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1.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204158

RESUMO

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Perfilação da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estatísticas não Paramétricas , Adulto Jovem
2.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199928

RESUMO

Pancreatic cancer (PC) is an aggressive cancer with a high mortality rate, necessitating the development of effective diagnostic, prognostic and predictive biomarkers for disease management. Aberrantly fucosylated proteins in PC are considered a valuable resource of clinically useful biomarkers. The main objective of the present study was to identify novel plasma glycobiomarkers of PC using the iTRAQ quantitative proteomics approach coupled with Aleuria aurantia lectin (AAL)-based glycopeptide enrichment and isotope-coded glycosylation site-specific tagging, with a view to analyzing the glycoproteome profiles of plasma samples from patients with non-metastatic and metastatic PC and gallstones (GS). As a result, 22 glycopeptides with significantly elevated levels in plasma samples of PC were identified. Fucosylated SERPINA1 (fuco-SERPINA1) was selected for further validation in 121 plasma samples (50 GS and 71 PC) using an AAL-based reverse lectin ELISA technique developed in-house. Our analyses revealed significantly higher plasma levels of fuco-SERPINA1 in PC than GS subjects (310.7 ng/mL v.s. 153.6 ng/mL, p = 0.0114). Elevated fuco-SERPINA1 levels were associated with higher TNM stage (p = 0.024) and poorer prognosis for overall survival (log-rank test, p = 0.0083). The increased plasma fuco-SERPINA1 levels support the utility of this protein as a novel prognosticator for PC.


Assuntos
Biomarcadores Tumorais/sangue , Fucose/química , Glicoproteínas/sangue , Lectinas/química , Neoplasias Pancreáticas/diagnóstico , Proteoma/metabolismo , alfa 1-Antitripsina/sangue , Estudos de Casos e Controles , Cromatografia de Afinidade , Feminino , Fucose/metabolismo , Humanos , Lectinas/metabolismo , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Proteoma/análise , Taxa de Sobrevida , alfa 1-Antitripsina/química
3.
Tumour Biol ; 43(1): 115-127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219680

RESUMO

BACKGROUND: The widespread introduction of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) has led to durable responses but still many patients fail and are treated beyond progression. OBJECTIVE: This study investigated whether readily available blood-based tumor biomarkers allow accurate detection of early non-responsiveness, allowing a timely switch of therapy and cost reduction. METHODS: In a prospective, observational study in patients with NSCLC treated with nivolumab or pembrolizumab, five serum tumor markers were measured at baseline and every other week. Six months disease control as determined by RECIST was used as a measure of clinical response. Patients with a disease control <  6 months were deemed non-responsive. For every separate tumor marker a criterion for predicting of non-response was developed. Each marker test was defined as positive (predictive of non-response) if the value of that tumor marker increased at least 50% from the value at baseline and above a marker dependent minimum value to be determined. Also, tests based on combination of multiple markers were designed. Specificity and sensitivity for predicting non-response was calculated and results were validated in an independent cohort. The target specificity of the test for detecting non-response was set at >  95%, in order to allow its safe use for treatment decisions. RESULTS: A total of 376 patients (training cohort: 180, validation cohort: 196) were included in our analysis. Results for the specificity of the single marker tests in the validation set were CEA: 98·3% (95% CI: 90·9-100%), NSE: 96·5% (95% CI: 87·9-99·6%), SCC: 96·5% (95% CI: 88·1-99·6%), Cyfra21·1 : 91.8% (95% CI: 81·9-97·3%), and CA125 : 86·0% (95% CI: 74·2-93·7%). A test based on the combination of Cyfra21.1, CEA and NSE accurately predicted non-response in 32.3% (95% CI 22.6-43.1%) of patients 6 weeks after start of immunotherapy. Survival analysis showed a significant difference between predicted responders (Median PFS: 237 days (95% CI 184-289 days)) and non-responders (Median PFS: 58 days (95% CI 46-70 days)) (p <  0.001). CONCLUSIONS: Serum tumor marker based tests can be used for accurate detection of non-response in NSCLC, thereby allowing early and safe discontinuation of immunotherapy in a significant subset of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Imunoterapia/mortalidade , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Técnicas de Apoio para a Decisão , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
4.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207359

RESUMO

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients' prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. METHODS: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. RESULTS: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. CONCLUSION: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.


