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Pedro Arriola-Villalobos, Blanca Benito-Pascual, David Díaz-Valle, José M Benítez-Del-Castillo
PURPOSE: To report 2 cases of cornea verticillata (CV) after vandetanib treatment for medullary thyroid carcinoma (MTC). METHODS: In this retrospective interventional, case-report study, 2 patients who under vandetanib treatment for MTC were referred to our ophthalmology department because of vision complaints. Both subjects underwent a complete ophthalmologic examination, including confocal microscopy (CM) using the Heidelberg Retina Tomograph and Rostock Cornea Module...
March 6, 2018: Cornea
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Anna Fioravanti, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice...
March 8, 2018: Oncology Reports
Nicholas Thomas, John Glod, Claudia Derse-Anthony, Emma L Baple, Nigel Obsborne, Rachel Sturley, Bijay Vaidya, Kate Newbold, Antonia Brooke
Vandetanib is a tyrosine kinase inhibitor (TKI) used in the treatment of medullary thyroid carcinoma occurring in >95% of patients with multiple endocrine neoplasia type 2b (MEN 2b). Pregnancy in women with MEN 2b on vandetanib is previously unreported and has multiple potential implications for both the mother and developing fetus [1]. We describe the case of a 22 year old woman with a background of MEN 2b who was first diagnosed aged 6 presenting with marfanoid habitus, and oral mucosal neuromas. This article is protected by copyright...
February 19, 2018: Clinical Endocrinology
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
Ekaterini Christina Tampaki, Athanasios Tampakis, Raoul Droeser, Efstratios Patsouris, Gregory Kouraklis
No abstract text is available yet for this article.
February 14, 2018: Cancer Biology & Therapy
Changchun Li, Chao Yang, Guanghui Wei
Resistance is the major cause of cisplatin treatment failure in neuroblastoma (NB). Vandetanib is widely used in the treatment of several cancers. In the present study, we aimed to determine the potential of vandetanib in cisplatin‑resistant NB therapy. Immunohistochemistry (IHC) staining was employed to detect p‑RET and CXCR4 expression in cisplatin‑resistant or ‑sensitive NB tissues from patients. Vandetanib was added to treat selected cisplatin‑resistant SH‑SY5Y cells (SH‑SY5Y‑R); this was followed by CCK8 assay, colony formation assay, and invasion assay...
February 9, 2018: Oncology Reports
Takashi Nakaoku, Takashi Kohno, Mitsugu Araki, Seiji Niho, Rakhee Chauhan, Phillip P Knowles, Katsuya Tsuchihara, Shingo Matsumoto, Yoko Shimada, Sachiyo Mimaki, Genichiro Ishii, Hitoshi Ichikawa, Satoru Nagatoishi, Kouhei Tsumoto, Yasushi Okuno, Kiyotaka Yoh, Neil Q McDonald, Koichi Goto
Resistance to vandetanib, a type I RET kinase inhibitor, developed in a patient with metastatic lung adenocarcinoma harboring a CCDC6-RET fusion that initially exhibited a response to treatment. The resistant tumor acquired a secondary mutation resulting in a serine-to-phenylalanine substitution at codon 904 in the activation loop of the RET kinase domain. The S904F mutation confers resistance to vandetanib by increasing the ATP affinity and autophosphorylation activity of RET kinase. A reduced interaction with the drug is also observed in vitro for the S904F mutant by thermal shift assay...
February 12, 2018: Nature Communications
Kan Chen, Yun Gao, Fei Shi, Guangqiang Cao, Jiandong Bao
Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently approved by the US Food and Drug Administration, which are not affordable for most Chinese patients. Herein, we report a case of an MTC patient who responded to apatinib, a Chinese homemade tyrosine kinase inhibitor-targeted vascular endothelial growth factor receptor...
2018: OncoTargets and Therapy
Liu Yang, Man Zhu, Yuan Kang, Tianfeng Yang, Weina Ma
The binding property between a ligand and its receptor is very important for numerous biological processes. In this study, we developed a high epidermal growth factor receptor (EGFR)-expression cell membrane chromatography (CMC) method to investigate the binding characteristics between EGFR and the ligands gefitinib, erlotinib, canertinib, afatinib, and vandetanib. Competitive binding analysis using gefitinib as the marker was used to investigate the interactions that occurred at specific binding sites on EGFR...
January 24, 2018: Journal of Molecular Recognition: JMR
Paola Romeo, Carla Colombo, Roberta Granata, Giuseppina Calareso, Ambra V Gualeni, Matteo Dugo, Loris De Cecco, Maria Grazia Rizzetti, Angela Zanframundo, Antonella Aiello, Maria Luisa Carcangiu, Annunziata Gloghini, Stefano Ferrero, Lisa Licitra, Angela Greco, Laura Fugazzola, Laura D Locati, Maria Grazia Borrello
This study aimed to identify circulating miRNAs as novel non-invasive biomarkers for prognosis and vandetanib response in advanced medullary thyroid cancer (MTC) patients. We prospectively recruited two independent cohorts of locally advanced/metastatic MTC patients including a subgroup of vandetanib-treated subjects: a discovery cohort (n = 20), including matched plasma/tissue samples (n = 17/20), and a validation cohort, yielding only plasma samples (n = 17). Plasma samples from healthy subjects (n = 36) and MTC patients in remission (n = 9) were used as controls...
