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https://www.readbyqxmd.com/read/29298817/circulating-mir-375-as-a-novel-prognostic-marker-for-metastatic-medullary-thyroid-cancer-patients
#1
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
https://www.readbyqxmd.com/read/29284153/role-of-ret-protein-tyrosine-kinase-inhibitors-in-the-treatment-ret-driven-thyroid-and-lung-cancers
#2
REVIEW
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
https://www.readbyqxmd.com/read/29243843/signaling-cascades-in-thyroid-cancer-increasing-the-armory-of-archers-to-hit-bullseye
#3
Faiza Abdul Rashid, Qaisar Mansoor, Hafsa Aziz, Sobia Tabassum, 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
https://www.readbyqxmd.com/read/29230133/invasive-insular-thyroid-carcinoma-presenting-as-nonparalytic-dysphonia
#4
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
https://www.readbyqxmd.com/read/29220734/high-throughput-routine-determination-of-17-tyrosine-kinase-inhibitors-by-lc-ms-ms
#5
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...
November 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29197033/establishment-and-proteomic-characterization-of-patient-derived-clear-cell-sarcoma-xenografts-and-cell-lines
#6
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...
December 1, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/29187393/outcomes-of-children-and-adolescents-with-advanced-hereditary-medullary-thyroid-carcinoma-treated-with-vandetanib
#7
Ira Lignugaris Kraft, Srivandana Akshintala, Yuelin J Zhu, Haiyan Lei, Claudia Derse-Anthony, Eva Dombi, Seth M Steinberg, Maya Lodish, Steven Waguespack, Oxana Kapustina, Elizabeth Fox, Frank M Balis, Maria J Merino, Paul S Meltzer, John 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...
November 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29165288/treatment-related-noncontiguous-radiologic-changes-in-children-with-diffuse-intrinsic-pontine-glioma-treated-with-expanded-irradiation-fields-and-antiangiogenic-therapy
#8
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
https://www.readbyqxmd.com/read/29069010/risk-of-rash-associated-with-vandetanib-treatment-in-non-small-cell-lung-cancer-patients-a-meta-analysis-of-9-randomized-controlled-trials
#9
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)
https://www.readbyqxmd.com/read/29057215/targeted-therapy-for-medullary-thyroid-cancer-a-review
#10
REVIEW
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
https://www.readbyqxmd.com/read/29026147/vascular-endothelial-growth-factor-in-cartilage-development-and-osteoarthritis
#11
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
https://www.readbyqxmd.com/read/29025983/predictive-value-of-fdg-pet-in-patients-with-advanced-medullary-thyroid-carcinoma-treated-with-vandetanib
#12
Rudolf A Werner, Jan Stefan Schmid, Takahiro Higuchi, Mehrbod Som Javadi, Steven P Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K Buck, Michael Kreissl, Constantin Lapa
Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We aimed to assess the role of metabolic imaging using 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline (18)F-FDG PET/CT prior to and 3 months after TKI treatment initiation...
October 12, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28942113/novel-serms-based-on-3-aryl-4-aryloxy-2h-chromen-2-one-skeleton-a-possible-way-to-dual-er%C3%AE-vegfr-2-ligands-for-treatment-of-breast-cancer
#13
Guoshun Luo, Xinyu Li, Guoqing Zhang, Chengzhe Wu, Zhengpu Tang, Linyi Liu, Qidong You, Hua Xiang
There is considerable interest in developing new SERMs as multifunctional agents in women's health. Development of dual selective estrogen receptor modulators/VEGFR-2 inhibitors (SERMs/V-2I) has been an attractive strategy for the discovery of new breast cancer therapeutic agents. Our previous efforts led to the preparation of a series of 3-aryl-4-anilino-2H-chromen-2-ones endowed with potent estrogen receptor binding affinity and anti-proliferative efficacy. In this study, various structurally related 3-aryl-4-anilino/aryloxy-2H-chromen-2-one analogues were rationally designed, synthesized and evaluated as a new chemo-type of dual ERα and VEGFR-2 inhibitors...
