Consistency of pituitary adenomas: Amounts of collagen types I and III and the predictive value of T2WI MRI.

Pituitary adenomas, the most common type of lesion in the sellar region, rank third among all brain tumors, with an incidence of 73-94 cases per 100,000 individuals. Due to its high resolution, MRI is highly efficient in brain imaging and has emerged as the most appropriate method for tumor consistency evaluation. The present study aimed to assess the levels of collagen types I and III in pituitary adenomas with different consistencies and to determine the value of T2-weighted imaging (T2WI) MRI for predicting tumor consistency. A total of 55 patients with pituitary adenomas were divided into the soft and firm tumor groups according to intraoperative tumor consistency. The ratio of the tumor to Pons' signal intensities on T2WI scans was determined. A receiver operating characteristic curve was plotted to assess the specificity and sensitivity of T2WI in predicting tumor consistency. Average optical density (AOD) values for collagen types I (0.046±0.008 vs. 0.052±0.012, P=0.033) and III (0.044±0.008 vs. 0.050±0.010, P=0.016) were significantly lower in the soft tumor group compared with those in the firm tumor group. There was no significant difference in the ratio of the tumor to Pons' signal intensities on T2WI scans. The area under the ROC curve was 0.595±0.078 (P=0.250). The maximum tumor diameter significantly differed between the soft and firm tumor groups (P=0.001). AOD values for collagen types I and III were significantly correlated with the maximum tumor diameter (P<0.001). The amounts of collagen types I and III were elevated in firm pituitary tumors compared with the soft ones. The ratio of tumor to Pons' signal intensities on T2WI scans was not able to accurately predict tumor consistency. The size of pituitary adenomas may be associated with the expression levels of collagen types I and III.

Preoperative prediction of cavernous sinus invasion by pituitary adenomas using a radiomics method based on magnetic resonance images.

OBJECTIVES: To predict cavernous sinus (CS) invasion by pituitary adenomas (PAs) pre-operatively using a radiomics method based on contrast-enhanced T1 (CE-T1) and T2-weighted magnetic resonance (MR) imaging. METHODS: A total of 194 patients with Knosp grade two and three PAs (training set: n = 97; test set: n = 97) were enrolled in this retrospective study. From CE-T1 and T2 MR images, 2553 quantitative imaging features were extracted. To select the most informative features, least absolute shrinkage and selection operator (LASSO) was performed. Subsequently, a linear support vector machine (SVM) was used to fit the predictive model. Furthermore, a nomogram was constructed by incorporating clinico-radiological risk factors and radiomics signature, and the clinical usefulness of the nomogram was validated using decision curve analysis (DCA). RESULTS: Three imaging features were selected in the training set, based on which the radiomics model yielded area under the curve (AUC) values of 0.852 and 0.826 for the training and test sets. The nomogram based on the radiomics signature and the clinico-radiological risk factors yielded an AUC of 0.899 in the training set and 0.871 in the test set. CONCLUSIONS: The nomogram developed in this study might aid neurosurgeons in the pre-operative prediction of CS invasion by Knosp grade two and three PAs, which might contribute to creating surgical strategies. KEY POINTS: • Pre-operative diagnosis of CS invasion by PAs might affect creating surgical strategies • MRI might help for diagnosis of CS invasion by PAs before surgery • Radiomics might improve the CS invasion detection by MR images.

Role and mechanisms of a three-dimensional bioprinted microtissue model in promoting proliferation and invasion of growth-hormone-secreting pituitary adenoma cells.

Growth-hormone-secreting pituitary adenoma (GHSPA) is a benign tumour with a high incidence and large economic burden, which greatly affects quality of life. The aetiological factors are yet to be clarified for GHSPA. Conventional two-dimensional (2D) monolayer culture of tumour cells cannot ideally reflect the growth status of tumours in the physiological environment, and insufficiencies of in vitro models have severely restricted the progress of cancer research. Three-dimensional (3D) bioprinting technology is being increasingly used in various fields of biology and medicine, which allows recapitulation of the in vivo growth environment of tumour cells. In this study, a GHSPA microtissue model was established using 3D bioprinting. Tumour cells in the 3D environment exhibited more active cell cycle progression, secretion, proliferation, invasion, and tumourigenesis compared with those in the 2D environment. Furthermore, the molecular mechanisms of the 3D-printed microtissue model were explored. We demonstrated that the 3D-printed microtissue provides an excellent in vitro model at the tissue level for oncological research and may facilitate in-depth studies on the aetiology, treatment, drug resistance, and long-term prognosis of GHSPA .

Tumor-like lung cancer model based on 3D bioprinting.

Currently, there is still a lack of appropriate in vitro model for studying lung cancers, especially for recapitulating their invasion and metastasis properties. To develop an appropriate in vitro model for lung cancer research, low-temperature molding principle of biological manufacturing and 3D bioprinting was used in this study to fabricate a cell-laden hydrogel grid scaffold structure, using gelatin-sodium alginate-lung cancer cell A549/95-D suspension as the bio-ink. Cells distributed evenly in this model with high viability, and can be cultured sustainably. This model can be cultured for up to 28 days and maintained its structural integrity. Histology, gene analysis, and scratch test showed that 3D printed cells had enhanced invasion and migration capability compared to those cultured in 2D environment, indicating that the in vitro model developed in this study was more biomimetic compared to 2D models, and it is highly valuable in biomedical research.

