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1.
NPJ Digit Med ; 7(1): 13, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38225423

ABSTRACT

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

2.
Nat Biomed Eng ; 7(10): 1270-1281, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37537304

ABSTRACT

In microneurosurgery, it is crucial to maintain the structural and functional integrity of the nerve through continuous intraoperative identification of neural anatomy. To this end, here we report the development of a translatable system leveraging soft and stretchable organic-electronic materials for continuous intraoperative neurophysiological monitoring. The system uses conducting polymer electrodes with low impedance and low modulus to record near-field action potentials continuously during microsurgeries, offers higher signal-to-noise ratios and reduced invasiveness when compared with handheld clinical probes for intraoperative neurophysiological monitoring and can be multiplexed, allowing for the precise localization of the target nerve in the absence of anatomical landmarks. Compared with commercial metal electrodes, the neurophysiological monitoring system allowed for enhanced post-operative prognoses after tumour-resection surgeries in rats. Continuous recording of near-field action potentials during microsurgeries may allow for the precise identification of neural anatomy through the entire procedure.

3.
Bioeng Transl Med ; 8(4): e10532, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37476052

ABSTRACT

We aimed to develop a new biocompatible gastrin-releasing peptide receptor (GRPR) targeted optical probe, IRDye800-RM26, for fluorescence image-guided surgery (FGS) of brain malignancies in near-infrared window II (NIR-II) imaging. We developed a novel GRPR targeting probe using a nine-amino-acid bombesin antagonist analog RM26 combined with IRDye800CW, and explored the fluorescent probe according to optical properties. Fluorescence imaging characterization in NIR-I/II region was performed in vitro and in vivo. Following simulated NIR-II image-guided surgery, we obtained time-fluorescent intensity curves and time-signal and background ratio curves. Further, we used histological sections of brain from tumor-beating mice model to compare imaging specificity between 5-aminolevulinic acid (5-ALA) and IRDye800-RM26, and evaluated biodistribution and biocompatibility. IRDye800-RM26 had broad emission ranging from 800 to 1200 nm, showing considerable fluorescent intensity in NIR-II region. High-resolution NIR-II imaging of IRDye800-RM26 can enhance the advantages of NIR-I imaging. Dynamic and real time fluorescence imaging in NIR-II region showed that the probe can be used to treat brain malignancies in mice between 12 and 24 h post injection. Its specificity in targeting glioblastoma was superior to 5-ALA. Biodistribution analysis indicated IRDye800-RM26 excretion in the kidney and liver. Histological and blood test analyses did not reveal acute severe toxicities in mice treated with effective dose (40 µg) of the probe for NIR-II imaging. Because of the considerable fluorescent intensity in NIR-II region and high spatial resolution, biocompatible and excretable IRDye800-RM26 holds great potentials for FGS, and is essential for translation into human use.

4.
Transl Lung Cancer Res ; 12(3): 547-565, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37057123

ABSTRACT

Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer and is often accompanied by brain metastasis (BM). The heterogeneity of the tumor renders all current conventional treatments less effective. This study aims to dissect tumor cell heterogeneity and identify potential therapeutic targets. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) in 8 patients with treatment-naïve LUAD BM and included scRNA-seq data of 10 primary LUAD samples and their matched adjacent normal tissue from GSE131907 to determine the tumor cell heterogeneity. Results: Our analyses revealed tumor cells derived from brain metastases were more heterogeneous. Tumor cells from BM harbored significantly more copy number variants (CNVs), and cells of magnoid subtype were the critical source of malignant cells both in BM and the primary lung tumor. Pseudo-time trajectory analysis revealed that malignant cells had upregulated genes enriched for cell cycle and cell division. Integrated analysis of tumor cells revealed 2 distinct malignant cell clusters (cluster 4 and cluster 6) and their marker genes. The signatures identified in the single-cell profile had prognostic value in the bulk tumor profiles. Moreover, the signature of cluster 4 had significant prognostic value in predicting patients surviving longer than 3.5 years, while the signature of cluster 6 showed better predictive ability within 1 year. Magnoid-type cells are most likely to develop into the riskiest cell type and potentially promote tumor progression. Conclusions: scRNA profiling that integrates LUAD BM and primary LUAD can provide information on those malignant cells with BM potential, offering additional prognostic information at cellular level, and may serve as a foundational resource for further tumor cell dissection and therapeutic target exploration.

