A rare case of primary central nervous system histiocytic sarcoma harboring a novel ARHGAP45::BRAF fusion: a case report and literature review.

INTRODUCTION: Patients with histiocytic sarcoma occurring in the central nervous system (CNS) are rare and have a very poor prognosis. The increased use of molecular diagnostic approaches in solid tumors has brought more opportunities for the diagnosis and treatment of central nervous system histiocytic sarcoma (CNSHS). CASE DESCRIPTION: A 9-year-old girl was admitted to the hospital with pain in her head and neck, as well as vomiting. Imaging scans showed a prominent abnormality in the anterior falciform region, and histopathology revealed the presence of CD68 (+) and CD163 (+) cells, leading to a preliminary diagnosis of primary intracerebral CNSHS. Molecular profiling tests identified a new variant of ARHGAP45::BRAF fusion in this case, which has not been reported in any other tumor. The patient underwent surgical removal of the tumor and will require long-term monitoring. CONCLUSION: The presence of the BRAF point mutation, predominantly BRAF p.V600E, has been documented in prior literature of CNSHS. This is the first case of pediatric histiocytic sarcoma in the anterior falciform region who has a unique ARHGAP45::BRAF fusion. The findings of our study indicate that a broader range of molecular assays should be employed in the diagnosis of CNSHS and opens up new possibilities for the treatment of the patient.

Efficacy and safety of acupuncture for hand osteoarthritis: study protocol for a multi-center, randomized, sham-controlled clinical trial.

BACKGROUND: Hand osteoarthritis (OA) is a prevalent disorder in the general population. Patients with hand OA often report symptoms of pain, stiffness, and functional limitations, which cause clinical burden and impact on quality of daily life. However, the efficacy of current therapies for hand OA is limited. Other therapies with better effects and less adverse events are in urgent need. Acupuncture is well known for analgesia and has been proved effective in treating basal thumb joint arthritis. This study aims to clarify the efficacy and safety of acupuncture treatment for clinical symptomatic improvement of hand OA. METHODS: This will be a sham-controlled, randomized, multi-center clinical trial. A total of 340 participants will be recruited and randomly allocated to either traditional acupuncture group or sham acupuncture group. All participants will receive 12 treatment sessions over 4 weeks and 2 follow-up assessments in the following 3 months at week 8 and week 16. The primary outcome will be the proportion of responders at week 5. Secondary outcomes will include visual analog scale, Australian Canadian Osteoarthritis Hand Index, Functional Index for hand OA, the number of symptomatic joints, hand grip strength and pinch strength, global assessment, the World Health Organization Quality of Life abbreviated version and expectations. Safety will be evaluated during the whole process of the trial. All outcomes will be analyzed following the intention-to-treat principle. DISCUSSION: This prospective trial will provide high-quality evidence on evaluating the efficacy and safety of acupuncture treatment for hand OA. Results of this trial might contribute in offering a new option to clinical recommendations. Trial registration ClinicalTrials.gov Identifier: NCT05267093. Registered 23 February 2022.

Genetic Variations of CARMN Modulate Glioma Susceptibility and Prognosis in a Chinese Han Population.

Background: This study aimed to evaluate the relationship between CARMN polymorphisms and glioma risk and prognosis in a Chinese Han population. Methods: Seven single nucleotide polymorphisms (SNPs) in CARMN were genotyped among 592 glioma patients and 502 healthy controls. Log-additive models were used for risk assessment by the odds ratios (ORs) and 95% confidence intervals (CIs). Univariate and multivariate Cox regression analysis was applied to calculate Hazard ratios (HRs) and 95% CIs for prognosis assessment. Results: CARMN rs13177623 was a protective factor for glioma susceptibility (OR = 0.78, p = 0.043). In addition, rs13177623, rs11168100, rs12654195 and rs17796757 were associated with the risk of glioma among the subgroup stratified by age or gender. We also found that G rs13177623G rs12654195 haplotype was related to the decreased risk of glioma (OR = 0.61, p = 0.005). Importantly, rs13177623 [overall survival (OS): HR = 0.83, p = 0.047, and progression free survival (PFS): HR = 0.82, p = 0.031], rs12654195 (OS: HR = 0.64, p = 0.005 and PFS: HR = 0.65, p = 0.007) and rs11168100 (OS: HR = 0.71, p = 0.035) were associated with a better prognosis for glioma, especially in grade I-II glioma. In patients with grade III-IV glioma, rs17796757 polymorphism presented an improved OS. Conclusion: Our results firstly reported the contribution of CARMN variants (rs11168100, rs12654195, rs13177623, and rs17796757) to the susceptibility and prognosis of glioma in a Chinese Han population, which provided a novel insight on the relationship between CARMN gene and glioma tumorigenesis.

