Intra-arterial microguidewire electrocoagulation to treat intracranial vascular diseases.

OBJECTIVE: To investigate the therapeutic effect of intra-arterial microguidewire electrocoagulation on intracranial vascular diseases. METHODS: Data from 10 patients with cerebral aneurysms between May 2018 and September 2022 were analysed. Patients were treated with endovascular coil embolisation and microguidewire electrocoagulation. XperCT scans were conducted to identify new intracranial haemorrhage, infarction and hydrocephalus. Follow-up examinations were conducted 1, 3, 6 and 12 months after discharge. RESULTS: After the patients received electrocoagulation for different durations, Raymond Grade 1 embolisation was achieved in all 10 patients. No complications, such as haemorrhage, infarction or hydrocephalus, were found during or after surgery. Ten patients were followed up for 6-12 months, and none had any symptoms or new neurological dysfunction 1 month after their operation. Among them, nine were followed up for 12 months, and digital subtraction angiography showed no recurrence of aneurysms or occlusion of parent arteries. CONCLUSION: Intra-arterial microguidewire electrocoagulation can be used as a supplementary treatment for cerebral aneurysms. In cases of incomplete lesion embolisation and cases where tamponade treatment cannot continue, immediate thrombosis may occur. Thus, intra-arterial microguidewire electrocoagulation can help achieve patients' treatment goals.

N6-methyladenosine reader IGF2BP3 as a prognostic Biomarker contribute to malignant progression of glioma.

Background: Glioblastoma (GBM) is a highly aggressive cancer having a dismal prognosis. N6-methyladenosine (m6A) is closely related to GBM progression. The significance of m6A modifications depends on the m6A readers, whose functions in glioma progression are largely unknown. This study sought to investigate the expression of the m6A related gene in glioma and its effect on the malignant progression of glioma. Methods: The expression differences between low-grade gliomas (LGGs) and high-grade gliomas (HGGs), and among 19 m6A-related genes were analyzed by The Cancer Genome Atlas (TCGA). Survival probability was analyzed in terms of the high or low expression of insulin growth factor-2 binding protein 3 (IGF2BP3) in the TCGA data set. The clinicopathological data of 40 patients with glioma were analyzed retrospectively, and the expression of IGF2BP3 in the tumor tissues was analyzed by immunohistochemistry (IHC). Lentiviral vectors harboring short-hairpin RNA (shRNA) were used to knock down IGF2BP3 in the glioma cell lines U87 and U251, and the results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. The effects of IGF2BP3 on the proliferation, invasion, and tumorigenicity of the glioma cells were verified by Cell Counting Kit-8 (CCK-8), transwell invasion, and subcutaneous tumorigenesis experiments in nude mice. The cell cycle phases were measured by flow cytometry. Results: The sequencing of TCGA data identified IGF2BP3 as the most significantly altered m6A-related gene. Patients with high IGF2BP3 expression had a significantly reduced survival probability (P<0.001) compared to those with low IGF2BP3 expression. IGF2BP3 was more upregulated in the HGGs than the LGGs. The downregulation of IGF2BP3 inhibited the proliferation, migration, and invasiveness of the glioma cells, and xenograft tumor growth in the mice. According to TCGA data, IGF2BP3 was closely related to cell cycle regulators, such as cyclin-dependent kinase 1 (CDK1) and cell-division cycle protein 20 homologue (CDC20). Further, the knockdown of IGF2BP3 affected the expression of CDK1 and the cell cycle process. Conclusions: IGF2BP3 expression in glioma is positively correlated with tumor grade and enhanced glioma cell proliferation, invasion, and tumorigenicity. IGF2BP3 knockdown decreased the expression of CDK1 and the cell cycle process. The current study showed that IGF2BP3 may serve as a biomarker of prognosis and a therapeutic target in glioma.

Case report: emergent endovascular treatment for carotid cavernous fistulas presenting as intracranial hemorrhage.

