less likely PLR) can be used as an index for differentiating between glioblastoma and brain metastasis before surgery.


Assuntos
Plaquetas/patologia , Neoplasias Encefálicas/secundário , Glioblastoma/diagnóstico , Linfócitos/patologia , Monócitos/patologia , Procedimentos Neurocirúrgicos , Neutrófilos/patologia , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Glioblastoma/cirurgia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Contagem de Plaquetas , Período Pré-Operatório , Estudos Retrospectivos
11.
Medicine (Baltimore) ; 98(50): e18310, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852114

RESUMO

PURPOSE: We designed the study to investigate the incidence risk of Programmed Cell Death-1 (PD-1) or Ligand 1 (PD-L1) inhibitor-related endocrine dysfunction in patients with lung cancer. METHOD: All the data were collected by 1 primary reviewer and then independently reviewed by 2 secondary reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) guidelines. Incidence risk of all-grade and grade 3-5 PD-1/PD-L1 inhibitors related endocrine dysfunction in patients with lung cancer were taken into account. RESULTS: Overall, 12 clinical trials comprising 6108 patients were identified in this systematic review and meta-analysis. The incidence risk of hypothyroidism, hyperthyroidism and adrenal insufficiency was higher in NSCLC patients receiving combination treatments. The incidence rate of all-grade of hypothyroidism was lower in PD-1/PD-L1 inhibitor subgroup compared to chemotherapy (OR = 22.62, 95%CI:9.79-52.25), while the similar result was seen in another treatment regimen (PD-1 + platinum-based chemotherapy vs platinum-based chemotherapy) (OR = 2.93, 95%CI: [2.08, 4.11). The different result can be seen in the group related to the other treatment regimen (1PD-1/PD-L1 inhibitor vs 2 PD-1/PD-L1 inhibitors) (OR = 0.40, 95%CI:0.21-0.76). All the results of the above analysis were considered to be statistical significant. Similar result could also be seen in meta-analysis related to hyperthyroidism and adrenal insufficiency. CONCLUSION: The incidence risk of endocrine dysfunctions, including hypothyroidism, hyperthyroidism and adrenal insufficiency, were higher for PD-1/PD-L1 inhibitors group.


Assuntos
Antígeno B7-H1/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Doenças do Sistema Endócrino/sangue , Neoplasias Pulmonares/sangue , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/sangue , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Saúde Global , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico
12.
Medicine (Baltimore) ; 98(45): e17931, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702677

RESUMO

When making clinical decisions concerning additional treatment for patients who have undergone radical prostatectomy (RP), adverse laboratory/pathological features are considered major factors. We investigated and compared the prognostic efficacy of adverse laboratory/pathological features in predicting overall survival (OS) and biochemical failure (BCF) in these patients.The Korean Prostate Cancer Database was used to identify patients undergoing RP between May 2001 and April 2013. Patients with incomplete clinicopathological data or positive lymphadenectomy results were excluded. Finally, 4486 patients included in the final analysis were categorized based on their adverse laboratory/pathological features.Adverse pathological features and detectable prostate-specific antigen (PSA) levels 6 weeks after surgery were observed in 1977 (44.1%) and 634 (14.1%) patients, respectively. PSA levels, pathological Gleason score ≥8, adverse pathological features [positive surgical margin (PSM), seminal vesicle invasion (SVI), and extracapsular extension (ECE)], and adverse laboratory features (detectable PSA levels after 6 weeks) together were significant predictors of BCF-free survival (BCFFS). SVI was identified as a predictor of OS. Additionally, patients with ECE, PSM, and detectable PSA levels after 6 weeks, but without SVI, showed similar OS to those without ECE, PSM, and detectable PSA levels after 6 weeks and with SVI (log-rank test, P = .976).We successfully stratified patients based on adverse laboratory/pathological features after RP and demonstrated that these are important prognostic factors for OS and BCFFS. Additionally, we identified the criteria for selecting appropriate patients for undergoing additional treatment based on OS and BCFFS.