ARRDC3 polymorphisms may affect the risk of glioma in Chinese Han.

This study ascertained to explore the potential contribution of ARRDC3 polymorphisms in the risk and prognosis of glioma. One thousand sixty-one patients and healthy controls were conducted to assess whether ARDC3 polymorphism was associated with glioma risk and prognosis. Four sites in ARRDC3 were selected and genotyped in MassARRAY platform. The calculated odd ratios and 95% confidence intervals from logistic regression were applied for risk assessment. The relationship between ARRDC3 variants and glioma prognosis was evaluated using log-rank test, Kaplan-Meier analysis, and so on. Also, false-positive report probability (FPRP) and statistical power were also assessed. Our findings suggested the negative role of ARRDC3 polymorphisms in the glioma risk. We also found the effect of candidate SNPs in ARRDC3 on the susceptibility to glioma was dependent on the age, gender, and histology of glioma patients. The results suggested that the genetic polymorphisms of ARRDC3 were related to an increased risk of glioma.

Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC50 dose was obtained at 30 µM. For further studies, we selected the 30 µM IC50 dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.

Genetic variants of CYP4F12 gene are associated with glioma susceptibility.

Glioma is a common and fatal primary malignant tumor of the central nervous system, and its prognosis is poor. To determine the susceptibility markers of gliomas in Chinese population we conducted a genome-wide association study (GWAS) of glioma in the Han Chinese population, with a total of 485 glioma cases and 485 controls. Genotyping was conducted using the Applied Biosystems Axiom Precision Medicine Diversity Array. Besides, we carried out imputation using IMPUTE 2.0 software, and the 1000 Genomes Phase 3 was used as the reference panel. The logistic regression model was used to analyze the association of each SNP with glioma risk, assuming an additive genetic model, which was implemented in PLINK version 1.9. Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression analysis with adjustment for age and gender. The results revealed that the SNP (rs688755) in the exon region of CYP4F12 at 19p13.12 reached genome-wide significance associated with gliomas (P = 2.35 × 10-8 , OR = 3.55, 95% CI = 2.20-5.74). Our findings provide deeper insight into the genetic contribution to glioma in different populations.

The ADCY9 genetic variants are associated with glioma susceptibility and patient prognosis.

PURPOSE: Genetic factor is a risk factor in glioma occurrence. This study was designed to detect the effect of ADCY9 polymorphisms on glioma risk and prognosis. METHODS: We performed a case-control study of 1080 participants (584 cases and 496 controls) to assess the relationship of ADCY9 polymorphisms with the risk and prognosis of glioma among the Chinses Han population. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the relationship between ADCY9 variants and glioma risk. The correlation of SNPs with survival was analyzed by the Cox regression model. RESULTS: Our study showed that rs2230742 and rs2531992 polymorphisms played protective roles in glioma susceptibility (OR 0.65, p = 0.001; OR 0.73, p = 0.038, respectively). While rs2230742 significantly increased the susceptibility of III-V grade glioma patients (OR 1.50, p = 0.036). Haplotype analysis revealed that Crs879620Ars2230742Ars2230741 haplotype was related to a significantly decreased glioma risk (OR 0.65, p = 0.002). Notably, rs2531995 and rs879620 polymorphisms significantly enhanced death risk in high-grade glioma patients (hazard ratio [HR] 1.36, p = 0.041; HR 1.37, p = 0.042; respectively). For rs2230742 and rs2531992 SNPs, glioma patients had a worse prognosis (HR 2.30, p = 0.021; HR 2.30, p = 0.021; respectively). We further observed that age, chemotherapy, and surgical scope can affect the glioma prognosis. CONCLUSION: We firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.

miR-188 Inhibits Glioma Cell Proliferation and Cell Cycle Progression Through Targeting ß-Catenin.

