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Antígeno B7-H1 , Neoplasias Encefálicas , Glioblastoma , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Encefálicas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Resultado do Tratamento , Masculino , Pessoa de Meia-Idade , FemininoRESUMO
BACKGROUND: Glioblastoma multiforme (GBM) is identified as one of the most prevalent and malignant brain tumors, characterized by poor treatment outcomes and a limited prognosis. CMTM6, a membrane protein, has been found to upregulate the expression of programmed cell death 1 ligand 1 protein (PD-L1) and acts as an immune checkpoint inhibitor by inhibiting the programmed death 1 protein/PD-L1 signaling pathway. Recent research has demonstrated a high expression of CMTM6 in GBM, suggesting its potential role in influencing the pathogenesis and progression of GBM, as well as its association with immune cell infiltration in the tumor microenvironment. However, the underlying mechanism of CMTM6 in GBM requires further investigation. METHODS: Data from cancer patients in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas cohorts were consolidated for the current study. Through multi-omics analysis, the study systematically examined the expression profile of CMTM6, epigenetic modifications, prognostic significance, biological functions, potential mechanisms of action and alterations in the immune microenvironment. Additionally, the study investigated CMTM6 expression in GBM cell lines and normal cells using reverse transcription PCR and western blot analysis. The impact of CMTM6 on GBM cell proliferation, migration and invasion was evaluated using a combination of cell counting kit-8 assay, clone formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, wound healing assay and Transwell assay. In order to explore the mechanism of CMTM6, the Wnt/ß-catenin signaling pathway and autophagy-related genes were further verified through western blot analysis. RESULTS: CMTM6 is highly expressed in multiple tumors, particularly GBM. CMTM6 has been shown to be a valuable diagnostic and prognostic biomarker by various bioinformatics approaches. Additionally, CMTM6 plays a pivotal role in the pathogenesis of cancer, specifically GBM, by modulating various biological processes such as DNA methyltransferase expression, RNA modification, copy number variation, genomic heterogeneity, tumor stemness and DNA methylation. The findings of the experiment indicate a significant correlation between elevated CMTM6 expression and the proliferation, invasion, migration and autophagy of GBM cells, with potential key roles mediated through the Wnt/ß-catenin signaling pathway. Furthermore, CMTM6 is implicated in modulating tumor immune cell infiltration and is closely linked to the expression of various immune checkpoint inhibitors and immune modulators, particularly within the context of GBM. High levels of CMTM6 expression also enhance the responsiveness of GBM patients to radiotherapy and chemotherapy, thereby offering valuable insights for guiding treatment strategies for GBM. CONCLUSIONS: Autophagy-related CMTM6 is highly expressed in various types of cancer, especially GBM, and it can regulate GBM progression through the Wnt/ß-catenin signaling pathway and is capable of being used as an underlying target for the diagnosis, treatment selection and prognosis of patients with GBM.
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Autofagia , Biomarcadores Tumorais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glioblastoma , Proteínas com Domínio MARVEL , Microambiente Tumoral , Via de Sinalização Wnt , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteínas com Domínio MARVEL/metabolismo , Proteínas com Domínio MARVEL/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Autofagia/genética , Prognóstico , Proliferação de Células , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteínas da Mielina/genética , Proteínas da Mielina/metabolismo , Movimento Celular/genética , beta Catenina/metabolismo , beta Catenina/genéticaRESUMO
BACKGROUND AND OBJECTIVES: Craniopharyngiomas originate from the pituitary stalk (PS) and extend along the pituitary-hypothalamic axis. Peripheral retroinfundibular craniopharyngiomas, particularly, may have worse surgery outcomes than other types. This study aims to investigate the advantage of using "one-and-a-half" interdural transcavernous pituitary transposition/rotation to dissect the tumor from the residual stalk and hypophyseal portal system for this subtype of craniopharyngioma. METHODS: From August 2018 to February 2023, patients with peripheral retroinfundibular craniopharyngioma underwent surgical treatment. We analyzed clinical information, surgical records, imaging, and examination findings. The surgical procedure, including "one-and-a-half" interdural transcavernous pituitary transposition and rotation, was explained. Postoperative follow-up included endocrinological tests, MRI examinations, and urination surveys. RESULTS: Among the 52 patients diagnosed with craniopharyngioma who underwent surgical treatment, 9 were classified as peripheral retroinfundibular craniopharyngioma, and they received "one-and-a-half" interdural transcavernous pituitary transposition and stalk rotation. In 6 cases, the residual PS and most of the hypophyseal portal system were preserved. Gross total resection was achieved in 5 patients and near total resection in 1 patient. One patient had a transection of the bilateral inferior hypophyseal arteries and 5 unilaterally. None experienced permanent diabetes insipidus, but varying degrees of anterior pituitary dysfunction postoperatively required hormone replacement therapy, which gradually decreased over time. CONCLUSION: The natural anatomic corridor, "one-and-a-half" interdural transcavernous pituitary transposition, and stalk rotation provide increased working space compared with intradural or extradural pituitary transposition. Simultaneously rotating the tumor and pituitary enables a specific attack angle for lesion dissection after the anteriorly displaced residual stalk is rotated laterally. This approach preserves the residual PS and hypophyseal portal system, avoiding complications of diabetes insipidus and hypopituitarism. In most cases, only one side of the inferior hypophyseal artery needs to be sacrificed, ensuring normal pituitary function.
