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1.
EBioMedicine ; 55: 102767, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32361251

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis. The performance of clinicopathologic parameters and molecules as prognostic factors remains limited and inconsistent. The present study aimed to construct a multi-molecule biomarker panel to more accurately predict post-resectional prognosis of PDAC patients. METHODS: Firstly, a novel computational strategy integrating prognostic evidence from omics and literature on the basis of bioinformatics prediction (CIPHER) to generate the network, was designed to systematically identify potential high-confidence PDAC-related prognostic candidates. After specimens from 605 resected PDAC patients were retrospectively collected, 23 candidates were detected immunohistochemically in tissue-microarrays for the development cohort to construct a multi-molecule panel. Lastly, the panel was validated in two independent cohorts. FINDINGS: According to the constructed five-molecule panel, disease-specific survival (DSS) was significantly poorer in high-risk patients than in low-risk ones in development cohort (HR 2.15, 95%CI 1.51-3.05, P<0.0001; AUC 0.67). In two validation cohorts, similar significant differences between the two groups were also observed (HR 3.18 and 3.31, 95%CI 1.89-5.37 and 1.78-6.16, All P<0.0001; AUC 0.72 and 0.73). In multivariate analyses, this panel was the sole prognosticator that was significant in each cohort. Furthermore, its predictive power for long-term survival, higher than its individual constituents, could be largely enhanced by combination with traditional clinicopathological variables. Finally, adjuvant chemotherapy (ACT) correlated with better DSS only in high-risk patients, uni- and multi-variately, in all the cohorts. INTERPRETATION: The novel prognostic panel developed by a systematically network-based strategy presents strong ability in prediction of post-resectional survival of PDAC patients. Furthermore, panel-defined high-risk patients might benefit more from ACT.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32285172

RESUMO

The interactions between tumor immune microenvironment (TIME) and pancreatic cancer cells can affect chemotherapeutic efficacy; however, the mechanisms still remain largely unknown. Thirty items in TIME were comprehensively screened by using tissue microarray from pancreatic cancer patients. Their expressions, interconnections and predictive roles for survival were analyzed. Twenty-one of 30 items could stratify the survival of the patients; however, multivariate analysis found that only 5 independent risk factors could predict worse survival (M2-polarized tumor-associated macrophages (TAMs), IgG4 positive cells, TGF-ß1, GM-CSF and lymphangiogenesis). They had a much higher expression levels in tumoral tissue, compared to peritumoral tissue. The Spearman analysis showed that M2-polarized TAM, TGF-ß1 and GM-CSF were positively correlated with pancreatic cancer stem cells (PCSC), angiogenesis and lymphangiogenesis. Both human and murine pancreatic cancer cells could induce M2-polarized TAM, which showed substantial roles to decease chemotherapeutic effects. After treated by gemcitabine, both human and murine pancreatic cancer cell lines expressed higher level of immune check points, PCSC markers and varieties of immunosuppressive factors; however, TGF-ß1 and GM-CSF had the highest increase. Based on the above results, TGF-ß1 and GM-CSF were proposed to be the optimal potential targets to improve chemotherapeutic effects. In immunocompetent murine models, we demonstrated that combined blockade of TGF-ß1 and GM-CSF improved the chemotherapeutic effects by inhibition of M2-polarized TAM and induction of CD8 positive T cells. This study presents a novel promising combined strategy to improve the chemotherapeutic effects for pancreatic cancer.

3.
Sci Rep ; 10(1): 4444, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157155

RESUMO

Surgery for metastatic pancreatic cancer remains controversial as the survival benefit is questionable. The aim of the present study was to analyze the survival of these patients using data extracted from the surveillance, epidemiology, and end results (SEER) program database. Further, studies on resection for metastatic disease to the lung were systematically reviewed. A total of 11,541 cases with synchronous distant metastasis were analyzed. The median survival of single-organ metastasis was better than of multi-organ metastasis (single-organ 4.0 ± 0.07 months, two-organs 3.0 ± 0.13 months, three/four-organs 2.0 ± 0.19 months; p < 0.0001). Single organ lung metastasis had longer median survival times compared to the other sites (lung 6.0 ± 0.32 months, HR 0.87, 95% CI 0.78-0.97; p = 0.013). Resection of the primary tumor was associated with longer survival in synchronous single-organ metastasis to the lung compared to no resection (14.0 ± 1.93 months vs 6.0 ± 0.31 months, p < 0.0001). A systematic literature review identified 79 cases of metachronous lung metastasis with a survival of 120.0 ± 6.32 months and 83.0 ± 24.84 months following resection of the primary tumor and metastasis, respectively. Lower TNM staging, longer interval to metastasis, and single metastatic lesion correlated with better survival. Resection in highly selected pancreatic cancer patients with synchronous and metachronous lung only metastasis might confer a survival benefit and should be considered on an individual basis.

