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1.
Oral Oncol ; 98: 141-146, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586896

RESUMO

OBJECTIVES: This study aimed to validate the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for nasopharyngeal carcinoma (NPC) in non-endemic region. MATERIALS AND METHODS: We recruited 607 patients with histology-proven, previously untreated, non-metastatic NPC treated by intensity-modulated radiotherapy (IMRT) at our center. Harrell's concordance index (c-index) and Akaike information criterion (AIC) were applied to compare the prognostic discrimination between the 7th and 8th edition staging system. RESULTS: For T category, the local recurrence-free survival (LRFS) Kaplan-Meier curves of T1, T2 and T3 were well separated in the 8th edition; however, LRFS did not significantly differ between T3 and T4 (P = 0.166). Moreover, the 7th edition achieved higher c-index (0.702 [95% CI, 0.618-0.787] vs. 0.685 [95% CI, 0.604-0.767]) and lower AIC (766.1 vs. 770.8) than 8th edition for LRFS. With regard to N category, the 8th edition achieved higher c-index (0.796 [95% CI, 0.749-0.843] vs. 0.751 [95% CI, 0.696-0.805]) and lower AIC (1439.4 vs. 1471.9) for distant metastasis-free survival. In terms of overall stage, the 8th edition also had higher c-index (0.798 [95% CI, 0.753-0.844] vs. 0.721 [95% CI, 0.672-0.770]) and lower AIC (1963.9 vs. 2007.2) compared with the 7th edition for overall survival. Furthermore, interval validation by bootstrapping the sample randomly for ~100-1000 times also validated above findings. CONCLUSION: The 8th edition of AJCC/UICC TNM staging system achieved significantly better prognostic discrimination than the 7th edition with regard to N category and overall stage but not T category.

2.
Aging (Albany NY) ; 11(19): 8463-8473, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31586991

RESUMO

PURPOSE: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. RESULTS: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. CONCLUSIONS: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. PATIENTS AND METHODS: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

3.
BMC Cancer ; 19(1): 843, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455274

RESUMO

BACKGROUND: Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection. METHODS: Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy. RESULTS: Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%). CONCLUSIONS: This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.

4.
Cancer Med ; 8(13): 6049-6063, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433128

RESUMO

An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR-449b-3p was downregulated in NPC specimens (P < .001) and cells (P < .05). Cytological and animal experiments provided evidence that miR-449b-3p inhibited NPC metastasis in vitro and in vivo. Disintegrin and metalloproteinase 17 (ADAM17) was revealed as a direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in the miR-449b-3p knockdown cells partially reversed the inhibition of cell invasion and migration. Luciferase reporter assay, chromatin immunoprecipitation assay, and Western blot analysis showed that ADAM17 could suppress the promoter activity and expression of miR-449b-3p by inducing NF-κB transcriptional activity. In conclusion, our study provided new insights into the underlying mechanism of the invasion and metastasis of NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop could be a target for the clinical treatment of NPC.

5.
Biometals ; 32(4): 683-693, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286331

RESUMO

Prolonged exposure to gadolinium-based contrast agents has been reported to trigger nephrogenic systemic fibrosis in end stage renal disease patients. However, the exact molecular mechanisms are not fully understood, and no effective therapy is available to date. In the present study, we report that gadolinium chloride (Gd3+) concentration- and time-dependently promoted the proliferation of HEK293 human embryonic kidney cells by increasing DNA synthesis. Gd3+ treatment increased the protein levels of phosphorylated Akt and MAPKs. Inhibition of Akt and ERK by pharmacological inhibitors abolished the increased proliferation and cell cycle progression. Furthermore, Gd3+ activated EGFR signaling possibly by enhancing EGFR clustering on the cell membrane. Inhibition of EGFR by gefitinib blocked Gd3+-induced proliferation. Gd3+ exposure also upregulated the mRNA levels of TGFß-1, TGFßR1, TNFα, TIMP-1 and integrin αV, ß1 which could also be attenuated by the inhibition of Akt and ERK signaling. Our study provides new clues for the etiological role of Gd3+ in the pathogenesis of nephrogenic systemic fibrosis, and suggests the inhibition of EGFR/Akt/ERK signaling as a potential treatment strategy.

