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Thyroid resistance

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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/28440417/increased-cd19-cd24-cd27-b-regulatory-cells-are-associated-with-insulin-resistance-in-patients-with-type-i-hashimoto-s-thyroiditis
#2
Min Yang, Changji Du, Yinping Wang, Jun Liu
Hashimoto's thyroiditis (HT) is characterized by dysregulated immune responses and is commonly associated with insulin resistance. However, the mechanism of insulin resistance in HT remains to be fully elucidated. The aim of the present study was to investigate the correlation between the percentage of B regulatory lymphocytes (Bregs) and insulin resistance in patients with HT but with normal thyroid function (type I). A total of 59 patients with type I HT and 38 healthy volunteers were enrolled in the study...
April 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28436990/tcrp1-promotes-nih-3t3-cell-transformation-by-over-activating-pdk1-and-akt1
#3
C Wang, H Liu, Q Qiu, Z Zhang, Y Gu, Z He
Tongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our precious studies demonstrated that TCRP1 was involving in chemotherapy and radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian cancer cells. In this study, we showed that TCRP1 overexpression promotes cell transformation and tumorigenesis through hyperphosphorylation of the oncogenic kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1-mediated cell transformation...
April 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28428941/cardiovascular-risk-may-be-increased-in-women-with-unexplained-infertility
#4
Fatma Ferda Verit, Fadile Yildiz Zeyrek, Ali Galip Zebitay, Hurkan Akyol
OBJECTIVE: Growing evidence suggests that increased cardiovascular disease (CVD) risk is associated with female infertility caused by conditions such as polycystic ovarian disease, obesity, thyroid dysfunction, and endometriosis. The aim of this study was to evaluate whether any relationship exists between CVD and unexplained infertility. METHODS: Sixty-five women with unexplained infertility and 65 fertile controls were enrolled in the study. CVD risk markers such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG), insulin resistance (defined by the homeostasis model assessment ratio), and high-sensitivity C-reactive protein (hs-CRP) were assessed...
March 2017: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28428267/association-of-nf%C3%AE%C2%BAb-polymorphisms-with-clinical-outcome-of-non-medullary-thyroid-carcinoma
#5
Theo S Plantinga, Mirela Petrulea, Marije Oosting, Leo Joosten, Doina Piciu, Jan Wa Smit, Romana T Netea-Maier, Carmen Georgescu
The NF-κB inflammatory pathway plays a major role in cancer development and clinical progression. Activation of NF-κB signaling is promoted by NFKB1 and inhibited by NFKBIA. The present study aimed to determine the relevance of NFKB1 rs4648068 and NFKBIA rs2233406 genetic variants for non-medullary thyroid cancer (NMTC) susceptibility, progression and clinical outcome. This case-control and cohort study consists of a Romanian discovery cohort (157 patients, 258 controls) and a Dutch validation cohort (138 patients, 188 controls)...
April 20, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#6
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/28405484/thyroid-associated-ophthalmopathy
#7
REVIEW
Esra Şahlı, Kaan Gündüz
Thyroid-associated ophthalmopathy is the most frequent extrathyroidal involvement of Graves' disease but it sometimes occurs in euthyroid or hypothyroid patients. Thyroid-associated ophthalmopathy is an autoimmune disorder, but its pathogenesis is not completely understood. Autoimmunity against putative antigens shared by the thyroid and the orbit plays a role in the pathogenesis of disease. There is an increased volume of extraocular muscles, orbital connective and adipose tissues. Clinical findings of thyroid-associated ophthalmopathy are soft tissue involvement, eyelid retraction, proptosis, compressive optic neuropathy, and restrictive myopathy...
April 2017: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/28400827/effects-of-vitamin-d-deficiency-treatment-on-metabolic-markers-in-hashimoto-thyroiditis-patients
#8
Parichehr Vahabi Anaraki, Ashraf Aminorroaya, Massoud Amini, Awat Feizi, Bijan Iraj, Azamosadat Tabatabaei
BACKGROUND: The aim of the current trial was to investigate the effect of Vitamin D treatment on metabolic markers in people with Vitamin D deficiency and thyroid autoimmunity. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 65 Vitamin D deficient euthyroid or hypothyroid patients with positive TPO-Ab were enrolled. They randomly allocated into two groups to receive oral Vitamin D3 (50000 IU weekly) and placebo for 12 weeks...
