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1.
Nat Med ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38942993

ABSTRACT

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

2.
Int J Biol Macromol ; 261(Pt 2): 129929, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38311139

ABSTRACT

Recently, metal-organic frameworks (MOFs) have been widely developed due to the rich porosity, excellent framework structure and multifunctional nature. Meanwhile, a series of MOFs crystals and MOF-based composites have been emerged. However, the widespread applications of MOFs are hindered by challenges such as rigidity, fragility, solution instability, and processing difficulties. In this study, we addressed these limitations by employing an in-situ green growth approach to prepare a zeolitic imidazolate frameworks-8@poly (γ-glutamic acid) hydrogel (ZIF-8@γ-PGA) with hierarchical structures. This innovative method effectively resolves the inherent issues associated with MOFs. Furthermore, the ZIF-8@γ-PGA hydrogel is utilized for dye adsorption, demonstrating an impressive maximum adsorption capacity of 1130 ± 1 mg/g for methylene blue (MB). The adsorption behavior exhibits an excellent agreement with both the kinetic model and isotherm. Meanwhile, because the adsorbent raw materials are all green non-toxic materials, multiple applications of materials can also be realized. Significantly, the results of antibacterial experiments showed that the ZIF-8@γ-PGA hydrogel after in-situ growth of ZIF-8 had better antibacterial properties. Thus, the ZIF-8@γ-PGA hydrogel has great potential for development in wound dressings, sustained drug owing to its biocompatibility and antibacterial activity.


Subject(s)
Metal-Organic Frameworks , Zeolites , Hydrogels/chemistry , Glutamic Acid , Adsorption , Zeolites/chemistry , Anti-Bacterial Agents
3.
Front Immunol ; 15: 1337396, 2024.
Article in English | MEDLINE | ID: mdl-38380330

ABSTRACT

Objective: This study aimed to explore the efficacy of transarterial chemoembolization (TACE) combined with microwave ablation (MWA) adjuvant to lenvatinib and anti-PD-1 antibodies for patients with hepatocellular carcinoma (HCC). Methods: A retrospective analysis of 67 patients with HCC treated at our hospital between October 2018 and May 2022 was conducted. All patients underwent a combination of TACE and MWA. Among them, 29 received postoperative treatment with molecular-targeted agents, like lenvatinib, along with anti-PD-1 antibodies such as sindilizumab, karelizumab, or tirilizumab. The remaining 38 patients did not receive postoperative systemic therapies, like targeted or immunotherapy. The survival and prognosis of all patients were analyzed. Results: Nine patients in the observation group and 29 patients in the control group experienced recurrence, and the median progression-free survival 1 (PFS1) was not reached 'Not Applicable'(NA) and 17.05 months (P=0.035), respectively. Failure to combine adjuvant therapy was identified as an independent risk factor for tumor recurrence, and the observation group had a 0.245 times lower risk of recurrence compared to that in the control group (P=0.005). Multivariable Cox regression analysis confirmed that the maximum tumor size, and tumor number were risk factors for tumor recurrence. Patients with a large maximum tumor size had a 1.519 times higher risk of recurrence compared to those with a small maximum tumor size (P=0.006), and patients with a large number of tumors had a 5.978 times higher risk of recurrence compared to those with a small number of tumors (P=0.02). The median PFS2 of the two groups was 11.795 and 21.257 months, respectively, though not statistically significant (P=0.955). However, there was a disparity in the percentage of BCLC stages associated with recurrence between the two groups. In the observation group approximately 22.22% of patients progressed to stage C, while in the control group, this proportion was 34.48%. The observation group exhibited a lower risk of distant metastasis compared to the control group. Conclusion: Adjuvant treatment of HCC following TACE combined with MWA improved PFS and achieved better clinical outcomes compared to that with TACE combined with MWA alone.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/therapy , Retrospective Studies , Microwaves/therapeutic use , Treatment Outcome , Chemoembolization, Therapeutic/adverse effects
4.
Small ; 20(25): e2310046, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38183373

