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1.
J Cell Mol Med ; 25(7): 3524-3536, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33683826

RESUMO

It has been becoming increasingly evident that long non-coding RNAs (lncRNAs) play important roles in various human cancers. However, the biological processes and clinical significance of most lncRNAs in hepatoblastoma (HB) remain unclear. In our previous study, genome-wide analysis with a lncRNA microarray found that lncRNA HOXA-AS2 was up-regulated in HB. Stable transfected cell lines with HOXA-AS2 knockdown or overexpression were constructed in HepG2 and Huh6 cells, respectively. Our data revealed knockdown of HOXA-AS2 increased cell apoptosis and inhibited cell proliferation, migration and invasion in HB. Up-regulation of HOXA-AS2 promoted HB malignant biological behaviours. Mechanistic investigations indicated that HOXA-AS2 was modulated by chromatin remodelling factor ARID1B and transcription co-activator SUB1, thereby protecting HOXA3 from degradation. Therefore, HOXA-AS2 positively regulates HOXA3, which might partly demonstrate the involvement of HOXA3 in HOXA-AS2-mediated HB carcinogenesis. In conclusion, HOXA-AS2 is significantly overexpressed in HB and the ARID1B/HOXA-AS2/HOXA3 axis plays a critical role in HB tumorigenesis and development. These results might provide a potential new target for HB diagnosis and therapy.

2.
Cancer Biomark ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33780361

RESUMO

BACKGROUND: Hepatoblastoma (HB) is an embryonic solid tumor and the most common primary malignant liver tumor in children. HB usually occurs in infants and children. Although treatment diversity is increasing, some patients still have very poor prognosis. Many studies have investigated USP7 inhibitors for tumors. Using database information, we found that USP7 is highly expressed in HB. METHODS: Lentivirus-mediated USP7 knockdown and overexpression was performed in HB cell lines HepG2 and Huh6. CCK8 and transwell assays were used to determine cell viability and metastasis. Flow cytometry was used to study cell cycle and apoptosis. Levels of proteins were detected using western blots. RESULTS: Downregulation of USP7 resulted in significant decrease in cell proliferation, clonal formation, and cell migration and invasion. With overexpression of USP7, cellular malignant behavior increased. Cell cycle assays showed that USP7 knockdown inhibited G1 to S phase transition in the cell cycle. Upregulation of USP7 promoted the transition. Animal experiments showed USP7 facilitated tumor growth in vivo. Western blots indicated that USP7 may affect HB tumorigenesis through the PI3K/AKT signaling pathway. Furthermore, USP7 inhibitor P5091 inhibited HB development and PI3K/AKT pathway. CONCLUSION: USP7 upregulation contributed to HB genesis and development through the PI3K/AKT signaling pathway. USP7 could be a potential target for future HB treatment.

3.
Pharm Biol ; 59(1): 121-128, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33539718

RESUMO

CONTEXT: Berberine (Ber) can increase the survival rate of septic mice and inhibit inflammation, but whether it has a protective effect on septic cardiomyopathy (SCM) is unclear. OBJECTIVE: To investigate whether Ber ameliorates SCM in a rat model and its potential mechanism. MATERIALS AND METHODS: Male SD rats were randomly divided into three groups: control (Con, n = 6) (DD H2O, 2 mL/100 g, ig, qd × 3 d, then saline, 10 mg/kg, ip); sepsis [LPS (lipopolysaccharide), n = 18] (LPS 10 mg/kg instead of saline, ip); and berberine intervention (Ber, n = 18) (Ber, 50 mg/kg instead of DD H2O, ig, qd × 3 d, LPS instead of saline, ip). Hemodynamics, HE staining, ELISA and western blot were performed at 6, 24, and 48 h after intraperitoneal injection of LPS to evaluate the effect of berberine in septic rats. RESULT: Berberine could recover myocardial injury by partially increased ± dp/dt max (1151, 445 mmHg/s) and LVEDP levels (1.49 mmHg) with LPS-induced rats, as well as an ameliorated increase of cTnT (217.53 pg/mL) in the Ber group compared with that in the LPS group (at 24 h). In addition, HE staining results showed that berberine attenuated the myocardial cell swelling induced by LPS. In contrast to the LPS group, the up-regulation of TLR4, p65 TNF-α, and IL-1ß were attenuated in the Ber group. DISCUSSION AND CONCLUSIONS: Berberine showed a protective effect on septic cardiomyopathy rats possibly through inhibiting the activation of TLR4/NF-κB signalling pathway. Whether it improves SCM through other mechanisms is our ongoing research.

