Meningioma is a neoplasm arising from arachnoid cap cells and an important group of tumors of the meninges. The extent of surgical resection is one of the most important factors predicting recurrence along with histologic grading which in turn depends on factors such as the tumor site, vascularity, and peritumoral brain edema.

This study aimed to report our experiences with the safety and reliability of frameless stereotactic brain biopsy, including eloquent areas and small-sized lesions.

Identifying meningiomas that behave aggressively has proven challenging based on histopathology alone. Several authors have sought to supplement the World Health Organization (WHO) grading system with the use of molecular markers. Although some genetic alterations have been associated with prognosis of patients, it is imperative to validate such markers in different patient cohorts.

Patients with lateral lymph node metastasis (LLNM) present particular challenges for both diagnosis and treatment. This study aimed to assess whether indocyanine green (ICG)-assisted lymph node mapping with near-infrared imaging (NIRI) enhances the effectiveness of lateral lymph node dissection (LLND) by further categorizing the lateral lymph nodes in patients with mid-low rectal cancer.

tRNA-derived small RNAs (tsRNAs), newly developed non-coding RNAs with specialized biological features, are aberrantly expressed in the majority of malignancies. However, whether tsRNAs are involved in metabolic reprogramming of colorectal cancer (CRC) remains to be elucidated.

BACKGROUND Early postoperative recurrence in non-small cell lung cancer (NSCLC) significantly impacts survival outcomes, yet current staging systems often fail to accurately predict recurrence risk. In this study, we analyzed the risk factors associated with early postoperative recurrence in NSCLC and developed a nomogram model to enhance individualized risk assessment. MATERIAL AND METHODS A retrospective analysis was conducted on data from 286 NSCLC patients who underwent R0 resection between January 2020 and December 2022, categorized into a control group (n=235) and an observation group (n=51). Demographic and clinicopathological data were collected, and multivariate logistic regression was used to identify independent risk factors. A nomogram was developed and validated using internal resampling. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration performance was evaluated using the Hosmer-Lemeshow test and calibration curves. RESULTS Multivariate analysis identified elevated D-dimer levels (≥0.5 mg/L), pleural invasion, lymphovascular invasion, and lymph node metastasis as independent predictors of early recurrence. The nomogram achieved an AUC of 0.806, with a sensitivity of 78.9% and specificity of 80.1%. Internal validation yielded a corrected C-index of 0.689. Calibration curves demonstrated good agreement between predicted and observed recurrence probabilities. Decision curve analysis showed the model provided a higher net benefit compared to extreme intervention strategies. CONCLUSIONS Elevated D-dimer levels, pleural invasion, lymphovascular invasion, and lymph node metastasis were key risk factors predicting early postoperative recurrence in NSCLC. The nomogram demonstrated strong predictive accuracy and calibration, offering a useful tool for individualized risk assessment.

BCMA-directed CAR-T therapies have shown promising results in multiple myeloma (MM). However, patients continue to relapse. T cell exhaustion with increased TIGIT expression is a resistance mechanism which was confirmed in CAR-T cells from ARI0002h trial, an academic CAR-T developed in our institution. We aimed to analyze the impact of blocking TIGIT on the efficacy of ARI0002h. We used three different strategies to block TIGIT: (1) Addition of an external blocking anti-TIGIT-antibody (Ab), (2) Modify ARI0002h into a 4th generation CAR-T, named ARITIGIT, capable of secreting a soluble TIGIT-blocking scFv and (3) TIGIT knock-out in ARI0002h using CRISPR/Cas9. Each strategy was evaluated in vitro and in vivo. Adding a TIGIT-blocking Ab to ARI0002h improved in vitro cytotoxicity, but failed to enhance mice survival. The new 4th generation CAR-T, ARITIGIT, was also unable to achieve better survival outcomes despite favoring the in vivo model by using a myeloma cell line with high expression of the TIGIT ligand PVR. Interestingly, when mice were challenged with a second infusion of tumor cells, mimicking a relapse model, a trend for improved survival with ARITIGIT was observed (p = 0.11). Finally, TIGIT-knock-out on ARI0002h (KO-ARI0002h) using CRISPR/Cas9 showed similar in vitro activity to ARI0002h. In an in vivo stress model, TIGIT KO-ARI0002h prolonged survival (p = 0.02). However, this improvement was not significant compared to ARI0002h (p = 0.07). This study failed to demonstrate a significant benefit of TIGIT-blockade on ARI0002h cells despite using three different approaches, suggesting that targeting a single immune checkpoint may be insufficient.