6.
BMC Cancer ; 19(1): 538, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164099

RESUMO

BACKGROUND: Despite recent advances in the treatments of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains controversial. The purpose of this study was to investigate the prognostic performance of pretreatment albumin to C-reactive protein ratio (ACR) in patients with HCC. METHODS: This study included 409 initially diagnosed HCC patients retrospectively. The optimal cut-off points for distinguishing high and low ACR value was determined by the X-tile software. The chi-squared test was used for comparing the baseline clinicopathologic parameters in different groups and subgroups. The Cox regression with log-rank tests was used to analyze OS and DFS, and Kaplan-Meier curves was used to estimate the prognosis of HCC patients. RESULTS: Patients with lower ACR were significantly correlated with advanced clinical parameters, using a cut-off points of 5.4 (high ACR, n = 236 vs. low ACR, n = 173). Multivariate analysis demonstrated that ACR was associated with OS (HR = 0.544, 95% CI: 0.385-0.769, p = 0.001), with DFS (HR = 0.550, 95% CI: 0.392-0.772, p = 0.001). Treatment exposure (HR = 2.191; 95% CI: 1.533-3.132; p <  0.001), tumor size (HR = 1.973; 95% CI: 1.230-3.164; p = 0.005), serum AFP level (HR = 1.752; 95% CI: 1.277-2.403; p = 0.001), and TNM stage (HR = 0.470; 95% CI: 0.319-2.504; p <  0.001), were independent factors for OS in HCC patients. Treatment exposure (HR = 2.244; 95% CI: 1.590-3.166; p <  0.001), TNM stage (HR = 2.075; 95% CI: 1.436-3.000; p <  0.001), serum AFP level (HR = 1.819; 95% CI: 1.340-2.469; p = 0.001), tumor size (HR = 1.730; 95% CI: 1.113-2.689; p = 0.015), and ACR (HR = 0.550; 95% CI: 0.392-0.772; p = 0.001) were independent factors for DFS in HCC patients. CONCLUSIONS: Pretreatment ACR is a convenient and useful parameter for HCC patients predicting OS and DFS. Lower ACR was associated with advanced TNM stage, larger tumor size, and a high concentration of AFP. These results may help to design strategies to personalize management approaches among HCC patients.

7.
Leuk Lymphoma ; : 1-10, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31060406

RESUMO

We evaluated the effect of primary tumor invasion (PTI) on treatment selection in 1356 patients with extranodal nasal-type NK/T cell lymphoma who received non-anthracycline-based chemotherapy from the updated dataset of China Lymphoma Collaborative Group. 760 (56.0%) patients had PTI. PTI showed most prominent effect in stage I disease, with 5-year overall survival (OS) of 83.0% in PTI-absent patients and 69.5% in PTI-present patients (p < .001). Radiotherapy ± chemotherapy achieved higher OS in PTI-absent stage I patients (approximately 85%). Either radiotherapy alone or chemotherapy alone was associated with an unfavorable OS in PTI-present patients (approximately 55%). Compared to radiotherapy alone, combined modality treatment improved OS in PTI-present patients (78.3% vs. 56.6%; p = .001) but showed similar OS in PTI-absent patients (85.3% vs. 83.3%; p = .560). These findings were confirmed in multivariate analyses. PTI was a robust prognostic factor and indicator for additional chemotherapy in stage I NKTCL patients.

