miR-709 exerts an angiogenic effect through a FGF2 upregulation induced by a GSK3B downregulation.

The aim of this study was to identify angiogenic microRNAs (miRNAs) that could be used in the treatment of hindlimb ischemic tissues. miRNAs contained in extracellular vesicles (EVs) deriving from the plasma were analyzed in C57BL/6 mice, which have ischemia tolerance, and in BALB/c mice without ischemia tolerance as part of a hindlimb ischemia model; as a result 43 angiogenic miRNA candidates were identified. An aortic ring assay was employed by using femoral arteries isolated from BALC/c mice and EVs containing miRNA; as a result, the angiogenic miRNA candidates were limited to 14. The blood flow recovery was assessed after injecting EVs containing miRNA into BALB/c mice with hindlimb ischemia, and miR-709 was identified as a promising angiogenic miRNA. miR-709-encapsulating EVs were found to increase the expression levels of the fibroblast growth factor 2 (FGF2) mRNA in the thigh tissues of hindlimb ischemia model BALB/c mice. miR-709 was also found to bind to the 3'UTR of glycogen synthase kinase 3 beta (GSK3B) in three places. GSK3B-knockdown human artery-derived endothelial cells were found to express high levels of FGF2, and were characterized by increased cell proliferation. These findings indicate that miR-709 induces an upregulation of FGF2 through the downregulation of GSK3B.

Five-year follow-up of randomized clinical trial for pre-emptive inferior mesenteric artery embolization during endovascular aneurysm repair.

OBJECTIVE: Type II endoleak (T2EL) is the most common type of endoleak after endovascular aneurysm repair (EVAR) and a common indication for reintervention due to late sac enlargement. Although pre-emptive embolization of the inferior mesenteric artery (IMA) has been proposed to prevent this, no studies have prospectively demonstrated its efficacy. This study aimed to prove the validity of IMA embolization during EVAR in selective cases by analyzing the mid-term outcomes of a randomized clinical trial (RCT). METHODS: This single-center, parallel-group, non-blinded RCT included participants at high risk of T2EL, characterized by a patent IMA in conjunction with one or more following risk factors: a patent IMA ≥3 mm in diameter, lumbar arteries ≥2 mm in diameter, or an aortoiliac-type aneurysm. The participants were randomly assigned to two groups in a 1:1 ratio: one undergoing EVAR with IMA embolization and the other without. The primary endpoint was T2EL occurrence. The secondary endpoints included aneurysm sac changes and reintervention. In addition to RCT participants, outcomes of patients with low risk of T2EL were also analyzed. RESULTS: The embolization and non-embolization groups each contained 53 patients. Five-year follow-up after the last patient enrollment revealed that T2ELs occurred in 28.3% and 54.7% of patients in the IMA embolization and non-embolization groups, respectively (P = .006). Both freedom from T2EL-related sac enlargement ≥5 mm and cumulative incidence of sac shrinkage ≥5 mm were significantly higher in the IMA embolization group than in the non-embolization group (95.5% vs 73.6% at 5 years; P = .021; 54.2% vs 33.6% at 5 years; P = .039, respectively). The freedom from T2EL-related sac enlargement ≥10 mm, an alternative indicator for T2EL-related reintervention, showed similar results (100% vs 90.4% at 5 years; P = .019). Outcomes in the low-risk group were preferable than those in the non-embolization group and comparable to those in the IMA embolization group. CONCLUSIONS: A lower threshold for pre-emptive IMA embolization when implementing EVAR would be more appropriate if limited to patients at high risk of T2ELs.

Effectiveness of Stitch With Pledget to Prevent Prolonged Air Leak in Thoracoscopic Lung Resection.

INTRODUCTION: We previously demonstrated the usefulness of combining stitching with covering to seal alveolar air leaks in an animal model. This study aimed to clarify the effectiveness and feasibility of this sealing method in the clinical setting. METHODS: Data of 493 patients who underwent thoracoscopic anatomical resection between 2013 and 2020 for lung cancer were retrospectively reviewed. Prolonged air leak was defined as chest drain placement lasting 5 d or longer due to air leak. Until July 2017 (early study period), we covered air leaks using mesh. However, for sealing (late study period), we additionally stitched leaks with pledget in patients at high risk of prolonged air leak. The pneumostasis procedure, intraoperative confirmation test of pneumostasis, and chest tube management were uniform during both periods. RESULTS: The incidence of prolonged air leak was significantly lower in the late than in the early period (3.6% versus 12.5%), whereas pulmonary emphysema was more severe in the late period compared to the early period. Intraoperative failure of sealing air leaks was significantly reduced in the late period than in the early period. In both univariate and propensity score matching analysis, the study period was a significant predictor of prolonged air leak. CONCLUSIONS: The combination of stitching and covering with mesh may contribute to reducing prolonged air leak incidence in patients undergoing thoracoscopic anatomical lung resection for lung cancer.