MicroRNAs (miRNAs) play important roles in several human cancers. Although miR-188 has been suggested to function as a tumor repressor in cancers, its precise role in glioma and the molecular mechanism remain unknown. In the present study, we investigated the effect of miR-188 on glioma and explored its relevant mechanisms. We found that the expression of miR-188 is dramatically downregulated in glioma tissues and cell lines. Subsequent investigation revealed that miR-188 expression was inversely correlated with ß-catenin expression in glioma tissue samples. Using a luciferase reporter assay, ß-catenin was determined to be a direct target of miR-188. Overexpression of miR-188 reduced ß-catenin expression at both the mRNA and protein levels, and inhibition of miR-188 increased ß-catenin expression. Moreover, we found that overexpression of miR-188 suppressed glioma cell proliferation and cell cycle G1-S transition, whereas inhibition of miR-188 promoted glioma cell proliferation. Importantly, silencing ß-catenin recapitulated the cellular and molecular effects seen upon miR-188 overexpression, which included inhibiting glioma cell proliferation and G1-S transition. Taken together, our results demonstrated that miR-188 inhibits glioma cell proliferation by targeting ß-catenin, representing an effective therapeutic strategy for glioma.

Association between epidermal growth factor gene rs4444903 polymorphism and risk of glioma.

The development of glioma is a complex process which may be influenced by many factors including the epidermal growth factor (EGF) gene polymorphism. Previous studies showed that EGF rs4444903 polymorphism could result in increased risk of tumorigenesis in multiple human cancers, but published data regarding the association between EGF rs4444903 polymorphism and glioma risk were inconsistent. To derive a more precise estimation of the association between EGF rs4444903 polymorphism and glioma risk, we performed a systematic review and meta-analysis of previous published studies. PubMed, Embase, and the Wanfang databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Ten published studies with 1,891 glioma cases and 2,836 controls were finally included into the study. Overall, there was a significant association between EGF rs4444903 polymorphism and glioma risk in all four genetic models (the allele model: OR=1.25, 95 % CI 1.15-1.37, P<0.001; the codominant model: OR=1.65, 95 % CI 1.36-1.99, P<0.001; the dominant model: OR=1.27, 95 % CI 1.12-1.44, P<0.001; the recessive model: OR=1.48, 95 % CI 1.25-1.75, P<0.001). Subgroup analyses by ethnicity showed that EGF rs4444903 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In conclusion, the results suggest that there is a significant association between EGF rs4444903 polymorphism and glioma risk, and genotypes of EGF rs4444903 mutation contribute to increased host susceptibility to glioma.

Correlation of microRNA-375 downregulation with unfavorable clinical outcome of patients with glioma.

BACKGROUND AND AIM: MicroRNA-375 (miR-375) is frequently demonstrated to be frequently dysregulated and functions as a tumor suppressor or an oncogene in different cancer types. However, its roles in human gliomas have not been reported. The aim of this study was to investigate the expression pattern and clinical significance of miR-375 in patients with gliomas. METHODS: Real-time quantitative RT-PCR assay was performed to detect miR-375 expression in human gliomas and non-neoplastic brain tissues. Then, the association of miR-375 expression with clinicopathological factors and prognosis of glioma patients was also statistically analyzed. RESULTS: miR-375 expression was significantly decreased on average in glioma tissues relative to non-neoplastic brain tissues (P<0.0001) with ascending pathological grade. Then, the low miR-375 expression in glioma tissues was significantly associated with advanced pathological grade (P=0.003) and low Karnofsky performance score (KPS, P=0.01). Moreover, both univariate and multivariate Cox regression analyses determined that loss of miR-375 expression effectively predicted the decreased overall survival in patients with gliomas. CONCLUSIONS: These findings offer the first convinced evidence that the downregulation of miR-375 expression in human gliomas may play an inhibitory role during the tumor development. This miRNA might function as a candidate unfavorable prognostic marker for human gliomas.