4.
Pancreatology ; 20(2): 265-277, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31956070

RESUMO

BACKGROUND: Successful clinical evaluation of human tumors relies on proper handling of tissue samples to maximally preserve the cellular and metabolic states in vivo. Pancreatic samples are particularly sensitive to sample mishandling due to the abundance of digestive enzymes. We study how the duration of ischemia, in vivo and ex vivo, both of which are unavoidable lagging periods following surgical dissection, significantly impact the utility of pancreatic samples. METHODS: We systematically characterize a wide range of tissue integrity features, including histological patterns, cellular structures, DNA/RNA quality and activity of major signaling pathways in normal pancreases and pancreatic ductal adenocarcinoma (PDAC) tumor tissues from 41 patients with different ischemia. RESULTS: We reveal that tissues experiencing longer periods of ischemia exhibit significant deterioration and could potentially mislead disease diagnosis and preclinical research. Based on these analyses, we propose an optimal procedure that balances better clinical practice and high tissue sample quality. CONCLUSIONS: Our work provides a guideline for pancreatic sample handling and could have wide implications in clinical diagnosis and translational research.

5.
Clin Endocrinol (Oxf) ; 92(5): 461-467, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31943291

RESUMO

OBJECTIVE: A differential diagnosis between malignant and benign parathyroid lesions is difficult due to their overlapping clinicopathological characteristics. As such, molecular markers are urgently needed. Cancer-derived immunoglobulin G (CIgG) is a novel molecule playing important roles in carcinogenesis. The present study aimed to investigate the clinical significance of CIgG in parathyroid neoplasms. PATIENTS: Fifty patients with parathyroid carcinoma (PC), 50 patients with parathyroid adenoma (PA) and 9 patients with parathyroid hyperplasia (PH) were retrospectively enrolled in the current study. MEASUREMENTS: Immunohistochemistry was used to assess CIgG expression in these patients. The performance of CIgG expression in the differential diagnosis between parathyroid lesions was assessed by receiver operating characteristic (ROC) curves. The associations between CIgG expression and clinical outcomes were also analysed by Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: The expression level of CIgG was significantly higher in PC patients than in PA or PH patients (P < .001). CIgG expression discriminated PC from PA or PH, with an area under the ROC curve of 0.84 (76% sensitivity and 88% specificity). High CIgG expression was significantly associated with worse disease-free survival (DFS) in PC patients (P = .018) and was validated as an independent risk factor for DFS in the multivariable Cox regression analysis (P = .002). CONCLUSIONS: The ability of CIgG expression both in the differential diagnosis between malignant and benign parathyroid lesions and in the prognosis prediction for PC was shown in the present study. CIgG might be used as a novel biomarker of parathyroid lesions in future clinical practice.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31803141