Dependent Leg Edema in Older Patients with or without Skin Lesion.

Objective: This study aimed to clarify the features and causes of dependent edema (DE) in the legs of patients in geriatrics. Patients and Methods: We retrospectively reviewed 224 patients with DE, aged ≥65 years, who visited our clinic from April 2009-March 2022. DE was defined as bilateral leg edema in patients without known systemic edemagenic conditions, venous insufficiency confirmed by duplex venous scanning, or a cancer treatment history in the pelvic/inguinal lesions. Results: The median patient age was 77 years (range: 65-94 years), where 74% were female. Overall, 198 patients (88%) had gait disturbances caused mainly by musculoskeletal disorders, but 58 (26%) walked without aid. Compared with patients with DE only (N=129), patients with DE and venous stasis-related skin lesions (N=95) included a larger number of those with obesity than did those with DE only (26% vs. 14%, p=0.02). Conclusion: The primary cause of DE in older patients was the sedentary lifestyle secondary to aging and gait disturbance, not solely because of reduced leg function. The complications of obesity are associated with increased venous stasis-related skin lesions.

Laparoscopic-assisted thoracoscopic repair of latent traumatic diaphragmatic hernia: A case report.

Surgical approaches for traumatic diaphragmatic hernia include transabdominal, transthoracic, and thoracoabdominal. Selection of the optimal approach depends on the timing and organ damage, often minimally invasive approaches with laparoscopy or thoracoscopy are performed. A 47-year-old man with blunt chest trauma was diagnosed with left traumatic diaphragmatic hernia 1 month after the trauma. The prolapsed omentum was detached from the chest wall and around the hernia orifice and returned to the abdominal cavity by coordinated thoracoscopic and laparoscopic manipulations. The 4 × 2 cm herniation in the diaphragm was sutured closed from the thoracic side while preventing re-prolapse of the omentum and abdominal organs from the abdominal side. A combined thoracoscopic and laparoscopic approach can be effective in confirming organ damage, repositioning of prolapsed organs, and safe repair of the diaphragm in latent traumatic diaphragmatic hernia.

Early and Late Surgical Outcomes after Geometrical Infarct Exclusion for Post-Infarct Ventricular Septal Perforation.

PURPOSE: Ventricular septal perforation (VSP) is a critical complication of acute myocardial infarction. Various surgical procedures for it have been developed; however, surgical outcomes remain unsatisfactory. In 2010, we introduced geometrical infarct exclusion (GIE) as a modification of the Komeda-David technique. This retrospective study compared the surgical outcomes of our geometric infarct exclusion technique to those of other surgical procedures. METHODS: This study included 38 patients who underwent surgery for VSP. They were divided into patients who underwent GIE (GIE group; n = 17) and those who underwent other procedures (non-GIE group; n = 21). The clinical outcomes of the two groups were compared. RESULTS: Operation, cardiopulmonary bypass, and cardiac arrest times in the GIE group were significantly longer than those in the non-GIE group (p <0.001). A residual shunt was observed in one patient (5.8%) in the GIE group and eight (38.0%) in the non-GIE group (p = 0.026). No patients in the GIE group required a reoperation for the residual shut, while two patients required it in the non-GIE group (p = 0.492). Operative mortality was insignificantly different between the two groups. CONCLUSION: Geometric infarct exclusion has a longer procedural time than does other surgical procedures but can reduce the rates of residual shunts and reoperations.

Allogenic multilayered fibroblast sheets promote anastomotic site healing in a rat model of esophageal reconstruction.

