Hsa_circ_0005529 promotes ZEB1 expression by regulating miR-873-5p and enhancing proliferation, invasion, and migration in gastric cancer cell lines.

BACKGROUND: Gastric cancer is a relatively common tumor. As circular RNAs (circRNAs) are documented to modulate proliferation and metastasis in various cancers, we evaluated the functions of circRNAs, in particular, hsa_circ_0005529, in gastric cancer cells. METHODS: Levels of hsa_circ_0005529 and miR-873-5p were examined by qRT-PCR, and the presence of hsa_circ_0005529 was confirmed by RNase R treatment. CCK-8, wound-healing, and Transwell assays were used to assess proliferation, migration, and invasion, respectively, while Western blotting was used to determine levels of zinc finger E-box-binding homeobox 1 (ZEB1) and dual-luciferase reporter assays to examine relationships between hsa_circ_0005529 and miR-873-5p. RESULTS: hsa_circ_0005529 was strongly expressed in gastric cancer where it stimulated tumorigenic behavior. Furthermore, hsa_circ_0005529 was shown to promote ZEB1 expression by sponging miR-873-5p, an inhibitor of ZEB1 expression. CONCLUSION: Our research showed that hsa_circ_0005529 promoted tumorigenic behavior in gastric cancer cells by adsorbing miR-873-5p to modulate ZEB1 levels. This suggests that hsa_circ_0005529 may be useful as a biomarker and target for diagnosing and treating gastric cancer.

Establishment of a prediction model of postoperative infection complications in patients with gastric cancer and its impact on prognosis.

Background: Postoperative infection delays postoperative adjuvant therapy and can lead to poor prognosis in gastric cancer patients. Therefore, accurately identifying patients at high risk of postoperative infection in patients with gastric cancer is critical. We therefore conducted a study to analyze the impact of postoperative infection complications on long-term prognosis. Methods: From January 2014 to December 2017, we retrospectively collected the data of 571 patients with gastric cancer admitted to the Affiliated People's Hospital of Ningbo University. The patients were divided into an infection group (n=81) and control group (n=490) according to whether the patients experienced postoperative infection. The clinical characteristics of the 2 groups were compared, and the risk factors of postoperative infection complications in patients with gastric cancer were analyzed. Finally, the prediction model of postoperative infection complications was established. Results: There were significant differences in age, diabetes, preoperative anemia, preoperative albumin, preoperative gastrointestinal obstruction, and surgical methods between the 2 groups (P<0.05). Compared with that in the control group, the mortality rate of patients in the infection group at 5 years after surgery was significantly increased (39.51% vs. 26.12%; P=0.013). Multivariate logistics regression analysis showed that age >65 years, preoperative anemia, albumin <30 g/L, and gastrointestinal obstruction were risk factors of postoperative infection in patients with gastric cancer (P<0.05). The data set was randomly divided into a training set and validation set; the sample size of the training set was 286 while the sample size of the validation set was 285. In terms of the predictive model's value in predicting postoperative infection in patients with gastric cancer, the area under the curve of the receiver operating characteristic (ROC) curve in the training set was 0.788 (95% confidence interval: 0.711-0.864), and the area under the curve of the ROC curve in the validation set was 0.779 (95% confidence interval: 0.703-0.855). In the validation set, the model was evaluated with the Hosmer-Lemeshow goodness-of-fit test, resulting in a chi-squared value of 5.589 and a P value of 0.693. Conclusions: The present model can effectively identify patient as high risk of postoperative infection.

Oxidative stress in the tumor microenvironment in gastric cancer and its potential role in immunotherapy.

Gastric cancer (GC) is the fourth leading cause of cancer-related death and the fifth most common malignant tumor globally. However, the clinical efficacy of conventional therapies is limited. Currently, immunotherapy is considered an effective therapeutic strategy for the management of various cancers, especially GC, but is of only limited benefit for GC patients. Accumulating evidence has revealed that oxidative stress plays a critical role in the regulation of immune responses within the tumor microenvironment (TME), affecting the efficacy of immunotherapies. Reactive oxygen species exert critical roles in enhancing antigen presentation, regulating immune responses, and preventing immunoescape. In this review, we summarize the dominant cancer immunotherapeutic strategies and describe the interaction between oxidative stress and the immune TME. We emphasize the underlying mechanisms of the efficacy of cancer immunotherapy, which involves its effects on oxidative stress, in the context of GC. We also highlight the therapeutic potential of regulating oxidative stress to improve immunotherapies, which may have benefits for clinical practice.

Immunotherapeutic strategy in the management of gastric cancer: molecular profiles, current practice, and ongoing trials.

Gastric cancer (GC) is the one of the most commonly solid cancer worldwide. Although under the aggressive treatment, the poor clinical outcomes of patients with GCs have not been improved. Current studies emphasized that targeting therapies or immune response-based therapeutic strategy may be a potential approach to improve the clinical outcomes. Moreover, accumulative evidence has reported the increasing expression of PD-L1 expression in GC cells and highlighted its role in the tumor progression. Currently, great development has been established in the immune checkpoint inhibitors (ICIs) and further changed the clinical practice of GC treatment and prognosis. In addition, the combination therapies with targeting therapy or traditional therapies are expected to push the development of immunotherapies. In our present review, we predominantly focus on the biomarkers and molecular profiles for immunotherapies in GCs and highlight the role and administration of ICIs-based immunotherapeutic strategies against the GCs.

