Search

Objective To compare the affinity with sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) and anti-inflammatory effects of 18 traditional Chinese medicine polysaccharides in order to explore a new mechanism for the anti-inflammatory effects of these polysaccharides. Methods Aqueous alcohol precipitation was used to extract polysaccharides from 18 traditional Chinese medicines with different medicinal properties. Phenol sulfuric acid method was employed to detect the content of the polysaccharides, high performance liquid chromatography (HPLC) was utilized to measure the monosaccharide composition of the polysaccharides, and infrared spectroscopy was applied to detect the structure of the polysaccharides of Chinese medicines. The affinity of polysaccharide to Siglec-9 was detected by competitive ELISA, and the effects of the polysaccharides on LPS-induced inflammatory responses in macrophages and R848-induced NETosis in neutrophils were investigated. Primary cultured macrophages and neutrophils derived from myeloid-specific Siglec-E knockout mice (Lyz2-cre: Siglec-Eflox/flox) were used to further clarify the mechanism of the anti-inflammation of the polysaccharides. Results All these 18 traditional Chinese medicines had the content of polysaccharide over 55%, and mainly composed of mannose, glucose, galactose, arabinose and glucuronic acid, with different composition ratio of monosaccharide separately. Infrared spectroscopy revealed that there were typical polysaccharide absorption peaks in all 4 representative polysaccharides, and the polysaccharides from Bupleurum chinense and Dandelion had glucuronic acid structures. The affinities with Siglec-9 in the polysaccharides from Lycium barbarum and Astragalus showed no inhibitory effect on LPS-induced inflammatory responses in macrophages and R848-induced NETosis in neutrophils. While, Bupleurum chinense and dandelion polysaccharides presented strong affinities with Siglec-9 (P < 0.01), and exerted obvious inhibitory effect on above inflammatory reactions, but the anti-inflammatory effects were lost disappeared in the macrophages and neutrophils derived from Siglec-E conditional knockout mice. Conclusion The affinity between Chinese herbal polysaccharide and Siglec-9 has a possibility to be a potential novel pharmacological mechanism of the anti-inflammatory effects of traditional Chinese medicine.

Background and purpose: Metastasis remains the cause of 90% of death from cancer. By analyzing the distribution of metastatic sites and survival status of 20 000 metastatic cancer patients from a hospital-based cancer registry database, this study provides the real-world data for the cancer treatment and survival management in China. Methods: A total of 20 067 cancer patients who were diagnosed as having metastatic caner or developed metastasis during the follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study. Medical records review, telephone visits and death registry data linkage were applied in collecting endpoint data. The first follow-up date was the diagnosis date of metastasis, and the last follow-up date was November 1, 2020. Kaplan-Meier method was applied in evaluating the 1-, 3- and 5-year overall survival (OS) rates for overall cancer and site-specific cancer patients. Results: The median follow-up time was 46.7 months, 13 170 cases died during the follow- up, 60.05% was single-site metastasis, and 39.95% was multiple-site metastasis. Among all metastable sites, the proportion of metastasis to liver was 33.82%, 26.25% to lung, 26.22% to bone, and 9.22% to brain. The incidence of brain metastasis was the highest in lung cancer patients among all cancer types (31.14%). Liver was the most frequent metastatic site in pancreatic cancer (77.85%), and bone was the most frequent metastatic site in patients with prostate cancer (83.20%). Subgroup analysis showed that liver metastasis was easier to be observed in males than in females (35.46% vs 31.89%, P

Background: Tissue factor pathway inhibitor 2 (TFPI‐2) has been recently identified as a tumor suppressor gene in several human cancers, whereas its role in thyroid cancer has been unclear. Methods: The TFPI‐2 protein level in thyroid cancer tissues and cell lines (8305C and B‐CPAP) were examined using immunohistochemistry and immunoblotting. The TFPI‐2 promoter methylation was examined using methylation‐specific polymerase chain reaction (MSP). Lentivirus containing TFPI‐2 cDNA (Lenti‐TFPI‐2) was constructed to elevate TFPI‐2 expression in 8305C and B‐CPAP cells. The effects of Lenti‐TFPI‐2 on cell proliferation in vitro and in vivo were evaluated by MTT assay and mouse xenograft model. Annexin V/PI double staining assay was performed to detect the effect of Lenti‐TFPI‐2 on cell apoptosis. Results: TFPI‐2 protein level were decreased in cancer tissues and lymph node metastasis, and TFPI‐2 protein level is positively associated with survival time. The promoter of TFPI‐2 is hypermethylated in cancer tissues. TFPI‐2 mRNA and protein levels were abundant in normal human thyroid follicular cell line Nthy‐ori 3‐1 cells, whereas they were decreased in 8305C and B‐CPAP cells. pcDNA‐TFPI‐2 elevated TFPI‐2 mRNA and protein in 8305C and B‐CPAP cells. TFPI‐2 overexpression suppressed proliferation and induced apoptosis of 8305C and B‐CPAP cells. Conclusions: TFPI‐2 inactivation may play a role in thyroid cancer tumorigenesis and development. TFPI‐2 overexpression suppressed cell proliferation through induction of cell apoptosis, suggesting that TFPI‐2 may serve as a novel and effective target for thyroid cancer therapy. [ABSTRACT FROM AUTHOR]