OBJECTIVE: Anastomotic leakage is a common and severe complication of esophageal reconstruction. Accordingly, there is a clinical need for novel methods to prevent it. We developed multilayered, growth factor-secreting fibroblast sheets that promote wound healing and angiogenesis. The present study aimed to assess the utility of allogenic multilayered fibroblast sheets in preventing esophageal anastomotic leakage in a rat model of esophageal reconstruction. METHODS: Allogenic multilayered fibroblast sheets prepared from oral mucosal tissues were implanted at esophageal anastomotic sites. RESULTS: The allogenic multilayered fibroblast sheet group had significantly higher burst pressure and collagen deposition compared to a control group five days postoperatively. The expression levels of collagen type I and III mRNAs around esophageal suture sites were higher in the allogenic multilayered fibroblast sheet group compared to the control group on postoperative days 0, 3, and 5. There was a trend toward lower anastomotic leakage and lower abscess scores in the allogenic multilayered fibroblast sheet group compared to the control group; however, these differences did not reach statistical significance. Allogenic multilayered fibroblast sheets completely disappeared at ten days after implantation. Further, no inflammation was observed at suture sites with implanted allogenic multilayered fibroblast sheets at five days after surgery. CONCLUSION: Allogenic multilayered fibroblast sheets may represent a promising method of preventing esophageal anastomotic leakage.

Leg volume reduction during tiptoe movement is caused by venous ejection and calf muscle contraction.

OBJECTIVES: To clarify the cause of leg volume reduction during tiptoe movement in the standing position. METHODS: The right legs of 20 participants were assessed. The participants performed tiptoe movement in the supine position, and then stood up and performed the tiptoe movement and ankle dorsiflexion. Leg volume changes were recorded continuously using air plethysmography. RESULTS: Differences between leg volume changes due to tiptoe movement and the refilling volumes were not significantly different between the supine (59 mL) and standing (49 mL) positions, indicating that this amount of motion artifact was included in the downward trace recorded by tiptoe movement in the standing position. CONCLUSIONS: Leg volume reduction during tiptoe movement in the standing position included a significant amount of motion artifacts. Therefore, it may be difficult to accurately measure the ejection volume using tiptoe movement in the standing position.

Postoperative changes in a bronchial stump following covering with free fat tissue in a rat model.

OBJECTIVES: Covering the bronchial stump with free fat tissue has been used as minimally invasive prophylaxis against bronchial stump fistulas; however, postoperative changes in the bronchial stump have not been well validated. Our goal was to examine changes in the bronchial stump in response to covering with free fat tissue in a rat model. METHODS: A left pneumonectomy was performed on 16 Wistar/ST rats, 12 of which had a bronchial stump covered with free subcutaneous fat tissue. Four rats that underwent a left pneumonectomy alone were sacrificed on postoperative day 7, and the 12 rats whose bronchial stumps were additionally covered with fat tissue were sacrificed on postoperative days 7, 14 and 56. Macroscopic and histological changes and pressure resistance of the bronchial stumps due to coverage with free fat tissue were examined. RESULTS: None of the rats showed macroscopic infection or necrosis in the thoracic cavity at the time of the rethoracotomy. The normal bronchial stumps remained mostly exposed, whereas the bronchial stumps covered with fat tissue were well-coated with tissue mass. Histologically, fibrous connective tissue containing microvessels gradually formed around the bronchial stump covered with fat tissue, and some of the tissue masses still had normal fat structures 56 days postoperatively. Covering with fat tissue significantly increased the pressure resistance of the bronchial stump 7 days postoperatively and further increased with time. CONCLUSIONS: Covering the bronchial stump with free fat tissue formed fibrous connective tissue around the bronchial stump and reinforced its closure.

Dry preserved multilayered fibroblast cell sheets are a new manageable tool for regenerative medicine to promote wound healing.

This study investigated the therapeutic effects of dry-preserved multi-layered fibroblast cell sheets (dry sheets) on cutaneous ulcers. Dry sheets were prepared by air-drying multi-layered fibroblast cell sheets (living sheets) to cease their life activities. Before in vivo application, we tested the release of growth factors into the medium to examine the mechanisms of dry sheets in wound healing. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were released from both dry and living sheets, while high levels of fibroblast growth factor-2 (FGF-2) and high mobility group box 1 (HMGB1) protein were only from dry sheets. An in vitro fibroblast proliferation assay revealed that the dry sheet eluate significantly enhanced cell proliferation and VEGF and HGF production compared with living sheet eluate. FGF-2-neutralizing antibodies significantly blocked this proliferative response. In wounds created on diabetic mice, the dry sheet-treatment groups using autologous or allogeneic cells showed significantly accelerated wound closure compared with that in the no-treatment group. The storage stability of the dry sheet was better at refrigeration temperature than at room temperature and remained stable for at least 4 weeks. Our data indicated that allogeneic dry sheets represent a promising new tool for regenerative medicine that promotes wound healing.

Fate of dissected arch vessels by adventitial inversion technique for acute type A aortic dissection repair.

