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1.
J Environ Manage ; 366: 121904, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39029165

ABSTRACT

Coarse textured soils have low potential to store carbon (C) due to lack of mineral oxides and have low clay content to protect C from biodegradation and leaching. This study evaluated the potential of stabilizing C by adding metal oxyhydroxide-rich water treatment residuals (WTRs) to an aeolian pure sand (<5% clay) topsoil amended with anaerobic digestate (AD) sludge. The AD sludge was applied at 5% (w/w) with aluminum based WTR (Al-WTR) and iron based WTR (Fe-WTR) co-applied at 1:1 and 2:1 WTR:AD (w/w) ratios and incubated at room temperature for 132 days. The cumulative mineralized C was normalized to the total organic C of the treatments. Co-addition with Al-WTR showed to be more effective in stabilizing C through decreased cumulative mineralized C by 48% and 57% in 1Al-WTR:1AD and 2Al-WTR:1AD, respectively, compared to AD sludge sole amendment. Co-application with Al-WTR also decreased permanganate oxidizable C by 37% and dissolved organic C by 51%. Co-application with Fe-WTR did not decrease the concentration of these labile C pools to the same extent, possibly due to the selective use of Fe-WTRs to treat organic-rich raw water. This makes it less effective in stabilizing C in a pure sand relative to Al-WTR due to chemical instability of the Fe-organic complexes. The Al-WTR provides a promising co-amendment to increase C sequestration in pure sands when co-applied with biosolids. The co-amendment approach will not only facilitate C sequestration but also contributes to waste management, aligning to the objectives of a circular economy.

2.
ANZ J Surg ; 92(9): 2167-2173, 2022 09.
Article in English | MEDLINE | ID: mdl-35916436

ABSTRACT

BACKGROUND: Groove pancreatitis (GP) is an underrecognised subtype of chronic pancreatitis, focally affecting the area between the duodenum and pancreatic head. It most commonly affects males between 40 and 50 years of age with a history of alcohol misuse. Patients most commonly complain of abdominal pain and vomiting. Due to its focal nature, it is a potentially surgically treatable form of chronic pancreatitis. We report results of patients surgically treated for groove pancreatitis followed by a literature review of patient outcomes post resection. METHODS: A retrospective chart review of patients with histopathologically confirmed GP post-surgical resection at the Princess Alexandra Hospital and Greenslopes Private Hospital in Brisbane, Australia was conducted between 2013 and 2020. Diagnosis was confirmed histologically when Brunner gland hyperplasia and chronic inflammation/fibrosis were found within the pancreaticoduodenal interface. Preoperative and postoperative symptoms were analysed along with complications. Additionally, a systematic review on outcomes of patients undergoing pancreaticoduodenectomy (PD) for GP was performed from three databases. RESULTS: Eight patients underwent surgery for GP. Elimination of preoperative symptoms was achieved in five of the eight patients. Major complications included one take back to theatre for pancreatic leak. Our literature review found complete resolution of pain and vomiting in 80% of GP patients after PD. CONCLUSION: Optimal management of GP begins with early recognition. Symptoms from GP are likely to respond well to surgical intervention. We advocate for aggressive surgical resection in a patient with a high index of suspicion for GP.


Subject(s)
Pancreatitis, Chronic , Diagnostic Errors , Fibrosis , Humans , Male , Pancreaticoduodenectomy/methods , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/pathology , Pancreatitis, Chronic/surgery , Retrospective Studies , Vomiting
3.
Clin Podiatr Med Surg ; 38(1): 99-110, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33220747

ABSTRACT

The induced membrane technique is a simple, effective, and reproducible treatment method for segmental bone defects. It is a 2-stage approach that requires eventual autologous bone graft to manage the deficit. The first stage requires debridement of all nonviable tissue while preserving a healthy soft tissue envelope. A polymethylmethacrylate is implanted between the osseous segments to maintain length. The osseous defect can be stabilized internally or externally. During the second stage, a vascularized induced membrane is formed and produces multiple growth factors. The induced membrane technique is a valuable option for limb salvage in cases of segmental bone defects.


