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1.
Medicine (Baltimore) ; 99(38): e22281, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957383

RESUMO

The regulation of the gene-regenerating family member 1 alpha (REG Iα) played important roles in cancer cell biology. However, the correlation between its gene product serum REG Iα and cancer has not been evaluated. In this observational study, 130 hospitalized patients from the department of internal medicine in Zhongda Hospital Southeast University were included and assigned to cancer or noncancer groups. History, clinical, and laboratory data were obtained. Serum REG Iα levels and alanine aminotransferase were found significantly higher in patients with cancer (P < .001 and P < .05 respectively). Logistic regression analysis indicated that REG Iα was an independent risk factor for cancer (P < .001). The area under the curve of REG Iα was 0.764 and the optimal cut-off point of REG Iα was 46.97 ng/mL. Besides, the cancer patients with metastasis had significantly higher serum REG Iα levels than those in nonmetastasis cancer group (P < .05). In conclusion, serum REG Iα was significantly elevated in patients with cancer, and it might be a potential biomarker in predicting cancer occurrence and development.


Assuntos
Biomarcadores Tumorais/sangue , Litostatina/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
Tumour Biol ; 42(9): 1010428320958603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32964798

RESUMO

This study aimed to investigate whether changes in progastrin-releasing peptide (ProGRP) levels correlate with treatment response and can be used to optimize clinical management of patients with small-cell lung cancer. Patients with small-cell lung cancer (any stage) receiving chemotherapy were eligible. ProGRP was measured in serum/plasma at baseline and after each chemotherapy cycle using the Elecsys® ProGRP assay (Roche Diagnostics). Treatment response was assessed by computed tomography scan. The primary objective was to examine whether changes in ProGRP levels correlated with computed tomography scan results after two cycles of chemotherapy. The prognostic value of ProGRP among patients receiving first-line chemotherapy was also assessed. Overall, 261 patients from six centers were eligible. Among patients with elevated baseline ProGRP (>100 pg/mL), a ProGRP decline after Cycle 2 was associated with nonprogression (area under the curve: 84%; 95% confidence interval: 72.8-95.1; n = 141). ProGRP changes from baseline to end of Cycle 1 were predictive of response, as determined by computed tomography scan 3 weeks later (area under the curve: 87%; 95% confidence interval: 74.1-99.2; n = 137). This was enhanced by repeat measurements, with a 92% area under the curve (95% confidence interval: 85.3-97.8) among patients with ProGRP data after both Cycles 1 and 2 (n = 123); if a patient experienced a ≥25% decline in ProGRP after Cycle 1, and ProGRP remained stable or decreased after Cycle 2, the probability of finding progression on the interim computed tomography scan at the end of Cycle 2 was almost zero (sensitivity: 100%, specificity: 71%). Both ProGRP levels at baseline and at the end of first-line chemotherapy were prognostic; the latter provided a moderately improved hazard ratio of 2.43 (95% confidence interval: 1.33-4.46; n = 110) versus 1.87 (95% confidence interval: 1.04-3.37; n = 216). In summary, for patients with small-cell lung cancer and elevated baseline ProGRP levels, ProGRP may be a simple, reliable, and repeatable tool for monitoring response to chemotherapy and provide valuable prognostic information.


Assuntos
Neoplasias Pulmonares/sangue , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/sangue , China , Europa (Continente) , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
3.
Medicine (Baltimore) ; 99(39): e22322, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991441