Objectives: This study aimed to discuss the clinical characteristics and emergent endovascular treatment of carotid cavernous fistulas presenting as intracranial hemorrhage. Methods: The clinical data of five patients with carotid cavernous fistulas, who presented with intracranial hemorrhage and who were admitted from January 2010 to April 2017, were analyzed retrospectively, and the diagnoses were confirmed by head computed tomography. Digital subtraction angiography was carried out in all the patients for the diagnosis and further emergent endovascular procedures. All patients were followed up to assess the clinical outcomes. Results: In total, five patients harbored five mono-lateral lesions; two of them were obliterated by detachable balloons, two by detachable coils, and one by detachable coils and Onyx glue. Only one patient was cured by another detachable balloon in the second session, and the other four patients were cured in the first session. At the 3- to 10-year follow-up, there was no intracranial re-hemorrhage in any of the patients; there was no recurrence of symptoms; and delayed occlusion of the parent artery was noted in one case. Conclusion: Emergent endovascular therapy is indicated for carotid cavernous fistulas presenting as intracranial hemorrhage. Individualized treatment according to the characteristics of different lesions is safe and effective.

Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion.

Pilocytic astrocytoma is mostly a pediatric tumor with the majority of patients under age 20. Although tumors can occur throughout neuraxis, most tumors are in the cerebellum and optic chiasm. Pilocytic astrocytoma in unusual locations is often associated with different genetic alterations than the classic KIAA1549::BRAF fusion. We report a rare adult pilocytic astrocytoma of the septum pellucidum that presented with progressive headache. A detailed genomic evaluation found a fusion between BRAF and a novel partner RIN2, a gene overexpressed in both low-grade glioma and glioblastoma. The RIN2::BRAF transcript encodes a chimeric protein containing a dimerization domain SH2 and an intact kinase domain, consistent with a prototypic oncogenic kinase rearrangement. In addition, we discuss the potential oncogenic mechanisms of BRAF signaling and its implication in targeted therapy with kinase inhibitors.

Case Report: A novel LHFPL3::NTRK2 fusion in dysembryoplastic neuroepithelial tumor.

Neurotrophic tyrosine receptor kinase (NTRK) rearrangements are oncogenic drivers of various types of adult and pediatric tumors, including gliomas. However, NTRK rearrangements are extremely rare in glioneuronal tumors. Here, we report a novel NTRK2 rearrangement in a 24-year-old female with dysembryoplastic neuroepithelial tumor (DNT), a circumscribed WHO grade I benign tumor associated with epilepsy. By utilizing targeted RNA next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), reverse transcriptase PCR (RT-PCR), and Sanger sequencing, we verified an in-frame fusion between NTRK2 and the lipoma HMGIC fusion partner-like 3 (LHFPL3). This oncogenic gene rearrangement involves 5' LHFPL3 and 3' NTRK2, retaining the entire tyrosine kinase domain of NTRK2 genes. Moreover, the targeted DNA NGS analysis revealed an IDH1 (p.R132H) mutation, a surprising finding in this type of tumor. The pathogenic mechanism of the LHFPL3::NTRK2 in this case likely involves aberrant dimerization and constitutive activation of RTK signaling pathways.

Spontaneous subarachnoid hemorrhage caused by ruptured aneurysm of basilar trunk perforator: a case report and literature review.

BACKGROUND: Aneurysm of basilar perforator was rarely reported in the literature. It is difficult to treat due to its small size and deep-seated location. Excessive treatment may cause complications that resulted from ischemic events of parent perforators. Therefore, it is important to make clinical strategy for such patients to improve the prognosis. CASE PRESENTATION: One case, who presented as spontaneous subarachnoid hemorrhage, despite the negative result in computed tomography angiography firstly, was diagnosed angiographically as a ruptured aneurysm of the basilar perforator. A good clinical outcome of the case was achieved during the follow-up after conservative observation for 2 months, as well as the disappearance of previous lesion from angiography. CONCLUSIONS: Aneurysm located at perforator of basilar trunk was rare and difficult to treat. Conservative observation for certain cases with periodic angiography follow-up was considered in order to prevent the patients from potential iatrogenic effects.

