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AIMS: Investigate the effect and mechanism of COX-2 on viability, intestinal metaplasia, and atypia in human esophageal squamous and Barrett esophageal cell lines. METHODS: Human esophageal squamous and Barrett esophageal cell lines were transfected with a COX-2 expression vector and a COX-2 siRNA, and then were treated with acid, bile salts, and a mixture of both. Cell viability, the expression of COX-2, NF-κB(p65), CDX-2, MUC2, c-myb, and BMP-4, and the morphology and microstructure of cells were then observed. RESULTS: The viability of COX-2 overexpressed cells was significantly higher than that of control cells, while the viability of COX-2 siRNA-treated cells was significantly lower than that of control cells. Intestinal metaplasia and atypia were observed in cells overexpressing COX-2. Acid, bile salts, and their mixture inhibited the viability of these two cell lines, but the inhibitory effect of the mixture was stronger than a single treatment in either. SiRNA mediated knockdown of COX-2 strengthened the antiproliferative effects of the mixture on HET-1A and BAR-T cells. The expression of p-p65, CDX-2, and BMP-4 was positively correlated with COX-2 expression, while the expression levels of p65, MUC2, and c-myb remained unchanged. CONCLUSION: COX-2 may influence the viability, atypia, and intestinal metaplasia of human esophageal cells and Barrett esophageal cells. Activation of the p-p65, CDX-2, and BMP-4 signaling pathways by COX-2 may be part of this mechanism.
Subject(s)
Barrett Esophagus , Bile Acids and Salts , Cyclooxygenase 2 , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Barrett Esophagus/genetics , Barrett Esophagus/metabolism , Bile Acids and Salts/pharmacology , CDX2 Transcription Factor/genetics , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Metaplasia , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolismABSTRACT
BACKGROUND: Serum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC. METHODS: Patients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis. RESULTS: We included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040). CONCLUSIONS: Early postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.
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Objective To investigate the expressions of large tumor suppressor kinase 1 (LATS1) and large tumor suppressor kinase 2 (LATS2) proteins in gastric cancer tissues, and to explore the correlation between expressions of LATS1 and LATS2 proteins and the occurrence and development of gastric cancer. Methods A total of 93 gastric cancer paraffin tissues and the corresponding adjacent gastric normal mucosa in the Department of Pathology in Baotou Cancer Hospital from September 2008 to June 2010 were collected. The immunohistochemistry was used to detect the expressions of LATS1 and LATS2 proteins in gastric cancer and adjacent normal tissues. The differences of the expressions of LATS1 and LATS2 proteins in gastric cancer and adjacent normal tissues were compared by usingχ2 test. The relationship between the expressions of LATS1 and LATS2 proteins and the clinicopathological features was also analyzed. Results In gastric cancer tissues, LATS1 was negatively expressed in 54 cases (58.1％), weakly positive expressed in 15 cases (16.1％), moderately positive expressed in 16 cases (17.2％), and strongly positive expressed in 8 cases (8.6％);in adjacent normal tissues, LATS1 was negatively expressed in 17 cases (18.3％), weakly positive expressed in 16 cases (17.2％), moderately positive expressed in 31 cases (33.3％), and strongly positive expressed in 29 cases (31.2％). The positive expression rate of LATS1 in gastric cancer tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (χ2=37.460, P<0.01). In gastric cancer tissues, LATS2 was negatively expressed in 28 cases (30.1％), weakly positive expressed in 17 cases (18.3％), moderately positive expressed in 33 cases (35.5％), strongly positive expressed in 15 cases (16.1％);in adjacent normal tissues, LATS2 was negatively expressed in 5 cases (5.4％), weakly positive expressed in 7 cases (7.5％), moderately positive expressed in 32 cases (34.4％), strongly positive expressed in 49 cases (52.7％). The positive expression rate of LATS2 in gastric cancer tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (χ2=38.275, P<0.01). The expressions of LATS1 and LATS2 were not related to patients'age, gender, lymph node metastasis, degree of differentiation and tumor diameter (all P>0.05). Conclusion LATS1 and LATS2 proteins may be involved in the occurrence of gastric cancer and have the inhibiting effect on the occurrence and development of gastric cancer.
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Objective To investigate the expressions of B7-H1 and Bcl-2 proteins in epithelial ovarian cancer,and to explore the association of the expressions of B7-H1 and Bcl-2 with clinicopathological features.Methods The expressions of B7-H1 and Bcl-2 proteins were detected by immunohistochemistry in 80 cases of epithelial ovarian cancer tissues and 20 normal ovary tissues.The association of the expressions of B7-H1 and Bcl-2 with the clinicopathological features was analyzed.Results The positive expression rates of B7-H1 and Bcl-2 in epithelial ovarian cancer tissues were 77.5％ (62/80) and 58.8％ (47/80),both higher than 15.0％ (3/20) and 10.0％ (2/20) in normal ovary tissues with significant difference (x2 =27.473,P ＜ 0.05 ; x2 =15.216,P ＜ 0.05).Both of Bcl-2 and B7-H1 expressions in epithelial ovarian cancer tissues were negatively correlated with the differentiation degree of epithelial ovarian cancer (x2 =9.367,P ＜ 0.01 ; x2 =11.702,P ＜ 0.01).The Bcl-2 expression in epithelial ovarian cancer tissues was positively correlated with the FIGO stage (x2 =7.766,P ＜ 0.01).The expression of B7-H1 was positively correlated with the expression of Bcl-2 in epithelial ovarian cancer (r =0.400,P ＜0.01).Conclusion The expressions of B7-H1 and Bcl-2 are up-regulated in epithelial ovarian cancer and they correlate to each other positively.The expressions of B7-H1 and Bcl-2 are correlated with the invasion and metastasis of epithelial ovarian cancer.The detection of B7-H1 combined with Bcl-2 may have an important clinical significance in the diagnosis and treatment for patients with epithelial ovarian cancer.
