- 同
- thyroid transcription factor-1
- 甲状腺、及び末梢肺において上皮細胞の核に出現する核転写蛋白。
- ●甲状腺
- 瀘胞上皮を由来とする腫瘍(乳頭癌papillary carcinoma、濾胞癌follicular carcinomaなど)。髄様癌medullary carcinomaにも高率に陽性。(Hirsch at.alなど)
- ●肺
- 肺原発の腫瘍であることの確認。悪性腫瘍での陽性率は以下のとおり
- 腺癌(80%程度)
- 小細胞癌(90%程度)
- カルチノイド(50%以上)
- 大細胞性神経内分泌細胞癌(約50%)
- 大細胞癌では低率(10%以下)
- 肺扁平上皮癌では通常陰性(10%以下には陽性Pelosi et.al)。
- 中皮腫では陰性であるため、肺腺癌との鑑別に有用。
- ただし、特異度は完全ではない。特に小細胞癌は肺原発以外のもの(前立腺、膀胱、食道、子宮頚部、胃、大腸、外陰部)にも陽性が報告されているため、小細胞癌の発生部位の鑑別には有用ではない。
参考
- http://immuno.med.kobe-u.ac.jp/TTF-1/TTF-1.shtml
WordNet
- the 20th letter of the Roman alphabet (同)t
PrepTutorEJDIC
- tritiumの化学記号
- 《略》 teetotal; teetotaller; tuberculin-tested
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/03/25 16:18:45」(JST)
[Wiki en表示]
Not to be confused with transcription termination factor, RNA polymerase I or TTF1.
NK2 homeobox 1 |
PDB rendering based on 1ftt. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1ftt
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Identifiers |
Symbols |
NKX2-1 (; BCH; BHC; NK-2; NKX2.1; NKX2A; TEBP; TITF1; TTF-1; TTF1) |
External IDs |
OMIM: 600635 MGI: 108067 HomoloGene: 2488 GeneCards: NKX2-1 Gene |
Gene Ontology |
Molecular function |
• DNA binding
• sequence-specific DNA binding transcription factor activity
• RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
• protein binding
• sequence-specific DNA binding
• transcription regulatory region DNA binding
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Cellular component |
• nucleus
• nucleoplasm
• transcription factor complex
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Biological process |
• negative regulation of transcription from RNA polymerase II promoter
• neuron migration
• phospholipid metabolic process
• axon guidance
• brain development
• endoderm development
• locomotory behavior
• response to hormone stimulus
• positive regulation of gene expression
• negative regulation of epithelial to mesenchymal transition
• globus pallidus development
• hippocampus development
• cerebral cortex cell migration
• forebrain dorsal/ventral pattern formation
• forebrain neuron fate commitment
• cerebral cortex GABAergic interneuron differentiation
• pituitary gland development
• lung development
• negative regulation of cell migration
• negative regulation of transforming growth factor beta receptor signaling pathway
• thyroid gland development
• forebrain development
• developmental induction
• Leydig cell differentiation
• menarche
• positive regulation of transcription, DNA-dependent
• positive regulation of transcription from RNA polymerase II promoter
• anatomical structure formation involved in morphogenesis
• oligodendrocyte differentiation
• lung saccule development
• epithelial tube branching involved in lung morphogenesis
• Clara cell differentiation
• Type II pneumocyte differentiation
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
|
Entrez |
7080 |
21869 |
|
Ensembl |
ENSG00000136352 |
ENSMUSG00000001496 |
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UniProt |
P43699 |
P50220 |
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RefSeq (mRNA) |
NM_001079668 |
NM_001146198 |
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RefSeq (protein) |
NP_001073136 |
NP_001139670 |
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Location (UCSC) |
Chr 14:
36.99 – 36.99 Mb |
Chr 12:
56.53 – 56.54 Mb |
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PubMed search |
[1] |
[2] |
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NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1 (TTF-1), is a protein which in humans is encoded by the NKX2-1 gene.[1][2]
Contents
- 1 Function
- 2 Clinical significance
- 3 Interactions
- 4 References
- 5 Further reading
- 6 External links
Function[edit]
Thyroid transcription factor-1 (TTF-1) is a protein that regulates transcription of genes specific for the thyroid, lung, and diencephalon. It is also known as thyroid specific enhancer binding protein. It is used in anatomic pathology as a marker to determine if a tumor arises from the lung or thyroid. NKX2.1 can be induced by activin A via SMAD2 signaling in a human embryonic stem cell differentiation model.[3]
Clinical significance[edit]
Micrograph of a metastatic lung adenocarcinoma (found in the brain) that exhibits nuclear staining (brown) for TTF-1.