4.
Mol Ther Oncolytics ; 19: 149-162, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33209975

RESUMO

A previous study on hepatoblastoma revealed novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex, including the tumor suppressor speckle-type BTB/POZ (SPOP). Moreover, the SPOP gene affected cell growth, and its S119N mutation was identified as a loss-of-function mutation in hepatoblastoma. This study aimed to explore more functions and the potential mechanism of SPOP and its S119N mutation. The in vitro effects of SPOP on cell proliferation, invasion, apoptosis, and in vivo tumor growth were investigated by western blot analysis, Cell Counting Kit-8, colony formation assay, flow cytometry, and xenograft animal experiments. The substrate of SPOP was discovered by a protein quantification assay and quantitative ubiquitination modification assay. The present study further proved that SPOP functioned as an anti-oncogene through the phosphatidylinositol 3-kinase/Akt signaling pathway to affect various malignant biological behaviors of hepatoblastoma both in vitro and in vivo. Furthermore, experimental results also suggested that solute carrier family 7 member 1 (SLC7A1) might be a substrate of SPOP and influence cell phenotype by regulating arginine metabolism. In conclusion, these findings demonstrated the function of SPOP and revealed a potential substrate related to hepatoblastoma tumorigenesis, which might thus provide a novel therapeutic target for hepatoblastoma.

5.
Adv Skin Wound Care ; 33(11): 1-5, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33065687

RESUMO

BACKGROUND: Conjoined twins are a rare congenital anomaly. If separation of the conjoined organs is feasible, reconstruction of the skin and tissue defects is a challenge for the plastic surgeon. This article describes the use of opposing triangle flaps in the separation of three different kinds of conjoined twins. METHODS: Plastic surgeons measured each conjoined area and designated the vertical length as a and the width as b. The length of the base of the opposing triangle flap was calculated to match a, and the height of the triangle to match b. RESULTS: After detailed calculations and careful surgery, the area of the opposing triangle flaps nearly covered the areas exposed after separation, and the three conjoined twins achieved primary closure of their wounds. The pygopagus and ischiopagus twins recovered uneventfully. The omphalopagus twins developed a wound infection, but after daily wound care, the twins recovered within a week. CONCLUSIONS: With precise calculations, the opposing triangle flap is a feasible and effective method for defect closure after separation of conjoined twins in certain cases. Clinicians may prefer this technique because it avoids the complications and second surgery necessitated by tissue expanders.

6.
Oral Dis ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33125794

RESUMO

OBJECTIVE: This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi-square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. RESULTS: TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+ CD4+ and TIGIT+ CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-α and IFN-γ), and TIGIT+ CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-α, and IFN-γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. CONCLUSIONS: TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.

