Wang Z.,University of Wolverhampton |
Tan J.,University of the Southwest |
McConville C.,University of Birmingham |
Kannappan V.,University of Wolverhampton |
And 13 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2017
Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2 minutes to 7 hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment. © 2016 The Authors
Zhou Z.-H.,Chongqing Medical University |
Zhou Z.-H.,Key Laboratory of Tumor Immunopathology |
Zhou Z.-H.,The 101 Hospital Of Peoples Liberation Army |
Ji C.-D.,Chongqing Medical University |
And 8 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2017
Purpose: To evaluate the prognostic value and pathobiological significance of Glasgow microenvironment score (GMS), a parameter based on tumor stroma percentage and inflammatory cell infiltration, in gastric cancer. Methods: A total of 225 cases of gastric cancer were histologically reviewed, and GMS was evaluated for each case. The association between GMS and patients’ survival was investigated. Then the relationship between GMS and mismatch repair (MMR) status, Epstein–Barr virus (EBV) infection were determined using immunohistochemistry (IHC) and in situ hybridization, and the expression of PD1/PD-L1 was examined. Furthermore, the amount of cancer-associated fibroblasts (CAFs), the content and maturity of collagen components were detected using IHC, Picrosirius Red staining and second harmonic generation imaging. Results: GMS was significantly associated with clinical outcomes of gastric cancer, and multivariate analysis indicated that GMS was an independent factor (HR 1.725, P = 0.002). Low GMS was a manifestation of better prognosis and inflammatory tumor microenvironment, which was related to MMR deficiency (P = 0.042) and EBV infection (P = 0.032), and within this microenvironment, expression of PD-L1 in carcinoma cells (P = 0.030) or in inflammatory cells (P = 0.029) was significantly higher. In contrast, high GMS linked to a poorer survival and desmoplastic stroma, in which there existed markedly increased CAFs and collagen deposition. Conclusion: GMS can serve as a useful prognostic factor for gastric cancer, and according to GMS, the tumor microenvironment in this cancer type may be partially classified as inflammatory or desmoplastic microenvironment that possesses different pathobiological features. © 2017 Springer-Verlag Berlin Heidelberg
Luo M.,University of Sichuan |
Lin H.,Sichuan Agricultural University |
Gao J.,Chongqing Medical University |
Gao J.,Key Laboratory of Tumor Immunopathology |
And 5 more authors.
Acta Physiologiae Plantarum | Year: 2015
MicroRNAs (miRNAs) are a set of small, non-coding RNAs that negatively and post-transcriptionally mediate their respective target mRNAs by directing the target mRNA cleavage or translational repression. Plant miRNAs have been involved in developmental processes and adaption to biotic and abiotic stresses in their environment. The banded leaf and sheath blight (BLSB) caused by Rhizoctonia solani is extremely harmful to maize. To investigate the functions of miRNAs under R. solani inoculation, miRNA expression in R. solani infected maize (Zea mays L.) was profiled using deep sequencing. In total, 41 significantly differentially expressed known miRNAs and 39 novel R. solani-responsive miRNAs were identified, of which 9 identified miRNAs were further validated by qRT-PCR, and 2 important miRNAs were analyzed by in situ hybridization. Target genes were also predicted for these R. solani-responsive miRNAs; most of these putative target genes encoded transcription factors and proteins associated with metabolic processes or stress responses. In addition, the mRNA expression levels of several target genes that negatively correlated with the levels of corresponding miRNAs under R. solani inoculation were validated by qRT-PCR. These findings hypothesized that these miRNAs play an important role in R. solani resistance in maize, highlighting novel molecular mechanisms of R. solani resistance in plants. © 2015, Franciszek Górski Institute of Plant Physiology, Polish Academy of Sciences, Kraków.
Wang B.,Chongqing Medical University |
Wang B.,Key Laboratory of Tumor Immunopathology |
Wang Q.,Chongqing Medical University |
Wang Q.,Key Laboratory of Tumor Immunopathology |
And 26 more authors.
