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1.
Artigo em Inglês | MEDLINE | ID: mdl-32209261

RESUMO

Charcoal-stripped fetal bovine serum (CS-FBS) is frequently used in studies on hormone-responsive cancers to provide hormone-free cell culture conditions. CS-FBS may influence the growth of cancer cells; however, the underlying mechanisms remain unclear. In this study, we aimed to clarify the effects of CS-FBS on distinct subtypes of breast cancer cells. We found that the crucial oncoprotein c-Myc was significantly inhibited in estrogen receptor alpha (ER-α)-positive breast cancer cells when cultured in CS-FBS-supplemented medium, but it was not suppressed in ER-α-negative cells. The addition of 17ß-estradiol (E2) to CS-FBS-supplemented medium rescued the CS-FBS-induced inhibition of c-Myc, while treatment with 5α-dihydrotestosterone (DHT) suppressed c-Myc expression. Our data demonstrated that CS-FBS may impede the growth of ER-α-positive breast cancer cells via c-Myc inhibition, and this was possibly due to the removal of estrogen. These results highlighted that the core drivers of c-Myc expression were subtype-specific depending on the distinct cell context and special caution should be exercised when using CS-FBS in studies of hormone-responsive cancer cells.

2.
BMC Cancer ; 20(1): 89, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013967

RESUMO

BACKGROUND: We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. METHODS: The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses. RESULTS: A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. CONCLUSIONS: In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

3.
Hum Vaccin Immunother ; : 1-8, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048897

RESUMO

Background: This study aimed to evaluate the age-appropriate coverage and its associated risk factors for the primary vaccination of Polio containing vaccine (PCV) and measles-containing vaccine (MCV) through the secondary use of the 2018 Zhejiang provincial coverage survey among children aged 12-23 months.Methods: Data were collected through structured pre-tested Chinese version questionnaire by face-to-face interview among 770 mothers whose children aged 12-23 months. Age-appropriate vaccination coverage was measured using Chinese vaccination schedule recommendation. Bivariate and multivariate logistic regression models were adopted to identify determinants of the age-inappropriate vaccination.Results: The age-appropriate vaccination coverage of PCV1, PCV2, PCV3, and MCV was 88.8%, 80.8%, 73.6%, and 75.7%, respectively. The risk factors associated with the age-inappropriate vaccination of PCV 1-3 dose and MCV included child's gender, birthplace, living area, maternal education level, immigration status, monthly household income, participation of the pregnant women's seminar, antenatal care follow-up, knowledge on vaccination.Conclusion: The proportions of age-appropriate vaccination coverage were low compared with the up-to-date coverage. Modifiable factors were associated with age-inappropriate vaccinations. Vaccination interventions should consider identified modifiable factors to improve age-appropriate vaccination coverage.

4.
Radiother Oncol ; 145: 101-108, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931288

RESUMO

BACKGROUND AND PURPOSE: To evaluate the prognostic value of MRI-detected residual retropharyngeal lymph node (RRLN) at three months after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and second, to establish a nomogram for the pretherapy prediction of RRLN. MATERIALS AND METHODS: We included 1103 patients with NPC from two hospitals (Sun Yat-Sen University Cancer Center [SYSUCC, n = 901] and Dongguan People's Hospital [DGPH, n = 202]). We evaluated the prognostic value of RRLN using Cox regression model in SYSUCC cohort. We developed a nomogram for the pretherapy prediction of RRLN using logistic regression model in SYSUCC training cohort (n = 645). We assessed the performance of this nomogram in an internal validation cohort (SYSUCC validation cohort, n = 256) and an external independent cohort (DGPH validation cohort, n = 202). RESULTS: RRLN was an independent prognostic factor for OS (HR 2.08, 95% CI 1.32-3.29), DFS (HR 2.45, 95% CI 1.75-3.42), DMFS (HR 3.31, 95% CI 2.15-5.09), and LRRFS (HR 3.04, 95% CI 1.70-5.42). We developed a nomogram based on baseline Epstein-Barr virus DNA level and three RLN status-related features (including minimum axial diameter, extracapsular nodal spread, and laterality) that predicted an individual's risk of RRLN. Our nomogram showed good discrimination in the training cohort (C-index = 0.763). The favorable performance of this nomogram was confirmed in the internal and external validation cohorts. CONCLUSION: MRI-detected RRLN at three months after IMRT was an unfavorable prognostic factor for patients with NPC. We developed and validated an easy-to-use nomogram for the pretherapy prediction of RRLN.

