It is one of the main characters of malignant tumors that malignant tumor cells invade surrounding tissues and metastasize to distant tissues .Multiple factors are involved in this complicated dynamic process .Metastasis is the major factor influencing recurrence and prognosis .Therefore, it is important to explore the mechanism of invasion and metastasis for reducing recurrence rate and mortality of malignant tumors .Engulfment and cell mobility ( ELMO) family is one kind of conserved protein in evolutional process .It includes 3 members, ELMO1, ELMO2 and ELMO3.The members of ELMO family play an important role in cell phagocytosis and cell migration , and they also have close correlation with ma-lignant tumor cell invasion and metastasis .In this paper , we review the progress of the relationship between ELMO family and malignant tumor invasion and metastasis .

Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor, Member 6b ; metabolism

Antibodies, Neutralizing ; Apoptosis ; Hep G2 Cells ; Humans ; Receptors, Tumor Necrosis Factor, Member 6b ; immunology ; metabolism

AIM:To reveal the role and function of engulfment and cell mobility 1 (ELMO1) in the invasion and migration of gastric cancer cells.METHODS:The expression of ELMO1 at protein and mRNA levels was detected in 5 kinds of gastric cancer cells and 1 normal human gastric epithelial cells by Western blot and real-time PCR, and the gastric cancer cells with the highest expression of ELMO1 were screened out.The cell transfection experiment was used to silence ELMO1 expression in the gastric cancer cells, and the effect of ELMO1 silencing on the invasion and migration of the gastric cancer cells was detected by Transwell assay.RESULTS:The expression level of ELMO1 in the gastric cancer cells was significantly higher than that in human normal gastric epithelial cells (P<0.01), and the SGC7901 cells had the highest expression level of ELMO1.ELMO1-siRNA significantly silenced the expression of ELMO1 in the SGC7901 cells (P<0.01).Silencing of ELMO1 expression significantly reduced the invasion and migration abilities of the human gastric can-cer cells (P<0.01).CONCLUSION:ELMO1 is highly expressed in the gastric cancer cells, and promotes the invasion and migration abilities of the gastric cancer cells.ELMO1 may become an effective target for the treatment of invasion and metastasis of gastric cancer.

To investigate the effect of microRNA-221 (miR-221) on cell viability and apoptosis of hepatocellular carcinoma HepG2 cells. MiR-221 inhibitors and mimics were transfected into HepG2 cells. The expression of miR-221 was detected by real time quantitative RT-PCR. CellTiter-blue cell viability kit, Hoechst 33342/propidium iodide (PI) double staining assay, flow cytometry and Apo-ONE homogeneous caspase-3/7 kit were used to measure cell viability and apoptosis. MiR-221 inhibitors significantly inhibited the cell growth and miR-221 mimics increased cell viability 48 hours post-transfection measured by both CellTiter-blue cell viability kit and Hoechst 33342/PI assay (P is less than to 0.05). There was a positive correlation between these two assays (r = 0.993, P is less than to 0.01). With miR-221 mimics, the number of G1 stage cells (47.67%+/-1.53%) was significantly reduced as compared to the blank control (59.00%+/-1.00%) and the negative control (58.00%+/-1.00%, F = 81.77, P is less than to 0.01), and it was significantly raised in S stage (20.33%+/-1.15%) than in blank control (11.00%+/-1.00%) and negative control (12.00%+/-1.00%, F = 70.9, P is less than to 0.01) with flow cytometry analysis. More cell apoptosis and necrosis were significantly induced by miR-221 inhibitors 48 hours post-transfection detected by both Hoechst 33342/PI assay and flow cytometry PE Annexin V kit (P is less than to 0.05). The result from Apo-ONE homogeneous caspase-3/7 kit was consistent with the above two apoptotic assays, which showed that with miR-221 inhibitors, the activity of caspase-3/7 was significantly enhanced (P is less than to 0.05). MiR-221 contributes to the growth of hepatocellular carcinoma cells and miR-221 inhibition can induce cell apoptosis. miR-221 has the potential to become one of the new molecular targets for liver cancer therapy.
Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; Cell Proliferation ; drug effects ; Hep G2 Cells ; Humans ; Liver Neoplasms ; MicroRNAs ; metabolism

