Unveiling the intratumoral microbiota within cancer landscapes.

Recent advances in cancer research have unveiled a significant yet previously underappreciated aspect of oncology: the presence and role of intratumoral microbiota. These microbial residents, encompassing bacteria, fungi, and viruses within tumor tissues, have been found to exert considerable influence on tumor development, progression, and the efficacy of therapeutic interventions. This review aims to synthesize these groundbreaking discoveries, providing an integrated overview of the identification, characterization, and functional roles of intratumoral microbiota in cancer biology. We focus on elucidating the complex interactions between these microorganisms and the tumor microenvironment, highlighting their potential as novel biomarkers and therapeutic targets. The purpose of this review is to offer a comprehensive understanding of the microbial dimension in cancer, paving the way for innovative approaches in cancer diagnosis and treatment.

Deciphering the link: ferroptosis and its role in glioma.

Glioma, as the most frequently occurring primary malignancy in the central nervous system, significantly impacts patients' quality of life and cognitive abilities. Ferroptosis, a newly discovered form of cell death, is characterized by significant iron accumulation and lipid peroxidation. This process is fundamentally dependent on iron. Various factors inducing ferroptosis can either directly or indirectly influence glutathione peroxidase, leading to reduced antioxidant capabilities and an increase in lipid reactive oxygen species (ROS) within cells, culminating in oxidative cell death. Recent research indicates a strong connection between ferroptosis and a range of pathophysiological conditions, including tumors, neurological disorders, ischemia-reperfusion injuries, kidney damage, and hematological diseases. The regulation of ferroptosis to intervene in the progression of these diseases has emerged as a major area of interest in etiological research and therapy. However, the exact functional alterations and molecular mechanisms underlying ferroptosis remain to be extensively studied. The review firstly explores the intricate relationship between ferroptosis and glioma, highlighting how ferroptosis contributes to glioma pathogenesis and how glioma cells may resist this form of cell death. Then, we discuss recent studies that have identified potential ferroptosis inducers and inhibitors, which could serve as novel therapeutic strategies for glioma. We also examine the current challenges in targeting ferroptosis in glioma treatment, including the complexity of its regulation and the need for precise delivery methods. This review aims to provide a comprehensive overview of the current state of research on ferroptosis in glioma, offering insights into future therapeutic strategies and the broader implications of this novel cell death pathway in cancer biology.

CAR-T cell therapy for hematological malignancies: History, status and promise.

For many years, the methods of cancer treatment are usually surgery, chemotherapy and radiation therapy. Although these methods help to improve the condition, most tumors still have a poor prognosis. In recent years, immunotherapy has great potential in tumor treatment. Chimeric antigen receptor T-cell immunotherapy (CAR-T) uses the patient's own T cells to express chimeric antigen receptors. Chimeric antigen receptor (CAR) recognizes tumor-associated antigens and kills tumor cells. CAR-T has achieved good results in the treatment of hematological tumors. In 2017, the FDA approved the first CAR-T for the treatment of B-cell acute lymphoblastic leukemia (ALL). In October of the same year, the FDA approved CAR-T to treat B-cell lymphoma. In order to improve and enhance the therapeutic effect, CAR-T has become a research focus in recent years. The structure of CAR, the targets of CAR-T treatment, adverse reactions and improvement measures during the treatment process are summarized. This review is an attempt to highlight recent and possibly forgotten findings of advances in chimeric antigen receptor T cell for treatment of hematological tumors.

CD47 as a promising therapeutic target in oncology.

CD47 is ubiquitously expressed on the surface of cells and plays a critical role in self-recognition. By interacting with SIRPα, TSP-1 and integrins, CD47 modulates cellular phagocytosis by macrophages, determines life span of individual erythrocytes, regulates activation of immune cells, and manipulates synaptic pruning during neuronal development. As such, CD47 has recently be regarded as one of novel innate checkpoint receptor targets for cancer immunotherapy. In this review, we will discuss increasing awareness about the diverse functions of CD47 and its role in immune system homeostasis. Then, we will discuss its potential therapeutic roles against cancer and outlines, the possible future research directions of CD47- based therapeutics against cancer.

ELF1 Transcription Factor Enhances the Progression of Glioma via ATF5 promoter.