Subject(s)
Foreign-Body Reaction , Fractures, Bone/surgery , Intercellular Signaling Peptides and Proteins/metabolism , Membranes/growth & development , Membranes/metabolism , Soft Tissue Injuries/surgery , Autografts , Bone Regeneration , Cancellous Bone/transplantation , Debridement , Humans , Limb Salvage/methods
6.
Transl Androl Urol ; 9(6): 3025-3035, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33457276

ABSTRACT

Radical prostatectomy (RP) is a common treatment choice for localized prostate cancer. While there is increasing utilisation of robotic assisted RP in some centres, open RP (ORP) remains well established and commonly performed in many parts of the world. The goals of modern ORP are to remove the prostate en-bloc with negative surgical margins, while minimising blood loss and preserving urinary continence and erectile function. We present a technical review of ORP incorporating contemporary techniques for control of the deep venous complex, additional haemostatic measures, nerve-sparing and vesicourethral reconstruction.

7.
BMJ Case Rep ; 12(11)2019 Nov 26.
Article in English | MEDLINE | ID: mdl-31776148

ABSTRACT

A 49-year-old man presented with a 2-week history of gradual onset progressively worsening left upper quadrant pain. Ten months prior, he had a laparoscopic roux-en-Y gastric bypass (LRYGBP) for severe gastro-oesophageal reflux disease and obesity. On examination, his abdomen was not distended and was soft to palpation. The haemoglobin, white cell count, liver function test, lipase and lactate were normal. An abdominal CT scan demonstrated swirl sign. Given the suspicion of internal herniation, laparoscopy was performed demonstrating only partial closure of the jejuno-jejunal mesodefect resulting in herniation of the small bowel alimentary limb. Internal herniation should be considered as a differential diagnosis in all patients with previous LRYGBP and unexplained abdominal pain, nausea or vomiting. If closure of a mesodefect is to be attempted, a running, braided, non-absorbable suture should be used as a purse-string to avoid small defects with subsequent weight and mesenteric fat loss following bariatric surgery.


Subject(s)
Gastric Bypass/methods , Herniorrhaphy/methods , Jejunal Diseases/surgery , Laparoscopy , Postoperative Complications/surgery , Wound Closure Techniques , Abdomen , Gastric Bypass/adverse effects , Hernia/etiology , Humans , Jejunal Diseases/etiology , Laparoscopy/adverse effects , Male , Middle Aged , Postoperative Complications/etiology
8.
BMJ Case Rep ; 12(10)2019 Oct 05.
Article in English | MEDLINE | ID: mdl-31586954

ABSTRACT

Small bowel diaphragm disease (SBDD) is characterised by circumferential lesions of short length (<5 mm), causing intrinsic stenosis of the small bowel lumen. A 63-year-old women with a history of long-term non-steroidal anti-inflammatory use, presented with a 12-month history of intermittent episodes of colicky abdominal pain, nausea and vomiting. Her only past surgery was a laparoscopic hysterectomy. Abdominal CT demonstrated an area of thickening in the mid small bowel, however a diagnostic laparoscopy failed to demonstrate adhesions or any external abnormality. A capsule endoscope did not progress beyond the mid small bowel at the site of a suspected diaphragm. The patient underwent a laparotomy and using the retained capsule as a marker, the area of bowel affected by SBDD was identified. With an ageing population and the widespread use of non-steroidalanti-inflammatory drugs, general surgeons may see an increase in the incidence of SBDD.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Ileal Diseases/diagnosis , Intestinal Obstruction/diagnosis , Abdominal Pain , Anastomosis, Surgical , Capsule Endoscopy , Diagnosis, Differential , Female , Humans , Ileal Diseases/chemically induced , Ileal Diseases/diagnostic imaging , Ileal Diseases/surgery , Intestinal Obstruction/chemically induced , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/surgery , Laparotomy , Middle Aged , Tomography, X-Ray Computed
9.
BMJ Case Rep ; 12(8)2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31420438

ABSTRACT

Biliary colic is a pain in the right upper quadrant or epigastrium thought to be caused by functional gallbladder spasm from a temporary obstructing stone in the gallbladder neck, cystic duct or common bile duct. A 56-year-old man presented with frequent episodes of typical biliary colic. At initial laparoscopy, the gallbladder was absent from its anatomic location. Further inspection revealed a left-sided gallbladder (LSGB), suspended from liver segment 3. Preoperative ultrasound, the most common imaging modality for symptomatic gallstones, has a low positive predictive value for detecting LSGB (2.7%). Laparoscopic cholecystectomy (LC) was delayed to attain additional imaging. A magnetic resonance cholangiopancreatography demonstrated the gallbladder left of the falciform ligament with the cystic duct entering the common hepatic duct from the left. The patient underwent an elective LC 8 weeks later. The critical view of safety is paramount to safe surgical dissection and could be safely achieved for LSGB.