Assuntos
Biomarcadores Tumorais/sangue , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Humanos , Masculino , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Prostatectomia/mortalidade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Sistema de Registros , Glândulas Seminais/patologia
13.
Anticancer Res ; 39(11): 6125-6133, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704840

RESUMO

AIM: The aim of the study was to identify novel biomarkers that are vital for improving management of patients with gastric cancer (GC). MATERIALS AND METHODS: An RNA-sequencing analysis was conducted using gastric tissue from patients with metastatic GC. In vitro cell functions were evaluated by siRNA-mediated knockdown assays. A total of 230 pairs of gastric tissue were subjected to expression analysis of mRNA and protein in situ. The serum levels of the candidate biomarker were determined by ELISA. RESULTS: MELTF was identified as a candidate biomarker. Inhibition of MELTF expression suppressed the invasion ability of GC cells. Increased tissue MELTF mRNA expression was associated with shorter survival. Furthermore, staining intensity of tissue MELTF protein was linked to recurrence rates. Serum MELTF levels gradually were increased from healthy controls to advanced GC. Patients with high serum MELTF levels had poor prognosis. CONCLUSION: Both tissue and serum MELTF levels may serve as biomarkers of GC progression.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Glicoproteínas de Membrana/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirurgia , Células Tumorais Cultivadas
14.
Anticancer Res ; 39(11): 6193-6196, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704847

RESUMO

BACKGROUND/AIM: Carbohydrate antigen 19-9 (CA19-9) is a tumor marker for pancreatic cancer. Irreversible electroporation (IRE) is an experimental treatment modality for pancreatic cancer. The aim of this study was to evaluate whether percutaneous IRE lowers the CA19-9 level in pancreatic cancer and whether this correlates with improved overall survival. PATIENTS AND METHODS: Seventy-one patients with locally advanced pancreatic cancer or local recurrence after resection were treated. Patients with missing data, metastatic disease and normal serum CA19-9 before IRE were excluded. This left 35 cases for analysis. RESULTS: The median CA19-9 did not decrease in the cohort after IRE treatment (282 U/ml before versus 315 U/ml after; p=0.80). The 25th percentile of patients with the best CA19-9 response had improved overall survival compared to the 25th percentile with the worst response (mean 13.1 versus 8.1 months, respectively; p=0.01). CONCLUSION: IRE did not lower the level of CA19-9 in pancreatic cancer cases. However, a response in CA19-9 was correlated with improved survival.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Eletroporação/métodos , Recidiva Local de Neoplasia/sangue , Neoplasias Pancreáticas/sangue , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Taxa de Sobrevida
15.
Anticancer Res ; 39(11): 6231-6240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704852

RESUMO

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Interferon gama/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Tuberculose Latente/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos , Linfócitos T/imunologia , Fatores de Tempo
16.
Anticancer Res ; 39(11): 6317-6324, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704862

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate N-acetylgalactosamine-6-sulfatase (GALNS) as a new biomarker candidate for detecting lung cancer. Glycodelin or PAEP, the serum levels of which are known to be elevated in lung and other cancers, served as a benchmark for comparison. PATIENTS AND METHODS: A total of 170 serum samples from healthy controls and patients with pneumonia, lung cancer, breast cancer, colon cancer, liver cancer, and head and neck cancer were analyzed for the levels of GALNS and PAEP by ELISA. RESULTS: The median serum levels of GALNS and PAEP in all cancer types as well as pneumonia patients were significantly higher than those of the healthy controls. CONCLUSION: In addition to previously known cancers, the median serum levels of PAEP were also found to be higher in liver and head and neck cancer patients. GALNS and PAEP are promising general biomarkers for multiple cancers and deserve further evaluation.


