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1.
J Cell Mol Med ; 28(8): e18332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38661644

RESUMO

The role of KIAA0040 role in glioma development is not yet understood despite its connection to nervous system diseases. In this study, KIAA0040 expression levels were evaluated using qRT-PCR, WB and IHC, and functional assays were conducted to assess its impact on glioma progression, along with animal experiments. Moreover, WB was used to examine the impact of KIAA0040 on the JAK2/STAT3 signalling pathway. Our study found that KIAA0040 was increased in glioma and linked to tumour grade and poor clinical outcomes, serving as an independent prognostic factor. Functional assays showed that KIAA0040 enhances glioma growth, migration and invasion by activating the JAK2/STAT3 pathway. Of course, KIAA0040 enhances glioma growth by preventing tumour cell death and promoting cell cycle advancement. Our findings suggest that targeting KIAA0040 could be an effective treatment for glioma due to its role in promoting aggressive tumour behaviour and poor prognosis.


Assuntos
Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma , Janus Quinase 2 , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Camundongos Nus , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética
2.
Eur Radiol ; 34(4): 2468-2479, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37812296

RESUMO

OBJECTIVE: The purpose of this study was to develop and validate a nomogram combined multiparametric MRI and clinical indicators for identifying the WHO grade of meningioma. MATERIALS AND METHODS: Five hundred and sixty-eight patients were included in this study, who were diagnosed pathologically as having meningiomas. Firstly, radiomics features were extracted from CE-T1, T2, and 1-cm-thick tumor-to-brain interface (BTI) images. Then, difference analysis and the least absolute shrinkage and selection operator were orderly used to select the most representative features. Next, the support vector machine algorithm was conducted to predict the WHO grade of meningioma. Furthermore, a nomogram incorporated radiomics features and valuable clinical indicators was constructed by logistic regression. The performance of the nomogram was assessed by calibration and clinical effectiveness, as well as internal validation. RESULTS: Peritumoral edema volume and gender are independent risk factors for predicting meningioma grade. The multiparametric MRI features incorporating CE-T1, T2, and BTI features showed the higher performance for prediction of meningioma grade with a pooled AUC = 0.885 (95% CI, 0.821-0.946) and 0.860 (95% CI, 0.788-0.923) in the training and test groups, respectively. Then, a nomogram with a pooled AUC = 0.912 (95% CI, 0.876-0.961), combined radiomics score, peritumoral edema volume, and gender improved diagnostic performance compared to radiomics model or clinical model and showed good calibration as the true results. Moreover, decision curve analysis demonstrated satisfactory clinical effectiveness of the proposed nomogram. CONCLUSIONS: A novel nomogram is simple yet effective in differentiating WHO grades of meningioma and thus can be used in patients with meningiomas. CLINICAL RELEVANCE STATEMENT: We proposed a nomogram that included clinical indicators and multi-parameter radiomics features, which can accurately, objectively, and non-invasively differentiate WHO grading of meningioma and thus can be used in clinical work. KEY POINTS: • The study combined radiomics features and clinical indicators for objectively predicting the meningioma grade. • The model with CE-T1 + T2 + brain-to-tumor interface features demonstrated the best predictive performance by investigating seven different radiomics models. • The nomogram potentially has clinical applications in distinguishing high-grade and low-grade meningiomas.


Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Meningioma/diagnóstico por imagem , Estudos Retrospectivos , Nomogramas , Neoplasias Meníngeas/diagnóstico por imagem , Aprendizado de Máquina , Edema , Organização Mundial da Saúde
3.
World J Surg Oncol ; 22(1): 137, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790064

RESUMO

BACKGROUND: Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs. OBJECT AND METHOD: We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management. RESULT: Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21-22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31-0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12-0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06-0.15, p < 0.001) and visual outcomes (visual improvement: OR = 3.42, 95%CI: 1.24-9.40, p = 0.017; visual deficit: OR = 0.30, 95%CI: 0.26-0.35) with decreases in postoperative stroke (OR = 0.58, 95%CI: 0.51-0.66, p < 0.001), hydrocephalus, and infections (OR = 0.32, 95%CI: 0.24-0.42, p < 0.001). CONCLUSION: Compared with the traditional TCA in primary CP resection, the development and wide application of EEA optimistically decreased the recurrence rate of CP, alleviated hypopituitarism with improvement in the GTR rate of pediatric patients, and significantly improved the visual outcomes, hydrocephalus, postoperative stroke, survival, and infection rates of the patients. Therefore, EEA is an optimal approach for primary CP resection.


Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Humanos , Craniofaringioma/cirurgia , Craniofaringioma/patologia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Endoscopia/métodos
4.
J Transl Med ; 21(1): 28, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647156

RESUMO

BACKGROUND: Glioma is the most prevalent primary tumor of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant form of glioma with an extremely poor prognosis. A novel, regulated cell death form of copper-induced cell death called "cuproptosis" provides a new prospect for cancer treatment by regulating cuproptosis. METHODS: Data from bulk RNA sequencing (RNA-seq) analysis (The Cancer Genome Atlas cohort and Chinese Glioma Genome Atlas cohort) and single cell RNA-seq (scRNA-seq) analysis were integrated to reveal their relationships. A scoring system was constructed according to the cuproptosis-related gene expression, and core genes were experimentally verified using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Moreover, cell counting kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, transwell, and flow cytometry cell cycle were performed to evaluate cell proliferation, invasion, and migration. RESULTS: The Cuproptosis Activation Scoring (CuAS) Model has stable and independent prognostic efficacy, as verified by two CGGA datasets. Epiregulin (EREG), the gene of the model has the most contributions in the principal component analysis (PCA), is an onco-immunological gene that can affect immunity by influencing the expression of programmed death-ligand 1 (PD-L1) and mediate the process of cuproptosis by influencing the expression of ferredoxin 1 (FDX1). Single cell transcriptome analysis revealed that high CuAS GBM cells are found in vascular endothelial growth factor A (VEGFA) + malignant cells. Oligodendrocyte transcription factor 1 (OLIG1) + malignant is the original clone, and VEGF and CD99 are the differential pathways of specific cell communication between the high and low CuAS groups. This was also demonstrated by immunofluorescence in the tissue sections. Furthermore, CuAS has therapeutic potential for immunotherapy, and we predict that many drugs (methotrexate, NU7441, KU -0063794, GDC-0941, cabozantinib, and NVP-BEZ235) may be used in patients with high CuAS. CONCLUSION: EREG is the core onco-immunological biomarker of CuAS and modulates the cross-talk between VEGF and CD99 signaling in glioblastoma, and CuAS may provide support for immunotherapy and chemotherapy.


Assuntos
Apoptose , Epirregulina , Glioblastoma , Glioma , Humanos , Antígeno 12E7 , Biomarcadores , Glioblastoma/genética , Glioma/genética , Peptídeos e Proteínas de Sinalização Intercelular , Fator A de Crescimento do Endotélio Vascular
5.
J Mol Neurosci ; 73(7-8): 608-627, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37488455

RESUMO

Inflammatory response plays a crucial role in the development and progression of gliomas. Whereas the prognostic esteem of inflammatory response-related genes has never been comprehensively explored in glioma, the RNA-seq information and clinical data of patients with glioma were extracted from TCGA, CGGA, and Rembrandt databases. The differentially expressed genes (DEGs) were picked out between glioma tissue and non-tumor brain tissue (NBT). Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct the prognostic signature in the TCGA cohort and verified in other cohorts. Kaplan-Meier survival analyses were conducted to compare the overall survival (OS) between the high and low-risk groups. Univariate and multivariate Cox analyses were subsequently used to confirm the independent prognostic factors of OS, and then, the nomogram was established based them. Furthermore, immune infiltration, immune checkpoints, and immunotherapy were also probed and compared between high and low-risk groups. The four genes were also analyzed by qRT-PCR, immunohistochemistry, and western blot trials between glioma tissue and NBT. The 39 DEGs were identified between glioma tissue and NBT, of which 31 genes are associated to the prognosis of glioma. The 8 optimal inflammatory response-related genes were selected to construct the prognostic inflammatory response-related signature (IRRS) through the LASSO regression. The effectiveness of the IRRS was verified in the TCGA, CGGA, and Rembrandt cohorts. Meanwhile, a nomogram with better accuracy was established to predict OS based on the independent prognostic factors. The IRRS was highly correlated with clinicopathological features, immune infiltration, and genomic alterations in glioma patients. In addition, four selective genes also verified the difference between glioma tissue and NBT. A novel prognostic signature was associated with the prognosis, immune infiltration, and immunotherapy effect in patients with gliomas. Thus, this study could provide a perspective for glioma prognosis and treatment.