8.
Cancer Med ; 8(6): 2759-2768, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30983159

RESUMO

BACKGROUND: The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity-modulated radiotherapy (IMRT). METHODS: A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109 /L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). RESULTS: Sixty-nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high-grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. CONCLUSIONS: HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

9.
Nanoscale ; 11(16): 7744-7753, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30949642

RESUMO

This paper reports a fast and efficient excimer ultraviolet (EUV) radiation method to prepare carbon-coated mixed tin oxide-loaded exfoliated graphite (SnOx@C-G) nanocomposites. The SnOx small nanoparticles (SNPs) are isolated using oxidized sucrose and uniformly deposited onto mildly oxidized exfoliated graphite during the 20-minute EUV radiation process. XPS and ESR analyses suggest the existence of abundant oxygen vacancies in the SnOx SNPs. The electrochemical kinetics of SnOx@C-G, which are determined by in situ electrochemical impedance analysis, demonstrated a high reversible capacity of approximately 740 mA h g-1 after 250 cycles at a current density of 1.6 A g-1, and an impressive reversible rate performance exceeding 450 mA h g-1 can be obtained even at a high current density of 3.2 A g-1 when applied as an anode for lithium storage. This improved cycling stability and rate capability benefit from the carbon coating, which not only buffers the volume change of SnOx SNPs but also provides a path for electron transport on the surface of the SnOx SNPs during the electrochemical process. Furthermore, the oxygen vacancies in SnOx SNPs result in a large capacitive contribution to capacity. The EUV radiation method used to synthesize SnOx@C-graphite nanosheets is universally applicable to prepare a high-performance SNPs/carbon-based anode for lithium-ion batteries.

10.
Artif Cells Nanomed Biotechnol ; 47(1): 833-843, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30862190

RESUMO

We aimed to explore the mediating role of Notch signal in macrophage polarization. This signal was knocked out from macrophages of Lyz2 cre and RBP-J flox mice. Bone marrow-derived macrophages (BMDMs) were isolated and polarized. The expressions of polarization markers in BMDMs 24 h after transfection were detected by qPCR. After Notch knockout, the expressions of M1 markers decreased but those of M2 markers increased significantly. MiR-125a/miR-99b and Spaca6 were highly and lowly expressed upon M1 and M2 polarizations, respectively. The expressions of experimental group were significantly lower than those of control group. Overexpression of miR-125a significantly promoted the expressions of M1 markers, whereas inhibited those of M2 markers. NO release in the culture supernatant of miR-125a overexpression group significantly exceeded that of control group. Transfection with miR-125a inhibitor significantly down-regulated IL-12 expression but up-regulated MR expression in BMDMs. The supernatant secreted by M1 macrophages significantly facilitated BS524 cell apoptosis, which was enhanced after miR-125a overexpression. The TNF-α expression of miR-99b overexpression group increased whereas that of MR decreased significantly. The miR-125a/miR-99b cluster contained an RBP-J specific recognition site in the first intron of initial transcript. The Notch signalling pathway promoted macrophage polarization into M1 phenotype by up-regulating miR-125a/miR-99b expression.


Assuntos
Regulação da Expressão Gênica , Macrófagos/imunologia , MicroRNAs/genética , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Técnicas de Inativação de Genes , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Ativação de Macrófagos/genética , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/antagonistas & inibidores , Fenótipo , Receptores Notch/genética , Proteínas de Plasma Seminal/genética
11.
JAMA Netw Open ; 2(3): e190194, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30821826