5.
Cancer Med ; 9(3): 920-930, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31834990

RESUMO

BACKGROUND: To explore the prognostic value of early radiological response (ERR) to first-line platinum-containing chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC), as well as its correlation with the best radiological response (BRR). PATIENTS AND METHODS: A total of 756 mNPC patients with measurable lesions who received first-line platinum-containing chemotherapy were enrolled in this study. ERR was defined as complete or partial response after 6 weeks of chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. We performed survival analyses according to the radiological response after repeated chemotherapy. Log-rank test and Cox regression were used to analyze the survival data. RESULTS: About 470 patients achieved ERR and 78 patients achieved subsequent response (objective response after repeated chemotherapy). ERR patients had better OS (P < .001, median OS: 34.3 vs 22.2 months) and PFS (P < .001, median PFS: 10.2 vs 7.4 months) than non-ERR ones. ERR (OS: HR = 0.591, 95% CI, 0.495-0.705, P < .001, PFS: HR = 0.586, 95% CI, 0.500-0.686, P < .001) was independently prolonged survival compared with non-ERR ones. Besides, ERR was significantly correlated with the BRR (Kappa: 0.73; Pearson: 0.74, P < .001), and had significantly longer OS and PFS than patients with subsequent response, respectively. CONCLUSION: ERR is an independent prognostic factor in determining survival in mNPC patients received first-line platinum-containing chemotherapy, which may be a more sensitive predictor to assess overall efficacy of systemic treatment than BRR in mNPC. Prospective validation studies are needed.

6.
Cancer Manag Res ; 11: 9813-9827, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819619

RESUMO

Purpose: This large population-based analysis aims to investigate whether the additional induction chemotherapy to concurrent chemoradiotherapy improved overall survival (OS) and disease-free survival (DFS) for locoregionally advanced nasopharyngeal carcinoma (LRANPC). Patients and Methods: The study group comprised 3,980 patients who were treated either with IC+CCRT (1,888 patients) or CCRT alone (2,092 patients) between January 1998 and June 2013. Survival outcomes were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods. Primary outcome variables included OS and DFS. Results: Kaplan-Meier analysis showed that CCRT and IC+CCRT were of similar benefit to OS (P=0.099), whereas there was a marginal benefit of CCRT to DFS (P=0.063) in the overall cohort, which showed no differences between the two treatment regimens using multivariate Cox analysis and propensity score. Interestingly, for patients with 2D radiationtherapy (2DRT), CCRT had OS and DFS benefits for stage III, with 5-year and 10-year OS for CCRT vs IC+CCRT being 88% and 75% vs 81% and 67%, respectively (P=0.002); 5-year and 10-year DFS for CCRT vs IC+CCRT being 84% and 74% vs 76% and 66%, respectively (P=0.002). In contrast, IC + CCRT had OS and DFS benefits for stage IVa-b, with 5-year and 10-year OS for CCRT vs IC+CCRT being 71% and 55% vs 76% and 60%, respectively (P=0.037, HR=0.786); 5-year and 10-year DFS for CCRT vs IC+CCRT were 64% and 50% vs 69% and 58%, respectively (P=0.038, HR=0.801). No difference was found in intensity-modulated radiotherapy (IMRT) subgroup. Conclusion: Our study indicates that CCRT and IC+CCRT may have similar OS and DFS benefits for overall LRANPC. Stage-specific chemoradiotherapy may be administered based on the greatest benefit of IC+CCRT for stage IVa-b patients and CCRT alone for stage III patients received 2DRT. The optimal chemotherapy pattern in combination with IMRT needs further investigation. Trial registration:  ClinicalTrials.gov ID: NCT02604472.

