Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation / 中华肿瘤杂志

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.

Research progress on active ingredients from traditional Chinese medicine as inhibitors of PD-1/PD-L1 of cancer immune checkpoint / 药学实践杂志

Tumor immunotherapy has become a new cancer treatment which has been expected to eliminate tumors. Immune checkpoint inhibitors, especially programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies, have achieved significant clinical efficacy in the treatment of solid tumors. But biologics possess disadvantages such as strong immunogenicity and high cost. Therefore, the discovery of small molecule drugs as immune checkpoint inhibitors may overcome the shortcomings of biologics and become a new challenge for future tumor immunotherapy. The active small molecules from traditional Chinese medicine that inhibit the expression of PD-1/PD-L1 and their regulatory effects on the tumor immune microenvironment were reviewed in this paper.

A cervical cancer tissue-derived decellularized extracellular matrix scaffold for cervical cancer tissue reconstruction in vitro / 南方医科大学学报

OBJECTIVE@#The prepare decellularized extracellular matrix (ECM) scaffold materials derived from human cervical carcinoma tissues for 3D culture of cervical carcinoma cells.@*METHODS@#Fresh human cervical carcinoma tissues were treated with sodium lauryl ether sulfate (SLES) solution to prepare decellularized ECM scaffolds. The scaffolds were examined for ECM microstructure and residual contents of key ECM components (collagen, glycosaminoglycan, and elastin) and genetic materials by pathological staining and biochemical content analysis. In vitro 3D culture models were established by injecting cultured cervical cancer cells into the prepared ECM scaffolds. The cells in the recellularized scaffolds were compared with those in a conventional 2D culture system for cell behaviors including migration, proliferation and epithelial-mesenchymal transition (EMT) wsing HE staining, immunohistochemical staining and molecular biological technology analysis. Resistance to 5-fluorouracil (5-Fu) of the cells in the two culture systems was tested by analyzing the cell apoptosis rates via flow cytometry.@*RESULTS@#SLES treatment effectively removed cells and genetic materials from human cervical carcinoma tissues but well preserved the microenvironment structure and biological activity of ECM. Compared with the 2D culture system, the 3D culture models significantly promoted proliferation, migration, EMT and 5-Fu resistance of human cervical cancer cells.@*CONCLUSION@#The decellularized ECM scaffolds prepared using human cervical carcinoma tissues provide the basis for construction of in vitro 3D culture models for human cervical cancer cells.

Tumor microenvironments self-activated nanoscale metal-organic frameworks for ferroptosis based cancer chemodynamic/photothermal/chemo therapy

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS

Optimization of Microenvironments Inducing Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Endothelial Cell-Like Cells

BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments.METHODS: TMSCs were preconditioned with Dulbecco's Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers.RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells.CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.

Trends in the scientific production on aquatic microhabitats phytotelmata: a scientometric study / Tendências na produção científica sobre microhabitats fitotelmata: um estudocienciométrico

We performed a scientometry to validate trends in the scientific production on phytotelmata and the importance of these microenvironments in the maintenance of biodiversity. We searched for articles in the Web of Science and looked at publications from 1987 to 2016. We collected years of publication, surveyed organisms, countries where the surveys took place, plants that accumulate phytotelmata, scientific journals that publish more about the topic and their respective IFs (Impact Factor) and the keywords of each article. We built a heatmap using the most frequent keywords in the studies, to investigate the topics studied over the years. We have found 293 publications, increasing over the years. Insects, anurans and crustaceans were the most studied organisms. The most studied plant families were Bromeliaceae, Poaceae and Apiaceae. The published studies analized were carried out mainly in Brazil, Argentina and Peru. The most published journals on the subject are: Zootaxa, Hydrobiologia, Biotropica and Journal of Natural History. Some main global concerns such as climate change, habitat fragmentation has gained the attention of the phytotelmata studies in the recent years. The results contribute to the knowledge about phytotelmata accumulated biodiversity and research trends.

Realizamos uma cienciometria para demonstrar tendências na produção científica sobre fitotelmata e a importância desses microambientes na manutenção da biodiversidade. Buscamos artigos no Web of Science e analisamos publicações de 1987 até 2016. Coletamos os anos de publicação, organismos estudados, países onde ocorreram as pesquisas, plantas que acumulam fitotelmata, revistas científicas que mais publicam sobre o tema e seus respectivos FIs (Fator de Impacto) e as palavras-chave de cada artigo. Fizemos um heatmap, utilizando as palavras-chave mais frequentes nos estudos, para investigar os tópicos estudados ao longo dos anos. Encontramos 293 publicações, com aumento ao longo dos anos. Os insetos, anuros e crustáceos foram os organismos mais estudados. As famílias de plantas mais estudadas foram Bromeliaceae, Poaceae e Apiaceae. As pesquisas foram realizadas, principalmente, no Brasil, na Argentina e no Peru. Os periódicos que mais publicam sobre o tema são: Zootaxa, Hydrobiologia, Biotropica e Journal of Natural History. Os resultados contribuem para o conhecimento sobre a biodiversidade acumulada em fitotelmata e tendências nas pesquisas.

Tumor microenvironment and tumor / 国际肿瘤学杂志

Rational microenvironment contributes actively to cancer development through multiple mechanisms including triggering genomics instability,providing shield,promoting immune escape,inducing differentiation and permissive nich.Tumorigenesis reversely promotes the form of tumor microenvironment composed of hypoxia,decreasing pH,angiogenesis and nutrition deficiency.Tumor microenvironment not only is the reasons but also results in cancer development and progression.A better understanding of how the tumor environment affects cancer progression would provide the new strategy for cancer therapy.