Novel enhanced GFP-positive congenic inbred strain establishment and application of tumor-bearing nude mouse model.

Transgenic GFP gene mice are widely used. Given the unique advantages of immunodeficient animals in the field of oncology research, we aim to establish a nude mouse inbred strain that stably expresses enhanced GFP (EGFP) for use in transplanted tumor microenvironment (TME) research. Female C57BL/6-Tg(CAG-EGFP) mice were backcrossed with male BALB/c nude mice for 11 generations. The genotype and phenotype of novel inbred strain Foxn1nu .B6-Tg(CAG-EGFP) were identified by biochemical loci detection, skin transplantation and flow cytometry. PCR and fluorescence spectrophotometry were performed to evaluate the relative expression of EGFP in different parts of the brain. Red fluorescence protein (RFP) gene was stably transfected into human glioma stem cells (GSC), SU3, which were then transplanted intracerebrally or ectopically into Foxn1nu .B6-Tg(CAG-EGFP) mice. Cell co-expression of EGFP and RFP in transplanted tissues was further analyzed with the Live Cell Imaging System (Cell'R, Olympus) and FISH. The inbred strain Foxn1nu .B6-Tg(CAG-EGFP) shows different levels of EGFP expression in brain tissue. The hematological and immune cells of the inbred strain mice were close to those of nude mice. EGFP was stably expressed in multiple sites of Foxn1nu .B6-Tg(CAG-EGFP) mice, including brain tissue. With the dual-fluorescence tracing transplanted tumor model, we found that SU3 induced host cell malignant transformation in TME, and tumor/host cell fusion. In conclusion, EGFP is differentially and widely expressed in brain tissue of Foxn1nu .B6-Tg(CAG-EGFP), which is an ideal model for TME investigation. With Foxn1nu .B6-Tg(CAG-EGFP) mice, our research demonstrated that host cell malignant transformation and tumor/host cell fusion play an important role in tumor progression.

Dexamethasone inhibits the proliferation of tumor cells.

OBJECTIVE: Dexamethasone (DEX) is a glucocorticoid that is commonly used in clinics. Previously, DEX has been shown to inhibit the function of immune system; however, DEX is often used to treat side reactions, such as nausea and vomiting caused by chemotherapy in clinics. Therefore, it is necessary to study the role of DEX in the treatment of cancer. METHODS: The effects of DEX on HepG2 were studied in vitro by Cell Counting Kit-8 method, cell cycle, and scratch test. The transplanted tumor model of HepG2 was established in nude mice to study the anti-tumor effect of DEX in vivo. In addition, in order to study the effect of DEX on the immune system, we also established a transplanted tumor model of 4T1 in normal immunized mice to study treatment effect and mechanism of DEX in mice of normal immune function. RESULTS: The results showed that DEX inhibited the proliferation of HepG2 in vitro and in vivo, affecting the cycle and migration of HepG2 cells, and the expression of c-Myc and the activation of mTOR signaling pathway were inhibited. The expression of key enzymes related to glucose metabolism is altered, especially that of phosphoenolpyruvate carboxykinase2 (PCK2). In normal immunized mice, DEX also inhibits the proliferation of tumor cells 4T1, while the proportion of CD4+CD45+T cells and CD8+CD45+ T cells in CD45+ cells in the lymph nodes upregulated, the proportion of Treg cells in CD4+ T cells downregulated in lymph nodes, and the proportion of MDSCs in tumor tissues downregulated. CONCLUSION: DEX can inhibit tumor cells in vitro and in vivo. The mechanism is to inhibit the activation of mTOR signaling pathway by inhibiting the expression of c-Myc, further affecting the expression of key enzymes involved in glucose metabolism, especially PCK2. In addition, DEX has an inhibitory effect on the immune system, which may be the reason why DEX still has anti-tumor effect in normal mice.

Glioma stem cells reconstruct similar immunoinflammatory microenvironment in different transplant sites and induce malignant transformation of tumor microenvironment cells.