RESUMO

Background: The incidence of papillary thyroid carcinoma (PTC) is high and increasing worldwide. Although prognosis is relatively good, it is important to select the minority of patients with poorer prognosis to avoid side effects associated with unnecessary over-treatment in low-risk patients; this requires accurate prognostic predictions. Materials and Methods: Six PTC expression datasets were obtained from the gene expression omnibus (GEO) database. Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) database. Through integrated analysis of these datasets, highly reliable differentially-expressed genes (DEGs) between tumor and normal tissue were identified and lasso Cox regression was applied to identify DEGs related to the progression-free interval (PFI) and to establish a prognostic gene signature. The performance of a five-gene signature was evaluated based on a Kaplan-Meier curve, receiver operating characteristic (ROC), and Harrell's concordance index (C-index). Multivariate Cox regression analysis was used to identify factors associated with PTC prognosis. Finally, a prognostic nomogram was established based on the TCGA-THCA dataset. Results: A novel five-gene signature was established to predict the PTC PFI, which included PLP2, LYVE1, FABP4, TGFBR3, and FXYD6, and the ROC curve and C-index showed good performance in both training and validation datasets. This could classify patients into high- and low-risk groups with distinct PFIs and differentiate PTC tumors from normal tissue. Univariate Cox regression revealed that this signature was an independent prognostic factor for PTC. The established nomogram, incorporating the prognostic gene signature and clinical parameters, was able to predict the PFI with high efficiency. The gene signature-based nomogram was superior to the American Thyroid Association (ATA) risk stratification to predict PTC PFI. Conclusions: Our study identified a five-gene signature and established a prognostic nomogram, which were reliable in predicting the PFI of PTC; this could be beneficial for individualized treatment and medical decision making.

7.
Cancer Cell Int ; 19: 300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787848

RESUMO

The complement system has traditionally been considered a component of innate immunity against invading pathogens and "nonself" cells. Recent studies have demonstrated the immunoregulatory functions of complement activation in the tumor microenvironment (TME). The TME plays crucial roles in tumorigenesis, progression, metastasis and recurrence. Imbalanced complement activation and the deposition of complement proteins have been demonstrated in many types of tumors. Plasma proteins, receptors, and regulators of complement activation regulate several biological functions of stromal cells in the TME and promote the malignant biological properties of tumors. Interactions between the complement system and cancer cells contribute to the proliferation, epithelial-mesenchymal transition, migration and invasion of tumor cells. In this review, we summarize recent advances related to the function of the complement system in the TME and discuss the therapeutic potential of targeting complement-mediated immunoregulation in cancer immunotherapy.

8.
Ann Transl Med ; 7(20): 532, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807514

RESUMO

Background: Pancreatic stellate cells (PSCs) is a highly heterogeneic stroma cell population in pancreatic cancer tissue. Interaction between PSCs and pancreatic cancer cells has not been well elucidated. This research was aimed to study the relationship between fibroblast activation protein α (FAPα)-positive (FAPα+) PSCs and the pathological features and prognosis of pancreatic cancer. The effects and mechanisms of FAPα + PSCs in pancreatic cancer were also explored. Methods: Tissue microarray analysis was used to detect FAPα expression in tumor and adjacent tissues. The relationship between FAPα expression and pancreatic pathological features and prognosis were analyzed. The effects of FAPα+ PSCs on the proliferation, migration and invasion of pancreatic cancer were detected in vitro and in vivo. A cytokine chip was used to detect the differential expression of cytokines in FAPα-positive (FAPα+) and FAPα-negative (FAPα-) PSCs. Phosphorylated tyrosine kinase receptors were detected by a human phosphotyrosine kinase receptor protein chip. The interaction between differential cytokine and tyrosine kinase receptors was detected by immunoprecipitation. Results: Compared with the adjacent tissues, pancreatic cancer stromal tissues showed high FAPα expression. FAPα was mainly expressed in the PSCs. FAPα+ PSCs were associated with lymph node metastasis. Higher numbers of FAPα+ PSCs predicted shorter survival. Pancreatic cancer cells released TGFß1 and induced PSCs to express FAPα. FAPα+ PSCs released the chemokine CXCL1 and promoted the phosphorylation of the tyrosine kinase receptors EphB1 and EphB3 in pancreatic cancer cells. CXCL1, EphrinB1, and EphrinB3 worked together to promote the migration and invasion of pancreatic cancer cells by Akt phosphorylation. Talabostat (PT100), an FAPα inhibitor, inhibited the roles of FAPα+ PSCs. Conclusions: FAPα+ PSCs can promote the migration, invasion, and metastasis of pancreatic cancer by the Akt signaling pathway. This interaction of FAPα+ PSCs with pancreatic cancer cells may become a new strategy for the comprehensive treatment of pancreatic cancer.

