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   2022| April-June  | Volume 5 | Issue 2  
    Online since July 26, 2022

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Interactive relationship between neuronal circuitry and glioma: A narrative review
Jie Liu, Wei Shi, Yu Lin
April-June 2022, 5(2):43-49
Glioma is the most common primary central nervous system tumor. Despite extensive basic research on the tumor, the overall therapeutic effect of glioma remains unsatisfactory. Glioma grows within the framework of complex neural circuitry, which influences both neural network and tumor biology. On the one hand, the growth of gliomas continuously invades and destroys normal neural structures, which stimulate the dynamic remodeling of neural networks to maintain neural function. On the other hand, glioma can also induce neurons to form synaptic connections with it to promote tumor growth. Interventions targeting the interaction between gliomas and the neuronal circuitry provide opportunities for both tumor therapy and neuroplasticity at the same time. Noninvasive brain stimulation (NiBS) technology can actively regulate the excitability of targeted brain regions which can actively induce the remodeling of neural function and may perturb the interference of neuronglioma synapses. This article will review the interaction between gliomas and neural networks, including tumor-induced neuroplasticity, neuron-glioma synaptic connections, and the application and prospect of NiBS techniques.
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The role of collagens in glioma: A narrative review
Yi Wang, Toshiya Ichinose, Mitsutoshi Nakada
April-June 2022, 5(2):50-55
Glioma is the most common brain tumor in the central nervous system and characterized by diffuse invasion into adjacent brain tissue. The extracellular matrix (ECM) is an essential component of the tumor microenvironment and it contributes to tumor progression through close interactions with glioma cells. Accumulated evidence has indicated that collagen levels, which are the most critical components of the ECM, are elevated in gliomas and collagen contributes to glioma progression. In this review, we provide a comprehensive summary of the roles of various collagens in glioma. A better understanding of the interactions of various collagens with glioma cells may provide new therapeutic strategies for gliomas.
  1,162 141 -
Postoperative radiotherapy with concomitant temozolomide plus anlotinib for newly diagnosed glioblastoma: Study protocol for a multicenter, double-blind, randomized phase II trial
Yuanyuan Chen, Baiqiang Dong, Guihong Liu, Pengfei Sun, Meihua Li, Xuejun Yang, Shiyu Feng, Liang Wang, Yonghong Hua, Ming Zhao, Yanhui Liu, Juntao Ran, Li Qiao, Xueguan Lu, Hao Jiang, Deqiang Mao, Junxin Wu, Xianming Li, Wei Zheng, Zhigang Liu, Song Lin, Meiling Deng, Qunying Yang, Chengcheng Guo, Jing Li, Zhong-ping Chen
April-June 2022, 5(2):69-76
Background and Aim: Postoperative radiotherapy with concomitant temozolomide (TMZ) followed by ≤ six cycles of adjuvant TMZ chemotherapy (Stupp regimen) is the standard treatment for newly diagnosed glioblastoma (GBM); however, its effectiveness is limited. Anlotinib inhibits both tumor angiogenesis and tumor cell proliferation by targeting multiple kinases, and showing promising results in preclinical GBM models. We designed a Phase II trial to assess the efficacy and safety of the Stupp regimen plus anlotinib. Methods/Design: This is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib (Stupp regimen + anlotinib) or placebo (Stupp regimen + placebo). Postoperative patient recruitment will begin in July 2021, the analysis of primary outcome measures will be completed in July 2023, and the study will finish in July 2024. Major eligibility criteria include histologically confirmed newly diagnosed GBM and an Eastern Cooperative Oncology Group performance score ≤2. Other criteria for inclusion include age ≥18 years and lack of significant comorbidity. In this study, the primary endpoint will be the median progression-free survival (PFS). Secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity. The protocol has received approval from Sun Yat-sen University Cancer Center Ethics Committee (Approval No. B2021-073-01; approved on April 19, 2021). Discussion: Updated treatment modalities are required for newly diagnosed GBM. Our proposed treatment modality of the Stupp regimen combined with anlotinib therapy are waiting conclusion. Trial Registration: This study was registered with ClinicalTrials.gov under identifier NCT04959500 on July 13, 2021.