RESUMO

Importance: Prognosis of early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is usually estimated and stratified at diagnosis, but how the prognosis actually evolves over time for patients who survived after curative treatment is unknown. Objective: To assess conditional survival and failure hazard over time based on risk categories, previous survival, and treatment. Design, Setting, and Participants: This retrospective cohort study reviewed the clinical data of 2015 patients with early-stage NKTCL treated with radiotherapy identified from the China Lymphoma Collaborative Group multicenter database between January 1, 2000, and December 31, 2015. Patients were stratified into low-, intermediate- and high-risk groups according to a previously established prognostic model. Median follow-up was 61 months for surviving patients. Data analysis was performed from December 1, 2017, to January 30, 2018. Exposures: All patients received radiotherapy with or without chemotherapy. Main Outcomes and Measures: Conditional survival defined as the survival probability, given patients have survived for a defined time, and annual hazard rates defined as yearly event rate. Results: A total of 2015 patients were included in the study (mean [SD] age, 43.3 [14.6] years; 1414 [70.2%] male); 1628 patients (80.8%) received radiotherapy with chemotherapy, and 387 (19.2%) received radiotherapy without chemotherapy. The 5-year survival rates increased from 69.1% (95% CI, 66.6%-71.4%) at treatment to 85.3% (95% CI, 81.7%-88.2%) at year 3 for conditional overall survival and from 60.9% (95% CI, 58.3%-63.3%) at treatment to 84.4% (95% CI, 80.6%-87.6%) at year 3 for conditional failure-free survival. The annual hazards decreased from 13.7% (95% CI, 13.0%-14.3%) for death and 22.1% (95% CI, 21.0%-23.1%) for failure at treatment to less than 5% after 3 years (death: range, 0%-3.9% [95% CI, 3.7%-4.2%]; failure: 1.2% [95% CI, 1.0%-1.4%] to 4.2% [95% CI 3.9%-4.6%]). Intermediate-risk (11.4% [95% CI, 10.5%-12.3%]) and high-risk (21.6% [95% CI, 20.0%-23.2%]) patients had initially higher but significantly decreased death hazards after 3 years (<6%, range: 0%-5.9% [95% CI, 5.2%-6.7%]), whereas low-risk patients maintained a constantly lower death hazard of less than 5% (range, 0%-4.8%; 95% CI, 4.4%-5.3%). In high-risk patients, radiotherapy combined with non-anthracycline-based regimens were associated with higher conditional overall survival before year 3 compared with anthracycline-based regimens (hazard ratio [HR] for death, 1.49; 95% CI, 1.13-1.95; P = .004 at treatment; HR, 1.60; 95% CI, 1.07-2.39; P = .02 at 1 year; and HR, 1.77; 95% CI, 0.94-3.33; P = .07 at 2 years) or radiotherapy alone (HR, 2.42; 95% CI, 1.73-3.39; P < .001 at treatment; HR, 1.82; 95% CI, 1.05-3.17; P = .03 at 1 year; and HR, 2.69; 95% CI, 1.23-5.90; P = .01 at 2 years). Conclusions and Relevance: The survival probability increased and the hazards of failure decreased in a risk-dependent manner among patients with early NKTCL after radiotherapy. These dynamic data appear to provide accurate information on disease processes and continual survival expectations and may help researchers design additional prospective clinical trials and formulate risk-adapted therapies and surveillance strategies.

13.
Cancer Med ; 8(5): 2031-2040, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30848102

RESUMO

In the current study, we tried to study the expression of LGALS3 and LGALS3BP, their potential as prognostic markers and the possible genetic/epigenetic mechanisms underlying their dysregulation in different subtypes of glioblastoma (GBM). An in silico retrospective study was performed using large online databases. Results showed that LGALS3 and LGALS3BP were upregulated at both RNA and protein levels in GBM tissue and were generally associated with shorter overall survival (OS) in GBM patients. However, in subgroup analysis, we only found the association in proneural subtype. The copy number alterations did not necessarily lead to LGALS3/LGALS3BP dysregulation. In the proneural subtype of GBM patients, hypermethylation of the two CpG sites (cg19099850 and cg17403875) was associated with significantly lower expression of LGALS3. In univariate and multivariate analysis, LGALS3 expression independently predicted shorter OS in the proneural subtype of GBM (HR: 1.487, 95% CI: 1.229-1.798, P < 0.001), after adjustment of age, gender, IDH1 mutations, temozolomide chemotherapy, radiotherapy and LGALS3BP expression. In comparison, LGALS3BP lost the prognostic value in multivariate analysis. Based on these findings, we infer that LGALS3 expression serves as an independent biomarker of shorter OS in the proneural subtype of GBM, the expression of which might be regulated in an epigenetic manner.