PURPOSE: This study aimed to examine whether the different tumor-transplanted sites could construct a similar immunoinflammatory microenvironment and to investigate the interactions between tumor microenvironment cells. METHODS: The red fluorescent protein-SU3 (SU3-RFP) or SU3 glioma stem cells (GSC) were inoculated into the brain, liver, abdominal cavity, and subcutis of green fluorescent protein (GFP)-nude mice. The tumor tissues were taken to observe the tissue cell distribution. The single cell suspension of tumor tissues was prepared and cultured, while the SU3-RFP cells were co-cultured with the cells from GFP-transgenic mice. The RFP+, GFP+, and RFP+/GFP+ cells were traced by fluorescence microscope, and their protein expressions were determined by Western blot analysis. The markers of immunoinflammatory cells, including F4/80, CD11b, CD11c, CD80, CD47, and SIRP-α, were determined by RT-PCR and immunocytochemistry assays, respectively. RESULTS: The xenograft models of all transplant sites were inducible, and the red tumor cells of tumor tissues were encircled by a great quantity of host-derived green cells, including immunoinflammatory cells with CD80, F4/80, CD11b, and CD11c expressions, which might generate the cell colonies and possess the pseudopodia. Additionally, the interactions between red tumor cells and green immunoinflammatory cells, including cell fusion process and yellow fusion cell formation, were observed in cultured cells. The fusion cells-derived B4 cells with expressions of CD47 and SIRP-α proteins had the strong proliferation ability and tumorigenic effect. CONCLUSIONS: The similar tumor immunoinflammatory microenvironment was constructed by GSC in different transplant sites, and the cell fusion indicated a malignant transformation of the tumor microenvironment cells.

Hyperbaric oxygen therapy sensitizes nimustine treatment for glioma in mice.

Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P < 0.05), 6.03 ± 1.47, 4.13 ± 1.82 (P < 0.05), 2.39 ± 0.25 (P < 0.05), and 1.43 ± 0.38 (P < 0.01), respectively. The expressions of TNF-α, MMP9, HIF-α, VEGF, NF-κB, and IL-1ß were associated with the infiltration of inflammatory cells and the inhibition rate of tumor cells. Hyperbaric oxygen therapy (HBOT) could inhibit glioma cell proliferation and inflammatory cell infiltration, and exert a sensitizing effect on ACNU therapy partially through enhancing oxygen pressure (PO2 ) in tumor tissues and lower expression levels of HIF-1α, TNF-α, IL-1ß, VEGF, MMP9, and NF-κB.

Establishment of a green fluorescent protein tracing murine model focused on the functions of host components in necrosis repair and the niche of subcutaneously implanted glioma.

Due to progress in the research of glioma stem cells and the glioma niche, development of an animal model that facilitates the elucidation of the roles of the host tissue and cells is necessary. The aim of the present study was to develop a subcutaneous xenograft green fluorescent protein nude mouse model and use this model to analyze the roles of host cells in tumor necrosis repair. Tumors derived from the human glioma stem/progenitor cell line SU3 were subcutaneously implanted in green fluorescent protein nude mice. The implanted tumors were then passed from animal to animal for 10 generations. Finally, subcutaneous xenografts were assayed with traditional pathology, immunopathological techniques and fluorescence photography. For each generation, the tumorigenicity rate was 100%. Subcutaneous xenografts were rich in blood vessels, and necrotic and hemorrhagic foci, which highly expressed hypoxia-inducible factor-1α, tumor necrosis factor, Ki-67, CD68 and CD11b. In the interstitial tissue, particularly in old hemorrhagic foci, there were numerous cells expressing green fluorescent protein, CD68 and CD11b. Green fluorescent protein nude mouse subcutaneous xenografts not only consistently maintained the high invasiveness and tumorigenicity of glioma stem/progenitor cells, but also consisted of a high concentration of tumor blood vessels and necrotic and hemorrhagic foci. Subcutaneous xenografts also expressed high levels of tumor microenvironment-related proteins and host-derived tumor interstitial molecules. The model has significant potential for further research on tumor tissue remodeling and the tumor microenvironment.