7.
Curr Neurovasc Res ; 16(4): 373-381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31490756

RESUMO

OBJECTIVE: Dysregulation of miR-34a has been reported for its implication in neuronal development. This study aims to explore the effect and possible mechanism of miR-34a on neuron apoptosis induced by Spinal Cord Injury (SCI). MATERIALS AND METHODS: SCI model was established using Allen's weight-drop method and rats in the sham group were performed with laminectomy without weight-drop injury. Basso Bcattie Bresnahan (BBB) rating scale was applied to evaluate the locomotor function of rats. Pathological changes of spinal cord tissues in SCI rats were observed after hematoxylin and eosin (HE) staining. Rats were separately injected with miR-34a agomir, miR-34a agomir NC, si-CD47 and si- CD47 NC before their spinal cord tissues were collected for terminal-deoxynucleoitidyl Transferase Mediated nick end labeling (TUNEL) staining. Expressions of miR-34a, si-CD47, apoptosis related proteins and AKT pathway related proteins were measured by quantitative reverse transcription- polymerase chain reaction (qRT-PCR) and western blot. RESULTS: SCI rat models were successfully established evidenced by decreased BBB scores and HE staining. Injection of miR-34a agomir and/or si-CD47 could suppress neuron cell apoptosis, with deceased apoptotic index (AI) and pro-apoptotic protein (cleaved caspase-3 and Bax) levels, and increased expressions of anti-apoptotic proteins (Bcl-2 and Mcl-1). Phosphorylated levels of phatidylinositol 3-kinase (PI3K) and AKT were further increased in rats injected with miR-34a agomir and si-CD47, compared with miR-34a agomir or si-CD47 injection alone. CONCLUSION: MiR-34a can downregulate CD47 expression to activate PI3K/AKT signal pathway, and thus inhibit SCI induced spinal neuron apoptosis.

8.
Ecotoxicol Environ Saf ; 184: 109636, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31536849

RESUMO

Bioremediation of chromium (Cr(Ⅵ)) contaminations has been widely reported, but the research on its removal mechanism is still scarce. Studies on Cr(Ⅵ) removal by strains affiliated to genus Pseudochobactrum revealed the Cr(Ⅵ) efficiency removal through the reduction of Cr(Ⅵ) to Cr(Ⅲ). However, the location of Cr(Ⅵ) reduction reaction and exact mechanism are still unspecified. In this work, a Gram-positive bacterial strain, Pseudochrobactrum saccharolyticum W1 (P. saccharolyticum W1) was isolated and tested to remove approximately 53.7% of Cr(Ⅵ) (initial concentration was 200 mg L-1) from the MSM medium. Analysis of SEM-EDS and TEM-EDS indicated that chromium-containing particles precipitated both on the cell surface and in the cytoplasm. Batch experiments indicated that the heat-treated bacterial cells almost had no ability to remove Cr(Ⅵ) from solution, while the resting cells could remove 62.0% of Cr(Ⅵ) at the initial concentration of 10 mg L-1. Additionally, at this concentration, 64.8% and 70.8% of Cr(Ⅵ) was reduced by cell envelope components and intracellular soluble substances after 6 h, respectively. These results suggested that the removal of Cr(Ⅵ) by P. saccharolyticum W1 was through direct reduction, which occurred on both cell envelop and cytoplasm. The results also showed that cytoplasm was the main site for Cr(Ⅵ) reduction compared to the cell envelop. Further analysis of FTIR and XPS verified that C-H, C-C, CO, C-OH and C-O-C groups of cells involved in correlation with chromium during Cr(Ⅵ) reduction. The study offered an insight into the Cr(VI) reduction mechanism of P. saccharolyticum W1.


