Synthesis and crystal structure of a novel copper(ii) complex of curcumin-type and its application in in vitro and in vivo imaging

2014 ◽  
Vol 2 (23) ◽  
pp. 3659-3666 ◽  
Author(s):  
Guoyong Xu ◽  
Jiafeng Wang ◽  
Tao Liu ◽  
Mahong Wang ◽  
Shuangsheng Zhou ◽  
...  

The results of TPEF imaging in a tumor-bearing mouse model demonstrated the potential of the obtained complex for in vivo tumor diagnosis.

2015 ◽  
Vol 4 (11) ◽  
pp. 1767-1780 ◽  
Author(s):  
Narayanan K. Narayanan ◽  
Kazuhiro Kunimasa ◽  
Yukio Yamori ◽  
Mari Mori ◽  
Hideki Mori ◽  
...  

Talanta ◽  
2017 ◽  
Vol 175 ◽  
pp. 421-426 ◽  
Author(s):  
Hong-Wen Liu ◽  
Xiao-Xiao Hu ◽  
Longmin Zhu ◽  
Ke Li ◽  
Qiming Rong ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Ramazan Rezaei ◽  
Kaveh Baghaei ◽  
Seyed Mahmoud Hashemi ◽  
Mohammad Reza Zali ◽  
Hossein Ghanbarian ◽  
...  

Exosomes have been introduced as a new alternative delivery system for the transmission of small molecules. Tumor-derived exosomes (TEXs) not only contain tumor-associated antigens to stimulate antitumor immune responses but also act as natural carriers of microRNAs. The aim of the current study was to evaluate the efficacy of miR-124-3p-enriched TEX (TEXomiR) as cell-free vaccine in the induction of antitumor immune responses in a mouse model of colorectal cancer. Briefly, the exosomes were isolated from cultured CT-26 cell line, and modified calcium chloride method was used to deliver miR-124-3p mimic into the exosomes. We used a CT-26-induced BALB/c mouse model of colorectal cancer and analyzed the effect of TEXomiR on survival, tumor size, spleen and tumor-infiltrated lymphocytes, and splenocyte proliferation. Furthermore, intra-tumor regulatory T cells, cytotoxic activity of the splenocytes, and cytokine secretion was also evaluated to describe the anti-tumor immune response. When the tumor size reached 100 mm3, the mice were injected with TEXomiR, TEX, and/or phosphate-buffered saline (PBS) subcutaneously three times with 3-day interval, and then tumor size was monitored every 2 days. The in vitro results indicated that TEXs could efficiently deliver functional miR-124-3p mimic. The in vivo evaluation in tumor-bearing mice showed that treatment with TEXomiR can elicit a stronger anti-tumor immune response than unloaded TEX and PBS. Significant tumor growth inhibition and increased median survival time was achieved in tumor-bearing mice treated with TEXomiR. A significant decrease in CD4/CD8 and Treg/CD8 ratio in tumor tissue was demonstrated. Moreover, increased cytotoxicity and proliferation of splenocytes in the TEXomiR group compared to the TEX and PBS groups were identified. Taken together, our data demonstrated that tumor-derived exosomes efficiently deliver miR-124-3p mimic, and TEXomiR promotes anti-tumor immune responses.


2020 ◽  
Author(s):  
Yaojun Yu ◽  
jing zhang ◽  
Leyi Ni ◽  
Yuesheng Zhu ◽  
Hejie Yu ◽  
...  

Abstract Background: The role of neoantigens in cancer immunotherapy is crucial. However, the effectiveness and safety of personalized neoantigen vaccines in colorectal cancer (CRC), especially in Chinese population, has not been well studied. This paper mainly explores the feasibility and effectiveness of personalized neoantigen vaccines in CRC treatment. Methods: Whole-exome sequencing and transcriptome sequencing were used to identify somatic mutations, RNA expression and human leukocyte antigen (HLA) alleles. Neoantigens were predicted, and the immunogenicity of neoantigen candidates was evaluated by ELISPOT in vitro. To verify the immunogenicity in vivo, neoantigen candidates from HLA-A0201+PW11 were used to immunized female 6-8-week-old HLA-A2.1/Kb-transgenic (Tg) mice. Neoantigen-reactive T cells (NRTs) were induced by immunogenic peptides from autologous HLA-A2.1/Kb to adoptive transfer transgenic mice, and C57BL/6nu/nu mice were used for in vivo antitumor response assays.Results: Compared to medium alone (no peptide) or the unrelated peptide VSV-NP43-69, the neoantigens TSHZ3-L523P, RARA-R83H, TP53-R248W, EYA2-V333I and NRAS-G12D from Patient 4 (PW4); HAVCR2-F39V, SEC11A-R11L, TASP1-P161L, RAP1GAP-S215R, MOSPD1-V63I and NAV2-D1973N from Patient 10 (PW10); and SMPDL3B-T452M, LRFN3-R118Q and ULK1-S248L from Patient 11 (PW11) induced notable peptide-specific T cell responses. The results indicated that about half of the predicted neoantigens for all 3 patients can stimulate T cell responses and antitumor effects in CRC. In addition, predicted neoantigens from PW11 (HLA-A0201) showed promising antitumor efficacy in HLA-A2.1/Kb-Tg mice and tumor-bearing mouse models.Conclusion: With the application of next-generation sequencing (NGS) sequencing of patient specimens, neoantigen prediction and a rapid immunoassay system, an evaluation system utilizing in vitro studies and in vivo transgenic and tumor-bearing mouse models can be used to screen strong immunogenic neoantigens in CRC patients. Accurate identification of neoantigens with strong immunogenicity would promote personalized cancer vaccine development.