14.
Oncol Rep ; 41(4): 2168-2180, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816522

RESUMO

In patients with head and neck cancer (HNC), lymph node (N) metastases are associated with cancer aggressiveness and poor prognosis. Identifying meaningful gene modules and representative biomarkers relevant to the N stage helps predict prognosis and reveal mechanisms underlying tumor progression. The present study used a step­wise approach for weighted gene co­expression network analysis (WGCNA). Dataset GSE65858 was subjected to WGCNA. RNA sequencing data of HNC downloaded from the Cancer Genome Atlas (TCGA) and dataset GSE39366 were utilized to validate the results. Following data preprocessing, 4,295 genes were screened, and blue and black modules associated with the N stage of HNC were identified. A total of 16 genes [keratinocyte differentiation associated protein, suprabasin, cornifelin (CNFN), small proline rich protein 1B, desmoglein 1 (DSG1), chromosome 10 open reading frame 99, keratin 16 pseudogene 3, gap junction protein ß2, dermokine, LY6/PLAUR domain containing 3, transmembrane protein 79, phospholipase A2 group IVE, transglutaminase 5, potassium two pore domain channel subfamily K member 6, involucrin, kallikrein related peptidase 8] that had a negative association with the N­stage in the blue module, and two genes (structural maintenance of chromosomes 4 and mutS homolog 6) that had a positive association in the black module, were identified to be candidate hub genes. Following further validation in TCGA and dataset GSE65858, it was identified that CNFN and DSG1 were associated with the clinical stage of HNC. Survival analysis of CNFN and DSG1 was subsequently performed. Patients with increased expression of CNFN displayed better survival probability in dataset GSE65858 and TCGA. Therefore, CNFN was selected as the hub gene for further verification in the Gene Expression Profiling Interactive Analysis database. Finally, functional enrichment and gene set enrichment analyses were performed using datasets GSE65858 and GSE39366. Three gene sets, namely 'P53 pathway', 'estrogen response early' and 'estrogen response late', were enriched in the two datasets. In conclusion, CNFN, identified via the WGCNA algorithm, may contribute to the prediction of lymph node metastases and prognosis, probably by regulating the pathways associated with P53, and the early and late estrogen response.


Assuntos
Biomarcadores Tumorais/metabolismo , Desmogleína 1/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Metástase Linfática/diagnóstico , Proteínas de Membrana/metabolismo , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Metástase Linfática/patologia , Prognóstico , Análise de Sobrevida
15.
Biomed Res Int ; 2019: 4012590, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809541

RESUMO

Introduction: Radiotherapy is the mainstay in the treatment of prostate cancer. However, significant radioresistance of castration-resistant prostate cancer (CRPC) cells constitutes a main obstacle in the treatment of this disease. By using bioinformatic data mining methods, LOXL2 was found to be upregulated in both androgen-independent prostate cancer cell lines and radioresistant tumor samples collected from patients with prostate cancer. We speculate that LOXL2 may play an important role in the radioresistance of CRPC cells. Methods: The effect of LOXL2 knockdown on the radiosensitivity of androgen-independent prostate cancer cells lines was measured by the clonogenic assay and xenograft tumor experiments under in vitro and in vivo conditions, respectively. In studies on the mechanism, we focused on the EMT phenotype changes and cell apoptosis changes induced by LOXL2 knockdown in DU145 cells. The protein levels of three EMT biomarkers, namely, E-cadherin, vimentin, and N-cadherin, were measured by western blotting and immunohistochemical staining. Cell apoptosis after irradiation was measured by flow cytometry and caspase-3 activity assay. Salvage experiment was also conducted to confirm the possible role of EMT in the radiosensitization effect of LOXL2 knockdown in CRPC cells. Results: LOXL2 knockdown in CRPC cells enhanced cellular radiosensitivity under both in vitro and in vivo conditions. A significant reversal of EMT was observed in LOXL2-silenced DU145 cells. Cell apoptosis after irradiation was significantly enhanced by LOXL2 knockdown in DU145 cells. Results from the salvage experiment confirmed the key role of EMT process reversal in the radiosensitization effect of LOXL2 knockdown in DU145 cells. Conclusions: LOXL2 plays an important role in the development of cellular radioresistance in CRPC cells. Targeting LOXL2 may be a rational avenue to overcome radioresistance in CRPC cells. A LOXL2-targeting strategy for CRPC treatment warrants detailed investigation in the future.


