Discover. Oncology最新文献

Background: Hepatocellular carcinoma (HCC), a malignant tumor that seriously endangering health, has aroused widespread concern in the field of public health. Previous researches have noted the relationships between immune cells and HCC, but the causal relationship was uncertain.

Methods: In this study, a bidirectional two sample Mendelian randomization (MR) analysis was utilized to access the causal relationship between immune cell characteristics and HCC. According to the open-access data, we investigated the causal relationship between 731 immune cell characteristics and HCC risk.

Results: After screening by IVW approach, increased levels of 8 immune traits and reduced levels of 7 immune traits could lead to changes in HCC risk. These 15 immune cells were distributed in the Monocyte (4 cells), Treg panel (4 cells), TBNK (3 cells), Maturation stages of T cell panel (3 cells), and cDC panel (1 cells). Furthermore, HCC was identified to have causal effects on 21 immunophenotypes. Among these immune cells, hepatocarcinogenesis had the greatest impact on CD4 on EM CD4 + and CD33 on Mo MDSC.

Conclusions: This study enhances our comprehension of the interaction between immune cells and HCC risk, furnishing novel avenues to explore the mechanisms of HCC.

Objectives: Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drug and suppresses T-cell proliferation and activity by inhibiting pyrimidine synthesis using dihydroorotase dehydrogenase (DHODH); however, several studies have demonstrated that LEF possesses anticancer and antiangiogenic effects in some malignant tumors. Therefore, we investigated the anticancer and antiangiogenic effects of LEF on oral squamous cell carcinoma (OSCC).

Methods: To evaluate the inhibitory effect of LEF on OSCC, cell proliferation and wound-healing assays using human OSCC cell lines were performed. The DHODH inhibitory effect of LEF was evaluated by Western blot. To assess the suppression of pyrimidine biosynthesis induced by LEF on OSCC, cell proliferation assays with or without uridine supplementation were performed. The antiangiogenic effect of LEF was evaluated by in vitro tube formation assay using immortalized human umbilical vein endothelial cells, which were electroporatically transfected with hTERT. The tumor-suppressive effect of LEF in vivo was examined in both immunodeficient and syngeneic mice by implanting mouse OSCC cells. Tumor vascularization was evaluated by immunohistochemistry of the tumor extracted from syngeneic mice.

Results: LEF dose-dependently inhibited OSCC proliferation and migration. LEF significantly inhibited DHODH expression, and uridine supplementation rescued the inhibitory effect of LEF. LEF dose-dependently suppressed endothelial tube formation. In the animal study, LEF significantly suppressed tumor growth in both immunodeficient and syngeneic mice. Histologically, LEF decreased DHODH expression and tumor vascularization.

Conclusion: LEF is a potent anticancer agent with antiangiogenic effects on OSCC and might be clinically applicable to OSCC by drug repositioning.

Objective: Rosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and a variety of malignant tumors. However, its specific mechanism for the treatment of lung adenocarcinoma (LUAD) has not been fully elucidated. Therefore, this study aims to clarify the mechanism of RosA in the treatment of LUAD by integrating bioinformatics, network pharmacology and in vivo experiments, and to explore the potential of the active ingredients of traditional Chinese medicine in treating LUAD.

Methods: Firstly, the network pharmacology was used to screen the RosA targets, and LUAD-related differential expressed genes (DEGs) were acquired from the GEO database. The intersection of LUAD regulated by RosA (RDEGs) was obtained through the Venn diagram. Secondly, GO and KEGG enrichment analysis of RDEGs were performed, and protein-protein interaction networks (PPIs) were constructed to identify and visualize hub RDEGs. Then, molecular docking between hub RDEGs and RosA was performed, and further evaluation was carried out by using bioinformatics for the predictive value of the hub RDEGs. Finally, the mechanism of RosA in the treatment of LUAD was verified by establishing a xenograft model of NSCLC in nude mouse.

Results: Bioinformatics and other analysis showed that, compared with the control group, the expressions of MMP-1, MMP-9, IGFBP3 and PLAU in LUAD tissues were significantly up-regulated, and the expressions of PPARG and FABP4 were significantly down-regulated, and these hub RDEGs had potential predictive value for LUAD. In vivo experimental results showed that RosA could inhibit the growth of transplanted tumors in nude mice bearing tumors of lung cancer cells, reduce the positive expression of Ki67 in lung tumor tissue, and hinder the proliferation of lung tumor cells. Upregulated expression of PPARG and FABP4 by activating the PPAR signaling pathway increases the level of ROS in lung tumor tissues and promotes apoptosis of lung tumor cells. In addition, RosA can also reduce the expression of MMP-9 and IGFBP3, inhibit the migration and invasion of lung tumor tissue cells.

