Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition

Zhong, Yi-Cun; Zhang, Ting; Di, Wen; Li, Weiping

doi:10.3802/jgo.2013.24.3.265

Cited by 32 publications

(23 citation statements)

References 39 publications

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“…Characteristics of the mesenchymal phenotype include the expression of vimentin, α-SMA, fibronectin and N-cadherin. These EMT-related events were observed not only in CRC, but also in various types of human cancers [11,15], including esophageal cell carcinoma, and gastric, ovary and breast cancer [16,17,18,19]. …”

Section: Discussionmentioning

confidence: 99%

Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer

Yun

Kim²,

Hong³

et al. 2014

Oncology

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Purpose: The epithelial-mesenchymal transition (EMT) is known to be associated with tumor progression, invasion and metastasis in colorectal cancer (CRC). Materials and Methods: Tissue samples obtained from 409 patients with stage III CRC treated from 2006 to 2007 were examined by immunohistochemistry to reveal the expression levels of E-cadherin, fibronectin, vimentin and α-smooth muscle actin (SMA). Results: Among the 409 patients, 402 cases (98.3%) showed positive E-cadherin expression. Positive E-cadherin expression was associated with well or moderately differentiated cell types and a stable microsatellite status. In multivariate analysis, a preoperative carcinoembryonic antigen level >5 ng/ml (p = 0.021), advanced N stage (p = 0.017), positive vascular invasion (p = 0.048), positive perineural invasion (p = 0.002) and negative E-cadherin expression (p = 0.002, relative risk = 5.098, 95% CI = 1.801-14.430) were poor prognostic factors affecting disease-free survival. The declining E-cadherin expression was associated with a poor outcome in terms of overall survival in univariate (p = 0.016) but not in multivariate analyses (p = 0.303, relative risk = 1.984, 95% CI = 0.539-7.296). Fibronectin, vimentin and α-SMA were of no prognostic value in this study. Conclusion: The expression pattern of EMT markers in stage III CRC suggests that declining E-cadherin expression is a possible immunohistochemical predictor of patient prognosis.

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Section: Discussionmentioning

confidence: 99%

Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer

Yun

Kim²,

Hong³

et al. 2014

Oncology

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“…It has been shown that EMT in ovarian cancer is controlled by different cytokines and growth factors, such as mucin (MUC4) and CA125 (Ponnusamy et al 2010;Theriault et al 2011), bone morphogenetic protein 4 (BMP4), endothelin-1 (ET-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and transforming growth factor-β (TGF-β) (Vergara et al 2010). More recently in an in vitro study, thrombin induced the expression of EMT proteins in EOC cells (Skov-3), which could be reversed with the use of inhibitors against thrombin (hirudin); this indicates that the use of anticoagulants might serve in the control of EOC progression (Zhong et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Adham

Al-Harrasi

Haddabi

et al. 2014

J Histochem Cytochem.

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The mechanism by which neuropilin-1 (NRP-1) induces malignancy in Epithelial Ovarian Cancer (EOC) is still unknown. This study is the first to demonstrate the relationship between NRP-1 expression and EMT markers vimentin, N-cadherin, E-cadherin and Slug. We used tissue microarrays containing the three main subtypes of EOC tumors: serous, mucinous cystadenocarcinoma and endometrioid adenocarcinoma and representative cases retrieved from our pathology archives. Immunohistochemistry was performed to detect the expression levels and location of NRP-1 and the aforementioned EMT proteins. NRP-1 was mainly expressed on cancer cells but not in normal ovarian surface epithelium (OSE). The Immunoreactive Scoring (IRS) values revealed that the expression of NRP-1, Slug and E-cadherin in the malignant subtypes of ovarian tissues was significantly higher (5.18 ± 0.64, 4.84 ± 0.7, 4.98 ± 0.68, respectively) than their expression in the normal and benign tissues (1.04 ± 0.29, 0.84 ± 0.68, 1.71 ± 0.66, respectively), with no significant differences among the studied subtypes. Vimentin was expressed in the cancer cell component of 43% of tumors and it was exclusively localized in the stroma of all mucinous tumors. The Spearman’s rho value indicated that NRP-1 is positively related to the EMT markers E-cadherin and Slug. This notion might indicate that NRP-1 is a partner in the EMT process in EOC tumors.

