ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Chenglin Li,Rui Li,Xueyuan Wu,Yifan Zuo,Guixiang Xiong,Meng Huang,Yuqing Sun,Rong Liao,Yang Xiao,Lili Hu,Chao Gao,Yanyan Yu
Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial–mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe3O4@SiO2@PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe3O4@SiO2, which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe3O4@SiO2 improved the anti-nonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe3O4@SiO2@PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.
研究领域:
癌症生物学
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生物医学工程
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临床肿瘤学
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分子诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Oncology
·
2024
·
IF 4.5
Zhan Li,Guanyu Yan,Meiqi Yang,Xingwu Liu,Yuan Lian,Mingjun Sun,Wenjun Pan
CBLC (CBL proto-oncogene C) is an E3 ubiquitin protein ligase that plays a key role in cancers. However, the function and mechanism of CBLC in colorectal cancer (CRC) has not been fully elucidated. The aim of this study was to investigate the function of CBLC in CRC and its underlying molecular mechanism. High CBLC levels were certified in tumor tissues of CRC patients, and its expression was positively associated with TNM stage. Next, we explored the role of CBLC in CRC using gain or loss of function. For biological function analysis, CCK-8 cell proliferation, colony formation, flow cytometry, scratch, and transwell assays collectively suggested that CBLC overexpression promoted cell proliferation, cell cycle progression, migration and invasion. As observed, CBLC knockdown exhibited exactly opposite effects, resulting in impaired tumorigenicity in vitro . Xenograft studies displayed that CBLC overexpression accelerated tumor growth and promoted tumor metastasis to the lung, while the inhibitory effects of CBLC knockdown on tumorigenicity and metastasis ability of CRC cells was also confirmed. Furthermore, the molecular mechanism of CBLC in CRC was explored. CBLC induced the activation of ERK signaling pathway, further leading to its pro-tumor role. Notably, CBLC decreased ABI1 (Abelson interactor protein-1, a candidate tumor suppressor) protein levels through its ubiquitin ligase activity, while ABI1 upregulation abolished the effects of CBLC on the tumorigenesis of CRC. Taken together, these results demonstrate that CBLC acts as a tumor promoter in CRC through triggering the ubiquitination and degradation of ABI1 and activating the ERK signaling pathway. CBLC may be a potential novel target for CRC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Fang Shi,Yong-Sheng Gao,Shu-Mei Han,Cheng-Suo Huang,Qing-Sheng Hou,Xiao-wen Wen,Ben-Shi Wang,Zhen-Yu Zhu,Lei Zou
Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10 -/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.
研究领域:
胃肠病学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2024
·Vol. 43
·期 1
·1-27
·
IF 11.4
Shan Junqi,Li Xinyu,Sun Runqi,Yao Yao,Sun Yan,Kuang Qin,Dai Xianling,Sun Yanlai
Background The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches. Imbalances in the processes of lipid oxidation and biosynthesis of fatty acids are significant risk factors for the development of CRC. Therapeutic intervention that specifically targets the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream response element, in response to lipid metabolism, has been found to promote the growth of tumors and has shown significant clinical advantages in cancer patients. Methods Clinical CRC samples and extensive in vitro and in vivo experiments were carried out to determine the role of ZDHHC6 and its downstream targets via a series of biochemical assays, molecular analysis approaches and lipid metabolomics assay, etc. Results To study the effect of ZDHHC6 on the progression of CRC and identify whether ZDHHC6 is a palmitoyltransferase that regulates fatty acid synthesis, which directly palmitoylates and stabilizes PPARγ, and this stabilization in turn activates the ACLY transcription-related metabolic pathway. In this study, we demonstrate that PPARγ undergoes palmitoylation in its DNA binding domain (DBD) section. This lipid-related modification enhances the stability of PPARγ protein by preventing its destabilization. As a result, palmitoylated PPARγ inhibits its degradation induced by the lysosome and facilitates its translocation into the nucleus. In addition, we have identified zinc finger-aspartate-histidine-cysteine 6 (ZDHHC6) as a crucial controller of fatty acid biosynthesis. ZDHHC6 directly interacts with and adds palmitoyl groups to stabilize PPARγ at the Cys-313 site within the DBD domain of PPARγ. Consequently, this palmitoylation leads to an increase in the expression of ATP citrate lyase (ACLY). Furthermore, our findings reveals that ZDHHC6 actively stimulates the production of fatty acids and plays a role in the development of colorectal cancer. However, we have observed a significant reduction in the cancer-causing effects when the expression of ZDHHC6 is inhibited in in vivo trials. Significantly, in CRC, there is a strong positive correlation between the high expression of ZDHHC6 and the expression of PPARγ. Moreover, this high expression of ZDHHC6 is connected with the severity of CRC and is indicative of a poor prognosis. Conclusions We have discovered a mechanism in which lipid biosynthesis is controlled by ZDHHC6 and includes the signaling of PPARγ-ACLY in the advancement of CRC. This finding provides a justification for targeting lipid synthesis by blocking ZDHHC6 as a potential therapeutic approach.