Assuntos
Aminoácido Oxirredutases/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias de Próstata Resistentes à Castração/radioterapia , Tolerância a Radiação/genética , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Cancer Med ; 8(3): 1197-1208, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30741461

RESUMO

Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR-130a-3p in the progression of transforming growth factor-ß (TGF-ß)-induced EMT in vivo and in vitro. The expression of miR-130a-3p in ESCC cell line and normal esophageal epithelial cell was determined by RT-qPCR. The protein expression levels of TGF-ß-induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual-luciferase report assays were used to validate the regulation of miR-130a-3p-SMAD4 axis. The effect of miR-130a-3p and SMAD4 in TGF-ß-induced migration, invasion in the ESCC cell line EC-1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF-ß-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. miR-130a-3p, which directly targets SMAD4, is down-regulated in ESCC. miR-130a-3p inhibits the migration and invasion of EC-1 cells both in vitro and in vivo. Finally, miR-130a-3p inhibits TGF-ß-induced EC-1 cell migration, invasion, and EMT progression in a SMAD4-dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF-ß/miR-130a-3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.

17.
World Neurosurg ; 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30639503

RESUMO

BACKGROUND: Dumbbell-shaped tumor is a type of the inner and outer cervical spinal canal tumor, and most of them are neurogenic tumors. Desmoid tumor is a rare tumor, and no case of them involving intervertebral foramen formed dumbbell-shaped in cervical spine have been reported before in English literature. Here we report a case of desmoid tumor arising in the cervical spine which is presented as typical dumbbell-shaped tumor. CASE DESCRIPTION: A 47-year-old female was admitted to our department with a mass in her left neck. The tumor was initially thought to be a neurogenic cervical dumbbell tumor based on physical and radiological examination. Postoperative HE and immunohistochemical staining verified the diagnosis of a cervical dumbbell desmoid tumor, which had never been reported before. We report our experience and reviewed literature about desmoid tumor to share our experience and explore proper treatment option of such lesion. CONCLUSION: Desmoid tumors in the head and neck may present as cervical dumbbell-shaped tumors. Before the treatment plan was undertaken, thorough examinations including surgical pathology were necessary.

18.
Biomed Pharmacother ; 109: 2228-2236, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551480

RESUMO

OBJECTIVE: Esophageal cancer is one of the deadliest cancers worldwide occurring at upper gastrointestinal tract. This study aimed to explore the possible role of long non-coding RNA X Inactive Specific Transcript (XIST) in the development of esophageal cancer. MATERIAL AND METHODS: The lncRNA XIST expressions both in esophageal cancer tissues and in cells were investigated. The TE-1 and SKGT-4 cells were transfected with LV-sh-XIST and LV-scramble for the further detection of the effects of XIST expression on cell biological processes, including proliferation, apoptosis and the expression of apoptosis-related proteins, migration, invasion and the expression of epithelial-mesenchymal transition markers. Additionally, the regulatory relationships between lncRNA XIST and miR-494, between miR-494 and CDK6, between miR-494/CDK6 and JAK2/STAT3 pathway were investigated. RESULTS: LncRNA XIST was overespressed in esophageal cancer tissues and cells. Suppression of XIST significantly inhibited the proliferation, migration and invasion, but induced apoptosis of two kinds of cells, TE-1 and SKGT-4. Moreover, miR-494 was down-regulated in esophageal cancer tissues and cells. XIST could sponge miR-494 and inhibition of miR-494 reversed the effects of XIST suppression on the malignant behaviors of TE-1 cells. Also, CDK6 was a target of miR-494 and CDK6 knockdown reversed the effects of miR-494 inhibition on the malignant behaviors of TE-1 cells. Besides, the expression of p-JAK2 and p-STAT3 was increased after miR-494 inhibition, which was reversed after inhibition of miR-494 and CDK6 at the same time. CONCLUSIONS: The data presented in this study revealed that XIST abnormal expression may play an oncogenic role in the development of esophageal cancer via miR-494/CDK6 axis through JAK2/STAT3 signal pathway. This study may provide theoretical basis for the molecular mechanism investigation of esophageal cancer.