9.
Cell Death Dis ; 10(11): 836, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685825

RESUMO

Tumor-associated macrophages (TAMs) are versatile immune cells that promote a variety of malignant behaviors of pancreatic cancer. CD59 is a GPI-anchored membrane protein that prevents complement activation by inhibiting the formation of the membrane attack complex, which may protect cancer cells from complement-dependent cytotoxicity (CDC). The interactions between CD59, TAMs and pancreatic cancer remain largely unknown. A tissue microarray of pancreatic cancer patients was used to evaluate the interrelationship of CD59 and TAMs and their survival impacts were analyzed. In a coculture system, THP-1 cells were used as a model to study the function of TAMs and the roles of pancreatic cancer-educated macrophages in regulating the expression of CD59 in pancreatic cancer cells were demonstrated by real-time PCR, western blot and immunofluorescence staining. The effects of macrophages on regulating CDC in pancreatic cancer cells were demonstrated by an in vitro study. To explore the potential mechanisms, RNA sequencing of pancreatic cancer cells with or without co-culture of THP-1 macrophages was performed, and the results showed that the IL-6R/STAT3 signaling pathway might participate in the regulation, which was further demonstrated by target-siRNA transfection, antibody neutralization and STAT3 inhibitors. Our data revealed that the infiltration of TAMs and the expression of CD59 of pancreatic cancer were paralleled, and higher infiltration of TAMs and higher expression of CD59 predicted worse survival of pancreatic cancer patients. Pancreatic cancer-educated macrophages could protect cancer cells from CDC by up-regulating CD59 via the IL-6R/STAT3 signaling pathway. These findings uncovered the novel mechanisms between TAMs and CD59, and contribute to providing a new promising target for the immunotherapy of pancreatic cancer.

10.
Analyst ; 144(22): 6578-6585, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31596276

RESUMO

Low-molecular-weight (LMW) thiols are important small molecules that regulate or maintain redox homeostasis in physiological and pathological processes. Assessing the concentrations of LMW thiols in biological systems may provide valuable information regarding physiological processes and the early diagnosis of some diseases. Here, we developed a method to simultaneously determine the concentrations of multiple LWM thiols in single cells by chemical derivatization assisted liquid chromatography-mass spectrometry (LC-MS). In this method, we synthesized a pair of stable isotope reagents, N-(acridin-9-yl)-2-bromoacetamide (AYBA) and N-(1,2,3,4-[2H4]-acridin-9-yl)-2-bromoacetamide ([2H4]AYBA). AYBA was used to derivatize LWM thiols in human cervical cancer (HeLa) cells, while [2H4]AYBA was used to derivatize standard LWM thiols to prepare internal standards for the LC-MS method development. The proposed AYBA derivatization greatly enhanced the detection sensitivity of LWM thiols by LC-MS, and thereby achieved the simultaneous detection of multiple LWM thiols by LC-MS in ∼1000 HeLa cells. Finally, the developed method was successfully utilized for the quantitative analysis of multiple LWM thiols in a single HeLa cell and the content changes of LWM thiols in a single HeLa cell before and after oxidative stress treatment. Accordingly, six LMW thiols were detected, including cysteamine, cysteine, glutathione, homocysteine, hydrogen sulfide, and pantetheine.

11.
J Nucl Med ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601698

RESUMO

Purpose: We aimed to assess the value of 11C-choline positron emission tomography (PET) in patients with primary hyperparathyroidism (pHPT) with negative or discordant results in methoxyisobutylisonitrile (MIBI) imaging and neck ultrasound. Methods: Eighty-seven patients with pHPT and negative or discordant neck ultrasound and MIBI single photon emission computed tomography/computed tomography (SPECT/CT) were assessed using 11C-choline PET/CT and subsequently received a parathyroidectomy. PET/CT image data were analysed semi-quantitatively using maximum standardised uptake value (SUVmax) and ratios (target to the contralateral thyroid gland and carotid artery). A positive PET/CT was defined as a focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered to be positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT was considered be negative. Results: When dichotomizing the 11C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, 84 of 92 lesions (91.3%) were found to have true-positive uptake versus 8 lesions (8.7%) with false-positive uptake. One lesion showed a false-negative uptake; sensitivity was 98.8%. The corresponding lesioned positive predictive value was 91.3%. The mean SUVmax was 6.15±4.92 in 72 lesions with positive uptake (70 patients); and mean SUVmax was 2.96±2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that11C-choline PET/CT is a promising tool for PTA localisation, in cases in which ultrasound and MIBI imaging yield negative or discordant results.