September 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28934120/angiogenesis-inhibitors-in-nsclc
#14
REVIEW
Anna Manzo, Agnese Montanino, Guido Carillio, Raffaele Costanzo, Claudia Sandomenico, Nicola Normanno, Maria Carmela Piccirillo, Gennaro Daniele, Francesco Perrone, Gaetano Rocco, Alessandro Morabito
Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC). Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL) that demonstrated an improvement of about two months in progression-free survival (PFS) in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS) also...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28932277/a-retrospective-review-of-the-multidisciplinary-management-of-medullary-thyroid-cancer-eligibility-for-systemic-therapy
#15
Georgia Geller, Janessa Laskin, Winson Y Cheung, Cheryl Ho
BACKGROUND: Medullary thyroid carcinoma (MTC) accounts for 1-2% of all thyroid cancers. The clinical course of metastatic disease can be indolent. Our aim was to characterize the natural history of disease to evaluate the true proportion of patients who would be eligible for the currently available systemic therapies. METHODS: The British Columbia Cancer Agency (BCCA) provides cancer care to a population of 4.6 million. A retrospective chart review was conducted of all patients with MTC referred to the BCCA from 1991 to 2013...
2017: Thyroid Research
https://www.readbyqxmd.com/read/28911730/management-of-tyrosine-kinase-inhibitors-tki-side-effects-in-differentiated-and-medullary-thyroid-cancer-patients
#16
REVIEW
C Resteghini, S Cavalieri, D Galbiati, R Granata, S Alfieri, C Bergamini, P Bossi, L Licitra, L D Locati
Four tyrosine kinase inhibitors (TKIs) have been recently licensed in thyroid cancer (TC), sorafenib and lenvatinib for differentiated TC, vandetanib and cabozantinib for medullary TC. Others TKIs such as axitinib, pazopanib, sunitinib, have been tested within phase II trials. The toxicity burden associated to TKIs is not negligible. Drug reductions and interruptions are common, definitive drug withdrawals have also been reported as well as toxic deaths in more rare cases. In this context, the prevention of toxicities is mandatory to allow patients to stay on treatment as long as possible without dose and schedule modifications...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28911729/chemotherapy-and-tyrosine-kinase-inhibitors-for-medullary-thyroid-cancer
#17
REVIEW
Julien Hadoux, Martin Schlumberger
Medullary thyroid cancer (MTC) represents 3% of all clinical thyroid cancers and arises from thyroid C cells that produce calcitonin. Locally advanced or metastatic MTC requires a careful work-up including measurement of serum calcitonin and carcinoembryonic antigen, determination of their doubling time and comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for treatment. Cytotoxic chemotherapy can control tumor burden in some patients with response rates of around 20% in old series...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28860428/-current-status-and-future-perspectives-of-scrum-japan
#18
REVIEW
Atsushi Ohtsu, Koichi Goto, Takayuki Yoshino, Wataru Okamoto, Katsuya Tsuchihara
SCRUM-Japan was launched as a nation-wide genome screening consortium for recruiting patients to 35 sponsor-/investigator- initiated registration trials in collaboration with 15 pharmaceutical companies and 240 hospitals. During the first period between February 2015 and March 2017, a total of 4,805 patients have been enrolled. Genomic profiling of each cancer were analyzed and newdrug applications of label expansion are in preparation based on the results of several registration studies including investigator-initiated trial of vandetanib for RET fusion gene positive non-small cell lung cancer...
August 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28851502/overcoming-abc-transporter-mediated-multidrug-resistance-the-dual-role-of-tyrosine-kinase-inhibitors-as-multitargeting-agents
#19
Giovanni Luca Beretta, Giuliana Cassinelli, Marzia Pennati, Valentina Zuco, Laura Gatti
Resistance to conventional and target specific antitumor drugs still remains one of the major cause of treatment failure and patience death. This condition often involves ATP-binding cassette (ABC) transporters that, by pumping the drugs outside from cancer cells, attenuate the potency of chemotherapeutics and negatively impact on the fate of anticancer therapy. In recent years, several tyrosine kinase inhibitors (TKIs) (e.g., imatinib, nilotinib, dasatinib, ponatinib, gefitinib, erlotinib, lapatinib, vandetanib, sunitinib, sorafenib) have been reported to interact with ABC transporters (e...
August 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28843881/biophysical-and-computational-characterization-of-vandetanib-lysozyme-interaction
#20
Md Zahirul Kabir, Nur Aziean Binti Hamzah, Hamidah Ghani, Saharuddin B Mohamad, Zazali Alias, Saad Tayyab
Interaction of an anticancer drug, vandetanib (VDB) with a ligand transporter, lysozyme (LYZ) was explored using multispectroscopic techniques, such as fluorescence, absorption and circular dichroism along with computational analysis. Fluorescence data and absorption results confirmed VDB-LYZ complexation. VDB-induced quenching was characterized as static quenching based on inverse correlation of KSV with temperature as well as kq values. The complex was characterized by the weak binding constant (Ka=4.96-3...
August 18, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
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