Assuntos
Brucellaceae/metabolismo , Cromo/análise , Modelos Teóricos , Biodegradação Ambiental , Brucellaceae/ultraestrutura , Membrana Celular/metabolismo , Cromo/metabolismo , Citoplasma/metabolismo , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Oxirredução
9.
J Exp Clin Cancer Res ; 38(1): 152, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961661

RESUMO

BACKGROUND: With the rapid development of the high throughput detection techniques, tumor-related Omics data has become an important source for studying the mechanism of tumor progression including breast cancer, one of the major malignancies worldwide. A previous study has shown that the G2 and S phase-expressed-1 (GTSE1) can act as an oncogene in several human cancers. However, its functional roles in breast cancer remain elusive. METHOD: In this study, we analyzed breast cancer data downloaded from The Cancer Genome Atlas (TCGA) databases and other online database including the Oncomine, bc-GenExMiner and PROGgeneV2 database to identify the molecules contributing to the progression of breast cancer. The GTSE1 expression levels were investigated using qRT-PCR, immunoblotting and IHC. The biological function of GTSE1 in the growth, migration and invasion of breast cancer was examined in MDA-MB-231, MDA-MB-468 and MCF7 cell lines. The in vitro cell proliferative, migratory and invasive abilities were evaluated by MTS, colony formation and transwell assay, respectively. The role of GTSE1 in the growth and metastasis of breast cancer were revealed by in vivo investigation using BALB/c nude mice. RESULTS: We showed that the expression level of GTSE1 was upregulated in breast cancer specimens and cell lines, especially in triple negative breast cancer (TNBC) and p53 mutated breast cancer cell lines. Importantly, high GTSE1 expression was positively correlated with histological grade and poor survival. We demonstrated that GTSE1 could promote breast cancer cell growth by activating the AKT pathway and enhance metastasis by regulating the Epithelial-Mesenchymal transition (EMT) pathway. Furthermore, it could cause multidrug resistance in breast cancer cells. Interestingly, we found that GTSE1 could regulate the p53 function to alter the cell cycle distribution dependent on the mutation state of p53. CONCLUSION: Our results reveal that GTSE1 played a key role in the progression of breast cancer, indicating that GTSE1 could serve as a novel biomarker to aid in the assessment of the prognosis of breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Ciclo Celular/fisiologia , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Associadas aos Microtúbulos/biossíntese , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Transfecção
10.
Cancer Commun (Lond) ; 39(1): 14, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925939

RESUMO

BACKGROUND: Currently, the diagnosis and treatment of nasopharyngeal carcinoma (NPC) patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging. We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus (EBV) DNA in these patients. METHODS: This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy. Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction (qPCR) before the initiation of treatment and before neck dissection. Fine needle aspiration cytology (FNAC) was performed in 21 patients. All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analysis was used to estimate the effect of potential prognostic factors on survival. RESULTS: Following a median follow-up of 52.6 months, compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy, the patients with positive findings had a significantly lower 3-year PFS rate (49.9% vs. 83.3%, P = 0.008). Among NPC patients with residual cervical lymphadenopathy, the patients with preoperative plasma EBV DNA > 0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA (43.7% vs. 61.1%, P = 0.031). In addition, combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity. Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS. CONCLUSIONS: Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Linfadenopatia/virologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/virologia , Adulto , Idoso , Infecções por Vírus Epstein-Barr/sangue , Feminino , Humanos , Linfonodos/patologia , Linfadenopatia/sangue , Linfadenopatia/diagnóstico , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/sangue , Neoplasias Nasofaríngeas/sangue , Pescoço , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
11.
Elife ; 82019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30735121

