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Thyroid resistance

Zengli Zhang, Huiqian Wang, Qifeng Ding, Yufei Xing, Zhonghua Xu, Chun Lu, Dongdong Luo, Longjiang Xu, Wei Xia, Caicun Zhou, Minhua Shi
The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days)...
2018: PloS One
Ludmila S Almeida, Maidane C Araújo, Denise E Zantut-Wittmann, Lígia V Assumpção, Thiago F Souza, Cleide M Silva, Juliana L Argenton, Allan O Santos, Jair Mengatti, Celso D Ramos, Elba C Etchebehere
BACKGROUND: Radioiodine-refractory thyroid carcinomas (RAIRs) are characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin levels, and negative whole-body radioiodine scans. Interestingly, RAIRs continue to express somatostatin receptors and can be identified with Ga-DOTATATE PET/CT imaging. OBJECTIVE: The objective of this study was to compare lesion detectability in Ga-DOTATATE PET/CT performed with elevated thyroid-stimulating hormone (eTSH) levels with suppressed thyroid-stimulating hormone (sTSH) levels...
March 14, 2018: Nuclear Medicine Communications
Min Yang, Li Su, Qin Tao, Chenxi Zhang, Yueyue Wu, Jun Liu
Hashimoto's Thyroiditis (HT) is a common organ-specific autoimmune disorder associated with a high incidence, and insulin resistance is highly related to autoimmune. Here, we examined the insulin sensitivity in HT patients and found decreased insulin sensitivity occurred in HT patients. To explore the relationship between impaired insulin sensitivity and immune status, we established HT model mice which showed similar pathological features and immune features to HT patients. In HT model mice, reinfusion of regulatory T cells (Tregs) from peripheral blood of normal mice could improve insulin sensitivity and decrease the inflammation...
2018: Frontiers in Physiology
Ling Ma, Qiao Cheng
Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid malignancies and resistant to chemotherapy. Little is known on the underlying mechanisms of ATC resistance to chemotherapy. In our work, we identified that 6-phosphogluconate dehydrogenase (6PGD) is critically involved in the development of ATC resistance to doxorubicin. We found that 6PGD mRNA, protein and enzyme activity levels are significantly upregulated in ATC cells during the prolonged exposure to doxorubicin in a time-dependent manner...
March 10, 2018: Biochemical and Biophysical Research Communications
Mehmet Tecellioglu, Ozden Kamisli, Suat Kamisli, Fatma Ebru Yucel, Cemal Ozcan
BACKGROUND: Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. AIMS: To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. METHODS: Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified...
March 9, 2018: Irish Journal of Medical Science
Danyang Shen, Xiaoming Yu, Yan Wu, Yuanlei Chen, Gonghui Li, Feng Cheng, Liqun Xia
Retinoic acid X receptors play key roles in tumor cell proliferation, differentiation, apoptosis and angiogenesis via transcriptional regulation. Bexarotene is a specific RXRs agonist which has been granted by FDA approval for the clinical treatment of cutaneous T cell lymphoma (CTCL). Its cancer prevention and treatment potentials in various tumors have been under investigation over the past decade. Areas covered: This review summarizes the efficacy and underlying mechanisms of bexarotene for the treatment of multiple cancers based on the launched clinical trials as well as the basic studies...
March 9, 2018: Expert Review of Anticancer Therapy
Sibel Azizenur Ozturk, Ebru Alp, Atiye Seda Yar Saglam, Ece Konac, Emine Sevda Menevse
Context: Thyroid cancers (TCs) are the most common endocrine malignancies. There were two problems with the current cancer chemotherapy: the ineffectiveness of treatment due to resistance to cancer cell, and the toxic effect on normal cells. Aims: This study was aimed to determine the effects of thymoquinone (TQ) and genistein (Gen) phytotherapeutics on telomerase activity, angiogenesis, and apoptosis in follicular and anaplastic thyroid cancer cells (TCCs). Materials and Methods: Cell viability, caspase-3 (CASP-3) activity, and messenger RNA (mRNA) expression levels of human telomerase reverse transcriptase (hTERT), phosphatase and tensin homolog (PTEN), nuclear factor-kappa B (NF-kB), cyclin-dependent kinase inhibitor 1 (p21), and vascular endothelial growth factor-A (VEGF-A) genes were analyzed...
