Yawen Pan

Objective: Atypical fibrous histiocytoma (AFH) is an uncommon intermediate-grade fibrohistiocytic tumor that typically arises in the dermis or superficial soft tissues. Primary involvement of the skull is exceedingly rare and poses significant diagnostic challenges. We report a rare case of primary AFH arising in the temporal bone of an adult patient and provide a focused review of previously reported skull-based cases to clarify its clinicopathologic features, diagnostic pitfalls, and management considerations. Methods: A 34-year-old man presented with progressive right-sided tinnitus and sensorineural hearing loss. Computed tomography and magnetic resonance imaging demonstrated an osteolytic temporal bone lesion with intracranial extension and compression of the adjacent temporal lobe. Gross total surgical resection was performed. Detailed histopathological evaluation and an extended immunohistochemical panel were used to establish the diagnosis. A literature review of reported skull AFH cases was conducted for comparison. Results: Histologic examination revealed a moderately cellular spindle-cell tumor arranged in fascicles and storiform patterns, accompanied by multinucleated giant cells, hemosiderin-laden macrophages, and reactive bone formation. Immunohistochemistry showed diffuse vimentin positivity, weak cytoplasmic CD68 expression, and a Ki-67 proliferation index of approximately 20%, with negative staining for epithelial, melanocytic, neural crest, smooth muscle, and Langerhans cell markers. These findings supported the diagnosis of atypical fibrous histiocytoma. Postoperatively, tinnitus improved, while hearing loss showed limited recovery. No evidence of recurrence was observed during follow-up. Conclusion: Primary AFH of the temporal bone is an exceptionally rare entity that can mimic other destructive skull lesions on imaging and intraoperative inspection. Accurate diagnosis relies on careful histopathologic evaluation and exclusion of histologic mimickers using a comprehensive immunohistochemical panel. Complete surgical excision remains the cornerstone of treatment, and long-term follow-up is recommended due to the tumor’s intermediate malignant potential.

Resistance to temozolomide (TMZ) chemotherapy is the main reason for treatment failure in patients with glioblastoma (GBM). In the present study, we investigated biochanin A (BCA) a potent sensitizer of TMZ in GBM. We observed that BCA significantly enhanced cell sensitivity to TMZ in vitro and in vivo. Mechanistically, the specific chemosensitizing effect of BCA is mediated by autophagy inhibition. Moreover, by performing a molecular docking analysis, we demonstrated that BCA interacts with AMPK residues and impairs autophagy by regulating the AMPK/ULK1 pathway. These results suggest that BCA is a potential therapeutic agent that sensitizes GBM to TMZ and provide new insight into its therapeutic potential in chemoresistant GBM.

Introduction Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection. We investigated the association between the expression level of CTSL and overall survival in Glioblastoma multiforme (GBM) patients, to better understand the possible route and risks of new coronavirus infection for patients with GBM. Methods The expression level of CTSL in GBM was analyzed using TCGA and CGGA databases. The relationship between CTSL and immune infiltration levels was analyzed by means of the TIMER database. The impact of CTSL inhibitors on GBM biological activity was tested. Results The findings revealed that GBM tissues had higher CTSL expression levels than that of normal brain tissues, which was associated with a significantly lower survival rate in GBM patients. Meanwhile, the expression level of CTSL negatively correlated with purity, B cell and CD8⁺ T cell in GBM. CTSL inhibitor significantly reduced growth and induced mitochondrial apoptosis. Conclusion According to the findings, CTSL acts as an independent prognostic factor and can be considered as promising therapeutic target for GBM.

Abnormal metabolism serves a critical role in glioblastoma (GBM). Biochanin A (BCA), a flavonoid phenolic compound found in edible and herbal plants, has antioxidative and antitumor activities. However, it remains unclear whether BCA has an effect on energy metabolism. The aim of the present study was to evaluate the anticancer effects and molecular mechanism of the effect of BCA on energy metabolism. We observed that BCA inhibited the growth of U251 cells by the mitochondria-mediated intrinsic apoptotic pathway. BCA treatment reduced metabolic function, repressed mitochondrial membrane potential, and increased the production of reactive oxygen species (ROS) in GBM. In addition, we found that BCA decreased aerobic glycolysis by inactivation of the AKT/mTOR pathway. Taken together, the results demonstrate that treatment with BCA inhibited the proliferation of GBM by regulating metabolic reprogramming.