RESUMO

MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and a central player in liver biology and disease. Herein, we report a previously unknown role for miR-122 in hepatocyte intrinsic innate immunity. Restoration of miR-122 levels in hepatoma cells markedly enhanced the activation of interferons (IFNs) in response to a variety of viral nucleic acids or simulations, especially in response to hepatitis C virus RNA and poly (I:C). Mechanistically, miR-122 downregulated the phosphorylation (Tyr705) of STAT3, thereby removing the negative regulation of STAT3 on IFN-signaling. STAT3 represses IFN expression by inhibiting interferon regulatory factor 1 (IRF1), whereas miR-122 targets MERTK, FGFR1 and IGF1R, three receptor tyrosine kinases (RTKs) that directly promote STAT3 phosphorylation. This work identifies a miR-122-RTKs/STAT3-IRF1-IFNs regulatory circuitry, which may play a pivotal role in regulating hepatocyte innate immunity. These findings renewed our knowledge of miR-122's function and have important implications for the treatment of hepatitis viruses.

12.
Microb Drug Resist ; 25(1): 127-132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29708845

RESUMO

Flies play an important role as vectors in the transmission of antimicrobial-resistant bacteria (ARB) and are hypothesized to transfer ARB between internal and external livestock housing areas. The aim of this study was to understand the role that flies may play in the maintenance of ARB in the farm environment. We first evaluated the fate of ingested antimicrobial-resistant Escherichia coli harboring a plasmid containing antimicrobial-resistance genes (ARGs) throughout the housefly (Musca domestica) life cycle, from adult to the subsequent F1 generation. Antimicrobial-resistant E. coli was isolated from different life cycle stages and ARG carriage quantified. The ingested E. coli persisted throughout the fly life cycle, and ARG carriage was maintained at a constant level in the housefly microbiota. To clarify the transmission of ARB from flies to livestock, 30-day-old chickens were inoculated with maggots containing antimicrobial-resistant E. coli. Based on the quantification of bacteria isolated from cecal samples, antimicrobial-resistant E. coli persisted in these chickens for at least 16 days. These results suggest that flies act as a reservoir of ARB throughout their life cycle and may therefore be involved in the maintenance and circulation of ARB in the farm environment.


Assuntos
Antibacterianos/farmacologia , Dípteros/microbiologia , Escherichia coli/genética , Animais , Galinhas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fazendas , Moscas Domésticas/microbiologia , Plasmídeos/genética
13.
Anticancer Drugs ; 30(2): 186-194, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30418194

RESUMO

Using five bioinformatics analysis software, we identified Golgi protein 73 (GP73) as a putative target of microRNA-27b (miR-27b), which is closely related to various biological processes or diseases such as bone metabolism disease, adipose cell and muscle cell development, pulmonary hypertension, cervical cancer, and breast cancer. However, the clinical significance of miR-27b in hepatocellular carcinoma (HCC) is still unclear. The differential expression of miR-27b in HCC and adjacent normal liver tissues was measured by quantitative reverse transcription PCR. Our results showed that the expression of miR-27b in tumor tissues is lower than that in adjacent nontumor tissues. The expression of miR-27b was significantly lower in HCC tissues with high expression of GP73, when compared with adjacent nontumor tissues. Moreover, down-regulated expression of miR-27b was closely correlated with serum GP73, tumor-node-metastasis stage, tumor size, and portal vein thrombosis. GP73 mRNA might be a target of miR-27b. The 5-year overall survival rate of the low miR-27b expression group was significantly lower than that of the high miR-27b expression group. Moreover, multivariate analysis of prognostic factors, with a Cox proportional hazards model, showed that low miR-27b expression was a significant and independent predictor of poor survival in HCC. Hence, the abnormal expression of miR-27b might be related to the occurrence and development of tumors. Similarly, a study in the Cancer Genome Atlas database demonstrated that the expression of miR-27b in 50 normal individuals was 1.6 times higher than that of 372 patients with liver cancer. The overall survival rate of the low GP73 expression group (275 liver cancer patients) was significantly longer than that of the high GP73 expression group (90 normal individuals). MiR-27b suppresses the expression of GP73 and is therefore a potential prognostic biomarker and therapy target in HCC.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(6): 1858-1862, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30501734