Assuntos
Antígeno B7-H1/sangue , Neoplasias do Sistema Biliar/sangue , Biomarcadores Tumorais/sangue , Colangiocarcinoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Nat Commun ; 12(1): 4172, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234141

RESUMO

Cell-free DNA (cfDNA) is attractive for many applications, including detecting cancer, identifying the tissue of origin, and monitoring. A fundamental task underlying these applications is SNV calling from cfDNA, which is hindered by the very low tumor content. Thus sensitive and accurate detection of low-frequency mutations (<5%) remains challenging for existing SNV callers. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this challenge. Furthermore, by leveraging cfDNA's comprehensive coverage of tumor clonal landscape, cfSNV can profile mutations in subclones. In both simulated and real patient data, cfSNV outperforms existing tools in sensitivity while maintaining high precision. cfSNV enhances the clinical utilities of cfDNA by improving mutation detection performance in medium-depth sequencing data, therefore making Whole-Exome Sequencing a viable option. As an example, we demonstrate that the tumor mutation profile from cfDNA WES data can provide an effective biomarker to predict immunotherapy outcomes.


Assuntos
DNA Tumoral Circulante/genética , Análise Mutacional de DNA/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias/genética , Sequenciamento Completo do Exoma/métodos , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biópsia , DNA Tumoral Circulante/sangue , Simulação por Computador , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Sensibilidade e Especificidade
6.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34210107

RESUMO

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations. While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Células Neoplásicas Circulantes/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Detecção Precoce de Câncer , Vesículas Extracelulares/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Biópsia Líquida , Células Neoplásicas Circulantes/metabolismo , O(6)-Metilguanina-DNA Metiltransferase/genética , Prognóstico
7.
Medicine (Baltimore) ; 100(27): e26548, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232194

RESUMO

BACKGROUND: To evaluate whether the preoperative serum albumin level can predict the survival outcome in patients with bladder urothelial carcinoma (BUC) undergoing transurethral resection of bladder tumor (TURBT). METHODS: Four hundred fifty six newly diagnosed patients with BUC who underwent TURBT between January 2014 and December 2017 were retrospectively enrolled. Patients were categorized into low albumin (<40 g/L) and high albumin (≥40 g/L) groups. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional analyses were used to determine the hazard ratios (HRs) for overall survival (OS). Of patients with available data, 108 (24%) and 348 (76%) patients were classified into the low albumin (<40 g/L) and high albumin (≥40 g/L) groups, respectively. RESULTS: The results of the Kaplan-Meier analysis and log-rank test showed a significantly worse 5-year OS (P = .003) in the low albumin group than in the high albumin group. In the multivariate Cox regression analysis, after adjusting for confounding variables, the preoperative albumin level remained an independent predictor for 5-year OS (HR: 0.434, 95% confidence interval: 0.221-0.852; P = .015). CONCLUSION: Our study determined that a low preoperative albumin level predicted poor OS in patients with BUC who underwent TURBT. Preoperative serum albumin is an inexpensive and easily available marker that has the potential to be a good prognostic factor for predicting mortality in patients with BUC treated with TURBT.


Assuntos
Carcinoma de Células de Transição/sangue , Cistectomia , Albumina Sérica/metabolismo , Neoplasias da Bexiga Urinária/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia
8.
Anticancer Res ; 41(8): 3885-3889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281850

RESUMO

BACKGROUND/AIM: Currently, there is no established prognostic serum parameter except PSA in clinically regional lymph node-positive prostate cancer. The aim of this study was to identify serum prognostic factors in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: Patients diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017 were included. The prognostic value of serum parameters for progression-free survival (PFS) and overall survival (OS) was investigated. RESULTS: Univariate and multivariate analyses showed a statistically significant increased hazard risk for PFS and OS for men with lactate dehydrogenase (LDH) ≥230 IU/l at diagnosis. PFS at 5 years for patients with high and low LDH levels were 69.9% (95% CI=56.8-79.8%) and 18.9% (95% CI=1.23-53.2%), respectively (p=0.003). OS at 5 years for low and high LDH levels were 89.2% (95% CI=78.6-94.7%) and 46.3 (95% CI=11.2-76.2%), respectively (p=0.006). CONCLUSION: This study shows that LDH is an independent predictor of PFS and OS in patients with regional lymph node metastatic prostate cancer.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , L-Lactato Desidrogenase/sangue , Metástase Linfática , Neoplasias da Próstata/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Metástase Linfática/radioterapia , Masculino , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia
9.
Int J Mol Sci ; 22(14)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34299031

