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Deborah E Joekel, Britta Lundström-Stadelmann, Beat Müllhaupt, Andrew Hemphill, Peter Deplazes
Infection with the larval stage (metacestode) of the fox tapeworm Echinococcus multilocularis leads to a primary hepatic disease referred to as alveolar echinococcosis (AE). The progressive disease can be lethal if untreated. In cases where complete parasite resection by surgery is not feasible, the current treatment regimens of AE consist of chemotherapy with the parasitostatic benzimidazoles albendazole or mebendazole over decades. Kinase-inhibitors currently administered in various cancer treatments are of increasing interest also as anti-parasitic drugs due to previous promising in vitro results...
April 3, 2018: Experimental Parasitology
Steve J Edwards, Victoria Wakefield, Peter Cain, Charlotta Karner, Kayleigh Kew, Mariana Bacelar, Natalie Masento, Fatima Salih
BACKGROUND: Several therapies have recently been approved for use in the NHS for pretreated advanced or metastatic renal cell carcinoma (amRCC), but there is a lack of comparative evidence to guide decisions between them. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of axitinib (Inlyta®, Pfizer Inc., NY, USA), cabozantinib (Cabometyx®, Ipsen, Slough, UK), everolimus (Afinitor®, Novartis, Basel, Switzerland), nivolumab (Opdivo®, Bristol-Myers Squibb, NY, USA), sunitinib (Sutent®, Pfizer, Inc...
January 2018: Health Technology Assessment: HTA
Nancy D Perrier
INTRODUCTION: Pancreas, parathyroid, and pituitary, are referred to as the "3 Ps" of MEN1. The time has come to move beyond those Ps and begin to discuss (1) prediction, (2) pausing progression, and (3) prevention of MEN1. METHODS: In preparation for the International Association of Endocrine Surgeons State of the Art address, updates and uncertainties of MEN were reviewed. This included a detailed examination of the MEN1 gene and the library of implicated mutations, exon sequencing databases and cell cycle pathways...
April 2018: World Journal of Surgery
Hoda Abel Mahedi Mohamed, Charlotte Emilie Nor Nielsen, Morten Schiodt
OBJECTIVE: The aim of this study was to report cases of medication-related osteonecrosis of the jaws (MRONJ) associated with targeted therapy (TT) with or without concomitant antiresorptive treatment, among the Copenhagen ONJ cohort, which includes all consecutive cases of MRONJ seen in Copenhagen. STUDY DESIGN: We retrospectively studied the treatment of 204 consecutive patients with MRONJ, seen between January 2010 and May 2016, to identify those associated with TT...
February 2018: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Ali Yaghobi Joybari, Payam Azadeh
BACKGROUND Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome manifested by a spectrum of benign and malignant tumors.  CASE REPORT The patient presented here was a 31-year-old female with unremarkable family history who presented initially complaining of intermittent abdominal pain. Abdominal CT scan revealed an inhomogeneous solid mass (13×9×7 cm) originating from the tail of the pancreas with splenic and gastric invasion as well as several pancreatic cysts. A nucleotide scan showed left adrenal involvement...
November 17, 2017: American Journal of Case Reports
Hoda Anwar, Christos Sachpekidis, Matthias Schwarzbach, Antonia Dimitrakopoulou-Strauss
We report on a 27 years old female patient who was referred to our department for whole-body as well as dynamic positron emission tomography/computed tomography (dPET/CT) scan of the upper and middle abdomen with fluorine-18-fluorodeoxy glucose ((18)F-FDG), for further evaluation of a mass in the left adrenal gland region. Positron emission tomography showed a suspicious, enlarged, hypermetabolic mass with an average standardized uptake value (SUV) of 4.5 and a maximum SUV of 5.9. The patient was referred for biopsy, which revealed an angiomyolipoma, a perivascular epithelioid cell tumor (PEComa) of the adrenal gland...
May 2017: Hellenic Journal of Nuclear Medicine
Stephen H Hare, Amanda J Harvey
The mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces hygroscopicus. mTOR is serine/threonine kinase belonging to the phosphoinositide 3-kinase related kinase (PIKK) family. It forms two distinct complexes; mTORC1 and mTORC2. mTORC1 has a key role in regulating protein synthesis and autophagy whilst mTORC2 is involved in regulating kinases of the AGC family. mTOR signaling is often over active in multiple cancer types including breast cancer...