OBJECTIVES: The adventitial inversion technique is used widely for aortic reconstruction for acute type A aortic dissection, as it easily controls the bleeding at anastomotic sites and closes the patent false lumen. However, this technique for arch vessel reconstruction has not been previously reported. Therefore, we applied the adventitial inversion technique for dissected arch vessel reconstruction to close the patent false lumen. METHODS: Among 57 consecutive patients who underwent emergency surgical treatment for acute type A aortic dissection from July 2006 to July 2012, the adventitial inversion technique for the dissected arch vessels was performed in 26 patients (42 arch vessel stumps). The patency and morphologic change of the false lumen of the arch vessels were evaluated using contrast-enhanced computed tomography. RESULTS: Overall, 2 hospital deaths were recorded, and the hospital mortality rate was 4%. No postoperative cerebral strokes and reoperations due to bleeding occurred. Follow-up by contrast-enhanced computed tomography was completed in 24 patients (37 stumps) with a mean duration of 99 ± 35 months. The postoperative closure rate of the false lumen after adventitial inversion was 86%, which was higher than when adventitial inversion was not used. No adverse events including stroke occurred during follow-up period. CONCLUSIONS: This technique facilitates the closure of the false lumen of dissected arch vessels and might improve clinical outcomes.

Intimal-protected adventitial inversion technique accelerates the obliteration of a patent false lumen.

BACKGROUND AND AIMS: The optimal procedure for reconstructing the dissected aortic stump for acute type A dissection remains controversial. We routinely used the intimal-protected adventitial inversion technique (iPAIT), a modified adventitial inversion technique, to protect the fragile intima by inserting a graft and assessed the safety and efficacy of this technique. METHODS: Between August 2008 and April 2020, 146 consecutive patients with acute type A dissections underwent thoracic aortic surgery in our hospital. Extended total aortic arch replacement was performed in 119 patients (81.5%). Sixty-nine patients underwent treatment for distal aortic anastomosis with the iPAIT. To compare the iPAIT to a historical control, we assessed 69 iPAIT patients and 25 patients who underwent total arch replacement using gelatin-resorcinol-formaldehyde (GRF) glue. RESULTS: Hospital mortality was 2.9% in the iPAIT group and 8.0% in the GRF group. Perioperative characteristics were similar between the two groups. However, postoperative computed tomography revealed that the obliteration rate was significantly higher in the iPAIT group (60/66, 90.9%) than in the GRF group (15/23, 65.2%) (p = .01), not including the patients who had died or developed severe renal dysfunction. The 8-year aortic event-free survival rate in the iPAIT group (81.3%) was significantly higher than that in the GRF group (47.4%). CONCLUSIONS: The use of this technique for acute type A dissections resulted in a low mortality rate and demonstrated promising midterm survival and may accelerate the obliteration of a patent false lumen and prevent late aortic events.

Feasibility of open chest management with modified negative pressure wound therapy immediately after cardiac surgery.

OBJECTIVES: To evaluate the feasibility of open chest management with our modified negative pressure wound therapy immediately after cardiac surgery as a therapy for atypical tamponade. METHODS: Open chest with modified negative pressure wound therapy was performed immediately after cardiac surgery. The surface of the heart and the vessels were covered with non-adherent siliconized gauze. The sternal halves were stented using edge-cut disposable syringes to maintain a larger mediastinal cavity. Approximately 45 mm of distance was kept between the sternal edges. A trimmed sterile polyvinyl foam sponge was inserted into the mediastinum, the entire wound was sealed and negative pressure (-50 to -75 mmHg) was applied using a suction generator. Delayed chest closure was performed in a standard manner once the haemodynamic status was stabilizsed. RESULTS: The mortality rate was 3/15 (20%) patients. Deep sternal wound infection occurred in 1/15 (6.7%) patients. Five patients were extubated during the open chest management. Sternal closure was delayed for median of 3 days after the initial surgery. There was no incidence of bleeding complications or need for additional haemostatic procedures. CONCLUSIONS: Negative pressure wound therapy performed immediately after cardiac surgery was feasible in our small number of patients. CLINICAL REGISTRATION NUMBER: Study ID: 2020-149.

[Subcutaneous Bronchogenic Cyst in the Anterior Chest Diagnosed before Coronary Artery Bypass Grafting:Report of a Case].

