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https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#1
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439108/phase-i-trial-of-systemic-administration-of-edmonston-strain-of-measles-virus-genetically-engineered-to-express-the-sodium-iodide-symporter-in-patients-with-recurrent-or-refractory-multiple-myeloma
#2
A Dispenzieri, C Tong, B LaPlant, M Q Lacy, K Laumann, D Dingli, Y Zhou, M J Federspiel, M A Gertz, S Hayman, F Buadi, M O'Connor, V J Lowe, K-W Peng, S J Russell
MV-NIS is an Edmonston-lineage oncolytic measles virus expressing the human sodium-iodide symporter--a means for monitoring by noninvasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide two days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to 4 dose-levels without reaching MTD and subsequently to 2 higher dose-levels when improved virus manufacture technology made it possible...
April 25, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28436606/early-and-late-adverse-effects-of-radioiodine-for-pediatric-differentiated-thyroid-cancer
#3
Domenico Albano, Francesco Bertagna, Maria Beatrice Panarotto, Raffaele Giubbini
BACKGROUND: Radioiodine-131 (I131) therapy for differentiated thyroid cancer (DTC) is generally a safe and effective treatment, but it has some potential side effects, which have been well described in adults but less analyzed in children. Our aim was to describe early and late adverse events of radioactive I131 in pediatric patients. METHODS: All consecutive patients ≤18 years treated for DTC in the period 1980-2015 were retrospectively analyzed for early and late side effects of radioiodine...
April 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#4
Lingxiao Cheng, Yuchen Jin, Min Liu, Maomei Ruan, Libo Chen
Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with radioiodine represents a good choice for radioiodine-refractory differentiated thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance mechanism, and combination with HER inhibitor to prevent MAPK rebound may sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To evaluate if inhibiting both BRAF/MEK and HER can produce stronger redifferetiation effect, we tested the effects of BRAF/MEK inhibitor dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on the expression and function of iodine- and glucose-handling genes in BRAFV600E-positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement as control...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418955/late-124i-pet-ct-uptake-measurement-assessment-of-appropriate-examination-protocol-in-benign-thyroid-diseases
#5
Martin Freesmeyer, Anja S Gabler, Christian Kühnel, Thomas Winkens
PURPOSE: This study aimed at investigating the performance of late I PET/CT for radioiodine uptake (RAIU) measurement at 336 hours after administration in patients with benign thyroid diseases requiring radioiodine therapy. Special attention was paid to the comparability of I uptake (I-RAIU) to the clinical standard (I-RAIU, probe measurement). Considering cost aspects, we sought to establish an economically reasonable examination protocol based on scan duration and administered activity...
April 17, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28414279/short-term-effects-of-radioiodine-therapy-on-auditory-function
#6
Deniz Tuna Edizer, Suat Bilici, Muhammet Yıldız, Özgür Yiğit, Tevfik Fikret Çermik
OBJECTIVE: Radioiodine therapy (RIT) is frequently utilized as an adjunctive treatment option for differentiated thyroid carcinoma following surgical intervention. The side effects of RIT are considered to emerge as a result of radioiodine accumulation in non-thyroidal tissues capable of iodine uptake. We aimed to evaluate the effects of RIT on auditory function. MATERIALS AND METHODS: Patients who had undergone total thyroidectomy and diagnosed to have differentiated thyroid carcinoma were analyzed...
April 17, 2017: Journal of International Advanced Otology
https://www.readbyqxmd.com/read/28414189/radioiodinated-hypericin-disulfonic-acid-sodium-salts-as-a-dna-binding-probe-for-early-imaging-of-necrotic-myocardium
#7
Xinghua Duan, Zhiqi Yin, Cuihua Jiang, Qiaomei Jin, Dongjian Zhang, Ziping Sun, Wencai Ye, Jian Zhang
Necrotic myocardium imaging can provide great indicators of salvaged myocardial areas for clinical guidances to patients with myocardial infarction (MI). One of the key challenges in necrotic myocardium imaging however, is lack of ideal necrotic imaging tracers for exactly and timely depicting the necrotic myocardium. (131)I-hypericin ((131)I-Hyp) is a promising tracer in exact necrotic myocardium delineation. However, it can't clearly image necrotic myocardium until 9 h post injection (p.i.) for the high background signals in blood and lung due to the strong lipophilicity...
April 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28412971/appraising-the-holistic-value-of-lenvatinib-for-radio-iodine-refractory-differentiated-thyroid-cancer-a-multi-country-study-applying-pragmatic-mcda
#8
Monika Wagner, Hanane Khoury, Liga Bennetts, Patrizia Berto, Jenifer Ehreth, Xavier Badia, Mireille Goetghebeur
BACKGROUND: The objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts. METHODS: The study was designed to enable comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current disease context (watchful waiting, sorafenib) of France, Italy and Spain...