Assuntos
Glioma , Humanos , Glioma/genética , Glioma/terapia , Imunoterapia , Encéfalo , Western Blotting , Bases de Dados Factuais
6.
Front Oncol ; 12: 755342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223463

RESUMO

OBJECTIVE: Craniopharyngioma has always been a challenge for the neurosurgeon, and there is no consensus on optimal treatment. The objective of this study was to compare surgical outcomes and complications between transcranial surgery (TCS) and endoscopic endonasal surgery (EES) of craniopharyngiomas. METHODS: A retrospective review of patients who underwent craniopharyngioma resection at Wuhan Union Hospital between January 2010 and December 2019 was performed. A total of 273 patients were enrolled in this retrospective study. All patients were analyzed with surgical effects, endocrinologic outcomes, complications, and follow-up results. RESULTS: A total of 185 patients underwent TCS and 88 underwent EES. There were no significant differences in patient demographic data, preoperative symptoms, and tumor characteristics between the two groups. The mean follow-up was 30.5 months (range 8-51 months). The EES group had a greater gross total resection (GTR) rate (89.8% EES vs. 77.3% TCS, p < 0.05) and lower rate of hypopituitarism (53.4% EES vs. 68.1% TCS, p < 0.05) and diabetes insipidus (DI) (51.1% EES vs. 72.4% TCS, p < 0.05). More postoperative cerebrospinal fluid (CSF) leaks occurred in the EES group (4.5% EES vs. 0% TCS, p < 0.05). More patients in the EES group with preoperative visual deficits experienced improvement after surgery (74.5% EES vs. 56.3% TCS, p < 0.05). There were statistical differences in the recurrence rates (12.5% EES vs. 23.8% TCS, p < 0.05) between the 2 groups. CONCLUSION: These data support the view that EES is a safe and effective minimally invasive surgery compared to TCS. Compared to TCS, EES has fewer surgical complications and a lower recurrence rate.

7.
Mol Neurobiol ; 59(6): 3829-3844, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35420382

RESUMO

Glioma is the most common and malignant brain tumor with poor prognosis. We investigated the effects of LINC01564 on temozolomide (TMZ) resistance of glioma cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the high expression of LINC01564 in human TMZ-resistant glioma cell lines. Functional experiments verified that LINC01564 and SRSF1 promote the proliferation and TMZ resistance and inhibit the apoptosis of TMZ-treated glioma cells. Iron and ROS detection analyses showed that LINC01564 and SRSF1 suppress ferroptosis in glioma cells. Western blot proved that LINC01564 is positively associated with NFE2L2. Mechanism experiments verified the interaction between SRSF1 and MAPK8 3' UTR. In vitro kinase assays showed that MAPK8 can phosphorylate NFE2L2. Rescue experiments showed that MAPK8 reverses the effect of LINC01564 ablation on cell apoptosis and ferroptosis. Meanwhile, NFE2L2 countervails the effect of MAPK8 ablation on the apoptosis and ferroptosis of glioma cells. Animal experiments proved that LINC01564 and MAPK8 facilitate the TMZ resistance of glioma cells in vivo. In conclusion, LINC01564 promotes the TMZ resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis, which might offer a new perspective into TMZ treatment of glioma. The diagram of the specific mechanism that LINC01564 promotes the TMZ resistance of glioma cells by upregulating NFE2L2 expression to inhibit ferroptosis.