Prostate adenocarcinoma (PRAD) is asymptomatic in the early stages and most patients are diagnosed at an advanced stage, which leads to a poor prognosis. Therefore, an effective prognostic marker is required to improve PRAD prognosis.

Colorectal liver metastases (CRLM) are the leading cause of colorectal cancer (CRC)-related mortality. Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNAs (sncRNA), regulate gene expression, stress response, and immune functions in cancer. While increasingly implicated in CRC progression, their prognostic significance in CRLM remains unknown. This study investigates the abundance and prognostic value of genomic (ge) and mitochondrial (mt) tRFs in CRLM.

Circulating tumor DNA (ctDNA) holds promise for guiding immune checkpoint inhibitor (ICI) therapy and stratifying responders from non-responders. While tumor-informed ctDNA detection approaches are sensitive and mutation-inclusive, they require tumor tissue, which limits applicability in real-world settings. Conversely, tumor-agnostic methods often have limited genomic coverage. In this study, we evaluated a tumor-agnostic, broad-panel ctDNA assay in patients with advanced melanoma treated with ICI.

The role of axillary surgery in ductal carcinoma in situ (DCIS) remains controversial, particularly for cases diagnosed via vacuum-assisted biopsy (VAB), which may reduce "upstage" to invasive disease. This study evaluates the incidence of axillary metastasis and pathologic upstaging in DCIS to identify subgroups where axillary staging can be safely omitted.

Given the limited treatment options recommended for cancer of unknown primary (CUP), especially the role of immune checkpoint inhibitors (ICIs), our study aimed to evaluate the efficacy of ICIs and identify associated genomic biomarkers in these patients.

Pembrolizumab is a novel humanized anti-PD-1 monoclonal antibody capable of enhancing T-cell mediated antitumor immunity. However, the function of pembrolizumab on tumor cells themselves and relative molecular mechanism in ovarian cancer remain unknown. Our study demonstrated pembrolizumab exerted remarkable suppressive impacts on proliferation, colony formation and migration of ovarian cancer cells in vitro. Furthermore, pembrolizumab treatment delayed cell cycle progress from G1 to S phase transition and suppressed cell growth in ovarian cancer cells. Mechanistically, pembrolizumab decreased the stability of CDK6 protein through a polyubiquitin-mediated proteasomal degradation pathway. Meanwhile, pembrolizumab treatment dose-dependently reduced Snail, Vimentin and N-cadherin expressions and enhanced E-cadherin expressions. Additionally, the combined treatment of pembrolizumab and cisplatin effectively enhanced anti-proliferative effect of cisplatin on HO-8910 cells. These findings suggested pembrolizumab efficiently suppressed malignant progression of ovarian cancer cells and facilitated proteasomal degradation of CDK6 and increased cisplatin inhibition of HO-8910 cells proliferation, therefore providing a promising therapeutic strategy for ovarian cancer.

We investigated trends in the use of perioperative therapy and the efficacy of adjuvant immunotherapy on the prognosis of patients with muscle-invasive urothelial carcinoma (MIUC). The usage and trends in neoadjuvant and adjuvant therapy were examined, and the efficacy of adjuvant immunotherapy was assessed using propensity score-adjusted Cox multivariate analysis. We investigated 1383 patients with muscle-invasive bladder cancer and 1124 patients with upper tract urothelial carcinoma; 1095 (43.7%) patients received neoadjuvant therapy and 366 (14.6%) patients received adjuvant therapy. Adjuvant therapy usage rate increased from 30.3% before 2022 to 61% after 2022 in patients with pathological high-risk cancer (pT3-4, ypT2-4, or pN+). The adjuvant immunotherapy usage rate increased from 2.8% before 2022 to 67.5% after 2022. Sixty-three (18.9%) of the 334 patients with pathological high-risk cancer who were treated with adjuvant therapy were treated with adjuvant immunotherapy. The propensity score-adjusted Cox multivariate analysis showed that adjuvant immunotherapy significantly improved disease-free survival (Hazard ratios (HR) 0.39, P < 0.005) and overall survival (HR 0.20, P < 0.005) compared with conventional adjuvant chemotherapy. In conclusion, the introduction of adjuvant immunotherapy led to the increased use of adjuvant therapy and improved prognoses in patients with MIUC in real-world practice.