RESUMO

RATIONALE: Bronchiolar adenoma (BA) is a newly designated rare entity of the lung, including both the currently designated ciliated muconodular papillary tumor (CMPT) and so-called non-classic CMPT. The most prominent histological feature of BAs is the bilayered cell structures composed of the continuous basal cell layer and the luminal layer which consists of different proportion of mucinous cells, ciliated cells, Clara cells and/or type II pneumocytes. BA purely covered by mucinous cells without other components in the luminal layer has never been reported. PATIENT CONCERNS: An 82-year-old female patient was detected a 0.8 cm ground glass nodule in the left lower lobe of the lung. DIAGNOSES: The serum levels of tumor markers were normal. INTERVENTIONS: The patient underwent a segmentectomy of the left lower lobe. OUTCOMES: The postoperative pathological diagnosis was BA. Molecular analysis revealed that the tumor harbored ALK rearrangement and BRAF mutations simultaneously. There was no recurrence in 17 months of follow-up. LESSONS: BA can be lined only by mucinous cells, without any cuboidal and/or ciliated cells in the surface layer. This sets a dangerous pitfall in differentiation diagnosis with invasive mucinous adenocarcinoma especially during intraoperative frozen pathological diagnosis.


Assuntos
Adenoma/metabolismo , Bronquíolos/patologia , Neoplasias Pulmonares/patologia , Biologia Molecular/métodos , Adenoma/cirurgia , Assistência ao Convalescente , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Pneumonectomia/métodos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Resultado do Tratamento
4.
Maturitas ; 140: 64-71, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32972637

RESUMO

OBJECTIVES: Progesterone receptor membrane component-1 (PGRMC1) in breast cancer tissue has been suggested to predict a worse prognosis. The aim of this study was to assess for the first time whether PGRMC1 expressed in cancer tissue is associated with PGRMC1 blood concentrations and whether both are correlated with clinical tumour characteristics known to predict a worse outcome. METHODS: In total, 201 patients with invasive breast cancer and 65 with benign breast disease (control group) were recruited. PGRMC1 blood concentrations were measured by a recently developed ELISA, PGRMC1 in breast cancer tissue was assessed by immunohistochemistry, and the correlation between the two was calculated. Receiver-operating characteristic (ROC) curve analysis was used to assess area under the curve (AUC). Furthermore, PGRMC1 was correlated with tumour characteristics such as tumour diameter, tumour grade and metastatic status, and with known blood tumour markers. RESULTS: AUC for the breast cancer group was 0.713, which was significantly higher than in the control group (p < 0.01). Blood PGRMC1 concentrations had a strong (positive) correlation with tissue PGRMC1 expression (p < 0.01) but were not associated with serum tumour markers CEA, CA125, CA153 and TPS. Tissue PGRMC1, ER and cancer stage were positively associated with blood PGRMC1 (p < 0.05). CONCLUSIONS: As PGRMC1 expression levels in cancer tissue were significantly correlated with PGRMC1 in blood, and because concentrations in blood were also positively associated with breast tumour characteristics known to predict a worse prognosis, PGRMC1 may be valuable as a new tumour marker and may be superior to known tumour markers such as CEA, CA125, CA153 and TPS.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismo , Receptores de Progesterona/sangue , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
5.
Anticancer Res ; 40(10): 5679-5685, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988893

RESUMO

BACKGROUND/AIM: The presence of circulating tumor cells (CTC) has been reported to have an impact on prognosis in different tumor entities. Little is known about CTC morphology and heterogeneity. PATIENTS AND METHODS: In a multicenter setting, pre-therapeutic peripheral blood specimens were drawn from patients with non-metastatic esophageal adenocarcinoma (EAC). CTCs were captured by size-based filtration (ScreenCell®), subsequently Giemsa-stained and evaluated by two trained readers. The isolated cells were categorized in groups based on morphologic criteria. RESULTS: Small and large single CTCs, as well as CTC-clusters, were observed in 69.2% (n=81) of the 117 specimens; small CTCs were observed most frequently (59%; n=69), followed by large CTCs (40%; n=47) and circulating cancer-associated macrophage-like cells (CAMLs; 34.2%, n=40). Clusters were rather rare (12%; n=14). CTC/CAML were heterogeneous in the cohort, but also within one specimen. Neither the presence of the CTC subtypes/CAMLs nor the exact cell count were associated with the primary clinical TNM stage. CONCLUSION: Morphologically heterogenic CTCs and CAMLs are present in patients with non-metastatic, non-pretreated EAC.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias Esofágicas/sangue , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/patologia , Contagem de Células , Separação Celular , Neoplasias Esofágicas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/patologia , Prognóstico
6.
Nat Commun ; 11(1): 4881, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985506