Assuntos
Neoplasias Encefálicas , Ferroptose , Glioma , Animais , Apoptose/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Proteína Quinase 8 Ativada por Mitógeno , Temozolomida/farmacologia
8.
Front Surg ; 9: 979940, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117830

RESUMO

Background: Tuberculum sellae meningioma (TSM), a common benign tumor in the sellae region, usually causes neurological deficits, such as vision impairment, by squeezing the peripheral neurovascular structures. Surgical management is recommended as the optimal strategy for TSM treatment and vision restoration. However, it remains challenging to resect TSM in the traditional transcranial approach (TCA). Recently, the endoscopic endonasal approach (EEA) has emerged as an effective option in skull base surgeries. Besides the effectivity, the advantages and limitations of EEA in TSM surgery remain controversial. Object: We compared the surgical outcomes and complications between TCA and EEA surgeries to identify the principles in TSM surgical management. Methods: Retrospective analysis was performed on the patients, who underwent TSM surgery in Wuhan Union Hospital between January 2017 and December 2021. The patients were assigned to TCA or EEA group according to the surgery they experienced. All patients were analyzed with the extent of tumor resection, vision outcome, postoperative complications, and follow-up results. Results: A total of 112 patients were enrolled in this study, including 78 in TCA group and 34 in EEA group. The mean follow-up was 20.5 months (range 3-36 months). There were no statistically significant differences in patient demographic data, preoperative symptoms, and tumor characteristics between TCA and EEA groups. Both TCA and EEA surgeries are effective in TSM resection with relatively high gross total resection rates (85.9% in TCA vs. 91.2% in EEA, p > .05). Meanwhile, EEA surgery has a better outcome in vision restoration or stabilization than TCA surgery (74.6% in TCA vs. 93.1% in EEA, p < .05). Whereas EEA surgery causes more occurrences of cerebrospinal fluid (CSF) leakage than TCA surgery (0% in TCA vs. 11.8% in EEA, p < .05). Conclusion: Both TCA and EEA surgeries are effective in TSM resection. EEA surgery has a better outcome in vision restoration or stabilization than TCA surgery, but induces higher risk of CSF leakage. As each approach has unique advantages and limitations, we must take all aspects into consideration, including approach feathers, tumor characteristics, and clinical requirements, to make the optimal choice in TSM surgical management.

9.
Front Oncol ; 12: 875219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600354

RESUMO

Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors. Materials and Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice. Results: 71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFß). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice. Conclusion: Human pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.

10.
Front Oncol ; 11: 714904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35096558

RESUMO

RPP25, a 25 kDa protein subunit of ribonuclease P (RNase P), is a protein-coding gene. Disorders associated with RPP25 include chromosome 15Q24 deletion syndrome and diffuse scleroderma, while systemic sclerosis can be complicated by malignancy. However, the functional role of RPP25 expression in glioblastoma multiforme (GBM) is unclear. In this study, comprehensive bioinformatics analysis was used to evaluate the impact of RPP25 on GBM occurrence and prognosis. Differential analysis of multiple databases showed that RPP25 was commonly highly expressed in multiple cancers but lowly expressed in GBM. Survival prognostic results showed that RPP25 was prognostically relevant in six tumors (CESC, GBM, LAML, LUAD, SKCM, and UVM), but high RPP25 expression was significantly associated with poor patient prognosis except for CESC. Analysis of RPP25 expression in GBM alone revealed that RPP25 was significantly downregulated in GBM compared with normal tissue. Receiver operating characteristic (ROC) combined with Kaplan-Meier (KM) analysis and Cox regression analysis showed that high RPP25 expression was a prognostic risk factor for GBM and had a predictive value for the 1-year, 2-year, and 3-year survival of GBM patients. In addition, the expression of RPP25 was correlated with the level of immune cell infiltration. The gene set enrichment analysis (GSEA) results showed that RPP25 was mainly associated with signalling pathways related to tumor progression and tumor metabolism.

