Objectives
Transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in the progression of cancer including epithelial-to-mesenchymal transition (EMT). The aim of this study is to characterize the regulatory mechanisms of FOXM1 in EMT via pancreatic cancer metabolism.
Methods
We investigated the regulation of EMT via mitochondrial respiration by FOXM1 using pancreatic cancer cell lines HPAC and PANC-1 and normal human pancreatic duct epithelial cells.
Results
Forkhead box protein M1 and Snail were strongly expressed in HPAC and PANC-1. Epithelial-to-mesenchymal transition–modulated claudin-1 level was lower in PANC-1 than in HPAC. In both cell lines in low-glucose medium, FOXM1 and Snail were decreased and claudin-1 was increased. Knockdown of FOXM1 increased claudin-1 and decreased Snail in both cell lines. Low-glucose medium and downregulation of FOXM1 inhibited the cell migration in both cell lines. In both cell lines, mitochondrial respiration was at higher levels in low-glucose medium than in high-glucose medium. Downregulation of FOXM1 induced mitochondrial respiration in high-glucose medium. In normal human pancreatic duct epithelial cells, FOXM1 and Snail were low and claudin-1 was highly expressed, whereas overexpression of FOXM1 decreased claudin-1.
Conclusions
Glucose-dependent FOXM1 promoted EMT via Snail and pancreatic cancer metabolism.
BACKGROUND
During pancreaticoduodenectomy in patients with celiac axis (CA) stenosis due to compression by the median arcuate ligament (MAL), the MAL has to be divided to maintain hepatic blood flow in many cases. However, MAL division often fails, and success can only be determined intraoperatively. To overcome this problem, we performed endovascular CA stenting preoperatively, and thereafter safely performed pancreaticoduodenectomy. We present this case as a new preoperative treatment strategy that was successful.
CASE SUMMARY
A 77-year-old man with a diagnosis of pancreatic head cancer presented to our department for surgery. Preoperative assessment revealed CA stenosis caused by MAL. We performed endovascular stenting in the CA preoperatively because we knew that going into the operation without a strategy could lead to ischemic complications. Double-antiplatelet therapy (DAPT) – which is needed when a stent is inserted – was then administered in parallel with neoadjuvant chemotherapy (NAC). This allowed us to administer DAPT for a sufficient period before the main pancreaticoduodenectomy procedure while obtaining therapeutic effects from NAC. Subtotal stomach-preserving pancreaticoduodenectomy was then performed. The operation did not require any unusual techniques and was performed safely. Postoperatively, the patient progressed well, without any ischemic complications. Histopathologically, curative resection was confirmed, and the patient had no recurrence or complications due to ischemia up to six months postoperatively.
CONCLUSION
Preoperative endovascular stenting, with NAC and DAPT, is effective and safe prior to pancreaticoduodenectomy in potentially resectable pancreatic cancer.
It has been reported that use of the free dermal fat graft (FDFG) technique produces a good cosmetic outcome for breast cancer. An FDFG is harvested from the lower abdomen as a columnar-shaped specimen and implanted into the defect of the breast after a partial mastectomy as a volume replacement technique. In this report, two patients who underwent breast-conserving surgery with immediate reconstruction using an autologous FDFG are described in order to show the difference in status between one case with and one without blood flow in the graft. To assess the benefit of this technique using FDFGs, their cosmetic satisfaction was evaluated using a questionnaire, graft shrinkage was measured by CT, and blood flow was assessed using contrast-enhanced ultrasound (CEUS). Both patients scored 10 of 12 points on the questionnaire. After 2 years, shrinkage of the grafts was 21.6 and 25.2 %, respectively. Although one patient had no blood flow in the center of the graft, the other had blood flow from the pectoralis major muscle to the center of the graft. While satisfaction and graft shrinkage were similar in the two patients, one case showed blood flow and had a somewhat softer graft than the other. The graft status was maintained with a good cosmetic outcome for 3 years after breast-conserving surgery with immediate reconstruction using an autologous FDFG, despite mild shrinkage and hardness of the graft. It is notable that blood flow was observed into the graft on CEUS, and more distinct perfusion was seen in the softer graft case after more than 3 years.
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