Subject(s)
Cholecystectomy, Laparoscopic/methods , Gallbladder Diseases/surgery , Gallbladder/abnormalities , Gallbladder/surgery , Humans , Male , Middle Aged
10.
BMJ Case Rep ; 12(7)2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31266754

ABSTRACT

An 81-year-old man presented to medical services with pelvic pain and evolving urinary retention over 3 months. The patient was found to have a tense glans and penile shaft with surrounding induration consistent with malignant priapism. The extent of the induration included the suprapubic region, scrotum, left iliac region and left flank. A CT scan demonstrated an enhancing, pedunculated lesion arising from the anterior bladder wall measuring 30×31×20 mm. There were multiple enlarged left inguinal lymph nodes. Core biopsies of the subcutaneous tissue on the anterior abdominal wall demonstrated plasmacytoid urothelial carcinoma. The majority of patients with plasmacytoid variant of transitional cell carcinoma will present with >stage 3 bladder disease.


Subject(s)
Carcinoma, Transitional Cell/diagnostic imaging , Carcinoma, Transitional Cell/pathology , Penile Neoplasms/secondary , Priapism/diagnostic imaging , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Aged, 80 and over , Biopsy , Carcinoma, Transitional Cell/complications , Humans , Male , Priapism/etiology , Tomography, X-Ray Computed/methods , Urinary Bladder/diagnostic imaging , Urinary Bladder Neoplasms/complications
11.
BMJ Case Rep ; 12(6)2019 Jun 21.
Article in English | MEDLINE | ID: mdl-31229969

ABSTRACT

A 35-year-old man presented to a regional hospital after being kicked by a horse in the right upper quadrant. He was transferred to our hepatobiliary unit with bile peritonitis 8 days post trauma. Laparoscopic cholecystectomy and intraoperative cholangiography were performed, demonstrating distal common bile duct (CBD) obstruction with contrast extravasation from the distal duct. The CBD was drained with a T-tube via laparotomy. On postoperative day 14, T-tube cholangiography demonstrated no extravasation of contrast from the distal CBD and minor stricturing with eventual duodenal drainage. The T-tube was clamped and 5 weeks later, the patient represented with peri-T-tube bile leakage and right upper quadrant pain. A T-tube cholangiogram confirmed a complex distal CBD stricture. Two attempts at ERCP with intent of stenting the stricture were unsuccessful. The patient underwent an end to side Roux-en-Y choledochojejunostomy and was discharged home 4 days postoperatively on simple analgesia.


Subject(s)
Bile Ducts, Extrahepatic/injuries , Choledochostomy/methods , Drainage/methods , Peritonitis/pathology , Wounds, Nonpenetrating/pathology , Wounds, Nonpenetrating/therapy , Adult , Animals , Behavior, Animal , Bile Ducts, Extrahepatic/physiopathology , Cholecystectomy, Laparoscopic , Hoof and Claw , Horses , Humans , Laparoscopy , Male , Peritonitis/therapy , Treatment Outcome
12.
J Gastrointest Surg ; 23(8): 1694-1700, 2019 08.
Article in English | MEDLINE | ID: mdl-31197695

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is one of the most common general acute surgical presentations. Current recommendations are that idiopathic acute pancreatitis (IAP) should account for no more than 20% of AP cases. Some studies suggest gallbladder microlithiasis is the aetiology in up to 75% of IAP patients. Endoscopic ultrasound (EUS) has been reported to be effective in the detection of microlithiasis and choledocholithiasis as well as pancreatic parenchymal, ductal and ampullary disorders. The aims of this study were to evaluate the usefulness of EUS in establishing aetiology in IAP patients and to assess if there is a role for EUS in the selection criteria for laparoscopic cholecystectomy to treat a potential biliary cause in IAP patients. METHODS: A systematic review following PRISMA guideline was performed to gather data on patients with IAP undergoing EUS for further investigation. Three databases (MEDLINE, PubMed, and EMBASE) were searched to 28 July 2018. RESULTS: Our systematic review included 28 studies, comprising 1850 patients with an initial diagnosis of IAP prior to having EUS. Diagnosis of a potential aetiology or associated pancreatic pathology was established in 1095 (62%, p < 0.001) of cases. A biliary aetiology (microlithiasis or choledocholithiasis) was found in 37%. Chronic pancreatitis and associated pancreatic findings (dilated pancreatic duct, pancreatic duct stricture or stone) were found in 21%. Pancreatic neoplasms were found in 6%. Of the patients who had identifiable biliary pathology on EUS that proceeded to cholecystectomy, 2% had a recurrence of AP during a mean follow-up period of 20.5 months. CONCLUSIONS: There is a likely role for the routine use of EUS in the assessment of patients with IAP. The routine use of EUS may decrease the proportion of cases with a diagnosis of IAP. EUS may provide better selection criteria for laparoscopic cholecystectomy in patients with an initial diagnosis of IAP.