Assuntos
Quinase 6 Dependente de Ciclina/biossíntese , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Adulto , Quinase 6 Dependente de Ciclina/genética , Neoplasias Esofágicas/genética , Feminino , Células HEK293 , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética
19.
Hematology ; 24(1): 10-19, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30024839

RESUMO

OBJECTIVES: The effect of methotrexate (MTX)-related adverse reaction on hematologic neoplasms patients is controversial. We performed this meta-analysis to assess the association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphism and the adverse reaction after MTX using. METHODS: We searched for qualified studies according to PubMed, the Cochrane Library, and the Web of Science. The meta-analysis was performed by Review Manager 5.3. The analysis was conducted to compare risk ratios (RRs) with the corresponding 95% confidence interval (95% CI) to evaluate the relationship between different toxicity reactions and the genotype of MTHFR. RESULTS: We included 17 studies which satisfied with the criteria in this meta-analysis. The results of our statistical analysis showed that no significant correlation between MTHFR C677T/A1298C genetic polymorphism and patients' toxicity or the relapse and survival associated with MTX chemotherapy (P > .05). But we observed that a tendency toward increased risk of hepatotoxicity was also present for acute lymphoblastic leukemia in the mutation model (CT/TT vs. CC: RR: 1.92, 95% CI: 1.01-3.67; P = .05). CONCLUSION: The polymorphism of MTHFR C677T/A1298C may not be an important indicator for the accurate detection of side effects of chemotherapy after using MTX. More relative research is needed.


Assuntos
Neoplasias Hematológicas , Metotrexato/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2) , Polimorfismo Genético , Intervalo Livre de Doença , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/enzimologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Humanos , Metotrexato/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Sobrevida
20.
Onco Targets Ther ; 11: 7483-7492, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498361

RESUMO

Background: Nasopharyngeal carcinoma (NPC) is a common malignant tumor characterized by highly malignant local invasion and distant metastasis. Recently, increasing attention has been paid to long noncoding RNAs (lncRNAs), which play significant roles in tumorigenesis and progression. However, little is known about the potential role of the lncRNA urothelial carcinoma-associated 1 (UCA1) in NPC cell invasion and migration. Methods: Real-time quantitative PCR was used to analyze the expression of lncRNA UCA1 in NPC cell lines and NP69. lncRNA UCA1 knock-down nasopharyngeal carcinoma cell line models were established through siRNA. Cell viability was evaluated by Cell counting kit-8 and Colony forming assay. The migration and invasion capacities were evaluated by wound healing and transwell migration and invasion assays. Western blot analysis were used to examine protein changes followed by UCA1 knock-down. Results: Our study confirmed that UCA1 was upregulated in NPC cell lines and involved in NPC tumorigenesis according to our established UCA1-associated competing endogenous RNA network. Moreover, functional analyses indicated that the downregulation of UCA1 exerted inhibitory effects on cell proliferation, invasion, and migration. Mechanistic analyses revealed that UCA1 was the target of miR-145 and functioned as a sponge to repress miR-145 expression. Rescue experiments suggested that lncRNA UCA1 reversed the miR-145-mediated inhibition on oncogene ADAM17 expression, thus promoting the proliferation, invasion, and migration of NPC cells. Conclusion: LncRNA UCA1 functions as a tumor promoter in NPC. UCA1 promotes the proliferation and invasion of NPC cells by sponging miR-145, functionally altering ADAM17 expression targeted by miR-145. Our exploration of the underlying mechanism of UCA1 in NPC may provide novel therapeutic targets for NPC.

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