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Many researchers have explored the potential association between one neurosurgical disease and coronavirus disease 2019 (COVID-19), but few systematically analyzed the association and causality between COVID-19 and various neurosurgical diseases. A Mendelian randomization analysis was conducted to evaluate the causal association between COVID-19 (including critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 30 neurosurgical diseases within European populations. The consequences of inverse variance weighted models suggest that genetic susceptibility of critically ill COVID-19 may increase the risk of cerebral infarction (odds ratio [OR] = 1.02; p-value = 0.006), genetic susceptibility of SARS-CoV-2 infection may increase the risk of stroke (OR = 1.02; p-value = 0.047), and conversely, genetic susceptibility of hospitalized COVID-19 may reduce the risk of pituitary adenoma and craniopharyngioma (OR = 0.90; p-value = 0.032). In addition, evidences revealed potential associations between genetic susceptibility of COVID-19 and spinal stenosis (OR = 1.03; p-value = 0.028), diffuse brain injury (OR = 1.21; p-value = 0.040) and focal brain injury (OR = 1.12; p-value = 0.040). By testing for heterogeneity and pleiotropy, the above causal conclusions are robust. In summary, our analysis shows that COVID-19 has an independent and powerful causal influence on multiple neurosurgical disorders.
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COVID-19 , Humanos , SARS-CoV-2 , Estado Terminal , Análise da Randomização Mendeliana , Predisposição Genética para Doença , Estudo de Associação Genômica AmplaRESUMO
Despite the tremendous progress in cancer treatment in recent decades, cancers often become resistant due to multiple mechanisms, such as intrinsic or acquired multidrug resistance, which leads to unsatisfactory treatment effects or accompanying metastasis and recurrence, ultimately to treatment failure. With a deeper understanding of the molecular mechanisms of tumors, researchers have realized that treatment designs targeting tumor resistance mechanisms would be a promising strategy to break the therapeutic deadlock. Nanodelivery systems have excellent physicochemical properties, including highly efficient tissue-specific delivery, substantial specific surface area, and controllable surface chemistry, which endow nanodelivery systems with capabilities such as precise targeting, deep penetration, responsive drug release, multidrug codelivery, and multimodal synergy, which are currently widely used in biomedical researches and bring a new dawn for overcoming cancer resistance. Based on the mechanisms of tumor therapeutic resistance, this review summarizes the research progress of nanodelivery systems for overcoming tumor resistance to improve therapeutic efficacy in recent years and offers prospects and challenges of the application of nanodelivery systems for overcoming cancer resistance.
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Nanomedicina , Neoplasias , Humanos , Resistencia a Medicamentos Antineoplásicos , Sistemas de Liberação de Fármacos por Nanopartículas , Neoplasias/tratamento farmacológico , Falha de TratamentoRESUMO
Glioblastoma multiforme (GBM) is recognized as the prevailing malignant and aggressive primary brain tumor, characterized by an exceedingly unfavorable prognosis. Cuproptosis, a recently identified form of programmed cell death, exhibits a strong association with cancer progression, therapeutic response, and prognostic outcomes. However, the specific impact of cuproptosis on GBM remains uncertain. To address this knowledge gap, we obtained transcriptional and clinical data pertaining to GBM tissues and their corresponding normal samples from various datasets, including TCGA, CGGA, GEO, and GTEx. R software was utilized for the analysis of various statistical techniques, including survival analysis, cluster analysis, Cox regression, Lasso regression, gene enrichment analysis, drug sensitivity analysis, and immune microenvironment analysis. Multiple assays were conducted to investigate the expression of genes related to cuproptosis and their impact on the proliferation, invasion, and migration of glioblastoma multiforme (GBM) cells. The datasets were obtained and prognostic risk score models were constructed and validated using differentially expressed genes (DEGs) associated with cuproptosis. To enhance the practicality of these models, a nomogram was developed.Patients with glioblastoma multiforme (GBM) who were classified as high risk exhibited a more unfavorable prognosis and shorter overall survival compared to those in the low risk group. Additionally, we specifically chose FDX1 from the differentially expressed genes (DEGs) within the high risk group to assess its expression, prognostic value, biological functionality, drug responsiveness, and immune cell infiltration. The findings demonstrated that FDX1 was significantly upregulated and associated with a poorer prognosis in GBM. Furthermore, its elevated expression appeared to be linked to various metabolic processes and the susceptibility to chemotherapy drugs. Moreover, FDX1 was found to be involved in immune cell infiltration and exhibited correlations with multiple immunosuppressive genes, including TGFBR1 and PDCD1LG2. The aforementioned studies offer substantial assistance in informing the chemotherapy and immunotherapy approaches for GBM. In summary, these findings contribute to a deeper comprehension of cuproptosis and offer novel perspectives on the involvement of cuproptosis-related genes in GBM, thereby presenting a promising therapeutic strategy for GBM patients.