2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Zhang ◽  
Qi Yin ◽  
Haidong Huang ◽  
Jingjing Lu ◽  
Hao Qin ◽  
...  

ObjectiveTo develop a neoantigen-targeted personalized cancer treatment for non-small cell lung cancer (NSCLC), neoantigens were obtained from collected human lung cancer samples, and the utility of neoantigen and neoantigen-reactive T cells (NRTs) was assessed.MethodsTumor specimens from three patients with NSCLC were obtained and analyzed by whole-exome sequencing, and neoantigens were predicted accordingly. Dendritic cells and T lymphocytes were isolated, NRTs were elicited and IFN-γ ELISPOT tests were conducted. HLA-A2.1/Kb transgenic mice were immunized with peptides from HLA-A*02:01+patient with high immunogenicity, and NRTs were subjected to IFN-γ, IL-2 and TNF-α ELISPOT as well as time-resolved fluorescence assay for cytotoxicity assays to verify the immunogenicity in vitro. The HLA-A*02:01+lung cancer cell line was transfected with minigene and inoculated into the flanks of C57BL/6nu/nu mice and the NRTs induced by the immunogenic polypeptides from autologous HLA-A2.1/Kb transgenic mice were adoptively transfused to verify their immunogenicity in vivo.ResultsMultiple putative mutation-associated neoantigens with strong affinity for HLA were selected from each patient. Immunogenic neoantigen were identified in all three NSCLC patients, the potency of ACAD8-T105I, BCAR1-G23V and PLCG1-M425L as effective neoantigen to active T cells in suppressing tumor growth was further proven both in vitro and in vivo using HLA-A2.1/Kb transgenic mice and tumor-bearing mouse models.ConclusionNeoantigens with strong immunogenicity can be screened from NSCLC patients through the whole-exome sequencing of patient specimens and machine-learning-based neoantigen predictions. NRTs shown efficient antitumor responses in transgenic mice and tumor-bearing mouse models. Our results indicate that the development of neoantigen-based personalized immunotherapies in NSCLC is possible.PrecisNeoantigens with strong immunogenicity were screened from NSCLC patients. This research provides evidence suggesting that neoantigen-based therapy might serve as feasible treatment for NSCLC.


Author(s):  
Han Li ◽  
Wenyan Shen ◽  
Yanjie Xu ◽  
Zien Wang ◽  
Linghao Wang ◽  
...  

AbstractGranulocytes play important roles in cancer, and their apoptotic status is often changed by the influence of tumor environment. However, the changes and the function on granulocyte apoptosis in cancer are unclear. In this study, we used tumor-bearing mouse model and tumor patients to analyzed the apoptosis of granulocytes in different tissues by flow analysis and TUNEL fluorescence staining, and found that the percentage of apoptosis cells in granulocytes was significantly decreased in late-stage tumor-bearing mouse and patients. The in vitro co-culture experiment showed that these antiapoptotic granulocytes could significantly inhibit T cell proliferation, and RNA-seq proved that there was obvious difference on the transcriptome between these cells and control cells, particularly immune-related genes. What is important, adoptive transfer of these antiapoptotic granulocytes promoted tumor progress in mouse model. Conclusively, we found that granulocytes in late-stage tumor could delay the process of apoptosis, inhibit T cell proliferation, and acquire pro-tumor activity, which provides a new therapeutic target for tumor immunity.


2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Tian Xiang ◽  
Chunhui Yuan ◽  
Xia Guo ◽  
Honghao Wang ◽  
Qinzhen Cai ◽  
...  

AbstractHelicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.


2020 ◽  
Vol 21 (10) ◽  
pp. 955-964 ◽  
Author(s):  
Mengjie Liu ◽  
John Wade ◽  
Mohammed Akhter Hossain

: Ghrelin is a 28-amino acid octanoylated peptide hormone that is implicated in many physiological and pathophysiological processes. Specific visualization of ghrelin and its cognate receptor using traceable ligands is crucial in elucidating the localization, functions, and expression pattern of the peptide’s signaling pathway. Here 12 representative radio- and fluorescently-labeled peptide-based ligands are reviewed for in vitro and in vivo imaging studies. In particular, the focus is on their structural features, pharmacological properties, and applications in further biochemical research.


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