Apatinib manifests an unexpectedly favorable outcome in the management of axillary lymph node follicular dendritic cell sarcoma: a case report.

We present a case of follicular dendritic cell sarcoma in the axillary lymph node, which unexpectedly showed favorable outcomes after the application of apatinib. Follicular Dendritic Cell Sarcoma (FDCS) exhibits a rare incidence and an unclear pathogenic mechanism, contributing to the limited breakthroughs in its treatment to date within the medical field. The current mainstream therapeutic approaches include surgery, CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone), ICE(ifosfamide, carboplatin, etoposide), ABVD(doxorubicin, bleomycin, vinblastine, dacarbazine), and immune checkpoint inhibitors. A 38-year-old male patient was admitted to the hospital due to a lump in the right axilla and underwent surgical treatment. Postoperative pathology confirmed the diagnosis of follicular dendritic cell sarcoma. Two months post-surgery, he faced a recurrence, prompting a subsequent surgical intervention complemented by tumor radiofrequency ablation. Despite these interventions, the treatment response was suboptimal. Subsequently, the patient was treated with the CHOP regimen, but after two cycles, he developed bone metastasis. Due to the patient's limited financial resources and refusal of immunotherapy, we switched to a regimen of gemcitabine and docetaxel, but the disease progressed again after two cycles. A one-cycle trial of albumin-bound paclitaxel yielded unsatisfactory results. Ultimately, the patient was treated with Apatinib, achieving a 10-month progression-free survival. Due to the patient's limited financial circumstances, we, in the absence of guideline recommendations and evidence from evidence-based medicine, achieved a 10-month progression-free survival (PFS) solely based on experiential use of the anti-angiogenic drug, Apatinib. The purpose of this case report is to provide additional therapeutic options for FDCS treatment and to pave the way for exploring the mechanism of action of Apatinib in FDCS.

An exosome mRNA-related gene risk model to evaluate the tumor microenvironment and predict prognosis in hepatocellular carcinoma.

BACKGROUND: The interplay between exosomes and the tumor microenvironment (TME) remains unclear. We investigated the influence of exosomes on the TME in hepatocellular carcinoma (HCC), focusing on their mRNA expression profile. METHODS: mRNA expression profiles of exosomes were obtained from exoRBase. RNA sequencing data from HCC patients' tumors were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). An exosome mRNA-related risk score model of prognostic value was established. The patients in the two databases were divided into high- and low-risk groups based on the median risk score value, and used to validate one another. Functional enrichment analysis was performed based on a differential gene prognosis model (DGPM). CIBERSORT was used to assess the abundance of immune cells in the TME. The correlation between the expression levels of immune checkpoint-related genes and DGPM was analyzed alongside the prediction value to drug sensitivity. RESULTS: A prognostic exosome mRNA-related 4-gene signature (DYNC1H1, PRKDC, CCDC88A, and ADAMTS5) was constructed and validated. A prognostic nomogram had prognostic ability for HCC. The genes for this model are involved in extracellular matrix, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Expression of genes here had a positive correlation with immune cell infiltration in the TME. CONCLUSIONS: Our study results demonstrate that an exosome mRNA-related risk model can be established in HCC, highlighting the functional significance of the molecules in prognosis and risk stratification.

Benefits and risks of PD-1/PD-L1 inhibitors for recurrent small cell lung cancer: A systematic review and meta-analysis.

The development of immune checkpoint inhibitors(ICIs) has revolutionized the progress of solid tumors. Ongoing clinical trials are exploring the use of checkpoint inhibitors in recurrent small-cell lung cancer and achieving specific results. Although studies have been conducted to systematically review this issue, we conducted this single-arm meta-analysis in light of the emergence of several new clinical studies. In total, 854 individuals from 11 clinical investigations were enrolled in this single-arm meta-analysis. Median progression-free survival, median overall survival, and objective response rate were 1.65 months, 6.83 months, and 20.5%, respectively, according to pooled analyses. The best treatment regimen in the subgroup analysis was a dual checkpoint inhibitor combined with other treatments, and the drug that worked well for treatment was pembrolizumab. The benefit of programmed death 1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors alone is limited, and their combination with other therapies is a promising treatment option. Among PD-1/PD-L1 inhibitors, pembrolizumab is the recommended drug.

A prognostic model of drug tolerant persister-related genes in lung adenocarcinoma based on single cell and bulk RNA sequencing data.

Background: Acquired resistance to targeted drugs is a major challenge in cancer. The drug-tolerant state has been proposed to be an initial step towards acquisition of real drug-resistance. Drug tolerant persister (DTP) cells are purported to survive during treatment and stay dormant for several years. Single cell sequencing can provide a comprehensive landscape of gene expression in DTP cells, which can facilitate investigation of heterogeneity of a drug tolerant state and identification of new anticancer targets. Methods: The genetic profiling of DTPs was explored by integrating Gene Expression Omnibus (GEO) datasets, and a prognostic signature of DTP-related genes (DTPRGs) in lung adenocarcinoma of TCGA LUAD cohort was constructed. The scores of infiltrating immune cells were calculated and activity of immune-related pathways was evaluated by single-sample gene set enrichment analysis (ssGSEA). Functional enrichment analysis of the DTPRGs between low- and high-risk groups was performed. Immune cell subtypes and immune-related pathways were analyzed. Results: An 11-gene panel (MT2A, UBE2S, CLTB, KRT7, IGFBP3, CTSH, NPC2, HMGA1, HNRNPAB, DTYMK, and IHNA) was established. DTPRGs were mainly correlated with nuclear division, chromosome segregation, and cell cycle pathways. Infiltration of immune cells was lower in the high-risk group while the inflammation-promoting and MCH-class I response pathway had higher activity in the high-risk group. A nomogram was generated with prognostic accuracy, further validated using clinical outcomes following therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Discussion: A prognostic model of lung adenocarcinoma based on DTPRGs was constructed. Targeting DTP cells is a potential therapeutic approach to prevent a drug tolerant state.