RESUMO

Mesenchymal stem cells (MSC) have the potential of multi-directional differentiation, and can recruit endothelial cells, promote their proliferation, migration and angiogenesis, improve blood perfusion and oxygen suppliment, and repair damaged tissue. Exosome secreted by MSC contain mother cell-specific proteins, lipids and nucleic acids, and acts as signaling molecule, playing an important role in cell communication, thereby altering target cell function. In this review, the biological characteristics of MSC and its exosome, the mechanism of promoting vascular regeneration in patients with ischemic diseases, and the mechanism of hypoxia-inducible factor-1α(HIF-1α) in the vascular ischemia of ischemic diseases are all summarized briefly.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Diferenciação Celular , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neovascularização Patológica , Neovascularização Fisiológica
15.
Mol Oncol ; 12(11): 1949-1964, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30171794

RESUMO

miR-372/373, a cluster of stem cell-specific microRNAs transactivated by the Wnt pathway, has been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, the unique role of these microRNAs in cancer remains to be discovered. In the present study, we characterized the upregulation in expression of miR-372/373 in CRC tissues from The Cancer Genome Atlas data, and then showed that overexpression of miR-372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24-positive cell population and promoting self-renewal, chemotherapy resistance and the invasive potential of CRC cells. To clarify the mechanism underlying microRNA-induced stemness, we profiled 45 cell signaling pathways in CRC cells overexpressing miR-372/373 and found that stemness-related pathways, such as Nanog and Hedgehog, were upregulated. Instead, differentiation-related pathways, such as NFκB, MAPK/Erk and VDR, were markedly repressed by miR-372/373. Numerous new targets of miR-372/373 were identified, including SPOP, VDR and SETD7, all of which are factors important for cell differentiation. Furthermore, in contrast to the increase in miR-372/373 expression in CRC tissues, the expression levels of SPOP and VDR mRNA were significantly downregulated in these tissues, indicative of the poor differentiation status of CRC. Taken together, our findings suggest that miR-372/373 enhance CRC cell stemness by repressing the expression of differentiation genes. These results provide new insights for understanding the function and mechanisms of stem cell-specific microRNAs in the development of metastasis and drug resistance in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , RNA Neoplásico/metabolismo , Animais , Células CACO-2 , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/patologia , RNA Neoplásico/genética
16.
Cancer Commun (Lond) ; 38(1): 59, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30253801

RESUMO

BACKGROUND: Due to the occult anatomic location of the nasopharynx and frequent presence of adenoid hyperplasia, the positive rate for malignancy identification during biopsy is low, thus leading to delayed or missed diagnosis for nasopharyngeal malignancies upon initial attempt. Here, we aimed to develop an artificial intelligence tool to detect nasopharyngeal malignancies under endoscopic examination based on deep learning. METHODS: An endoscopic images-based nasopharyngeal malignancy detection model (eNPM-DM) consisting of a fully convolutional network based on the inception architecture was developed and fine-tuned using separate training and validation sets for both classification and segmentation. Briefly, a total of 28,966 qualified images were collected. Among these images, 27,536 biopsy-proven images from 7951 individuals obtained from January 1st, 2008, to December 31st, 2016, were split into the training, validation and test sets at a ratio of 7:1:2 using simple randomization. Additionally, 1430 images obtained from January 1st, 2017, to March 31st, 2017, were used as a prospective test set to compare the performance of the established model against oncologist evaluation. The dice similarity coefficient (DSC) was used to evaluate the efficiency of eNPM-DM in automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images, by comparing automatic segmentation with manual segmentation performed by the experts. RESULTS: All images were histopathologically confirmed, and included 5713 (19.7%) normal control, 19,107 (66.0%) nasopharyngeal carcinoma (NPC), 335 (1.2%) NPC and 3811 (13.2%) benign diseases. The eNPM-DM attained an overall accuracy of 88.7% (95% confidence interval (CI) 87.8%-89.5%) in detecting malignancies in the test set. In the prospective comparison phase, eNPM-DM outperformed the experts: the overall accuracy was 88.0% (95% CI 86.1%-89.6%) vs. 80.5% (95% CI 77.0%-84.0%). The eNPM-DM required less time (40 s vs. 110.0 ± 5.8 min) and exhibited encouraging performance in automatic segmentation of nasopharyngeal malignant area from the background, with an average DSC of 0.78 ± 0.24 and 0.75 ± 0.26 in the test and prospective test sets, respectively. CONCLUSIONS: The eNPM-DM outperformed oncologist evaluation in diagnostic classification of nasopharyngeal mass into benign versus malignant, and realized automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images.


