HMGA1 Induces Intestinal Polyposis in Transgenic Mice and Drives Tumor Progression and Stem Cell Properties in Colon Cancer Cells

Although metastatic colon cancer is a leading cause of cancer death worldwide, the molecular mechanisms that enable colon cancer cells to metastasize remain unclear. Emerging evidence suggests that metastatic cells develop by usurping transcriptional networks from embryonic stem (ES) cells to facilitate an epithelial-mesenchymal transition (EMT), invasion, and metastatic progression. Previous studies identified HMGA1 as a key transcription factor enriched in ES cells, colon cancer, and other aggressive tumors, although its role in these settings is poorly understood.To determine how HMGA1 functions in metastatic colon cancer, we manipulated HMGA1 expression in transgenic mice and colon cancer cells. We discovered that HMGA1 drives proliferative changes, aberrant crypt formation, and intestinal polyposis in transgenic mice. In colon cancer cell lines from poorly differentiated, metastatic tumors, knock-down of HMGA1 blocks anchorage-independent cell growth, migration, invasion, xenograft tumorigenesis and three-dimensional colonosphere formation. Inhibiting HMGA1 expression blocks tumorigenesis at limiting dilutions, consistent with depletion of tumor-initiator cells in the knock-down cells. Knock-down of HMGA1 also inhibits metastatic progression to the liver in vivo. In metastatic colon cancer cells, HMGA1 induces expression of Twist1, a gene involved in embryogenesis, EMT, and tumor progression, while HMGA1 represses E-cadherin, a gene that is down-regulated during EMT and metastatic progression. In addition, HMGA1 is among the most enriched genes in colon cancer compared to normal mucosa.Our findings demonstrate for the first time that HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and induces metastatic progression and stem-like properties in colon cancer cells. These findings indicate that HMGA1 is a key regulator, both in metastatic progression and in the maintenance of a stem-like state. Our results also suggest that HMGA1 or downstream pathways could be rational therapeutic targets in metastatic, poorly differentiated colon cancer

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients

Endovascular treatment with Onyx of arterio-venous fistula around the transverse sinus presenting with ocular symptoms. Case report

Introduction: Dural arterio-venous fistulas /DAVF/ are rare vascular malformations that represent around 10–15% of all intracranial vascular malformations. The DAVF could be asymptomatic or produce a variety of symptoms – headache, pulsatile tinnitus, characteristic bruit over the site of the fistula, ocular symptoms – chemosis, proptosis, or other neurological symptoms due to intracerebral haemorrhage of the DAVF. We present a rare clinical case of a transverse sinus DAVF with ipsilateral ocular symptoms and maybe the first case to our knowledge occluded with Onyx with preservation of the transverse sinus. Clinical case: A 46-year-old male patient presented with headache, redness of the left eye and left-sided proptosis. The symptoms started after a heavy physical exertion two months ago. MRI scan and DSA confirmed the presence of a DAVF located around the left transverse sinus with venous ectasia and retrograde flow up to the left cavernous sinus. Transarterial endovascular embolization of the DAVF with Onyx was performed with complete resolution of the symptoms of the patient. Discussion: The more posteriorly located the DAVF the less likely is to present with ocular symptoms. Sometimes these are the first signs of the presence of a DAVF and especially of higher grade DAVF that could lead to intracerebral haemorrhage. The Borden Grade 2 and 3 DAVF risk of intracerebral haemorrhage is 17 % and 46 %, respectively. Cognard Grade IIa + b around 40 % and all grades III-V − 80–100 %. The high risk of intracranial haemorrhage and the ocular symptoms are indication for treatment. Conclusion: Transarterial embolization of DAVF with Onyx is safe, with high initial occlusion rate (55–85%). Ocular symptoms of DAVF have a benign course after successful embolization

Diagnostic and surgical treatment of lumbar spine synovial cyst in 26 patients

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Surgical results in 26 patients operated for lumbar arthrosynovial cysts

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Kystes arthro-synoviaux multiples durachis lombaire: à propos de 5 cas

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