Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

PURPOSE: Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. METHODS: A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry. RESULTS: Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model. CONCLUSIONS: We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drug's potential utility to slow down leptomeningeal spread.

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification.

Astragali Radix (AR) is a common Chinese medicine and food. This article aims to reveal the active role of AR in treating Type 2 diabetes mellitus (T2DM) and its renal protective mechanism. The hypoglycemic active fraction was screened by α-glucosidase and identified by UPLC-QE-Orbitrap-MS spectrometry. The targets and KEGG pathway were determined through the application of network pharmacology methodology. Molecular docking and molecular dynamics simulation technology were used for virtual verification. Subsequently, a mouse model of T2DM was established, and the blood glucose and renal function indexes of the mice after administration were analyzed to further prove the pharmacodynamic effect and mechanism of AR in the treatment of T2DM. HA was determined as the best hypoglycemic active fraction by the α-glucosidase method, with a total of 23 compounds identified. The main active components, such as calycoside-7-O-ß-D-glucoside, methylnisoline, and formononetin, were revealed by network pharmacology. In addition, the core targets and the pathway have also been determined. Molecular docking and molecular dynamics simulation techniques have verified that components and targets can be well combined. In vivo studies have shown that AR can reduce blood sugar levels in model mice, enhance the anti-inflammatory and antioxidant activities of kidney tissue, and alleviate kidney damage in mice. And it also has regulatory effects on proteins such as RAGE, PI3K, and AKT. AR has a good therapeutic effect on T2DM and can repair disease-induced renal injury by regulating the RAGE/PI3K/Akt signaling pathway. This study provides ideas for the development of new drugs or dietary interventions for the treatment of T2DM.

UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction.

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.

Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

Screening of the Active Compounds against Neural Oxidative Damage from Ginseng Phloem Using UPLC-Q-Exactive-MS/MS Coupled with the Content-Effect Weighted Method.

The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg1 and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.

[Targeted Drug Therapy for Intracranial Tumors].

Intracranial tumors seriously affect the physical and mental health of humans. Due to variations in the nature and the growth site of tumors, individualized and specific treatment of patients with intracranial tumor has become a hotspot topic of research, and targeted drug therapy of intracranial tumors, an important subspecialty of precision medicine, has become a key issue that scientists are working hard to tackle. At present, the rapid development in molecular biology and genomics has provided corresponding targets for precision therapies of tumors. However, the blood-brain barrier and blood-tumor barrier prevent drugs from reaching intracranial targets. Therefore, finding effective ways to elevate the concentration of intracranial drugs has become the key issue concerning existing targeted therapies for intracranial tumors. Herein, we reviewed the current status of targeted drug therapy for different intracranial tumors and discussed their efficacy, intending to provide new perspectives for the treatment of intracranial tumors with targeted drugs in the future.

Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing.

BACKGROUND: Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. METHODS: In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. RESULTS: We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer ß-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. CONCLUSIONS: Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of ß-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.

MIF-mediated NF-κB signaling pathway regulates the pathogenesis of polycystic ovary syndrome in rats.

Polycystic ovary syndrome (PCOS) resulting from abnormal glucose metabolism is a relatively common and complex endocrine disorder among women in their reproductive years, However, the pathogenesis of PCOS is still unclear. The purpose of this study is to investigate the macrophage migration inhibitory factor (MIF) involvement of the nuclear factor (NF)-κB in rats with PCOS. Results indicated that testosterone promoted the increase in the levels of MIF and luteinizing hormone (LH) but inhibited the increase in the level of follicular stimulating hormone (FSH). The MIF antibody could alleviate the process of PCOS to a certain extent. Testosterone promoted the expression of interleukin 1-beta (IL-1ß), interleukin 6 (IL-6), Inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TNF-α); the MIF antibody could reverse this effect. Testosterone could inhibit the expression of NF-κB protein whereas MIF antibody could promote the expression in the ovarian cytoplasm. Testosterone promoted the expression of NF-κB protein in the nucleus, this effect also could be reversed by the MIF antibody. Hyperandrogenism activated the NF-κB pathway. After using the MIF antibody, this effect was reversed. This finding suggested that hyperandrogenism activated the NF-κB pathway through MIF. In short, increased MIF levels activated the NF-κB pathway in ovaries, leading to inflammation and the increase in the levels of relevant inflammatory indicators, which might be one of the important factors in the pathogenesis of PCOS.