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Objective To evaluate the clinical efficacy of modified Angelica Fritilaria Sophorae Pill assisting transcatheter arterial chemoembolization (TACE) to treat primary liver cancer. Methods Totally 84 patients with primary liver cancer were randomized into combination treatment group (42 cases) and conventional control group (42 cases). The conventional control group received TACE treatment, the combination treatment group received modified Angelica Fritilaria Sophorae Decoction and TACE. The tumor volume, TCM syndrome score, life quality, immune function and toxicity reaction of both groups were observed. Results Clinical observation was completed with 37 patients in each group. After three courses of treatment, the objective tumor response rate was 91.9% in combination treatment group and 86.4% in conventional control group (P<0.05). The clinical symptoms (fever, abdominal pain, vomiting, fatigue) in both groups were improved (P<0.05), with significant difference between the two groups (P<0.05). After treatment, KPS scores increased (P<0.05) in combination treatment group, and the scores of combination treatment group were significantly higher than those of the conventional control group (P<0.05). After treatment, Th1 function level increased (P<0.05) in combination treatment group, and that was better than the conventional control group (P<0.05). The incidence of liver toxicity and gastrointestinal reaction in the combination treatment group was significantly lower than that in the conventional control group (P<0.05). Conclusion Modified Angelica Fritilaria Sophorae Pill can enhance the efficacy of TACE treatment to treat primary liver cancer, reduce adverse reactions, and improve life quality of patients with primary liver cancer.
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MicroRNAs are endogenously expressed non-coding RNAs, which are composed of approximately 18 nucleotides to 25 nucleotides. Mature microRNAs regulate gene expression by base pairing with the 3'-untranslated region of target mRNAs. These mature microRNAs can degrade target mRNAs or inhibit translation. This process is a type of post-transcriptional regulation of gene ex-pression. Studies have shown that microRNAs are important in physiological and pathological processes, such as cell proliferation, cell differentiation, and cell death. This article provides an overview of the function of microRNAs in the regulation of macrophages.
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PURPOSE: Fanconi anemia complementation group F (FANCF) is a key factor to maintaining the function of Fanconi anaemia/BRCA (FA/BRCA) pathway, a DNA-damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. In the present study, we evaluated the chemosensitization effect of FANCF in breast cancer cells. METHODS: We performed specific knockdown of the endogenous FANCF in breast cancer cells by transfecting the cells with an FANCF short hairpin RNA (shRNA) vector. Cell viability was measured with a Cell Counting Kit-8, and DNA damage was assessed with the alkaline comet assay. The apoptosis, cell cycle, and drug accumulation were measured by flow cytometric analysis. Protein expression levels were determined by Western blot analysis, using specific antibodies. RESULTS: The analyses of two breast cancer cell lines (MCF-7 and MDA-MB-435S) demonstrated that the FANCF shRNA could effectively block the FA/BRCA pathway through the inhibition of Fanconi anemia complementation group D2 ubiquitination. Moreover, FANCF silencing potentiated the sensitivity of cells to mitomycin C (MMC), where combined FANCF shRNA/MMC treatment inhibited cell proliferation, induced S-phase arrest, apoptosis, and DNA fragmentation, and reduced the mitochondrial membrane potential, compared with MMC treatment alone. CONCLUSION: Taken together, this study demonstrates that the inhibition of FANCF by its shRNA leads to a synergistic enhancement of MMC cytotoxicity in breast cancer cells. These results suggest that the inhibition of the FA/BRCA pathway is a useful adjunct to cytotoxic chemotherapy for the treatment of breast cancer.
Subject(s)
Apoptosis , Blotting, Western , Breast , Breast Neoplasms , Cell Count , Cell Cycle , Cell Line , Cell Line, Tumor , Cell Proliferation , Cell Survival , Comet Assay , Complement System Proteins , DNA Damage , DNA Fragmentation , Fanconi Anemia , Fanconi Anemia Complementation Group F Protein , Membrane Potential, Mitochondrial , Mitomycin , RNA, Small Interfering , Ubiquitin , UbiquitinationABSTRACT
The antigens(3C9Ag)which could be recognized by the anti-lung cancer monoclonal antibody 3Ca were assayed with BA-ELISA immunobinding inhibition test in 50 lung cancer patients,21 patients with non-cancerous pulmonary diseases and 40 normal subjects.Meanwhile radioimmunoassay was used to determine serum CEA.It was found that the sensitivity,specificity and accuracy for 3C9Ag to diagnose lung cancer were 76%,90.5% and 80.3% respectively.Much higher positive rates could be found in NSCLC patients and in those with stage Ⅱ or Ⅲ cancer.3CsAg was superior to CEA in its sensitivity and accurracy.Combined assay with 3C9Ag and CEA could increase the positive rate.