Subject(s)
Endosonography/methods , Pancreas/diagnostic imaging , Pancreatitis/diagnosis , Acute Disease , Humans
13.
J Trauma Acute Care Surg ; 86(5): 896-901, 2019 05.
Article in English | MEDLINE | ID: mdl-31008893

ABSTRACT

BACKGROUND: Extrahepatic bile duct injuries (EHBDIs) are a rare consequence of blunt abdominal trauma. The purpose of this study was to establish mechanisms of injury, clinical indicators of EHBDI following blunt trauma (both with investigative modalities and intraoperatively), method and timing of injury detection, and definitive treatment options. METHODS: A systematic review was performed to gather data on patients with an EHBDI secondary to blunt trauma. Three databases (MEDLINE, PubMed, and EMBASE) were searched to July 19, 2018. RESULTS: Our systematic review included 51 studies, compromising a study population of 66 patients with EHBDIs sustained from blunt trauma. The three most common injuries included complete transection of the suprapancreatic common bile duct (29%, n = 19), complete transection of the intrapancreatic common bile duct (23%, n = 15) and partial laceration of the left hepatic duct (20%, n = 13). Of the hemodynamically stable group managed nonoperatively (n = 23), mean timing postinjury to diagnosis of EHBDI was 11 days. An EHBDI was recognized at initial laparotomy in 87% (n = 13) of hemodynamically stable patients. An EHBDI was recognized at initial laparotomy in 57% (n = 8) of hemodynamically unstable patients. CONCLUSION: The EHBDIs are a rare yet serious consequence of blunt trauma. To establish a timely diagnosis and limit complications of missed injuries, a heightened awareness is required by the attending surgeon with particular attention to subtle yet important clinical indicators. These vary depending on the hemodynamic stability of the patient and decision to manage injuries conservatively or surgically on presentation. LEVEL OF EVIDENCE: Systematic review, level III.


Subject(s)
Bile Ducts, Extrahepatic/injuries , Wounds, Nonpenetrating/complications , Humans , Wounds, Nonpenetrating/diagnosis
14.
ANZ J Surg ; 89(11): 1392-1397, 2019 11.
Article in English | MEDLINE | ID: mdl-30836441

ABSTRACT

BACKGROUND: A left-sided gallbladder (LSGB) is a rare anatomical anomaly that is often not discovered until surgery. Two cases of LSGB managed with laparoscopic cholecystectomy (LC) stimulated this systematic review. The aims of this study were in LSGB to define the rate of pre-operative detection, variations in biliary anatomy, laparoscopic techniques employed and outcomes of surgery for symptomatic gallstones. METHODS: A systematic review was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses principles. RESULTS: Fifty-three studies with 112 patients of which 90 (80.4%) had symptomatic gallstones. Pre-operative imaging was performed in 108 patients (96.4%) with an LSGB reported on imaging in 32 (29.6%) patients. The remainder of LSGB were discovered at surgery. Ultrasound detected an LSGB in three (2.7%) patients. Five variants of cystic union with the common hepatic duct (CHD) were identified. The most common (67.8%) was union on the right side of the CHD after a hairpin bend anterior to the CHD. A cholecystectomy for gallstone disease was performed in 90 patients, 23.3% open and 76.7% LC. Common variations in LC technique were different port site placement and techniques related to the falciform ligament to improve exposure. Common bile duct injury occurred in four (4.4%) patients. CONCLUSION: LSGB is a rare anatomical variation that in patients with symptomatic gallstones is usually discovered at surgery. Cholecystectomy is associated with a higher incidence of common bile duct injury.