研究领域:
癌症生物学
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分子生物学
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脂质代谢
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2024
·Vol. 7
·期 8
·2400045
·
IF 3.7
Shanshan Wang,Zhiqiang Bi,Tianming Lu,Ruoning Qian,Jie Yu,Qiang Zhang,Hao Yang,Wenli Lu,Yuanyuan Guo,Xiaoqing Xin,Yong Bian,Ruogu Qi
Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.
研究领域:
肿瘤学
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纳米技术
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药理学
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细胞生物学
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治疗学
✓ 已验证
产品关联
DOI
高影响因子
Gut Microbes
·
2024
·
IF 12.2
Fangfang Chen,Songhe Guo,Yiqiu Li,Yongfan Lu,Le Liu,Shengxin Chen,Jun An,Ge Zhang
The intracellular bacterium Fusobacterium nucleatum (Fn) mediates tumorigenesis and progression in colorectal cancer (CRC). However, the origin of intratumoral Fn and the role of Fn-infected immunocytes in the tumor microenvironment remain unclear. Here, we observed that Fn-infected neutrophils/macrophages (PMNs/MΦs), especially PMNs, accumulate in tumor tissues and fecal Fn abundance correlates positively with an abundance of blood PD-L1+ PMNs in CRC patients. Moreover, Fn accumulates in tumor tissues of tumor-bearing mice via intragingival infection and intravenous injection. Mechanistically, Fn can survive inside PMNs by reducing intracellular ROS levels and producing H2S. Specifically, the lysozyme inhibitor Fn1792 as a novel virulence factor of Fn suppressed apoptosis of phagocytes by inducing CX3CR1 expression. Furthermore, Fn-driven CX3CR1+PD-L1+ phagocytes transfer intracellular Fn to tumor cells, which recruit PMNs/MΦs through the CXCL2/8-CXCR2 and CCL5/CCR5 axes. Consequently, CX3CR1+PD-L1+ PMNs infiltration promotes CRC metastasis and weakens the efficacy of immunotherapy. Treatment with the doxycycline eradicated intracellular Fn, thereby reducing the CX3CR1+PD-L1+ PMNs populations and slowing Fn-promoted tumor growth and metastasis in mice. These results suggest phagocytes as Fn-presenting cells use mutualistic strategies to home to tumor tissues and induce immunosuppression, and treatment with ROS-enhanced antibiotics can inhibit Fn-positive tumor progression.
研究领域:
肿瘤学
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免疫学
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微生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Fang Shi,Yong-Sheng Gao,Shu-Mei Han,Huan Shi,Qing-Sheng Hou,Yang Gao,Xiao-Wen Wen,Zhen-Yu Zhu,Kai Liu,Wei-Peng Gong,Ben-Shi Wang,Xin Liu,Lei Zou
There is a growing amount of research that highlights the significant connection between the development of colitis and both metabolic imbalance and the inflammatory response. Tagatose, an inherent sweetening agent and alternative to sugar, plays a crucial role in the biosynthesis of several chemicals and metabolic pathways in living organisms. However, the specific biochemical mechanism via which tagatose hinders colitis is still not understood. According to recent study, tagatose plays a crucial role in safeguarding the integrity of tight junctions inside the intestinal mucosal barrier. Furthermore, it is crucial to acknowledge the presence of a correlation between the severity of inflammatory bowel disease (IBD) and the occurrence of colorectal cancer (CRC), chemically-induced colitis in rodents, and reduced blood levels of tagatose. The treatment of tagatose resulted in a decrease in intestinal mucosal injury in mice with colitis, regardless of whether it was caused by dextran sodium sulfate (DSS) or spontaneous colitis in IL-10 -/- mice and C3H/HeJBir mice. The introduction of tagatose in a colitis model triggers a cascade of events, wherein it hinders the expulsion of cathepsin B and enhances lysosomal cohesiveness. The aforementioned method successfully inhibits the activity of myosin light chain kinase (MLCK) in the context of intestinal epithelial damage, hence impeding the deterioration of tight junction integrity and the initiation of mitochondrial dysfunction. In summary, the outcomes of the study have provided empirical evidence that substantiates the beneficial effects of tagatose in mitigating the progression of colitis. The ability to prevent the disruption of the intestinal barrier is responsible for this achievement. Hence, tagatose has promise as a therapeutic adjunct for the management of colitis.