RESUMO

Thymoma is the most common tumor of the anterior mediastinum. Routine imaging methods such as computed tomography or magnetic resonance imaging often lead to misdiagnosis between thymoma and other thymic abnormalities. Therefore, urgently needed is to develop a new diagnostic strategy. Here we identify interleukin-8 (IL-8) as a biomarker for auxiliary diagnosis of thymoma. We find that IL-8 levels in naïve T cells are markedly elevated in patients with thymoma compared to those with other thymic tumors. IL-8 levels in naive T cells are significantly decreased after surgical resection in thymoma patients, and rise again when thymoma recurs. A receiver operating characteristic curve analysis shows that IL-8 evaluation performs well in thymoma identification, with high specificities and sensitivities. We also observe significant clinical relevance between IL-8 levels in naïve T cells and clinicopathological features. In conclusion, our study suggests that IL-8 is a biomarker for thymoma identification and recurrence surveillance.


Assuntos
Interleucina-8/sangue , Recidiva Local de Neoplasia/sangue , Timoma/sangue , Neoplasias do Timo/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Interleucina-8/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Timoma/genética , Timoma/patologia , Neoplasias do Timo/genética , Neoplasias do Timo/patologia , Adulto Jovem
7.
PLoS One ; 15(8): e0237506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790768

RESUMO

Circulating tumor cells (CTCs) invade blood vessels in solid tumors and promote metastases by circulating in the blood. CTCs are thus recognized as targets for liquid biopsy and can provide useful information for design of treatments. This diagnostic approach must consider not only the number of CTCs but also their molecular and genetic characteristics. For this purpose, use of devices that enrich CTCs independent of these characteristics and detectors that recognize various CTC characteristics is essential. In the present study, we developed a CTC detection system comprising ClearCell FX and ImageStream Mark II. We clarified the analytical performance of this system by evaluating recovery rate, lower limits of detection, and linearity. These parameters are critical for detecting rare cells, such as CTCs. We tested these parameters using three cell lines with different expression levels of the epithelial marker-epithelial cell adhesion molecule (EpCAM) and spiked these cells into whole-blood samples from healthy donors. The average recovery rate and lower limit of detection were approximately 40% and five cells/7.5 mL of whole blood, respectively. High linearity was observed for all evaluated samples. We also evaluated the ability of the system to distinguish between normal and abnormal cells based on protein expression levels and gene amplification and found that the system can identify abnormal cells using these characteristics. The CTC detection system thus displays the ability to distinguish specific characteristics of CTC, thereby providing valuable information for cancer treatment.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Molécula de Adesão da Célula Epitelial/metabolismo , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Tumorais Cultivadas
8.
Medicine (Baltimore) ; 99(31): e21210, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756098

RESUMO

RATIONALE: Procalcitonin (PCT) has been identified as a tumor biomarker in medullary thyroid carcinoma. Other neuroendocrine carcinomas with elevated PCT levels are relatively rare, and are mainly reported in the lung, digestive tract, and pancreas. No studies in the literature have reported a case of primary hepatic carcinoma complicated with unexpectedly elevated PCT levels. PATIENT CONCERNS: A 78-year-old man with persistent fatigue and mild fever was complicated with an extremely high PCT level. Radiological examination revealed a single hypodense lesion in the left lobe of the liver with a "rapid enhancement and rapid washout" pattern. Pathological analysis showed a poorly differentiated neuroendocrine carcinoma (grade 3) with multiple genetic mutations. DIAGNOSIS: Primary hepatic neuroendocrine carcinoma. INTERVENTIONS: The patient received antibiotic therapy and subsequent transcatheter hepatic arterial chemoembolization; a PCT assessment and computed tomography were performed during the follow-up. OUTCOMES: The PCT level did not decline after antibiotic therapy but greatly declined in response to effective transcatheter hepatic arterial chemoembolization. The patient survived and is still being followed up. LESSONS: An extremely elevated PCT level may raise a suspicion of a neuroendocrine carcinoma and plays an indicative role as a biomarker during therapy.


