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Objective To investigate the effect and the possible mechanism of Lanthanum Citrate on the proliferation and apoptosis of human hepatocellular carcinoma cell line SMMC-7721 through the Hedgehog signaling pathway.Methods Hhsignaling pathway inhibitor KAAD-cyclopamine and Lanthanum Citrate in different concentrations were used to treat human hepatocellular carcinoma cell line SMMC-7721.Cell proliferation was detected by MTT method.The apoptosis rate was detected by Annexin V/PI flow cytometry.The expressions of the regulative genes,such as CyclinD1,p21,Caspase-3,Bcl-2,Gli1,Shh were detected by Western blot.The mRNA expressions of Gli1 and Shh were detected by q-PCR.Results In control group,SMMC-7721 cells were treated with 0.1 mmol/L Lanthanum Citrate group,and 15 μnol/L KAAD-cyclopamine for 48 h,and expression of CyclinD1 protein in each group was (1.41 ± 0.21),(0.71 ±0.08) and (0.53 ±0.11);p21 protein was (0.49 ±0.08),(0.97 ±0.09) and (1.55 ±0.13);Caspase-3 protein was (0.36 ± 0.05),(0.67 ± 0.10) and (0.89 ± 0.11);the relative expression of Bcl-2 protein in each group was (0.61 ± 0.10),(0.48 ± 0.05) and (0.24 ± 0.08).Gli1,Shh mRNA and Gli1,Shh protein expression were decreased.AnnexinV-FITC double staining showed Lanthanum Citrate group and KAAD-cyclopamine group had increased apoptosis rate of SMMC-7721 cells by flow cytometry.Conclusion Lanthanum Citrate inhibits the proliferation and promotes apoptosis in hepatocellular carcinoma SMMC-772 cells through suppressing hedgehog signaling pathway.
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<p><b>OBJECTIVE</b>To investigate the prognostic value of lymphatic vascular invasion (LVI) for stage I( gastric cancer patients after radical gastrectomy.</p><p><b>METHODS</b>Clinicopathological and intact follow-up data of 469 stage I( gastric cancer patients who underwent radical gastrectomy with R0 resection and were pathologically proven as gastric adenocarcinoma without other malignancy at the Department of Digestive Surgery, The First Affiliated Hospital, The Fourth Military Medical University between February 2009 and December 2012 were retrospectively collected. Chi square test was used to examine the relationship between LVI and clinicopathological data; Log-rank test was used for survival analysis; Cox proportional hazards model was used for univariate and multivariate analysis to explore the prognostic influence of LVI on stage I( gastric cancer patients.</p><p><b>RESULTS</b>A total of 469 patients were enrolled, including 360 male (76.8%) and 109 female patients (23.2%). Median age was 58(25-82) years. There were 114 T1a cases (24.3%), 195 T1b cases (41.6%), and 160 T2 cases (34.1%). There were 439 (93.6%) cases without lymph node metastasis and 30 cases with lymph node metastasis. Presence of LVI was found in 52 patients (11.1%). LVI was closely associated with tumor grade, depth of invasion and status of lymph node metastasis (all P<0.05), rather than gender, age, tumor location and tumor diameter (all P>0.05). LVI detection rate was higher in poorly differentiated and undifferentiated group (14.3%, 32/223) than that in moderately and well differentiated group (8.1%, 20/246) (χ=4.590, P=0.032). LVI detection rate was higher in T2 (14.4%, 23/160) and T1b (13.3%, 26/195) group than that in T1a group (2.6%,3/114)(χ=11.020, P=0.004). LVI detection rate was higher in patients with lymph node metastasis (30.0%, 9/30) compared to those without lymph node metastasis (9.8%, 43/439) (χ=11.629, P=0.001). Median follow-up time was 63(3-74) months. There were totally 46 deaths (9.8%). The 5-year overall survival rate was 90.2%. The 5-year overall survival rate was 82.7% in patients with LVI and 91.1% without LVI, which was significantly different (P=0.039). Univariate analysis showed that age (P=0.012), AJCC T stage (8th edition) (P=0.011), and LVI (P=0.043) were closely associated with the prognosis of gastric cancer patients, while gender, tumor location, tumor diameter, tumor grade, lymph node metastasis or postoperative chemotherapy were not associated to the prognosis (all P>0.05). Multivariate analysis revealed that only age(HR=2.038, 95%CI:1.126 to 3.686, P=0.019) and advanced T stage (T1b: HR=1.427, 95%CI:0.554 to 3.678; T2: HR=2.926, 95%CI:1.199 to 7.140; P=0.017) were independent prognostic factors of stage I( gastric cancer patients (both P<0.05).</p><p><b>CONCLUSIONS</b>LVI is not an independent prognostic factor of stage I( gastric cancer patients. In clinical practice, we should consider adjuvant chemotherapy prudently for stage I( gastric cancer patients with LVI.</p>
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Objective:To investigate the number of metastasized lymph node groups (Ng) and the prognosis of gastric cancer pa-tients. Methods:Data from 1 009 patients receiving radical gastrectomy in the Cancer Center and with more than 15 lymph nodes re-trieved between January 2000 and September 2010 were included in the study. Lymph nodes were grouped by using the definition of the Japanese Research Society for Gastric Cancer (13th Japanese edition). Log-rank test and Cox regression analysis were used to ex-plore the relationship between the Ng and overall survival. Results:The metastasized lymph nodes were divided into 5 groups:1 group without lymph node metastasis (Ng0), 1 group with lymph node metastasis (Ng1), 2 groups with lymph node metastasis (Ng2), 3 to 5 groups with lymph node metastasis (Ng3), and more than 6 groups with lymph node metastasis (Ng4). The 3-year survival rates were 91.6%, 84.7%, 72.0%, 59.6%, and 43.0% for Ng0, Ng1, Ng2, Ng3, and Ng4, respectively. The 5-year survival rates were 89.9%, 82.4%, 66.9%, 54.6%, and 38.3%for Ng0, Ng1, Ng2, Ng3, and Ng4, respectively. These 3-and 5-year overall survival rates differed significantly among the groups (P<0.05). Gastric cancer patients with high Ng have low 3-year overall survival rates. Ng is an indepen-dent prognostic factor of gastric cancer. Conclusion:The concept of Ng can be a good supplement to existing UICC N staging.