Clinical Features and Prognostic Risk Factors of Choroid Plexus Tumors in Children.

BACKGROUND: Decision-making concerning the treatment of choroid plexus tumor (CPT) in pediatric patients remains a topic of considerable debate. The aim of this work was to describe clinical features and prognostic risk factors of CPT in the pediatric population and to provide theoretical opinions regarding clinical decisions for CPT. METHODS: The data of 96 patients with CPT and younger than 14 years were retrospectively analyzed. Clinical characteristics such as pathological type of CPTs, rate and severity of hydrocephalus, treatment and outcome, and recurrence were investigated. For categorical variables, the Pearson's Chi-square test was performed. The Mann-Whitney U-test was used for comparisons between nonnormally distributed parameters. Log-rank test was used for progression-free survival (PFS). RESULTS: The study included 70 choroid plexus papilloma (CPP) cases, 17 atypical choroid plexus papilloma (aCPP) cases, and 9 choroid plexus carcinoma (CPC) cases. Compared with patients with CPP or aCPP, patients with CPC had a shorter disease course (median: CPP, 4 months; aCPP, 2 months; CPC, 1 month; H: 23.5, P < 0.001), higher rate of acute hydrocephalus (CPP, 27.1%; aCPP, 52.9%; CPC, 77.8%; χ2 = 10.9, P < 0.05), and lower incidence of cure rate (CPP, 85.7%; aCPP, 70.5%; CPC, 33.3%; χ2 = 13.5, P < 0.05). The severity of hydrocephalus with tumor in the lateral or third ventricle was significantly higher than that with tumors in the fourth ventricle (severe hydrocephalus: lateral ventricle, 51.7%; third ventricle, 47.0%; fourth ventricle, 11.1%; χ2 = 26.0, P < 0.001). Patients with gross total surgical resection had no better PFS than those with partial resection because of the use of adjuvant therapy in the latter (χ2 = 4.0, P > 0.05). Patients with CPC experienced shorter time for recurrence than those with CPP or aCPP (χ2 = 40.1, P < 0.0001). CONCLUSIONS: Our results indicated that CPP in the fourth ventricle could trigger serious clinical symptoms at an early stage, requiring early intervention. Adjuvant treatment might be necessary for patients with partially resected CPP, aCPP, and CPC to achieve a favorable outcome.

Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis.

AIMS: To investigate the roles of Claudin-5 (CLDN5) in regulating the permeability of the blood-brain barrier (BBB) during lung cancer brain metastasis. RESULTS: By silencing and overexpressing the CLDN5 gene in human brain vascular endothelial (hCMEC/D3) cells, we demonstrated the attenuation of cell migration ability and CLDN5's significant positive role in cell proliferation in CLDN5-overexpressing hCMEC/D3 cells and observed the opposite result in the CLDN5 knockdown group. The reinforced CLDN5 expression reduced the paracellular permeability of hCMEC/D3 cells and decreased the invasion of lung adenocarcinoma A549 cells. Overall, 1685 genes were found to be differentially expressed between the CLDN5-overexpressing cells and the control cells using the Affymetrix Human Transcriptome Array 2.0 (HTA 2.0), and the function of these genes was determined by Gene Ontology and pathway analyses. The possible biological functions of the 1685 genes include cell proliferation, adhesion molecules, and the Jak-STAT, PI3K-Akt, Wnt, and Notch signaling pathways. The identified sets of mRNAs that were specific to CLDN5-overexpressing hCMEC/D3 cells were verified by a qRT-PCR experiment. CONCLUSION: CLDN5 regulates the permeability of BBB by regulating the proliferation, migration, and permeability of hCMEC/D3 cells, especially through the cell adhesion molecule signaling pathway, to enhance the function of the tight junctions, which was involved in reducing the formation of lung cancer brain metastasis.

Loss of Diacylglycerol Kinase-Ζ Inhibits Cell Proliferation and Survival in Human Gliomas.