January 2018: Journal of Cancer Research and Therapeutics
Berna Solak, Bahar Sevimli Dikicier, Nur Cihan Cosansu, Teoman Erdem
Introduction: There are a few studies showing an increased risk of insulin resistance, metabolic syndrome, and oxidative stress in patients with vitiligo. Aim: To investigate whether systemic inflammation is increased in vitiligo patients in a case-control study design. Material and methods: Nonsegmental vitiligo patients who had been followed at the outpatient dermatology clinic of a university-affiliated teaching hospital, and healthy controls were enrolled in the study...
October 2017: Postȩpy Dermatologii i Alergologii
Zhi-Bin Zhao, Jie Long, Yang-Yang Zhao, Jing-Bo Yang, Wei Jiang, Qing-Zhi Liu, Kai Yan, Liang Li, Yu-Cai Wang, Zhe-Xiong Lian
Sorafenib is a kinase inhibitor approved for the treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. However, sorafenib usually causes serious side effects, which limit its antitumor effect. Nanoparticle based drug delivery systems have been widely used to enhance the therapeutic effects and reduce the side effects of this drug by the enhanced permeability and retention (EPR) effect. Herein, to improve the therapeutic effect of sorafenib, we developed poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PEG-PLGA) based nanoparticles by a dialysis method for sorafenib encapsulation...
March 7, 2018: Biomaterials Science
Jianqiang Yang, Ning Yi, Junhui Zhang, Wen He, Di He, Wanwan Wu, Shuyang Xu, Feng Li, Guoping Fan, Xianmin Zhu, Zhigang Xue, Wensheng Zhou
Thyroid stimulating hormone receptor (TSHR), a G-protein-coupled receptor, is important for thyroid development and growth. In several cases, frameshift and/or nonsense mutations in TSHR were found in the patients with congenital hypothyroidism (CH), however they have not been functionally studied in an animal model. In the present work, we generated a unique TshrDf/Df rat model that recapitulates the phenotypes in TSHR Y444X patient by CRISPR/Cas genome editing technology. In this rat model, TSHR is truncated at the second transmembrane domain, leading to CH phenotypes as what was observed in the patients, including dwarf, thyroid aplasia, infertility, TSH resistant as well as low serum thyroid hormone levels...
March 5, 2018: Scientific Reports
Lu-Lu Fu, Ying Xu, Dan-Dan Li, Xiao-Wei Dai, Xin Xu, Jing-Shun Zhang, Hao Ming, Xue-Ying Zhang, Guo-Qing Zhang, Ya-Lan Ma, Lian-Wen Zheng
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. However, the exact pathophysiology of PCOS remains largely unclear. We performed deep sequencing to investigate the mRNA and long noncoding RNA (lncRNA) expression profiles in the ovarian tissues of letrozole-induced PCOS rat model and control rats. A total of 2147 mRNAs and 158 lncRNAs were differentially expressed between the PCOS models and control. Gene ontology analysis indicated that differentially expressed mRNAs were associated with biological adhesion, reproduction, and metabolic process...
March 2, 2018: Gene
Marta Kotlarek, Anna Kubiak, Małgorzata Czetwertyńska, Michał Świerniak, Wojciech Gierlikowski, Monika Kolanowska, Elwira Bakuła-Zalewska, Sissy M Jhiang, Krystian Jażdżewski, Anna Wójcicka
Aberrant expression of the sodium-iodide symporter (NIS) and the resistance to post-operative radioactive iodide treatment is a crucial cause of higher mortality of some thyroid cancer patients. In this study, we analyzed the impact of miR-146a on the expression and function of NIS and on the overall survival of thyroid cancer patients. The study included 2441 patients (2163 women; 278 men); including 359 cases with follicular variant of papillary thyroid carcinoma (fvPTC). miR: NIS interactions were analyzed in cell lines using in vivo binding and inhibition assays and radioactive iodine uptake assays...
