ObjectiveTo review the role of intestinal flora on the tumor microenvironment and the effect of both on the development of hepatocellular carcinoma (HCC), with a view to providing new ideas on the causes of HCC development and progression. MethodRelevant articles in the direction of intestinal flora and tumor microenvironment and HCC as well as the relationship between intestinal flora and tumor microenvironment in recent years were searched and summarized. ResultsThe tumor microenvironment played an important role in the occurrence, development and postoperative recurrence of HCC. The intestinal flora, as one of the important regulators of tumor microenvironment, could induce HCC by affecting the tumor microenvironment in addition to interacting with the liver through the gut-liver axis. ConclusionIntestinal flora can influence to HCC by regulating the tumor microenvironment, and its specific mechanism of action still needs to be further investigated, which can be a new direction for HCC research.
ObjectiveThis study aims to systematically review the dynamic evolution mechanisms of the tumor microenvironment (TME) in colorectal cancer liver metastasis (CRLM), to provide a theoretical basis for developing early diagnostic biomarkers and novel therapeutic targets for CRLM. MethodsBy integrating existing research, this review focuses on the key multi-step processes involved in CRLM-TME formation. It elaborates on the complex interactions among tumor cells, stromal cells, immune components, and key signaling pathways during this process, with an emphasis on their multi-factorial interplay. ResultsThe formation of the CRLM-TME involves several key steps: remote regulation by the primary tumor, specific recruitment of immune cells, adaptive remodeling of the liver microenvironment, and final colonization of the metastatic sites. This process is collectively driven by various factors such as tumor-derived metabolites, specific immune cell subsets, stromal components, and neovascularization, ultimately acts on the entire cascade of colorectal cancer cell invasion, migration, and colonization into the liver. ConclusionsThe CRLM-TME plays a critical role in the development, progression, treatment and drug resistance of CRLM. In-depth exploration of its mechanisms can provide direction for the development of early diagnostic biomarkers and therapies targeting the CRLM-TME, thereby aiming to improve the prognosis of CRLM patients.
ObjectiveTo investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7.MethodsTi6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR.ResultsCompared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant (P<0.05).Conclusion3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.
ObjectiveTo explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). MethodsThe Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. GO, KEGG, and GSEA enrichment analyses were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients' 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. ResultsDifferentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. ConclusionThe prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.
Objective To summarize the changes in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) in the context of immunotherapy and their impact on treatment outcomes. MethodsA systematic review of recent studies on the TME of PDAC was carried out to analyze the immune properties, intercellular interactions, and biological functions of its cellular and non-cellular components, disclose the molecular mechanisms of immunotherapy affects on the TME, explore the advancements in targeted therapy and potential biomarkers, and analyze the challenges in clinical applications and their impacts on the quality of life of patients. ResultsThe TME of PDAC exhibits highly immunosuppressive and heterogeneous characteristics, rich in diverse cells (such as pancreatic cancer cells, stellate cells, cancer-associated fibroblasts, immune cells) and non-cellular components (such as extracellular matrix). Immunotherapy is capable of regulating the immune balance in the TME and enhancing the anti-tumor response. Despite the progress made in multiple immunotherapy strategies (such as immune checkpoint inhibitors, chimeric antigen receptor cell therapy), challenges such as difficulty in selecting targets, drug resistance, and side effects still persist. Meanwhile, potential biomarkers such as leukemia inhibitory factor offer new directions for individualized treatment. ConclusionsThe TME of PDAC undergoes continuous changes during immunotherapy. In the future, it is requisite to integrate new technologies to deeply explore targets and biomarkers, optimize multimodal precise treatment strategies, enhance the safety and efficacy of immunotherapy, and improve the prognosis of patients.
Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
Lung cancer has a high morbidity and mortality, and invasion is one of the major factors that cause recurrence and death in lung cancer patients. Tumor-associated macrophages (TAMs) are cells that have the potential to secrete cytokines, growth hormones, inflammatory substrates, and protein hydrolases, which are associated with the growth, invasion and metastasis of tumors. In this article, we will explore the various chemicals that are manufactured to promote the invasion of lung cancer, as well as the numerous clinical therapeutic features that TAMs possess in the treatment of lung cancer. In addition, we look at the possibility that TAMs might be beneficial in the treatment of lung cancer. We have an innovative investigation of the huge variety of complex substances generated by TAMs, with the goal of determining whether or not the molecules under investigation have the potential to serve as new therapeutic targets. Throughout the whole of the presentation, a significant focus is placed on doing in-depth research to ascertain whether TAMs have the capability to reinforce as viable carriers for unique and creative medications. This not only provides novel concepts for the creation of new targeted therapies but also leads to the development of brand-new, cutting-edge methods for the manufacture of individualized medicines and drug carriers.