Assuntos
Carcinoma Neuroendócrino/diagnóstico , Neoplasias Hepáticas/diagnóstico , Pró-Calcitonina/sangue , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/terapia , Quimioembolização Terapêutica , Diagnóstico Diferencial , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Masculino , Tomografia Computadorizada por Raios X
9.
Medicine (Baltimore) ; 99(31): e21254, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756103

RESUMO

Retinol binding protein 4 (RBP4), as an adipokine, has been identified to be associated with several types of cancer. However, no studies have assessed its effect on non-small cell lung cancer (NSCLC) risk. The objective of this study was to assess the association between serum RBP4 levels and the risk of NSCLC.A case-control study design was used to recruit 256 confirmed NSCLC cases and 256 age- and gender-matched healthy controls by frequency between August 2017 and January 2019. Serum RBP4 was measured using enzyme-linked immune absorbent assay before treatment. Unconditional logistic regression analysis was applied to estimate the odds ratio and 95% confidence interval (CI).Serum RBP4 level was significantly higher in NSCLC patients than those in the healthy control group (36.05 ±â€Š8.28 vs 29.54 ±â€Š7.71 µg/mL, P < .05). Higher serum RBP4 level was associated with increased risk of NSCLC (P trend = .001). Compare with those in the lowest tertile, the adjusted odds ratios were 1.85 (95% CIs 1.07-3.2) (P = .029) for the second tertile and 2.18 (95% CIs 1.37-3.45) (P = .001) for the highest tertile after adjusting for confounding variables. No interactions were observed after stratified analyses by body mass index and smoking status (P for interaction: .584 and .357).Our study indicated that serum RBP4 level was positively related to the risk of NSCLC. Additional studies with prospective design are required to confirm this finding.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adulto , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco
10.
J Environ Pathol Toxicol Oncol ; 39(2): 113-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749121

RESUMO

Liver cancer or hepatocellular carcinoma is considered to be the third leading cause of death among all other cancers. The rate of liver cancer occurrence is high, and the rate of recovery is low. In this study, we investigated the therapeutic efficacy of vicenin-2 against the diethylnitrosamine-induced liver carcinoma in experimental rats. Diethylnitrosamine was widely employed as a carcinogenic agent to stimulate the cancer in animal models. Our results indicated that vicenin-2 administration effectively attenuates the diethylnitrosamine-induced physiological and pharmacological alterations in the experimental rats. Vicenin-2 treatment significantly enhanced the pathological lesions and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and α-fetoprotein (AFP) in serum. We also observed that vicenin-2 reduced the production of reactive oxygen species, decreased the liver weight, upregulated expression of apoptotic proteins, and decreased the histological changes in the liver, which are induced by the diethylnitrosamine in rats. Moreover, vicenin-2 downregulates antiapoptotic Bcl-2 and Bcl-xL, and upregulates the proapoptotic Bax and caspase. Hence, our results suggested that vicenin-2 had a highly therapeutic effect in reversing diethylnitrosamine-induced liver carcinoma in rats, which might be related to the apoptosis induced by vicenin-2. Therefore vicenin-2 could be a good candidate for future therapeutic use to inhibit chemically induced liver cancer.


