Objective To investigate the expression of a novel oncogene Stat3 in colorectal cancer. Methods Western blot analysis was performed on cancerous and normal colonic tissue of 45 patients with colorectal carcinoma. ResultsStat3 protein level increased in colorectal cancer compared with adjacent normal mucosa ( P

Adolescent ; Adult ; Aged ; Child ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage ; complications ; surgery ; Humans ; Hypertension, Portal ; mortality ; surgery ; Male ; Middle Aged ; Renal Veins ; surgery ; Splenic Vein ; surgery ; Time Factors

AIM: The purpose of the study was to examine colon cancer cell lines to determine whether Stat5b/Survivin plays an important role in the process of apoptosis in colon cancer cells. METHODS: Protein lysates were extracted from colon cancer cells. Human colon cancer cell line HT29 was transfected with Stat5b antisense oligonucleotide mediated by liposome. MTT assay was used to measure the proliferation. Flow cytometry was applied to analyze the cell cycle and apoptosis. EMSA was used to detect the activity of Stat5. Western blotting was applied to measure the expression of Stat5, p-Stat5, cyclin D1, Survivin, Bcl-2 and Bcl-xL. RESULTS: Targeting of Stat5 using antisense oligonucleotide against the translation site resulted in apoptosis and downregulaed the expressions of Stat5, p-Stat5, cyclin D1 and Survivin, but not Bcl-2 and Bcl-xL. CONCLUSION: Constitutive activation of Stat5 is associated with the carcinogenesis of colon cancer cells. Blocking of Stat5 signaling inhibits the expression of Survivin and induces apoptosis in colon cancer cells.

Objective To clarify the role of a cell cycle regulator, cyclin D1 and CDK6 in patients with gastric carcinoma. Method Tissue samples from 48 patients with gastric carcinoma were included in the current study. Expression levels of cyclin Dl and CDK6 in samples of normal mucosa and tumor tissue were analyzed by Western blot. Result Overexpression of cyclin Dl and CDK6 protein were demonstrated in 58% and 69% of gastric cancer tissues, respectively. Several clinicopathologic parameters, including depth of tumor invasion, pathologic lymph node status and tumor stage ( P

Objective To explore the effect of inhibition of miR-214 expression on the proliferation of hepatocellular carcinoma cells via regulation of E2F3 expression.Methods The expression of miR-214 in SMMC-7721, HepG2, SK-Hep-1 and Huh 7 cells was examined by RT-PCR.Hepatocellular carcinoma cells were transfected with miR-214 NC and miR-214 mimics with liposomes.The expression of miR-214 was detected by RT-PCR.The cell viability was detected by MTT assay.Cell apoptosis was detected by Hoechst staining.Cell cycle was detected by flow cytometry.Western blot, RT-PCR and dual luciferase reporter gene assay were used to detect whether E2F3 was a downstream target gene of miR-214.Results The expression of miR-214 in SMMC-7721, HepG2, SK-Hep-1 and Huh 7 cells was 0.83±0.08, 0.32±0.03, 0.33±0.03, and 0.08±0.01, respectively.The expression of miR-214 in the HepG2 cells was the lowest, so HepG2 cells were selected as the subsequent experimental cell line.Compared with the miR-214 NC group, the expression of miR-214 (0.65±0.06 vs.0.14±0.01) was up-regulated, the cell viability (0.35±0.03 vs.0.69±0.06) was decreased, cell apoptosis rate [(36.37±3.43)% vs.(3.74±0.34)%] was increased, the G1 phase of the cell cycle (57.79±5.78 vs.45.319±4.53) was prolonged, the expression of E2F3 protein (0.23±0.02 vs.0.98±0.09) and mRNA (0.24±0.02 vs.0.99±0.10) was significantly down-regulated in the miR-214 mimics group (P<0.01).Conclusion miR-214 mimics suppress the HepG2 cell proliferation via targeted down-regulation of E2F3 expression.

Objective To compare the efficacy and safety of standard or reduced doses of bortezomib combined with adriamycin and dexamethasone in patients with multiple myeloma (MM).Methods Fifty-two newly diagnosed,refractory and relapsed patients received bortezomib [1.3 mg/m2 (standard dose group,26 patients) or 1.0-1.1 mg/m2 (reduced dose group,26 patients) on day 1st,4th,8th and 11 th],and adriamycin (10 mg/m2) plus dexamethasone (40 mg/d) on day 1 st-4th,and were treated for 1-6 courses.Adverse events were graded and compared.Results After treatment,the overall response rate of standard dose group [80.8％(21/26)] and reduced dose group [88.5％(23/26)] had no significant difference (P =0.739).The rate of neutropenia and thrombocytopenia in two groups had no significant difference[23.1％(6/26) vs.15.4％(4/26),P=0.281 ; 11.5％(3/26) vs.7.7％(2/26),P=0.620].The rate of Ⅲ-Ⅳ grade peripheral nerve disease,herpes zoster,lack of power and abdominal distension in standard dose group were significantly higher than those in reduced dose group [15.4％(4/26) vs.3.8％(1/26),P =0.038;26.9％(7/26) vs.7.7％(2/26),P =0.029;38.5％(10/26) vs.15.4％(4/26),P=0.045; 19.2％(5/26)vs.3.8％ (1/26),P =0.028].Conclusion Reduced dose of bortezomib appears to result in similar overall response rate,but better tolerance and safety compared with standard dose.

