Smad7 induces hepatic metastasis in colorectal cancer

Although Smad signalling is known to play a tumour suppressor role, it has been shown to play a prometastatic function also in breast cancer and melanoma metastasis to bone. In contrast, mutation or reduced level of Smad4 in colorectal cancer is directly correlated to poor survival and increased metastasis. However, the functional role of Smad signalling in metastasis of colorectal cancer has not been elucidated. We previously reported that overexpression of Smad7 in colon adenocarcinoma (FET) cells induces tumorigenicity by blocking TGF-β-induced growth inhibition and apoptosis. Here, we have observed that abrogation of Smad signalling by Smad7 induces liver metastasis in a splenic injection model. Polymerase chain reaction with genomic DNA from liver metastases indicates that cells expressing Smad7 migrated to the liver. Increased expression of TGF-β type II receptor in liver metastases is associated with phosphorylation and nuclear accumulation of Smad2. Immunohistochemical analyses have suggested poorly differentiated spindle cell morphology and higher cell proliferation in Smad7-induced liver metastases. Interestingly, we have observed increased expression and junctional staining of Claudin-1, Claudin-4 and E-cadherin in liver metastases. Therefore, this report demonstrates, for the first time, that blockade of TGF-β/Smad pathway in colon cancer cells induces metastasis, thus supporting an important role of Smad signalling in inhibiting colon cancer metastasis

Head-to-body delivery by "two-step" approach: effect on cord blood hematocrit

Abstract Background: There is no study to support a relationship between placental transfusion and active management techniques of the second stage of labor. Objective: To examine the association between head-to-body delivery by a "two-step" approach (which includes waiting for the next contraction to deliver the shoulders) and its effect on the amount of blood that remains in the infant's circulation at birth. Study design: Observational study on 500 consecutive, singleton, and at term deliveries from January to June 2012 in Policlinico Abano Terme, Abano Terme, Italy. Umbilical artery hematocrit (Htc) was evaluated in reference to contemporary tested pH values, involving neonates vaginally delivered by the "two-step" approach and by cesarean section, respectively. Results: Head-to-body delivery by the "two-step" approach significantly increased Htc values with respect to cesarean delivery (50.16% versus 47.24%, p\u2009<\u20090.001) and at the same time reduced pH (7.31\u2009\ub1\u20090.09 versus 7.33\u2009\ub1\u20090.06, p\u2009=\u20090.007) in umbilical artery. In addition, Htc levels for this group were significantly negatively correlated with umbilical artery pH (r\u2009=\u2009-0.137, p\u2009<\u20090.018). Conclusion: Head-to-body delivery by the "two-step" approach increases the red cell mass in term infants without any clinical risk of neonatal acidemia