Head and neck squamous cell carcinoma (HNSCC) poses a global health challenge. The management of HNSCC is complicated by the difficulty in detecting occult lymph node metastases, leading to dilemmas in elective neck dissection decisions, which will impair patients' quality of life without improving survival for nodal negative patients. We conducted a comparative analysis of the clinical features, genomic alterations, gene expression and methylation, tumor microenvironment and cellular states between the clinically N0 and pathologically N0 (cN0-pN0) patients and occult lymph node metastatic patients. Patients with occult lymph node metastases typically present with more poorly differentiated primary tumors and higher rates of angiolymphatic and perineural invasion. We identified a distinctive genomic mutation spectrum in the primary tumors of patients with occult metastases, notably in genes such as NSD1, ARHGAP15 and SMARCA4. A whole-genome DNA hypomethylation and altered gene expression profiles are identified in occult lymph node metastatic patients. Analysis of the tumor microenvironment revealed an enrichment of CARNS1 + NK cells and CBX1 + tumor cells in occult metastatic patients. In conclusion, patients with occult lymph node metastases exhibit distinct molecular and clinical features compared with cN0-pN0 patients.

Tumor associated neutrophils (TANs) exert dual and opposing functions in tumors, acting pro-tumorigenic and anti-tumorigenic, depending on tumor progression, polarization state and subtype. Consequently, the prognostic impact of TANs in breast cancer is also contradictory. Since neutrophils are critically needed to fight infections in cancer patients, the mediators leading to tumor progression need more investigation as potential future targets. The neutrophil derived mediator myeloperoxidase (MPO) is a peroxidase with dual functions in tumors, acting both immune enhancing and suppressing. Patients with metastatic breast cancer (MBC) have aggressive tumors with a dismal prognosis and urgently need novel treatment strategies. Therefore, we here aimed to investigate the prognostic impact of TANs, MPO+ TANs and MPO+ non-neutrophils using a cohort with newly diagnosed MBC patients specifically. We show that high infiltration of MPO+ TANs and MPO+ non-neutrophils in the primary tumor (PT), was associated with clinicopathological features and worse prognosis in patients with MBC. However, only infiltration of MPO+ TANs showed independent prognostic impact in multivariable analysis adjusting for other prognostic factors in MBC. The results need to be validated in a larger cohort but suggests that MPO targeting strategies could be relevant in breast cancer patients with aggressive disease.

This study investigates the concentration-dependent cytotoxicity of aluminum-doped zinc oxide nanoparticles on breast cancer (MDA-MB-231) and normal mammary epithelial cells (MCF-10 A). Pure and Al-doped ZnO nanoparticles (Al-ZnO NPs, Zn1-xAlxO, x = 0.0: ZnO, 0.01: ZA1, 0.03: ZA3, and 0.05: ZA5) were synthesized by the gelatin-based sol-gel method. The properties of the pure and Al-doped ZnO nanoparticles were investigated by X-ray diffraction (XRD), field emission electron microscopy (FESEM), and ultra-violate-visible (UV-vis) spectroscopy. Using an indirect viability assay, the prepared samples were evaluated across a 5-500 µg/mL range, with IC50 (half-maximal inhibitory concentration) as the primary metric. Results demonstrated enhanced toxicity toward cancer cells, with IC50 values for ZnO, ZA1, ZA3, and ZA5 at (225, 100, 80, and 60 µg/mL) compared to normal cells (500 µg/mL, in the experimental range), respectively. Progressive doping (ZA1 → ZA5) improved cancer cell targeting by synergistically enhancing ROS generation and reducing normal cell susceptibility. These findings underscore Al-ZnO NPs as tunable, selective therapeutic agents, leveraging dopant-driven redox modulation to optimize oncological efficacy while sparing healthy tissue.