A 65-year-old woman was transported to our hospital by ambulance because of severe dyspnea. She had had a subcutaneous tumor on her anterior chest since her childhood. Coronary angiography revealed three vessel disease with significant stenosis in the left main trunk. Excision of anterior chest tumor, 70×60×50 mm in size, was performed before coronary artery bypass grafting( CABG). It was a unilocular cyst adhering to the sternum, and was composed of ciliated epitheliums, goblet cells and smooth muscle cells. Based upon the existence of smooth muscle cells, the tumor was diagnosed as bronchogenic cyst. CABG was performed through mid-sternum about two months after the tumor excision, and the postoperative course was uneventful.

Validity of direct bilateral axillary arterial cannulation in emergency surgery for acute type A aortic dissection.

BACKGROUND AND AIM OF THE STUDY: To assess the validity and long-term outcomes of direct bilateral axillary arterial cannulation for acute type A aortic dissection. METHODS: Between 2003 and 2020, 208 consecutive patients with acute type A aortic dissection underwent emergency surgical repair. Cardiopulmonary bypass was attempted to establish direct bilateral axillary arterial cannulation and bicaval drainage. Antegrade selective cerebral perfusion was established by axillary perfusion and direct cannulation of the left common carotid artery. RESULTS: Ascending aortic, partial arch, and extended total aortic arch replacement were performed in 50 (24.0%), 7 (3.4%), and 151 (72.6%) patients, respectively. Aortic root surgery and coronary artery bypass grafting were performed concomitantly in 23 and seven patients, respectively. Cardiopulmonary bypass was attempted only through bilateral axillary cannulation in all patients but was successful in 13 (6.3%) patients without bilateral axillary cannulation. No postoperative complications occurred related to this technique. There were seven hospital deaths (early mortality rate, 3.4%). Five patients had postoperative reoperation for bleeding, and nine (4.3%) were transferred to other hospitals due to postoperative permanent cerebral infarction, particularly two with arm ischemia. The 10-year survival rate of patients who underwent emergency surgical repair with this technique was 71.4%. CONCLUSIONS: Direct bilateral axillary arterial cannulation followed by selective cerebral perfusion was successful in 93.7% of patients and this may be an optimal solution for providing stable outcomes after emergency surgery for acute type A aortic dissection. However, we experienced two complications of arm ischemia, attention should be paid to potential arm ischemia.

Autologous transplantation of multilayered fibroblast sheets prevents postoperative pancreatic fistula by regulating fibrosis and angiogenesis.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is a serious complication after gastrointestinal or pancreatic surgery. Despite intensive investigations, the occurrence has not significantly decreased in the past decades. The aims of this study were to clarify the pathophysiology of POPF and establish the preventive measures using multilayered fibroblast sheets. METHODS: We developed a pancreatic fistula (PF) model of rat with transection of the splenic duct and surrounding pancreatic parenchyma. Multilayered fibroblast sheets prepared from tails were autologously transplanted to this model. The preventive effect was biochemically and histologically evaluated by measuring the ascitic levels of pancreatic enzymes and conducting immunohistochemistry and real-time polymerase chain reaction analyses of pancreatic tissue. Findings were compared to those obtained with acellular materials simply sealing the wound. RESULTS: In the PF model, the ascitic levels of pancreatic enzymes were transiently up-regulated. Inflammation and necrosis were histologically observed in a wide range. Islets were damaged even in remote areas. Transplantation of multilayered fibroblast sheets dramatically reduced the ascitic leakage of enzymes, suppressed inflammation, and broadly preserved the islets. Compared with acellular materials, these sheets offered superior prevention of cellular activity through the spaciotemporal regulation of fibrosis and angiogenesis. Notably, the leakage hole appeared to have been plugged with the fibrotic matrix, which might have been the most crucial mechanism minimizing pancreatic damage. CONCLUSIONS: The autologous transplantation of multilayered fibroblast sheets significantly prevented PF and protected the pancreas, underscoring the potential utility of this approach for POPF prevention.

Preoperative evaluation of aortic calcification by computed tomography in thoracic aortic disease.