RESUMO

Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Ácidos Nucleicos Livres/genética , Hispano-Americanos/genética , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Mutação , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/genética , Ácidos Nucleicos Livres/sangue , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etnologia , Cirrose Hepática/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/genética , Masculino
10.
Nat Commun ; 12(1): 3807, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155211

RESUMO

Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) is a re-oxygenating compound without apparent toxicity. In preclinical models, ITPP potentiates the efficacy of subsequent chemotherapy through vascular normalization. Here, we report the results of an unrandomized, open-labeled, 3 + 3 dose-escalation phase Ib study (NCT02528526) including 28 patients with advanced primary hepatopancreatobiliary malignancies and liver metastases of colorectal cancer receiving nine 8h-infusions of ITPP over three weeks across eight dose levels (1'866-14'500 mg/m2/dose), followed by standard chemotherapy. Primary objectives are assessment of the safety and tolerability and establishment of the maximum tolerated dose, while secondary objectives include assessment of pharmacokinetics, antitumor activity via radiological evaluation and assessment of circulatory tumor-specific and angiogenic markers. The maximum tolerated dose is 12,390 mg/m2, and ITPP treatment results in 32 treatment-related toxicities (mostly hypercalcemia) that require little or no intervention. 52% of patients have morphological disease stabilization under ITPP monotherapy. Following subsequent chemotherapy, 10% show partial responses while 60% have stable disease. Decreases in angiogenic markers are noted in ∼60% of patients after ITPP and tend to correlate with responses and survival after chemotherapy.


Assuntos
Neoplasias do Sistema Digestório/tratamento farmacológico , Hipóxia/tratamento farmacológico , Fosfatos de Inositol/uso terapêutico , Administração Intravenosa , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias do Sistema Digestório/patologia , Feminino , Humanos , Fosfatos de Inositol/farmacocinética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão
11.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067437

RESUMO

Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Subsequently, we identified three binding proteins of CCDC25 and found that kallikrein-11 (KLK11) expression was highest among those binding proteins. In this study, we investigated CCDC25 and KLK11 expression in CCA and adjacent normal tissues (n = 18) using immunohistochemistry. The results demonstrated that the expressions of CCDC25 and KLK11 in CCA tissues were both significantly higher than the adjacent tissues (p < 0.001 and p = 0.001, respectively). Then, using GEPIA bioinformatics analysis, KLK11 mRNA was significantly overexpressed in CCA tumor tissues compared with normal tissues (p < 0.05). Moreover, CCDC25 expression was positively correlated with KLK11 expression in CCA with lymph node metastasis (p = 0.028, r = 0.593). An analysis for the interaction of KLK11 with CCDC25 and other proteins, using STRING version 11.0, revealed that CCDC25 and KLK11 correlated with metastasis-related proteins. In addition, Kaplan-Meier survival curve analysis revealed that a high expression of KLK11 was associated with the poor prognosis of CCA. In conclusion, KLK11 is, as a binding protein for CCDC25, possibly involved in the metastatic process of CCA. KLK11 may be used as a prognostic marker for CCA.


Assuntos
Biomarcadores Tumorais/sangue , Colangiocarcinoma/tratamento farmacológico , Metástase Linfática , Proteínas de Membrana/sangue , Serina Endopeptidases/sangue , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Biologia Computacional , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Ligantes , Metástase Neoplásica , Prognóstico , Ligação Proteica , Domínios Proteicos , Mapeamento de Interação de Proteínas , Transdução de Sinais
12.
Br J Radiol ; 94(1123): 20201396, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34106751