Screening for genes and subnetworks associated with atypical teratoid/rhabdoid tumors using bioinformatics analysis.

Objectives: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, fast-growing lesions of central nervous system and their prognosis is poor. Nowadays, multimodal managements, including surgery, chemotherapy and radiation therapy are advocated; however, low survival rate and severe neurocognitive toxicity of chemotherapy as well as the irreversible long-term sequelae of irradiation in infants and young children with AT/RTs are alarming. The aim of our study is to provide valid biological information for more tailored advance therapy for these lesions.Methods: Gene expression profile of GSE94349 was downloaded from GEO database and was analyzed using limma R package. Function and enrichment analyses of DEGs were performed based on DAVID database. PPI network construction, hub gene selection and module analysis were conducted in Cytoscape software.Results: In this study, 224 up-regulated genes and 572 down-regulated genes were selected as DEGs. The up-regulated genes were mainly enriched in molecular function and cell component, which mainly included protein binding and nucleus, respectively. The down-regulated DEGs were significantly involved in cell component such as plasma membrane and integral component of membrane. Cell cycle and retrograde endocannabinoid signaling were the main KEGG pathway of up and down DEGs, respectively. CDK1, CCNA2, CDC20, TOP2A were identified as hub genes and two significant network modules were also obtained.Conclusions: Our study may help to further understand the molecular characteristics and provide more tailored targets for future treatment of AT/RTs. Hub genes CDK1, CCNA2, CDC20, TOP2A as well as cell cycle signaling pathway may be new more tailored targets for future treatment of AT/RTs.

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway.

OBJECTIVES: Adamantinomatous craniopharyngiomas (adaCP) accounts for 5.6% to 15% of intracranial tumors. High expression of chemokine (C-X-C motif) ligand 12 (CXCL12, also known as stromal cell-derived factor 1 [SDF1]) and its receptor CXC receptor type 4 (CXCR4) are widespread in various malignancy via multiple signal transduction pathways. This study aims to investigate the mechanism of CXCL12/CXCR4 promoting proliferation, migration, and invasion of adaCP. METHODS: Quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry were used to evaluate the expression of CXCL12/CXCR4 mRNA and protein in 10 human adaCP tissues. Three successfully primary cell lines were obtained from native mainly solid tumor specimens, and confirmed by the means of inverted contrast microscope directly and following hematoxylin and eosin staining. Immunofluorescence was used to detect protein expression in vivo for the verification of primary cell line. Proliferation, migration, and invasion assays were performed to assess the biological functional role of CXCL12/CXCR4 in adaCP. The signal pathways involved in the action of CXCL12/CXCR4 in adaCP were also evaluated. RESULTS: CXCL12 and CXCR4 were highly expressed in human adaCP samples. Primary adaCP cells were isolated and detected by the means of immunofluorescence for the detection of pan cytokeratin (pan-CK) and vimentin (VIM). Overexpression of CXCL12/CXCR4 significantly promoted the proliferation, migration, and invasion of primary adaCP cells. Moreover, cancer-promoting activity of CXCL12/CXCR4 is partially through its facilitation of PI3K/AKT signal pathway. CONCLUSIONS: Our data showed that CXCL12/CXCR4 promotes adaCP proliferation, migration, and invasion through PI3K/AKT signal pathway. These findings suggested that therapeutic strategies regulating CXCL12/CXCR4 expression may provide an effective treatment of adaCP.

