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1.
Molecules ; 27(23)2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36500553

ABSTRACT

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.


Subject(s)
Copper , Cyclization , Catalysis , Molecular Structure
2.
J Drug Target ; 29(3): 336-348, 2021 03.
Article in English | MEDLINE | ID: mdl-33115283

ABSTRACT

Insulin resistance promotes the occurrence of liver cancer and decreases its chemosensitivity. Rosiglitazone (ROSI), a thiazolidinedione insulin sensitiser, could be used for diabetes with insulin resistance and has been reported to show anticancer effects on human malignant cells. In this paper, we investigated the combination of ROSI and chemotherapeutics on the growth and metastasis of insulin-resistant hepatoma. In vitro assay, ROSI significantly enhanced the inhibitory effects of adriamycin (ADR) on the proliferation, autophagy and migration of insulin-resistant hepatoma HepG2/IR cells via downregulation of EGFR/ERK and AKT/mTOR signalling pathway. In addition, ROSI promoted the apoptosis of HepG2/IR cells induced by ADR. In vivo assay, high fat and glucose diet and streptozotocin (STZ) induced insulin resistance in mice by increasing the body weight, fasting blood glucose (FBG) level, oral glucose tolerance, fasting insulin level and insulin resistance index. Both the growth of mouse liver cancer hepatoma H22 cells and serum FBG level in insulin resistant mice were significantly inhibited by combination of ROSI and ADR. Thus, ROSI and ADR in combination showed a stronger anti-tumour effect in insulin resistant hepatoma cells accompanying with glucose reduction and might represent an effective therapeutic strategy for liver cancer accompanied with insulin resistant diabetes.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Doxorubicin/pharmacology , Liver Neoplasms/drug therapy , Rosiglitazone/pharmacology , Animals , Animals, Outbred Strains , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Blood Glucose/drug effects , Carcinoma, Hepatocellular/pathology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Doxorubicin/administration & dosage , Drug Therapy, Combination , Hep G2 Cells , Human Umbilical Vein Endothelial Cells , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Insulin Resistance , Liver Neoplasms/pathology , Male , Mice , Rosiglitazone/administration & dosage
3.
Oncol Lett ; 20(6): 360, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33133260

ABSTRACT

Research on the immunosuppression of cancer cells has attracted much attention in recent years. The present study sought to provide a new strategy for tumor immunotherapy targeting mast cells by studying the mechanisms underlying mast cell function in cancer immunosuppression. Between January 2015 and December 2017, the tumor tissues of 40 patients with gastric cancer (GC) were collected and grouped in Lihuili Hospital of Ningbo City, China. Pathological sections were prepared and an immunofluorescence assay was performed to analyze the expression of forkhead Box Protein P3 (FOXP3), tryptase, TGFß1, TGF-ßR, IL-9, IL-9R and Oxford 40 ligand (OX40L). Then, the correlations between FOXP3 and tryptase, TGFß1 and tryptase expression, and the expression of OX40L in patients with GC with different stages were analyzed. The results revealed that high levels of mast cells were present in patients GC, and tryptase and FOXP3 expressions were positively correlated. Mast cells regulate T regulatory (reg) cells in the gastric tumor microenvironment by secreting TGFß1. Tregs, in turn, promote the survival of mast cells in the tumor microenvironment by producing IL-9. Furthermore, OX40L expression in mast cells was significantly associated with Tumor-Node-Metastasis staging of GC. Overall, the present study reported a positive feedback system that functions through TGFß1 and IL-9 to allow cross-talk between Tregs and mast cells. Moreover, OX40L may be a potential target for the diagnosis and treatment of GC. These results may provide a new strategy for tumor immunotherapy targeting mast cells.

4.
Biomed Pharmacother ; 96: 659-666, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29035832

ABSTRACT

Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance. In this review, we focused on the application and resistance mechanisms of the Vinca alkaloids such as vinblastine, vincristine, vinorelbine and vinflunine in lung cancer. We reviewed characteristic resistance mechanisms in lung cancer including over-expression of ATP-binding cassette (ABC) transporters P-glycoprotein and structural, functional or expression alterations of ß-tubulin (ßII, ßIII, ßIV) which may devote to the development of acquired resistance to the Vinca alkaloids; multidrug-resistance proteins (MRP1, MRP2, MRP3) and RLIP76 protein have also been identified that probably play a significant role in intrinsic resistance. Lung resistance-related protein (LRP) is contributed to lung cancer therapy resistance, but is not deal with the Vinca alkaloids resistance in lung cancer. Understanding the principle of the Vinca alkaloids in clinical application and mechanisms of drug resistance will support individualized lung cancer therapy and improve future therapies.


Subject(s)
Drug Resistance, Neoplasm/drug effects , Genes, MDR/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Vinca Alkaloids/metabolism , Vinca Alkaloids/therapeutic use , Animals , Antineoplastic Agents, Phytogenic/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Binding Sites/drug effects , Binding Sites/physiology , Drug Resistance, Neoplasm/physiology , Genes, MDR/physiology , Humans , Microtubules/drug effects , Microtubules/metabolism , Tumor Cells, Cultured , Vinblastine/analogs & derivatives , Vinblastine/metabolism , Vinblastine/pharmacology , Vinca Alkaloids/pharmacology , Vincristine/metabolism , Vincristine/pharmacology , Vincristine/therapeutic use
5.
J Zhejiang Univ Sci B ; 15(11): 953-65, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25367788

ABSTRACT

It is important to understand the effects of temporal changes in microbial communities in the acidic soils of tea orchards with different fertilizers. A field experiment involving organic fertilizer (OF), chemical fertilizer (CF), and unfertilized control (CK) treatments was arranged to analyze the temporal changes in the bacterial and archaeal communities at bimonthly intervals based on the 16S ribosomal RNA (rRNA) gene using terminal restriction fragment length polymorphism (T-RFLP) profiling. The abundances of total bacteria, total archaea, and selected functional genes (bacterial and archaeal amoA, bacterial narG, nirK, nirS, and nosZ) were determined by quantitative polymerase chain reaction (qPCR). The results indicate that the structures of bacterial and archaeal communities varied significantly with time and fertilization based on changes in the relative abundance of dominant T-RFs. The abundancy of the detected genes changed with time. The total bacteria, total archaea, and archaeal amoA were less abundant in July. The bacterial amoA and denitrifying genes were less abundant in September, except the nirK gene. The OF treatment increased the abundance of the observed genes, while the CF treatment had little influence on them. The soil temperature significantly affected the bacterial and archaeal community structures. The soil moisture was significantly correlated with the abundance of denitrifying genes. Of the soil chemical properties, soil organic carbon was the most important factor and was significantly correlated with the abundance of the detected genes, except the nirK gene. Overall, this study demonstrated the effects of both temporal alteration and organic fertilizer on the structures of microbial communities and the abundance of genes involved in the nitrogen cycle.


Subject(s)
Archaea/isolation & purification , Bacteria/isolation & purification , Fertilizers/microbiology , Soil Microbiology , Tea/growth & development , Tea/microbiology , Archaea/classification , Archaea/genetics , Bacteria/classification , Bacteria/genetics , Microbial Consortia/physiology , Seasons , Temperature
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