Clinical implications of micro lymph node metastasis for patients with gastric cancer.

BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.

Formononetin inhibits colon carcinoma cell growth and invasion by microRNA­149­mediated EphB3 downregulation and inhibition of PI3K/AKT and STAT3 signaling pathways.

Formononetin (Form), a phytoestrogen extracted from the roots of Astragalus membranaceus, is one of the fundamental herbs used in traditional Chinese medicine because of its protective effects against certain malignant tumors. However, its role in colon carcinoma cells and the underlying molecular mechanisms have not been completely elucidated. The present study aimed to demonstrate that Form significantly inhibited the proliferation and invasion of the colon carcinoma cell lines SW1116 and HCT116. Mechanistic studies have suggested that Form suppresses colon carcinoma cell growth by downregulating cell cycle­associated protein (cyclin D1) expression and arresting the cell cycle at the G0­G1 checkpoint. Further studies revealed that treatment with Form inhibits matrix metalloproteinase (MMP)2 and MMP9 expression. Aditionally, the results demonstrated that Form significantly increased microRNA (miR)­149 expression. Following miR­149 overexpression in SW1116 and HCT116 cells using an miR­149 mimic, cell viability and Ephrin type­B receptor 3 (EphB3) levels decreased. Furthermore, the inhibitory effects of Form were associated with phosphatidylinositol 3­kinase (PI3K)/protein kinase B (AKT) and signal transducer and activator of transcription 3 (STAT3) signaling pathways. These results indicated the suppressive effect of Form on colon carcinoma cell proliferation and invasion, possibly via miR­149­induced EphB3 downregulation and the inhibition of the PI3K/AKT and STAT3 signaling pathways. Overall, Form may be used as a novel candidate for the clinical treatment of colorectal cancer in the future.

[Effect and mechanisms of TET on human gastric carcinoma cell line SGC7901 and SGC7901/ADR].

OBJECTIVE: To investigate the effect of tetrandrine (TET) on zinc finger protein 139 (ZNF139) and multidrug resistance (MDR) of human gastric carcinoma cell lines and possible mechanisms. METHODS: Cultured SGC7901 and SGC7901/ADR were treated with TET (0.5, 1.0, 1.5, 2.0, and 2.5 microg/mL), then inhibition rates were measured by MTT assay in vitro. The expressions of ZNF139, MRP-1, MDR1, and GST-pi were detected by RT-PCR. The correlation between ZNF139 and each multidrug resistance factor was analyzed using Spearman correlation analysis, and the coefficient correlation was calculated. RESULTS: The inhibition rate of TET (< or = 2.0 microg/mL) for SGC7901 and SGC7901/ADR was less than 10% with MTT assay. Expressions of ZNF139, MRP-1, MDR1, and GST-pi mRNA were higher in SGC7901/ADR than in SGC7901 (all P < 0.05). The expressions of ZNF139, MRP-1, MDR1, and GST--pi were down-regulated in SGC7901/ADR cells efficiently (all P < 0.01). Positive correlation existed between ZNF139 and MRP-1, ZNF139 and MDR1 before treated by TET in SGC7901/ADR, and this relationship also existed in SGC7901/ADR cells after treated by TET (all P < 0.05). CONCLUSION: TET could achieve MDR reversion in gastric cancer cells by down-regulating the expression of ZNF139, MRP-1, and MDR1.

[Drug distribution in gastric cancer and adjacent tissues by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome].

OBJECTIVE: To examine the distribution of fluorouracil in gastric cancer (CA), lymph node (LN), normal gastric mucosa (NG), peritoneum (PE), greater omentum (GO) and lesser omentum (LO) by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome (Co 5-Fu), and offer an experimental basis for clinic practice. METHODS: Ninety-six gastric cancer patients were divided into four groups: Co 5-Fu i.v. injection group (Co 5-Fu i.v.), Co 5-Fu intraperitoneal perfusion group (Co 5-Fu i.p.), 5-Fu i.v. injection group (5-Fu i.v.) and intraperitoneal perfusion group (5-Fu i.p.) given on day-2, day-1 and 60 minutes before operation. Fluorouracil concentration in all tissues collected during operation were examined by high performance liquid chromatography (HPLC). RESULTS: The fluorouracil concentration in the tissues in Co 5-Fu i.p. group was significantly higher than that in Co 5-Fu i.v. or 5-Fu i.p. group (P < 0.05 or P < 0.01), and that in 5-Fu i.p. group was greatly higher than that at 5-Fu i.v. group (P < 0.01). In Co 5-Fu i.p. group, the concentration of drug in LN, CA, PE, NG, GO and LO decreased gradually with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01), and adjacent lymph node was the highest. In Co 5-Fu i.v. group, the ranking was LN, CA, NG, PE, GO and LO with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01) and showing tumor tissues higher than the other tissues (P < 0.01). In 5-Fu i.p. group, the ranking was PE, LN, CA, NG, GO and LO with the former 2 tissues significantly higher than the latter tissues (P < 0.01). CONCLUSION: Co 5-Fu possesses drug targeting, slow release and long effect in gastric cancer tissues and adjacent lymph nodes. Preoperative chemotherapy with Co 5-Fu i.p. is more advantageous than 5-Fu given i.v. or 5-Fu i.p.