Objective To explore the mechanism of HPV infection in carcinogenesis and progression of colon cancer. Methods Human colon cancer cells, HCT116 (with wild-type p53) and SW480 (with mutant-type p53), were transfected by HPV16 E6E7 oncogenes using a recombinant adeno-associated virus vector system. The transfection efficiency was determined by flow cytometry. The expression of HPV16 E6 genes was determined by Western blot. The cell proliferation and cell cycle was studied by MTT method and flow cytometry. Results Western blot confirmed the expression of E6 gene in colon cells that were infected by rAAV-E6E7. The population doubling time of HCT116 cell, which was more than 48 hours at control group, decreased to 33 hours. HPV16 E6E7 increased cell percentage of S phase and decreased cell percentage of G0/G1. The population doubling time of SW480 cell was 77.06% decreased and the OD540 was 47.18% increased with interference of HPV16 E6E7 gene. Conclusion HPV16 E6E7 oncogene precipitates the proliferation and positively controls cell cycle of HCT116 and SW480 human colon cancer cells. HPV infection may closely relate to the carcinogenesis and progression of colon cancer.

Objective To investigate the relationship between HPV infection and human colorectal carcinogenesis. Methods Colorectal carcinoma specimens from 72 Chinese patients were studied. DNA extracted from colorectal tissue was screened for HPV L1 by polymerase chain reaction (PCR), HPV subtype 6,11, 16, and 18 were detected by PCR using specific primers and in situ hybridization using specific probe. Results Twenty-four specimens out of 72 (33%) colorectal cancer were HPV L1 positive. The normal colorectal mucosa was HPV L1 negative. The location, infiltration and metastasis of colorectal carcinoma were all significantly related with HPV infection. The predominant HPV subtype was HPV 16,which was found in 58% of all HPV-positive colorectal carcinoma. Conclusion The presence of HPV DNA suggests that HPV may be involved in the carcinogenesis of colorectal carcinoma. HPV infection is closely related with the malignant potential of colorectal cancer.

OBJECTIVETo detect protein expression of ERK(1), ERK(2), JNK(1), p38 and MEK(1), MEK(2) in human hepatocellular carcinoma and adjacent non-neoplastic liver.

METHODSIn 16 surgically resected hepatocellular carcinoma and para-carcinoma tissues, Western blotting was used to detect expression of ERK(1), ERK(2), JNK(1), p38 and MEK(1), MEK(2).

RESULTSIn all cases, ERK(1), ERK(2), p38 expression in hepatocellular carcinoma was significantly higher than that in para-carcinoma: integral optic density (IOD) of ERK(1) was 300 +/- 98 in carcinoma and 98 +/- 48 in para-carcinoma tissues (t = 2.519, P < 0.01); IOD of ERK(2) was 587 +/- 83 in carcinoma and 232 +/- 96 in para-carcinoma tissues (t = 2.745, P < 0.01); IOD of p38 was 270 +/- 85 in carcinoma and 107 +/- 88 in para-carcinoma tissues (t = 2.491, P < 0.01). JNK(1) expression in hepatocellular carcinoma was significantly lower than that in para-carcinoma; IOD of JNK(1) was 111 +/- 93 in carcinoma and 292 +/- 109 in para-carcinoma tissues (t = 2.473, P < 0.01). Protein levels of MEK(1) and MEK(2) in carcinoma were significantly higher than in para-carcinoma. IOD of MEK(1) was 1 418 +/- 244 in carcinoma and 806 +/- 90 in para-carcinoma tissues (t = 2.546, P < 0.01). IOD of MEK(2) was 1 041 +/- 122 in carcinoma and 468 +/- 40 in para-carcinoma tissues (t = 2.861, P < 0.01).

CONCLUSIONSERK(1), ERK(2), MEK(1) and MEK(2) in the signal transduction pathway for cell proliferation are significantly overexpressed and the expression of JNK(1) is lower in hepatocellular carcinoma. Their unbalance is one of the important reasons for the over growth and infinite proliferation of the hepatocellular carcinoma cell. The p38 and JNK(1) may be activated by different pathway.

Adult ; Aged ; Carcinoma, Hepatocellular ; enzymology ; Enzyme Activation ; Female ; Humans ; JNK Mitogen-Activated Protein Kinases ; Liver Neoplasms ; enzymology ; MAP Kinase Kinase 1 ; Male ; Middle Aged ; Mitogen-Activated Protein Kinase Kinases ; analysis ; Mitogen-Activated Protein Kinases ; metabolism ; Protein-Serine-Threonine Kinases ; analysis

Objective To explore the effect of EBV infection on proliferation and invasiveness of gastric cancer cell. Method BGC823, an EBV-negative human gastric cancer cell line, was infected by EBV. The cell proliferation and ability of invasion were studied by MTT method and in vitro invasive assay, respectively. Cell cycle was investigated by flow cytometry. RT-PCR was used to detect the EBNAs, LMP1 and EBER1 in the infected cell. Result The A ratio of EBV-infected cells increased by 34. 34% and the population of invasive cells increased by 28.72%. The cell percentage of S phase, which was 36. 7% at control group cell, was increased to 41. 9% while the cell percentage of G0/G1 was decreased. EBNA1 and EBER1 were detected in EBV infected gastric cancer cells while EBNA2 and LMP1 were both negative. Conclusion Epstein-Barr virus infection promoted proliferation and upregulated invasion of human gastric cancer cell. EBV infection may play an important role in the carcinogenesis and progression of human gastric cancer.