TTF-1 positive cells are found in the lung as type II pneumocytes and Clara cells. In the thyroid, follicular and parafollicular cells are also positive for TTF-1.
For lung cancers, adenocarcinomas are usually positive, while squamous cell carcinomas and large cell carcinomas are rarely positive. Small cell carcinomas (of any primary site) are usually positive. TTF1 is more than merely a clinical marker of lung adenocarcinoma. It plays an active role in sustaining lung cancer cells in view of the experimental observation that it is mutated in lung cancer.[4][5][6][7]
However others have found that TTF-1 staining is often positive in pulmonary adenocarcinomas, large cell carcinomas, small-cell lung carcinomas, neuroendocrine tumors other than small-cell lung carcinomas and extrapulmonary small-cell carcinomas.[8]
It is also positive in thyroid cancers and is used for monitoring for metastasis and recurrence.[9]
Interactions[edit]
NK2 homeobox 1 has been shown to interact with Calreticulin[10] and PAX8.[11]
References[edit]
- ^ "Entrez Gene: NKX2-1".
- ^ Guazzi S, Price M, De Felice M, Damante G, Mattei MG, Di Lauro R (November 1990). "Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity". EMBO J. 9 (11): 3631–9. PMC 552115. PMID 1976511.
- ^ Li Y, Eggermont K, Vanslembrouck V, Verfaillie C (December 2012). "NKX2-1 activation by SMAD2 signaling after definitive endoderm differentiation in Human ESC". Stem Cells Dev. doi:10.1089/scd.2012.0620. PMID 23259454.
- ^ Kendall J, Liu Q, Bakleh A, Krasnitz A, Nguyen KC, Lakshmi B, Gerald WL, Powers S, Mu D (October 2007). "Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer". Proc. Natl. Acad. Sci. U.S.A. 104 (42): 16663–8. doi:10.1073/pnas.0708286104. PMC 2034240. PMID 17925434.
- ^ Tanaka H, Yanagisawa K, Shinjo K, Taguchi A, Maeno K, Tomida S, Shimada Y, Osada H, Kosaka T, Matsubara H, Mitsudomi T, Sekido Y, Tanimoto M, Yatabe Y, Takahashi T. (July 2007). "Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1". Cancer Research 67 (13): 6007–11. doi:10.1158/0008-5472.CAN-06-4774. PMID 17616654.
- ^ Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA, et al. (December 2007). "Characterizing the cancer genome in lung adenocarcinoma". Nature 450 (7171): 893–8. doi:10.1038/nature06358. PMC 2538683. PMID 17982442.
- ^ Kwei KA, Kim YH, Girard L, Kao J, Pacyna-Gengelbach M, Salari K, Lee J, Choi YL, Sato M, Wang P, Hernandez-Boussard T, Gazdar AF, Petersen I, Minna JD, Pollack JR. (June 2008). "Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer.". Oncogene 27 (25): 3635–40. doi:10.1038/sj.onc.1211012. PMC 2903002. PMID 18212743.
- ^ Kalhor N, Zander DS, Liu J (August 2006). "TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material". Mod. Pathol. 19 (8): 1117–23. doi:10.1038/modpathol.3800629. PMID 16680154.
- ^ Espinoza CR, Schmitt TL, Loos U (August 2001). "Thyroid transcription factor 1 and Pax8 synergistically activate the promoter of the human thyroglobulin gene". J. Mol. Endocrinol. 27 (1): 59–67. doi:10.1677/jme.0.0270059. PMID 11463576.
- ^ Perrone L, Tell G, Di Lauro R (February 1999). "Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain". J. Biol. Chem. 274 (8): 4640–5. doi:10.1074/jbc.274.8.4640. PMID 9988700.
- ^ Di Palma T, Nitsch R, Mascia A, Nitsch L, Di Lauro R, Zannini M (January 2003). "The paired domain-containing factor Pax8 and the homeodomain-containing factor TTF-1 directly interact and synergistically activate transcription". J. Biol. Chem. 278 (5): 3395–402. doi:10.1074/jbc.M205977200. PMID 12441357.