Cancer Research | Year: 2014
Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D. Furthermore, the downregulation of MICA/MICB in BCSCs was mediated by aberrantly expressed oncogenic miR20a, which promoted the resistance of BCSC to NK cell cytotoxicity and resultant lung metastasis. The breast cancer cell differentiation-inducing agent, all-trans retinoic acid, restored the miR20a-MICA/MICB axis and sensitized BCSC to NK cell-mediated killing, thereby reducing immune escape-associated BCSC metastasis. Together, our findings reveal a novel mechanism for immune escape of human BCSC and identify the miR20a-MICA/MICB signaling axis as a therapeutic target to limit metastatic breast cancer. © 2014 American Association for Cancer Research.
Qi X.-W.,Chongqing Medical University |
Qi X.-W.,Key Laboratory of Tumor Immunopathology |
Zhang F.,Chongqing Medical University |
Wu H.,Luzhou Medical College |
And 5 more authors.
Scientific Reports | Year: 2015
Though proposed as a promising target antigen for cancer immunotherapy, the prognostic value of Wilms' tumor 1 (WT1) in solid tumors remains inconclusive. Here, we report a systematic review and meta-analysis of the association between WT1 expression and prognosis in solid tumors. PubMed, Web of Science and Google Scholar were searched to identify studies exploring the impact of WT1 on clinical outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), relapse/recurrence-free survival (RFS) or progression-free survival (PFS), in solid cancer patients. Hazard ratio (HR) and 95% confidence interval (CI) were applied to assess the strength of these associations. Finally, a total of 29 eligible studies with 4090 patients were identified for qualitative analysis, and 22 studies with 3620 patients were enrolled for quantitative synthesis. Overall, positive expression of WT1 was significantly associated with worse OS (metaHR = 1.48, 95% CI = 1.11-1.97) and DFS/RFS/PFS (metaHR = 2.14, 95% CI = 1.42-3.21). Subgroup analyses showed that WT1 positive expression could independently predict unfavorable DFS/RFS/PFS (metaHR = 1.86, 95%CI = 1.04-3.35). In summary, our study suggests that WT1 may be a potential marker to predict DFS/RFS/PFS in solid tumor patients. Further studies are needed to confirm the role of WT1 expression in clinical practice. © 2015, Nature Publishing Group.
Shen Z.,Chongqing Medical University |
Chen L.,Chongqing Medical University |
Yang X.,Chongqing Medical University |
Yang X.,Key Laboratory of Tumor Immunopathology |
And 5 more authors.
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013
Transcription factor FOXP3 (forkhead box P3) is found initially as a key regulator in regulatory T cells. Recently its expression has been demonstrated in some non-lymphoid normal and cancerous cells. Now FOXP3 has been proven to regulate cancer-related genes, especially suppressor genes in breast cancer. But the mechanisms by which FOXP3 regulates suppressor genes are not fully determined. In this study, we found the inverse correlation between FOXP3 and Ezh2, an enzyme for histone H3K27 trimethylation (H3K27me3) and a central epigenetic regulator in cancer. The overexpression of FOXP3 weakened Ezh2's enhancement on the mammosphere formation, cell proliferation, directional migration, and colony forming ability of T47D cells. We demonstrated that FOXP3 could downregulate Ezh2 protein level and this depended on not only the FOXP3 expression amount, but also the nuclear localization of FOXP3. More importantly, we demonstrated FOXP3 accelerated Ezh2 protein degradation through the polyubiquitination-proteasome pathway by enhancing the transcription of E3 ligase Praja1 directly. These results provided a new mechanism for FOXP3 in histone modifications as an Ezh2 suppressor and supported new evidence for FOXP3 as a tumor suppressor in breast cancer. © 2013 Elsevier B.V.