13.
Gut ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462556

RESUMO

OBJECTIVE: Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs. DESIGN: The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed. RESULTS: PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period. CONCLUSION: These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations.

14.
Cell Res ; 29(9): 725-738, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273297

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

15.
World J Gastroenterol ; 25(20): 2514-2523, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31171894

RESUMO

BACKGROUND: Pancreatic fistula is one of the most serious complications after pancreatoduodenectomy for treating any lesions at the pancreatic head. For years, surgeons have tried various methods to reduce its incidence. AIM: To investigate and emphasize the clinical outcomes of Blumgart anastomosis compared with traditional anastomosis in reducing postoperative pancreatic fistula. METHODS: In this observational study, a retrospective analysis of 291 patients who underwent pancreatoduodenectomy, including Blumgart anastomosis (201 patients) and traditional embedded pancreaticojejunostomy (90 patients), was performed in our hospital. The preoperative and perioperative courses and long-term follow-up status were analyzed to compare the advantages and disadvantages of the two methods. Moreover, 291 patients were then separated by the severity of postoperative pancreatic fistula, and two methods of pancreaticojejunostomy were compared to detect the features of different anastomosis. Six experienced surgeons were involved and all of them were proficient in both surgical techniques. RESULTS: The characteristics of the patients in the two groups showed no significant differences, nor the preoperative information and pathological diagnoses. The operative time was significantly shorter in the Blumgart group (343.5 ± 23.0 vs 450.0 ± 40.1 min, P = 0.028), as well as the duration of pancreaticojejunostomy drainage tube placement and postoperative hospital stay (12.7 ± 0.9 d vs 17.4 ± 1.8 d, P = 0.031; and 21.9 ± 1.3 d vs 28.9 ± 1.3 d, P = 0.020, respectively). The overall complications after surgery were much less in the Blumgart group than in the embedded group (11.9% vs 26.7%, P = 0.002). Patients who underwent Blumgart anastomosis would suffer less from severe pancreatic fistula (71.9% vs 50.0%, P = 0.006), and this pancreaticojejunostomy procedure did not have worse influences on long-term complications and life quality. Thus, Blumgart anastomosis is a feasible pancreaticojejunostomy procedure in pancreatoduodenectomy surgery. It is safe in causing less postoperative complications, especially pancreatic fistula, and thus shortens the hospitalization duration. CONCLUSION: Surgical method should be a key factor in reducing pancreatic fistula, and Blumgart anastomosis needs further promotion.


Assuntos
Fístula Pancreática/epidemiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento
16.
Small ; 15(48): e1901787, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31183973

RESUMO

Mitochondria are believed to be the major source of intracellular reactive oxygen species (ROS). However, in situ, real-time and quantitative monitoring of ROS release from mitochondria that are present in their cytosolic environment remains a great challenge. In this work, a platinized SiC@C nanowire electrode is placed into a single cell for in situ detection of ROS signals from intracellular mitochondria, and antineoplastic agent (paclitaxel) induced ROS production is successfully recorded. Further investigations indicate that complex IV (cytochrome c oxidase, COX) is the principal site for ROS generation, and significantly more ROS are generated from mitochondria in cancer cells than that from normal cells. This work provides an effective approach to directly monitor intracellular mitochondria by nanowire electrodes, and consequently obtains important physiological evidence on antineoplastic agent-induced ROS generation, which will be of great benefit for better understanding of chemotherapy at subcellular levels.