BACKGROUND: Computed tomography (CT) is a useful tool for the identification of calcified lesions in the aorta. However, no quantitative evaluation has been established to assess the applicability of simple anastomosis preoperatively. We conducted this retrospective study to establish a reference range of maximal CT attenuation values for application of simple anastomosis. METHODS: A total of 122 consecutive patients underwent replacement of the thoracic aorta between 2007 and 2011, excluding those with acute aortic dissection. The patients were divided into two groups: those who underwent simple anastomosis (simple group: n = 105), and those who required endarterectomy before anastomosis (manipulation group: n = 17). The maximal CT attenuation values at the anastomosis site were calculated by imaging software. RESULTS: The mean maximal CT attenuation values (Hounsfield unit [HU]) was significantly higher in the manipulation group (638.1 ± 269.5 [166-1304]) than in the simple group (94.7 ± 171.5 [0-790]; p < .0001). The maximal CT attenuation values enabled us to predict the simple anastomosis with the area under the receiver operating characteristic curve of 0.96 (p < .0001). The cut-off value was 325 HU (sensitivity 94.1%, specificity 81.7%). The 10-year survival rate was significantly lower in the manipulation group (11.8%) than in the simple group (43.2%). In the multivariate analysis, age (hazard ratio [HR]: 1.073), hypertension (HR: 2.382), and maximal CT attenuation values (HR: 1.001) were independently associated with long-term mortality. CONCLUSIONS: Preoperative evaluation of the maximal CT attenuation values is a useful tool in predicting whether simple anastomosis is applicable or not. Maximal CT attenuation values is a risk factor for long-term mortality.

[Transmitral Septal Myectomy and Mitral Valve Plasty for Hypertrophic Obstructive Cardiomyopathy Combined with Organic Mitral Regurgitation;Report of a Case].

A 60-year-old man with hypertrophic obstructive cardiomyopathy (HOCM) combined with organic mitral regurgitation underwent transmitral septal myectomy and mitral valve plasty. Although a transaortic septal myectomy (Morrow's procedure) is generally accepted as the standard surgical treatment for HOCM, it may be difficult to perform sufficient septal myectomy for mid-ventricular obstructive hypertrophic cardiomyopathy and apical hypertrophic cardiomyopathy (HCM). The transmitral approach with temporary detachment of the anterior mitral leaflet provides a good surgical view in the left ventricle, which allows sufficient septal myectomy from the outflow tract to the apex.

Preserving the endothelium in saphenous vein graft with both conventional and no-touch preparation.

BACKGROUND: Despite the inferior patency compared to arterial grafts, a saphenous vein graft (SVG) is widely used for coronary artery bypass grafting (CABG). A lower atherosclerosis rate and higher patency have been reported for SVG obtained via the no-touch technique (NT) than via conventional preparation (CV). Although CV-mediated endothelial dysfunction is implied, the precise mechanism underlying the higher patency with NT is poorly understood. METHODS: Human residual SVGs during CABG and SVG sections after autopsy were analyzed. The endothelial surface was observed using scanning electron microscopy (SEM) and blindly compared between CV and NT. The endothelial integrity was also analyzed with immunohistochemistry. RESULTS: Unexpectedly, the hyperfine structure on SEM was comparable between CV and NT before grafting, and microvillus, a characteristic of endothelium, was indistinguishable between them. Von Willebrand Factor, an endothelial marker, was equally detected throughout the vascular wall in both groups from residual and postmortem sections. CONCLUSIONS: The morphological integrity of the endothelium was successfully preserved in SVG with CV, even at an ultrastructural level. Although its functionality remains to be addressed, other factors than the endothelium may be involved in the high patency obtained by NT. The present findings suggest that the characteristics of NT and surgical methodology should be reconsidered.

Nuclear ß-catenin expression is positively regulated by JAB1 in human colorectal cancer cells.

Wnt/ß-catenin signaling is important for development and progression of colorectal cancer (CRC). The degradation complex for ß-catenin is functionally impaired in CRC cells, thereby resulting in the accumulation of ß-catenin and its translocation into the nucleus. Nuclear ß-catenin interacts with and co-activates T cell factor4 (TCF4), resulting in ß-catenin/TCF4-dependent transcription. Therefore, nuclear ß-catenin has been categorized as the main driving force in the tumorigenesis of CRC. Recent studies reveal that Jun activation domain-binding protein 1 (JAB1) enhances the degradation of seven in absentia homolog-1 (SIAH-1), a putative E3 ubiquitin ligase of ß-catenin, and positively regulates the expression of total ß-catenin in human CRC cells. An another recent study also shows that nuclear ß-catenin is ubiquitinated and degraded by an E3 ubiquitin ligase, tripartite motif-containing protein 33 (TRIM33). However, the regulatory mechanism for the expression of nuclear ß-catenin remains to be fully understood. In this study, we have demonstrated that JAB1 positively regulates the expression of nuclear ß-catenin, c-MYC as a ß-catenin/TCF4 target, and cell cycle regulators, such as Ki-67 and topoisomerase IIα, in human CRC cells. Taken together, these results suggest that JAB1 is considered as a promising target for novel CRC therapy.