Assuntos
Apigenina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Glucosídeos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Peso Corporal/efeitos dos fármacos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/toxicidade , Enzimas/sangue , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Soroglobulinas/análise
11.
PLoS One ; 15(8): e0238251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845921

RESUMO

Although mass spectrometry-based plasma proteomics enables sensitive and large-scale discovery and validation of biomarkers for various diseases, its integrative application to hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) is not well investigated. Therefore, we analyzed albumin- and immunoglobulin G-depleted plasma samples from 148 and 60 patients with HCC and CCA, respectively, using liquid chromatography-tandem mass spectrometry. The algorithm used to measure the content of each protein was the percentage of exponentially modified protein abundance index. From 5320 proteins assayed in plasma, 53 and 25 biomarker candidates were identified for HCC and CCA, respectively. The abundance of six and two HCC markers particularly protruded in stage II and III, respectively, whereas plasma serine protease inhibitor was the sole marker the level of which steadily decreased with CCA progression. From a prognostic facet, we showed candidate markers and their cutoff levels for evaluating probability of tumor recurrence and patient survival period. Combination Kaplan-Meier models showed that HCC stage III or IV and both the content of alpha-2-HS-glycoprotein and apolipoprotein CIII <0.2% exhibited the poorest post-surgical recurrence-free and overall survivals. Furthermore, the content of afamin ≥0.2% played a significant role on the poor prognosis in patients with CCA. Our findings, taken together, characterized novel plasma biomarker signatures in dissecting tumor stages and post-surgical outcomes of HCC and CCA.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína C-III/sangue , Ductos Biliares Intra-Hepáticos/patologia , Proteínas de Transporte/sangue , Feminino , Glicoproteínas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Proteoma/análise , Inibidores de Serino Proteinase/sangue , Albumina Sérica Humana , alfa-2-Glicoproteína-HS/análise
12.
Life Sci ; 258: 118226, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771555

RESUMO

AIM: Colorectal carcinoma (CRC) is one of the most prevalent cancers throughout the world. Circulating serum-derived microRNAs (miRNAs, miRs) can be used as non-invasive biomarkers for CRC diagnosis. This study aimed to identify a panel of six serum exosomal miRNAs as novel diagnostic biomarkers for CRC. MAIN METHODS: Exosomes were isolated and characterized from the conditioned media of the human colon adenocarcinoma cells (HCT-116 and Caco2). Sera were isolated from peripheral blood of 45 CRC and also 45 healthy individuals. The expression levels and diagnostic value of candidate circulating miRNAs (miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a) were measured through quantitative real-time PCR. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic accuracy of selected miRNAs. The association of candidate miRNAs and clinicopathological characteristics e.g. tumor node metastasis (TNM) staging and lymph node metastasis (LNM) were further evaluated. KEY FINDINGS: Circulating serum miR-19a, miR-20a, miR-150, and let-7a were significantly up-regulated in CRC patients, while miR-143 and miR-145 showed a significant down-regulation. The higher levels of miR-143 and miR-145 in patients with TNM stage I-II were detected, whereas miR-19a, miR-20a, miR-150, and let-7a were highly expressed in TNM stage III. The expression levels of miR-19a, miR-20a, and miR-150 were positively correlated with LNM status, while the expression levels of miR-143 and miR-145 were lower in patients with LNM. Area under the ROC curves of miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a were 0.87, 0.83, 0.75, 0.76, 0.78 and 0.71, respectively. SIGNIFICANCE: We established a panel of six-circulating miRNA signature (i.e. miR-19a, miR-20a, miR-143, miR-145, miR-150, and let-7a) in serum as a non-invasive biomarker for CRC diagnosis. These findings confirm that serum-derived miRNAs have a strong potential to be a diagnostic biomarker for patients with CRC.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , MicroRNAs/sangue , MicroRNAs/genética , Adulto , Idoso , Células CACO-2 , Exossomos/genética , Exossomos/metabolismo , Feminino , Redes Reguladoras de Genes/genética , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade
13.
PLoS One ; 15(8): e0236338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785215