A key transcriptional activator, activating transcription factor 5 (ATF5), is aberrantly overexpressed in glioma and supports both poor prognosis and antiapototic potential. Unfortunately, data on ATF5 is largely based on its regulatory mechanism. Further investigation of the upstream regulatory factor for ATF5 transcription in glioma is required. Clinical data for patients with diagnosed glioma were obtained from The Cancer Genome Atlas (TCGA). Additionally, transcription factors potentially regulating the ATF5 promoter in glioma were screened with bioinformatics. A further experimental study was performed to investigate both the role of E74-like factor 1 (ELF1) and the binding of ELF1 and the ATF5 promoter in glioma. We show that ATF5 expression is upregulated in glioma tissues and associated with tumor malignancy and worse prognosis. As a putative upstream regulator, silencing ELF1 inhibits glioma cell growth and migration with ATF5 involvement. Moreover, ELF1 upregulation is also associated with poor prognosis in glioma. Importantly, the luciferase assay and chromatin immunoprecipitation (ChIP) reveal that the ATF5 gene promoter is essential for ELF1-dependent activation of ATF5 gene transcription. These results indicate that a high expression of ELF1 may be related to the malignant behavior of human glioma and ELF1 promotes glioma development mediated by transactivation of the ATF5 gene.

Craniotomy for a Large and Aggressive De Novo Cavernous Malformation Resection in the Basal Ganglia Region.

BACKGROUND: Cerebral cavernous malformations (CCMs) are present in up to 0.5% of the general population. Although CCMs have been considered congenital lesions, numerous reports have observed de novo formations in patients with the familial form of CCM and in patients after cranial radiotherapy. Outside of these circumstances, there is scant evidence as to the potential etiologies of CCM. CASE DESCRIPTION: We present a 48-year-old woman with a medical history of endometrial hyperplasia concomitant endometrial polyps demonstrating a large de novo CCM, which grew to a large size in a period of 20 months. A previous magnetic resonance imaging scan showed no abnormalities. This CCM exhibited aggressive biological behavior characterized by recurrent overt bleeding and seizure. Histopathologic analysis confirmed the diagnosis of CCM. Here, we discuss the growth mechanisms of these lesions. CONCLUSIONS: Given the patient's medical history and imaging findings, we propose that de novo CCMs can arise directly from angiogenic proliferation, secondary to BCL-2 overexpression from underlying causes. We hypothesize that inappropriate secretion of estrogen could have set off a genetic cascade with attendant endothelial proliferation. Thus, female hormones may play an important role in influencing the biological behavior of CCMs. The relationship between estrogen and CCM needs further investigation.

Improved Microvascular Decompression in Treating Trigeminal Neuralgia: Application of Nest-Shaped Teflon Fibers.

OBJECTIVE: To develop an improved technique for microvascular decompression (MVD) surgery using nest-shaped Teflon fibers. METHODS: Eighteen consecutive patients with trigeminal neuralgia (TN) who underwent MVD using nest-shaped Teflon fibers between January 2012 and December 2013 were included in this investigation. During the surgery, the Teflon prosthesis was formed into a nest shape by gently pushing it from the center toward the periphery. Immediate postoperative outcomes were evaluated using a numerical rating scale score, and patients were followed up for recurrence. RESULTS: Immediately after the surgery, pain was completely relieved in 16 patients (88.9%) and partially relieved in 2 patients (11.1%). Seven patients (38.9%) developed postoperative complications. All complications were successfully mitigated before discharge. The patients were followed up for 2.0-3.4 years. During follow-up, recurrence was observed in 2 patients (11.1%). No Teflon adhesion or Teflon-induced granuloma was found. CONCLUSIONS: The nest-shaped Teflon fibers in MVD surgery for TN is safe and applicable. The long-term outcomes and the comparison between hollow nest-shaped implants and the standard cigar-shaped implants should be assessed in future investigations with larger sample sizes.

Expression and prognostic significance of CTBP2 in human gliomas.

