Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors

Gao, Fan; Tang, Ying; Liu, Wenlong; Zou, Mei‐Zhen; Huang, Chiu-Jung; Liu, Chuan-Jun; Zhang, Xian‐Zheng

doi:10.1002/adma.201904639

Cited by 275 publications

(230 citation statements)

References 47 publications

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“…Figure 3B shows that the mean particle size of PAMAM-PEG-EpDT3/pMEG3 NPs was 180±0.15 nm with a polydispersity of 0.236 and zeta potential 19.7±0.23 mV ( Figure 3C). The appropriate particle size and zeta potential ensure that the NPs are enriched in tumor tissues through the enhanced permeability and retention effect (EPR) effect and taken up by tumor cells [31,32].…”

Section: Resultsmentioning

confidence: 99%

Aptamer-Functionalized Dendrimer Delivery lncRNA MEG3 Enhances Castration-Resistant Prostate Cancer Gene Therapy

Tai¹,

Ma²,

Ding³

et al. 2020

Preprint

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Androgen castration therapy is an effective treatment method for prostate cancer patients who cannot be completely cured by surgery. However, drug resistance often leads to treatment failure and poor prognosis. For castration-resistant prostate cancer (CRPC), some new treatment methods have been gradually put into clinical validation or use. Considering the side effects of traditional treatment, gene therapy has been applied in recent studies to combat prostate cancer (PCa). A 19-nt RNA aptamer, termed as EpDT3, is endocytosed when bound to epithelial cell adhesion molecule EpCAM-overexpressing cells, including various types of prostate cancer cells. Therefore, poly (amidoamine) dendrimer (PAMAM) conjugated with EpDT3 on the surface was developed for gene delivery targeting the CRPC. Moreover, the PAMAM-PEG-EpDT3 vehicles were accumulated in CRPC cells. The CRPC-inhibitory effect of PAMAM modified with EpDT3 was significantly higher than that of the unmodified construct when loading the plasmid that encodes long noncoding (lnc) RNA MEG3 (pMEG3). In summary, the above results suggested that PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) have great potential for enhancing CRPC gene therapy.

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Section: Resultsmentioning

confidence: 99%

Aptamer-Functionalized Dendrimer Delivery lncRNA MEG3 Enhances Castration-Resistant Prostate Cancer Gene Therapy

Tai¹,

Ma²,

Ding³

et al. 2020

Preprint

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show abstract

“…In addition, through the pentose phosphate pathway (PPP)a bypass of glycolysis-glucose can be transformed into nucleotide, which is essential for tumor cell proliferation (43). Excess lactic acid production, a glycolysis product, plays a pro-inflammatory and anti-immune role in human cancer (44,45). TLRs have been reported to control glycolysis in immune system cells (46,47).…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin 2/Toll-Like Receptor 4 Axis Contributes to HIF-1α-Derived Glycolysis in Colorectal Cancer

Kuerbanjiang

et al. 2020

Front. Oncol.

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“…It has been reported that aerobic glycolysis in tumors constantly produces lactic acid, which provides energy for the tumor, and the increased lactic acid in the microenvironment could also affect the immunotherapy effect [43]. It has also been found that antitumor metabolism therapy combined with immunotherapy can effectively inhibit tumor growth [44]. To further explore the relationship between the glycolysis-related gene signature and immune cell in ltration and immune function, we rst analyzed the immune scores, stromal scores and ESTIMATE scores of patients in the high-risk subgroup and low-risk subgroup based on our gene signature.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Association Between the Glycolysis Prognostic Risk Signature and Immune Infiltration in Endometrial Cancer

Yang

Shen

et al. 2020

Preprint

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Background: Glycolysis is the primary mechanism of energy metabolism in tumor cells. The purpose of this study is to develop a glycolysis-related risk signature for endometrial cancer and analyze its relationship with immune function.Methods: The mRNA expression profiling and clinical information of endometrial cancer were downloaded from TCGA database. GSEA was performed to screen out gene sets related to glycolysis, and the R software was used to screen DEGs. Univariate Cox and LASSO regression analyses were used to construct a glycolysis-related prognostic signature for endometrial cancer. WGCNA were performed to identify the potential mechanisms associated with the prognostic signature. Immune scores, stromal scores and ESTIMATE scores were calculated based on the R “ESTIMATE” algorithm. The “CIBERSORT” algorithm was used to evaluate the infiltration of immune cells. ROC curve, nomogram, gene alteration, coexpression analyses and PPIs were also performed. Results: We identified a glycolysis-related gene signature (PFKM, PSMC4, NUP85, PDHA1, CDK1, CLDN9, CENPA, GPI, NUP155 and GPCI) for predicting the prognosis of endometrial cancer. Based on this gene signature, the patients were divided into high- and low-risk subgroups. The overall survival of patients in the high-risk subgroup was significantly lower than that of the low-risk group. Multivariate Cox regression analysis results showed that the ten-gene signature was an independent prognostic factor for endometrial cancer. The ROC curve confirmed the accuracy of the prognostic signature (AUC=0.730). The immune scores and ESTIMATE scores of patients in the high-risk subgroup were lower than those of the low-risk subgroup, while the low immune score and ESTIMATE scores were closely related to the poor prognosis of patients. The high-risk group was associated with lower cellular immune infiltration of resting dendritic cells, resting memory T cells and Tregs, while the overall survival rate of resting dendritic cells and Tregs in the low-proportion group was significantly lower than that in the high-proportion group. Conclusions: we constructed a glycolysis-related ten-gene signature to predict the survival and prognosis of endometrial cancer. Our findings may help to elucidate the mechanism of glycolysis and provide new ideas for targeted therapy and prognosis of endometrial cancer.

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Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors

Cited by 275 publications

References 47 publications

Aptamer-Functionalized Dendrimer Delivery lncRNA MEG3 Enhances Castration-Resistant Prostate Cancer Gene Therapy

Aptamer-Functionalized Dendrimer Delivery lncRNA MEG3 Enhances Castration-Resistant Prostate Cancer Gene Therapy

Thrombospondin 2/Toll-Like Receptor 4 Axis Contributes to HIF-1α-Derived Glycolysis in Colorectal Cancer

Comprehensive Analysis of the Association Between the Glycolysis Prognostic Risk Signature and Immune Infiltration in Endometrial Cancer

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