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Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Ferredoxinas , Imunoterapia , Apoptose , Microambiente Tumoral/genética , Cobre , PrognósticoRESUMO
Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.
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Craniofaringioma , Neoplasias Hipofisárias , Humanos , Craniofaringioma/genética , Craniofaringioma/diagnóstico , Craniofaringioma/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , Transcriptoma , Comunicação Celular , Análise de Sequência de RNA , Microambiente Tumoral/genéticaRESUMO
Background: Human anatomy is a predominant course that helps medical students enhance their performance in other clinical curricula. However, it is difficult for students to learn the relationship between anatomy and diseases, since the traditional teaching modality of anatomy courses does not contain enough clinical contents. Clinical anatomy education merges clinical diagnosis and treatment into anatomy learning. This study seeks to determine whether systematic clinical anatomy teaching can improve students' performance and interest in anatomy courses. Methods: This study was a retrospective study conducted at West China Medical School, Sichuan University. Medical students of the 8-year program who participated in the course "HUMAN MORPHOLOGY" in the academic years of 2014-2018 did not receive a systematic clinical anatomy course, while those in the academic years of 2018-2022 did. These two groups were involved to analyze their final examination. Then, a questionnaire for students in the academic year of 2021-2022 was conducted to assess their general satisfaction and opinions on the usefulness and learning modalities of clinical anatomy courses. Results: Students who received systematic clinical anatomy lessons performed significantly better than those who were not in the final examinations. The average grades were 73.64 and 79.90 in the 3rd semester of medicine (p < 0.0001) and 75.70 and 82.18 in the 4th semester of medicine (p < 0.0001) before and after 2018, respectively. The response rate of the questionnaire was 77.78%, and most of the students agreed that the clinical anatomy lessons were satisfactory, with 40 out of 71 (56.34%) strongly agreeing and 26 out of 71 (36.62%) agreeing. Conclusion: Clinical anatomy education should be more emphasized and merged into the gross anatomy curriculum owing to the better performance in the final examination and high rate of satisfaction.
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BACKGROUND: PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated. METHODS: By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes. RESULTS: PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs. CONCLUSIONS: Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.
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Adenoma , Fibroblastos Associados a Câncer , Neoplasias Hipofisárias , Humanos , Fibroblastos Associados a Câncer/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Microambiente Tumoral , Interferon gama , Adenoma/genética , Fibroblastos/metabolismoRESUMO
Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery of DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the regulation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting tumor apoptosis, suppressing tumor proliferation and angiogenesis. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future.
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Neoplasias Colorretais , Nanopartículas , Animais , Camundongos , Proteínas Nucleares , Linhagem Celular Tumoral , Quimera de Direcionamento de Proteólise , Proteólise , Fatores de Transcrição/metabolismo , Doxorrubicina/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológicoRESUMO
Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co-delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 ânm and a zeta potential of -0.25 âmV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma.
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BACKGROUND: Immunoglobulin G4 related disease (IgG4-RD) is a fibroinflammatory disease with markedly elevated serum IgG4 levels and fibrous tissue proliferation, accompanied by numerous plasma cells. IgG4 related hypertrophic pachymeningitis (IgG4-RHP) is relatively rare and indistinguishable from other phymatoid diseases before the operation. The risk of long-term immunosuppression needs to be balanced with disease activity. CASE SUMMARY: A 40-year-old man presented with headache and bilateral abducent paralysis. He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same. Before the operation and steroid therapy, the patient was suspected of having tubercular meningitis at a local hospital. A clivus lesion was found via brain magnetic resonance imaging (MRI) at this presentation. He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery. Transnasal endoscopic resection was performed to treat deterioration of nerve function. Postoperative pathologic examination suggested IgG4-RD. Moreover, the serum IgG4 was elevated at 1.90 g/L (reference range: 0.035-1.500 g/L). After steroid therapy for 2 mo, the lesion size diminished on MRI, and the function of bilateral abducent nerves recovered. CONCLUSION: IgG4-RHP is relatively rare and indistinguishable before the operation. Elevated serum IgG4 levels and imaging examination help in the diagnosis of IgG4-RHP. Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.