7.
Int J Oral Sci ; 12(1): 24, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934197

RESUMO

Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-negative cohorts. We detected the presence of TILs by staining CD8+ cytotoxic T cells and CD57+ NK cells as well. TLSs appeared as highly organized structures in 45 (26.8%) cases. TLS-positive patients had a better 5-year overall survival (OS) rate (88.9% vs. 56.1%, P < 0.001) and relapse-free survival (RFS) rate (88.9% vs. 63.4%, P = 0.002). Moreover, the presence of TLS was an independent prognostic factor for both the 5-year OS rate (hazard ratio [HR] = 3.784; 95% confidence interval [CI], 1.498-9.562) and RFS rate (HR = 3.296; 95% CI, 1.279-8.490) in multivariate analysis. Furthermore, a higher density of CD8+ T cells and CD57+ NK cells was found in TLS-positive sections than in TLS-negative counterparts (P < 0.001), and their combination provided a higher predictive accuracy (AUC = 0.730; 95% CI, 0.654-0.805). In conclusion, our results suggest that TLS is an independent positive prognostic factor for OSCC patients. These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.

8.
Cancer Cell ; 38(5): 716-733.e6, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32946775

RESUMO

Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.

9.
Oncol Lett ; 20(4): 1, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32774475

RESUMO

Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up- and 571 genes were downregulated, with 32 lncRNAs up- and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

10.
Oncol Rep ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31524279

RESUMO

Previous research from our group revealed that the long coding RNA (lncRNA) linc01105 is associated with neuroblastoma proliferation and apoptosis, and that its expression is correlated with the International Neuroblastoma Staging System stage. The purpose of the present study was to investigate the functions of Linc01105 in neuroblastoma. Lentivirus­mediated linc01105 knockdown was performed in the neuroblastoma cell line SH­SY5Y. The expression levels of linc01105 and of other associated genes were measured by reverse transcription­quantitative PCR. Cell Counting Kit­8 assay and flow cytometry were used to determine cell viability and apoptosis. The levels of proteins were detected using western blot analysis. Bioinformatics analysis and luciferase reporter assays were used to examine the relationship between linc01105, miR­6769b­5p and vascular endothelial growth factor A (VEGFA). Angiogenesis ability was measured using a tube formation assay. The results demonstrated that HIF­1α overexpression promoted the transcription of linc01105 by acting as a transcription factor. Knockdown of linc01105 inhibited neuroblastoma cell proliferation, migration and invasion, and it induced apoptosis. In addition, linc01105 affected the expression of p53 and Bcl­2 family proteins and activated the caspase signaling pathway. Further functional experiments revealed that linc01105 promoted the expression of the miR­6769b­5p target gene VEGFA by acting as a sponge of miR­6769b­5p. In conclusion, linc01105 may contribute to neuroblastoma tumorigenesis and development. The present findings indicated that the interplay between the p53/caspase pathway and the linc01105/miR­6769b­5p/VEGFA axis may have important roles in the development of neuroblastoma.

11.
Clin Cancer Res ; 25(20): 6180-6194, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31350312

RESUMO

PURPOSE: Multiple negative regulators restrict the ability of T cells to attack tumors. This work demonstrates the role of PI3K-interacting protein 1 (Pik3ip1) in restraining T-cell responses and antitumor immunity. EXPERIMENTAL DESIGN: An anti-Pik3ip1 mAb was generated to identify the Pik3ip1 expression pattern of hematopoietic cells. Pik3ip1 -/- mice and a Pik3ip1 fusion protein were generated to investigate the effect of Pik3ip1 on T-cell-mediated antitumor immunity in MC38 and B16-F10 tumor models. Immunoblotting and confocal microscopy were used to identify inhibitory effects of Pik3ip1 on T-cell receptor (TCR) signaling. Pik3ip1 expression was quantified, and its impact on T-cell function in human tumors was measured. RESULTS: We demonstrated that Pik3ip1 was predominantly expressed on T cells and served as an essential rheostat for T-cell-mediated immunity. A Pik3ip1 genetic deficiency led to enhanced T-cell responsiveness upon immunization with a neoantigen. Pik3ip1 -/- mice exhibited a marked increase in antitumor immunity and were resistant to tumor growth. Furthermore, Pik3ip1 extracellular domain fusion protein enhanced MC38 tumor growth was observed. Mechanistically, we found that Pik3ip1 inhibited TCR signaling by mediating the degradation of SLP76 through Pik3ip1 oligomerization via its extracellular region. Consistent with the results from the mouse models, PIK3IP1 expression correlated with T-cell dysfunction in human tumors. CONCLUSIONS: Our data reveal a critical role for Pik3ip1 as a novel inhibitory immune regulator of T-cell responses and provide a potential molecular target for cancer immunotherapy.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Neoplasias/imunologia , Linfócitos T/imunologia , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Humanos , Imunidade Celular , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Cultura Primária de Células , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
12.
Head Neck ; 41(5): 1517-1524, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30759319

