scholarly journals Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas

2003 ◽  
pp. 505-513 ◽  
Author(s):  
E Puxeddu ◽  
S Moretti ◽  
A Giannico ◽  
M Martinelli ◽  
C Marino ◽  
...  
Keyword(s):  
Genetic Study ◽  
Genetic Alterations ◽  
Biological Behavior ◽  
Tyrosine Kinase Domain ◽  
Fisher Exact Test ◽  
Pathological Features ◽  
Papillary Thyroid ◽  
Association Analyses ◽  
Thyroid Carcinomas ◽  
Clinical And Pathological Features

OBJECTIVE: RET proto-oncogene rearrangements (ret/PTCs) represent the most common genetic alterations found in papillary thyroid carcinomas (PTCs). Correlation of ret/PTC expression with clinical outcome is controversial. The aim of the present study was to analyze the frequency of RET rearrangements in adult PTCs, and to investigate if ret/PTCs influence biological behavior and clinical features of the cancers. DESIGN: Ret/PTC rearrangements were looked for in tIssue samples of 48 PTCs collected at our institution. Data about clinical and pathological features of the tumors were also reviewed. Three separate association analyses were carried out on the cohort evaluating the effects of, respectively, ret/PTC positivity, preferential RET tyrosine kinase domain (RET-TK) expression, and ret/PTC plus RET-TK positivity, on age, sex, tumor size, staging, number of neoplastic foci, and histological subtype. METHODS: The genetic study was conducted with the RT-PCR-Southern blot technique. Standard Student's t-test and Fisher exact test were applied for the association analyses. RESULTS: The molecular genetic study demonstrated the positivity of ret/PTC1 and ret/PTC3 in 13 of 48 tumors (27.1%), and an exclusive or preferential RET-TK expression in 17 cases (35.4%). None of the three genetico-clinical analyses showed any significant association between ret/PTC expression and the clinical and pathological features of the cancers. CONCLUSIONS: These data indicate that RET rearrangements may not play any distinctive role in driving histotype development and cancer progression in these neoplasms. Moreover, they weaken the possibility of using ret/PTC as a prognostic marker for papillary thyroid carcinomas.

Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A

1993 ◽  
Vol 13 (1) ◽  
pp. 358-366
Author(s):  
I Bongarzone ◽  
N Monzini ◽  
M G Borrello ◽  
C Carcano ◽  
G Ferraresi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Tyrosine Kinase ◽  
Kinase Domain ◽  
Regulatory Subunit ◽  
Tyrosine Kinase Domain ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Kinase A

The ret oncogene frequently has been found activated in papillary thyroid carcinomas. A previous characterization of ret activation revealed recombination of its tyrosine kinase domain and sequences derived from an uncharacterized locus (D10S170). The mechanism leading to this recombination was identified as a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with the breakpoints occurring where ret and D10S170 were mapped. To further characterize the activation of ret in papillary thyroid carcinomas, we have now isolated and sequenced a second type of ret oncogenic rearrangement not involving the D10S170 locus. The nucleotide sequence indicated that the transforming activity was created by the fusion of the ret tyrosine kinase domain with part of the RI alpha regulatory subunit of protein kinase A (PKA). This is the first example of an oncogenic activity involving a PKA gene. PKA is the main intracellular cyclic AMP receptor, and its RI alpha subunit gene is located on chromosome 17q. RI alpha-ret transcripts encode two isoforms of the chimeric protein (p76 and p81), which display constitutive tyrosine phosphorylation as well as a tyrosine kinase enzymatic activity. Under nonreducing conditions, both isoforms are found in a dimeric configuration because of both homo- and heterodimer formation. Thus, the in vivo activation of ret in human papillary thyroid carcinomas is provided by the fusion of its tyrosine kinase domain with different genes and can be mediated by different mechanisms of gene rearrangement.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Clinical and Pathological Features of 30 Cases

2018 ◽  
Vol 42 (11) ◽  
pp. 3616-3623 ◽  
Author(s):  
Junko Akaishi ◽  
Tetsuo Kondo ◽  
Kiminori Sugino ◽  
Yuna Ogimi ◽  
Chie Masaki ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Pathological Features ◽  
Papillary Thyroid ◽  
Cribriform Morular Variant ◽  
Clinical And Pathological Features

scholarly journals Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A.

1993 ◽  
Vol 13 (1) ◽  
pp. 358-366 ◽  
Author(s):  
I Bongarzone ◽  
N Monzini ◽  
M G Borrello ◽  
C Carcano ◽  
G Ferraresi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Tyrosine Kinase ◽  
Kinase Domain ◽  
Regulatory Subunit ◽  
Tyrosine Kinase Domain ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Kinase A

The ret oncogene frequently has been found activated in papillary thyroid carcinomas. A previous characterization of ret activation revealed recombination of its tyrosine kinase domain and sequences derived from an uncharacterized locus (D10S170). The mechanism leading to this recombination was identified as a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with the breakpoints occurring where ret and D10S170 were mapped. To further characterize the activation of ret in papillary thyroid carcinomas, we have now isolated and sequenced a second type of ret oncogenic rearrangement not involving the D10S170 locus. The nucleotide sequence indicated that the transforming activity was created by the fusion of the ret tyrosine kinase domain with part of the RI alpha regulatory subunit of protein kinase A (PKA). This is the first example of an oncogenic activity involving a PKA gene. PKA is the main intracellular cyclic AMP receptor, and its RI alpha subunit gene is located on chromosome 17q. RI alpha-ret transcripts encode two isoforms of the chimeric protein (p76 and p81), which display constitutive tyrosine phosphorylation as well as a tyrosine kinase enzymatic activity. Under nonreducing conditions, both isoforms are found in a dimeric configuration because of both homo- and heterodimer formation. Thus, the in vivo activation of ret in human papillary thyroid carcinomas is provided by the fusion of its tyrosine kinase domain with different genes and can be mediated by different mechanisms of gene rearrangement.

Cannabis-associated arteritis

VASA ◽  
2010 ◽  
Vol 39 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Grotenhermen
Keyword(s):  
Systematic Review ◽  
Case Reports ◽  
Case Series ◽  
Cardiovascular Effects ◽  
Causative Factor ◽  
Cannabis Use ◽  
Thromboangiitis Obliterans ◽  
Pathological Features ◽  
Scientific Support ◽  
Clinical And Pathological Features

Background: To investigate the hypothesis that cases of arteritis similar to thromboangiitis obliterans (TAO) and associated with the use of cannabis were caused by cannabis or THC (dronabinol), or that cannabis use is a co-factor of TAO. Patients and methods: A systematic review on case reports and the literature on so-called cannabis arteritis, TAO, and cardiovascular effects of cannabinoids was conducted. Results: Fifteen reports with 57 cases of an arteritis associated with the use of cannabis and two additional case series of TAO, in which some patients also used cannabis, were identified. Clinical and pathological features of cannabis-associated arteritis do not differ from TAO and the major risk factor of TAO, tobacco use, was present in most, if not in all of these cases. The proposed pathophysiological mechanisms for the development of an arteritis by cannabis use are not substantiated. Conclusions: The hypothesis of cannabis being a causative factor or co-factor of TAO or an arteritis similar to TAO is not supported by the available evidence. The use of the term “cannabis arteritis” should be avoided until or unless more convincing scientific support is forthcoming.

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