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Tumor cells exhibit enhanced uptake and processing of nutrients to fulfill the demands of rapid growth of tumor tissues. Tryptophan metabolizing dioxygenases are frequently up-regulated in several tumor types, which has been recognized as a crucial determinant in accelerated tumor progression. In our study, we explored the specific role of tryptophan 2,3-dioxygenase 2 (TDO2) in glioma progression. Analysis of mRNA profiles in 325 glioma patients based on the rich set of CCGA database was performed, which revealed that high TDO2 expression was tightly correlated with poor prognosis in glioma patients. TDO2 increased intracellular levels of tryptophan metabolism in the kynurenine (Kyn) pathway in vitro and in vivo, resulting in sustained glioma cell proliferation. Mechanistically, overexpression of TDO2 promoted the secretion of Kyn, which in turn stimulated the activation of the aryl hydrocarbon receptor (AhR)/AKT signaling pathway, resulting in heightened proliferative properties and tumorigenic potential in glioma cells. Meanwhile, Kyn produced by tumor cells further suppressed the proliferation of functional T cells, thereby resulting in immunosuppression and enhanced tumor growth in glioma. Our study showed that TDO2-induced increase in tryptophan metabolite Kyn played a pivotal role in glioma development via the AhR/AKT pro-survival signals and immunosuppressive effects, suggesting that the use of TDO2 inhibitors in combination with chemotherapy may be a novel strategy to effectively and synergistically eliminate glioma cells.
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Transnasal endoscopic skull base surgery has been increasing in volume in recent years and its indications are constantly expanding. The potential occurrence of intraoperative and postoperative neurovascular complications deserves special attention from neurosurgeons. Multimodal intraoperative neurophysiological monitoring technology allows neurosurgeons to monitor cerebral perfusion and the functional status of the associated cranial nerves in real time, thereby enabling surgeons to make prompt adjustments in surgical procedures and strategies and reduce the risks of postoperative neurological complications in patients. Based on available literature, we reviewed how appropriate monitoring strategies were optimized for different key components of transnasal endoscopic skull base procedures, intending to provide reference for clinicians.
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Monitorização Neurofisiológica Intraoperatória , Endoscopia , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/etiologia , Base do Crânio/cirurgiaRESUMO
The current studies associated with tumor biology continue to describe a high correlation between tryptophan (Trp) metabolism and tumor progression. These findings reflect the complex underlying mechanism of tumor development and highlight the need to explore additional drug targets for carcinoma-associated diseases. In our study, we reported that elevated Trp metabolism was observed in highly malignant glioma tumor tissues from patients. The elevated Trp metabolism in glioma cells were induced by the overexpression of Trp 2,3-dioxygenase 2 (TDO2), which further contributed to the production of the metabolite kynurenine (Kyn). Subsequently, the Kyn derived from Trp metabolism was able to mediate the activation of the aryl hydrocarbon receptor (AhR) and downstream PI3K/AKT signals, resulting in the strengthening of tumor stemness and growth. Meanwhile, the activation of the AhR could promote the process of epithelial-mesenchymal transition in gliomas through a TGF-ß-dependent mechanism, leading to enhanced tumor invasion in vitro and in vivo. Inhibition of the AhR using StemRegenin 1 was demonstrated to suppress glioma growth and improve the outcome of traditional chemotherapy in subcutaneous tumor-bearing mice, representing a promising therapeutic target for clinical glioma treatment.