2017: American Journal of Cancer Research
Steve Malangone, Christopher J Campen
A 60-year-old man initially presented with pain in the right upper quadrant in October 2010. A computed tomography (CT) scan of the abdomen pelvis completed at that time showed a mass at the junction of the body and tail of the pancreas and multiple large liver lesions. A CT-guided liver biopsy revealed low-grade neuroendocrine carcinoma. The patient was initially started on systemic treatment with sunitinib (Sutent) and octreotide. He developed intolerable side effects, including nausea and migraine. Therapy was discontinued in October 2011, when a CT scan revealed evidence of disease progression...
November 2015: Journal of the Advanced Practitioner in Oncology
Asona Lui, Jacob New, Joshua Ogony, Sufi Thomas, Joan Lewis-Wambi
BACKGROUND: mTOR inhibition of aromatase inhibitor (AI)-resistant breast cancer is currently under evaluation in the clinic. Everolimus/RAD001 (Afinitor®) has had limited efficacy as a solo agent but is projected to become part of combination therapy for AI-resistant breast cancer. This study was conducted to investigate the anti-proliferative and resistance mechanisms of everolimus in AI-resistant breast cancer cells. METHODS: In this study we utilized two AI-resistant breast cancer cell lines, MCF-7:5C and MCF-7:2A, which were clonally derived from estrogen receptor positive (ER+) MCF-7 breast cancer cells following long-term estrogen deprivation...
July 16, 2016: BMC Cancer
Stéphane Oudard, Florence Joly, Lionnel Geoffrois, Brigitte Laguerre, Nadine Houede, Philippe Barthelemy, Marine Gross-Goupil, Yann Vano, Oliver Lucidarme, Francois Bidault, Nadia Kelkouli, Khemaies Slimane, Bernard Escudier
BACKGROUND: Real-world data of everolimus after vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy in metastatic renal cell carcinoma (mRCC) are limited. PATIENTS AND METHODS: The retrospective, noninterventional SECTOR (SECond line with afiniTOR) study (N = 165) assessed outcomes of second-line everolimus after initial VEGFR-TKI (TKI-everolimus, n = 144) and of third-line VEGFR-TKI after everolimus (TKI-everolimus-TKI, n = 59) in patients with mRCC...
December 2016: Clinical Genitourinary Cancer
L V Spirina, E A Usynin, I V Kondakova, Z A Yurmazov, E M Slonimskaya
We analyzed the dynamics of the expression of transcription factors, VEGF and its receptor VEGFR2, serine-threonine protein kinase mTOR and activity of proteasome and calpain in patients with metastatic renal cancer during therapy with tyrosine kinase inhibitor Votrient and mTOR blocker Afinitor. The expression of hypoxic nuclear factor HIF-1α in the tumor tissue decreased during therapy with the target preparations. The decrease of VEGF and its receptor VEGFR2 was observed only in patients treated with mTOR inhibitor...
April 2016: Bulletin of Experimental Biology and Medicine
A Rose Brannon, Melissa Frizziero, David Chen, Jennifer Hummel, Jorge Gallo, Markus Riester, Parul Patel, Wing Cheung, Michael Morrissey, Carmine Carbone, Silvia Cottini, Giampaolo Tortora, Davide Melisi
The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER(+)/HER2(-) metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR(+))/HER2(-) stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy...
March 2016: Cold Spring Harbor Molecular Case Studies
Bartosz Szymanowski, Renata Duchnowska, Marek Bilski, Grażyna Łapińska, Beata Hryciuk, Grzegorz Kamiński, Cezary Szczylik
We are reporting a case of a 55-year-old woman who was diagnosed as having a non-functioning pancreatic neuroendocrine neoplasm (NF-PNEN), the World Health Organization (WHO) low grade (G1) with liver metastases. In the staging process the positron emission tomography - computed tomography with Fluorine-18-Fluorodeoxyglucose (F-FDG PET-CT) and spiral CT then the gallium-DOTA-octreotate positron emission tomography - computer tomography (⁶⁸Ga-DOTATATE PET-CT) shown difference in burden of disease. In first line therapy, everolimus (Afinitor®, Novartis Pharma GmbH, Germany) at the oral dose of 10 mg once daily and octreotide long-acting release (Sandostatin LAR®) 30 mg i...