RESUMO

The aim of this meta-analysis is to evaluate myeloblastosis (MYB) as a prognostic marker for patients with adenoid cystic carcinoma (ACC) with respect to MYB gene fusion, MYB protein expression, and tumor sites. We comprehensively searched PubMed, Embase, Web of Science, and Cochrane libraries. Ten studies concerning the prognostic comparisons between MYB positivity and negativity were included. The combined positive rates of MYB gene fusion and protein expression were 57.2% and 62.3%, respectively. Overall, no significant prognostic differences were observed between MYB-positive and MYB-negative ACCs. When further divided into MYB gene fusion and MYB protein expression subgroups, no significant differences were observed for any survival outcome (overall survival, disease-free survival, and local control rate). Moreover, MYB also demonstrated no prognostic value in head and neck ACCs. In conclusion, the current studies reveal that MYB is not a good prognostic marker for ACC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/genética , Genes myb , Neoplasias de Cabeça e Pescoço/genética , Neoplasias das Glândulas Salivares/genética , Idoso , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Sensibilidade e Especificidade
13.
Eur J Pediatr Surg ; 29(5): 401-407, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30372769

RESUMO

OBJECTIVE: To evaluate the outcome and safety of corticosteroids and vincristine (VCR) in the treatment of kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). MATERIALS AND METHODS: Clinical studies involving corticosteroids and VCR therapies in treating KHE/TA were identified by using PubMed, Cochrane Library, OVID, EBSCO, CNKI, VIP, and Wanfang databases from their establishment date to December 2017. Randomized controlled trials, case-control, or case series with more than five cases were included. The following data were extracted: study sample, demographics, responses rate, recurrence rate, and adverse reactions. Two reviewers completed screening and extraction. Methodological quality was evaluated with quality appraisal tool. RESULTS: A total of 266 studies were found, and 27 studies were finally included in this research; quality of all studies was low. Seven studies with a total of 123 participants, which compared the effect of systemic corticosteroids with that of VCR, were performed for the meta-analysis. The results indicated that the effect of VCR was significantly higher than that of corticosteroids (relative risk [RR] = 2.08, 95% confidence interval [CI]: 1.38-3.16). The recurrence rate of VCR (11.1%) was lower than that of corticosteroids (50%), but there was no statistical difference between the two therapies (p = 0.1312). The result of pooled adverse reactions response rate for VCR was 18.2%, significantly lower than that for corticosteroids, which was 52.0%. CONCLUSION: The present profile shows that VCR is relatively more effective and safer in treating KHE/TA than corticosteroids are. So, we believe VCR could be used as a first-line medication agent in the treatment of KHE/TA.


Assuntos
Corticosteroides/uso terapêutico , Hemangioendotelioma/tratamento farmacológico , Hemangioma/tratamento farmacológico , Síndrome de Kasabach-Merritt/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Vincristina/uso terapêutico , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Observacionais como Assunto , Recidiva , Resultado do Tratamento
14.
Cancer Immunol Res ; 7(1): 123-135, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30401678