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Dioxigenases , Glioma , Animais , Dioxigenases/metabolismo , Glioma/metabolismo , Cinurenina/metabolismo , Cinurenina/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Triptofano/metabolismo , Triptofano Oxigenase/metabolismoRESUMO
Glioma initiating cells (GICs), also known as glioma stem cells, display the capacity to recapitulate the functional diversity within the tumor. Despite the great progress achieved over the last decades, defining the key molecular regulators of GICs has represented a major obstacle in this field. In our study, data from The Cancer Genome Atlas database illustrated a relationship between C-X-C motif chemokine receptor 4 (CXCR4) expression and the survival of glioma patients. Mechanistically, we further indicated that CXCR4 mediated the upregulation of Kruppel like factor 5 (KLF5), a zinc-finger-containing transcription factor, to facilitate the proliferation of GICs. What's more, CXCR4 also enhanced the chemoresistance through KLF5/Bcl2-like 12 (BCl2L12) in glioma. The elevated expression of KLF5 and BCL2L12 induced by CXCR4 was dependent on phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (AKT) signaling. Importantly, combined application of temozolomide and a CXCR4 inhibitor efficiently reversed CXCR4 mediated drugs resistance and improved anticancer effects in vivo. Collectively, our findings confirmed that CXCR4 promoted GICs proliferation via the KLF5/BCL2L12 dependent pathway, which may enrich the understanding of GICs and help drive the design of efficacious therapeutic strategies.
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Neoplasias Encefálicas , Glioma , Receptores CXCR4 , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Glioma/tratamento farmacológico , Glioma/metabolismo , Humanos , Proteínas Musculares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais , Temozolomida/metabolismo , Temozolomida/farmacologiaRESUMO
BACKGROUND: Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years. METHODS: Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients' quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: Thirty-six patients with a mean follow-up period of 61.6 months (range 13-123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4-96 months) and 38 months (range 4-125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470-0.756) and 0.939 (95% CI 0.772-0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154-0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118-0.956) result in significantly longer PFS in patients with SFT/HPC. CONCLUSIONS: Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.
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Hemangiopericitoma , Neoplasias de Tecidos Moles , Tumores Fibrosos Solitários , Sistema Nervoso Central/patologia , Hemangiopericitoma/cirurgia , Humanos , Recidiva Local de Neoplasia/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Tumores Fibrosos Solitários/cirurgiaAssuntos
Malformações Vasculares do Sistema Nervoso Central , Hematoma Subdural Agudo , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Angiografia Cerebral , Hematoma Subdural Agudo/diagnóstico por imagem , Hematoma Subdural Agudo/etiologia , Hematoma Subdural Agudo/cirurgia , HumanosRESUMO
Microvascular decompression (MVD) is the first choice of surgery for hemifacial spasm (HFS). MVD surgery for vertebral artery (VA)-associated HFS is more difficult than for non-VA-associated HFS. There is controversy about the cure rate and complication of MVD for HFS in previous studies. We searched PubMed, Web of Science, and Embase for relevant publications. Based on the search results, we compared the outcomes of MVD for VA-associated HFS and non-VA-associated HFS. At the same time, we analyzed spasm-free rates and the complications and assessed the relationship between VA-associated HFS and gender, left side, and age. For analysis, six studies that included 2952 patients in the VA-associated group and 604 in the non-VA-associated group were selected. The effective rate of MVD was not significantly different between both groups (OR = 1.16, 95% CI 0.81-1.67, P = 0.42). Compared to non-VA-associated group, the transient complications (OR = 0.64, 95% CI 0.46-0.89, P = 0.008) and permanent complications (OR = 0.28, 95% CI 0.15-0.54, P = 0.0001) occurred more frequently in VA-associated group. The rate of hearing loss was significantly higher in VA-associated HFS than non-VA-associated HFS (OR = 0.35, 95% CI 0.19-0.64, P = 0.0007); the facial paralysis after operation was not significantly different between both groups (OR = 1.25, 95% CI 0.91-1.72, P = 0.17). There were older patients (WMD = 3.67, 95% CI 3.29-4.05, P < 0.00001) and more left-sided HFS (OR = 0.23, 95% CI 0.19 - 0.29, P < 0.0002) in the VA-associated HFS group than non-VA-associated HFS group, while the non-VA-associated HFS group was female-dominated (OR = 1.58, 95% CI 1.32 - 1.89, P < 0.00001). Both groups achieved good results in MVD cure rates. In VA-associated HFS, the complication rate of decompression and the rate of hearing loss after operation were higher than in non-VA-associated HFS, but the facial paralysis after operation was similar in both groups, and most complications were transient and disappeared during follow-up. VA-associated HFS is more prevalent in older adults, less prevalent in women, and more predominantly left-sided. More clinical studies are needed to better compare the efficacy and complication of MVD between both groups.
Assuntos
Paralisia Facial , Perda Auditiva , Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Idoso , Paralisia Facial/etiologia , Feminino , Perda Auditiva/cirurgia , Espasmo Hemifacial/etiologia , Humanos , Cirurgia de Descompressão Microvascular/efeitos adversos , Cirurgia de Descompressão Microvascular/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan-Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.