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Delia De Lisi, Ugo De Giorgi, Cristian Lolli, Giuseppe Schepisi, Vincenza Conteduca, Cecilia Menna, Giuseppe Tonini, Daniele Santini, Alberto Farolfi
To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular PI3K/AKT/mTOR pathway...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Ida Robertsen, Jean Debord, Anders Åsberg, Pierre Marquet, Jean-Baptiste Woillard
BACKGROUND AND OBJECTIVE: Intracellular exposure of everolimus may be a better marker of therapeutic effect than trough whole blood concentrations. We aimed to develop pharmacokinetic population models and Bayesian estimators based on a limited sampling strategy for estimation of dose interval exposures of everolimus in whole blood and peripheral blood mononuclear cells (PBMCs) in renal transplant recipients. METHODS: Full whole blood and PBMC concentration-time profiles of everolimus were obtained from 12 stable renal transplant recipients on two different occasions, 4 weeks apart...
March 20, 2018: Clinical Pharmacokinetics
Masashi Sakuma, Takahisa Nasuno, Shichiro Abe, Syotaro Obi, Shigeru Toyoda, Isao Taguchi, Ryoichi Sohma, Ken-Ichi Inoue, Setsu Nishino, Koichi Node, Guiherme Attizzani, Hiram Bezerra, Marco Costa, Daniel Simon, Teruo Inoue
Background: Bone marrow-derived progenitor cells likely contribute to both endothelial- and smooth muscle cell-dependent healing responses in stent-injured vessel sites. This study aimed to assess mobilization of progenitor cells and vessel healing after zotarolimus-eluting (ZES) and everolimus-eluting (EES) stents. Methods and results: In 63 patients undergoing coronary stent implantation, we measured circulating CD34 + CD133 + CD45low cells and serum levels of biomarkers relevant to stem cell mobilization...
March 2018: IJC Heart & Vasculature
Hiroshi Nomoto, Hideaki Miyoshi, Tomonori Sekizaki, Tatsuya Atsumi
No abstract text is available yet for this article.
March 16, 2018: Annals of Thoracic and Cardiovascular Surgery
Şuayib Yalçın, Ramazan Yildiz, Faysal Dane, Aziz Karaoğlu, Berna Öksüzoğlu, Özgür Özyılkan, Alper Sevinç, Feyyaz Özdemir, Hande Turna, Rüçhan Uslu, Esat Ulay
Introduction: The introduction of targeted therapies in renal cell carcinoma has significantly improved its prognosis and treatment outcomes in recent years. Such treatment options are targeted therapies of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of the rapamycin pathway. With the use of tyrosine kinase inhibitors (TKIs) and mammalian target of the rapamycin inhibitors, overall survival has increased up to 2 years. In Turkey, due to applicable reimbursement conditions for patients with metastatic renal cell carcinoma (mRCC), interferon use is mandated as a first-line treatment, thus providing information on the use of everolimus only after initial interferon and second-line VEGF-targeted treatments such as VEGF-TKI...
2018: OncoTargets and Therapy
Babita Saigal, Laura Guerra
BACKGROUND: A common class-specific toxicity of mammalian target of rapamycin (mTOR) inhibitors is stomatitis. Some patients experience a severe form of mTOR inhibitor-associated stomatitis (mIAS) that can have a negative effect on nutritional status, compromise quality of life, and potentially lead to nonadherence, reducing the efficacy of cancer therapy. OBJECTIVES: This article aims to address an unmet need for education about mIAS among oncology nurses and patients and to share findings about everolimus-related stomatitis from the SWISH trial...
April 1, 2018: Clinical Journal of Oncology Nursing
Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Yumiko Akamine, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3 / *3 . The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation...
March 16, 2018: International Journal of Molecular Sciences
Tobias Koppara, Tomohisa Tada, Erion Xhepa, Sebastian Kufner, Robert A Byrne, Tareq Ibrahim, Karl-Ludwig Laugwitz, Adnan Kastrati, Michael Joner
BACKGROUND: Drug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. METHODS: We compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months...
