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Akt1 thyroid

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https://www.readbyqxmd.com/read/27837029/digitalis-like-compounds-facilitate-non-medullary-thyroid-cancer-redifferentiation-through-intracellular-ca2-fos-and-autophagy-dependent-pathways
#1
Marika H Tesselaar, Thomas Crezee, Herman G Swarts, Danny Gerrits, Otto C Boerman, Jan B Koenderink, Hendrik G Stunnenberg, Mihai G Netea, Jan Wa Smit, Romana T Netea-Maier, Theo S Plantinga
Up to 20-30% of patients with metastatic non-medullary thyroid cancer have persistent or recurrent disease resulting from tumour dedifferentiation. Tumour redifferentiation to restore sensitivity to radioactive iodide (RAI) therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activators for redifferentiation of thyroid cancer cell lines. Five autophagy activating compounds, all known as digitalis-like compounds, restored hNIS expression and iodide uptake in TC cell lines...
November 11, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27618325/current-concepts-in-the-molecular-genetics-and-management-of-thyroid-cancer-an-update-for-radiologists
#2
Tatiana Kelil, Abhishek R Keraliya, Stephanie A Howard, Katherine M Krajewski, Marta Braschi-Amirfarzan, Jason L Hornick, Nikhil H Ramaiya, Sree Harsha Tirumani
Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/27112325/lack-of-mutation-histopathology-correlation-in-a-patient-with-proteus-syndrome
#3
Meggie E Doucet, Hadley M Bloomhardt, Krzysztof Moroz, Marjorie J Lindhurst, Leslie G Biesecker
Proteus syndrome (PS) is characterized by progressive, disproportionate, segmental overgrowth, and tumor susceptibility caused by a somatic mosaic AKT1 activating mutation. Each individual has unique manifestations making this disorder extremely heterogeneous. We correlated three variables in 38 tissue samples from a patient who died with PS: the gross affection status, the microscopic affection status, and the mutation level. The AKT1 mutation was measured using a PCR-based RFLP assay. Thirteen samples were grossly normal; six had detectable mutation (2-29%) although four of these six were histopathologically normal...
June 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/26635480/o-glcnacylation-enhances-the-invasion-of-thyroid-anaplastic-cancer-cells-partially-by-pi3k-akt1-pathway
#4
Peng Zhang, Chunli Wang, Tao Ma, Shengyi You
BACKGROUND: The PI3K family participates in multiple signaling pathways to regulate cellular functions. PI3K/Akt signaling pathway plays an important role in tumorigenesis and development. O-GlcNAcylation, a posttranslational modification, is thought to modulate a wide range of biological processes, such as transcription, cell growth, signal transduction, and cell motility. O-GlcNAcylation is catalyzed by the nucleocytoplasmic enzymes, OGT and OGA, which adds or removes O-GlcNAc moieties, respectively...
2015: OncoTargets and Therapy
https://www.readbyqxmd.com/read/26355276/multiple-mutations-detected-preoperatively-may-predict-aggressive-behavior-of-papillary-thyroid-cancer-and-guide-management-a-case-report
#5
Rupendra T Shrestha, Arivarasan Karunamurthy, Khalid Amin, Yuri E Nikiforov, M Luiza Caramori
BACKGROUND: Multiple gene mutations in thyroid nodules are rare. The presence of several oncogenic mutations could be associated with aggressive biological behavior of tumors. PATIENT FINDINGS: A 60-year-old female presented to her physician after she felt a lump in her neck. On ultrasound, she was found to have a 1.4 cm × 0.8 cm × 1.3 cm nodule in the isthmus and a 0.5 cm × 0.6 cm × 0.6 cm nodule with irregular margins and hypoechogenicity in the right thyroid lobe, warranting fine-needle aspiration (FNA)...
December 2015: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/26120150/cowden-syndrome-case-report-update-and-proposed-diagnostic-and-surveillance-routines
#6
Masuma Molvi, Yugal K Sharma, Kedarnath Dash
Cowden syndrome (CS) is an infrequent autosomal dominant multisystem genodermatosis, generally involving the skin, oral mucosa, thyroid, breast and gastrointestinal tract. It is characterized by a late onset in the 2(nd) or 3(rd) decade of life, an extraordinary potential for malignant transformation, especially of breast and thyroid, and an identifiable germline mutation. In 80% cases, the human tumor suppressor gene, phosphatase and tensin homolog (PTEN) is mutated; mutations involving KILLIN, SDH B/D, PIK3CA and AKT1 genes account for the rest of the cases...