5.
Open Med (Wars) ; 18(1): 20220574, 2023.
Article in English | MEDLINE | ID: mdl-36820064

ABSTRACT

More clinical evidence is needed regarding the relative priority of treatments for brain metastases (BMs) from EGFR/ALK-negative/unselected non-small cell lung cancer (NSCLC). PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov databases were searched. Overall survival (OS), central nervous system progression-free survival (CNS-PFS), and objective response rate (ORR) were selected for Bayesian network meta-analyses. We included 25 eligible randomized control trials (RCTs) involving 3,054 patients, investigating nine kinds of treatments for newly diagnosed BMs and seven kinds of treatments for previously treated BMs. For newly diagnosed BMs, adding chemotherapy, EGFR-TKIs, and other innovative systemic agents (temozolomide, nitroglycerin, endostar, enzastaurin, and veliparib) to radiotherapy did not significantly prolong OS than radiotherapy alone; whereas radiotherapy + nitroglycerin showed significantly better CNS-PFS and ORR. Surgery could significantly prolong OS (hazard ratios [HR]: 0.52, 95% credible intervals: 0.41-0.67) and CNS-PFS (HR: 0.32, 95% confidence interval: 0.18-0.59) compared with radiotherapy alone. For previously treated BMs, pembrolizumab + chemotherapy, nivolumab + ipilimumab, and cemiplimab significantly prolonged OS than chemotherapy alone. Pembrolizumab + chemotherapy also showed better CNS-PFS and ORR than chemotherapy. In summary, immune checkpoint inhibitor (ICI)-based therapies, especially ICI-combined therapies, showed promising efficacies for previously treated BMs from EGFR/ALK-negative/unselected NSCLC. The value of surgery should also be emphasized. The result should be further confirmed by RCTs.

6.
Front Endocrinol (Lausanne) ; 13: 857314, 2022.
Article in English | MEDLINE | ID: mdl-35634502

ABSTRACT

Pituitary adenomas in Knosp grade 4 are difficult to resect completely and are generally involved in poor prognosis, because of the close relationship between the tumor and internal carotid. In this study, the authors retrospectively reviewed the outcome of different transcranial approaches in the management of large-to-giant pituitary adenomas in Knosp grade 4. A total of 42 patients with large-to-giant pituitary adenomas in Knosp grade 4, who underwent craniotomy in the Pituitary Disease Subdivision, Department of Neurosurgery, Beijing Tiantan Hospital, between March 2012 and March 2015 were included in this study. Clinical characteristics, surgical methods, complications, and outcomes were evaluated. The median age was 45 years (range, 19-73 years old), and 42.9% of the enrolled cases were men. The mean tumor diameter was 43.6 mm, and the mean volume was 30.9 cm3. 26 patients underwent the frontolateral approach, while 16 cases accepted the frontotemporal approach. Gross total resection was achieved in 11 patients (26.2%), near total in 26 (61.9%), and subtotal in 5 (11.9%). The adenomas were larger, and the distance of the tumor extending to the lateral skull base was also further in the frontotemporal approach cases. The surgical time was shorter, and the bleeding volume was less in the frontolateral approach cases. Subsellar extension was associated with incomplete resection in pituitary macroadenomas of Knosp grade 4. The craniotomy is still an effective treatment for pituitary macroadenomas in Knosp grade 4.


Subject(s)
Adenoma , Pituitary Neoplasms , Adenoma/pathology , Adenoma/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methods , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Retrospective Studies , Treatment Outcome , Young Adult
7.
Exp Ther Med ; 22(5): 1255, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34603523

ABSTRACT

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.