May 1, 2018: International Journal of Cardiology
Hua Ye, Xuyu Chai, Xiaoyu Wang, Qi Zheng, Dingcheng Zheng, Feng Wu, Cheng Zheng, Ping Chen
The autophagy involved in the occurrence, development and prognosis of human epidermal growth factor receptor 2 (HER2) gene-amplified cancer also controls the resistance of this type of cancer to the monoclonal antibody, trastuzumab (Tzb). In the present study, Tzb resistance was established in HER2-positive NCI-N87 cell lines (Tzb-refractory cells). The cell viability, clonogenic assay, ratios of light chain 3 II/I, sequestosome 1 expression, and the phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) were investigated in the parental and Tzb-refractory cells...
April 2018: Oncology Letters
Laura Rosenberg, Charles H Yoon, Gaurav Sharma, Monica M Bertagnolli, Nancy L Cho
Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known anti-tumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action...
March 10, 2018: Carcinogenesis
Salvatore Cassese, Gjin Ndrepepa, Robert A Byrne, Sebastian Kufner, Anna Lena Lahmann, Nader Mankerious, Erion Xhepa, Karl-Ludwig Laugwitz, Heribert Schunkert, Massimiliano Fusaro, Adnan Kastrati, Michael Joner
AIMS: The ultrathin strut biodegradable-polymer sirolimus-eluting stent (SES) is a new-generation drug-eluting stent (DES) developed to improve the percutaneous treatment of patients with coronary artery disease. Here, we sought to investigate whether the performance of ultrathin strut biodegradable-polymer SES is superior to that of the benchmark thin-strut fluoropolymer-based everolimus-eluting stent (EES). METHODS AND RESULTS: We undertook a study-level meta-analysis of trials, in which patients receiving percutaneous coronary intervention (PCI) were randomly assigned to either SES or EES...
March 13, 2018: EuroIntervention
J Bennett, T Adriaenssens, K McCutcheon, J Dens, W Desmet, P Sinnaeve, M Vrolix, C Dubois
OBJECTIVES: We evaluated healing responses with optical coherence tomography, and long-term clinical outcomes after treatment with a dedicated stent versus a conventional culotte technique. BACKGROUND: Dedicated bifurcation stents have been proposed as an alternative treatment for coronary bifurcation lesions. The long-term performance of dedicated stents versus conventional dual-stent techniques for the treatment of complex coronary bifurcation lesions is unknown...
March 14, 2018: Catheterization and Cardiovascular Interventions
Shin Hwang, Chul-Soo Ahn, Ki-Hun Kim, Deok-Bog Moon, Tae-Yong Ha, Gi-Won Song, Dong-Hwan Jung, Gil-Chun Park, Sung-Gyu Lee
Backgrounds/Aims: Long-term immunosuppression regimens after liver transplantation (LT) are rarely reported in detail. We aimed to provide information on actual long-term immunosuppression regimens through this cross-sectional study. Methods: Our institutional LT database was searched for adult patients who underwent primary LT operation from 2000 to 2016. We identified 3620 live recipients with actual information on immunosuppressive agent use for 1-17 years. Results: The study cohort was divided into 7 groups according to posttransplantation period...
February 2018: Annals of Hepato-Biliary-Pancreatic Surgery
Tala Achkar, Siraj M Ali, Allison Welsh, Rajiv Dhir, Susanne M Gollin, Rahul A Parikh
Tumor genome sequencing has become an invaluable resource in determining targets for new therapies. In this report, we describe the case of a patient with metastatic urothelial carcinoma with sarcomatoid features. Sarcomatoid differentiation is a rare histologic subtype that confers a more aggressive course. The first-line treatment for patients with urothelial carcinoma is platinum-based chemotherapy. Next generation tumor sequencing performed using the FoundationOne assay revealed loss of one NF2 allele and an unbalanced der(22)t(10;22)(p11...