2016: Nuclear Medicine Review. Central & Eastern Europe
Mélanie Pouget, Catherine Abrial, Eloise Planchat, Isabelle Van Praagh, Marie Arbre, Fabrice Kwiatkowski, Pascale Dubray-Longeras, Hervé Devaud, Joyce Dohou, Pauline Herviou, Hakim Mahammedi, Xavier Durando, Philippe Chollet, Marie-Ange Mouret-Reynier
BACKGROUND: Everolimus (Afinitor®) plus exemestane are indicated for hormone receptor-positive, HER2/neu-negative metastatic breast cancer (MBC), in menopausal women without symptomatic visceral disease after recurrence or progression following aromatase inhibitors. But everolimus efficacy as late treatment has not been explored. METHODS: Sixty-three MBC patients progressing under hormonotherapy (HT; n = 30) or after chemotherapy (CT; n = 32) received everolimus plus HT (EHT) and were analyzed for safety, efficacy and overall survival (OS)...
2015: Oncology
Avital Nahmias, Simona Grozinsky-Glasberg, Asher Salmon, David J Gross
UNLABELLED: Approximately 35% of the pancreatic neuroendocrine tumors (pNETs) are functional, the most common of which is an insulinoma. Rarely can initially nonfunctioning tumor undergo biological transformation to a hormone-secreting tumor with subsequent changes in the clinical picture. We present here three unique patients with long-standing pNETs who developed life-threatening hyperinsulinemic hypoglycemia along with tumor progression. In two of the patients, everolimus (Afinitor) was administered in an attempt to control both tumor growth and hypoglycemia...
2015: Endocrinology, Diabetes & Metabolism Case Reports
G Jerusalem, A Rorive, J Collignon
Sequential endocrine treatments are recommended for estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER 2) negative metastatic breast cancers except in the case of symptomatic visceral disease. However, patients who suffer from disease progression while receiving a non-steroidal aromatase inhibitor (NSAI) have a very poor prognosis with standard endocrine therapy alone. Recently, based onthe results of the BOLERO 2 trial, the mammalian target of rapamycin (mTOR) inhibitor everolimus, combined with exemestane, a steroidal aromatase inhibitor, has been approved in Europe and the US for patients suffering from ER positive HER2 negative advanced breast cancer previously treated by a NSAI...
September 2014: Revue Médicale de Liège
Sara A Hurvitz, Ondrej Kalous, Dylan Conklin, Amrita J Desai, Judy Dering, Lee Anderson, Neil A O'Brien, Teodora Kolarova, Richard S Finn, Ronald Linnartz, David Chen, Dennis J Slamon
Everolimus (RAD001, Afinitor(®)) is an oral, selective mTOR inhibitor recently approved by the US-FDA in combination with exemestane for treatment of hormone receptor positive advanced breast cancer. To date, no molecular predictors of response to everolimus in breast cancer have been identified. We hypothesized predictive markers could be identified using preclinical models. Using a molecularly characterized panel of human breast cancer and immortalized breast epithelial cell lines, we determined sensitivity to everolimus alone or in combination with ER- or HER2- targeted therapy...
February 2015: Breast Cancer Research and Treatment
Wael A Harb
Endocrine therapy is an important treatment option for women with hormone receptor-positive (HR+) advanced breast cancer (ABC), yet many tumors are either intrinsically resistant or develop resistance to these therapies. Treatment of patients with ABC presenting with visceral metastases, which is associated with a poor prognosis, is also problematic. There is an unmet need for effective treatments for this patient population. Although chemotherapy is commonly perceived to be more effective than endocrine therapy in managing visceral metastases, patients who are not in visceral crisis might benefit from endocrine therapy, avoiding chemotherapy-associated toxicities that might affect quality of life...
2015: Cancer Management and Research
Antoine Thiery-Vuillemin, Christine Theodore, Lutz Jacobasch, Jörg Schmitz, Christos Papandreou, Aline Guillot, Christos Emmanouilides, Khemaies Slimane, Nadia Kelkouli, Stefano Kim, Thierry Nguyen Tan Hon
BACKGROUND: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism 1) trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients with mRCC...
June 2015: Clinical Genitourinary Cancer
Eleni-Marina Kalogirou, Konstantinos I Tosios, Evangelia P Piperi, Alexandra Sklavounou
Mammalian targets of rapamycin inhibitors (mTOR inhibitors, mTORI) are indicated for the management of several cancer types, including hormone receptor--positive or HER2-negative breast cancer, advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, and tuberous sclerosis complex-related tumors. Among the most common adverse events of mTORI medication are discrete, large, solitary or multiple, superficial ulcers, almost exclusively situated on nonkeratinized oral mucosa, described as mTORI-associated stomatitis (mIAS)...
January 2015: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
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