Further reading[edit]
- Lau SK, Luthringer DJ, Eisen RN (2002). "Thyroid transcription factor-1: a review.". Appl. Immunohistochem. Mol. Morphol. 10 (2): 97–102. doi:10.1097/00022744-200206000-00001. PMID 12051643.
- Guazzi S, Price M, De Felice M, et al. (1990). "Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity.". EMBO J. 9 (11): 3631–9. PMC 552115. PMID 1976511.
- Oguchi H, Pan YT, Kimura S (1995). "The complete nucleotide sequence of the mouse thyroid-specific enhancer-binding protein (T/EBP) gene: extensive identity of the deduced amino acid sequence with the human protein.". Biochim. Biophys. Acta 1261 (2): 304–6. doi:10.1016/0167-4781(95)00033-D. PMID 7711079.
- Saiardi A, Tassi V, De Filippis V, Civitareale D (1995). "Cloning and sequence analysis of human thyroid transcription factor 1.". Biochim. Biophys. Acta 1261 (2): 307–10. doi:10.1016/0167-4781(95)00034-E. PMID 7711080.
- Ikeda K, Clark JC, Shaw-White JR, et al. (1995). "Gene structure and expression of human thyroid transcription factor-1 in respiratory epithelial cells.". J. Biol. Chem. 270 (14): 8108–14. doi:10.1074/jbc.270.44.26460. PMID 7713914.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Ghaffari M, Zeng X, Whitsett JA, Yan C (1998). "Nuclear localization domain of thyroid transcription factor-1 in respiratory epithelial cells.". Biochem. J. 328 (3): 757–61. PMC 1218983. PMID 9396717.
- Hamdan H, Liu H, Li C, et al. (1998). "Structure of the human Nkx2.1 gene.". Biochim. Biophys. Acta 1396 (3): 336–48. doi:10.1016/S0167-4781(97)00210-8. PMID 9545595.
- Perrone L, Tell G, Di Lauro R (1999). "Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain.". J. Biol. Chem. 274 (8): 4640–5. doi:10.1074/jbc.274.8.4640. PMID 9988700.
- Naltner A, Ghaffari M, Whitsett JA, Yan C (2000). "Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent.". J. Biol. Chem. 275 (1): 56–62. doi:10.1074/jbc.275.1.56. PMID 10617585.
- Missero C, Pirro MT, Di Lauro R (2000). "Multiple ras downstream pathways mediate functional repression of the homeobox gene product TTF-1.". Mol. Cell. Biol. 20 (8): 2783–93. doi:10.1128/MCB.20.8.2783-2793.2000. PMC 85494. PMID 10733581.
- Naltner A, Wert S, Whitsett JA, Yan C (2000). "Temporal/spatial expression of nuclear receptor coactivators in the mouse lung.". Am. J. Physiol. Lung Cell Mol. Physiol. 279 (6): L1066–74. PMID 11076796.
- Yan C, Naltner A, Conkright J, Ghaffari M (2001). "Protein-protein interaction of retinoic acid receptor alpha and thyroid transcription factor-1 in respiratory epithelial cells.". J. Biol. Chem. 276 (24): 21686–91. doi:10.1074/jbc.M011378200. PMID 11274148.
- Missero C, Pirro MT, Simeone S, et al. (2001). "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription.". J. Biol. Chem. 276 (36): 33569–75. doi:10.1074/jbc.M104963200. PMID 11438542.
- Yi M, Tong GX, Murry B, Mendelson CR (2002). "Role of CBP/p300 and SRC-1 in transcriptional regulation of the pulmonary surfactant protein-A (SP-A) gene by thyroid transcription factor-1 (TTF-1).". J. Biol. Chem. 277 (4): 2997–3005. doi:10.1074/jbc.M109793200. PMID 11713256.
- Liu C, Glasser SW, Wan H, Whitsett JA (2002). "GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression.". J. Biol. Chem. 277 (6): 4519–25. doi:10.1074/jbc.M107585200. PMID 11733512.
- Ng WK, Chow JC, Ng PK (2002). "Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens.". Cancer 96 (1): 43–8. doi:10.1002/cncr.10310. PMID 11836702.
- Pohlenz J, Dumitrescu A, Zundel D, et al. (2002). "Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice.". J. Clin. Invest. 109 (4): 469–73. doi:10.1172/JCI14192. PMC 150877. PMID 11854318.
- Krude H, Schütz B, Biebermann H, et al. (2002). "Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency.". J. Clin. Invest. 109 (4): 475–80. doi:10.1172/JCI14341. PMC 150790. PMID 11854319.