Deregulated expression of C-terminal-binding protein 2 (CTBP2) has been observed previously in a number of tumors, such as hepatocellular carcinoma and prostatic cancer, in the colorectal cancer SW480 cell line and in the human embryonic kidney 293 cell line. In the present study, western blot analysis and immunohistochemistry were performed to investigate whether gliomas exhibit deregulated CTBP2 expression. Kaplan-Meier survival analyses were performed to evaluate the associations between CTBP2 expression, clinicopathological data and patient survival in glioma patients. The results revealed that CTBP2 expression was significantly upregulated in high grade glioma tissues compared with that in low grade glioma and normal brain tissues. Furthermore, increased CTBP2 expression in gliomas was significantly associated with a higher World Health Organization (WHO) tumor grade (P<0.005) and poorer disease-specific survival (P<0.005). In conclusion, these results suggest that CTBP2 may act as an intrinsic regulator of progression in glioma cells and thus may serve as an important prognostic factor for the disease.

Alpinetin targets glioma stem cells by suppressing Notch pathway.

Glioma is among the most common human malignancies with poor prognosis. Glioma stem cells (GSCs) are the culprit of glioma, suggesting that GSCs are potential therapeutic targets. Notch signaling pathway plays a pivotal role for the function of GSCs, implying that suppression of Notch pathway may be an effective strategy for GSC-targeting therapy. In this study, we found that alpinetin, a natural compound, can suppress the proliferation and invasiveness of GSCs and induce apoptosis in GSCs. Immunoblot analysis and luciferase assay revealed that Notch signaling was suppressed by alpinetin. Furthermore, restoration of Notch signaling activity rescued the effect of alpinetin on GSC's function. The anti-tumor activity of alpinetin was further confirmed in an animal model. Collectively, targeting of GSC by alpinetin is an effective strategy for glioma therapy.

The decreased expression of miR-625 predicts poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Previous study has detected the expression of miR-625 in esophageal squamous cell carcinoma (ESCC) and found that miR-625 was related to tumor depth, stage, and metastasis of ESCC. However, the prognostic value of miR-625 in ESCC has not yet been reported. METHODS: Real-time quantitative PCR was employed to measure the expression level of miR-625 in clinical ESCC tissues. Survival curves were made using the Kaplan-Meier method, and the log rank test was used to analyze the differences between clinicopathological characteristics and survival in ESCC patients. RESULTS: The expression level of miR-625 in ESCC tissues was significantly lower than that in adjacent non-tumor tissues (1.00 ± 0.38 vs. 3.25 ± 1.83, P < 0.0001). Low miR-625 expression was observed to be closely correlated with lymph node metastasis (P = 0.01), distant metastasis (P = 0.007), tumor differentiation (P = 0.04), and advanced TNM stage (P = 0.005). The 5-year overall survival rate in the low expression group was 38.1%, compared with 68.8% in the high expression group (log-rank test, P = 0.001). Multivariate Cox regression analysis showed that miR-625 expression level (HR = 3.72, 95% CI: 1.36-8.78, P = 0.005) was an independent factor in predicting the overall survival of ESCC patients. CONCLUSION: Our findings provide the convincing evidence for the first time that the down-regulation of miR-625 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of ESCC patients.

miR-30 overexpression promotes glioma stem cells by regulating Jak/STAT3 signaling pathway.

Malignant glioma is the most common intracranial tumor with poor prognosis. It is well believed that glioma stem cells (GSCs) are responsible for the initiation and progression of glioma. Janus kinase/signal transducer and activator of transcription (Jak/STAT3) pathway plays a key role in the functions of GSCs. However, the regulatory mechanism of Jak/STAT3 pathway has not been completely elucidated. This study employed multidisciplinary approaches to investigate the upstream regulators of Jak/STAT3 signaling in GSCs. miR-30 was found to be overexpressed in the GSCs derived from U-87 MG and primary glioma cells, compared with non-stem-cell-like glioma cells and normal cells. Downregulation of miR-30 was able to suppress Jak/STAT3 pathway and reduce the tumorigenecity of GSCs. miR-30 decreased the expression of suppressor of cytokine signaling 3 (SOCS3) expression by targeting 3'UTR of its mRNA. The silencing of SOCS3 abolished the effect of miR-30 downregulation on GSCs. Collectively, there is a regulatory pathway consisting of miR-30, SOCS3, and Jak/STAT3 in GSCs, and targeting this pathway may be a promising strategy to treat glioma.

miR-155 contributes to the progression of glioma by enhancing Wnt/ß-catenin pathway.