2017: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/28400547/anemia-in-thyroid-diseases
#9
Ewelina Szczepanek-Parulska, Aleksandra Hernik, Marek Ruchała
Anemia is a frequent, although often underestimated, clinical condition accompanying thyroid diseases. In spite of the fact that anemia and thyroid dysfunction often occur simultaneously, the causative relationship between these two disorders remains ambiguous. Thyroid hormones stimulate erythrocytes precursors proliferation directly, as well as via erythropoietin production enhancement, whereas iron-deficient anemia negatively influences thyroid hormonal status. Thus, different forms of anemia might emerge in the course of thyroid dysfunction...
March 28, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28400351/frequency-of-nodular-goiter-and-autoimmune-thyroid-disease-and-association-of-these-disorders-with-insulin-resistance-in-polycystic-ovary-syndrome
#10
Melia Karaköse, Sema Hepsen, Erman Çakal, Müyesser Saykı Arslan, Esra Tutal, Şafak Akın, İlknur Ünsal, Mustafa Özbek
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women. Nodular goiter and autoimmune thyroid disease (AITD) are the endocrinological abnormalities that have high prevalence. The purpose of our study was to detect the prevalence of AITD and nodular goiter in PCOS patients and investigate whether PCOS related hormones and metabolic factors affect these thyroid disorders. MATERIAL AND METHODS: Ninety-seven with PCOS and seventy-one healthy female volunteers were recruited in the study...
February 7, 2017: Journal of the Turkish German Gynecological Association
https://www.readbyqxmd.com/read/28399594/thyroid-stimulating-hormone-and-insulin-resistance-their-association-with-polycystic-ovary-syndrome-without-overt-hypothyroidism
#11
Cristina Laguna Benetti-Pinto, Vanessa Berini Piccolo, Daniela Angerame Yela, Heraldo Garmes
Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2...
April 11, 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28394318/the-evolving-concept-of-cancer-stem-like-cells-in-thyroid-cancer-and-other-solid-tumors
#12
Heather Hardin, Ranran Zhang, Holly Helein, Darya Buehler, Zhenying Guo, Ricardo V Lloyd
The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice...
April 10, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28391026/radiopharmaceuticals-in-the-elderly-cancer-patient-practical-considerations-with-a-focus-on-prostate-cancer-therapy-a-position-paper-from-the-international-society-of-geriatric-oncology-task-force
#13
John O Prior, Silke Gillessen, Manfred Wirth, William Dale, Matti Aapro, Wim J G Oyen
Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e...
April 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28390289/lenvatinib-an-oral-multi-kinases-inhibitor-associated-hypertension-potential-role-of-vascular-endothelial-dysfunction
#14
Daisuke Sueta, Koichi Suyama, Aiko Sueta, Noriaki Tabata, Takayoshi Yamashita, Mai Tomiguchi, Takashi Takeshita, Mutsuko Yamamoto-Ibusuki, Eiichiro Yamamoto, Yasuhiro Izumiya, Koichi Kaikita, Yutaka Yamamoto, Seiji Hokimoto, Hirotaka Iwase, Kenichi Tsujita
BACKGROUND AND AIMS: Lenvatinib (Lenvima(®)), an oral multi-kinase inhibitor, is effective in the treatment of differentiated thyroid carcinomas (DTCs). A severe adverse effect of lenvatinib is hypertension, thus limiting its use as an anti-cancer treatment. Although the pathogenesis of hypertension is generally assumed to involve microvascular bed reduction and an increase in peripheral vascular resistance due to a decrease in nitrogen oxide (NOx) production after vascular endothelial growth factor (VEGF) inhibition, the effects of hypertension on vascular endothelial function in actual patients remain unclear...