8.
Sci Transl Med ; 13(602)2021 07 14.
Article in English | MEDLINE | ID: mdl-34261799

ABSTRACT

Hearing loss is one of the most common symptoms of neurofibromatosis type 2 (NF2) caused by vestibular schwannomas (VSs). Fibrosis in the VS tumor microenvironment (TME) is associated with hearing loss in patients with NF2. We hypothesized that reducing the fibrosis using losartan, an FDA-approved antihypertensive drug that blocks fibrotic and inflammatory signaling, could improve hearing. Using NF2 mouse models, we found that losartan treatment normalized the TME by (i) reducing neuroinflammatory IL-6/STAT3 signaling and preventing hearing loss, (ii) normalizing tumor vasculature and alleviating neuro-edema, and (iii) increasing oxygen delivery and enhancing efficacy of radiation therapy. In preparation to translate these exciting findings into the clinic, we used patient samples and data and demonstrated that IL-6/STAT3 signaling inversely associated with hearing function, that elevated production of tumor-derived IL-6 was associated with reduced viability of cochlear sensory cells and neurons in ex vivo organotypic cochlear cultures, and that patients receiving angiotensin receptor blockers have no progression in VS-induced hearing loss compared with patients on other or no antihypertensives based on a retrospective analysis of patients with VS and hypertension. Our study provides the rationale and critical data for a prospective clinical trial of losartan in patients with VS.


Subject(s)
Hearing Loss , Neurilemmoma , Neurofibromatosis 2 , Animals , Humans , Losartan/pharmacology , Losartan/therapeutic use , Mice , Prospective Studies , Retrospective Studies , Rodentia , Treatment Outcome , Tumor Microenvironment
9.
Front Oncol ; 11: 566492, 2021.
Article in English | MEDLINE | ID: mdl-33791198

ABSTRACT

MicroRNAs (miRNAs) are involved in human glioblastoma (GB). MiR-935 has been reported to have both tumor-inhibiting and tumorigenesis effects, but its role in GB remains unclear. Because of the high mortality and morbidity associated with the malignancy of GB, a deeper understanding of the molecular crosstalk that occurs in GB is needed to identify new potential targets for treatment. At present, the mechanism of GB at the molecular level is not fully understood. With the aid of bioinformatic analysis, miR-935 was significantly downregulated in GB, and it presented a poorer outcome. In the glioma cell line and in the nude mice model, the miR-935 inhibited cell proliferation by modulating cell circles in vitro and in vivo. Then, the target genes of miR-935 were analyzed by using the online database, and the direct binding was tested with a luciferase analysis. FZD6 was found to be the direct target of miR-935. The effect of miR-935 was recovered by the overexpression of FZD6 in vitro. In addition, the negative correlation of miR-935 and the expression of FZD6 were confirmed in our clinical samples, and the expression of FZD6 has a strong correlation with tumor malignancy and prognosis. This study showed that miR-935 directly inhibited the expression of FZD6 and inhibited the cell proliferation, thereby suppressing the development of GB, suggesting that miR-935 is a cancer suppressor miRNA and may become a prognostic biomarker or a promising potential therapeutic target for human GBs.

10.
Oncol Lett ; 21(3): 179, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33574918

ABSTRACT

Brain metastases (BMs) are malignancies in the central nervous system with poor prognosis. Genetic landscapes of the primary tumor sites have been extensively profiled; however, mutations associated with BMs are poorly understood. In the present study, target exome sequencing of 560 cancer-associated genes in samples from 52 patients with brain metastasis from various primary sites was performed. Recurrent mutations for BMs from distinct origins were identified. There were both genetic homogeneity and heterogeneity between BMs and primary lung tumor tissues. The mutation rate of the major cancer driver gene, TP53, was consistently high in both the primary lung cancer sites and BMs, while some genetic alterations, associated with DNA damage response deficiency, were specifically enriched in BMs. The mutational signatures enriched in BMs could serve as actionable targets for treatment. The mutation in the primary site of the potential brain metastasis driver gene, nuclear mitotic apparatus protein 1 (NUMA1), affected the progression-free survival time of patients with lung cancer, and patients with the NUMA1 mutation in BMs had a good prognosis. This suggested that the occurrence and clinical outcome of brain metastases could be independent of each other.