ObjectiveTo investigate the effect of Wnt5a derived from tumor-associated fibroblasts （CAFs） on the migration and invasion of gastric cancer cells. MethodsThe differentially expressed genes Wnt5a between CAFs and normal gastric fibroblasts (NGFs) in gastric cancer tissues and their corresponding normal gastric tissues using the GEO database GSE194261 dataset were screened. Immunohistochemical method was used to detect the expression of Wnt5a protein in tissue samples of clinical gastric cancer patients, and the relationship between Wnt5a protein expression and clinicopathological features of gastric cancer was analyzed. CAFs and NGFs were extracted from fresh surgical specimens of gastric cancer patients, and the expression of Wnt5a in CAFs was detected by real-time fluorescence quantitative-polymerase chain reaction and Western blot experiment. Transwell invasion and migration experiment was used to observe the effects of CAFs, inhibition of Wnt5a expression in CAFs and different concentrations of recombinant Wnt5a protein on the migration and invasion ability of gastric cancer MGC-803 and MKN-28 cell lines in vitro. ResultsThrough the screening of GEO database GSE194261 data set, it was found that Wnt5a was more expressed in CAFs than NGFs (P<0.05). Immunohistochemical results showed that the expression of Wnt5a protein in gastric cancer tissues was significantly stronger than that in normal gastric tissues (P<0.05), and the expression of Wnt5a protein was related to T stage of tumor (χ2=5.035, P<0.05), but not related to gender, age, degree of tumor differentiation, lymph node metastasis, vascular invasion and nerve invasion (P>0.05). Inhibiting Wnt5a derived from CAFs could inhibit the invasion and migration of gastric cancer cells. By stimulating gastric cancer cells with different concentrations of human recombinant Wnt5a protein, it was found that when the concentration of human recombinant Wnt5a protein was greater than 100 ng/mL, the invasion and migration abilities of MGC-803 and MKN-28 gastric cancer cells were significantly increased (P<0.05). ConclusionWnt5a is highly expressed in CAFs derived from the interstitial tissue of gastric cancer, which is related to the invasion depth of gastric cancer and can promote the invasion and migration of gastric cancer cells.
ObjectiveTo summarize the latest research progress and related mechanisms of cancer-associated fibroblasts (CAFs) in invasion, metastasis and drug resistance of breast cancer, so as to seek the best treatment strategy for patients with breast cancer metastasis and drug resistance. MethodThe literatures about CAFs research in breast cancer in recent years were searched and summarized. ResultsCAFs was the main stromal cell in tumor microenvironment (TME). By changing TME, the biological characteristics of CAFs could be changed and the growth and invasion of breast cancer cells could be induced. CAFs in breast cancer promotes the invasion and metastasis of breast cancer cells by interacting with inflammatory factors and promoting the formation of pre-transplantation ecosystems, and CAFs also mediates chemotherapy resistance to breast cancer, target resistance, endocrine resistance, and radiation resistance through the secretion of various cellular factors. ConclusionsAt present, some progress has been made in the research of CAFs in breast cancer, but there is still a certain gap to clinical application CAFs has a variety of functional phenotypes, so it is necessary to identify and characterize specific CAFs subtypes when studying new anti-CAFs therapeutic strategies. It has been proved that CAFs has great potential as a specific target for breast cancer treatment, but CAFs still lacks specific biomarkers. Therefore, an in-depth understanding of the biological characteristics and heterogeneity of CAFs can provide a reliable theoretical basis for developing drugs targeting CAFs.
ObjectiveTo summarize the research results of metabolites of breast cancer based on metabonomics technology, and systematically reviews them in order to provide a new direction for the research of metabolism of breast cancer.MethodBy searching the relevant literatures in recent years, the application of metabonomics in identifying high-risk breast cancer population, monitoring the progress of tumor and evaluating the response of radiotherapy and chemotherapy were analyzed and summarized.ResultsWith the development of high-resolution, high-sensitivity and high-throughput bioanalysis platform technology, metabolomics had been widely used in breast cancer research field by virtue of its unique perspective and technical advantages to more accurately, systematically and dynamically monitor the changes of host metabolites.ConclusionMetabolomics technology provides a new research direction for primary prevention, early screening and diagnosis of breast cancer and optimal treatment strategy selection.