研究领域:
胃肠病学
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药理学
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免疫学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Minxuan Xu,Fang Shi,Yongshen Gao,Shumei Han,Chensuo Huang,Qinsheng Hou,Xiaoweng Wen,Bengshi Wang,Zhenyu Zhu,Lei Zou,Mingxin Xiong,Wei Dong,Jun Tan
There is a growing amount of research that highlights the significant involvement of metabolic imbalance and the inflammatory response in the advancement of colitis. Arabinose is a naturally occurring bioactive monosaccharide that plays a crucial role in the metabolic processes and synthesis of many compounds in living organisms. However, the more detailed molecular mechanism by which the administration of arabinose alleviates the progression of colitis and its associated carcinogenesis is still not fully understood. In the present study, arabinose is recognized as a significant and inherent protector of the intestinal mucosal barrier through its role in preserving the integrity of tight junctions within the intestines. Also, it is important to note that there is a positive correlation between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), as well as chemically-induced colitis in mice, and lower levels of arabinose in the bloodstream. In two mouse models of colitis, caused by dextran sodium sulfate (DSS) or by spontaneous colitis in IL-10 -/- mice, damage to the intestinal mucosa was reduced by giving the mice arabinose. When arabinose is administrated to model with colitis, it sets off a chain of events that help keep the lysosomes together and stop cathepsin B from being released. During the progression of intestinal epithelial injury, this process blocks myosin light chain kinase (MLCK) from damaging tight junctions and causing mitochondrial dysfunction. In summary, the results of the study have provided evidence supporting the beneficial effects of arabinose in mitigating the progression of colitis. This is achieved through its ability to avoid dysregulation of the intestinal barrier. Consequently, arabinose may hold promise as a therapeutic supplementation for the management of colitis.
研究领域:
胃肠病学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Ke Cai,Xin-Yue Cao,Fan Chen,Yue Zhu,Dong-Dong Sun,Hai-Bo Cheng,Jin-Ao Duan,Shu-Lan SU
ABSTRACT Background Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. Purpose The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. Methods The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. Results The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of β -catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1 , and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. Conclusion The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.