ABSTRACT

Hydrogels are widely used in tissue engineering, soft robotics and wearable electronics. However, it is difficult to achieve both the required toughness and stiffness, which severely hampers their application as load-bearing materials. This study presents a strategy to develop a hard and tough composite hydrogel. Herein, flexible SiO2 nanofibers (SNF) are dispersed homogeneously in a polyvinyl alcohol (PVA) matrix using the synergistic effect of freeze-drying and annealing through the phase separation, the modulation of macromolecular chain movement and the promotion of macromolecular crystallization. When the stress is applied, the strong molecular interaction between PVA and SNF effectively disperses the load damage to the substrate. Freeze-dried and annealed-flexible SiO2 nanofibers/polyvinyl alcohol (FDA-SNF/PVA) reaches a preferred balance between enhanced stiffness (13.71 ± 0.28 MPa) and toughness (9.9 ± 0.4 MJ m-3). Besides, FDA-SNF/PVA hydrogel has a high tensile strength of 7.84 ± 0.10 MPa, super elasticity (no plastic deformation under 100 cycles of stretching), fast deformation recovery ability and excellent mechanical properties that are superior to the other tough PVA hydrogels, providing an effective way to optimize the mechanical properties of hydrogels for potential applications in artificial tendons and ligaments.

5.
Biochem Genet ; 62(1): 371-384, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37351719

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.


Subject(s)
Inflammatory Bowel Diseases , Humans , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/genetics , Machine Learning , Computational Biology , Cytokines , Biomarkers
6.
Front Immunol ; 14: 1071023, 2023.
Article in English | MEDLINE | ID: mdl-36865549

ABSTRACT

Exosomes are progressively being detected as an indicator for the diagnosis and prognosis of cancer in clinical settings. Many clinical trials have confirmed the impact of exosomes on tumor growth, particularly in anti-tumor immunity and immunosuppression of exosomes. Therefore, we developed a risk score based on genes found in glioblastoma-derived exosomes. In this study, we used the TCGA dataset as the training queue and GSE13041, GSE43378, GSE4412, and CGGA datasets as the external validation queue. Based on machine algorithms and bioinformatics methods, an exosome-generalized risk score was established. We found that the risk score could independently predict the prognosis of patients with glioma, and there were significant differences in the outcomes of patients in the high- and low-risk groups. Univariate and multivariate analyses showed that risk score is a valid predictive biomarker for gliomas. Two immunotherapy datasets, IMvigor210 and GSE78220, were obtained from previous studies. A high-risk score showed a significant association with multiple immunomodulators that could act on cancer immune evasion. The exosome-related risk score could predict the effectiveness of anti-PD-1 immunotherapy. Moreover, we compared the sensitivity of patients with high- and low-risk scores to various anti-cancer drugs and found that patients with high-risk scores had better responses to a variety of anti-cancer drugs. The risk-scoring model established in this study provides a useful tool to predict the total survival time of patients with glioma and guide immunotherapy.


Subject(s)
Exosomes , Glioblastoma , Glioma , Humans , Glioblastoma/genetics , Prognosis , Exosomes/genetics , Biomarkers
7.
Technol Cancer Res Treat ; 22: 15330338231152350, 2023.
Article in English | MEDLINE | ID: mdl-36727222

ABSTRACT

Background: Chemotherapy combined with antivascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor monoclonal antibodies is the most promising approach to prolong survival and improve the quality of life of patients with unresectable metastatic colorectal cancer (mCRC). Anlotinib is an oral antiangiogenic tyrosine kinase inhibitor that targets VEGF receptors 1/2/3, fibroblast growth factor receptors 1-4, and platelet-derived growth factor receptors a/ß. Since anlotinib combined with oxaliplatin and capecitabine (CAPEOX) as a first-line treatment was previously shown to be effective and safe for patients with RAS/BRAF wild-type (WT) mCRC, we designed this randomized, open-label, parallel-group, non-inferiority, phase III study to evaluate the efficacy and safety of anlotinib plus CAPEOX versus bevacizumab plus CAPEOX in patients with RAS/BRAF WT mCRC. Methods/design: The primary inclusion criteria are Eastern Cooperative Oncology Group performance status 0/1, confirmed RAS/BRAF WT colorectal adenocarcinoma, and unresectable metastases assessed by a multidisciplinary team. The main exclusion criteria are as follows: high microsatellite instability or deficient mismatch repair status, resectable or potentially resectable metastases, and previous systemic therapy for mCRC. A total of 698 patients will be randomized into the anlotinib and bevacizumab groups in a 1:1 ratio. Patients will receive 4 to 8 cycles of induction therapy (CAPEOX plus anlotinib or bevacizumab), followed by maintenance treatment (capecitabine plus anlotinib or bevacizumab) until disease progression or unacceptable toxicity. Progression-free survival (PFS) assessed by an independent review committee is the primary endpoint, whereas investigator-assessed PFS, overall survival, objective response rate, disease control rate, duration of response, resection rate of liver metastases, quality of life, and safety are the secondary endpoints. Enrollment commenced in May 2021. Discussion: A prospective, randomized, phase III trial will provide a meaningful comparison of the efficacy and safety of anlotinib plus CAPEOX with standard treatment for patients with unresectable RAS/BRAF WT mCRC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Colorectal Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Capecitabine , Clinical Trials, Phase III as Topic , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Prospective Studies , Proto-Oncogene Proteins B-raf/genetics , Quality of Life , Randomized Controlled Trials as Topic
8.
ACS Appl Mater Interfaces ; 15(3): 4814-4825, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36633649