April 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28408701/low-grade-mucoepidermoid-tumor-of-parotid-gland-presenting-as-focal-asymmetry-in-the-follow-up-radioiodine-scan-in-a-patient-of-differentiated-papillary-carcinoma-of-thyroid
#9
Chinna Naik, Sandip Basu
Low grade mucoepidermoid tumor of the right parotid gland presenting as focal uptake in the follow-up whole body iodine scan in a patient of differentiated papillary carcinoma of thyroid 1 year after successful ablation is presented in this report. Following surgical excision, the histopathology was proven. The illustrated case represents false positive focal accumulation of (131)I in low grade mucoepidermoid carcinoma of the salivary gland that arose early in the follow-up course in differentiated thyroid carcinoma post-radioiodine (RAI)...
April 13, 2017: Journal of Nuclear Medicine Technology
https://www.readbyqxmd.com/read/28407689/radioiodinated-indomethacin-amide-for-molecular-imaging-of-cyclooxygenase-2-expressing-tumors
#10
Agnieszka Morgenroth, Andreas T J Vogg, Bernd Neumaier, Felix M Mottaghy, Boris D Zlatopolskiy
Cyclooxygenase-2 (COX-2) is an important biomarker in several tumors. Available imaging probes display relatively low tumor to background ratios (smaller than 2:1). We evaluated newly developed indomethacin (Ind) derivatives for in vivo molecular imaging of COX-2 expressing carcinoma. Radioiodinated Ind derivatives Ind-NH-(CH2)4-NH-3-[I-125]I-Bz ([I-125]5), Ind-NH-(CH2)4-NH-5-[I-124/125]I-Nic ([I-124/125]6) and Ind-NH-(CH2)4-NH-5-[I-125]I-Iphth ([I-125]7) were prepared from the respective SnBu3-precursors (45-80% radiochemical yield; > 95% radiochemical purity)...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401794/chinese-data-of-efficacy-of-low-and-high-dose-of-iodine-131-for-the-ablation-of-thyroid-remnant
#11
Chao Ma, Fang Feng, Shaoyan Wang, Hongliang Fu, Shuqi Wu, Zhiyi Ye, Suyun Chen, Hui Wang
BACKGROUND: Chinese data of efficacy of low- and high-dose of radioiodine for thyroid remnant is still absent. The aim of the study is to investigate whether the low-dose of radioiodine is as effective as high-dose for remnant ablation in Chinese patients. METHODS: Patients presenting for radioiodine ablation in our department were included. Inclusion criteria were an age of 16 years or older; total or near total thyroidectomy; tumor-node-metastasis (TNM) stage of pT1-3, any N stage and M0...
April 12, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28396808/usefulness-of-stereotactic-radiotherapy-using-cyberknife-for-recurrent-lymph-node-metastasis-of-differentiated-thyroid-cancer
#12
Joji Kawabe, Shigeaki Higashiyama, Mitsuharu Sougawa, Atsushi Yoshida, Kohei Kotani, Susumu Shiomi
A woman in her 60s presented with a recurrent lymph node metastasis from a papillary thyroid carcinoma in the right parapharyngeal space. She had already undergone total thyroidectomy, five resections for cervical lymph node metastases, and right carotid rebuilding. Surgical resection of the current metastasis was impossible. (131)I-radioiodine therapy (RIT) with 3.7 GBq (131)I was not effective; therefore, stereotactic radiation therapy (SRT) using a CyberKnife radiotherapy system was scheduled. The prescription dose was 21 Gy, and a dose covering 95% of the planning target volume (PTV) in three fractions was administered...
2017: Case Reports in Endocrinology
https://www.readbyqxmd.com/read/28394842/struma-ovarii-with-hyperthyroidism
#13
Lynn P Ang, Anca M Avram, Richard W Lieberman, Nazanene H Esfandiari
We report the case of a 61-year-old woman with persistent thyrotoxicosis for 7 years despite low thyroidal radioiodine uptake and methimazole treatment. Her initial I whole-body scan (WBS) was read as negative. Upon evaluation in our institution, she remained hyperthyroid after discontinuation of methimazole. Repeat WBS with SPECT/CT revealed low 24-hour thyroidal uptake (RAIU = 2%) and intensely focal radioiodine uptake in a large heterogeneous left pelvic mass, consistent with left adnexal struma ovarii. Resection of this mass confirmed benign struma ovarii...