Frequent B7-H3 overexpression in craniopharyngioma.

Craniopharyngiomas (CPs) are uncommon intracranial benign neoplasms that located in sellar/parasellar region with clinically challenging. B7-H3 is an immune checkpoint molecule highly expressed in many malignant tumors. In this study, we analyzed whether B7-H3 is expressed in 44 CPs samples (adamantinomatous CPs: n = 30 and papillary CPs: n = 14), and whether it could serve as an immunotherapy target in CPs. Immunohistochemical analysis showed that B7-H3 was highly expressed in adamantinomatous CPs (184.3 ±â€¯13.58) and papillary CPs (223.2 ±â€¯11.89), while almost undetectable in normal brain tissue (24 ±â€¯4.9). Besides, B7-H3 expression level was correlated with poor prognosis of patients with CPs. Immunofluorescence and Western blot analysis further suggested that ß-catenin co-localized with B7-H3 and could promote its expression in adaCPs. B7-H3 expression level was positively correlated with staining intensity of IBA1+ cells, but negatively with T cell infiltration in CPs, suggesting that B7-H3 might play a role in the regulation of tumor microenvironment in CPs. Moreover, B7-H3/CD3 bi-specific T cell engager (BiTE) efficiently inhibited the growth of human primary craniopharyngioma cells in a time- and dose-dependent manner. Our results revealed B7-H3 was highly expressed in CPs and targeting B7-H3 might therefore be an effective therapeutic strategy against craniopharyngioma.

Deep brain stimulation of the thalamic ventral intermediate nucleus for Benedikt's syndrome mainly present as tremor: a long-term case observation.

Benedikt's syndrome (BS) is caused by the lesion in the midbrain and specifically manifests a series of symptoms, including ipsilateral third nerve palsy, contralateral tremor, hemiataxia, and hyperactive tendon reflexes. Deep brain stimulation (DBS) for BS emerges as a new approach and achieves successfully results. We report a successful case report of thalamic ventral intermediate (VIM) nucleus DBS for a patient with BS. During follow-up of 3 years, DBS successfully control the tremor and greatly improve his living and working quality. We consider that VIM DBS may have sustained benefit for refractory BS that mainly presents as tremor.

Implementation of Enterprise Imaging Strategy at a Chinese Tertiary Hospital.

Medical images have become increasingly important in clinical practice and medical research, and the need to manage images at the hospital level has become urgent in China. To unify patient identification in examinations from different medical specialties, increase convenient access to medical images under authentication, and make medical images suitable for further artificial intelligence investigations, we implemented an enterprise imaging strategy by adopting an image integration platform as the main tool at Xuanwu Hospital. Workflow re-engineering and business system transformation was also performed to ensure the quality and content of the imaging data. More than 54 million medical images and approximately 1 million medical reports were integrated, and uniform patient identification, images, and report integration were made available to the medical staff and were accessible via a mobile application, which were achieved by implementing the enterprise imaging strategy. However, to integrate all medical images of different specialties at a hospital and ensure that the images and reports are qualified for data mining, some further policy and management measures are still needed.

Edaravone Reduces Iron-Mediated Hydrocephalus and Behavioral Disorder in Rat by Activating the Nrf2/HO-1 Pathway.