As the most common brain tumor, glioma is featured with poor prognosis due to its resistance to current therapeutic strategies. The elucidation of etiology is believed to facilitate the development of novel effective anti-glioma treatment modalities. As a confirmed oncogenic microRNA (miRNA) in many other types of cancers, the role of miR-155 in glioma is still unknown. This study is aimed to study the role of miR-155 in the progression of glioma. Our results revealed that miR-155 was overexpressed in the collected glioma specimen, compared with noncancerous brain tissues. The suppression of miR-155 attenuated the proliferation of glioma cells and the activation of Wnt pathway. Silencing miR-155 was also able to suppress the growth of U-87 MG glioma xenografts in mice. Pearson analysis indicated that miR-155 level was inversely correlated with the abundance of HMG-box transcription factor 1 (HBP1), a strong Wnt pathway inhibitor, in glioma samples. Further experiments confirmed that miR-155 suppressed the expression of HBP1 by targeting the putative miRNA recognition elements (MREs) within its messenger RNA (mRNA) 3' untranslated region (UTR). Furthermore, HBP1 small interfering RNA (siRNA) abolished the effect of miR-155 suppression on the proliferation of glioma and the activation of Wnt pathway. Taken together, miR-155 promoted the progression of glioma by enhancing the activation of Wnt pathway. Thus, targeting miR-155 may be an effective strategy for glioma treatment.

miR-96/HBP1/Wnt/ß-catenin regulatory circuitry promotes glioma growth.

We found that miR-96 is overexpressed in glioma, and its level inversely correlates with the survival of patients. The reduction in miR-96 abundance suppresses the proliferation and colony formation of glioma cells. The tumorigenicity of U-87 MG cells is reduced by miR-96 silencing. miR-96 contributes to the activation of Wnt/ß-catenin pathway in glioma cells. HMG-box transcription factor 1 (HBP-1), a Wnt/ß-catenin pathway inhibitor, is suppressed by miR-96. The reactivation of Wnt/ß-catenin signaling causes an increase in the proliferation of glioma cells, and a decrease in miR-96 expression. On the other hand, HBP1 silencing promotes miR-96 expression. Collectively, miR-96 contributes to the progression of glioma by enhancing the activation of the Wnt/ß-catenin pathway, and the miR-96/HBP1/Wnt/ß-catenin regulatory circuitry promotes the proliferation of glioma cells.

Diagnosis and microsurgical treatment of cavernous sinus hemangioma.

To investigate the diagnosis and microsurgical treatment of cavernous sinus hemangioma, the clinical data, including pathology, epidemiology, medical imaging, operation procedure, and post-operational complication of 12 cavernous sinus hemangioma patients undergoing operations in Affiliated Hospital of Medical College of Qingdao University from 1999 to 2008, were analyzed. There were 2 males and 10 females. The patients were aged from 28 to 61 years. Headaches and deficits of the cranial nerves coursing through the cavernous sinus were the principal symptoms at presentation. The common clinical manifestations were visual loss, diplopia, facial numbness, and extraocular muscle palsy. The radiological features in all patients were similar with a characteristic pattern of extension and encasement of carotid artery. CT showed the lesion as hypodense to isodense with marked enhancement after contrast administration. T1-weighted MR imaging showed the lesions as hypointense with marked enhancement after contrast administration. T2-weighted MR imaging showed the lesions as hyperintense. The maximum size of the lesion was 9 to 57 mm (mean 45 mm). Basal pterional craniotomies were used for eight patients. Orbitozygomatic osteotomies were used for two patients. Pterional approach was used for two patients. The lesions were removed through incising the lateral wall of the cavernous sinus. The tumor was totally removed in five cases, subtotally removed in four cases, and partially removed in two cases. The main post-operational complications included oculomotor nerve paralysis (four cases) and trigeminal nerve lesions (three cases). No postoperative death occurred. Operation is the best choice for cavernous sinous hemangioma. It was helpful to control bleeding through intradura and incising the lateral wall of the cavernous sinus.