Subject(s)
Cholecystectomy, Laparoscopic/adverse effects , Gallbladder Diseases/diagnostic imaging , Gallbladder/abnormalities , Gallstones/surgery , Cholecystectomy, Laparoscopic/methods , Common Bile Duct/injuries , Gallbladder/diagnostic imaging , Gallbladder/surgery , Gallbladder Diseases/epidemiology , Gallbladder Diseases/pathology , Hepatic Duct, Common/diagnostic imaging , Humans , Incidence , Perioperative Period/statistics & numerical data
15.
BMJ Case Rep ; 12(1)2019 Jan 22.
Article in English | MEDLINE | ID: mdl-30674499

ABSTRACT

A 57-year-old man presented with a 6-month history of pelvic fullness. He had no lower urinary tract symptoms or altered bowel habits. On examination, there was a non-tender pelvic mass which extended from the pubic symphysis to the level of the umbilicus. CT scan of the abdomen demonstrated a 22×11×11 cm cystic mass arising from the pelvis extending into the midline and superiorly to the umbilicus. Other than raised carcinoembryonic antigen of 7.6 ng/mL (<5.0), the remainder of his blood test were unremarkable. Flexible cystoscopy demonstrated a convex deformity of the bladder wall in keeping with the compression and displacement as seen on the CT. The patient underwent an open excision of the cystic structure (urachal remnant), partial cystectomy, partial excision of anterior abdominal wall and pelvic lymphadenectomy. A check cystogram performed 12 days following the initial operation was unremarkable.


Subject(s)
Abdominal Wall/surgery , Cystadenocarcinoma, Mucinous/diagnostic imaging , Cystadenocarcinoma, Mucinous/surgery , Urachus/abnormalities , Urachus/surgery , Abdominal Wall/diagnostic imaging , Abdominal Wall/pathology , Aftercare , Carcinoembryonic Antigen/analysis , Cystadenocarcinoma, Mucinous/metabolism , Cystadenocarcinoma, Mucinous/ultrastructure , Cystectomy/methods , Cystoscopy/methods , Humans , Lymph Node Excision/methods , Male , Middle Aged , Rare Diseases , Tomography, X-Ray Computed/methods , Treatment Outcome , Urachus/diagnostic imaging , Urachus/pathology , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery
16.
J Travel Med ; 25(1)2018 06 01.
Article in English | MEDLINE | ID: mdl-29924349

ABSTRACT

Background: Medical tourism has witnessed significant growth in recent years. The emerging trend towards international travel for cosmetic surgical interventions has not previously been reviewed. The current review aims to critically address the scale and impact of cosmetic surgical tourism and to delineate the complication profile of this form of medical tourism. Methods: Articles published in the English language on the PubMed database that were relevant to surgical tourism and the complications of elective surgical procedures abroad were examined. Reference lists of articles identified were further scrutinized. The search terms used included combinations of 'surgery abroad', 'cosmetic surgery abroad', 'cosmetic surgery tourism', 'cosmetic surgery complications' and 'aesthetic tourism'. Results: This article critically reviews the epidemiology of cosmetic surgical tourism and its associated economic factors. Surgical complications of selected procedures, including perioperative complications, are described. The implications for travel medicine practice are considered and recommendations for further research are proposed. Conclusion: This narrative literature review focuses on the issues affecting travellers who obtain cosmetic surgical treatment overseas. There is a lack of focus in the travel medicine literature on the non-surgery-related morbidity of this special group of travellers. Original research exploring the motivation and pre-travel preparation, including the psychological counselling, of cosmetic surgical tourists is indicated.


Subject(s)
Cosmetic Techniques/statistics & numerical data , Medical Tourism/statistics & numerical data , Patient Safety/statistics & numerical data , Surgery, Plastic/statistics & numerical data , Attitude to Health , Cosmetic Techniques/economics , Health Care Costs , Humans , Medical Tourism/economics , Postoperative Complications/epidemiology , Surgery, Plastic/economics , Travel , Travel Medicine
18.
Foot Ankle Spec ; 10(6): 560-566, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28874067

ABSTRACT

The sural flap procedure is a versatile technique that can be used to cover many types of defects about the lower extremity. The management of soft tissue defects of the lower extremity with underlying osteomyelitis is difficult. The goal for any of these patients is to create a biomechanically stable foot for weight-bearing purposes with no continued infection. Data were gathered using multiple databases from the years 2000 to 2016. Data were compiled looking at the number of subjects, age, comorbidities, number of complications, number of failures, and average flap size of complications/failures. A total of 110 patients were gathered using 5 separate articles. Twenty-two of the 110 patients had short-term complications. Flap failure was seen in 9/110 patients. A significant difference was noticed in flap size between flap failure and complication groups and nonfailure groups. The average flap size of patients who had some form of complication or failure was 51.87 cm2 in size. The average graft size for patients without complications during their recovery was 36.54 cm2. Within our study, the failure rate of 8.9% and complication rate of 13.7% are consistent with previous reports on sural perforator flaps. Last, with regard to the effect of flap size, there were significant differences between patients with a successful outcome and those who experienced complications or failures. LEVELS OF EVIDENCE: Therapeutic, Level III: Systematic review.