Conclusions: This study demonstrated that RosA could induce apoptosis by regulating the PPAR signaling pathway and the expression of MMP-9, inhibit the proliferation, migration and invasion of lung cancer cells, thereby exerting anti-LUAD effects. This study provides new insight into the potential mechanism of RosA in treating LUAD and provides a new therapeutic avenue for treatment of LUAD.

Background: The metabolism of stearoyl-GPE plays a key role in the liver metastasis of gastric cancer. This investigation delves into the mechanisms underlying the intricate tumor microenvironment (TME) heterogeneity triggered by stearoyl metabolism in gastric cancer with liver metastasis (LMGC), offering novel perspectives for LMGC.

Objective: Utilizing Mendelian randomization, we determined that stearoyl metabolism significantly contributes to the progression of gastric cancer (GC). Following this, bulk transcriptome analyses and single-cell multiomics techniques to investigate the roles of stearoyl-GPE metabolism-related genes, particularly NCOA4, in regulating LMGC TME.

Results: Our analysis highlights the crucial role of stearoyl metabolism in modulating the complex microenvironment of LMGC, particularly impacting monocyte cells. Through single-cell sequencing and spatial transcriptomics, we have identified key metabolic genes specific to stearoyl metabolism within the monocyte cell population, including NCOA4. Regarding the relationship between ferroptosis, stearoyl metabolism, and LMGC findings, it is plausible that stearoyl metabolism and LMGC pathways intersect with mechanisms involved in ferroptosis. Ferroptosis, characterized by iron-dependent lipid peroxidation, represents a regulated form of cell death. The activity of Stearoyl-CoA desaturase (SCD), a critical enzyme in stearoyl metabolism, has been associated with the modulation of lipid composition and susceptibility to ferroptosis. Furthermore, the LMGC is integral to cellular processes related to oxidative stress and lipid metabolism, both of which are significant factors in the context of ferroptosis.

Conclusion: This study enhances the understanding of the relationship between stearoyl metabolism and ferroptosis in promoting liver metastasis of gastric cancer and its role in the regulation of tumor heterogeneity. In addition, this study contributes to a deeper understanding of the dynamics of gastric cancer tumor microenvironment (TME) and provides a basis for the development of better interventions to combat cancer metastasis.

CAR-T cell therapies have risen to prominence over the last decade, and their indications are increasing with several products approved as early as second line in Large B Cell non-Hodgkin Lymphomas. Their major toxicities are the cytokine release syndrome (CRS) and the Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS). These entities involve a hyperinflammatory cascade which is amplified through the mononuclear phagocytic system (MPS). Herein, we review the immune mediated adverse events related to CAR therapy, including their pathophysiologies, and current therapies. In particular, we discuss the emerging role of the MPS in both the toxicity and efficacy of CAR-T therapy, and possible avenues for the modulation of the MPS to optimize efficacy while minimizing toxicity.

Background: Accurately distinguishing lymph node metastases (LNM) from papillary thyroid carcinomas (PTC) is crucial in clinical practice. The role of the immune system in PTC-LNM has attracted increasing attention. The aim of the present study was to evaluate the differential expression of 92 immune-related proteins in the serum and identify their potential diagnostic effects in patients with PTC-LNM.

Methods: The 92 immune-related proteins were analyzed using a proximity extension assay. In addition, logistic regression and least absolute shrinkage and selection operator regression methods were used to develop combined diagnostic markers for thyroid cancer. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic validity. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to analyze the potential regulatory pathways.

Results: Five proteins, including IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α, were significantly elevated in the serum of patients with LNM. The combined diagnosis of these five proteins demonstrated excellent diagnostic performance in distinguishing patients with PTC-LNM (area under the curve = 0.967, sensitivity = 0.941, and specificity = 0.889). Further analysis revealed that IL12B and IL1A mRNAs were significantly overexpressed in patients with PTC-LNM. This study also showed that the IL12B and IL1A was closely related to the PI3K-AKT, NF-κB, and MAPK signaling pathways.

Conclusion: The combination of IL-22RA1, IL-12B, CCL4, CCL3, and IL-1α represents a promising diagnostic panel for PTC-LNM. These findings provide a novel set of diagnostic markers for PTC-LNM based on serum inflammatory protein levels.

Sarcoma (SARC), a diverse group of stromal tumors arising from mesenchymal tissues, is often associated with a poor prognosis. Emerging evidence indicates that senescent cells within the tumor microenvironment (TME) significantly contribute to cancer progression and metastasis. Although the influence of senescence on SARC has been partially acknowledged, it has yet to be fully elucidated. In this study, we revealed that senescence level and age were associated with TME, immune treatment indicators, and prognosis in SARC. Utilizing the weighted gene co-expression network analysis and least absolute shrinkage and selection operator algorithm, we identified senescence-related genes and developed a senescence predictor. Three genes, RAD54, PIK3IP1, and TRIP13, were selected to construct a multiple linear regression model. Validation cohorts, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction confirmed that the predictor derived from these three genes possessed prognostic and pathological relevance. Our senescence predictor provides comprehensive insights into the molecular mechanisms of SARC and identifies potential biomarkers for prognosis, paving the way for effective treatments. The results of this study hold promise for developing therapeutic strategies tailored to the unique characteristics of SARC.