Diacylglycerol kinases ζ (DGKζ) is a critical lipid kinase which is involved in phosphatidic acid (PA) generation via diacylglycerol (DAG) phosphorylation. DGKζ is highly expressed in central nervous system and essential for brain development. Studies have indicated that DGKζ is associated with colon cancer invasion and metastasis. However, the involvement of DGKζ in human glioma development remains elusive. Here, we explored the impact and possible mechanisms of DGKζ knockdown on the proliferation and survival of glioma cells. The relationship between DGKζ expression status and human glioma stages was explored in 111 specimens of human gliomas via immunohistochemistry technology. Then the impact of DGKζ on cell proliferation, cell cycle, survival, and colony formation ability was determined in U-87 MG glioma cell lines via lentiviral-mediated small interfering (shRNA) strategy. The influence of DGKζ knockdown on global gene expression in U-87 MGglioma cell lines was further analyzed by microarray platform to reveal the possible molecular mechanisms underlying DGKζ-mediated glioma development and progression. Immunohistochemistry analysis revealed that DGKζ expression is positively correlated with human gliomagrade. Lentiviral-mediated small interfering (shRNA) strategyefficiently reduced DGKζ expression and DGKζ knockdown impaired cell proliferation, inhibited colony formation ability, and induced cell cycle arrest and cell apoptosis in U-87 MG glioma cells. Finally, microarray analysis revealed that multiple cancer-associated pathways and oncogenes were regulated by DGKζ knockdown, which provides insights into underlying mechansims of DGKζ-associated glioma development and progression. Our results established the positive correlation between DGKζ expression and gliomagrade. Furthermore, DGKζ knockdown in human glioma cell lines U-87 MG impaired cell proliferation, inhibited colony formation ability, and induced cell cycle arrest and apoptosis which microarray analysis showed that DGKζ knockdown interrupted multiple oncogenes and cancer-associated pathways. Taken together, we provided confidential evidence for the causal role of DGKζ in glioma development and progression.

Overexpression of HLA-DR is associated with prognosis of glioma patients.

AIMS: Since the poor prognosis of glioma, our study was aimed to find out the role of HLA-DR in the prognosis of glioma patients that may contribute to the timely post-operative treatment on the glioma patients. METHODS: 60 glioma patients were enrolled in the prospective cohort study. Western blotting was used to detect the content of HLA-DR. Kaplan-Meier curve was adopted to evaluate the effects of HLA-DR on the survival time of glioma patients. Cox regression analysis was used to evaluate the roles of clinical features and HLA-DR in the pathogenesis of glioma. RESULTS: The expression level of HLA-DR was higher in tumor tissue, compared with normal tissues (P<0.05). Moreover, expression levels of HLA-DR were correlated with the factors of pathological degree, Enneking staging and KPS score. The survival rate of patients with high content of HLA-DR was lower than those of patients with low content of HLA-DR. Cox regression analysis indicated that Enneking staging and HLA-DR were all associated with the prognosis of glioma (HR=14.43, 95% CI=1.05-199.16; HR=21.39, 95% CI=2.07-220.76). CONCLUSION: HLA-DR may serve as a biomarker for the prognosis of glioma patients.

Cloning, expression, and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action.

BACKGROUND: Cold-inducible RNA-binding protein (CIRP) is induced in response to hypothermia, where it exerts neuroprotective effects. Our preliminary studies revealed that it inhibits H2O2-induced apoptosis in rat neurons. In the current study, we report effective expression and purification approaches for the synthesis of CIRP, and assess its potential protective effects against oxidative stress. METHODS: CIRP-encoding was expressed using the prokaryotic expression system pGEX-4T-1, and SP-Sepharose and Sephacryl S-200 columns were used to purify rCIRP. To mimic ischemia/reperfusion injury-associated oxidative stress, neuro2a cells (N2a) were pre-treated with rCIRP for 2h, followed by hydrogen peroxide (H2O2 60 µmol/ml) for 24h. Cell viability was then quantified using an MTT assay. In addition, western blotting was performed to measure the cell cycle related signal transduction pathways. RESULTS: N2a cells exhibited decreased viability following H2O2 treatment, whereas rCIRP significantly improved viability following H2O2 treatment. CIRP also accelerated cell cycle progression from S to G2/M phase in cultured mouse neuroblastoma cells. In addition, CIRP increased levels of p-ERK and p-Akt, and also re-activated the cell cycle-related protein cyclin D1 and c-Myc. These results suggest that CIRP activated the Akt and ERK signal transduction pathways in N2a cells. CONCLUSIONS: Our findings suggest that CIRP could exert protective effects against oxidative stress, and that it might be a novel neuroprotective agent.

Evaluation of the association between CD143 gene polymorphism and psoriasis.

Increased CD143 activity has been detected in various skin tissues, and this increase is partially caused by the intronic ID polymorphism. The genetic contribution of CD143 ID polymorphism to the progression of psoriasis, the commonest skin disease, has been extensively investigated, but reported with inconsistent results. The aim of this work was to gain new insights to shed light on the association between CD143 ID polymorphism and psoriasis risk. We systematically identified the studies examining the association of CD143 ID polymorphism with psoriasis risk. A meta-analysis combining data from all eligible studies was carried out. To evaluate the genetic association, we calculated odds ratio (OR) and its 95 % confidence intervals (CIs) for both genotypic models and allelic model. The final pooling dataset comprised ten studies. Meta-analysis of total samples did not suggest a notable association with psoriasis risk. However, subgroup analysis by ethnicity revealed a statistically significant association in East Asian samples (DD + ID vs. II: OR 0.86, 95 % CI 0.75-0.99, P heterogeneity = 0.970; DD vs. ID: OR 0.85, 95 % CI 0.73-0.99, P heterogeneity = 0.868; D vs. I: OR 0.86, 95 % CI 0.76-0.97, P heterogeneity = 0.994). This meta-analysis demonstrated that the presence of CD143 ID polymorphism may modify the risk of psoriasis in individuals with East Asian ancestry.