NK3 and NK4 of HGF enhance filamin production via STAT pathway, but not NK1 and NK2 in human breast cancer cells.

AIM: The purpose of this study was to reveal the effects of hepatocyte growth factor (HGF) variants on human breast cancer cells and the differential signaling pathways of the variants in controlling cell proliferation and invasion. METHODS: Four HGF variants (NK1, NK2, NK3, and NK4) were created by gene engineering, and the variant DNA fragments were cloned into pGEM-T for DNA sequencing and then transferred to a pTrcHis-A plasmid for expression. Recombinant proteins were purified from Escherichia coli, and a series of assays, including cell proliferation and invasion were carried out. Phosphorylated components in the HGF-c-Met and STAT (signal transducers and activators of transcription) pathways were detected by immunoprecipitation-Western blots. RESULTS: All the HGF variants inhibited the vigorous growth of the cancer cells differently and dose-dependently, but the effect of NK3 or NK4 was 7.5-fold higher than NK1 or NK2. In addition, the assays for the phosphorylation of the components in the HGF-c-Met pathway showed that NK3 and NK4 inhibited invasion via the STAT pathway, whereas NK1 and NK2 were via the HGF-c-Met pathway. CONCLUSION: The engineered HGF variants inhibited the proliferation of human breast cancer cells via different signaling pathways, NK1 and NK2 via the HGF-c-Met pathways, and NK3 and NK4 via the STAT pathway, the latter being a possible key route for the inhibition of cell invasion. All of the HGF variants have the potential to become pharmaceutical drugs in the treatment of human cancer.

[Surgical approach for carcinoma in the gastric cardia].

OBJECTIVE: To explore the optimal surgical approach for carcinoma in the gastric cardia. METHODS: A total of 157 patients with carcinoma in the gastric cardia were assigned into 2 groups according to the surgical approaches adopted, namely transabdominal (57 patients) and transthoracic approaches (100 patients), and the therapeutic effects of the two approaches were compared. RESULTS: In the transabdominal group, the average volume of intraoperative blood transfusion was 164.91+/-36.83 ml, average operative time 219.04+/-10.72 min and average hospital stay 14.39+/-1.39 d, with an average number of 6.04+/-2.84 lymph nodes removed. In the transthoracic group, the 4 parameters were 575.50+/-40.12 ml, 286.40+/-7.94 min, 20.32+/-0.81 d, and 3.62+/-2.56 respectively. None of the cases developed pleural effusion in the former group, which had a tumor recurrence rate of 22.80% within the follow-up period for 3 to 60 months. In contrast, 15 cases had pleural effusion in the latter group with a tumor recurrence rate of 41.00%. There was a significant difference between the two groups in terms of the therapeutic effects. CONCLUSION: Transabdominal approach is the better alternative to transthoracic one for operation of carcinoma in the gastric cardia.