Sijunzi decoction (SJZD) is a traditional Chinese herbal medicine. Previous studies have indicated that SJZD exhibits antitumor activity. However, the underlying molecular mechanism has not been fully elucidated. To explore the antitumor mechanism of SJZD, the effects of serum from rats treated with SJZD on the proliferation of MKN-28 and HGC-27 gastric carcinoma cell lines were systematically investigated. It was found that SJZD-treated rat serum significantly inhibited the growth of MKN-28 and HGC-27 cells in vitro. The results obtained from a colony formation assay showed that SJZD-treated rat serum decreased the colony formation ability of MKN-28 and HGC-27 cells. The apoptosis rate in MKN-28 and HGC-27 cells was also increased following treatment with SJZD-treated rat serum. Flow cytometry with cell sorting revealed the presence of side population (SP) cells in MKN-28 and HGC-27 cells though Hoechst 33342 staining, and verapamil reduced the SP percentage. Further analysis showed that SJZD-treated rat serum promoted the apoptosis of SP cells in MKN-28 and HGC-27 cell lines by upregulating Bax, caspase-3 and PARP and downregulating bcl-2. These data revealed the therapeutic effect of SJZD-treated rat serum on gastric carcinoma. Following the preliminary identification of the inhibitory effect on the growth of gastric cancer cells in vitro, the growth inhibitory effect of SJZD-treated rat serum on SP cells was confirmed, and this inhibition particularly involved the induction of cell apoptosis. [ABSTRACT FROM AUTHOR]

Background: Tissue factor pathway inhibitor 2 (TFPI-2) has been recently identified as a tumor suppressor gene in several human cancers, whereas its role in thyroid cancer has been unclear., Methods: The TFPI-2 protein level in thyroid cancer tissues and cell lines (8305C and B-CPAP) were examined using immunohistochemistry and immunoblotting. The TFPI-2 promoter methylation was examined using methylation-specific polymerase chain reaction (MSP). Lentivirus containing TFPI-2 cDNA (Lenti-TFPI-2) was constructed to elevate TFPI-2 expression in 8305C and B-CPAP cells. The effects of Lenti-TFPI-2 on cell proliferation in vitro and in vivo were evaluated by MTT assay and mouse xenograft model. Annexin V/PI double staining assay was performed to detect the effect of Lenti-TFPI-2 on cell apoptosis., Results: TFPI-2 protein level were decreased in cancer tissues and lymph node metastasis, and TFPI-2 protein level is positively associated with survival time. The promoter of TFPI-2 is hypermethylated in cancer tissues. TFPI-2 mRNA and protein levels were abundant in normal human thyroid follicular cell line Nthy-ori 3-1 cells, whereas they were decreased in 8305C and B-CPAP cells. pcDNA-TFPI-2 elevated TFPI-2 mRNA and protein in 8305C and B-CPAP cells. TFPI-2 overexpression suppressed proliferation and induced apoptosis of 8305C and B-CPAP cells., Conclusions: TFPI-2 inactivation may play a role in thyroid cancer tumorigenesis and development. TFPI-2 overexpression suppressed cell proliferation through induction of cell apoptosis, suggesting that TFPI-2 may serve as a novel and effective target for thyroid cancer therapy., (© 2020 John Wiley & Sons Australia, Ltd.)

The present study aimed to investigate the expression of interleukin‑6 (IL‑6) in gallbladder cancer (GBC) tissues and its correlation with survival rate. The association between IL‑6 and epithelial‑mesenchymal transition (EMT)‑associated markers was also examined. Using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, the protein and mRNA expression levels of IL‑6, Twist, E‑cadherin and Vimentin in 20 GBC tissues were analyzed. The IL‑6, Twist and Vimentin proteins were overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The protein expression of E‑cadherin was higher in only 5% of the GBC samples. These differences were significant (P<0.05). Western blot analysis also revealed overexpression of IL‑6, Twist and Vimentin and underexpression of E‑cadherin in the GBC samples with poor differentiation, local invasion and a higher tumor‑node‑metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL‑6, Twist and Vimentin and a reduced expression level of E‑cadherin were also demonstrated in the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph node metastasis and clinical stage were significantly associated with the mRNA expression levels of IL‑6, Twist and E‑cadherin. The increased expression levels of IL‑6 and Twist and the reduced expression of E‑cadherin correlated with shorter median survival rates (P<0.05). Line regression results revealed correlation among the mRNA expression levels of IL‑6, Twist, E‑cadherin and Vimentin. To the best of our knowledge, the present study is the first to demonstrate that IL‑6 is associated with EMT‑associated markers, tumor differentiation, local invasion, TNM stage and survival rates in GBC.

Gallbladder cancer is the most common biliary tract malignancy and the fifth most common gastrointestinal malignancy. Chemo-resistance is the most remarkable characteristic of gallbladder cancer. The relatively dense extracellular space in tumor is the main barrier to nanotherapeutics' anticancer efficacy. Hyaluronan (HA) was shown in our previous study to significantly improve the myxoma virus distribution via promoting the MMP-9 production, which degrades collagen IV. We demonstrated that HA increased the chemo-sensitivity of gallbladder cancer cells both in vitro and in vivo. The in vivo chemo-sensitization effect of HA could partially be due to the penetration-promoting effect of HA via degrading collagen IV.