April 7, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28392335/graves-disease-in-a-3-year-old-patient-with-agranulocytosis-due-to-anti-thyroid-drugs-radioiodine-ablation-therapy-as-an-effective-alternative
#14
E Espinosa-Muñoz, D Ramírez-Ocaña, A M Martín-García, F J Ruiz-García, C Puentes-Zarzuela
The case is presented of a 3 year-old girl with mitochondrial disease (subacute necrotizing encephalomyelopathy of Leigh syndrome), v-stage chronic kidney disease of a diffuse mesangial sclerosis, as well as developmental disorders, and diagnosed with hyperthyroidism Graves-Basedow disease. Six weeks after starting the treatment with neo-carbimazole, the patient reported a serious case of agranulocytosis. This led to stopping the anti-thyroid drugs, and was treated successfully with (131)I ablation therapy...
April 6, 2017: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/28389624/modeling-therapeutic-response-to-radioiodine-in-metastatic-thyroid-cancer-a%C3%A2-proof-of-concept-study-for-individualized-medicine
#15
Dominique Barbolosi, Ilyssa Summer, Christophe Meille, Raphaël Serre, Antony Kelly, Slimane Zerdoud, Claire Bournaud, Claire Schvartz, Michel Toubeau, Marie-Elisabeth Toubert, Isabelle Keller, David Taïeb
PURPOSE: Radioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer. EXPERIMENTAL DESIGN: Data from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386277/thyroid-related-protein-expression-in-the-human-thymus
#16
Mi Jeong Kim, So Won Oh, Hyewon Youn, Juri Na, Keon Wook Kang, Do Joon Park, Young Joo Park, Ja June Jang, Kyu Eun Lee, Kyeong Cheon Jung, June-Key Chung
Radioiodine whole body scan (WBS), related to sodium iodide symporter (NIS) function, is widely used to detect recurrence/metastasis in postoperative patients with thyroid cancer. However, the normal thymic uptake of radioiodine has occasionally been observed in young patients. We evaluated the expression of thyroid-related genes and proteins in the human thymus. Thymic tissues were obtained from 22 patients with thyroid cancer patients of all ages. The expression of NIS, thyroid-stimulating hormone receptor (TSHR), thyroperoxidase (TPO), and thyroglobulin (Tg) was investigated using immunohistochemistry and quantitative RT-PCR...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28382700/thyroid-cysts-in-cats-a-retrospective-study-of-40-cases
#17
M L Miller, M E Peterson, J F Randolph, M R Broome, G D Norsworthy, M Rishniw
BACKGROUND: Thyroid cysts are rare in cats and poorly documented. OBJECTIVES: To report distinguishing clinical features and treatment responses of cats with thyroid cysts. ANIMALS: Forty client-owned cats. METHODS: Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded...
April 6, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28382170/obatoclax-and-ly3009120-efficiently-overcome-vemurafenib-resistance-in-differentiated-thyroid-cancer
#18
Wei-Jun Wei, Zhen-Kui Sun, Chen-Tian Shen, Hong-Jun Song, Xin-Yun Zhang, Zhong-Ling Qiu, Quan-Yong Luo
Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAF(V600E) mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28380100/short-and-long-term-effects-of-zinc-treatment-on-lacrimal-gland-histopathology-and-tear-functions-tests-in-radioiodine-administered-rats
#19
Firdevs Ornek, Damla Erginturk Acar, Ugur Acar, Ozdemir Ozdemir, Hasan Ikbal Atilgan, Nihat Yumusak, Basak Boztok Ozgermen
Purpose: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. Methods: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage...
January 2017: Arquivos Brasileiros de Oftalmologia
https://www.readbyqxmd.com/read/28362717/low-activity-versus-high-activity-noninferior-response-to-radioiodine-therapy-in-differentiated-patients-with-extrathyroid-extension
#20
Chen Wang, Teng Zhao, Hui Li, Wen Gao, Yansong Lin
OBJECTIVES: Radioactive iodine (RAI) therapy is recommended for differentiated thyroid cancer (DTC) patients with microscopic extrathyroid extension (ETE). Patients with a low preablative stimulated thyroglobulin (ps-Tg) level have a more favorable prognosis. It remains uncertain whether low-activity RAI could have the same efficacy in patients with low ps-Tg. This study aimed to evaluate the effectiveness of low-activity RAI therapy in low-level ps-Tg DTC with ETE. PATIENTS AND METHODS: The inclusion criteria for this retrospective study were as follows: (a) age 18 years or older, (b) DTC after total or near-total thyroidectomy of DTC, (c) no distant metastasis after thyroidectomy and before RAI therapy, (d) American Joint Committee on Cancer pT3 stage (with microscopic ETE) with any American Joint Committee on Cancer N stage, (e) ps-Tg level of 5 ng/ml or less, and (f) after the first time of RAI therapy...
May 2017: Nuclear Medicine Communications
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