Intraosseous hemangioma is a benign, rare neoplasm that accounts to 0.5 - 1% of all benign tumors of bones.1, 2 While most hemangiomas arise from soft tissues, it is uncommon for it to arise from bones.2 The most common sites of growth are in the vertebral body and the calvarium with frontal bone making up approximately 45% of calvarial cases.2,3 However, they are also encountered in the head and neck with sites such as the skull (53%), mandible (10.7%), nasal bones (9%), and cervical spine (6%).4 In the mandible, the body is mostly affected and 65% are found in the molar and premolar region.1 They are more common in adult females with peaks at the second and fifth decades of life.1-3 Hemangioma of the mandible is difficult to diagnose due to its nonspecific clinical presentation and radiographic features. It mimics various mass lesions in the mandible such as giant cell granuloma, fibrous dysplasia, multiple myeloma, osteosarcoma, ameloblastoma and keratocysts. Therefore, a comprehensive history taking and physical examination plus examination of the imaging studies available and tissue biopsy all play important roles in arriving at the final diagnosis.5 We present the case of an aggressive mandibular hemangioma in a young boy and our management involving a failed fibular free flap reconstruction.
Sirolimus ; Sirolimus

Proliferation signal inhibitors are a new class of immunosuppressant. They inhibit the mammalian target of rapamycin and blocks the cell cycle of various cell types, including T and B lymphocytes. PSI is used in renal transplantation as a maintenance immunosuppressant. The benefit of this drug in some immunologic and malignant disease is currently under being focused. Reports of synergism with cyclosporine and tacrolimus in preclinical and clinical studies, avoidance of nephrotoxicity and possible treatment or prevention of chronic allograft nephropathy are leading to high expectations for this new class of immunosuppressant. This review summarizes preclinical and clinical results published to date and evaluates the future value of PSI for renal transplantation.
Allografts ; B-Lymphocytes ; Cell Cycle ; Cyclosporine ; Everolimus ; Kidney Transplantation ; Sirolimus* ; Tacrolimus

Activation of the mammalian target of rapamycin (mTOR) signaling pathway is an important mechanism of resistance to endocrine therapy in breast cancer. Everolimus, an mTOR inhibitor, has been shown to increase the efficacy of endocrine therapy and overcome resistance to endocrine therapies. Clinical studies have suggested that everolimus combined with endocrine therapy prolongs progression-free survival in hormone receptor-positive breast cancer patients. However, because breast cancer includes a group of highly heterogeneous tumors, patients may have different responses to everolimus. Therefore, finding biomarkers that can predict a patient's positive response or resistance to everolimus is critical. Numerous preclinical studies have shown that PIK3CA/PTEN mutations are predictive of sensitivity to everolimus; however, clinical trials have not confirmed the correlation between mutation status and clinical response. KRAS or BRAF mutations can bypass the phosphatidylinositol 3-kinase pathway; therefore, mutations in KRAS or BRAF may lead to resistance to mTOR inhibitors, and preclinical studies have shown that PIK3CA mutant cells which also contain KRAS mutations are resistant to everolimus. However, there are no clinical data in breast cancer patients to support this conclusion. Therefore, large-scale clinical studies are needed to identify biomarkers of efficacy and resistance to everolimus.
Biomarkers* ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Everolimus* ; Humans ; Phosphatidylinositol 3-Kinase ; Sirolimus

Everolimus, an inhibitor of the mammalian target of the rapamycin (mTOR) pathway, is widely used as an immunosuppressant for the prevention of organ rejection following transplant and to treat metastatic clear-cell type renal cell carcinoma (RCC), breast cancer, and pancreatic neuroendocrine tumors. Everolimus commonly induces metabolic abnormalities such as hyperglycemia, hypercholesterolemia, and hypertriglyceridemia due to concomitant increases in blood glucose levels via the induction of insulin resistance and a decrease in beta cell function, which both lead to insulin deficiency. Although abnormal blood glucose levels are observed in more than 50% of patients treated with Everolimus, hyperglycemia exceeding 500 mg/dL is not common and there have been no reports of Everolimus-induced acute hyperglycemic crisis conditions. Here, a novel case of Everolimus-associated diabetic ketoacidosis (DKA) in a patient with RCC is reported.
Blood Glucose ; Breast Neoplasms ; Carcinoma, Renal Cell* ; Diabetic Ketoacidosis ; Humans ; Hypercholesterolemia ; Hyperglycemia ; Hypertriglyceridemia ; Insulin ; Insulin Resistance ; Neuroendocrine Tumors ; Sirolimus ; Everolimus