Assuntos
Biomarcadores Tumorais/sangue , Condroitina Sulfatases/sangue , Glicodelina/sangue , Neoplasias Pulmonares/sangue , Área Sob a Curva , Benchmarking , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias do Colo/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Neoplasias Hepáticas/sangue , Pulmão/metabolismo , Neoplasias Pulmonares/diagnóstico , Masculino , Pneumonia/sangue
17.
Klin Lab Diagn ; 64(10): 607-612, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31742954

RESUMO

Liver cirrhosis in the outcome of hepatitis C is the leading cause of hepatocellular carcinoma (HCC) in the world. Early diagnosis and timely treatment of HCC are important for reducing mortality and increasing life expectancy of patients with hepatocellular carcinoma. To assess the risk of HCC, the definition of alpha-fetoprotein (AFP) in the blood is most widely used, but low sensitivity limits its diagnostic value. In 2012, a new HCC biomarker - osteopontin (OPN), which is a secreted phosphoprotein that has a high affinity for integrins was proposed. The level of acute renal failure begins to rise in the early stages of malignancy, before the period of HCC detection by imaging methods, and has significantly better sensitivity than AFP. The purpose of this study is to evaluate the diagnostic efficacy of the combined determination of alpha-fetoprotein and osteopontin in prospective monitoring of patients with chronic hepatitis C in the advanced phase of liver fibrosis. Monitoring of 588 patients with hepatitis C was carried out from February 2013 to February 2019. HCC was detected in 55 of them (2.6% per year). The combination of 2 biomarkers showed better diagnostic efficacy than alpha-fetoprotein and osteopontin separately: AUC 0.85 (95% CI 0.80-0.90) versus AUC 0.63 (95% CI 0.57-0, 70) and AUC 0.82 (95% CI 0.77-0.88), respectively. This combination showed a sensitivity of 85.5% and made it possible to diagnose HCC with a prognostic level of a positive result of 72.3% at 19,4±0,8 weeks before the diagnosis was confirmed by instrumental imaging methods (ultrasound, MRI, CT). In the combined variant, ARF made the greatest contribution to the increase in diagnostic efficacy (AUC). At an early and very early stage of HCC development, isolated HCC elevations were found in only 5.4% of patients. Conclusion: the combined use of alphafetoprotein and osteopontin as a diagnostic panel can be recommended for monitoring patients with liver cirrhosis in the outcome of hepatitis C and predicting HCC at an early stage of development.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatite C/diagnóstico , Neoplasias Hepáticas/diagnóstico , Osteopontina/sangue , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , Humanos , Fragmentos de Peptídeos , Estudos Prospectivos
18.
Georgian Med News ; (294): 22-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687943

RESUMO

The aim is to discuss the contribution of the DR-70 for the patients with high PSA level and which cutofflevel of DR-70 must be consideredthe biopsy decision. 93 patients with high prostate specific antigen level were enrolled into the study. Before the prostate biopsy, total PSA (tPSA), free PSA (fPSA), free/total PSA rate (f/tPSA), PSA density (PSAD) and DR-70 levels were recorded. The patients were divided into two groups according to the pathological outcome of benign (G1) or malignant (G2). G1 and G2 were compared with Mann-Whitney U test, Spearman's rho and ROC curve for analysis. The significance level is taken as .05 for all tests. The median age of patients in G1 and G2 was 62.52 and 68.22 years, respectively. The mean PV in G1 and G2 were 52.16 and 39.6 mL, respectively. The mean tPSA, PSAD and DR-70 levels in G1 and G2 were found as 7.19 and 18.74 ng/mL, 0.14 and 0.48 ng/mL/cc and 0.44 and 0.5 µg/mL, respectively. The mean age of the patients in G2 was statistically significantly higher than G1 (p=.001).The mean PV of the patients in G2 was statistically significantly lower than G1 (p=.001).The mean PSAD of the patients in G2 was statistically significantly higher than G1 (p=.001). There was no statistically significant difference on DR-70 levelsbetween G1 and G2 (p=.38). In Spearman's rhocorrelationanalysis, there was nostatistically significant relationships between DR-70 levels and pathology results in G2 (p=.24). ROC curve of tPSA, fPSA, f/tPSA, PSAD and DR-70 levelswere evaluated. ROC curve of PSAD shows a fair discriminant power with AUC = 0.71 (95% CI: 0.607-0.828) for differentiation between PCa and benign tissue in prostate biopsy with moderate specificity and high sensitivity (62.5% and 75.7%, resp., cut-off level: 0.1377 ng/mL). Contrary to literature and guidelines, cutoff level of PSAD as 0.13ng/mL/cc should be kept in mind and accordingly, a biopsy decision should be made. We think that DR-70 is no needed for additional evaluation before prostate biopsy.