11.
Clin Neuroradiol ; 31(3): 599-610, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32720068

ABSTRACT

PURPOSE: The aim of this study was to investigate an imaging biomarker based on contrast enhanced T1-weighted and T2-weighted magnetic resonance imaging (MRI) to determine the hearing loss related to acoustic neuromas (AN). METHODS: In this retrospective study, 441 acoustic neuromas treated with microsurgery were included. The diagnostic and follow-up MRI and audiometry of these patients were compared. RESULTS: We discovered a new MRI grading biomarker based on the percentage of tumor filling the inner auditory canal (TFIAC classification). The area under the receiver operating characteristics (AUROC) curve was highest for TFIAC (0.675), followed by period of observation (0.615) and tumor size (0.6) (P < 0.001). The percentage of patients in TFIAC grade III (90.1%) experiencing hypoacusis prior to microsurgery was significantly higher than that in TFIAC grade I (72.7%, P = 0.037) and TFIAC grade IV patients had a higher rate of non-serviceable hearing compared to TFIAC grade III patients (P < 0.001). During the follow-up, TFIAC grade IV patients experienced a significantly higher rate of non-serviceable hearing than TFIAC grade III patients in all ANs (P < 0.001) and in serviceable hearing acoustic neuroma cases prior to surgery (TFIAC grade IV 55.4%, TFIAC grade III 69.0%, P = 0.045). The TFIAC grade IV patients experienced a significantly higher rate of facial nerve dysfunction than TFIAC grade III patients after surgery (grade IV 48.0%, grade III 26.1%, P < 0.001). CONCLUSION: The TFIAC classification serves as a potential imaging biomarker for preoperative and postoperative hearing prediction in ANs, which may aid neurosurgeons in predicting hearing loss and selecting optimal surgical strategies.


Subject(s)
Hearing Loss , Neuroma, Acoustic , Biomarkers , Hearing Loss/diagnostic imaging , Humans , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/surgery , Postoperative Complications , Retrospective Studies , Treatment Outcome
12.
Sci Rep ; 10(1): 16121, 2020 09 30.
Article in English | MEDLINE | ID: mdl-32999349

ABSTRACT

In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. If and how mechanical cues regulate tumour cell proliferation is currently not fully studied. PIEZO1 has recently been identified as a crucial mechanosensitive cation channel in multiple solid tumours. However, we didn't find any clinical data describing the association between PIEZO1 expression and glioma. To investigate the role of PIEZO1 in gliomas, we analysed PIEZO1 gene expression at the transcriptome level, genomic profiles and the association of PIEZO1 with clinical practice. In total, 1633 glioma samples with transcriptome data, including data from the Chinese Glioma Genome Atlas RNAseq, the Cancer Genome Atlas RNAseq and GSE16011 databases, were included in this study. Clinical information and genomic profiles including somatic mutations were also obtained. We found that PIEZO1 expression was highly correlated with malignant clinical and molecular subtypes of glioma. Gene ontology analysis showed that expression of PIEZO1 was correlated with tumour microenvironment-related genes that encode proteins involved in extracellular matrix (ECM) organization, angiogenesis and cell migration. Additionally, PIEZO1 was shown to be involved in tumour progression by serving as the central checkpoint of multiple ECM remodelling-related signalling pathways to modulate tumour cell proliferation and the tumour microenvironment in turn. Finally, high PIEZO1 expression was correlated with reduced survival time and acted as a robust biomarker for poor prognosis in gliomas. Taken together, the results indicated that high PIEZO1 expression is closely associated with highly malignant gliomas. Importantly, PIEZO1 serves as a key factor involved in sensing mechanical properties in the tumour and can regulate both tumour cells and their microenvironment to promote glioma progression, and it is also a potential therapeutic target for the treatment of gliomas.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Glioma/metabolism , Glioma/pathology , Ion Channels/metabolism , Animals , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Disease Progression , Gene Expression Regulation, Neoplastic/physiology , Humans , Mice , Prognosis , Signal Transduction/physiology , Transcriptome/physiology , Tumor Microenvironment/physiology
13.
J Neurooncol ; 149(3): 473-487, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33034841