Objective To assess mucin gene expression in Barrett's esophagus.Methods Mucin core protein-MUC1,MUC2,MUC3,MUCSAC and MUC6 were detected by immunohistochemistry.The re- lationship between mucin expression and magnification-endoscopic characteristics,pathohistologic epithelial types of Barrett's esophagus was analyzed.Results Mild expression of MUC1 was predominantly found in the superficial epithelium of both gastric and specialised intestinal metaplasia.In a small number of specimens, mild expression of MUC1 was also noted in glands.Strong MUC2 expression was noted only in the goblet cells in Barrett's oesophagus.MUC3 was expressed in the superficial columnar cells of specialized intestinal metaplasia with or without globlet cells but not in gastric metaplasia of the oesophagus.In some specimens MUC3 was expressed in the vacuolus of the globlet cells and the lumen of gland.Strong staining of MUCSAC was noted in the columnar epithelium of both gastric metaplasia and specialized intestinal metaplasia in Barrett's oesophagus,as well as expressed in the cytoplasm and vacuolus of the globlet cells in some speci- mens.Expression of MUC6 protein was detected at the basement of the crypts in gastric metaplasia and spe- cialised Barrett's glands.Expression of MUC2 and MUC3 protein was found much higher in villous or irregu- lar pit pattern than that in dot or rod pit pattern(P

OBJECTIVETo study the expression of decoy receptor 3 (DcR3) and its relationship with apoptosis and prognosis in hepatocellular carcinoma (HCC).

METHODSThe expression of DcR3 protein in 43 cases of HCC and 16 cases of non-cancerous liver (including cirrhotic liver tissue and normal liver tissue adjacent to cavernous hemangioma) was studied by immunohistochemistry (using EnVision method). The status of apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. Statistic analysis was carried out to assess the correlation between DcR3 expression, apoptotic index (AI) and clinicopathologic parameters.

RESULTSDcR3 protein was expressed in the cytoplasm of HCC cells. The positivity rate of DcR3 in HCC was 74.42% (32/43), which was significantly higher than that in the non-cancerous group (43.75%, P < 0.05). The positivity rate of DcR3 in HCC with metastasis detected within 20 months of diagnosis was 100% (22/22). This was significantly higher than that in HCC without metastasis (52.94%, P < 0.01). The DcR3 expression in HCC also correlated with serum alpha-fetoprotein level (r = 0.444, P < 0.01) and presence of tumor embolus in portal vein (r = 0.414, P < 0.01). However it had no relationship with the patient's age, sex, cirrhotic status, liver capsule invasion, number of tumor nodules and histologic differentiation (P > 0.05). The AI in HCC (0.78 +/- 0.64)% was significantly lower than that in the non-cancerous group [(3.32 +/- 1.81)%, P < 0.01]. The AI in clinical TNM stage I and II tumors (1.03 +/- 0.69)% was significantly higher than that in stage III and IV tumors [(0.52 +/- 0.48)%, P < 0.01]. The AI in HCC without metastasis (1.10 +/- 0.72)% was significantly higher than that in HCC without metastasis [(0.44 +/- 0.27)%, P < 0.05]. The AI correlated with serum alpha-fetoprotein level (r = -0.468, P < 0.01), presence of tumor embolus in portal vein (r = -0.434, P < 0.01) and liver capsule invasion (r = -0.331, P < 0.05). On the other hand, it had no relationship with patient's age, sex, cirrhotic status, number of tumor nodules and histologic differentiation (P > 0.05). The AI in DcR3-positive group (including both HCC and non-cancerous tissues) was significantly lower than that in DcR3-negative group (P < 0.01).

CONCLUSIONSThe expression of DcR3 in HCC correlates with apoptosis of tumor cells and may play a crucial role in tumor pathogenesis and progression. DcR3 protein expression and AI may also serve as important biologic indicators in predicting prognosis of HCC.

Adult ; Aged ; Apoptosis ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Receptors, Tumor Necrosis Factor, Member 6b ; metabolism ; physiology ; Retrospective Studies ; Young Adult

OBJECTIVETo study the effects of human telomerase reverse transcriptase (hTERT) RNA interference (RNAi) on biological characteristics of hepatocellular carcinoma cell lines HepG2 and SMMC-7721 and on apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

METHODSSmall hairpin hTERT (shTERT) sequence was identified by PCR method; hTERT expressions, morphological features, cell proliferation and replicative senescence were respectively determined using RT-PCR, hematoxylin-eosin (HE) staining, growth curve and beta-galactosidase (b-Gal) staining; cell cycle and apoptosis were identified using flow cytometry after propidium iodide (PI) staining and annexin V/PI double staining.