PLOD1 promotes cell growth and aerobic glycolysis by regulating the SOX9/PI3K/Akt/mTOR signaling pathway in gastric cancer.

Background: Evidences has showed that procollagen-lysine 2-oxoglutarate 5-dioxygenase 1 (PLOD1) participated in the many cancers' progression, such as bladder cancer and osteosarcoma. However, its role in gastric cancer (GC) remains elusive. The study, was aimed to investigate the role and of PLOD1 in GC progression and the underlying mechanism. Methods: MTT, Edu and colony formation assays were applied to detect cell viability and clonal expansion ability. TUNEL was used for cell apoptosis detection. Glucose uptake, lactate production, ATP contents, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) levels were used to reflect aerobic glycolysis level in GC cells. Results: The expression of PLOD1 in GC tissues and cells was higher than that in GES-1 cells. Overexpression of PLOD1 induced a significant enhancement in cell viability and increased glucose uptake, lactate production, ATP contents and ECAR, but decreased cell apoptosis and OCR level in AGS and HGC-27 cells. Knockdown of PLOD1 caused opposite results. In mechanism, the expression of PLOD1 in GC tissues was positively associated with SOX9, HK2 and LDHA levels, and overexpression of PLOD1 increased SOX9, p-Akt/Akt and p-mTOR/mTOR levels. Additionally, overexpression of SOX9 abolished PLOD1 downregulation-mediated inhibition on cell viability and aerobic glycolysis, promotion on cell apoptosis. Moreover, PLOD1 downregulation inhibited tumor formation in vivo. Conclusion: This study showed that PLOD1can promote cell growth and aerobic glycolysis through activating the SOX9/PI3K/Akt/mTOR signaling.

HOXD8 inhibits the proliferation and migration of triple-negative breast cancer cells and induces apoptosis in them through regulation of AKT/mTOR pathway.

HOXD8 (Homeobox D8) functions as an apoptotic inducer to suppress tumor progression. However, the role of HOXD8 in triple-negative breast cancer (TNBC) has not been fully understood. Firstly, HOXD8 was found to be reduced in TNBC tissues based on the TCGA samples through Ualcan (http://ualcan.path.uab.edu/analysis.html) prediction. Moreover, data from qRT-PCR and western blot confirmed the lower expression of HOXD8 in the TNBC tissues or cells than that in paracancerous tissues or human mammary epithelial cell line (MCF10A), respectively. Secondly, pcDNA-mediated over-expression of HOXD8 were conducted in TNBC cells, and the gain-of functional assays showed that over-expression of HOXD8 promoted TNBC cell progression with repressed cell apoptosis and induced proliferation, migration and invasion. Moreover, xenografted mouse model was constructed by injection of tumor cell line with stable over-expression of HOXD8 to assess the in vivo tumor growth, and the results revealed that over-expression of HOXD8 inhibited tumor growth. Lastly, our results showed that AKT and mTOR phosphorylation were repressed by HOXD8 over-expression in TNBC cells. In conclusion, HOXD8 functioned as an apoptotic inducer to suppress TNBC cell growth and progression by inhibition of AKT/mTOR pathway.

Targeting CXCL12-CXCR4 Signaling Enhances Immune Checkpoint Blockade Therapy Against Triple Negative Breast Cancer.

Insufficient T cell infiltration in triple-negative breast cancer (TNBC) has limited its response rate to immune checkpoint blockade (ICB) therapies and motivated the development of immunostimulatory approaches to enhance the ICB therapy. CXCR4 is a chemokine receptor highly upregulated both on cell surface and cytoplasm in tumor tissues. Activating CXCR4 has been associated with increased immunosuppression in the tumor microenvironment. Here, we developed a CXCR4-targeted liposomal formulation (Liposomal-AMD3100) to enhance therapeutic efficacy of AMD3100, a CXCR4 antagonist. Particularly, AMD3100 is not only encapsulated into the liposome but coated on the surface of the formulation to serve as a targeting moiety and a dual blocker capable of inhibiting CXCR4 activation extracellularly and intracellularly. The Liposomal-AMD3100 remodeled both immune and stromal microenvironment more efficiently compared with free AMD3100, indicating better pharmacodynamic profile of AMD3100 achieved by liposomal formulation. The combination of anti-PD-L1 with Liposomal-AMD3100 formulation exhibited an increased antitumor effect and prolonged survival time compared with monotherapies in a murine TNBC model (4T1). This work proves that immune activation via liposomal delivery of CXCR4 inhibitors has a great potential to expand ICB therapies to originally ICB-insensitive cancer types.

Removal of As(V) by iron-based nanoparticles synthesized via the complexation of biomolecules in green tea extracts and an iron salt.