Cancer vaccines are promising as an effective means of stimulating the immune system to clear tumors as well as to establish immune surveillance. In this paper, we discuss the main platforms and current status of cancer vaccines and propose a new cancer vaccine platform, the cytosolic vesicle vaccine. This vaccine has a unique structure that can integrate antigen and adjuvant carriers to improve the delivery efficiency and immune activation ability, which brings new ideas for cancer vaccine design. Tumor exosomes carry antigens and MHC-peptide complexes, which can provide tumor antigens to antigen-processing cells and increase the chances of recognition of tumor antigens by immune cells. DEVs play a role in amplifying the immune response by acting as carriers for the dissemination of antigenic substances in dendritic cells. OMVs, with their natural adjuvant properties, are one of the advantages for the preparation of antitumor vaccines. This paper presents the advantages of these three bacteria/extracellular vesicles as cancer vaccines and discusses the potential applications of functionally modified extracellular vesicles as cancer vaccines after cellular engineering or genetic engineering, as well as current clinical trials of extracellular vesicle vaccines. In summary, extracellular vesicle vaccines are a promising direction for cancer vaccine research.

Background: Nasopharyngeal cancer (NPC) is a common head and neck malignant tumor, which is difficult to treat at the advanced NPC due to its occult and high metastatic potential to the cervical lymph nodes and distant organs. Low-dose radiotherapy (LDRT) is increasingly being investigated for potential cancer treatment. When combined with immune checkpoint inhibitors, LDRT has been shown to significantly improve the immune microenvironment of tumors, thereby promote the immune attack on tumor cells. However, the therapeutic effect of LDRT combined with immunotherapy in advanced NPC is not well understood. We report a case of a 31-year-old man was diagnosed with advanced metastatic nasopharnygeal non-keratinizing carcinoma (T4N3M1 stage IVb AJCC8th). The patient was treated with a high-dose of radiation therapy combined with LDRT and immunotherapy to inhibit tumor cell proliferation and activate the body's immune system. The initial treatment procedure was as follows: chemotherapy regimen (nedaplatin + docetaxel + fluorouracil) induction, followed by radical radiotherapy for the primary lesion, LDRT for the L5 vertebral body metastasis, and concurrent use of low-dose capecitabine beat chemotherapy and toripalimab immunotherapy. The patient was also administered with human granulocyte-macrophage colony-stimulating factor and aspirin to enhance the immune function. This combination therapy approach alleviated patient symptoms, improved bone changes in the L5 vertebral body and resolved the tumor without any adverse effects signals. The progression-free survival (PFS) has reached 27 months and he is currently stable without tumor recurrence.

Conclusion: The combination of chemotherapy and LDRT with aspirin and human granulocyte macrophage colony-stimulating factor improved the disease state of advanced NPC cancer, effectively reducing the level of tumor markers, enhanced the immune function without significant adverse reactions.

Background: Recent studies have highlighted the role of RNA modification, that is, the dysregulation of epitranscriptomics, in tumorigenesis and progression. The potential for undoing epigenetic changes may develop novel therapeutic and prognostic approaches. However, the roles of these RNA modifications in the tumor microenvironment (TME) are still unknown.

Methods: We assessed the expression properties and genetic alterations of 26 RNA modification writers, including adenosine-to-inosine RNA editing, alternative polyadenylation, m1A, and m6A in 502 lung adenocarcinoma (LUAD) samples from the Cancer Genome Atlas (TCGA) datasets. Then, we used differentially expressed gene (DEGs) to develop a signature for predicting patient outcomes, which was dubbed the "writer score" for RNA-modified writers. In addition, we analyzed the association between TME features, molecular subtypes, treatment sensitivity, and immunotherapy efficacy.

Results: We comprehensively evaluated the changes in multilayer RNA modification writers and identified the role of RNA modification writer expression imbalances in LUAD emergence and progression. Additionally, we constructed a risk-score model based on six LUAD prognosis-associated differentially expressed RNA modification writer genes. Kaplan-Meier (K-M) analyses revealed that the low risk-score signature had high overall patient survival. The predictive significance of the risk-score model was demonstrated using both univariate and multivariate Cox analyses. The risk-score model was positively correlated with the immune- and proliferation-related pathways. In response to anti-cancer treatment, high-risk score is related with high TMB, which has been discovered to correlate with immunotherapy effectiveness.

Conclusion: This study showed a strong correlation between the TME variety, level of complexity, and the four types of RNA modification writers. In addition, this scoring system could potentially predict effective immunotherapy and deepens our understanding of TME characteristics.