January 3, 2018: Endocrine-related Cancer
Robert Roskoski, Abdollah Sadeghi-Nejad
RET is a transmembrane receptor protein-tyrosine kinase that is required for the development of the nervous system and several other tissues. The mechanism of activation of RET by its glial-cell derived neurotrophic factor (GDNF) ligands differs from that of all other receptor protein-tyrosine kinases owing to the requirement for additional GDNF family receptor-α (GFRα) co-receptors (GFRα1/2/3/4). RET point mutations have been reported in multiple endocrine neoplasia (MEN2A, MEN2B) and medullary thyroid carcinoma...
December 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Faiza Abdul Rashid, Qaisar Mansoor, Sobia Tabassum, Hafsa Aziz, Waleed O Arfat, George E Naoum, Muhammad Ismail, Ammad Ahmad Farooqi
Thyroid cancer is a multifaceted and therapeutically challenging disease and rapidly accumulating experimentally verified findings have considerably improve our understanding of the molecular mechanisms which underlie its development. Substantial fraction of information has been added into existing landscape of molecular oncology and we have started to develop a sharper understanding of the underlying mechanisms of thyroid cancer. Wealth of information demystified different intracellular signaling cascades which are frequently deregulated in thyroid cancer...
December 15, 2017: Journal of Cellular Biochemistry
Blake S Raggio, Blair M Barton, Maria C Grant, Judith A Fornadley, Jeffrey P Marino
Background: Patients with suspected thyroid malignancy often undergo preoperative laryngeal examination with a focus on vocal fold mobility. We present the unique case of a patient with invasive thyroid carcinoma who presented with dysphonia despite intact vocal fold motion. Case Report: A 73-year-old female with a remote thyroid lobectomy presented with dysphonia. Thyroid ultrasound and fine-needle aspiration revealed a 1.1-cm nodule consistent with a colloid cyst...
2017: Ochsner Journal
Camille Merienne, Marine Rousset, Dominique Ducint, Nadège Castaing, Karine Titier, Mathieu Molimard, Stéphane Bouchet
Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0...
February 20, 2018: Journal of Pharmaceutical and Biomedical Analysis
Marimu Sakumoto, Rieko Oyama, Mami Takahashi, Yoko Takai, Fusako Kito, Kumiko Shiozawa, Zhiwei Qiao, Makoto Endo, Akihiko Yoshida, Akira Kawai, Tadashi Kondo
Clear cell sarcoma (CCS) is an aggressive mesenchymal malignancy characterized by the unique chimeric EWS-ATF1 fusion gene. Patient-derived cancer models are essential tools for the understanding of tumorigenesis and the development of anti-cancer drugs; however, only a limited number of CCS cell lines exist. The objective of this study was to establish patient-derived CCS models. We established patient-derived CCS models from a 43-yr-old female patient. We prepared the patient-derived xenografts (PDXs) from tumor tissues obtained through biopsy or surgery and isolated stable cell lines from PDXs and the original tumor tissue...
February 2018: In Vitro Cellular & Developmental Biology. Animal
Ira L Kraft, Srivandana Akshintala, Yuelin Zhu, Haiyan Lei, Claudia Derse-Anthony, Eva Dombi, Seth M Steinberg, Maya Lodish, Steven G Waguespack, Oxana Kapustina, Elizabeth Fox, Frank M Balis, Maria J Merino, Paul S Meltzer, John W Glod, Jack F Shern, Brigitte C Widemann
Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously. Experimental Design: We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression. Results: Seventeen patients [8 male, age 13 (9-17)* years] enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zoltan Patay, Thomas E Merchant, Rosa Nguyen, Christopher R Pierson, Arzu Onar-Thomas, Alberto Broniscer
PURPOSE: We previously reported the cases of 3 children with diffuse intrinsic pontine glioma (DIPG) in whom noncontiguous treatment-related abnormalities (NCTRAs) developed in the brain after expanded-field radiation therapy (RT). To investigate the occurrence and putative mechanism of NCTRAs, we reviewed brain magnetic resonance imaging studies of patients with DIPG treated in 2 consecutive phase I clinical trials (trials 1 and 2). METHODS AND MATERIALS: The 55 children included in these trials received small-molecule inhibitors: vandetanib in trial 1 (n=32; mean age 6...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
Yuan Liu, Manli Qi, Shuping Hou, Lili Shao, Junyan Zhang, Yan Li, Quanzhong Liu
BACKGROUND: Vandetanib is a promising anticancer target agent for treating advanced carcinomas, such as non-small-cell lung cancer (NSCLC) and breast cancer. Rash is a frequently reported adverse event of vandetanib. We conducted this meta-analysis to determine the incidence rate and overall risks of all-grade and high-grade rash with vandetanib in NSCLC patients. METHODS: PubMed, Embase, Web of Science, American Society of Clinical Oncology, and Cochrane Library were systematically searched to identify studies with vandetanib and rash in NSCLC patients...
October 2017: Medicine (Baltimore)
S R Priya, Chandra Shekhar Dravid, Raghunadharao Digumarti, Mitali Dandekar
Medullary thyroid cancers (MTCs) constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS...
2017: Frontiers in Oncology
Masashi Nagao, John L Hamilton, Ranjan Kc, Agnes D Berendsen, Xuchen Duan, Chan Wook Cheong, Xin Li, Hee-Jeong Im, Bjorn R Olsen
Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is associated with osteoarthritis (OA), and increased VEGF expression correlates with increased disease severity. VEGF is also a chondrocyte survival factor during development and essential for bone formation, skeletal growth and postnatal homeostasis. This raises questions of how the important embryonic and postnatal functions of VEGF can be reconciled with an apparently destructive role in OA. Addressing these questions, we find that VEGF acts as a survival factor in growth plate chondrocytes during development but only up until a few weeks after birth in mice...
October 12, 2017: Scientific Reports
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