- Miccadei S, De Leo R, Zammarchi E, et al. (2002). "The synergistic activity of thyroid transcription factor 1 and Pax 8 relies on the promoter/enhancer interplay.". Mol. Endocrinol. 16 (4): 837–46. doi:10.1210/me.16.4.837. PMID 11923479.
External links[edit]
- TITF1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
PDB gallery
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1ftt: THYROID TRANSCRIPTION FACTOR 1 HOMEODOMAIN (RATTUS NORVEGICUS)
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Transcription factors and intracellular receptors
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(1) Basic domains
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(1.1) Basic leucine zipper (bZIP) |
- Activating transcription factor
- AP-1
- c-Fos
- FOSB
- FOSL1
- FOSL2
- JDP2
- c-Jun
- JUNB
- JunD
- BACH
- BATF
- BLZF1
- C/EBP
- CREB
- CREM
- DBP
- DDIT3
- GABPA
- HLF
- MAF
- NFE
- NFIL3
- NRL
- NRF
- XBP1
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(1.2) Basic helix-loop-helix (bHLH) |
- ATOH1
- AhR
- AHRR
- ARNT
- ASCL1
- BHLH
- ARNTL
- CLOCK
- EPAS1
- FIGLA
- HAND
- HES
- HEY
- HES1
- HIF
- ID
- LYL1
- MESP2
- MXD4
- MYCL1
- MYCN
- Myogenic regulatory factors
- Neurogenins
- NeuroD
- NPAS
- OLIG
- Pho4
- Scleraxis
- SIM
- TAL
- Twist
- USF1
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(1.3) bHLH-ZIP |
- AP-4
- MAX
- MITF
- MNT
- MLX
- MXI1
- Myc
- SREBP
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(1.4) NF-1 |
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(1.5) RF-X |
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(1.6) Basic helix-span-helix (bHSH) |
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(2) Zinc finger DNA-binding domains
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(2.1) Nuclear receptor (Cys4) |
subfamily 1 |
- Thyroid hormone
- CAR
- FXR
- LXR
- PPAR
- PXR
- RAR
- ROR
- Rev-ErbA
- VDR
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subfamily 2 |
- COUP-TF
- Ear-2
- HNF4
- PNR
- RXR
- Testicular receptor
- TLX
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subfamily 3 |
- Steroid hormone
- Androgen
- Estrogen
- Glucocorticoid
- Mineralocorticoid
- Progesterone
- Estrogen related
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subfamily 4 |
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subfamily 5 |
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subfamily 6 |
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subfamily 0 |
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(2.2) Other Cys4 |
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(2.3) Cys2His2 |
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(2.4) Cys6 |
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(2.5) Alternating composition |
- AIRE
- DIDO1
- GRLF1
- ING
- JARID
- JMJD1B
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(2.6) WRKY |
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(3) Helix-turn-helix domains
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(4) β-Scaffold factors with minor groove contacts
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(4.1) Rel homology region |
- NF-κB
- NFKB1
- NFKB2
- REL
- RELA
- RELB
- NFAT
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(4.2) STAT |
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(4.3) p53 |
- p53
- TBX
- 1
- 2
- 3
- 5
- 19
- 21
- 22
- TBR1
- TBR2
- TFT
- MYRF
- TP63
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(4.4) MADS box |
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(4.6) TATA-binding proteins |
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(4.7) High-mobility group |
- BBX
- HMGB
- HMGN
- HNF
- LEF1
- SOX
- 1
- 2
- 3
- 4
- 5
- 6
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 18
- 21
- SRY
- SSRP1
- TCF
- TOX
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(4.9) Grainyhead |
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(4.10) Cold-shock domain |
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(4.11) Runt |
- CBF
- CBFA2T2
- CBFA2T3
- RUNX1
- RUNX2
- RUNX3
- RUNX1T1
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(0) Other transcription factors
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(0.2) HMGI(Y) |
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(0.3) Pocket domain |
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(0.5) AP-2/EREBP-related factors |
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(0.6) Miscellaneous |
- ARID
- CAP
- IFI
- MLL
- MNDA
- NFY
- Rho/Sigma
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see also transcription factor/coregulator deficiencies
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
UpToDate Contents
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English Journal
- Large-cell neuroendocrine carcinoma of the skin: ultrastructural and immunohistochemical findings.
