No abstract available.
Everolimus* ; Eyelids* ; Humans ; Tuberous Sclerosis*

No abstract available.
Carcinoma, Renal Cell* ; Everolimus ; Humans ; Mycobacterium tuberculosis* ; Mycobacterium*

Pancreatic neuroendocrine tumors (pNETs) are diverse diseases with different prognosis. Among available various therapeutic options, curative resection should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs are used to control hormonal symptoms and also effective to inhibit the tumor progression in specific settings. The molecular targeted agents such as sunitinib and everolimus are efficacious treatments for metastatic WHO grade 1/2 pNETs. Chemotherapy is generally used in highly symptomatic and rapidly growing pNETs such as WHO grade 3. In addition, local ablative therapy should be considered in patients with hepatic predominant unresectable metastatic pNETs, and peptide receptor radionucleotide therapy, which is unavailable in Korea, could be considered after failure of initial medical therapy. The most important of all is a multidisciplinary approach to pNETs. This is essential to optimal management of pNETs regarding the diverse disease nature
Drug Therapy ; Everolimus ; Humans ; Korea ; Neuroectodermal Tumors, Primitive ; Neuroendocrine Tumors* ; Prognosis ; Receptors, Peptide ; Somatostatin

Neuroendocrine carcinoma (NEC) has been reported to comprise 25% of lung cancer cases. NEC is classified as typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma, and small-cell lung cancer. Carcinoid tumors are less aggressive and surgery is the mainstay of treatment; however, patients with metastatic or inoperable disease need systemic therapy to control carcinoid symptoms and improve survival. Somatostain analogues, targeted agents including everolimus, sunitinib, bevacizumab, and conventional chemotherapy have emerged as treatment options for such patients. Large-cell neuroendocrine carcinoma exhibits more aggressive behavior and has a poorer prognosis than carcinoid tumors. No standard adjuvant and palliative chemotherapeutic agents have yet been established. This review sets out the treatment options for neuroendocrine tumors.
Adenocarcinoma* ; Carcinoid Tumor ; Carcinoma, Neuroendocrine* ; Drug Therapy* ; Humans ; Lung Neoplasms ; Lung* ; Neuroendocrine Tumors ; Prognosis ; Bevacizumab ; Everolimus

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

Cardiac allograft vasculopathy is one of the most important causes of poor long-term survival after heart transplantation. The condition tends to be diffuse, usually affecting the mid-to-distal portions of the coronary artery. Reperfusion therapy is ineffective. Everolimus, an inhibitor of proliferation signaling, has been reported to prevent development of the condition; however, the efficacy thereof has not yet been fully accepted. The only definitive treatment for cardiac allograft vasculopathy is retransplantation. Herein, we describe the case of a 15-year-old boy who underwent heart retransplantation because of rapidly progressive cardiac allograft vasculopathy.
Adolescent ; Allografts* ; Coronary Vessels ; Everolimus ; Heart Transplantation ; Heart* ; Humans ; Male ; Reperfusion

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

BACKGROUND AND OBJECTIVES: Previous studies suggest that phenotypic conversion, proliferation and migration of adventitial fibroblasts after balloon injury have an important role in neointimal formation and vascular remodeling. The present study evaluated whether orally administered everolimus (a macrolide of the same family as sirolimus) reduces adventitial cell activation and neointimal formation in balloon-injured rat carotid arteries. MATERIALS AND METHODS: Oral everolimus (1.25 mg/kg/day), or a matching placebo, was administered daily to 30 rats by gavage, starting 3 days before balloon injury. The treatment effects were assessed 3, 7 and 14 days after injury. RESULTS: The oral everolimus group showed a significant reduction in adventitial cell proliferation at 3 days after injury and significant neointimal formation reduction compared to the control group at 7 and 14 days after injury (control group 0.06+/-0.01 mm2, everolimus group 0.01+/-0.01 mm2, p<0.01 and control group 0.28+/-0.06 mm2, everolimus group 0.08+/-0.03 mm2, p0.01). CONCLUSION: Oral everolimus reduces adventitial cell activation and neointima formation in balloon injured rat carotid arteries.
Angioplasty ; Animals ; Carotid Arteries* ; Cell Proliferation ; Fibroblasts ; Humans ; Neointima* ; Rats* ; Everolimus

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

To systematically review relevant literature on efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. In platinum pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer median overall survival (OS; 10.3 months vs. 7.4 months), a higher objective response rate (ORR; 21.1% vs. 11.4%, p=0.001), and a lower adverse event rate (60.9% vs. 90.2%). Three randomized controlled trials (RCTs) assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 months vs. 19.6 months) and the ORR (25% vs. 5%) were higher in patients treated with nivolumab compared with second-line everolimus. In patients with metastatic castration-resistant prostate cancer, 2 RCTs were identified, which did not show significant benefits for ipilimumab over placebo. In UCC and RCC, there was no conclusive association between programmed cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment, respectively. Therefore, in metastatic UCC and RCC, pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus, respectively. No beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome.
Carcinoma, Renal Cell ; Cell Death ; Drug Therapy ; Everolimus ; Humans ; Immunotherapy ; Platinum ; Prostatic Neoplasms ; Treatment Outcome ; Urologic Neoplasms