May 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28385173/novel-augmentation-strategies-in-major-depression
#15
Klaus Martiny
Hypothesis The hypotheses of all the four included studies share the common idea that it is possible to augment the effect of antidepressant drug treatment by applying different interventions and with each intervention attain a clinically meaningful better effect compared to a control condition, and with minor side effects, thus improving the short- and medium-term outcome in major depression. Procedures Study design The basic study design has been the double blind randomised controlled trial (RCT). In the light therapy study, all patients were treated with sertraline for the whole of the study duration...
April 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28382490/silencing-of-y-box-binding-protein-1-by-rna-interference-inhibits-proliferation-invasion-and-metastasis-and-enhances-sensitivity-to-cisplatin-through-nf-%C3%AE%C2%BAb-signaling-pathway-in-human-neuroblastoma-sh-sy5y-cells
#16
Hong Wang, Ruowen Sun, Zuofei Chi, Shuang Li, Liangchun Hao
Y-box binding protein-1 (YB-1), a member of Y-box protein family binding DNA and RNA, has been proposed as a novel marker in multiple malignant tumors and found to be associated with tumor malignancy. Neuroblastoma is an embryonal tumor arising from neuroblast cells of the autonomic nervous system, which is the most common cancer diagnosed in infants. It has been reported that YB-1 is highly expressing in various human tumors including nasopharynx, thyroid, lung, breast, colon, ovary, and prostate cancers. This study aimed to investigate the functional role of YB-1 in neuroblastoma by silencing YB-1 using RNA interference (shRNA) in neuroblastoma SH-SY5Y cells...
April 5, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28382170/obatoclax-and-ly3009120-efficiently-overcome-vemurafenib-resistance-in-differentiated-thyroid-cancer
#17
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/28379567/retinal-photoreceptor-functions-are-compromised-in-patients-with-resistance-to-thyroid-hormone-syndrome-rth%C3%AE
#18
Irene Campi, Gabriella Cammarata, Stefania Bianchi Marzoli, Paolo Beck-Peccoz, Diletta Santarsiero, Davide Dazzi, Alessandra Bottari de Castello, Elena Giuliana Taroni, Francesco Viola, Caterina Mian, Sara Watuntantrige-Fernando, Carla Pelusi, Marina Muzza, Maria Antonia Maffini, Luca Persani
CONTEXT: In animal models, disruption of thyroid hormone receptor-beta (TRβ) reduces the medium-wavelength (L/M) and increases the short-wavelength (S)-cones. The retinal photoreceptors (RPs) functions are unknown in patients with resistance to thyroid hormone syndrome with dominant-negative TRβ mutations (RTHβ). OBJECTIVE: to investigate RPs function in RTHβ. DESIGN, SETTING AND PARTICIPANTS: case-control study involving 27 RTHβ patients and 31 age-gender-matched controls, conducted in two tertiary referral centers in Italy...
March 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28374508/free-triiodothyronine-free-thyroxine-ratio-rather-than-thyrotropin-is-more-associated-with-metabolic-parameters-in-healthy-euthyroid-adult-subjects
#19
So Young Park, Se Eun Park, Sang Won Jung, Hyun Seok Jin, Ie Byung Park, Song Vogue Ahn, Sihoon Lee
OBJECTIVE: The interrelation between TSH, thyroid hormones, and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. DESIGN: This is a cross-sectional study that included subjects in a medical health check-up program at a single institution...
April 4, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28344765/new-insights-on-thyroid-hormone-mediated-regulation-of-herpesvirus-infections
#20
REVIEW
Robert W Figliozzi, Feng Chen, S Victor Hsia
Thyroid hormone (T3) has been suggested to participate in the regulation of herpesvirus replication during reactivation. Clinical observations and in vivo experiments suggest that T3 are involved in the suppression of herpes virus replication. In vitro, differentiated LNCaP cells, a human neuron-like cells, further resisted HSV-1 replication upon addition of T3. Previous studies indicate that T3 controlled the expression of several key viral genes via its nuclear receptors in differentiated LNCaP cells. Additional observation showed that differentiated LNCaP cells have active PI3K signaling and inhibitor LY294002 can reverse T3-mediated repression of viral replication...
2017: Cell & Bioscience
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