ABSTRACT

To coordinate the trade-off between the separation and permeation of the nanofiltration membrane for the separation of Mg2+/Li+, we regulated poly(ethyleneimine)/piperazine interface polymerization parameters to construct a positively/negatively charged ultrathin Janus nanofiltration membrane at a free aqueous-organic interface. At the optimized interfacial polymerization parameters, 0.03 wt % of piperazine reacted with trimethylbenzene chloride prior to poly(ethyleneimine), forming a primary polyamide layer with fewer defects or limiting large-scale defects of the polyamide layer. The controlled subsequent reaction of poly(ethyleneimine) and trimethylbenzene chloride results in a Janus nanofiltration membrane, with one side enriched with the carboxyl groups, the other side enriched with the amine groups, and a dense polyamide structure in the middle. Under the optimum conditions, the positive potential of the rear surface of the prepared membrane was 14.57 mV, and the water contact angle reached 71.31°, while the negative potential of the front surface was -25.48 mV, and the water contact angle was 12.93°, confirming a Janus membrane with opposite charges and large hydrophilicity differences in the front and rear surfaces. With a high cross-linking degree, a 40 nm thick polyamide layer is 29.09% more thinner than the traditional polyamide membrane. The ultrathin Janus nanofiltration membrane showed an excellent separation factor (SLi,Mg of 18.26), stability, and water permeability flux (10.6 L·m-2·h-1·bar-1). The rejections to MgCl2, CaCl2, MgSO4, and Na2SO4 are measured above 90% at a nearly constant permeability of 10.6 L·m-2·h-1·bar-1, particularly stable rejections to MgCl2 and Na2SO4.

9.
J Comput Assist Tomogr ; 47(1): 24-30, 2023.
Article in English | MEDLINE | ID: mdl-36055224

ABSTRACT

PURPOSE: The aim of the study is to assess the clinical value of the combined computed tomography (CT)/ultrasound (US) guidance in microwave ablation (MWA) for hepatocellular carcinoma (HCC). METHODS: From July 16, 2016, to June 20, 2021, medical records of 150 HCC patients treated with MWA were retrospectively analyzed. Ninety-two patients with 115 liver tumors underwent MWA under combined CT/US guidance, and 58 patients with 73 liver tumors received MWA under CT guidance alone. The clinical efficacy of combined CT/US-guided MWA was analyzed. We compared the complications, procedure time, and CT scan times between the 2 groups. RESULTS: The total complete ablation rate and complete ablation rate of high-risk location tumors were significantly higher in the group treated with combined CT/US guidance ( P = 0.0471 and P = 0.0347, respectively), the imaging guidance modality (odds ratio, 0.303; 95% confidence interval [CI], 0.095-0.970; P = 0.044) was an independent factor for ablation efficacy. These 2 groups also had significant differences in the procedure time ( P = 0.0171), the incidence rate of pneumothorax ( P = 0.0209), abdominal pain ( P = 0.0196), nausea or vomiting ( P = 0.0026), and intraoperative CT scan times ( P < 0.001). The overall complication rates ( P = 0.4023) and recurrence rates ( P = 0.5063) between the 2 groups were not statistically significant. However, CT/US group has a better short-term progressive free survival (log-rank P = 0.103, Breslow P = 0.030). In multivariate analysis, guidance modality (hazard ratio, 0.586; 95% CI, 0.368-0.934; P = 0.025) and Barcelona Clinic Liver Cancer stage (hazard ratio, 2.933; 95% CI, 1.678-5.127; P < 0.001) were risk factor for progressive free survival. CONCLUSIONS: Percutaneous MWA under the combined CT/US guidance for HCC can improve clinical benefits.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Microwaves/therapeutic use , Retrospective Studies , Tomography, X-Ray Computed/methods , Treatment Outcome , Catheter Ablation/methods
10.
ACS Appl Mater Interfaces ; 14(49): 55295-55306, 2022 Dec 14.
Article in English | MEDLINE | ID: mdl-36454694

