Objective
To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC).
Method
The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed.
Results
The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of the vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating the angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough.
Conclusion
Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.
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 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.
ObjectiveTo explore the changes of cytokines in the tumor microenvironment of colorectal cancer and the relationship between the expression of CD16a mRNA and cytokines in the microenvironment.MethodsRT-PCR and flow cytometry microsphere array (CBA) were used to detect the expressions of CD16a mRNA, as well as cytokines of Th1 ［interleukin (IL)-2, IL-12, and interferone-γ (IFN-γ)］, Th2 (IL-4, IL-6, and IL-10), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) in the tumor and the adjacent tissues of 42 patients with colorectal cancer, respectively, and the correlation between the expression of CD16a mRNA and cytokines in the microenvironment was analyzed.ResultsThe expressions of IL-6, TNF-α, and VEGF in colorectal cancer tissues were significantly higher than those in the adjacent tissues (P<0.05). There was no significant difference in the expression of IL-2,IL-4, IL-10, IL-12, and IFN-γ between the two kinds of tissues (P>0.05). Clinicopathological factor analysis showed that, the levels of IL-6 and VEGF in the colorectal cancer patients with preoperative normal CEA were significantly higher than those with elevated CEA (P<0.05). Correlation analysis showed that the expression of IL-6 was negatively correlated with expression of CD16a mRNA (P<0.05).ConclusionsThe expressions of IL-6, TNF-α, and VEGF in tumor tissues were significantly higher than adjacent tissues, and the effect of angiogenic and immunosuppression were enhanced. The expression of CD16a mRNA in the microenvironment of colorectal cancer tumor is negatively correlated with the expression of IL-6.
Objective
To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them.
Methods
Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma.
Result
Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma.
Conclusions
The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
ObjectiveTo summarize the research progress of hepatocellular carcinoma (HCC) based on tumor microenvironment immunophenotyping.MethodThe related literatures of basic and clinical studies on HCC immunophenotyping in the recent years were reviewed.ResultsHCC could be divided into different immunophenotypes based on tumor microenvironment, and it showed different immune molecular characteristics, immune cell infiltration characteristics, and anti-tumor ability. At the same time, the HCC immunophenotype was significantly associated with patients’ survival and had been proved to be able to better evaluate the prognosis of HCC patients. According to the relevant molecular characteristics in the HCC immune microenvironment, it could provide guidance for the drug regimen of immunotherapy.ConclusionHCC immunophenotyping is still in the early stage of research, and its clinical application value has been preliminarily shown for the evaluation of patients’ prognosis and immunotherapy decision-making, which is a new idea of individualized treatment of HCC in the future.
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.
ObjectiveTo summarize the molecular mechanisms and clinical treatment of gastric cancer with liver metastasis (GCLM), in order to provide new ideas for future treatment. MethodThe literatures about mechanism and treatment strategy of GCLM in recent years were searched and reviewed. ResultsMost patients with gastric cancer were in advanced stage or had developed distant metastases when they were first diagnosed, among which liver was the common site of metastasis. The complex molecular mechanisms of GCLM had not been fully clarified. Molecular mechanisms at different levels, including non-coding RNA, circulating tumor cells, exosomes, tumor microenvironment and signaling pathways, were relatively independent and interacted with each other, providing potential biomarkers and therapeutic targets for GCLM. At present, the best treatment method for patients with GCLM was mainly divided into local and systemic treatment. The local treatment included surgical treatment, radiofrequency ablation and proton beam therapy, while the systemic treatment included systemic chemotherapy, targeted therapy and immunotherapy, among which the targeted therapy and immunotherapy were the focus of recent research. ConclusionsThe mechanism of GCLM is the result of the interaction between tumor cells and the microenvironment at the site of metastasis. Understanding them is of great significance to guide clinical treatment and prognosis. At present, there is no unified treatment standard for GCLM. To achieve the ideal treatment effect, we should not only rely on single therapy, but also adopt multi-disciplinary and individual therapy according to the specific disease status of patients and the nature of tumors.
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.
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.