May 2015: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/25673849/trip6-promotes-dendritic-morphogenesis-through-dephosphorylated-grip1-dependent-myosin-vi-and-f-actin-organization
#7
Kaosheng Lv, Liang Chen, Yuanjun Li, Zenglong Li, Pengli Zheng, Yingying Liu, Jianguo Chen, Junlin Teng
Thyroid receptor-interacting protein 6 (Trip6), a multifunctional protein belonging to the zyxin family of LIM proteins, is involved in various physiological and pathological processes, including cell migration and tumorigenesis. However, the role of Trip6 in neurons remains unknown. Here, we show that Trip6 is expressed in mouse hippocampal neurons and promotes dendritic morphogenesis. Through interaction with the glutamate receptor-interacting protein 1 (GRIP1) and myosin VI, Trip6 is crucial for the total dendritic length and the number of primary dendrites in cultured hippocampal neurons...
February 11, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/25502934/glucose-dependent-glucose-transporter%C3%A2-1-expression-and-its-impact-on-viability-of-thyroid-cancer-cells
#8
Paweł Jóźwiak, Anna Krześlak, Magdalena Bryś, Anna Lipińska
Cancer cells exhibit an altered metabolism characterized by enhanced glycolysis and glucose consumption. In glucose‑addicted cancer cells upregulation of glucose transport across the plasma membrane is mediated by a family of facilitated glucose transporter proteins, particularly glucose transporter 1 (GLUT1). The aim of the present study was to investigate the impact of GLUT1 expression on glucose uptake and viability of FTC-133 and 8305c thyroid cancer cells growing in hypoglycemic, normoglycemic and hyperglycemic conditions...
February 2015: Oncology Reports
https://www.readbyqxmd.com/read/25231196/upregulation-of-the-pi3k-akt-pathway-in-the-tumorigenesis-of-canine-thyroid-carcinoma
#9
M Campos, M M J Kool, S Daminet, R Ducatelle, G Rutteman, H S Kooistra, S Galac, J A Mol
BACKGROUND: Information on the genetic events leading to thyroid cancer in dogs is lacking. HYPOTHESIS/OBJECTIVES: Upregulation of the PI3K/Akt pathway has an important role in the tumorigenesis of thyroid carcinoma in dogs. ANIMALS: Fifty-nine dogs with thyroid carcinoma and 10 healthy controls. METHODS: Quantitative RT-PCR was performed for VEGFR-1, VEGFR-2, EGFR, PIK3CA, PIK3CB, PDPK1, PTEN, AKT1, AKT2, COX-2, and CALCA...
November 2014: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/24424051/the-acute-inhibitory-effect-of-iodide-excess-on-sodium-iodide-symporter-expression-and-activity-involves-the-pi3k-akt-signaling-pathway
#10
Caroline Serrano-Nascimento, Silvania da Silva Teixeira, Juan Pablo Nicola, Renato Tadeu Nachbar, Ana Maria Masini-Repiso, Maria Tereza Nunes
Iodide (I(-)) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, because high concentrations of I(-) down-regulate sodium/iodide symporter (NIS) expression and function. In thyrocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) cascade also inhibits NIS expression and function. Because I(-) excess and PI3K/Akt signaling pathway induce similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt cascade mediates the acute and rapid inhibitory effect of I(-) excess on NIS expression/activity...
March 2014: Endocrinology
https://www.readbyqxmd.com/read/23725177/akt1-inhibitory-dnazymes-inhibit-cell-proliferation-and-migration-of-thyroid-cancer-cells
#11
Le Yang, Jin-Ting He, Hong Guan, Ya-Dong Sun
AKT1 is a member of the serine/threoine AGC protein kinase family involved in thyroid cancer metabolism, growth, proliferation and survival. It is overexpressed in thyroid tumors. In this study, we designed two AKT1 specific DNAzymes (DRz1 and DRz2) that target AKT1 mRNA. The results showed that DRz1 could decrease the expression of AKT1 by 58%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosis and inhibited invasion in SW597 cells. In addition, down-regulation of survivin expression was associated with decreased caspase-3, VEGF and MMP2 in SW597 cells after 24 h...