ABSTRACT

As an effective way to obtain freshwater resources, atmospheric water harvesting (AWH) technology has been a wide concern of researchers. Therefore, hydrogels gradually become key materials for atmospheric water harvesters due to their high specific surface area and three-dimensional porous structure. Here, we construct a core-shell hydrogel-based atmospheric water harvesting material consisting of a shell sodium polyacrylate (PAAS) hydrogel with an open pore structure and a core thermosensitive poly N-isopropylacrylamide (PNIPAAm) hydrogel with a large pore size. Theoretically, the mutual synergistic hygroscopic effect between the core layer and the shell layer accelerates the capture, transport, and storage of moisture to achieve continuous and high-capacity moisture adsorption. Simultaneously, the integration of polydopamine (PDA) with the hydrogel realizes solar-driven photothermal evaporation. Therefore, the prepared core-shell hydrogel material possesses great advantages in water adsorption capacity and water desorption capacity with an adsorption of 2.76 g g-1 (90% RH) and a desorption of 1.42 kg m-2 h-1. Additionally, the core-shell structure hydrogel collects 1.31 g g-1 day-1 of fresh water in outdoor experiments, which verifies that this core-shell hydrogel with integrated photothermal properties can capture moisture in a wide range of humidity without any external energy consumption, can further sustainably obtain fresh water in remote water-shortage areas.

11.
Front Mol Biosci ; 9: 823911, 2022.
Article in English | MEDLINE | ID: mdl-35281270

ABSTRACT

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in women. Recent studies have investigated the prognostic value of the tumor microenvironment (TME)-related genes in breast cancer. The purpose of this research is to identify the immune-associated prognostic signature for breast cancer evaluate the probability of their prognostic value and compare the current staging system. In this study, we comprehensively evaluated the infiltration patterns of TME in 1,077 breast cancer patients downloaded from TCGA by applying the ssGSEA method to the transcriptome of these patients. Thus, generated two groups of immune cell infiltration. Based on two groups of low infiltration and high infiltration immune cell groups, 983 common differentially expressed genes were found using the limma algorithm. In addition, studying potential mechanisms, the GSEA method was used to indicate some pathways with remarkable enrichment in two clusters of immune cell infiltration. Finally, the seven immune-associated hub genes with survival as prognostic signatures were identified by using univariate Cox, survival, and LASSO analyses and constructed a TME score. The prognostic value of the TME score was self-validated in the TCGA cohort and further validated in an external independent set from METABRIC and GEO database by time-dependent survival receiver operation. Univariate and multivariate analyses of clinicopathological characteristics indicated that the TME score was an independent prognostic factor. In conclusion, the proposed TME score model should be considered as a prognostic factor, similar to the current TNM stage, and the seven immune-related genes can be a valuable potential biomarker for breast cancer.

12.
Carcinogenesis ; 43(1): 40-51, 2022 02 11.
Article in English | MEDLINE | ID: mdl-34490878

ABSTRACT

Mortalin is involved in the malignant phenotype of many cancers. However, the specific molecular mechanisms involving Mortalin in lung adenocarcinoma remain unclear. In this study, we showed that both Mortalin mRNA and protein are overexpressed in lung adenocarcinoma. In addition, Mortalin overexpression was positively correlated with poor overall survival. In vitro experiments showed that Mortalin silencing inhibited the proliferation, colony formation and migration abilities of A549 and H1299 cells. Mortalin promotes EMT progression, angiogenesis and tumor progression by activating the Wnt/ß-catenin signaling pathway. In vivo experiments further confirmed that Mortalin promoted malignant progression of lung adenocarcinoma. Taken together, our data suggest that Mortalin represents an attractive prognostic marker and therapeutic target in lung adenocarcinoma patients.