Assuntos
Aprendizado Profundo/tendências , Endoscopia/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia
17.
J Cancer Res Clin Oncol ; 144(11): 2231-2243, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30109501

RESUMO

PURPOSE: To retrospectively investigate the optimal regimen of concurrent chemotherapy for nasopharyngeal carcinoma (NPC) by comparing clinical outcomes of patients who received platinum-based and non-platinum-based concurrent chemoradiotherapy (CCRT) regimens. METHODS: Based on a prospectively maintained database from 1998 to 2013 in an endemic area, a total of 4608 newly diagnosed, biopsy-proven, and non-disseminated NPC patients were identified and allocated into three cohorts based on concurrent chemotherapy regimens: cisplatin-based (CP) chemotherapy cohort, other platinum-based (OP) chemotherapy cohort, and non-platinum-based (NP) chemotherapy cohort. Overall survival (OS) and disease-free survival (DFS) were estimated using the Cox proportional hazards model and propensity score analysis of treatment using an inverse probability weighting model (PSA/IPTW). Finally, sensitivity analysis estimated the effects of potential unmeasured confounders. RESULTS: The median follow-up time was 68.5 months (range 2-194 months). The multivariate Cox model showed that NP regimens were significantly related with worse survival compared with CP or OP regimens (OS: HR 1.51, 95% CI 1.16-2.00, P = 0.002; HR 1.68, 95% CI 1.24-2.27, P = 0.001; DFS: HR 1.31, 95% CI 1.03-1.66, P = 0.031; HR 1.50, 95% CI 1.14-1.97, P = 0.004, respectively). Meanwhile, no significant survival difference was found between OP and CP regimens. The PSA/IPTW method, CCRT-specific and III-IVB NPC cohort subgroup analysis showed similar results. Sensitivity analysis confirmed the robustness of our results. CONCLUSIONS: Platinum-based concurrent chemotherapy, including both CP and OP regimens, yields better survival benefits for non-metastatic NPC patients than the NP regimen and remains the optimal regimen for these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Idoso , Criança , Cisplatino/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , /estatística & dados numéricos , Platina/administração & dosagem , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
18.
Cancer Manag Res ; 10: 1935-1946, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30022852