ABSTRACT

PURPOSES: Immunotherapies for solid tumor are gaining traction in the clinic, however, the immunological landscape of pituitary adenomas (PAs) is not well defined. In the present study, we used the RNA-seq data of PAs to investigate the impact of immunological landscape on clinical features of pituitary adenomas and aim to evaluate the potential immunotherapy for PAs. METHODS: We analyzed tumor-infiltrating immune cells in 115 PA samples using RNA-seq. Main immune cell types (B cells, CD8+ T cells, CD4+ T cells, macrophages and NK cells) were detected from the expression of genes. The association between immune cells abundance and immune checkpoint, as well as inflammatory factors were analyzed. 10 additional patients were enrolled for validation. RESULTS: In RNA sequencing data, landscape of PAs were identified. Our computationally inferred immune infiltrates significantly associate with patient clinical features. Growth hormone-secreting adenomas (GHomas) were found with higher B cells and CD8+ T cells infiltration. Moreover, GHomas showed relative different genetic background, significant invasive behavior and independently correlated with reduced progress-free time. Tumor progression was related to increased expression of PD-1/PD-L1 and was associated with higher immune infiltration. Analysis of cancer-testis antigen expression and CD8+ T-cell abundance suggested CTAG2 and TSPYL6 were potential immunotherapeutic targets in GHomas and non-functioning adenomas, respectively. CONCLUSIONS: Tumor-infiltrating immune cells confer important clinical and biological implications. Our results of immune-infiltrate levels in PAs may inform effective cancer vaccine and checkpoint blockade therapies and make it possible to take immunotherapy into invasive PAs.


Subject(s)
Adenoma/immunology , Biomarkers, Tumor/genetics , CD8-Positive T-Lymphocytes/immunology , Gene Expression Regulation, Neoplastic , Lymphocytes, Tumor-Infiltrating/immunology , Pituitary Neoplasms/immunology , Adenoma/genetics , Adenoma/pathology , Adult , Biomarkers, Tumor/immunology , Female , Follow-Up Studies , Humans , Immunotherapy , Male , Middle Aged , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathology , Prognosis , Retrospective Studies , Sequence Analysis, RNA
14.
Sci Rep ; 10(1): 4211, 2020 03 06.
Article in English | MEDLINE | ID: mdl-32144278

ABSTRACT

Neurofibromatosis type 2 (NF2) is an inherited disorder characterized by bilateral vestibular schwannomas (VS) that arise from neoplastic Schwann cells (SCs). NF2-associated VSs are often accompanied by meningioma (MN), and the majority of NF2 patients show loss of the NF2 tumor suppressor. mTORC1 and mTORC2-specific serum/glucocorticoid-regulated kinase 1 (SGK1) are constitutively activated in MN with loss of NF2. In a recent high-throughput kinome screen in NF2-null human arachnoidal and meningioma cells, we showed activation of EPH RTKs, c-KIT, and SFK members independent of mTORC1/2 activation. Subsequently, we demonstrated in vitro and in vivo efficacy of combination therapy with the dual mTORC1/2 inhibitor AZD2014 and the multi-kinase inhibitor dasatinib. For these reasons, we investigated activated mTORC1/2 and EPH receptor-mediated signaling in sporadic and NF2-associated VS. Using primary human VS cells and a mouse allograft model of schwannoma, we evaluated the dual mTORC1/2 inhibitor AZD2014 and the tyrosine kinase inhibitor dasatinib as monotherapies and in combination. Escalating dose-response experiments on primary VS cells grown from 15 human tumors show that combination therapy with AZD2014 and dasatinib is more effective at reducing metabolic activity than either drug alone and exhibits a therapeutic effect at a physiologically reasonable concentration (~0.1 µM). In vivo, while AZD2014 and dasatinib each inhibit tumor growth alone, the effect of combination therapy exceeds that of either drug. Co-targeting the mTOR and EPH receptor pathways with these or similar compounds may constitute a novel therapeutic strategy for VS, a condition for which there is no FDA-approved pharmacotherapy.