Subject(s)
Leg Injuries/surgery , Myocutaneous Flap/transplantation , Osteomyelitis/surgery , Plastic Surgery Procedures/methods , Soft Tissue Injuries/surgery , Female , Foot Injuries/diagnosis , Foot Injuries/surgery , Graft Rejection , Graft Survival , Humans , Injury Severity Score , Leg Injuries/diagnosis , Male , Myocutaneous Flap/blood supply , Osteomyelitis/diagnosis , Predictive Value of Tests , Soft Tissue Injuries/diagnosis , Treatment Outcome , Wound Healing/physiology
19.
Int J Low Extrem Wounds ; 16(3): 208-211, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28825333

ABSTRACT

Loss of soft tissue coverage distally around the foot poses threats of amputation of the exposed boney structures. An amputation of a portion of the foot leads to loss of the biomechanical structural integrity of the foot. This promulgates an imbalance with its inherent risks of developing new ulcers. This in turn potentiates the limb loss cycle. The reverse abductor hallucis muscle flap is ideally suited for small to moderate-sized defects in the vicinity of the first metatarsophalangeal joint based on its arc of rotation. In this article, we present cases of 5 patients who failed local wound care and healing by secondary intention for at least 6 months duration. The patients were treated successfully using reverse abductor hallucis muscle flap.


Subject(s)
Diabetic Foot/surgery , Metatarsophalangeal Joint/surgery , Myocutaneous Flap/transplantation , Plastic Surgery Procedures/methods , Wound Healing/physiology , Adult , Diabetic Foot/physiopathology , Female , Follow-Up Studies , Graft Rejection , Graft Survival , Humans , Male , Metatarsophalangeal Joint/pathology , Middle Aged , Myocutaneous Flap/blood supply , Retrospective Studies , Sampling Studies , Treatment Outcome
20.
J Biol Chem ; 287(30): 24955-66, 2012 Jul 20.
Article in English | MEDLINE | ID: mdl-22679017

ABSTRACT

Ran (Ras-related nuclear) protein, a member of the Ras superfamily of GTPases, is best known for its roles in nucleocytoplasmic transport, mitotic spindle fiber assembly, and nuclear envelope formation. Recently, we have shown that the overexpression of Ran in fibroblasts induces cellular transformation and tumor formation in mice (Ly, T. K., Wang, J., Pereira, R., Rojas, K. S., Peng, X., Feng, Q., Cerione, R. A., and Wilson, K. F. (2010) J. Biol. Chem. 285, 5815-5826). Here, we describe a novel activated Ran mutant, Ran(K152A), which is capable of an increased rate of GDP-GTP exchange and an accelerated GTP binding/GTP hydrolytic cycle compared with wild-type Ran. We show that its expression in NIH-3T3 fibroblasts induces anchorage-independent growth and stimulates cell invasion, as well as activates signaling pathways that lead to extracellular regulated kinase (ERK) activity. Furthermore, Ran(K152A) expression in the human mammary SKBR3 adenocarcinoma cell line gives rise to an enhanced transformed phenotype and causes a robust stimulation of both ERK and the N-terminal c-Jun kinase (JNK). Microarray analysis reveals that the expression of the gene encoding SMOC-2 (secreted modular calcium-binding protein-2), which has been shown to synergize with different growth factors, is increased by at least 50-fold in cells stably expressing Ran(K152A) compared with cells expressing control vector. Knocking down SMOC-2 expression greatly reduces the ability of Ran(K152A) to stimulate anchorage-independent growth in NIH-3T3 cells and in SKBR3 cells and also inhibits cell invasion in fibroblasts. Collectively, our findings highlight a novel connection between the hyper-activation of the small GTPase Ran and the matricellular protein SMOC-2 that has important consequences for oncogenic transformation.


Subject(s)
Cell Transformation, Neoplastic/metabolism , Mutation, Missense , ran GTP-Binding Protein/metabolism , Amino Acid Substitution , Animals , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Enzyme Activation/genetics , Humans , Mice , NIH 3T3 Cells , ran GTP-Binding Protein/genetics
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