17.
RNA Biol ; 16(9): 1228-1236, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31213128

RESUMO

Circular RNAs (circRNAs) are a recently identified class of non-coding RNAs that participate in multiple biological processes and tumour progression. However, circRNA expression pattern in parathyroid neoplasms remains unknown. The circRNA profile of 6 parathyroid carcinomas (PCs), 6 parathyroid adenomas (PAs) and 4 normal parathyroid tissues was assessed by a microarray. Bioinformatic analyses were performed to investigate potential core circRNAs via co-expression network. CircRNA and corresponding mRNA expression were validated in a cohort of parathyroid neoplasms by RT-qPCR and fluorescence in situ hybridization (FISH). Compared to normal parathyroid, 5310 and 1055 circRNAs were differentially expressed in PC and PA tissues, respectively. The differential expression of 4 circRNAs (hsa_circRNA_0035563 (p = 0.006), hsa_circRNA_0017545 (p = 0.009), hsa_circRNA_0001687 (p = 0.005) and hsa_circRNA_0075005 (p = 0.001)) and 4 mRNAs (MYC, FSCN1, ANXA2 and AKR1C3) between PC and PA tissues were confirmed by RT-qPCR. In addition, high expression of hsa_circ_0035563 was related to CDC73 mutations (p = 0.022) and recurrence in PC patients (p = 0.042). Furthermore, hsa_circ_0075005 helped distinguish PCs from benign lesions using FISH, and the area under the curve was 0.779 (p = 0.013). Our findings describe the circRNA profile of PC for the first time and suggest that circRNAs and mRNAs interact in parathyroid tumourigenesis. This study demonstrates that hsa_circ_0075005 and MYC mRNA may be used for the differential diagnosis of PC and PA. The expression levels of hsa_circ_0035563 are related to CDC73 mutations and recurrence in malignancy, highlighting the significance of this parameter in prognosis of PC patients.

18.
Cell Res ; 29(7): 599, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31110249

RESUMO

In the initial published version of this article, there was a mistake in the P value for the correlation between gene-expression changes and 5 hmC changes in tumors. The correct P value should be same as the P value shown in Fig. S6A: 9.8 × 10-6 (mistakenly shown as "9.8 × 106" in the main text). This correction does not affect the description of results or the conclusions of this study, since the range of P value is between 0 and 1.

19.
Nanoscale ; 11(22): 10702-10708, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31140521

RESUMO

Glucose metabolism plays an important role in cell energy supply, and quantitative detection of the intracellular glucose level is particularly important for understanding many physiological processes. Glucose electrochemical sensors are widely used for blood and extracellular glucose detection. However, intracellular glucose detection cannot be achieved by these sensors owing to their large size and consequent low spatial resolution. Herein, we developed a single nanowire glucose sensor for electrochemical detection of intracellular glucose by depositing Pt nanoparticles (Pt NPs) on a SiC@C nanowire and further immobilizing glucose oxidase (GOD) thereon. Glucose was converted by GOD to an electroactive product H2O2 which was further electro-catalyzed by Pt NPs. The glucose nanowire sensor is endowed with a high sensitivity, high spatial-temporal resolution and enzyme specificity due to its nanoscale size and enzymatic reaction. This allows the real-time monitoring of the intracellular glucose level, and the increase of the intracellular glucose level induced by a novel potential hypoglycemic agent, reinforcing its potential application in lowering the blood glucose level. This work provides a versatile method for the construction of enzyme-modified nanosensors to electrochemically detect intracellular non-electroactive molecules, which is of great benefit for physiological and pathological studies.


Assuntos
Técnicas Biossensoriais , Enzimas Imobilizadas/química , Glucose Oxidase/química , Glucose/análise , Nanopartículas Metálicas/química , Nanofios/química , Platina/química , Animais , Bovinos , Linhagem Celular , Células Endoteliais da Veia Umbilical Humana , Humanos
20.
Angew Chem Int Ed Engl ; 58(23): 7753-7756, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-30969456

RESUMO

The existence of a homeostatic mechanism regulating reactive oxygen/nitrogen species (ROS/RNS) amounts inside phagolysosomes has been invoked to account for the efficiency of this process but could not be unambiguously documented. Now, intracellular electrochemical analysis with platinized nanowire electrodes (Pt-NWEs) allowed monitoring ROS/RNS effluxes with sub-millisecond resolution from individual phagolysosomes impacting onto the electrode inserted inside a living macrophage. This shows for the first time that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes. These results establish the existence of the long-postulated ROS/RNS homeostasis and allows its kinetics and efficiency to be quantified. ROS/RNS concentrations may then be maintained at sufficiently high levels for sustaining proper pathogen digestion rates without endangering the macrophage internal structures.

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