Subject(s)
Benzamides/pharmacology , Dasatinib/pharmacology , Disease Models, Animal , Morpholines/pharmacology , Neurofibromin 2/physiology , Neuroma, Acoustic/drug therapy , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , Animals , Drug Therapy, Combination , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurofibromin 2/genetics , Neurofibromin 2/metabolism , Neuroma, Acoustic/metabolism , Neuroma, Acoustic/pathology , Receptor, EphA1/metabolism
15.
Front Oncol ; 10: 597877, 2020.
Article in English | MEDLINE | ID: mdl-33614485

ABSTRACT

Glycolysis refers to one of the critical phenotypes of tumor cells, regulating tumor cell phenotypes and generating sufficient energy for glioma cells. A range of noticeable genes [such as isocitrate dehydrogenase (IDH), phosphatase, and tensin homolog (PTEN), or Ras] overall impact cell proliferation, invasion, cell cycle, and metastasis through glycolysis. Moreover, long non-coding RNAs (LncRNAs) are increasingly critical to disease progression. Accordingly, this study aimed to identify whether glycolysis-related LncRNAs have potential prognostic value for glioma patients. First, co-expression network between glycolysis-related protein-coding RNAs and LncRNAs was established according to Pearson correlation (Filter: |r| > 0.5 & P < 0.001). Furthermore, based on univariate Cox regression, the Least Absolute Shrinkage and Selection Operator (LASSO) analysis and multivariate Cox regression, a predictive model were built; vital glycolysis-related LncRNAs were identified; the risk score of every single patient was calculated. Moreover, receiver operating characteristic (ROC) curve analysis, gene set enrichment analysis (GSEA), GO and KEGG enrichment analysis were performed to assess the effect of risk score among glioma patients. 685 cases (including RNA sequences and clinical information) from two different cohorts of the Chinese Glioma Genome Atlas (CGGA) database were acquired. Based on the mentioned methods, the risk score calculation formula was yielded as follows: Risk score = (0.19 × EXPFOXD2-AS1) + (-0.27 × EXPAC062021.1) + (-0.16 × EXPAF131216.5) + (-0.05 × EXPLINC00844) + (0.11 × EXPCRNDE) + (0.35 × EXPLINC00665). The risk score was independently related to prognosis, and every single mentioned LncRNAs was significantly related to the overall survival of patients. Moreover, functional enrichment analysis indicated that the biologic process of the high-risk score was mainly involved in the cell cycle and DNA replication signaling pathway. This study confirmed that glycolysis-related LncRNAs significantly impact poor prognosis and short overall survival and may act as therapeutic targets in the future.

16.
Gland Surg ; 8(6): 648-656, 2019 Dec.
Article in English | MEDLINE | ID: mdl-32042672

ABSTRACT

BACKGROUND: There is no comprehensive and objective method existing for predicting early recurrence of pituitary adenomas (PAs). The most advanced gene sequencing technology can be applied to build a prognostic model that can effectively predict early recurrence of PAs. METHODS: In this study, using mRNA-Seq data, the corresponding postoperative early recurrence status, and other clinical features of 107 PA samples were obtained and randomly divided into the training and validation groups. Cox regression and receiver operating characteristic (ROC) analysis accompanied by the risk score method was used to build a seven-gene prediction model. RESULTS: Area under curve values was 0.857 in the training group, 0.936 in the validation group, and 0.848 in all patients. Patients with low-risk scores had a significantly lower probability of early postoperative recurrence compared to those acquiring high-risk scores in the training group, validation group, and all patient (P<0.0001) groups. In addition, 6 out of these 7 significant genes were highly correlated to the early recurrence of PAs. CONCLUSIONS: This prediction model derived from mRNA-Seq data may help in identifying the early recurrence of PAs, consequently aiding in the classification of patients with PAs and the administration of the appropriate therapeutic and follow-up strategy for these patients.