Subject(s)
Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Epithelial-Mesenchymal Transition/genetics , HSP70 Heat-Shock Proteins/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Neovascularization, Pathologic/genetics , A549 Cells , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neovascularization, Pathologic/pathology , Prognosis , Wnt Signaling Pathway/genetics
13.
Chem Commun (Camb) ; 57(94): 12623-12626, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34761755

ABSTRACT

Medical research reveals that keeping the skin surface dry can effectively prevent a variety of fungal skin diseases. Therefore, it is of great practical significance to develop a light, thin, comfortable and breathable functional garment fabric with efficient one-way water transmission for people's requirements. Here, we successfully prepared a three-layer stacking sandwich coating to construct a Janus nonwoven material with efficient unidirectional water transport function, viz. PDMS-ormosil-PDMS@nonwoven fabric (PDMS-ormosil-PDMS@NF). Theoretical analysis showed that the loading of ormosil particles could enhance the surface roughness, while PDMS could strengthen the hydrophobic properties and bondability between the ormosil particles and fabric, thus acting as an environmentally friendly fluorine-free treating agent. The results revealed that the hydrophilic-hydrophobic PDMS-ormosil-PDMS@nonwoven fabric maintained excellent hydrophobic stability and good air permeability even after abrasion, which solved the existing problems of aerogel poor deposition and PDMS poor permeability, benefiting the application of textiles with unidirectional water transport performance.

14.
Exp Mol Pathol ; 118: 104593, 2021 02.
Article in English | MEDLINE | ID: mdl-33309613

ABSTRACT

Mortalin is a member of the heat shock protein 70 (HSP70) family that promotes the development of many cancers. It is reportedly a tumor promoter, but the mechanism of Mortalin in breast cancer is unclear. We designed a series of experiments to explore the correlation between Mortalin and the malignancy of breast cancer, and to assess the potential of Mortalin as a novel therapeutic target in breast cancer. The expression level of Mortalin in breast cancer tissues was detected. Then, we did a series of functional experiment. The findings indicated that Mortalin facilitates the proliferation, metastasis, and endothelial-to-mesenchymal transition (EMT) process of breast cancer. In our research, Mortalin is regulated EMT process and malignant progression of breast cancer through Wnt/ß-Catenin signaling pathway. The findings imply that Mortalin significantly promotes the progression of breast cancer malignancy and reduces patient survival, suggesting that Mortalin as a biomarker and prognostic factor in breast cancer.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , HSP70 Heat-Shock Proteins/metabolism , Mitochondrial Proteins/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Movement , Cell Proliferation , Female , HSP70 Heat-Shock Proteins/genetics , Humans , Mitochondrial Proteins/genetics , Prognosis , Survival Rate , Tumor Cells, Cultured , Wnt Signaling Pathway
15.
Aging (Albany NY) ; 13(1): 1032-1050, 2020 12 03.
Article in English | MEDLINE | ID: mdl-33293473

ABSTRACT

SPOCK1 is highly expressed in many types of cancer and has been recognized as a promoter of cancer progression. Its regulatory mechanism in breast cancer (BC) remains unclear. This study aimed to explore the precise function of SPOCK1 in BC progression and to identify the mechanism by which SPOCK1 is involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) experiments and database analysis showed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of in vitro and in vivo assays elucidated that altering the SPOCK1 level led to distinct changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 to enhance cell proliferation, cell cycle progression and EMT by activating the AKT/mTOR pathway, whereas inhibition of the AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, the SPOCK1/SIX1 axis promoted BC progression by activating the AKT/mTOR pathway to accelerate cell proliferation and promote metastasis in BC, so the SPOCK1/SIX1 axis might be a promising clinical therapeutic target for preventing BC progression.