2013: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/23543667/genomic-dissection-of-hurthle-cell-carcinoma-reveals-a-unique-class-of-thyroid-malignancy
#12
COMPARATIVE STUDY
Ian Ganly, Julio Ricarte Filho, Stephanie Eng, Ronald Ghossein, Luc G T Morris, Yupu Liang, Nicholas Socci, Kasthuri Kannan, Qianxing Mo, James A Fagin, Timothy A Chan
CONTEXT: Hurthle cell cancer (HCC) is an understudied cancer with poor prognosis. OBJECTIVE: Our objective was to elucidate the genomic foundations of HCC. DESIGN AND SETTING: We conducted a large-scale integrated analysis of mutations, gene expression profiles, and copy number alterations in HCC at a single tertiary-care cancer institution. METHODS: Mass spectrometry-based genotyping was used to interrogate hot spot point mutations in the most common thyroid oncogenes: BRAF, RET, NRAS, HRAS, KRAS, PIK3CA, MAP2K1, and AKT1...
May 2013: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/23246288/germline-pik3ca-and-akt1-mutations-in-cowden-and-cowden-like-syndromes
#13
Mohammed S Orloff, Xin He, Charissa Peterson, Fusong Chen, Jin-Lian Chen, Jessica L Mester, Charis Eng
Cowden syndrome (CS) is a difficult-to-recognize multiple hamartoma syndrome with high risks of breast, thyroid, and other cancers. Germline mutations in PTEN on 10q23 were found to cause 85% of CS when accrued from tertiary academic centers, but prospective accrual from the community over the last 12 years has revealed a 25% PTEN mutation frequency. PTEN is the phosphatase that has been implicated in a heritable cancer syndrome and subsequently in multiple sporadic cancers and developmental processes. PTEN antagonizes the AKT1/PI3K signaling pathway and has roles in cell cycle, migration, cell polarity, and apoptosis...
January 10, 2013: American Journal of Human Genetics
https://www.readbyqxmd.com/read/22199277/mutational-screening-of-ret-hras-kras-nras-braf-akt1-and-ctnnb1-in-medullary-thyroid-carcinoma
#14
Hans-Juergen Schulten, Jaudah Al-Maghrabi, Khalid Al-Ghamdi, Sherine Salama, Saad Al-Muhayawi, Adeel Chaudhary, Osman Hamour, Adel Abuzenadah, Mamdooh Gari, Mohammed Al-Qahtani
BACKGROUND: Screening medullary thyroid carcinomas (MTCs) for rearranged during transfection (RET) mutations becomes increasingly important for clinical assessment of the disease. The role of mutations in other genes including RAS (i.e. HRAS, KRAS, and NRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-akt murine thymoma viral oncogene homolog 1 (AKT1), and CTNNB1 (β-catenin) is unknown or not fully explored yet for this disease. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded (FFPE) material was the primary source for screening 13 sporadic and inherited MTCs and matched non-tumor specimens...
December 2011: Anticancer Research
https://www.readbyqxmd.com/read/21898122/expression-localization-and-phosphorylation-of-akt1-in-benign-and-malignant-thyroid-lesions
#15
Anna Krześlak, Lech Pomorski, Anna Lipińska
The serine/threonine protein kinase Akt is a key molecule in the phosphatidyl inositol 3-kinase pathway that is often overactivated in human cancers. Three Akt isoforms (Akt1, Akt2, Akt3) have been identified in human cells and they show different distribution and have non-redundant functions. The aim of this study was to determine whether the expression, phosphorylation, and localization of Akt1 isoform in human thyroid malignant lesions are different from those in benign lesions. Nuclear and cytoplasmic fractions were isolated from tissue samples and Western blot method was used to detect Akt1 presence in both cellular fractions...
