ABSTRACT
BACKGROUND: Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis. METHODS: The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated. RESULTS: Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (P = 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (P = 0.001) and overall survival, OS (P = 0.011). CONCLUSIONS: Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Nuclear Proteins/metabolism , Twist-Related Protein 1/metabolism , Vascular Endothelial Growth Factor C/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/surgery , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Prognosis , Survival RateABSTRACT
PURPOSE: ZFP36 ring finger protein (ZFP36) and the suppressor of cytokine signaling 3 (SOCS3) have been reported to, respectively, regulate NF-κB and STAT3 signaling pathways. To better understand the correlation of NF-κB and STAT3 negative regulates pathway, we have investigated the involvement of ZFP36 and SOCS3 expressions in human prostate cancer (PCa). METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the ZFP36 protein expression was quantitated as immunoreactive scores in patients with PCa. Associations between ZFP36/SOCS3 expression and various clinicopathological features and prognosis of PCa patients were statistically analyzed based on the Taylor database. Then, the functions of ZFP36 and SOCS3 in cancerous inflammation were determined using qPCR and immunohistochemistry in vitro and in vivo. RESULTS: ZFP36 protein expression in PCa tissues was significantly lower than those in non-cancerous prostate tissues (P < 0.05). In mRNA level, ZFP36 and SOCS3 had a close correlation with each other (P < 0.01, Pearson r = 0.848), and its upregulation was both significantly associated with low Gleason score (P < 0.001 and P < 0.001, respectively), negative metastasis (P < 0.001 and P < 0.001, respectively), favorable overall survival (P < 0.001 and P < 0.05, respectively), and negative biochemical recurrence (P < 0.001 and P < 0.001, respectively). Functionally, LPS treatment could lead to the overexpression of ZFP36 and SOCS3 in vitro and vivo. CONCLUSIONS: Our data offer the convincing evidence for the first time that the aberrant expressions of ZFP36 and SOCS3 may be involved into the progression and patients' prognosis of PCa, implying their potentials as candidate markers of this cancer.
Subject(s)
Biomarkers, Tumor/analysis , Prostatic Neoplasms/pathology , Suppressor of Cytokine Signaling 3 Protein/biosynthesis , Tristetraprolin/biosynthesis , Aged , Aged, 80 and over , Animals , Disease-Free Survival , Humans , Immunohistochemistry , Inflammation/metabolism , Inflammation/pathology , Kaplan-Meier Estimate , Male , Middle Aged , Polymerase Chain Reaction , Prognosis , Proportional Hazards Models , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/mortality , Rats , Rats, Sprague-Dawley , Suppressor of Cytokine Signaling 3 Protein/analysis , Tissue Array Analysis , Tristetraprolin/analysisABSTRACT
To determine the relationship between gastroesophageal reflux (GER) and pulmonary diseases, we studied 29 chronic bronchitis, 32 asthmatic patients, and 9 control subjects. GER was diagnosed by esophageal endoscopy and gastroesophageal scintiscanning. Evidence of GER in the chronic bronchitic patients was 51.74%; in the asthmatics it was 37.5%; and no GER was confirmed in the control subjects. Gastroesophageal scintiscan had 100% sensitivity, but only 68.42% specificity. The mechanism whereby reflux triggers pulmonary problems was investigated by using the scintiscan for pulmonary aspiration, but no pulmonary aspiration was detected in all subjects. Pulmonary function tests did not show any differences between patients with or without reflux (P > 0.05). Thus, our results show that GER is common in chronic bronchitics and asthmatics, which indicates that there is some relationship between GER and chronic bronchitis as well as asthma.