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the histolopathogical effects among the biolimus, zotarolimus, and everolimus eluting stent (EES) in the porcine coronary restenosis model. SUBJECTS AND METHODS: Pigs were randomized into three groups in which the coronary arteries (15 pigs, 10 coronaries in each group) had either a biolimus A9 eluting stent (BES, n=10), zotarolimus eluting stent (ZES, n=10) or an EES (n=10). Histopathologic analysis was performed at 28 days after stenting. RESULTS: There were no significant differences in the injury score among the three groups. There was a significant difference in the internal elastic lamina, lumen area, neointima area, percent area stenosis, and the fibrin and inflammation score among the three groups (4.3+/-0.53 mm2, 2.5+/-0.93 mm2, 1.8+/-1.03 mm2, 40.7+/-20.80%, 1.7+/-0.41, 1.4+/-0.72 in the BES group vs. 5.1+/-0.55 mm2, 2.3+/-1.14 mm2, 2.8+/-1.00 mm2, 55.4+/-21.23%, 2.0+/-0.39, 1.6+/-0.76 in the ZES group vs. 4.4+/-0.53 mm2, 1.7+/-1.22 mm2, 2.8+/-1.23 mm2, 64.0+/-26.00%, 1.8+/-0.76, 2.1+/-0.90 in the EES group, respectively). BES is more effective in inhibiting neointimal hyperplasia compared to ZES and EES (p<0.0001). According to the fibrin and inflammation score, BES and EES are more effective in decreasing the fibrin deposition compared to ZES (p<0.001). Moreover, BES and ZES are more effective in reducing the inflammatory reaction compared to EES (p<0.001). CONCLUSION: The result demonstrates that BES shows better histopathological characteristics than ZES and EES at one month after stenting in the porcine coronary restenosis model.
Alkanesulfonic Acids ; Constriction, Pathologic ; Coronary Restenosis* ; Coronary Vessels ; Drug-Eluting Stents ; Fibrin ; Hyperplasia ; Inflammation ; Neointima ; Percutaneous Coronary Intervention ; Sirolimus ; Stents* ; Swine ; Everolimus

BACKGROUND: Everolimus and cyclosporine (CsA) exhibit synergistic immunosuppressive activity when used in combination. We analyzed preliminary data about the use of everolimus with a CsA-sparing strategy in de novo renal transplant recipients. METHODS: A comparative, parallel, randomized, open-label, 1 year study has been performed in 117 patients from 5 transplant centers to compare the efficacy and tolerability of everolimus (EVE)+reduced-dose CsA or enteric-coated mycophenolate sodium (Myfortic)+standard-dose CsA in combination with basiliximab and steroids. It ended on August 24, 2011. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated at 1, 3, 5, and 12 months post-transplantation. RESULTS: Efficacy failure was comparable between the two groups. Only one graft loss has been reported in the control group and no patient death reported in either group. There was no significant difference in the incidence of biopsy-proven acute rejection until 3 and 5 month post-transplantation (P>0.05). The mean e-GFR of the group of EVE+reduced-dose CsA was significantly higher than that of the control group at 3 (65.6+/-16.9 mL/mim/1.73 m2 vs. 56.7+/-14.4 mL/mim/1.73 m2; P=0.007) and 5 (68.6+/-18.8 mL/mim/1.73 m2 vs. 58.1+/-16.2 mL/mim/1.73 m2; P=0.009) months. There was no significant difference in the incidence of discontinuations and serious adverse events between the groups (P>0.05). CONCLUSIONS: The regimen of EVE+reduced-dose CsA seems to be tolerated well, with comparable efficacy failure and better renal function than enteric-coated mycophenolate sodium+standard-dose CsA.
Antibodies, Monoclonal ; Cyclosporine ; Everolimus ; Graft Rejection ; Humans ; Immunosuppression ; Incidence ; Kidney ; Kidney Transplantation ; Mycophenolic Acid ; Recombinant Fusion Proteins ; Rejection (Psychology) ; Sirolimus ; Sodium ; Steroids ; Transplants

Everolimus, an inhibitor of the mammalian target of rapamycin, is an active agent against metastatic renal cell carcinoma. Treatment with everolimus prolongs progression-free survival in patients with clear cell-type renal cell carcinoma that has progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitors, such as sunitinib and/or sorafenib. Everolimus-induced interstitial pneumonitis is not rare and is sometimes fatal. Due to the potential for pulmonary toxicity due to everolimus, it is recommended that pulmonary complications be periodically evaluated. We report a case of everolimus-associated interstitial pneumonitis in a patient with metastatic renal cell carcinoma.
Carcinoma, Renal Cell ; Disease-Free Survival ; Humans ; Indoles ; Lung Diseases, Interstitial ; Niacinamide ; Phenylurea Compounds ; Protein-Tyrosine Kinases ; Pyrroles ; Receptors, Vascular Endothelial Growth Factor ; Sirolimus ; Everolimus

Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with mast cell activation following an allergic insult. We report a 56-year-old man who experienced a ST-segment elevation myocardial infarction after wasp stings. The patient presented without signs of anaphylaxis or shock. Coronary angiography showed an everolimus-eluting stent thrombosis (ST) of the left anterior descending artery occluding the vessel completely which was deployed for stable angina 3 years ago. The patient had been compliant with anti-platelet therapy, and no relevant cardiovascular events occurred until the day of admission. We interpreted our patient's condition as a manifestation of Kounis syndrome. To our knowledge, this is the first case of Kounis syndrome showing very late ST in a second-generation drug-eluting stent caused by wasp stings.
Acute Coronary Syndrome ; Angina, Stable ; Bites and Stings ; Coronary Angiography ; Drug-Eluting Stents ; Humans ; Hypersensitivity ; Mast Cells ; Middle Aged ; Myocardial Infarction ; Sirolimus ; Stents ; Thrombosis ; Wasps ; Everolimus

Mammalian target of rapamycin inhibitors (mTOR-I)* is a novel immunosuppressive agent that has the variable action mode, such as anti-fibroblastic, anti-tumor and anti-atherosclerotic effect, but doesn't have a nephrotoxicity. Since March 2006, two types of mTOR-I, sirolimus and everolimus, are clinically available in Korea. In this article, we summarize the pharmacologic characteristics of mTOR-I and review the clinical application of mTOR-I as the component of immunosuppressive regimen after kidney transplantation. Sirolimus and everolimus share the same action mode resulting in an arrest of cell cycle (G1 to S phase arrest). Despite the similarities of chemical structure between sirolimus and everolimus, there are remarkable pharmacokinetic differences between the two molecules. In summary, the half-life and time to reach steady state of everolimus is shorter than those of sirolimus. Therefore, there are significant difference in administration interval and mode. Four types of clinical application of mTOR-I were tried in de Novo renal transplant recipients; (1) for replacement of calcineurin inhibitor (CNI), (2) for replacement of antimetabolites, (3) in combination CNI with low dose mTOR-I versus high dose mTOR-I, (4) standard dose CNI plus low dose mTOR-I versus low dose CNI plus high dose mTOR-I. Generally, mTOR-I shows superior results in graft survival rate, acute rejection free rate and graft renal function (eGFR), but shows inferior results in maintenance rate of regimen and occurrence of side effect (such as proteinuria, wound healing problem and dyslipidemia). Conversion from CNI to mTOR-I was tried in recipients with de Novo post- transplant malignancy or chronic allograft dysfunction. These clinical trial data suggest that mTOR-I may be useful in management of selective type of post-transplant malignancy (such as non-melanoma skin cancer, Kaposi's sarcoma and post- transplant lymphoproliferative disease) or chronic allograft dysfunction with CNI nephrotoxicity. Clinical application of mTOR-I makes variable combination of immunosuppressive agent possible. Therefore, it is possible to make the selective or tailored immunosuppressive regimen that yields the best outcome with minimal adverse effect.
Antimetabolites ; Calcineurin ; Cell Cycle ; Everolimus ; Graft Survival ; Half-Life ; Kidney ; Kidney Transplantation ; Korea ; Proteinuria ; Rejection (Psychology) ; S Phase ; Sarcoma, Kaposi ; Sirolimus ; Skin Neoplasms ; Transplantation, Homologous ; Transplants ; Wound Healing

Hepatocellular carcinoma (HCC) is a highly malignant tumor that has limited treatment options in its advanced state. The efficacy of current anti-cancer chemotherapy in advanced HCC has not been satisfactory, and the management of HCC remains a major challenge for physicians. However, recent advancement in our understanding of the molecular mechanisms underlying carcinogenesis has provided novel targets in key signaling pathways for tumor development. Recently, Sorafenib (Nexavar), a multi-kinase inhibitor targeting membrane receptors involved in angiogenic and mitogenic intra-cellular signaling including Raf, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptors (PDGFR), has been approved worldwide as a new target agent for HCC, and subsequent clinical trials of newly developed molecular target agents such as Brivanib and Everolimus are being conducted globally. In the near future, continued research will lead to the identification of additional molecular targets in HCC and lead to treatments with enhanced efficacy and improved tolerability.
Alanine ; Carcinoma, Hepatocellular ; Membranes ; Molecular Targeted Therapy ; Niacinamide ; Phenylurea Compounds ; Receptors, Platelet-Derived Growth Factor ; Receptors, Vascular Endothelial Growth Factor ; Signal Transduction ; Sirolimus ; Triazines ; Everolimus