- Nagase K1, Kimura H2, Yonekura N2, Koba S2, Inoue T2, Narisawa Y2.
- Journal of cutaneous pathology.J Cutan Pathol.2016 Nov;43(11):1067-1073. doi: 10.1111/cup.12794. Epub 2016 Sep 9.
- Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive neuroendocrine tumor, found mainly in the lung. Although LCNEC has been reported in various organs, LCNEC of the skin is extremely rare, poorly recognized and probably underestimated. Here we report a case of LCNEC of the skin
- PMID 27514507
- Concurrent spindle-cell thymoma and thymic cysts in a Barbary sheep (Ammotragus lervia): case report and review of the literature.
- Li WT1, Chang HW1, Jeng CR1, Liu CH1, Wang FI1, Chang LJ1, Pang VF2.
- Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.J Vet Diagn Invest.2016 Nov;28(6):744-749. Epub 2016 Oct 3.
- An ~21-year-old female Barbary sheep (Ammotragus lervia) died spontaneously following a lengthy episode of difficulty in walking. An ~6 × 3 × 3 cm, unilocular cystic growth was found in the cranioventral thorax. The fibrotic cystic wall, lined by a single layer of flattened to cuboidal epithelial
- PMID 27698165
- [BEDT-TTF][Fe(C2O4)Cl2]: an organic-inorganic hybrid semiconductive antiferromagnet.
- Zhang B1, Zhang Y2, Wang Z3, Yang D4, Gao Z5, Wang D6, Guo Y6, Zhu D1, Mori T7.
- Dalton transactions (Cambridge, England : 2003).Dalton Trans.2016 Oct 25;45(42):16561-16565.
- A radical cation salt composed of an organic donor, BEDT-TTF1.0+, and a one-dimensional inorganic anion, [Fe(C2O4)Cl2-]n, was obtained by electrocrystallization, and was identified as a semiconductor with values of σ300K = 3.0 × 10-5 S cm-1. Spin-canted antiferromagnetic long-range ordering was ob
- PMID 27344978
- Papillary Thyroid Carcinoma Cervical Lymph Node Metastasis with Cystic Change Differentiated from Congenital Cystic Lesions with the Assistance of Immunohistochemistry: A Case Study.
- Liang Y1, Zuo T2.
- Head and neck pathology.Head Neck Pathol.2016 Oct 21. [Epub ahead of print]
- Diagnosis of cystic papillary thyroid carcinoma (PTC) lymph node metastasis at head neck region can be a challenge in the absence of known PTC history. The congenital cystic lesions of head neck, especially thyroglossal duct cyst (TGDC) and branchial cleft cyst (BCC), are major differential diagnose
- PMID 27770399
Japanese Journal
- 臨牀指針 TTF-1陰性であったEGFR遺伝子変異陽性肺腺癌の一例
- 肺腺がんにおけるTTF-1/NKX2-1の相反する2つの機能 (特集 肺がんの個別化医療)
- <原著>IASLC/ATS/ERS分類に基づいた肺腺癌組織亜型の分子生物学的特徴--既知の予後予測マーカーとの関連
- 近畿大学医学雑誌 = Medical Journal of Kinki University 40(1-2), 47-54, 2015-06-01
- NAID 120005736749
- 症例 術中TTF-1免疫染色と血清ProGRPは肺癌と卵巣癌による腹膜播種・副腎転移の鑑別に有用である : 卵巣粘液性腫瘍を合併した小細胞肺癌の一例
Related Links
- Thyroid transcription factor-1 (TTF-1) はホメオボックスを有するホメオドメインタンパクファミリーに属し、甲状腺、肺、間脳で特異的に発現している転写因子です。このタンパクは甲状腺特異遺伝子の転写調節因子であり、また肺特異分化 ...
- TTF-1 (Thyroid transcription factor 1) 肺腺癌と甲状腺癌で陽性。他の腺癌で陰性。 Surfactant apoprotein 肺腺癌の一部で陽性。 Cytokeratin 7 / Cytokeratin 20 肺腺癌はCK7(+), CK20(-) 大腸癌はCK7(-), CK20(+), CDX-2(+) 乳癌で ...
- 原発性肺癌におけるThyroid Transcription Factor-1(TTF-1)発現の免疫組織化学的検討 Immunohistochemical Study of Thyroid Transcription Factor-1 ... 石和 直樹 Ishiwa Naoki 横浜市立大学医学部附属病院病理部:横浜市立大学第1外科 ...
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