RESUMO

Elucidation of the mechanisms of T-cell-mediated antitumor responses will provide information for the rational design and development of cancer immunotherapies. Here, we found that calnexin, an endoplasmic reticulum (ER) chaperone protein, is significantly upregulated in oral squamous cell carcinoma (OSCC). Upregulation of its membranous expression on OSCC cells is associated with inhibited T-cell infiltration in tumor tissues and correlates with poor survival of patients with OSCC. We found that calnexin inhibits the proliferation of CD4+ and CD8+ T cells isolated from the whole blood of healthy donors and patients with OSCC and inhibits the secretion of IFNγ, TNFα, and IL2 from these cells. Furthermore, in a melanoma model, knockdown of calnexin enhanced the infiltration and effector functions of T cells in the tumor microenvironment and conferred better control of tumor growth, whereas treatment with a recombinant calnexin protein impaired the infiltration and effector functions of T cells and promoted tumor growth. We also found that calnexin enhanced the expression of PD-1 on CD4+ and CD8+ T cells by restraining the DNA methylation status of a CpG island in the PD-1 promoter. Thus, this work uncovers a mechanism by which T-cell antitumor responses are regulated by calnexin in tumor cells and suggests that calnexin might serve as a potential target for the improvement of antitumor immunotherapy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Calnexina/imunologia , Carcinoma de Células Escamosas/imunologia , Neoplasias Bucais/imunologia , Idoso , Animais , Calnexina/genética , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia
15.
EBioMedicine ; 35: 244-250, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30104180

RESUMO

Detecting circulating tumor cells (CTCs) has proven valuable for evaluating the prognosis of cancer patients and for studying the mechanisms of treatment resistance. Owing to the lack of universal and specific tumor markers for neuroblastoma (NB), in this prospective study, we adopted an EpCAM-independent method to detect CTCs in the peripheral blood of NB patients. We used an EpCAM-independent assay to delete leukocytes and to enrich the CTCs. CTCs were identified by immunostaining of CD45, DAPI and DNA fluorescence in situ hybridization (FISH) of the centromere of chromosome 8 probe (CEP8). Cells that were DAPI+/CD45-/CEP8 ≥ 3 were considered CTCs. We collected peripheral blood from 28 NB patients as well as clinical and follow-up data. The number of CTCs among the different risk groups were significantly different (p = .0208, Kruskal-Wallis test). Patients with metastasis had more CTCs than those without metastasis (p < .0001, Mann-Whitney test). Patients with ≥3 CTCs per 4 ml of peripheral blood had an increased likelihood of having metastasis (sensitivity, 88.89%; specificity, 78.59%), and patients with ≥10 CTCs per 4 ml of peripheral blood had poorer overall survival. The EpCAM-independent assay along with immunostaining-FISH (i-FISH) described here can detect CTCs in patients with NB at a high sensitivity and may have clinical value for prognosis evaluation and diagnosing metastasis when imaging data are ambiguous.


Assuntos
Molécula de Adesão da Célula Epitelial/metabolismo , Hibridização in Situ Fluorescente , Células Neoplásicas Circulantes/patologia , Neuroblastoma/patologia , Criança , Pré-Escolar , Cromossomos Humanos Par 8/genética , Feminino , Imunofluorescência , Amplificação de Genes , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Proteína Proto-Oncogênica N-Myc/genética , Metástase Neoplásica , Neuroblastoma/genética , Neuroblastoma/urina , Fosfopiruvato Hidratase/metabolismo , Modelos de Riscos Proporcionais , Fatores de Risco , Ácido Vanilmandélico/urina
16.
Sensors (Basel) ; 18(8)2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30044437

RESUMO

In order to improve the keyway broaching process and verify the feasibility of vibration-assisted broaching process, an experimental study on a novel hydraulic vibration assisted broaching (HVAB) system with double-valve electro-hydraulic exciter (DVEHE) is proposed in this paper. The performances of HVAB at different excitation frequencies were compared from three aspects: (a) the cutting force under the different vibration frequencies, (b) the surface roughness of the workpiece, and (c) the flank face wear of the tool. For precision on-line measurement of larger broaching forces, four piezoelectric sensors were fixed on the broaching machine. The experimental results show that HVAB can effectively improve the performance of the broaching process, approximately reduce the broaching force by as much as 9.7% compared to conventional broaching (CB) and improve the surface quality of workpiece. Some explanations are offered to support the observations.