Case Report: Recurrent meningioma with multiple metastases.

Post-surgery recurrence of meningiomas with multiple extracranial metastases is rare. Currently, information on extracranial metastases is limited, and no clear predictors and standardized treatment protocols can be applied clinically. Herein, we report a case of meningioma that recurred after two surgeries and had multiple distant metastases. Computed tomography revealed multiple enlarged lymph nodes in the para-aortic arch, left lower lung region, retroperitoneum, and abdominopelvic region, as well as soft tissue mass-like lesions under the liver capsule in the right lobe of the liver. Magnetic resonance imaging showed space-occupying lesions under the cranial plate of the left parietal lobe. Tissue biopsy confirmed the diagnosis of recurrent meningioma with extracranial metastases. Immune checkpoint inhibitors and anti-angiogenic drugs were administered. After two treatment cycles, the patient's clinical symptoms were significantly relieved, and the imaging assessment confirmed a stable disease. Although it did not meet our expectations, this combination therapy still demonstrated a possible benefit in improving meningioma patients' survival and quality of life. In this report, along with the case, we also review the relevant literature on the subject and discuss the associated risk factors and treatment options.

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis.

Background: Cancer is concerning owing to its high mortality rate. Consequently, methods of prolonging the life of patients with cancer have become the primary focus of attention research. In recent years, immune checkpoint inhibitors (ICIs) have achieved good clinical efficacy as antitumor drugs; however, their severe adverse effects have made their use challenging. In order to clarify the predictors of adverse effects, scientists have conducted a series of studies. Blood counts can potentially monitor risk factors associated with the occurrence of immune-related adverse events (irAEs). Herein, a meta-analysis was performed to clarify further the guiding significance of blood counts in the clinical setting. Methods: Studies that satisfied the inclusion criteria were obtained by searching the database. Included studies were those in which irAEs had been observed, and evidence of an association between blood counts and irAEs was reported. The included ones were evaluated for quality. In addition to sensitivity analysis and subgroup analysis, a meta-analysis was performed using the odds ratio (OR) and 95% confidence interval (CI) for each study. Results: A total of 18 articles were included in our study. The analyses were performed separately according to different blood cell count indicators. The blood cell count metrics associated with irAEs were: absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio. Conclusion: Our review and meta-analysis of studies suggest that absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio may serve as predictors of the emergence of irAEs. Given the small number of studies focusing on the relationship between patient blood cell counts and the risk of irAEs, future studies need to further explore the mechanisms of occurrence and potential associations.

SChLAP1 contributes to non-small cell lung cancer cell progression and immune evasion through regulating the AUF1/PD-L1 axis.

SChLAP1 is recently reported as a key oncogenic long non-coding RNA in human cancer. However, whether SChLAP1 functions in non-small cell lung cancer (NSCLC) and its specific potential regulatory mechanism remain unexplored. In this study, we found that depletion of SChLAP1 significantly inhibited NSCLC cell proliferation, migration and invasion in vitro, and retarded tumour growth and lung metastasis in vivo. SChLAP1 facilitated NSCLC cell immune evasion against CD8+ T cells through PD-1/PD-L1 immune checkpoint. In detail, SChLAP1 was able to directly interact with AUF1, antagonizing the binding between AUF1 and PDL1 mRNA 3'-UTR, resulting in increasing PDL1 mRNA stability and expression, thereby repressing CD8+ T cell function. Consistently, anti-PD-1/PD-L1 treatment evidently blocked the enhanced cell proliferation and invasion caused by SChLAP1 overexpression. Importantly, SChLAP1 was significantly upregulated in NSCLC cell lines, serum and tissues, which was identified as an excellent indicator for the diagnosis and prognosis of NSCLC. In conclusion, our data for the first time uncover that SChLAP1 functions an oncogene in NSCLC by promoting cancer cell immune evasion via regulating the AUF1/PDL1 axis, targeting of SChLAP1 may be a potential approach to improve the efficacy of immunotherapy in NSCLC patients.

MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells.

BACKGROUND: MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. METHODS: One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain- and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. RESULTS: Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients' lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. CONCLUSION: All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance.

BACKGROUNDS: Hepatocellular carcinoma (HCC) is an epithelial cancer that originates from hepatocytes and it is the most common primary malignant tumor of the liver. Till now the prognosis of HCC patients is generally poor. The molecular mechanism giving rise to HCC development and recurrence is still largely unknown. MicroRNA-31 (miR-31) is among the most commonly altered microRNAs in human cancers, and alternations of miR-31 expression were reported to play pivotal roles in tumorigenesis and tumor progression. METHODS: In this work, the primary biological function of miR-31 in HCC tumorigenesis was investigated. RESULTS: Our data showed that overexpression of miR-31 induced markedly inhibition of HCC cell proliferation, migration in vitro and inhibited xenograft tumor growth in vivo. One target gene of miR-31, NDRG3, was also demonstrated indispensable for HCC cell survival. Furthermore, miR-31 and NDRG3 were both essential for HCC cell drug resistance in adriamycin. CONCLUSIONS: We conclude that miR-31 is a crucial regulator in hepatocellular carcinoma, miR-31 and its target gene NDRG3 may be potential therapeutic targets for HCC treatment in the future.