CTSL is one of the SARS-entry-associated CoV-2's proteases and plays a key role in the virus's entry into the cell and subsequent infection. We investigated the association between the expression level of CTSL and overall survival in TCGA and CGGA databases, in order to better understand the possible route and risks of new coronavirus infection for patients with GBM. Meanwhile, the relationship between CTSL and immune infiltration levels was analyzed by means of the TIMER database. The impact of CTSL inhibitors on GBM biological activity was tested. The findings revealed that GBM tissues had higher CTSL expression levels than that of normal brain tissues, which was associated with a significantly lower survival rate in GBM patients. Meanwhile, CTSL was very negatively correlated with purity, B cell and CD8⁺ T cell in GBM. CTSL inhibitor significantly reduced U251 cell growth and invasion in vitro and induced mitochondrial apoptosis. According to the findings of this study, CTSL acts as an independent prognostic factor and can be considered as promising therapeutic target for GBM.

CD44 is involved in malignant processes including cell motility, tumor growth and angiogenesis. To explore the potential role of CD44 as a prognostic biomarker in low grade gliomas (LGG), the mRNA expression levels of CD44 in tissues from 12 patients with glioma were evaluated by microarray analysis. The mRNA level of CD44 in LGG and glioblastoma multiforme (GBM) were analyzed using datasets downloaded from the publicly available Oncomine database. Reverse transcription‑quantitative PCR and western blotting were used to further analyze the CD44 expression level in a set of 53 patients. Kaplan‑Meier analysis was performed to identify the prognostic roles of CD44 mRNA in LGG and GBM, with data obtained from the OncoLnc and Gene Expression Profiling Interactive Analysis databases and clinical follow‑ups. The present results revealed that CD44 mRNA expression levels were elevated in LGG and GBM compared with normal brain tissues. Furthermore, increased CD44 expression was associated with poor survival rates in LGG. The present study suggested that CD44 may act as an independent prognostic factor for LGG, and may be a potential therapeutic target for gliomas.

Certain microRNAs (miRNAs/miRs) may be used as prognostic biomarkers in various types of cancer. The purpose of the present study was to identify miRNAs that were abnormally expressed in glioma of different grades, and to evaluate their clinical implications in patients with glioma. The differentially expressed miRNAs were evaluated from the expression profiles of six glioma tissues (three low‑grade and three high‑grade gliomas) determined using a microarray platform. Reverse transcription‑quantitative polymerase chain reaction analysis was used to further verify the aberrant expression of the candidate miRNA in a set of 42 patients and 5 healthy controls. The miRNA target genes were predicted and the protein‑protein interaction network was generated; furthermore, functional enrichment analysis of the target genes in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed. Kaplan‑Meier curves and Log‑rank analysis, as well as multivariate Cox regression analysis were performed to assess the association of the candidate miRNA with patient survival. A total of 15 differentially expressed miRNAs, including 13 downregulated and 2 upregulated miRNAs, were identified by comparison of low‑grade and high‑grade glioma tissues. The miR‑374a expression of high‑grade gliomas was significantly lower than that of low‑grade gliomas (fold change, ‑4.43; P=0.027). The expression levels of miR‑374a gradually decreased with the increase of the pathological grade of glioma. Pearson's Chi‑square test was used to determine the association of miR‑374a expression with several clinicopathological factors. Furthermore, low expression of miR‑374a was determined to be an independent prognostic marker and that it was significantly associated with overall survival (P=0.0213). GO and KEGG pathway analysis revealed that the target genes of miR‑374a may be involved in the regulation of the RNA polymerase II promoter and mTOR signaling pathway. The four hub genes (CCND1, SP1, CDK4, CDK6) were also identified by PPI network analysis. In conclusion, the present study indicated that miR‑374a may be used as a promising prognostic biomarker for the screening of high‑risk populations and for the assessment of the prognosis of patients with glioma.