While iron-based nanoparticles (nFe) prepared using green tea extracts have been successfully used to degrade many organic contaminants, their application to remove As(V) remains limited. Thus, in this work, nFe (GT-1) prepared using a green tea extract was used to removal As(V). The maximum adsorption capacity of GT-1 for As(V) was 19.9 mg g-1 at 298 K. The formation of GT-1 and the removal mechanism of As(V) by GT-1, was examined using XRD, TEM and SEM, which showed that GT-1 was composed of amorphous particulates sized between 50 and 100 nm. GC-MS and LC-MS analysis also showed that biomolecules presented in the green tea extract, including polyphenols and L-theanine, participated in the formation of GT-1. Mössbauer spectral analysis confirmed that an organo-Fe(III) complex was formed due to the reaction between biomolecules and Fe(III). FTIR and XPS showed that the adsorption of As(V) by GT-1 occurred both via complexation with Fe(III) in GT-1 and via coordination of As(V) with free hydroxyl groups on the surface of GT-1. Batch experiments showed that adsorption was spontaneous and conformed to the pseudo-second order kinetic model. Finally, mechanisms for the formation of GT-1 and the removal of As (V) by GT-1 were proposed.

Usefulness of postoperative serum translocator protein as a predictive marker for delirium after breast cancer surgery in elderly women.

OBJECTIVE: Postoperative delirium (POD) has rarely been investigated in breast cancer patients. Herein, we assessed the association between serum levels of the inflammatory biomarker translocator protein (TP) and the occurrence of POD in breast cancer patients. METHODS: In this prospective, observational study, TP levels were detected in preoperative and postoperative serum samples from 152 elderly breast cancer patients, samples from 152 healthy elderly women, and samples from 152 elderly women with benign breast diseases. The relationship between serum TP levels and POD was investigated using multivariate analysis. RESULTS: TP levels in postoperative patient serum samples were significantly higher than in preoperative patient serum samples and serum from women in the two control groups. Postoperative serum TP levels were independently correlated with serum C-reactive protein levels and the occurrence of POD. Postoperative serum TP levels had a high discriminatory ability for POD under the receiver operating characteristic curve. CONCLUSIONS: Increased postoperative serum TP levels are independently associated with the degree of inflammatory response and the risk of POD in elderly breast cancer patients, substantializing TP as an inflammatory biomarker that can efficiently discriminate POD after breast cancer surgery.

Mechanism of As(V) removal by green synthesized iron nanoparticles.

The application of green synthesized iron nanoparticles (nFe) for the removal of arsenic (As) from contaminated sites has often been proposed as one of the most promising remediation methods. In this work, TEM analysis showed that As(V) was uniformly adsorbed on the surfaces of nFe, while FTIR analysis confirmed that adsorption was mainly via an FeOAs bond, and XPS analysis indicated that only As(V) was adsorbed. Hence, the removal mechanism proposed for As(V) is based on initially nFe reacting with As(V) to form a monodentate chelating ligand and subsequently a bidentate binuclear complex. The initially high surface area (51.14 m2 g-1) of nFe was decreased by half (26.03 m2 g-1) after As(V) adsorption, where the materials high As(V) adsorption capacity(21.59 mg g-1) was attributed to unique properties derived from the green synthesis. Adsorption isotherm modeling indicated that As(V) adsorption by nFe best fit the Langmuir equation (RL2 = 0.9903), and thus suggested chemisorption was occurring. The adsorption also fitted the pseudo second-order kinetic rate equation well, which confirmed that adsorption was via chemisorption. Overall, the green synthesis of nFe exhibited great application potential for As(V) removal due to high As(V) adsorption capacity and simplicity of synthesis.

[Suppression of Kiss-1 gene inhibits HCT116 human colorectal carcinoma cell migration in vitro via nuclear factor-κB signaling pathway].

OBJECTIVE: To investigate the effect of Kiss-1 gene suppression on the metastatic capacity of HCT116 human colorectal carcinoma cells in vitro and the involvement of nuclear factor-κB (NF-κB) signaling pathway. METHODS: A recombinant lentiviral vector of Kiss-1 gene pGC-LV-Kiss-1-EGFP or the empty vector was transfected in HCT116 cells. Cell Counting Kit-8 (CCK8) and Transwell chamber assay were used to detect the changes in cell proliferation, invasion and migration ability after the transfection. Western blotting was used to detect the expression of I-κB, the inhibitive protein of NF-κB signal pathway, and the expression of the downstream effector MMP-9 before and after transfection. RESULTS: In cells over-expressing Kiss-1, I-κB expression increased and MMP-9 expression decreased significantly compared to those in the blank control and vector-transfected cells (P<0.05). Kiss-1 gene over-expression resulted in significant inhibition of HCT116 cell proliferation, invasion, and migration as compared to the control cells (P<0.05). CONCLUSION: Lentivirus-mediated Kiss-1 gene over-expression can inhibit the proliferation, invasion, and migration of HCT116 cells via the NF-B signaling pathway.