RESUMO

Dysregulation of BCL2 is a pathophysiology observed in haematological malignancies. For implementation of available treatment-options it is preferred to know the relative quantification of BCL2 mRNA with appropriate reference genes. For the choice of reference genes-(i) Reference Genes were selected by assessing variation of >60,000 genes from 4 RNA-seq datasets of haematological malignancies followed by filtering based on their GO biological process annotations and proximity of their chromosomal locations to known disease translocations. Selected genes were experimentally validated across various haematological malignancy samples followed by stability comparison using geNorm, NormFinder, BestKeeper and RefFinder. (ii) 43 commonly used Reference Genes were obtained from literature through extensive systematic review. Levels of BCL2 mRNA was assessed by qPCR normalized either by novel reference genes from this study or GAPDH, the most cited reference gene in literature and compared. The analysis showed PTCD2, PPP1R3B and FBXW9 to be the most unregulated genes across lymph-nodes, bone marrow and PBMC samples unlike the Reference Genes used in literature. BCL2 mRNA level shows a consistent higher expression in haematological malignancy patients when normalized by these novel Reference Genes as opposed to GAPDH, the most cited Reference Gene. These reference genes should also be applicable in qPCR platforms using Taqman probes and other model systems including cell lines and rodent models. Absence of sample from healthy-normal individual in diagnostic cases call for careful selection of Reference Genes for relative quantification of a biomarker by qPCR.BCL2 can be used as molecular diagnostics only if normalized with a set of reference genes with stable yet low levels of expression across different types of haematological malignancies.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Neoplasias Hematológicas/diagnóstico , Proteínas Proto-Oncogênicas c-bcl-2/isolamento & purificação , RNA Mensageiro/isolamento & purificação , RNA-Seq/normas , Animais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Estudos de Viabilidade , Regulação Neoplásica da Expressão Gênica , Genes Essenciais , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Leucócitos Mononucleares , Proteínas Proto-Oncogênicas c-bcl-2/sangue , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/normas , Padrões de Referência
14.
PLoS One ; 15(8): e0236569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756596

RESUMO

BACKGROUND: The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. METHODS: Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. RESULTS: Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). CONCLUSION: The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Intervalo Livre de Progressão
15.
Int J Nanomedicine ; 15: 4933-4941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764926

RESUMO

Purpose: The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. Materials and Methods: Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. Results: The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p>0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p<0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p<0.05. Conclusion: We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer.


Assuntos
Fluorescência , Lipossomos/química , Neoplasias Hepáticas/diagnóstico , Mutação , Polímeros/química , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo , Adulto , Área Sob a Curva , Automação , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Imãs/química , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
16.
PLoS One ; 15(8): e0237370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857769

RESUMO

BACKGROUND: Copper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib. METHODS: We enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy. RESULTS: The serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival. CONCLUSIONS: The Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Cobre/sangue , Neoplasias Hepáticas/sangue , Metalotioneína/sangue , Zinco/sangue , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico
17.
PLoS One ; 15(8): e0237793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822383

RESUMO

PURPOSE: It has been demonstrated that, for various types of cancer, the pretreatment albumin/alkaline phosphatase ratio (AAPR) was a prognostic factor. Therefore, in order to determine AAPR's prognostic effect on cancer, the meta-analysis was hereby performed. PATIENTS AND METHODS: The relevant studies conducted before November 10, 2019, were comprehensively searched in Web of Science, PubMed, and Embase. HRs(hazard ratios) with related 95%CIs(confidence intervals) were adopted to estimate AAPR's prognostic impact on overall survival (OS) & disease-free survival (DFS). RESULTS: Our meta-analysis involved thirteen cohort studies, which included 5,204 cases of 8 types. The results of this meta-analysis indicated that higher AAPR was corrected with better OS (pooled HR = 0.52; 95%CI = 0.47-0.58; P<0.001) and DFS (pooled HR = 0.55; 95%CI = 0.47-0.66; P<0.001). Subgroup analysis on OS was based on the cancer system, treatment methods, and cutoff value. Moreover, higher AAPR was statistically in associated with lighter infiltration (pooled OR = 0.79; 95%CI = 0.73-0.85; P<0.001), no lymph nodes metastasis (pooled OR = 0.89; 95%CI = 0.83-0.95; P = 0.001), and no distant metastasis (pooled OR = 0.92; 95%CI = 0.86-0.99; P = 0.028). CONCLUSION: Higher AAPR was related to better prognosis of cancer, and in cancer therapy, AAPR could be taken as a promising marker of prognosis. It might help physicians to select the most appropriate treatments by evaluating the current status of patients with cancer. Future multicenter prospective clinical trials were required to verify its applications.