Subject(s)
Adenocarcinoma/genetics , Breast Neoplasms/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Homeodomain Proteins/genetics , Proteoglycans/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Female , Homeodomain Proteins/metabolism , Humans , MCF-7 Cells , Mice , Mice, Nude , Middle Aged , Neoplasm Grading , Proteoglycans/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Tumor Stem Cell Assay
16.
Int Immunopharmacol ; 81: 106028, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31801690

ABSTRACT

PURPOSE: To investigate the effect of miR-200c/PAI-2 on macrophage polarization into M2-type TAMs in TNBC. METHODS AND MATERIALS: PAI-2 expression in MDA-MB-231con, MDA-MB-231miR-200ab and MDA-MB-231miR-200c breast cancer cells was evaluated by RT-PCR and immunofluorescence (IF), while the expression of the TAM marker F4/80 and the M2-type TAM marker CD206 in MDA-MB-231con, MDA-MB-231miR-200c and MDA-MB-231miR-200c/siPAI-2 mouse lung metastatic tumor tissues was examined with immunohistochemistry (IHC). The effects of RAW264.7 cells on MDA-MB-231con, MDA-MB-231miR-200c and MDA-MB-231miR-200c/siPAI-2 were examined by transwell co-culture. CD206 expression in RAW264.7 cells were confirmed by immunostaining. The level of PAI-2 and IL-10 in the co-culture supernatants were assessed using ELISA. RESULTS: 1. RT-PCR and IF analysis showed that PAI-2 was upregulated in MDA-MB-231miR-200c cells. 2. IHC assays analysis showed that the numbers of F4/80 and CD206 positive cells were increased in MDA-MB-231miR-200c tumor tissues, while in MDA-MB-231miR-200c/siPAI-2 tumor tissues were decreased. 3. Transwell co-culture assays analysis showed that MDA-MB-231miR-200c cells significantly promoted the cell migration ability compared with the control group, while knockdown PAI-2 significantly inhibited the cell migration ability (P < 0.05). 4. Transwell co-culture and immunostaining assays analysis showed that overexpression miR-200c in MDA-MB-231 cell line increased the CD206 expression in RAW264.7 cells, while knockdown PAI-2 decreased. 5. ELISA assays analysis showed that miR-200c-mediated MDA-MB-231 cells significantly increased the secretion of PAI-2 and IL-10, while decreased the secretion of PAI-2 and IL-10 in MDA-MB-231 miR-200c/siPAI-2 cells. CONCLUSIONS: miR-200c promotes the malignant progressions of TNBC by PAI-2 upregulation and M2 phenotype macrophages polarization.


Subject(s)
Lung Neoplasms/immunology , Macrophages/immunology , MicroRNAs/metabolism , Plasminogen Activator Inhibitor 2/genetics , Triple Negative Breast Neoplasms/pathology , Animals , Cell Line, Tumor , Coculture Techniques , Disease Progression , Female , Gene Expression Regulation, Neoplastic/immunology , Gene Knockdown Techniques , Humans , Lectins, C-Type , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Macrophage Activation/genetics , Macrophage Activation/immunology , Macrophages/metabolism , Mannose Receptor , Mannose-Binding Lectins , Mice , RAW 264.7 Cells , Receptors, Cell Surface , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/immunology , Up-Regulation/immunology , Xenograft Model Antitumor Assays
17.
Cancer Manag Res ; 11: 6531-6542, 2019.
Article in English | MEDLINE | ID: mdl-31372054

ABSTRACT

PURPOSE: Human hydroxysteroid dehydrogenase-like 2 (HSDL2) is a characterized SDR gene that not only catalyses the oxidation and reduction of multiple substrates but also regulates different metabolic and signalling pathways. Accumulating evidences suggest that HSDL2 play an important role in cancer progression. However, the role of HSDL2 in breast cancer has not yet been determined. Thus, this study aims to explore the relevance of HSDL2 in breast cancer progression. PATIENTS AND METHODS: The location of HSDL2 protein was detected in MDA-MB-231 breast cancer cells by using immunofluorescence (IF) staining. The expression level of HSDL2 was evaluated by immunohistochemical (IHC) staining in 119 breast cancer tissues and 40 normal breast tissues. Then, the correlations between the overexpression of HSDL2 and clinicopathological features of breast cancer patients were evaluated by using the chi-square test, and the survival rates were calculated by the Kaplan-Meier method. In addition, the role of HSDL2 in breast cancer proliferation was assessed by MTT and colony formation assays, and cell cycle distribution was detected by flow cytometry analysis and Western blot. RESULTS: IF staining and IHC analysis consistently showed that HSDL2 was predominantly expressed in the cytoplasm of breast cancer cells. The positive rate of HSDL2 protein was significantly higher in breast cancer tissues (87.4%, 104/119) than in adjacent normal breast tissues (25%, 10/40) (p<0.01). A high expression of HSDL2 protein was significantly associated with high histological grades, late clinical stages and low survival rates. Moreover, multivariate analysis indicated that HSDL2 protein was an independent prognostic factor in breast cancer patients. Studies in vitro showed that HSDL2 depletion reduced cell proliferation and induced cell cycle arrest in breast cancer. CONCLUSION: In conclusion, this study indicated that HSDL2 plays a role in promoting the development of breast cancer. HSDL2 could be a valuable prognostic biomarker and a potential therapeutic target for patients with breast cancer.