Ferroptosis is a form of iron-dependent cell death of interest for the development of novel anti-cancer therapies. Ferroptosis research uses a process of elimination based on assumed ferroptosis-specific inducers and inhibitors; these molecules however have off-target effects and cannot provide a comprehensive picture of overlapping pathways. We investigated whether pyroptosis-a form of inflammatory cell death-is initiated in cancer cells following treatment with the ferroptosis inducer RSL3. We treated 6 cancer cell lines with RSL3 alone or in combination with inhibitors of ferroptosis (Ferrostatin-1), caspases (zVADfmk), necroptosis (Necrostatin-1), BID (BI-6C9), or STING (H-151). Biomarkers of pyroptosis and ferroptosis were assessed using our novel quantitative multiplex immunoassay. Increased secretion of pyroptosis-associated cytokines (IL-1α, IL-1β, IL-18), and gasdermin D and E (GSDMD/E) cleavage with parallel loss of respective full-length proteins-both hallmarks of pyroptosis-were recorded in 5/6 cell lines following RSL3 treatment. RSL3 cytotoxicity was blocked by Ferostatin-1; BID and STING inhibitors also prevented GSDMD/E cleavage. We conclude that the ferroptosis-inducer RSL3 triggers pyroptosis in cancer cells; further work is required to elucidate the role of mitochondria in this process. Measurement of pathway-specific protein biomarkers is therefore necessary to identify the exact mechanism of action of novel cytotoxic agents.

Hilar cholangiocarcinoma (hCCA), a rare cancer of the biliary system, has a poor prognosis. This study aimed to investigate the risk factors affecting the survival of patients with hCCA after curative-intent resection and establish a survival predictive model. Clinical data from 340 hCCA patients who underwent curative-intent resection at the First Affiliated Hospital of Xi'an Jiaotong University between 2010 and 2021 were collected. The patients were randomly assigned to a training set and a testing set in a 7:3 ratio. Risk factors selection was performed by five machine learning (ML) algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO) Regression, Forward Stepwise Cox regression, Boruta feature selection, Random Forest and eXtreme Gradient Boosting (XGBoost). A nomogram was constructed based on identified risk factors. The independent risk factors for the postoperative survival in hCCA patients included positive margin, lymph node metastasis, low total lymph node count (TLNC) and poor tumor differentiation. In the training and testing sets, the consistency index (C-index) of ML-based nomogram was 0.731 (95% CI: 0.684-0.753) and 0.714 (95% CI: 0.661-0.775), while the 3-year AUC of the nomogram was 0.784 (95% CI: 0.724-0.844) and 0.770 (95% CI: 0.763-0.867), respectively. The calibration curves for the nomogram showed good concordance. Based on the decision curve analysis, the nomogram had a good clinical application value, outperforming both the TNM staging system and the Bismuth-Corlette classification. Furthermore, patients were stratified into three groups with varying risks of overall survival (OS): the low-risk, middle-risk and high-risk group according to the nomogram, with statistically significant differences observed among these groups (p < 0.001). The ML-based nomogram provided a personalized prognostic prediction model for hCCA patients after surgical resection.

Low-grade glioma(LGG) is a prevalent primary brain tumor, and type I interferons(IFN-Is) can exert a multifaceted influence on the regulation of the tumor microenvironment during its initiation and progression. To investigate the role of IFN-Is in the progression of LGG, we screened public databases for features based on IFN-alpha(IFN-α) response genes (IRGs), a risk model was constructe and its relationship to tumor immunity and prognosis was evaluated. In addition, the expression and regulation of IRGs in LGG were further studied in vitro biological function experiments and immunohistochemistry of clinical samples. 20 differential genes associated with LGG-IRGs were found, then 6-IRGs-based signature was found by using of univariate COX, LASSO and SVM-RFE. ROC curves also supported the value of signature. CIBERSORT results demonstrated the crucial role played by these key signature genes in immune response. Additionally, aggregation analysis of relevant immune-related genes revealed that cluster 1 exhibited the lowest expression of RIPK2 and SELL. Moreover, GSVA results suggested that diagnostic immune-related genes may regulate LGG by influencing immune cells. We further validated these findings using external datasets and provided additional evidence supporting the predictive value of signature genes associated with IRGs in LGG through immunohistochemical testing on clinical samples and in vitro experiments. These 6 diagnostic IRGs genes can help differentiate and predict the prognosis and immune status of patients with LGG, thereby providing new strategies for precise and personalized immunotherapy.