RESUMO

OBJECTIVES: Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response. METHODS: In this prospective cohort study, dynamic contrast-enhanced MRI was performed in 35 females with breast cancer before and after one cycle of epirubicin and cyclophosphamide-based NACT (EC90). Estimates of tumour blood flow and tumour volume were compared with pathological response obtained at surgery following completion of NACT. RESULTS: Tumour blood flow at baseline (mean ± SD; 0.32 ± 0.17 ml/min/ml) reduced slightly after one cycle of NACT (0.28 ± 0.18 ml/min/ml). Following treatment 15 patients were identified as pathological responders and 20 as non-responders. There were no relationships found between tumour blood flow and pathological response. Conversely, tumour volume was found to be a good predictor of pathological response (smaller tumours did better) at both baseline (area under the receiver operating characteristic curve 0.80) and after one cycle of NACT (area under the receiver operating characteristic curve 0.81). CONCLUSION & ADVANCES IN KNOWLEDGE: The change in breast tumour blood flow following one cycle of EC90 did not predict pathological response. Tumour volume may be a better early marker of response with such agents.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores Tumorais/sangue , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Meios de Contraste , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Humanos , Meglumina , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organometálicos , Valor Preditivo dos Testes , Estudos Prospectivos , Trastuzumab , Carga Tumoral
13.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070921

RESUMO

Breast cancer is the most common malignancy in women with high mortality. Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are needed for the diagnosis, treatment and prognosis of breast cancer and many other diseases. At present, non-invasive diagnostic methods are gaining more and more prominence, which enable a relatively fast and painless way of detecting many diseases. Metabolomics is a promising analytical method, the principle of which is the study and analysis of metabolites in biological material. It represents a comprehensive non-invasive diagnosis, which has a high potential for use in the diagnosis and prognosis of cancers, including breast cancer. This short review focuses on the targeted metabolomics of steroid hormones, which play an important role in the development and classification of breast cancer. The most commonly used diagnostic tool is the chromatographic method with mass spectrometry detection, which can simultaneously determine several steroid hormones and metabolites in one sample. This analytical procedure has a high potential in effective diagnosis of steroidogenesis disorders. Due to the association between steroidogenesis and breast cancer progression, steroid profiling is an important tool, as well as in monitoring disease progression, improving prognosis, and minimizing recurrence.


Assuntos
Androstenodiona/sangue , Neoplasias da Mama/diagnóstico , Desidroepiandrosterona/sangue , Di-Hidrotestosterona/sangue , Estradiol/sangue , Estrona/análogos & derivados , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Estrona/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoensaio , Redes e Vias Metabólicas , Metabolômica/instrumentação , Metabolômica/métodos , Recidiva , Espectrometria de Massas em Tandem
14.
Medicine (Baltimore) ; 100(26): e26336, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190151

RESUMO

ABSTRACT: We aimed to determine the clinical characteristics and prognosis factors of young patients with gastric cancer (GC).A total of 101 young patients with GC referred to Zhengzhou University People's Hospital, Henan province, China between January 1st, 2003 and June 1st, 2015 were retrospectively reviewed. The medical records included ages, genders, marital status, family history of tumors, comorbidity, Helicobacter pylori (H.pylori) infection, fibrinogen, prealbumin, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), tumor location, tumor size, TNM stage, differentiation of the tumor, WHO type, treatment method and prognostic factors effect were further assessed.The mean age of GC patients in our group was 26.0 years. The incidence was slightly higher in females (female: male = 1.1:1). Some patients had the family history of tumor and H.pylori infection (2.0%, 6.9%). The tumor sizes were mainly under 5 cm (52.4%) and the most locations were in the antrum (43.5%) and body (42.5%). A large number of patients were diagnosed as adenocarcinomas (66.3%) and the main histological of GC was poor differentiated (72.3%). Moreover, a high proportion of patients were diagnosed at the stages III-IV (61.4%), and most patients received surgery combined chemotherapy (63.4%), however, the survival outcome was poor. In univariate Cox analysis, tumor sizes, TNM stage were significantly associated with overall survival (OS) and the multivariate Cox analysis demonstrated that TNM stage was significantly associated with OS.GC in young patients has its unique biological and clinical features. A large majority of young patients were diagnosed at their advanced stages with poor prognostic. TNM stage was an independent prognostic factor for young patients with GC, early GC screening in young people should be actively promoted.