18.
Chem Asian J ; 13(23): 3658-3663, 2018 Dec 04.
Article in English | MEDLINE | ID: mdl-30281925

ABSTRACT

A Pd0 -catalyzed four-component cascade reaction of an aryl halide, CO, an N-tosylhydrazone, and an amine affording α-amino ketone has been developed. This reaction involves a sequential carbonylation, metal carbene migratory insertion, and amination. Control experiments and DFT calculations further reveal the reaction sequence and chemoselectivity of individual components in this cascade process.

19.
Int J Surg ; 58: 37-45, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30121307

ABSTRACT

BACKGROUND: Recently, long non-coding RNA activated by transforming growth factor beta (TGF-ß) (lncRNA ATB) was shown to be useful in cancer prognosis, however, its prognostic value in human cancer has been inconsistent. Our study aimed to explore the prognostic role of lncRNA ATB expression in cancer prognosis. METHODS: PubMed, Embase, and Cochrane Library databases were thoroughly searched to retrieve studies focusing on the prognostic role of lncRNA ATB expression in cancer, and meta-analysis was performed. RESULTS: A total of 15 studies were included into this meta-analysis. High lncRNA ATB expression was significantly related to shorter overall survival (OS) (HR = 2.44, 95%CI = 1.98-3.01, P < 0.01), recurrence-free survival (RFS) (HR = 1.85, 95%CI = 1.42-2.40, P < 0.01), disease-free survival (DFS) (HR = 3.61, 95%CI = 2.45-5.33, P < 0.01), and progression-free survival (PFS) (HR = 2.97, 95%CI = 2.12-4.16, P < 0.01) when compared with low lncRNA ATB expression in cancer. Moreover, Patients with high lncRNA ATB expression tended to have worse tumor differentiation (P < 0.01), more advanced clinical stage (P < 0.01), deeper tumor invasion (P < 0.01), earlier distant metastases (P = 0.02), lymph node metastases (P = 0.04), and vascular invasion (P < 0.01) when compared with those with low lncRNA ATB expression. CONCLUSIONS: High lncRNA ATB expression was significantly associated with worse prognosis in cancer. LncRNA ATB expression could be used as a prognostic biomarker for human cancer.


Subject(s)
Neoplasms/mortality , RNA, Long Noncoding/physiology , Transforming Growth Factor beta/physiology , Female , Humans , Lymphatic Metastasis , Neoplasms/genetics , Neoplasms/pathology , Prognosis , RNA, Long Noncoding/analysis
20.
Small ; 13(48)2017 12.
Article in English | MEDLINE | ID: mdl-29058767

ABSTRACT

Ice accumulation poses a series of severe issues in daily life. Inspired by the nature, superwettability surfaces have attracted great interests from fundamental research to anti-icing and ice-phobic applications. Here, recently published literature about the mechanism of ice prevention is reviewed, with a focus on the anti-icing and ice-phobic mechanisms, encompassing the behavior of condensate microdrops on the surface, wetting, ice nucleation, and freezing. Then, a detailed account of the innovative fabrication and fundamental research of anti-icing materials with special wettability is summarized with a focus on recent progresses including low-surface energy coatings and liquid-infused layered coatings. Finally, special attention is paid to a discussion about advantages and disadvantages of the technologies, as well as factors that affect the anti-icing and ice-phobic efficiency. Outlooks and the challenges for future development of the anti-icing and ice-phobic technology are presented and discussed.

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