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“…The manufacturer states that long-term animal studies to evaluate the carcinogenic potential of Floseal ® matrix have not been performed (13). In ovarian cancers -whose first-line treatment requires extensive surgery with high bleeding potential -thrombin has been shown to stimulate the growth of cancer cells in vitro (37). In our opinion, as long as the application of HM is restricted to the bleeding surface and all of the thrombin from HM is incorporated into the clot, the pro-cancerogenic action of HM will remain rather speculative.…”

Section: Discussionmentioning

confidence: 98%

Improvement of Perioperative Outcomes in Major Gynecological and Gynecologic–Oncological Surgery with Hemostatic Gelatin–Thrombin Matrix

Watrowski

Jäger

Förster

2017

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Abstract. Aim: To assess the impact of the use of intraoperative hemostatic gelatin-thrombin matrix (HM)( (168 vs. 199 min, p=0.02) and hospitalization (9 vs. 14 days, p<0.001) times. The mean postoperative Hb drop (3.33 vs. 4.51 g/dl, p<0.001), and the mean postoperative increase in CRP (94.9 vs. 149.1 mg/l, p<0.001) were significantly less pronounced within the HM group. Despite more prevalent coagulopathy (48 vs. 31%, p=0.02), e.g. due to anticoagulant use (15.7 vs. 3%, p<0.001), patients treated using HM needed less frequent transfusions of packed red blood cells [odds ratio (OR)= 0.13, 95% confidence interval (CI) =0.07-0.24) and fresh frozen plasma (OR=0.51,. In comparison to controls, the need for surgical revisions (OR 0.1,) and intensive-care unit admissions (OR 0.15, Intraoperative bleeding is a complication of gynecological surgery (1, 2). Increased perioperative blood loss (PBL) disrupts the operation, impairs organ exposure, contributes to prolonged surgical and hospitalization times, increases the need for transfusion, and negatively impacts therapy costs (1, 3). In non-oncological gynecological surgery, acute postoperative hemorrhage is the most frequent cause of returning to the operating theater (2). A PBL of more than 1 l complicates 15-40% of radical oncological operations, resulting in transfusion rates of 30-60% (4-6). In general surgery, intraoperative transfusion of only one to two units of packed red blood cells (PRBC) has been shown to significantly elevate the risk for surgical-site infection, pneumonia, sepsis and 30-day mortality (7). In gynecological patients, blood transfusions are clearly associated with increased surgical wound infections and composite morbidity and mortality (8). Additionally, a low perioperative hemoglobin (Hb) level and blood transfusions themselves may worsen the prognosis of pelvic cancers (9, 10). Typical intraoperative hemostatic maneuvers comprise of compression, sutures, clips and electrocoagulation. However, in some cases, conventional hemostasis can be insufficient (e.g. due to intraoperative coagulopathy), unsafe (e.g. due to proximity of structures sensitive to thermal damage) or impractical (e.g. diffuse bleeding area) (1, 11). Additionally, a subset of patients undergoing surgery have impaired hemostasis, e.g. due to use of oral anticoagulant. In the past two decades, an increasing number of topical hemostats, sealants and adhesives have been available to surgeons (1,12 in vivo 31: 251-258 (2017) Patients and MethodsPatients and definitions. This was a retrospective single-center study, conducted at the St. Josefskrankenhaus, Academic Teaching Hospital of the University of Freiburg, Freiburg, Germany. The study period was January 1, 2008 to October 30, 2013. The study was approved by the Institutional Review Board of the University of Freiburg (Reference No. 194/12), and was registered with the German Clinical Trials Register (DRKS), a primary register of the WHO International Clinical Trials Registry Platform, trial number DRKS00004...

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Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition

Cited by 32 publications

References 39 publications

Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer

Loss of E-Cadherin Expression Is Associated with a Poor Prognosis in Stage III Colorectal Cancer

Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Improvement of Perioperative Outcomes in Major Gynecological and Gynecologic–Oncological Surgery with Hemostatic Gelatin–Thrombin Matrix

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