RESULTSshRNA were found in 6/8 HepG2 and 6/6 SMMC-7721 cell clones transformed by the recombined plasmid pSilencer 3.1-H1 neo-shTERT. The interference rates of hTERT on HepG2 and SMMC-7721 were 100% and 43.3% respectively. Cells in G2-M phases increased from 7.1% to 10.6% and from 6.9% to 7.9% respectively; and the percentage of replicative senenscence cells increased from 0 to 20.4% and from 3.6% to 10.0% respectively. The nucleus/cytoplasm ratios of the cells were obviously decreased after hTERT RNAi treatment. Moreover, apoptosis of hepatocellular carcinoma cells and apoptosis induced by TRAIL were strikingly increased by hTERT RNAi (P < 0.05). For example, apoptosis rates were increased from 3.5% to 5.2% in HepG2 cells and from 4.8% to 7.9% in SMMC-7721 cells after hTERT RNAi treatment. Apoptosis rates were increased from 5.3% to 10.4% in HepG 2 cells and from 13.9% to 77.2% in SMMC-7721 cells after being treated by 100 ng/ml TRAIL for 24 h. However, there were no remarkable changes between control cells and untransformed cells.

CONCLUSIONhTERT RNAi not only has a significant effect on biological characteristics of hepatocellular carcinoma cells, but also obviously can increase cell apoptosis induced by TRAIL.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Humans ; Liver Neoplasms ; pathology ; RNA Interference ; RNA, Small Interfering ; genetics ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology ; Telomerase ; genetics ; Tumor Cells, Cultured

OBJECTIVETo evaluate the relationship between mitochondrial DNA instability (mtMSI) and interleukin-8 (IL-8) activity in gastric mucosa of various lesions.

METHODSIL-8 level in gastric mucosa was assayed using ELISA method. The mtMSI was detected by PCR-SSCP techniques.

RESULTSmtMSI was observed in 11 out of 30 (36.7%) gastric cancers, 2 of 15 (13.3%) intestinal metaplasia, 2 of 10 dysplasia and 1 of 10 chronic atrophic gastritis. IL-8 level in mtMSI+ group [(76.8 +/- 3.8) pg/mg] was significantly higher than that in mtMSI- group [(48.3 +/- 3.6) pg/mg, P < 0.05].

CONCLUSIONmtMSI closely correlates with IL-8 level in gastric mucosa and is involved in gastric carcinogenesis.

DNA, Mitochondrial ; genetics ; Enzyme-Linked Immunosorbent Assay ; Gastric Mucosa ; metabolism ; pathology ; Gastritis, Atrophic ; genetics ; metabolism ; Genomic Instability ; Humans ; Interleukin-8 ; metabolism ; Metaplasia ; genetics ; metabolism ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Precancerous Conditions ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism

AIMTo explore whether the anti-tumor action of 17beta-estradiol is enhanced by re-expression of the homeodomain transcription factor Nkx3.1 in PC3 human prostate cancer cells.

METHODSPC3 cells were stably transfected with pcDNA3.1-Nkx3.1-His vector, which carries a full-length cDNA of human Nkx3.1. The PC3 cells stably transfected with vector pcDNA3.1 were set as a control. The expression of Nkx3.1 protein in the cells was confirmed by Western blot analysis. The effect of Nkx3.1 on cell proliferation of PC3 cells was examined with MTT assay. The antiproliferative and apoptotic effects of 17beta-estradiol alone or in combination with Nkx3.1 were estimated on PC3 cells by using MTT growth tests and flow cytometric analyses. The expression of apoptosis-related proteins was analyzed using Western blotting.

RESULTSThe plasmid carrying Nkx3.1 gene induced high expression of Nkx3.1 protein in PC3 cells. The re-expression of exogenous Nkx3.1 did not cause a significant reduction in cellular proliferation, whereas the expression of Nkx3.1 enhanced the 17beta-estradiol anti-proliferative effect in PC3 cells. Nkx3.1 expression promoted 17beta-estradiol-induced apoptosis of PC3 cells, as shown by analysis of Bcl-2, Bax, Caspase-3 and poly (ADP-ribose) polymerase expression.

CONCLUSIONThe present study demonstrates that re-expression of Nkx3.1 enhances 17beta-estradiol anti-tumor action in PC3 human prostate cancer cells. The in vitro study suggests that re-expression of Nkx3.1 is worthy of further consideration as an adjuvant treatment of androgen independent prostate cancer with estrogen anti-tumor therapies.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Androgen-Insensitivity Syndrome ; drug therapy ; genetics ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Estradiol ; pharmacology ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; genetics ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; genetics ; pathology ; Transcription Factors ; genetics ; metabolism ; Transfection