Search

The kallikrein-related peptidase 10 (KLK10) gene has tumor-suppressive function in various types of human cancer. However, previous studies showed that KLK10 also acts as an oncogene and is upregulated in gastrointestinal tumors. The role of KLK10 in human esophageal cancer (EC) remains unclear. In the present study, the expression of KLK10 in human esophageal and non-esophageal cancer tissues was investigated by immunohistochemistry. Quantitative RT-PCR and western blot analysis were utilized to detect KLK10 mRNA and protein expression in human esophageal cancer cell lines (TE-1 and Eca-109). Small interference RNA was utilized to specifically knockdown KLK10 expression in Eca-109 and TE-1 cells. Cell proliferation, cell cycle analysis as well as CDDP-dependent apoptosis were determined using a CCK-8 assay and flow cytometry. The results showed that, KLK10 was positive in 67 out of 83 (80.72%) human EC and positive in 3 out of 11 (27.27%) normal tissues (P=0.001). The present study indicated that KLK10 potentially plays a crucial role in Eca-109 cell growth. Additionally, the downregulation of KLK10 induced S-phase arrest and promoted cisplatin-induced apoptosis. The resutls of the present study suggested that KLK10 is a promising novel marker for the diagnostic and therapeutic target of esophageal cancer.

Background: A novel reporter system, streptavidin (SA)- [68 Ga]Ga-labeled biotin ([68 Ga]Ga-DOTA-biotin), was constructed and its ability for PET imaging the behaviors of CAR T cells were also evaluated in this study. Methods: In vitro activity and cytotoxicity of the SA transduced anti-CD19-CAR T (denoted as SA-CD19-CAR T) cells were determined. The feasibility of monitoring proliferation profiles of SA-CD19-CAR T cells using [68 Ga]Ga-DOTA-biotin was firstly investigated in a solid tumor model. Also, the pharmacodynamics and pharmacokinetics of the CAR T cells in whole-body hematologic neoplasms were evaluated by bioluminescence imaging and [68 Ga]Ga-DOTA-biotin PET imaging simultaneously. Results: After transduction with SA, the activity and cytotoxicity of the modified CAR T cells were not affected. PET images revealed that the uptakes of [68 Ga]Ga-DOTA-biotin in CD19+ K562 solid tumors were 0.67 ± 0.32 ID%/g and 1.26 ± 0.13 ID%/g at 30 min and 96 h p.i. after administration of SA-CD19-CAR T cells respectively. It confirmed that the SA-CD19-CAR T cells could effectively inhibit the growth of Raji hematologic tumors. However, low radioactivity related to the proliferation of CD19-CAR T cells was detected in the Raji model. Conclusion: SA-CD19-CAR T cells were constructed successfully without disturbing the antitumor functions of the cells. The proliferation of the CAR T cells in solid tumors could be early detected by [68 Ga]Ga-DOTA-biotin PET imaging. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation plays a significant role in the occurrence and development of non‐small cell lung cancer (NSCLC). Hydroxysafflor yellow A (HSYA), a chemical compound of the yellow color pigments extracted from the safflower, has been widely used in clinical treatment with positive antioxidation, anti‐inflammation, and antitumor effects. However, the role and underlying mechanisms of HYSA on development and progress in inflammation‐mediated NSCLC are unknown. Methods: Cell counting kit‐8, colony formation, EdU, cell apoptosis, wound healing, Transwell migration and invasion, and enzyme‐linked immunosorbent assays; flow cytometry; and Western blotting were conducted using human NSCLC cell lines A549 and H1299. Results: Lipopolysaccharide (LPS) significantly promoted the proliferation and enhanced colony formation of A549 and H1299 cells, while HYSA notably reversed the effects of LPS. HYSA induced apoptosis of LPS‐mediated A549 and H1299 cells in a dose dependent manner; and remarkably suppressed migration, invasion, and epithelial–mesenchymal transition (EMT), significantly regulated production of LPS‐induced inflammation cytokines, and downregulated protein expression of PI3K/Akt/mTOR and ERK/MAPK signaling pathways in LPS‐induced A549 and H1299 cells. Furthermore, PI3K (LY294002) and ERK (SCH772984) inhibitors remarkably inhibited proliferation, migration, invasion, and EMT, and induced apoptosis in LPS‐mediated A549 and H1299 cells. These effects were even more obvious in the presence of HYSA and LY294002 or SCH772984 compared to those of either agent alone. Conclusion: HYSA suppressed LPS‐mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation‐mediated NSCLC. [ABSTRACT FROM AUTHOR]

Two new steroidal glycosides characterized with 2,6-dideoxypyranoses as component sugars have been isolated from roots of Cynanchum wallichii Wight. Their structure elucidation and cytotoxic activities against HL-60 and PC-3 cells are reported. [ABSTRACT FROM AUTHOR]

Three new compounds, 4-hydroxyphenethyl-2'-hydroxypropanoate (1), 6-(1',2'-dimethyloxiran-1'-yl)-4-methoxy-3-methyl-2H-pyran-2-one (2), 6-(1-hydroxyethyl)-4-methoxy-3-methyl-2H-pyran-2-one (3), along with the two known compounds, nectriapyrone (4) and wermopyrone (5), have been isolated from the endophytic fungus of Cephalotaxus hainanensis. Their structures were determined on the basis of chemical and spectroscopic methods. [ABSTRACT FROM AUTHOR]

Six undescribed monoterpenoids, together with twelve known compounds were isolated and identified from Hyssopus cuspidatus Boriss. Their structures were established by spectroscopic analysis, and the absolute configurations were established by ECD calculations and single-crystal X-ray diffraction crystallography. The isolated compounds were tested for their anti-inflammatory, antibacterial and antitumor activities. Most of the compounds showed potent anti-inflammatory activities. Among them, 3 β -hydroxy-7,8-dihydro- β -ionone (8), oleanolic acid (17) and acetylpleamolic acid (18) showed strong anti-inflammatory activity against IL-6 and TNF- α in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Several compounds showed moderate inhibitory activities against Staphylococcus aureus , Candida albicans , and Escherichia coli. And (4 S)- p -menth-l-ene-7,8-diol 8- O - β -D-glucopyranoside (16) showed antitumor activities against MCF-8 and HT-29 cell lines with IC 50 values of 93.39 ± 3.69 and 71.89 ± 2.94 μ M, respectively. Oleanolic acid (17) showed moderate antitumor activity against HT-29 cell lines with an IC 50 value of 52.62 ± 1.63 μ M. In this study, the discovery of anti-inflammatory, antibacterial and antitumor components from H. cuspidatus could benefit further development and utilization of this plant. [Display omitted] • Eighteen terpenoids including six new ones were isolated from Hyssopus cuspidatus. • Most of the compounds showed potent anti-inflammatory activities. • Compound 8 showed strong anti-inflammatory activity against IL-6 and TNF-α. • Several compounds showed good activities against MCF-8, HT-29 and HT-29 cell lines. • Several compounds showed moderate antimicrobial activities. [ABSTRACT FROM AUTHOR]