11.
Front Neurol ; 12: 707985, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526959

RESUMO

Background: Vertebrobasilar dolichoectasia (VBD) is one of the rare causes of trigeminal neuralgia (TN). The common surgical treatments for patients with TN caused by VBD (VBD-TN) are microvascular decompression (MVD) and Gamma Knife radiosurgery (GKRS). However, the therapeutic effects of the two methods have not been clinically compared, so this study was performed to evaluate the treatment outcomes of MVD and GKRS for patients with VBD-TN. Methods: The retrospective study was performed from March 2011 to March 2019 in Wuhan Union Hospital. A total of 80 patients diagnosed with VBD-TN were included in this study, and they were divided into the MVD group (n = 46) and GKRS group (n = 34) according to the surgical methods. The imaging data, intraoperative findings, treatment outcomes, and complications of the two groups were analyzed and compared. Meanwhile, the influencing factors of the treatment effect are also explored on the two groups. Results: Patients who underwent MVD were younger than patients who underwent GKRS (median ages were 61.1 and 65.4 years old, respectively, p = 0.03). The median follow-up was 61.1 months for the MVD group and 56.8 months for the GKRS group. The favorable outcomes [Barrow Neurological Institute (BNI) pain score, BNI scores I-II] occurred in 97.8% of patients treated with MVD and in 78.9% of patients treated with GKRS (p = 0.009). The favorable outcomes in the percentage of patients after MVD 1, 3, 5, and 7 years were 95.7, 85.1, 74.2, and 74.2%, respectively, whereas the corresponding percentages after GKRS were 76.5, 66.2, 56.6, and 47.2%, respectively (p = 0.031). The postoperative complications (except facial numbness) in the MVD group were higher than those in the GKRS group (p = 0.036), but the incidence of new and worsening facial numbness was lower in the GKRS group (p < 0.001). Conclusions: MVD is superior to GKRS in obtaining and maintaining favorable outcomes for patients with VBD-TN, but it also comes with more complications other than facial numbness. Thus, the treatment program can be tailored to a patient's unique condition and wishes.

12.
Oxid Med Cell Longev ; 2021: 9107857, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804371

RESUMO

BACKGROUND: Ferroptosis is a recently identified cell death pathway, and the susceptibility to ferroptosis inducers varies among cancer cell types. There have been recent attempts to clarify the mechanisms implicated in ferroptosis, glioma invasion, and the immune microenvironment but little is known about ferroptosis regulation in GBM. METHODS: Screening ferroptosis-related genes from published reports and existing databases, we constructed an integrated model based on the RNA-sequencing data in GBM. The association of FRGPRS and overall survival is identified and validated across several different datasets. Genomic and clinical characteristics, immune infiltration, enriched pathways, pan-cancer, drug resistance, and immune checkpoint inhibitor therapy are compared among various FRGPRS subgroups. RESULTS: We identified and confirmed the influences of five ferroptosis key hub genes in the FRGPRS model. The FRGPRS model could serve to predict overall survival and progression-free survival in GBM patients, and high FRGPRS was associated with comparatively stronger immunity, higher proportions of tumour tissue, and good cytolytic immune and chemotherapeutics response in GBM patients. CONCLUSIONS: The five ferroptosis key hub genes constituting the FRGPRS model could serve to predict overall survival and progression-free survival in patients with GBM and help guide timely and efficacious therapeutic strategies customised and optimised for each individual patient. This discovery may lay the foundation for the development and optimisation of other iterations of this model for the improved forecasting, detection, and treatment of other malignancies notorious for their drug resistance and immune escape.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/patologia , Ferroptose , Glioblastoma/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Radioterapia/métodos , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Estudos de Casos e Controles , Feminino , Seguimentos , Glioblastoma/imunologia , Glioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
13.
Front Oncol ; 11: 709321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307178