February 26, 2018: International Journal of Molecular Sciences
Agathocles Tsatsoulis
Thyroid follicular cells, as well as adrenocortical cells, are endowed by an intrinsic heterogeneity regarding their growth potential, in response to various stimuli. This heterogeneity appears to constitute the underlying cause for the focal cell hyperplasia and eventually the formation of thyroid and adrenal nodules, under the influence of growth stimulatory factors. Among the main stimulatory factors are the pituitary tropic hormones, thyroid-stimulating hormone (TSH) or thyrotropin and adrenocorticotropic hormone (ACTH), which regulate the growth and function of their respective target cells, and the insulin/insulin-like growth factor system, that, through its mitogenic effects, can stimulate the proliferation of these cells...
February 26, 2018: Journal of Clinical Medicine
M Dold, L Bartova, J Mendlewicz, D Souery, A Serretti, S Porcelli, J Zohar, S Montgomery, S Kasper
OBJECTIVE: This multicenter, multinational, cross-sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). METHOD: Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses...
February 28, 2018: Acta Psychiatrica Scandinavica
Afaque H Khan, Samina Zaidi
We report five cases of treatment-resistant schizophrenia that presented with prominent negative and positive symptoms. They fulfill the criteria of diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). They showed lack of response despite receiving multiple trials of first and second generation psychotropic agents. We decided to give these patients a trial of clozapine to improve their negative and positive symptoms as well as their quality of life...
December 20, 2017: Curēus
Lei Cai, Theodoros Michelakos, Teppei Yamada, Song Fan, Xinhui Wang, Joseph H Schwab, Cristina R Ferrone, Soldano Ferrone
Malignant transformation of cells is frequently associated with defective HLA class I antigen processing machinery (APM) component expression. This abnormality may have functional relevance, since it may have a negative impact on tumor cell recognition by cognate T cells. Furthermore, HLA class I APM abnormalities appear to have clinical significance, since they are associated with poor prognosis in several malignant diseases and may play a role in the resistance to immune checkpoint inhibitor-based immunotherapy...
February 27, 2018: Cancer Immunology, Immunotherapy: CII
Francesca Galdiero, Anna Maria Bello, Anna Spina, Anna Capiluongo, Sophie Liuu, Margot De Marco, Alessandra Rosati, Mario Capunzo, Maria Napolitano, Emilia Vuttariello, Mario Monaco, Daniela Califano, Maria Caterina Turco, Gennaro Chiappetta, Joëlle Vinh, Giovanni Chiappetta
BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies...
January 30, 2018: Oncotarget
Thomas C Beadnell, Kelsey W Nassar, Madison M Rose, Erin G Clark, Brian P Danysh, Marie-Claude Hofmann, Nikita Pozdeyev, Rebecca E Schweppe
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway...
February 28, 2018: Oncogenesis
Anna Chorzalska, Nagib Ahsan, R Shyama Prasad Rao, Karim Roder, Xiaoqing Yu, John Morgan, Alexander Tepper, Steven Hines, Peng Zhang, Diana O Treaba, Ting C Zhao, Adam J Olszewski, John Reagan, Olin Liang, Philip A Gruppuso, Patrycja M Dubielecka
The introduction of tyrosine kinase inhibitors (TKI) has transformed chronic myeloid leukemia (CML) into a chronic disease with long-term survival exceeding 85%. However, resistance of CML stem cells to TKI may contribute to the 50% relapse rate observed after TKI discontinuation in molecular remission. We previously described a model of resistance to imatinib mesylate (IM), in which K562 cells cultured in high concentrations of imatinib mesylate showed reduced Bcr-Abl1 protein and activity levels while maintaining proliferative potential...
February 27, 2018: Molecular Oncology
Y-M Fan, S-P Ding, Z-J Bao, L-M Wu, L-B Zhen, Q Xia, M Zhu
OBJECTIVE: To examine the clinical outcomes and associated prognostic factors among patients with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: This retrospective study involved 243 patients with MDR-TB. All patients received standard regimens containing para-amino salicylic acid (PAS) and/or cycloserine (CS). The demographic, social and clinical characteristics of patients were recorded and the patients were followed up for 24 months. RESULTS: Treatment success was closely associated with young age, non-farming occupations, shorter history or smoking, normal urine results, initial MDR-TB treatment regimen, increased haemoglobin, direct bilirubin, uric acid and thyroid stimulating hormone (TSH) levels, and lower white blood cell, neutrophil and blood platelet counts (all P < 0...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
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