December 2011: Endocrine Pathology
https://www.readbyqxmd.com/read/21743498/the-effect-akt2-deletion-on-tumor-development-in-pten-mice
#16
P-Z Xu, M-L Chen, S-M Jeon, X-d Peng, N Hay
The serine/threonine kinase Akt is frequently activated in human cancers and is considered an attractive therapeutic target. However, the relative contributions of the different Akt isoforms to tumorigenesis, and the effect of their deficiencies on cancer development are not well understood. We had previously shown that Akt1 deficiency is sufficient to markedly reduce the incidence of tumors in Pten(+/-) mice. Particularly, Akt1 deficiency inhibits endometrial carcinoma and prostate neoplasia in Pten(+/-) mice...
January 26, 2012: Oncogene
https://www.readbyqxmd.com/read/21726664/multiplex-mutation-screening-by-mass-spectrometry-evaluation-of-820-cases-from-a-personalized-cancer-medicine-registry
#17
Carol Beadling, Michael C Heinrich, Andrea Warrick, Erin M Forbes, Dylan Nelson, Emily Justusson, Judith Levine, Tanaya L Neff, Janice Patterson, Ajia Presnell, Arin McKinley, Laura J Winter, Christie Dewey, Amy Harlow, Oscar Barney, Brian J Druker, Kathryn G Schuff, Christopher L Corless
There is an immediate and critical need for a rapid, broad-based genotyping method that can evaluate multiple mutations simultaneously in clinical cancer specimens and identify patients most likely to benefit from targeted agents now in use or in late-stage clinical development. We have implemented a prospective genotyping approach to characterize the frequency and spectrum of mutations amenable to drug targeting present in urothelial, colorectal, endometrioid, and thyroid carcinomas and in melanoma. Cancer patients were enrolled in a Personalized Cancer Medicine Registry that houses both clinical information and genotyping data, and mutation screening was performed using a multiplexed assay panel with mass spectrometry-based analysis to detect 390 mutations across 30 cancer genes...
September 2011: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/21637923/down-regulation-of-%C3%AE-n-acetyl-d-glucosaminidase-increases-akt1-activity-in-thyroid-anaplastic-cancer-cells
#18
Anna Krześlak, Paweł Jóźwiak, Anna Lipińska
O-GlcNAcylation is a common and dynamic modification of intracellular proteins in which β-N-acetyl-glucosamine moieties are attached to hydroxyl groups of serine or threonine residues (O-GlcNAc). Accumulating evidence suggests the critical role of protein O-GlcNAcylation in signal transduction, transcriptional control, cell cycle regulation and protein degradation. However, the exact role of O-GlcNAc modification in tumor pathogenesis or progression remains to be established. In the present study, we investigated the effect of increased O-GlcNAcylation of cellular proteins on IGF‑1 signaling in 8305C thyroid anaplastic cancer cells...
September 2011: Oncology Reports
https://www.readbyqxmd.com/read/21532616/akt1-deficiency-delays-tumor-progression-vascular-invasion-and-distant-metastasis-in-a-murine-model-of-thyroid-cancer
#19
M Saji, K Narahara, S K McCarty, V V Vasko, K M La Perle, K Porter, D Jarjoura, C Lu, S-Y Cheng, M D Ringel
Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis in vivo in several model systems. In contrast, clinical and in vitro studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression in vivo using thyroid hormone receptor (TR) β(PV/PV) knock-in (PV) mice, which develop metastatic thyroid cancer...
October 20, 2011: Oncogene
https://www.readbyqxmd.com/read/21196242/contribution-of-pkb-akt-signaling-to-thyroid-cancer
#20
REVIEW
Giuseppe Viglietto, Nicola Amodio, Donatella Malanga, Marianna Scrima, Carmela De Marco
The family of serine/threonine kinases B/Akt (hereafter Akt) represents a central node in signalling pathways downstream of growth factors, cytokines, and other cellular stimuli. In mammalian cells the Akt family comprises three highly homologous members -known as Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma- that regulate several processes including cell proliferation and survival, growth and response to nutrient availability, migration, tissue invasion and angiogenesis. Aberrant activation of Akt is involved in a variety of human cancers including those arising in the thyroid gland...
2011: Frontiers in Bioscience (Landmark Edition)
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