Our previous studies have demonstrated that hemorrhage-derived iron has a key role in causing brain injury after intraventricular hemorrhage (IVH). Based on this finding, we hypothesized that edaravone, a free-radical scavenger, has the potential to alleviate hydrocephalus and neurological deficits post-IVH by suppressing iron-induced oxidative stress. Thus, this study aimed to investigate the efficacy of edaravone for rats with FeCl3 injection, as well as to explore the related molecular mechanism. An experimental model was established in adult male Sprague-Dawley rats via FeCl3 injection into the right lateral ventricle. Edaravone or vehicle was administered immediately, 1 day and 2 days after intraventricular injection. Brain water content, magnetic resonance imaging, neurological score, oxidative stress assays, Western blot analysis, and electron microscopy were employed to evaluate brain injury in these rats. Intraventricular injection of FeCl3 induced brain edema, ventricular dilation, and neurobehavioral disorder in rats. Edaravone treatment significantly attenuated the above symptoms, reduced ependymal cilia and neuron damage, and inhibited oxidative stress (elevated levels of an antioxidant, superoxide dismutase; decreased levels of an oxidant, malondialdehyde). Moreover, edaravone administration effectively activated the Nrf2/HO-1 signaling pathway in rat brain following FeCl3 injection. These results showed that edaravone treatment alleviated brain edema, ventricular expansion, and neurological disorder after FeCl3 injection. The possible mechanism is by protecting ependymal cilia and neurons from oxidative stress injury and activating the Nrf2/HO-1 signaling pathway. These results provide further experimental evidence for edaravone application in the treatment of IVH.

Clinical and prognostic role of annexin A2 in adamantinomatous craniopharyngioma.

Annexin A2 (AnxA2) is a highly conserved Ca2+-regulated membrane binding protein, which affects cell mobility and tumor progression. Adamantinomatous craniopharyngioma (AdaCP) are a kind of epithelial tumors of the sellar region with high tendency to recur. Robust biomarkers are required to predict tumor behavior and to establish follow-up individualized treatment approaches. In this study, we firstly compared four surgical AdaCP samples with normal brain by two-dimensional gel electrophoresis (2DE) proteomic analysis. Potential prognostic biomarkers were further validated in a large cohort of 65 AdaCPs by immunohistochemistry. The effects of AnxA2 on AdaCP cells proliferation and migration were analyzed in vitro with isolated primary AdaCP cells as well as SV40T-immortalized cells. Finally, the gefitinib sensitivity of AdaCPs with differentially expressed AnxA2 and the potential molecular mechanisms were examined by flow cytometric analysis, Real-time PCR and immunoblot assays. Proteomic analysis indicated that AnxA2 was the protein spot with the most elevated expression in AdaCP samples. Immunohistochemistry assays indicated the expression level of AnxA2 was significantly higher in recurrent AdaCPs compared with primary ones. Moreover, AnxA2+ AdaCP cells exhibited enhanced proliferation and migration ability compared with AnxA2- AdaCP cells in vitro. Further, we show that AnxA2+ AdaCP cells exhibited elevated expression of EGFR and downstream p-AKT (S308) and p-AKT (S473), and were more sensitive to tyrosine kinase inhibitor gefitinib. Our data suggest that AnxA2 may serve as a promising biomarker for AdaCP progression, recurrence and drug susceptibility. Our data support potential clinical implications for the follow-up treatment of AdaCP patients with high AnxA2 expression.

Ferric ion induced enhancement of ultraviolet vapour generation coupled with atomic fluorescence spectrometry for the determination of ultratrace inorganic arsenic in surface water.

A novel method of ultraviolet vapour generation (UVG) coupled with atomic fluorescence spectrometry (AFS) was developed for the determination of ultratrace inorganic arsenic (iAs) in surface water. In this work, different ferric species were utilised for the first time as an enhancement reagent for the ultraviolet vapour generation of As(III), and their UVG efficiencies for volatile species of arsenic were investigated. 15 mg L(-1) of ferric chloride provided the greatest enhancement of approximately 10-fold, using 20% acetic acid combined with 4% formic acid with 30 s ultraviolet irradiation at 200 mL min(-1) Ar/H2 flow rate. Under the optimised conditions, the linear range was 1.0 µg L(-1)-100.0 µg L(-1), and the spiked recoveries were 92%-98%. The limit of detection was 0.05 µg L(-1) for iAs, and the relative standard deviation (RSD) value of the repeated measurements was 2.0% (n = 11). This method was successfully applied to the determination of ultratrace iAs in tap water, river water, and lake water samples using 0.2% H2SO4 (v : v) as the sample preserver. The obtained values for the water samples of certified reference materials (CRMs) including GSB-Z50004-200431, GBW08605 and GBW(E)080390 were all within the certified ranges.