Assuntos
Neoplasias Gástricas/patologia , Adenocarcinoma/complicações , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adolescente , Adulto , Idade de Início , Biomarcadores Tumorais/sangue , Carcinoma de Células em Anel de Sinete/complicações , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , China/epidemiologia , Feminino , Predisposição Genética para Doença , Infecções por Helicobacter/complicações , Humanos , Masculino , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/mortalidade , Carga Tumoral , Adulto Jovem
15.
Medicine (Baltimore) ; 100(26): e26487, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190174

RESUMO

ABSTRACT: To evaluate the effect of preoperative serum alpha-fetoprotein(AFP) level to total tumor volume (TTV) ratio as a prognostic marker on predicting the tumor recurrence and overall survival time of patients with hepatocellular carcinoma (HCC) after liver transplantation.One-hundred eight patients with HCC who underwent liver transplantation in Beijing Chaoyang Hospital from April 2013 to October 2017 were studied. Divided into AFP/TTV≤2 group and AFP/TTV>2 group by the best cut-off score calculated by receiver operation characteristic curve, the clinical and pathological data of the patients in two groups were compared to explore the relationship between AFP/TTV and tumor recurrence together with the prognosis of HCC patients after liver transplantation. Risk factors of early tumor recurrence and poor prognosis of HCC in patients after liver transplantation were studied by multivariate regression analysis. Kaplan-Meier survival analysis was used to compare the tumor-free survival and overall survival between the two groups of patients.In 108 patients, 47 patients have AFP/TTV≤2 while 61 patients have AFP/TTV>2. Patients in AFP/TTV≤2 group have longer tumor-free survival time and overall survival time compared with patients in AFP/TTV>2 group. The age, total bilirubin level, serum AFP level, TTV, portal vein tumor thrombus and AFP/TTV (all P < .05) of patient with HCC are closely related to poor prognosis after liver transplantation. Multivariate regression analysis showed that have portal vein tumor thrombus (hazard ratio [HR] = 2.345, P < .05), TTV≥65.5 cm3 (HR = 2.701, P < .05) and AFP/TTV > 2 (HR = 4.624, P < .05) are independent risk factors for poor prognosis of patients with HCC after liver transplantation while TTV≥65.5 cm3 (HR = 2.451, P < .05) and AFP/TTV > 2 (HR = 4.257, P < 0.05) were independent risk factors for tumor recurrence at the same time.The tumor recurrence and the prognosis of patients with HCC after liver transplantation is affected by many factors. AFP/TTV ratio has important predictive value for the tumor recurrence and the prognosis of patients with HCC after liver transplantation. AFP/TTV>2 is an independent risk factor for both early tumor recurrence and poor prognosis of patients with HCC after liver transplantation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Recidiva Local de Neoplasia , Veia Porta , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Testes de Função Hepática/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos , Fatores de Risco , Carga Tumoral
16.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071592

RESUMO

Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and without lung cancer. METHODS: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non-smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Serum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. RESULTS: 15 miRNAs were differentially expressed between lung cancer and healthy non-smoking participants, with the greatest single miRNA being miR-205-5p (AUC 0.850), improving to AUC 0.993 in combination with miR-199a-5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR-497-5p (AUC 0.873), improving to AUC 0.953 in combination with miR-22-5p; 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR-27a-3p (AUC 0.803), with two other miRNAs (miR-106b-3p and miR-361-5p) further improving discriminatory power (AUC 0.870). CONCLUSION: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.


Assuntos
Biomarcadores Tumorais/genética , Vesículas Extracelulares/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/genética , Fumar/genética , Idoso , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Curva ROC
17.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073560