RESUMO

Purpose: Tumor stroma cells play an important role in the carcinogenesis and progression of cancer. The aim of the present investigation was to explore the predictive role of carcinoma-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) in nasopharyngeal carcinoma (NPC). Patients and methods: The densities of CAFs and TAMs were measured by immunohistochemistry staining for α-smooth muscle actin (α-SMA), CD68, and CD163 in two sets of tissue microarrays including 260 pretreatment NPC tissues, that is, a training test comprising of 152 patients and a validation set comprising of 108 patients. Chi-square tests were performed for comparisons among the groups. Survival rates were estimated by using the Kaplan-Meier method and compared with log-rank tests. Cox proportional hazards models were used to identify significant independent variables. Results: Patients older than 50 years showed a lower expression of CD68, and there was a positive relationship between the densities of CAFs and CD163+ TAMs (p=0.001). In the multivariate analysis of the training test, both α-SMA and CD163 were independent prognostic factors for overall survival and progression-free survival (all p<0.05). Based on the expression levels of α-SMA and CD163, patients were categorized into three groups: high-risk, intermediate-risk, and low-risk groups according to both high, either high, and both low, respectively. Survival analysis and Cox multivariate analysis showed that the risk groups based on α-SMA and CD163 expression were independent predictors for the survival of patients with NPC in the training test, which was also confirmed by the validation test. Conclusion: A patient's risk group based on the level of CD163+ TAMs and CAFs was an independent predictor of survival, which may facilitate patient counseling and individualized treatment.

19.
Ther Adv Med Oncol ; 10: 1758835918782331, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30046357

RESUMO

Background: In the intensity-modulated radiotherapy (IMRT) era, the survival benefit of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains undetermined. This study aimed to evaluate the benefits of IMRT with concurrent chemotherapy compared with IMRT alone for LA-NPC patients with different plasma Epstein-Barr virus (EBV) DNA levels. Methods: Patients were identified from a prospectively maintained database in an endemic area between November 2002 and December 2013. Cox proportional hazards models, propensity score matching, and inverse probability weighting models were established for survival analysis. Stratification analysis was performed based on interaction effects analysis. Finally, sensitivity analysis was performed considering unmeasured confounders. Results: A total of 1357 eligible patients were enrolled (median follow up 62.4 months; range 3.5-155.8 months). No significant survival differences were observed between groups in the entire cohort. Notably, a significant interaction effect was observed between treatment regimens and EBV DNA levels. In patients with high EBV DNA levels (>4000 copies/ml), all three models showed that IMRT with concurrent chemotherapy significantly improved overall survival [hazard ratio (HR) 2.521, 95% confidence interval (CI) 1.218-5.216], disease-free survival (HR 2.168, 95% CI 1.349-3.483), and distant metastasis-free survival (HR 2.331, 95% CI 1.194-4.551) compared with IMRT alone. No differences were found in patients with low EBV DNA levels. Sensitivity analysis confirmed the robustness of the results. Conclusion: In the IMRT era, concurrent chemotherapy treatment of LA-NPC patients with high EBV DNA levels is reasonable. However, the optimal regimen for LA-NPC patients with low EBV DNA levels needs further validation in randomized clinical trials.

20.
Cancer Commun (Lond) ; 38(1): 21, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29764487

RESUMO

BACKGROUND: Available data in the literature comparing different induction chemotherapy (IC) regimens on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane, cisplatin and 5-fluorouracil (TPF) or cisplatin and 5-fluorouracil (PF) as IC followed by concurrent chemoradiotherapy (CCRT). METHODS: In total, 1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study. We compared overall survival (OS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival, using the propensity score method. RESULTS: In total, 1256 patients received TPF or PF as IC backbone. The TPF group showed significantly better OS (hazard ratio [HR], 0.660; 95% confidence interval [CI] 0.442-0.986; P = 0.042), DSS (HR, 0.624; 95% CI 0.411-0.947; P = 0.027) and DMFS (HR, 0.589; 95% CI 0.406-0.855; P = 0.005) compared with the PF group in multivariable analyses. Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS (88.1% vs. 80.7%; P = 0.042), DSS (88.5% vs. 80.7%; P = 0.021) and DMFS (87.9% vs. 78.6%; P = 0.012) rates compared with the PF group. There were no significant differences in locoregional relapse-free survival before or after matching. CONCLUSIONS: In our study, IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen. However, a prospective randomized clinical trial to validate these findings is necessary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Náusea/etiologia , Recidiva Local de Neoplasia , Neutropenia/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Vômito/etiologia
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