17.
Eur Radiol ; 29(3): 1625-1634, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30255254

ABSTRACT

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.


Subject(s)
Adenoma/pathology , Cavernous Sinus/pathology , Magnetic Resonance Imaging/methods , Pituitary Neoplasms/pathology , Support Vector Machine , Adenoma/diagnostic imaging , Adult , Aged , Area Under Curve , Cavernous Sinus/diagnostic imaging , Contrast Media , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Nomograms , Pituitary Neoplasms/diagnostic imaging , Retrospective Studies , Risk Factors
18.
Chin Med J (Engl) ; 131(24): 2938-2946, 2018 Dec 20.
Article in English | MEDLINE | ID: mdl-30539906

ABSTRACT

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.


Subject(s)
Choroid Plexus Neoplasms/mortality , Child , Child, Preschool , Choroid Plexus Neoplasms/pathology , Choroid Plexus Neoplasms/surgery , Female , Humans , Hydrocephalus/etiology , Infant , Male , Neoplasm Metastasis , Neoplasm Recurrence, Local , Prognosis , Risk Factors
19.
Asian J Androl ; 20(1): 43-49, 2018.
Article in English | MEDLINE | ID: mdl-28816201

ABSTRACT

The impact of sexual dysfunction (SD) is distressing to many male patients with pituitary adenomas which affect both physical and psychological health. The research explored to identify risk factors affecting sexual function and the prognosis of male patients with pituitary adenomas. Two hundred and fifty-four male patients, who aged between 18 and 60 (mean ± s.d.: 44.16 ± 10.14) years and diagnosed with pituitary adenomas, were retrospectively analyzed. One hundred and fifty-nine patients (62.6%) complained of SD prior to surgery. The mean International Index of Erectile Function (IIEF-5) in patients with giant adenomas was 16.13 ± 2.51, much smaller than those with microadenomas or macroadenomas (P < 0.05). All the patients showed significant improvement in terms of erectile dysfunction (ED) following surgery (P < 0.05). In addition, complete resection achieved a higher degree of SD relief than partial resection. The incidence of SD in functioning pituitary adenomas (FPAs) was much higher than that in nonfunctioning pituitary adenomas (NFPAs) (P < 0.05). In addition, compared with NFPAs, males with prolactinomas (82.8%) had the higher prevalence of SD and significantly improvement following surgical intervention (P < 0.05). An inverse relationship was identified between decreasing testosterone levels and increasing incidence of SD before surgery (P < 0.05). There was no significant difference between 6 months and 12 months after surgery in serum testosterone level (P > 0.05). Our results indicated that surgical therapy could be optimized for improvements in SD and that testosterone levels can be used as a sensitive indicator to predict the recovery rate of sexual function in patients with pituitary adenomas following surgery and the serum testosterone level will stay stable in 6 months after surgery.


Subject(s)
Adenoma/complications , Pituitary Neoplasms/complications , Sexual Dysfunction, Physiological/etiology , Adenoma/pathology , Adenoma/surgery , Adolescent , Adult , Cohort Studies , Erectile Dysfunction/epidemiology , Erectile Dysfunction/etiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Predictive Value of Tests , Prognosis , Prolactinoma/complications , Prolactinoma/surgery , Retrospective Studies , Risk Factors , Sexual Dysfunction, Physiological/epidemiology , Testosterone/blood , Treatment Outcome , Young Adult
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