RESUMO

There exist many different human cancers, but regardless of the cancer type, an early diagnosis is a necessary condition for further optimal outcomes from the disease. Therefore, efficient specific and sensitive cancer biomarkers are urgently needed. This is especially true for the cancers depicting a silent progression, and those only diagnosed in an already metastatic state with a poor survival prognostic. After a rapid overview of the previous methods for cancer diagnosis, the outstanding characteristics of extracellular vesicles (EVs) will be presented, as new interesting candidates for early cancer diagnosis in human biofluid non-invasive liquid biopsy. The present review aims to give the state-of-the-art of the numerous searches of efficient EV-mediated cancer diagnosis. The corresponding literature quest was performed by means of an original approach, using a powerful Expernova Questel big data platform, which was specifically adapted for a literature search on EVs. The chosen collected scientific papers are presented in two parts, the first one drawing up a picture of the current general status of EV-mediated cancer diagnosis and the second one showing recent applications of such EV-mediated diagnosis for six important human-specific cancers, i.e., lung, breast, prostate, colorectal, ovary and pancreatic cancers. However, the promising perspective of finally succeeding in the worldwide quest for the much-needed early cancer diagnosis has to be moderated by the many remaining challenges left to solve before achieving the efficient clinical translation of the constantly increasing scientific knowledge.


Assuntos
Biomarcadores Tumorais/sangue , Micropartículas Derivadas de Células , Detecção Precoce de Câncer , Vesículas Extracelulares , Neoplasias , Micropartículas Derivadas de Células/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Humanos , Biópsia Líquida , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/patologia
18.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064646

RESUMO

Even though colorectal cancer (CRC) is one of the most preventable cancers, it is currently one of the deadliest. Worryingly, incidence in people <50 years has increased unexpectedly, and for unknown causes, despite the successful implementation of screening programs in the population aged >50 years. Thus, there is a need to improve early diagnosis detection strategies by identifying more precise biomarkers. In this scenario, the analysis of exosomes is given considerable attention. Previously, we demonstrated the exosome lipidome was able to classify CRC cell lines according to their malignancy. Herein, we investigated the use of the lipidome of plasma extracellular vesicles as a potential source of non-invasive biomarkers for CRC. A plasma exosome-enriched fraction was analyzed from patients undergoing colonoscopic procedure. Patients were divided into a healthy group and four pathological groups (patients with hyperplastic polyps; adenomatous polyps; invasive neoplasia (CRC patients); or hereditary non-polyposis CRC. The results showed a shift from 34:1- to 38:4-containing species in the pathological groups. We demonstrate that the ratio Σ34:1-containing species/Σ38:4-containing species has the potential to discriminate between healthy and pathological patients. Altogether, the results reinforce the utility of plasma exosome lipid fingerprint to provide new non-invasive biomarkers in a clinical context.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/patologia , Exossomos/metabolismo , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/química , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Humanos
19.
Nat Commun ; 12(1): 3430, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34078895

RESUMO

The limited availability of nasopharyngeal carcinoma-related progression biomarker array kits that offer physicians comprehensive information is disadvantageous for monitoring cancer progression. To develop a biomarker array kit, systematic identification and differentiation of a large number of distinct molecular surface-enhanced Raman scattering (SERS) reporters with high spectral temporal resolution is a major challenge. To address this unmet need, we use the chemistry of metal carbonyls to construct a series of unique SERS reporters with the potential to provide logical and highly multiplex information during testing. In this study, we report that geometric control over metal carbonyls on nanotags can produce 14 distinct barcodes that can be decoded unambiguously using commercial Raman spectroscopy. These metal carbonyl nanobarcodes are tested on human blood samples and show strong sensitivity (0.07 ng/mL limit of detection, average CV of 6.1% and >92% degree of recovery) and multiplexing capabilities for MMPs.


Assuntos
Técnicas Biossensoriais/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Análise Espectral Raman , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/química , Progressão da Doença , Metaloproteinases da Matriz/sangue , Metaloproteinases da Matriz/química , Nanopartículas Metálicas/química , Nanogéis/química , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Compostos Organometálicos/química , Sensibilidade e Especificidade , Propriedades de Superfície
20.
Nat Commun ; 12(1): 3515, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112774

RESUMO

MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 µl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Detecção Precoce de Câncer/métodos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias da Próstata/diagnóstico , Imagem Individual de Molécula/métodos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , MicroRNA Circulante/análise , MicroRNA Circulante/sangue , Detecção Precoce de Câncer/instrumentação , Fluorescência , Perfilação da Expressão Gênica , Humanos , Biópsia Líquida , Masculino , MicroRNAs/análise , MicroRNAs/sangue , MicroRNAs/genética , Nanoporos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
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