Ping Y.-F.,Chongqing Medical University |
Ping Y.-F.,Key Laboratory of Tumor Immunopathology |
Zhang X.,Chongqing Medical University |
Zhang X.,Key Laboratory of Tumor Immunopathology |
And 2 more authors.
Cancer Letters | Year: 2015
Cancer stem cells (CSCs) locate in and interact with particular vascular niches to maintain their stemness. CSCs induce, remodel and participate in the formation of microenvironmental niches to facilitate survival, stemness and escape from radio-/chemo-/bio-therapies. Neovasculature in tumor is often basement membrane-deficient and enriched with CSC-derived endothelial cells (ECs) and other mural cells, which may promote tumor invasion and metastasis. The aim of this review is to summarize recent findings about the crosstalk between CSCs and their vascular niches and discuss the potential therapeutic significance. © 2015 Elsevier Ireland Ltd.
Liao W.-L.,Chongqing University of Arts and Sciences |
Li S.-Q.,Chongqing University of Arts and Sciences |
Wang J.,Chongqing University of Arts and Sciences |
Zhang Z.-Y.,Chongqing University of Arts and Sciences |
And 7 more authors.
ACS Combinatorial Science | Year: 2016
Two series of benzimidazoisoquinoline and fused benzimidazoisoquinoline-benzimidazole derivatives have been synthesized using an efficient one-pot procedure. This process involves an intramolecular nucleophilic substitution reaction and provides facile access to two series of complexes and potentially interesting biologically active scaffolds. © 2015 American Chemical Society.
Chen L.,Chongqing Medical University |
Chen L.,Key Laboratory of Tumor Immunopathology |
Li Q.,Chongqing Medical University |
Li Q.,Key Laboratory of Tumor Immunopathology |
And 15 more authors.
International Immunopharmacology | Year: 2014
Infiltration of inflammatory cells and production of pro-angiogenic factors are important in lung cancer immunity. The distributions of those cells and their contributions to the production of pro-angiogenic factors and the activation phenotype of macrophages in bronchoalveolar lavage fluid (BALF) from lung cancer patients remain unclear. We analyzed the presence of distinct inflammatory cells and the macrophage activation phenotype together with the levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) within BALF from 54 smoking lung cancer patients including 36 squamous cell carcinoma (SCC), 9 adenocarcinoma (AC), and 9 small cell lung cancer (SCLC) in comparison with those from 13 non-smoking and 7 smoking patients with nonspecific chronic inflammation and 8 non-smoking normal controls. We found a significantly lower percentage of total macrophages and a much higher percentage of neutrophils among all inflammatory cells in BALF from lung cancer and non-specific chronic inflammation patients. BALF from AC patients had a significantly higher percentage of lymphocytes. CD163+) macrophages predominantly existed in BALF from SCLC patients. BALF of lung cancer patients had markedly higher levels of IL-8 and VEGF. Interestingly, IL-8 level was positively correlated to the numbers of neutrophils and lymphocytes. VEGF level was inversely correlated to the number of lymphocytes but positively to cancer cells in SCC cases, whereas no correlation existed between CD163+) macrophages and the levels of IL-8 and VEGF. Our results suggest that the detection of infiltrating inflammatory cells and pro-angiogenic factors in BALF will be helpful for diagnosis of cancerous inflammation in lungs. © 2014 Published by Elsevier B.V.
PubMed | Key Laboratory of Tumor Immunopathology, Chongqing University of Arts and Sciences and Sichuan Academy of Medical science & Sichuan Provincial Peoples Hospital
Type: Journal Article | Journal: ACS combinatorial science | Year: 2016
Two series of benzimidazoisoquinoline and fused benzimidazoisoquinoline-benzimidazole derivatives have been synthesized using an efficient one-pot procedure. This process involves an intramolecular nucleophilic substitution reaction and provides facile access to two series of complexes and potentially interesting biologically active scaffolds.