RESUMO

BACKGROUND: Given the similarities in clinical manifestations of cystic-solid pituitary adenomas (CS-PAs) and craniopharyngiomas (CPs), this study aims to establish and validate a nomogram based on preoperative imaging features and blood indices to differentiate between CS-PAs and CPs. METHODS: A departmental database was searched to identify patients who had undergone tumor resection between January 2012 and December 2020, and those diagnosed with CS-PAs or CPs by histopathology were included. Preoperative magnetic resonance imaging (MRI) features as well as blood indices were retrieved and analyzed. Radiological features were extracted from the tumor on contrast-enhanced T1 (CE-T1) weighted and T2 weighted sequences. The two independent samples t-test and principal component analysis (PCA) were used for feature selection, data dimension reduction, and radiomics signature building. Next, the radiomics signature was put in five classification models for exploring the best classifier with superior identification performance. Multivariate logistic regression analysis was then used to establish a radiomic-clinical model containing radiomics and hematological features, and the model was presented as a nomogram. The performance of the radiomics-clinical model was assessed by calibration curve, clinical effectiveness as well as internal validation. RESULTS: A total of 272 patients were included in this study: 201 with CS-PAs and 71 with CPs. These patients were randomized into training set (n=182) and test set (n=90). The radiomics signature, which consisted of 18 features after dimensionality reduction, showed superior discrimination performance in 5 different classification models. The area under the curve (AUC) values of the training set and the test set obtained by the radiomics signature are 0.92 and 0.88 in the logistic regression model, 0.90 and 0.85 in the Ridge classifier, 0.88 and 0.82 in the stochastic gradient descent (SGD) classifier, 0.78 and 0.85 in the linear support vector classification (Linear SVC), 0.93 and 0.86 in the multilayers perceptron (MLP) classifier, respectively. The predictive factors of the nomogram included radiomic signature, age, WBC count, and FIB. The nomogram showed good discrimination performance (with an AUC of 0.93 in the training set and 0.90 in the test set) and good calibration. Moreover, decision curve analysis (DCA) demonstrated satisfactory clinical effectiveness of the proposed radiomic-clinical nomogram. CONCLUSIONS: A personalized nomogram containing radiomics signature and blood indices was proposed in this study. This nomogram is simple yet effective in differentiating between CS-PAs and CPs and thus can be used in routine clinical practice.

14.
Front Endocrinol (Lausanne) ; 12: 726448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745002

RESUMO

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.


Assuntos
Adenoma/imunologia , Biomarcadores Tumorais/metabolismo , Proteínas de Checkpoint Imunológico/metabolismo , Recidiva Local de Neoplasia/imunologia , Neoplasias Hipofisárias/imunologia , Evasão Tumoral , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Proteínas de Checkpoint Imunológico/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Prognóstico
15.
Bosn J Basic Med Sci ; 19(4): 375-383, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31202257

RESUMO

We evaluated characteristics and different prognostic factors for survival in age-stratified high-grade glioma in a U.S. cohort. Eligible patients were identified in the Surveillance, Epidemiology, and End Results (SEER) registries and stratified into 3 age groups: 20-39 years old (1,043 patients), 40-59 years old (4,503 patients), and >60 years old (5,045 patients). Overall and cancer-related survival data were obtained. Cox models were built to analyze the outcomes and risk factors. It showed that race was a prognostic factor for survival in patients 40 to 59 years old and in patients ≥60 years old. Partial resection was associated with lower overall survival and cause-specific survival in all age groups (overall survival: 20-39 yr: HR = 6.41; 40-59 yr: HR = 4.84; >60 yr: HR = 5.06; cause-specific survival: 20-39 yr: HR = 5.87; 40-59 yr: HR = 4.01; >60 yr: HR = 3.36). The study highlights that, while some prognostic factors are universal, others are age-dependent. The effectiveness of treatment approaches differs for patients in different age groups. Results of this study may help to develop personalized treatment protocols for glioma patients of different ages.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Glioma/diagnóstico , Glioma/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Geografia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Resultado do Tratamento , Estados Unidos , Adulto Jovem
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