Domain position prediction based on sequence information by using fuzzy mean operator.

The prediction of protein domain region is an advantageous process on the study of protein structure and function. In this study, we proposed a new method, which is composed of fuzzy mean operator and region division, to predict the particular positions of domains in a target protein based on its sequence. The whole sequence is aligned and scored by using fuzzy mean operator, and the final determination of domain region position is realized by region division. A published benchmark is used for the comparison with previous researches. In addition, we generate two extra datasets to examine the stability of this method. Finally, the prediction accuracy of independent test dataset achieved by our method was up to 84.13%. We wish that this method could be useful for related researches.

[Clinical classification and selection of surgical approaches for cervical spinal dumbbell tumors].

OBJECTIVE: To explore the clinical classification and selection of surgical approaches for cervical spinal dumbbell tumors. METHODS: The clinical data of 87 patients with cervical spinal dumbbell tumors undergoing surgical operations from January 2005 to December 2012 at our hospital were analyzed retrospectively. According to the size of inner and outer parts of tumors and the presence or absence of spinal bone damage, the cervical spinal dumbbell tumors were divided into 4 types of intraspinal predominant (I, n = 48), extraspinal predominant (II, n = 1), intrapinal and extraspinal without damage of spinal bone (III, n = 15) and intrapinal and extraspinal type with damage of spinal bone (IV, n = 7). Different surgical approaches were selected on the basis of tumor classification: posterior median-hemilamina approaches for type I tumors, lateral-muscle gap approaches for type II tumors, ateral-muscle gap-hemilamina or lateral-muscle gap-posterior median-hemilamina approaches for type III tumors, posterior far lateral-muscle gap-hemilamina or posterior median-muscle gap-hemilamina approaches plus posterior occipital cervical or cervical spinal bone graft fusion and internal fixation for type IV tumors. RESULTS: Among them, 83 cases underwent total resection and another 4 subtotal resection in one-stage operation. The postoperative follow-up period had a range of 9 months to 6 years (mean, 3.2 years). There was no recurrence of tumors for total resection and 1 case of tumor recurrence for subtotal resection. During the follow-up period, the clinical manifestations of 85 patients improved while another 2 deteriorated. And there was no occurrence of spinal deformity. CONCLUSION: Clinical classification of cervical spinal dumbbell tumor plays an important guiding role in the selection of surgical approaches. Adopting appropriate surgical approaches based on tumor type can not only improve the rate of total resection of tumor but also reduce the incidence of postoperative spinal deformity.

Repurposing mebendazole against triple-negative breast cancer leptomeningeal disease.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype that often metastasizes to the brain. Leptomeningeal disease (LMD), a devastating brain metastasis common in TNBC, has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. Methods: A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, LMD was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry. Results: Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced tumor growth and extended survival in the LMD model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model. Conclusions: We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC LMD. Our findings are concordant with previous efforts involving MBZ and central nervous system pathology and further support the drug's potential utility as an alternative therapeutic for TNBC LMD.

Tumor-associated macrophage-related strategies for glioma immunotherapy.

High-grade glioma is one of the deadliest primary tumors of the central nervous system. Despite the many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results in clinical studies. The reason may be due to the suppressive tumor microenvironment of gliomas that limits the function of specific immune cells (e.g., T cells) which are currently the primary targets of immunotherapy. However, tumor-associated macrophage, which are enriched in tumors, plays an important role in the development of GBM and is becoming a research hotspot for immunotherapy. This review focuses on current research advances in the use of macrophages as therapeutic targets or therapeutic tools for gliomas, and provides some potential research directions.