The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only ...plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE
, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will ...help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advanced HCC, including immune checkpoint inhibitors, adoptive cell therapy, engineered cytokines, and therapeutic cancer vaccines. In this review, we summarize the current landscape and research progress of different immunotherapy strategies in the treatment of HCC. The challenges and opportunities of this research field are also discussed.
Exosomal miRNAs in tumor microenvironment Tan, Shiming; Xia, Longzheng; Yi, Pin ...
Journal of experimental & clinical cancer research,
04/2020, Volume:
39, Issue:
1
Journal Article
Peer reviewed
Open access
Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, ...such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.
CO2-based poly(ester-co-carbonate)s synthesized through the copolymerization of epoxides and CO2 with cyclic anhydrides and/or cyclic esters have continuously received attention due to their tunable ...degradability and adjustable thermal and mechanical properties. A variety of catalysts have been developed for this methodology, including zinc, cobalt, and chromium complexes, which can provide well-defined polymers. In this review, we provide a thorough account of the catalysts used in the copolymerization of epoxides and CO2 with cyclic anhydrides and/or cyclic esters. The development direction and future perspectives of catalyst design are also discussed.A variety of catalysts including zinc, cobalt and chromium complexes were reviewed for the copolymerization of epoxides and CO2 with cyclic anhydrides and/or cyclic esters to synthesize CO2-based poly(ester-co-carbonate)s. The structure and structure-performance relationship of the as-prepared copolymers were discussed in detailed.
•A dynamic model to evaluate ecological cumulative effect in mining area was proposed.•The model was built on 3 dimensions, namely pixels, the whole time series and ESV.•The model has advantages in ...revealing spatial heterogeneity and dynamic process.•ESV obtained by RS-based dynamic equivalent factor method has high credibility.
Study on the ecological cumulative effect (ECE) in mining area is an effective way to understand the impact of long-term coal mining on the ecological environment. However, the existing quantitative models to evaluate the ECE in mining area focus more on region-wide features, static analysis and multi-temporal comparison with numerical results, but less on the spatial heterogeneity, dynamic changes trajectory and visual mapping of ECE. In order to fill this gap, we have proposed a pixel-based time series model of ecosystem service value (ESV) to quantify the ECE in mining area and reveal its spatial distribution, heterogeneity and dynamic process. The model was constructed from three dimensions, namely space, time and element, which were analyzed from pixel scale, the whole research period and the perspective of ESV respectively. Taking Yanzhou coalfield as the study area, from 1987 to 2016 as the time span, the model was used to analyze the ECE. The study results showed that: 1) it could display the detail about each pixel’s spatio-temporal change of ESV credibly by dynamic equivalent factor method based on time-series remote sensing (RS), with equivalent factor rectified by remote sensing-based ecological index (RSEI) and modified normalized difference water index (MNDWI) pixel by pixel. 2) The pixel-based time series model of ESV showed a good performance in reflecting the spatial distribution and heterogeneity of ECE, revealing the direction and extent of accumulation, and achieving the dynamic evaluation of ECE in the time dimension. 3) The change of ecosystem service value cumulant (COESVC) in Yanzhou coalfield decreased by 644.49 million RMB, showing obviously negative ECE. The areas with negative ECE were mainly distributed outside the area above mining faces, while that with positive ECE mostly appeared in waterlogged areas, especially those within the area above mining faces. The evaluation result of ECE could be used in decision-making for improving ecological quality and developing coal mining strategies. This paper may also offer an idea and method for dynamic and quantitative evaluation of the ECE in mining and similar area by time-series Landsat-based RS.
Cancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of POU domain class 2 ...transcription factor 1 (POU2F1) on metabolic reprogramming in colon cancer. The POU2F1 expression was analyzed in GEO dataset, TCGA cohorts and human colon cancer tissues by bioinformatics and immunohistochemistry. The effects of altered POU2F1 expression on proliferation, glucose metabolism and oxaliplatin sensitivity of colon cancer cells were tested. The impacts of POU2F1 on aldolase A (ALDOA) expression and malignant behaviors of colon cancer cells were examined. We found that up-regulated POU2F1 expression was associated with worse prognosis and oxaliplatin resistance in colon cancer. POU2F1 enhanced the proliferation, aerobic glycolysis and the pentose phosphate pathway (PPP) activity, but reduced oxidative stress and apoptosis in colon cancer cells, dependent on up-regulating ALDOA expression. Mechanistically, POU2F1 directly bound to the ALDOA promoter to enhance the ALDOA promoter activity in colon cancer cells. Moreover, activation of the POU2F1-ALDOA axis decreased the sensitivity to oxaliplatin in colon cancer cells. These data indicate that the POU2F1-ALDOA axis promotes the progression and oxaliplatin resistance by enhancing metabolic reprogramming in colon cancer. Our findings suggest that the POU2F1-ALDOA axis may be new therapeutic targets to overcome oxaliplatin resistance in colon cancer.
Reprogramming of cancer metabolism is a newly recognized hallmark of malignancy. The aberrant glucose metabolism is associated with dramatically increased bioenergetics, biosynthetic, and redox ...demands, which is vital to maintain rapid cell proliferation, tumor progression, and resistance to chemotherapy and radiation. When the glucose metabolism of cancer is rewiring, the characters of cancer will also occur corresponding changes to regulate the chemo- and radio-resistance of cancer. The procedure is involved in the alteration of many activities, such as the aberrant DNA repairing, enhanced autophagy, oxygen-deficient environment, and increasing exosomes secretions, etc. Targeting altered metabolic pathways related with the glucose metabolism has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of glucose metabolism in chemo- and radio-resistance malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.
RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, ...morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.
Objective
For microtia patients with excessively insufficient postauricular skin, it is difficult to obtain a satisfied outcome with existing strategies. In this study, we developed a modified tissue ...expander method for auricular reconstruction.
Methods
The modified tissue expander method divided into 4 stages. In the first stage, a 30 ml or 50 ml kidney-shaped tissue expander was implanted in the mastoid region. A short time expansion (average 33.5 days) was conducted subsequently. In the second stage, the expander was removed and a modified cartilage framework without tragus was inserted through the same incision. A crescent-shaped cartilage pad was inserted into the incision of cartilage-harvest site at the same time. In the third stage, the reconstructed ear was elevated. Lobule rotation and remanent modification were performed in the fourth stage. The patients were followed up between half a year and 10 years. The outcomes of the reconstructed ears were scored with evaluation criteria.
Results
From January 2010 to December 2019, a total of 45 microtia patients with excessively insufficient postauricular skin were performed the modified tissue expander method. Fourty-two patients showed satisfied outcomes. Complications such as hyperpigmentation in the skin graft area (3, 6.7%), scar hyperplasia (3, 6.7%) and folliculitis (1, 2.2%) were found. There were no complications related to the tissue expander.
Conclusion
The modified tissue expander method is an effective and safe technique for auricular reconstruction in patients having excessively insufficient postauricular skin, with satisfying medium-term results.