Assuntos
Fosfatase Alcalina/sangue , Neoplasias/diagnóstico , Albumina Sérica/análise , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Humanos , Neoplasias/sangue , Neoplasias/terapia , Prognóstico
18.
Br J Radiol ; 93(1114): 20200484, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706988

RESUMO

With increasing evidence to support prostate artery embolization (PAE) in the treatment of benign prostatic hyperplasia (BPH)-induced lower urinary tract symptoms (LUTS), Interventional Radiologists have begun to play an important role in the management of these patients. One area of knowledge needed when developing a PAE practice is knowledge of prostate-specific antigen (PSA) and other biomarkers utilized to detect prostate cancer in this population and what role they should play in the work up and follow-up of patients presenting with presumed BPH-induced LUTS. Furthermore, understanding how to evaluate presumed BPH-induced LUTS and stratify the risk of prostate cancer is an important skill to develop. The goal of this review is to provide Interventional Radiologists who have begun or aim to begin a PAE practice with the information they need to know regarding PSA levels and prostate cancer risk stratification for this patient population.


Assuntos
Biomarcadores Tumorais/sangue , Sintomas do Trato Urinário Inferior/terapia , Hiperplasia Prostática/terapia , Radiografia Intervencionista , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem
19.
PLoS One ; 15(7): e0235865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634155

RESUMO

HIV-associated/epidemic Kaposi's sarcoma (EpKS) is an AIDS-defining angio-proliferative malignancy. It can be treated with antiretroviral therapy (ART) alone or with ART plus cytotoxic chemotherapy. ART-treated EpKS can either respond or worsen upon treatment. This study aimed at identifying immunological markers of ART-treatment response. We compared responders (those with clinical EpKS tumor regression) versus poor responders (those with progressive or non-responsive EpKS). We measured plasma cytokine and chemokine levels using cytometric bead assays. Kaposi's sarcoma herpesvirus (KSHV) neutralizing antibody (nAb) responses were also quantified to test associations with treatment outcome. Interleukin (IL)-5 levels were significantly elevated in responders versus poor-responders at baseline (0.76pg/ml vs. 0.37pg/ml; p<0.01) and follow-up (0.56pg/ml vs. 0.37pg/ml; p<0.01); IL-6 was lower in responders than poor-responders at follow-up (600fg/ml vs. 4272fg/ml; p<0.05). IP-10/CxCL-10 was significantly lower at follow-up in responders versus poor-responders (187pg/ml vs. 528pg/ml; p<0.01). KSHV nAb were not significantly differential between responders and poor-responders. In conclusion, high plasma IL-5 at baseline could be a marker for ART-treated KS tumor regression, whereas increased pro-inflammatory cytokine IL-6, and the chemokine IP-10, associate with KS tumor progression.


Assuntos
Biomarcadores Tumorais/sangue , Citocinas/sangue , Infecções por HIV/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/sangue , Sarcoma de Kaposi/complicações , Resultado do Tratamento , Carga Viral
20.
Ann Surg ; 272(2): 342-351, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675548

RESUMO

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Linfócitos/metabolismo , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
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