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The X-linked transcription factor FOXP3 is expressed by epithelial cells of organs including the breast, where it is considered a tumour suppressor. The chemokine receptor CXCR4 also regulates the development of breast cancer by stimulating cell migration towards CXCL12-expressing sites of metastatic spread. During activation, human T cells show reciprocal regulation of FOXP3 and CXCR4. This study was designed to examine the role FOXP3 plays in metastatic breast cancer, with a particular focus on its potential to regulate CXCR4. Human breast cancer samples showed significantly decreased FOXP3 protein expression but an increased number of CXCR4 transcripts. In comparison with normal primary breast epithelial cells, FOXP3 was down-regulated at both transcript and protein levels in the breast cancer cell lines MCF-7 and MDA-MB-231. In the invasive MDA-MB-231 cells, the remaining FOXP3 was located predominately within the cytoplasm. Following stable FOXP3 overexpression in MDA-MB-231 cells, significant decreases were observed in the expression of ErbB2/HER2, SKP2, c-MYC, and CXCR4. In contrast, an increase in p21 expression led to inhibition of cell proliferation, with a greater proportion in the G1 phase of the cell cycle suggesting the induction of senescence. Specific knockdown of FOXP3 in normal human breast epithelial cells with siRNA significantly increased ErbB2/HER2, SKP2, c-MYC, and CXCR4, and decreased p21 expression. These cells also showed a significantly increased chemotactic response towards CXCL12, consistent with a role for FOXP3 in the regulation of cell migration. Results from this study are consistent with FOXP3 functioning as an important tumour suppressor in breast cancer. Indeed, the potential functions of FOXP3 in breast epithelium can now be extended to include regulation of CXCR4 expression and response to the pro-metastatic chemokine CXCL12., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Context: Pancreaticobronchial fistula is a rare complication of severe pancreatitis. Various diagnostic methods have been described previously., Case Report: The presentation, diagnostic methods, management and 5-year follow-up of a 40-year-old woman with severe gallstone induced pancreatitis complicated by a pancreaticobronchial fistula were reviewed. Diagnosis was made on the endotracheal intubation when amylase rich-fluid was drained via the tube and confirmed by CT scanning. Successful management was achieved by an open pancreatic necrosectomy, during which air bubbles were seen emerging from the pancreatic collection which supported the diagnosis of the fistula. Five-year follow-up did not reveal any complications., Conclusions: Pancreaticobronchial fistulas have the potential to cause severe respiratory complications and mortality. Awareness of this condition is important in the treatment of complicated cases of pancreatitis.