研究领域:
肿瘤学
·
药理学
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微生物学
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代谢组学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Zhipeng Jiang,Zehui Hou,Wei Liu,Zhuomin Yu,Zhiqiang Liang,Shuang Chen
The dysregulated circular RNAs (circRNAs) are linked to progression and chemoresistance in colorectal cancer (CRC). However, the role of circRNA protein tyrosine kinase 2 (circPTK2) in CRC progression and chemoresistance is uncertain. The circPTK2, microRNA (miR)-136-5p, m6A ‘reader’ protein YTH domain family protein 1 (YTHDF1), β-catenin and cyclin D1 abundances were examined via quantitative reverse transcription PCR or Western blotting. The progression was investigated by cell counting kit-8 (CCK-8), colony formation, transwell and xenograft analysis. The resistance to 5-fluorouracil (5-FU) and oxaliplatin was analyzed via detecting cell viability and apoptosis using CCK-8 analysis and flow cytometry. The binding relationship was examined through dual-luciferase reporter, RNA immunoprecipitation and pull-down analysis. In our study, circPTK2 abundance was enhanced in CRC and associated with liver metastasis, clinical stage and chemoresistance. CircPTK2 knockdown constrained cell proliferation, migration, invasion, resistance to 5-FU and oxaliplatin, and the Wnt/β-catenin signaling. MiR-136-5p was bound with circPTK2 and downregulated in CRC. MiR-136-5p knockdown attenuated the influence of circPTK2 silence on CRC progression and chemoresistance. YTHDF1 was targeted via miR-136-5p and upregulated in CRC samples and cells. MiR-136-5p targeted YTHDF1 to restrain CRC progression and chemoresistance. In addition, we confirmed that circPTK2 silence reduced xenograft tumor growth. In conclusion, circPTK2 interference suppressed CRC proliferation, migration, invasion and chemoresistance via regulating miR-136-5p and YTHDF1.Abbreviations: circRNAs: circular RNAs; CRC: colorectal cancer; circPTK2: circRNA protein tyrosine kinase 2; miR: microRNA; YTHDF1: YTH domain family protein 1; CCK-8: cell counting kit-8; 5-FU: 5-fluorouracil; RIP: RNA immunoprecipitation.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jianqing Peng,Jia Zhou,Xing Liu,Xiaobo Zhang,Xiang Zhou,Zipeng Gong,Yi Chen,Xiangchun Shen,Yan Chen
Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H 2 O 2 ). Given that H 2 O 2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H 2 O 2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l -lactide- co -glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to “fix” CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution . This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.
研究领域:
癌症生物学
·
药学
·
纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2025
·
IF 5.9
Xin Wei,Yuyan Guo,Jianyuan Lei,Na Chen
Introduction Microsatellite stable colorectal cancer (MSS-CRC) is referred to as an immune desert-type tumor. Emerging studies have demonstrated that inhibition of the Wnt/β-catenin pathway can enhance the anti-tumor immune response. This research focuses on synthesizing the human serum albumin (HSA) -based Wnt inhibitor GHSACA and assessing its internalization pathway and therapeutic effectiveness in conjunction with PD-1 antibody for treating MSS-CRC. Methods Glucosamine was covalently conjugated to HSA via EDC/NHS activation to generate GHSA, which was subsequently coupled with carnosic acid (CA) -Wnt pathway inhibitor, to synthesize GHSACA. For in vitro studies, LOX1- and CD44- deficient MC38 and CT26 colon cancer cell lines, validated by RT-qPCR, were used to investigate the cellular uptake mechanism and macropinocytic activity of GHSACA using flow cytometry. The effectiveness of GHSACA in targeting tumors in vivo was assessed in CT26 tumor-bearing BALB/c mice via fluorescence imaging. Therapeutic efficacy was assessed in MSS-CRC patient-derived xenograft (PDX). Results RT-qPCR confirmed efficient knockdown of LOX1 and CD44 in both MC38 and CT26 cell lines. Cellular uptake assay demonstrated that GHSACA internalization is predominantly mediated by the LOX1-dependent macropinocytosis pathway. In vivo fluorescence imaging revealed sustained accumulation of GHSACA in tumor and rapid clearance from normal organs. In the PDX model, GHSACA monotherapy significantly suppressed tumor growth (TGI = 59.3%). The combination with PD-1 antibody (G&P group) resulted in further enhancement of antitumor efficacy (TGI = 87.9%). TUNEL assays showed the most pronounced induction of tumor cell apoptosis in the G&P group. Immunohistochemical analysis demonstrated that GHSACA suppressed the Wnt/β-catenin signaling cascades, alongside with lower Ki67 expression. The G&P combination increased PD-L1 expression and significantly boosted Granzyme B-positive cytotoxic immune responses. Immunofluorescence double staining showed the highest infiltration of CD3 + /CD8 + cytotoxic T lymphocytes of the G&P group, with a concurrent decrease in CD4 + /CD25 + regulatory T cells. GHSACA was found to have favorable systemic biocompatibility and safety. Discussion GHSACA achieves efficient targeted cellular internalization via a macropinocytosis pathway regulated by the LOX1 receptor rather than the CD44 receptor, simultaneously inhibiting the Wnt/β-catenin signaling while activating anti-tumor immune responses. It provides a highly promising translational therapeutic approach for overcoming immune resistance in MSS-CRC.
研究领域:
肿瘤学
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纳米医学
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免疫治疗
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分子生物学
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药物递送
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癌症免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）