Assuntos
Biomarcadores Tumorais/sangue , Fibrina/análise , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Idoso , Biópsia , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade
19.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 634-637, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594082

RESUMO

Objective: To explore the diagnostic value of single or combined detection of serum tumor markers alpha-fetoprotein (AFP), α-fetoprotein (AFP)-L3 and abnormal clotting (PIVKA-II) in the primary hepatic carcinoma. Methods: Serum AFP, AFP-L3 and PIVKA-II of 56 cases with primary hepatic carcinoma, 46 cases with cirrhosis, 45 cases with other liver disease and 41 healthy persons (control group) were examined by chemiluminescence method, and the differences in the levels of AFP, AFP-L3 and PIVKA-II in each group were compared. Results: Serum level of AFP, AFP-L3 and PIVKA-II in patients with primary liver cancer was significantly higher than that of the cirrhosis, other liver disease and control groups, and the difference was statistically significant (P < 0.05). The receiver operating characteristic curve analysis showed that the areas under the curve for the diagnosis of primary hepatic carcinoma by AFP, AFP-L3 and PIVKA-II were 0.887, 0.846 and 0.885, respectively. The combined use of the three tumor markers for the diagnosis of primary hepatic carcinoma increased the area under the curve to 0.899. Among the single detection, AFP had the highest sensitivity of 91.07% and PIVKA-II had the highest specificity at 88.63%. In the combined detection, AFP/PIVKA-II combination had the highest sensitivity of 94.64 %, while the AFP + AFP-L3 + PIVKA-II combination had the highest specificity at 98.48%. Conclusion: Combined detection of AFP, AFP-L3 and PIVKA-II could improve the diagnostic specificity and the sensitivity of primary hepatic carcinoma; thereby make up the deficiency of single detection and improve the early diagnosis rate.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Protrombina/análise , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Humanos , Cirrose Hepática , Neoplasias Hepáticas/sangue
20.
Anticancer Res ; 39(10): 5345-5352, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570428

RESUMO

BACKGROUND/AIM: Accurate and timely assessment of the human epidermal growth factor receptor 2 (HER2/neu) overexpression is pivotal for the identification of breast cancer (BC) patients that could benefit from HER2-targeted therapy. Currently approved tissue-based HER2 assays (tHER2) are limited to testing HER2 status on tumor samples obtained at a few points in time during the course of the disease. Herein, we assessed serum HER2 (sHER2) status longitudinally in 81 serial samples prospectively collected from 43 consenting patients pre- and post-therapy to revisit the idea of serum testing in the follow-up of BC patients. PATIENTS AND METHODS: The cohort included 11 patients with early BC (EBC), 17 with locally advanced BC (LABC), and 15 with metastatic BC (MBC). sHER2 concentrations were measured using a quantitative ELISA-based technique, using 15 ng/ml as the cut-off for positivity. RESULTS: At baseline, sHER2 was negative in all EBC patients while positive in 1 LABC and 5 MBC patients. Sixteen BC patients (10 LABC, 1 EBC, and 5 MBC) were tHER2 positive. sHER2 and tHER2 results were discordant in 14 patients. Among the 16 tHER2 positive patients, 9 LABC, 1 EBC and 2 MBC patients were sHER2 negative. Conversely, 2 MBC patients were sHER2 positive, despite being tHER2 negative. A rise or drop of sHER2 by >20% correlated with disease progression or pathological response to therapy, respectively. CONCLUSION: The study demonstrated the technical validity and feasibility of the sHER2 assay. Findings suggest that post initial tissue diagnosis (tHER2), sHER2 assay may supplement subsequent tissue tests to monitor disease status and response to therapy. Further studies to assess the role of HER2 targeted therapies in sHER-positive/tHER2-negative cases upon disease progression are warranted.


Assuntos
Neoplasias da Mama/sangue , Receptor ErbB-2/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos , Oncogenes/genética , Projetos Piloto
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