17.
Materials (Basel) ; 11(3)2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29518950

RESUMO

Potassium (K⁺) ion is an important biological substance in the human body and plays a critical role in the maintenance of transmembrane potential and hormone secretion. Several detection techniques, including fluorescent, electrochemical, and electrical methods, have been extensively investigated to selectively recognize K⁺ ions. In this work, a highly sensitive and selective biosensor based on single-layer graphene has been developed for K⁺ ion detection under Van der Pauw measurement configuration. With pre-immobilization of guanine-rich DNA on the graphene surface, the graphene devices exhibit a very low limit of detection (≈1 nM) with a dynamic range of 1 nM-10 µM and excellent K⁺ ion specificity against other alkali cations, such as Na⁺ ions. The origin of K⁺ ion selectivity can be attributed to the fact that the formation of guanine-quadruplexes from guanine-rich DNA has a strong affinity for capturing K⁺ ions. The graphene-based biosensors with improved sensing performance for K⁺ ion recognition can be applied to health monitoring and early disease diagnosis.

18.
Clin Immunol ; 191: 27-33, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29562205

RESUMO

Thrombomodulin (TM, also known as CD141), which functions as an anticoagulant, is widely expressed on cell surface of a variety of cell types, including human blood cells as well as certain immune cells. To determine whether TM could be a potential marker for OSCC diagnosis as well as a molecular target for OSCC therapy, we examined the expression of TM in an oral cancer tissue microarray with 153 oral cancer tissues. Further, we also analyzed the expression of TM on DCs of 36 OSCC patients and 36 healthy donors. The expression of TM was determined using standard immunohistochemistry on a tissue microarray of 153 OSCC patients. Flow cytometric analyses were performed to determine the proportions of CD141+ DCs in the PBMC of 36 OSCC patients and 36 healthy donors. Clinicopathological correlations were performed based on the available clinical data. Our results showed that in the univariate analysis, high TM expression was significantly associated with well differentiation of tumor cells (P=.001), but not correlated with overall survival and disease-free survival (P>.05). In addition, CD141+ DCs were both present in OSCC patients and healthy donors with about 0.04%. There was no significant difference with the percentages of CD141+ DCs in the PBMC of OSCC patients and that of the normal control group (P>.05). This study indicates that TM expression might play the most critical role in the differentiation of OSCC tumors. Functional distinctions of CD141+ DCs in OSCC patients deserve further investigation to provide important therapeutic understandings for future immunotherapy.


Assuntos
Neoplasias Bucais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Trombomodulina/fisiologia , Idoso , Antígenos de Superfície/análise , Diferenciação Celular , Células Dendríticas/imunologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Trombomodulina/análise , Análise Serial de Tecidos
19.
Cell Physiol Biochem ; 45(2): 706-719, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29414822

RESUMO

BACKGROUND/AIMS: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. METHODS: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. RESULTS: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were "chromosome organization", "cytoplasm", and "organic cyclic compound binding". Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. CONCLUSIONS: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.


Assuntos
Hepatoblastoma/patologia , Neoplasias Hepáticas/patologia , RNA/metabolismo , Adolescente , Adulto , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Pré-Escolar , Regulação para Baixo , Feminino , Redes Reguladoras de Genes , Hepatoblastoma/genética , Humanos , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA/antagonistas & inibidores , RNA/genética , RNA Circular , Transdução de Sinais , Junções Íntimas/genética , Junções Íntimas/metabolismo , Regulação para Cima , Adulto Jovem
20.
Oncoimmunology ; 7(2): e1388484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29308315

RESUMO

Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in "activated" T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.

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