ABSTRACT
Objective To investigate the expression of Notch receptors and its relationship with clinicopathological features and prognosis in gastric cancer tissues. Methods Immunohistochemical SP method was used to detect the expression levels of Notch1, Notch2, Notch3 and Notch4 corresponding receptors in 45 patients with gastric cancer from January 2014 to May 2015 in the Third Affiliated Hospital of Hunan University of Traditional Chinese Medicine. The correlation between expression levels of Notch receptors and lymph node metastasis, TNM staging, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Notch1, Notch2, Notch3 and Notch4 corresponding receptors were mainly distributed in the cytoplasm, and the positive expression rates in gastric cancer tissues were 93.3％ (42/45), 86.7％ (39/45), 80.0％ (36/45), and 77.8％ (35/45), which were higher than those in adjacent tissues [31.1％ (14/45), 24.4％(11/45), 40.0％ (18/45), and 46.7％ (21/45)], and the differences were statistically significant (all P< 0.05). There was no correlation between the expression of Notch1, Notch2, Notch3 and Notch4 corresponding receptors and lymph node metastasis, TNM staging, DFS and OS in gastric cancer tissues (all P> 0.05). Conclusion Notch receptors are highly expressed in gastric cancer tissues, and have no correlation with lymph node metastasis, TNM staging, DFS and OS of patients after surgery.
ABSTRACT
BACKGROUND: The effects of the Notch signaling pathway in fibroproliferative skin diseases have not been fully elucidated. OBJECTIVE: The aim of this study was to investigate the expression of activated Notch signaling molecules in various skin fibroproliferative diseases. METHODS: Immunohistochemical analysis of Notch intracellular domain (NICD) expression in keloid, hypertrophic scar, morphea, dermatofibroma, and normal control skin specimens was performed, and the clinical characteristics of patients with various skin fibroproliferative diseases were analyzed. RESULTS: NICD was highly expressed in fibroblasts of keloids and moderately to highly expressed in hypertrophic scars and dermatofibromas, whereas low or no expression was detected in the fibroblasts of normal skin specimens and morpheas. NICD was constitutively expressed in keratinocytes, endothelial cells, and immune cells in normal skin specimens. CONCLUSION: NICD was significantly expressed in human fibroproliferative skin disorders, especially keloids, suggesting that an activated Notch signaling pathway is involved in the pathogenesis of skin fibrosis.
Subject(s)
Humans , Cicatrix, Hypertrophic , Endothelial Cells , Fibroblasts , Fibrosis , Histiocytoma, Benign Fibrous , Keloid , Keratinocytes , Receptors, Notch , Scleroderma, Localized , Skin Diseases , SkinABSTRACT
Objective To investigate the changes of Notch signaling pathway activity in human pancreatic cancer cell lines (SW1990, BxPC3 )after gemcitabine induction, and to study its relationship with pancreatic cancer resistant to gemcitabine chemotherapy. Methods The pancreatic cancer cell lines SW1990 and BxPC3 were cultured with different concentrations of gemcitabine for 48 hours. The Notch signaling pathway receptors ( Notch1, Notch2, Notch3, Notch4), ligands (Jagged1, Jagged2) and downstream target Hesl mRNAs expression were detected by quantitative real-time PCR (Q-PCR). Protein levels of Hes1 were determined by Western blotting. Results After treatment with 2 μmol/L gemcitabine for 48 hours, the expression of Notch1, Notch2, Notch3, Jagged1, Jagged2 and Hes1 mRNAs in SW1990 cells were 8.26 ±0.48, 39.12 ±4.87, 0.84 ±0.06, 105.8 ± 17.92, 6.59 ±0.32 and 17.30 ±2.96, which were significantly elevated when compared with those without gemcitabine treatment ( 1.02 ± 0. 15, 15.25 ± 1.28, 0. 12 ± 0.02,32.66 ± 1.98, 1.88 ± 0.29 and 5.02 ± 0.64, P < 0.05 or P < 0. 01 ); the expression in BxPC3 cells was 7.87 ±0.59, 109.4 ± 10.98, 0.74 ±0.19, 62.73 ± 13.50, 2.09 ±0.16 and 15.38 ± 1.06, which were significantly elevated when compared with those without gemcitabine treatment ( 1.14 ±0.43, 58.96 ±2.63,0.10 ± 0.02, 16.95 ± 3.79, 0.98 ± 0.02 and 2.04 ± 0.16, P < 0.05 or P < 0.01 ). The expressions of Hes1protein in SW1990 cells after 1, 2 μmol/L gemcitabine treatment for 48 h were 0.30 ±0.03, 0.42 ±0.03;and the expressions in BxPC3 cells were 0.33 ± 0.02, 0.45 ± 0.03, which were significantly increased when compared with those without gemcitabine treatment (0.13 ± 0.01, F = 33.71,0.09 ± 0.02, F = 38.54, P <0.01 ). Conclusions The Notch signaling pathway is significantly activated in pancreatic cancer cells SW1990 and BxPC3 by gemcitabine, which may be one of the mechanisms of chemoresistance.