  1,056 79 -
Overcoming T-cell exhaustion in glioblastoma: A narrative review
Xuya Wang, Xisen Wang, Jiabo Li
April-June 2022, 5(2):56-61
Immunotherapy is typically ineffective against glioblastoma (GBM) due to inherent and adaptive resistance. Initial immunotherapy results for GBM have been disappointing. In this regard, T-cell exhaustion is a major barrier to successful treatment. The recognition of exhausted CD8+ T cell (Tex) pedigree is currently undergoing a paradigm shift. This review introduces major findings in this field to provide an up-to-date perspective on epigenetic, transcriptional, metabolic, and spatial heterogeneity, as well as interactions with tumor microenvironment cells of anti-tumoral CD8+ Tex from the following aspects: (i) Epigenetic and transcriptional mechanisms underlying T-cell exhaustion, (ii) Metabolic factors underpinning T-cell exhaustion, (iii) Contribution of multiple cell types to T-cell exhaustion, (iv) Occurrence of T-cell exhaustion at multiple locations, and (v) T-cell exhaustion may not always be terminal. These novel insights afford a wide range of new therapeutic approaches to overcome T-cell exhaustion in GBM.
  1,010 120 -
Advanced modalities and surgical theories in glioma resection: A narrative review
Jiahe Guo, Yiming Li, Kai Zhang, Jiabo Li, Ping Liu, Haolang Ming, Yi Guo, Shengping Yu
April-June 2022, 5(2):62-68
Surgical resection is the core of the comprehensive treatment of glioma. However, with infiltrative growth features, glioma often invades the surrounding area, making surgical resection more difficult. This review introduces relevant topics presented at the World Federation of Neurosurgical Societie Foundation Asian Congress of Neurological Surgeons (ACNS) Minimally Invasive Neurosurgery Web Seminar in 2022. First, we review assistive surgical techniques' characteristics, advantages, and disadvantages. Second, we summarize some state-of-the-art surgical views in glioma resection. Advanced modalities and surgical theories in glioma resection make better “maximum safe resection” achievable.
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Cerebral CD1a positive Rosai–Dorfman disease with coexistent granulomatous angiitis: A case report
Sweety Vijay Shinde, Asha Sharad Shenoy
April-June 2022, 5(2):77-79
Rosai–Dorfman disease (RDD) is a nonneoplastic histiocytic proliferation. RDD is CD1a negative as opposed to Langerhans cell histiocytosis (LCH). The lesion was positive for CD1a immunohistochemistry in our RDD patient, suggesting an overlap with LCH. In addition, our case exhibited granulomatous angiitis (GA) on microscopy. We report the first triad of coexistent intracranial RDD-LCH-GA. A 30-year-old man presented with seizures, limb weakness, and violent behavior for 3 months. There was no fever, lymphadenopathy, or hepatosplenomegaly. Laboratory test results were normal. Radioimaging revealed an 8.6 cm × 7.4 cm × 3.2 cm mass in the parietotemporal lobe. It was hypointense on T1W1 and hypointense on T2W1, suggestive of glioma or tumefactive demyelination. A subtotal resection was performed. Histopathology exhibited mature lymphocytes, plasma cells, and histiocytes with emperipolesis. Vessels showed transmural granulomatous inflammation. Fungal and mycobacterial stains were negative. Immunohistochemistry revealed positivity for CD68, S100, and CD1a. The patient refused to undergo postoperative adjuvant radiotherapy. He remained asymptomatic for 6 months but was lost to follow-up thereafter. RDD-LCH concurrence may represent a clonal transformation in a common precursor histiocyte. Coexistent GA requires resection followed by steroid or cyclophosphamide therapy to prevent disease progression.
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