March 13, 2018: Genes, Chromosomes & Cancer
David K Lau, Rebecca Y Tay, Yvonne H Yeung, Fiona Chionh, Jennifer Mooi, Carmel Murone, Effie Skrinos, Timothy J Price, John M Mariadason, Niall C Tebbutt
BACKGROUND: Advanced biliary tract cancers (BTCs) have a poor prognosis and limited treatment options. This exploratory phase II study aimed to evaluate the activity of the mTOR inhibitor everolimus in advanced BTC and explore prognostic biomarkers. METHODS: Patients with advanced BTCs, who had not received chemotherapy for advanced disease, were enroled to receive everolimus (10 mg daily). The primary endpoint was disease control rate (DCR) at 12 weeks. Secondary endpoints included overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events...
March 12, 2018: British Journal of Cancer
Misato Okazaki, Yoshiya Horimoto, Masahiko Tanabe, Yuko Ichikawa, Emi Tokuda, Atsushi Arakawa, Toshiyuki Kobayashi, Mitsue Saito
Metastatic breast cancer (MBC) is essentially incurable despite recent improvements in systemic therapies. We often encounter difficulties in choosing the most appropriate treatments, with optimal timing, for individual patients. Everolimus, one of the mTOR inhibitors, is usually used with endocrine therapy for MBC. Identification of predictive markers for everolimus-based treatment remains a major issue, but to date, no predictive markers have been established. We retrospectively investigated predictive markers for treatments with everolimus plus exemestane in patients with ER-positive and HER2-negative breast cancer...
March 8, 2018: Medical Oncology
Paolo Zocca, Marlies M Kok, Kenneth Tandjung, Peter W Danse, Gillian A J Jessurun, Raymond W M Hautvast, K Gert van Houwelingen, Martin G Stoel, Alexander R Schramm, R Melvyn Tjon Joe Gin, Frits H A F de Man, Marc Hartmann, J Hans W Louwerenburg, Gerard C M Linssen, Marije M Löwik, Carine J M Doggen, Clemens von Birgelen
OBJECTIVES: The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents (ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts). BACKGROUND: The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents...
March 12, 2018: JACC. Cardiovascular Interventions
Toshirou Fukushima, Daisuke Gomi, Noriko Seno, Takahiko Gibo, Takashi Kobayashi, Nodoka Sekiguchi, Hirohide Matsushita, Yoshiko Kasahara, Keiko Mamiya, Tomonobu Koizumi
Pulmonary neuroendocrine tumors are rare, and there have been very few reports regarding optimal chemotherapeutic regimens. Two molecular targeted agents, everolimus and sunitinib, have recently been shown to provide an additional treatment benefit for pulmonary neuroendocrine tumors. However, little information is available regarding the usefulness of streptozocin chemotherapy. Here, we encountered a case of relapsed and refractory mediastinal atypical carcinoid tumor associated with multiple endocrine neoplasia type 1 for various cytotoxic and molecular targeted agents...
January 2018: Case Reports in Oncology
Giuseppe Tarantini, Giulia Masiero, Alberto Barioli, Valeria Paradies, Georgios Vlachojannis, Paola Tellaroli, Bernardo Cortese, Gaetano di Palma, Attilio Varricchio, Alfonso Ielasi, Bruno Loi, Giuseppe Steffenino, Daisuke Ueshima, Marco Mojoli, Pieter Smits
BACKGROUND: Patients with small vessel disease (SVD) are at higher risk of adverse events after PCI compared to non-SVD patients. In this subset, the use of bioresorbable vascular scaffolds (BVS) has raised particular concern. OBJECTIVE: We aimed to compare outcomes of Absorb BVS versus a 2nd-generation metallic everolimus-eluting stents (EES) in the SVD setting, by pooling patients from three large, prospective studies. METHODS: Patients with SVD (reference vessel diameter ≤2...
March 7, 2018: Catheterization and Cardiovascular Interventions
Rajiv Ananthakrishna, William Kristanto, Li Liu, Siew-Pang Chan, Poay Huan Loh, Edgar L Tay, Koo Hui Chan, Mark Y Chan, Chi-Hang Lee, Adrian F Low, Huay Cheem Tan, Joshua P Loh
OBJECTIVES: To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population. BACKGROUND: Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months. METHODS: This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015...
March 7, 2018: Catheterization and Cardiovascular Interventions
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