The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells

INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment

Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells

After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig. 5b. The Skp1 loading control was accidentally duplicated. We apologize for this error, which did not affect any of the interpretations or conclusions of the article

Lymphaticovenular-anastomosis treatment of the peripheral component in chyle leakage after axillary surgery: case report and review

Axillary lymph node dissection-dependent chyle leakage is a rare complication with an incidence of < 0.7%. The morbidity could be high, and the management prolonged and not clear. The literature offers us many therapeutical tools, yet there is no consensus about the management of this complication. Usually, the management focuses on reducing the chyle flow in the thoracic duct (central origin), neglecting the possibility of a parallel lymphorrhea from other regional lymphatic vessels (peripheral origin), which causes a prolonged approach with high morbidity. In this paper, we introduce the supermicrosurgery technique as a surgical therapeutic option for chyle leakage. To decrease morbidity and shorten treatment duration, we offer a therapeutic algorithm based on the literature and our experience

Cecal Fibromatosis (Desmoid Tumor) Mimicking Periappendicular Abscess: A Case Report

A 32-year-old man presented to our department with abdominal pain and fever. In an earlier hospitalization he was diagnosed with periappendicular abscess and treated with antibiotics. Due to fever and ‘non-resolution’ of the abscess and due to its deep location in the lower abdomen, which excluded percutaneous drainage, we elected to operate the patient. A large mass in the cecum accompanied with an abscess resulted in a right hemicolectomy. The pathological examination revealed a desmoid tumor of the cecum. The patient’s recovery was uneventful

Ganglioneuroma of the Adrenal Gland: A Rare Tumor in a Rare Location

A 62-year-old man presented to his general practitioner complaining of non-specific back pain. He underwent a computerized tomography scan and magnetic resonance imaging that revealed a large left adrenal mass. A thorough investigation of this mass revealed it to be a non-secreting tumor. At surgery, a large tumor of the left adrenal was found. The final pathology report revealed a ganglioneuroma of the adrenal gland

A unique case of metastatic spinal epidural abscess associated with liver abscess following ascending cholangitis and Escherichia coli bacteremia

Pyogenic liver abscess (PLA) is a life-threatening infection that may develop as a result of an underlying hepatobiliary disease. A possible complication of PLA is metastatic spread, resulting in distant seeding of infection in other organs, and occasionally in the epidural space. Spinal epidural abscess (SEA) is a rare infection with severe potential complications. We describe a 71-year-old patient who presented with ascending cholangitis that was complicated by micro PLA, with a subsequent Escherichia coli bacteremia and metastatic SEA. An emergent surgical intervention with laminotomy and drainage of the epidural collection was performed. The patient was treated with a prolonged antibiotic regimen, with uneventful recovery and no neurologic sequelae. To our knowledge, this is the first reported case of a SEA following E. coli PLA