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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using monoclonal antibodies (MoABs) against blood group determinants and related carbohydrate sequences, it is now possible to clarify their carcinoma-associated modulation at a molecular level. In the present study a panel of MoABs against different type 1 chain derived blood group antigens, comprising A, B, H type 1, Le(a), sialyl-Le(a) (CA 19-9), sialyl type 1 structure (CA 50), and Le(b) was used to investigate their immunoreactivity in 38 medullary carcinomas of the thyroid (MTC) and in normal thyroid tissue. The antigens were not expressed in normal follicular or C-cells but were expressed to a various extent in MTC. The studies revealed some characteristic anomalies in the frequency and patterns of tumor-associated antigen expression. The MoAB C 50 stained 32 of the 38 tumors, H type 1 (Le(d)) was demonstrated in 21 and the Le(b) antigen in 27. The Le(a)- and the A antigen were detected in 10 and 12 tumors and the B antigen in one. From the results some rules about the pathways for tumor-associated re-expression of these antigens can be deduced. Le(a) antigen expression was significantly correlated with the CA 50 and Le(b) antigens. The significant relation observed between A-, H1-, and Le(b) antigen formation in MTC suggests the existence of a carcinoma-associated fucosyltransferase committing the type 1 precursor chain along the H1-antigen pathway, and by further glycosylation to an A-, B-, or a Le(b) antigen. Comparative studies of tumor-associated H type 1 and H type 2 antigen expression revealed that H type 2 antigen synthesis was significantly related to a blood type 0 in the host. On the other hand, H1 antigen reactivity was independent of the AB0 blood type of the hosts and was also detected in H type 2 antigen-negative tumors. These findings support the proposal that even in tumor tissue, H antigen expression is still determined by the interaction of at least two different genes. Despite the occurrence of the precursor substance (CA 50) and the formation of the Le(a)- and Le(b) antigens, indicating the presence of a alpha 1,4-fucosyl-transferase (Lewis-enzyme), only two tumors showed the formation of CA 19-9. In conclusion, the investigations demonstrated the dominant re-expression of three type 1 chain-derived structures in MTC, namely H type 1, Le(b), and CA 50. These findings support the general concept demonstrated in other carcinomas, that fucosyl- and sialyltransferases are preferentially activated in MTC.(ABSTRACT TRUNCATED AT 400 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Blood group antigen expression in medullary carcinoma of the thyroid. An immunohistochemical study on the occurrence of type 1 chain-derived antigens. 135 24

The colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-on e (MTC) was found to inhibit concanavalin A- and formyl-methionyl-leucyl-phenylalanine-stimulated human neutrophil degranulation and to depolymerize the microtubule network at low concentrations. The inhibitory capacity of MTC for neutrophil degranulation was similar to that of nocodazole and taxol. The mechanistically distinct actions of these three drugs on microtubules support the notion that microtubules are required for neutrophil enzyme release in response to different stimuli. MTC affected both degranulation and microtubule integrity rapidly and reversibly, after only a 5-min preincubation. At these short periods of incubation, colchicine irreversibly affected neutrophil degranulation only at concentrations in the millimolar range and behaved similarly to its microtubule-inactive analogue lumicolchicine. At longer times of incubation (30-60 min), low concentrations of both MTC and colchicine induced a drastic shortening and depolymerization of microtubules, preserving the microtubule-organizing center, but only MTC was able to completely inhibit the secretory response of neutrophils. These results suggest that the colchicine effect on neutrophil degranulation is not specifically mediated by its action on the microtubule network of these cells. In contrast, the specific and reversible effects of the colchicine analogue MTC suggest that it may be a useful agent with which to study the role of microtubules in this cellular function.
Mol Pharmacol 1989 Oct
PMID:Cytoplasmic microtubules in human neutrophil degranulation: reversible inhibition by the colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1- one. 268 3

The utility of polymerase-mediated assays in the detection of the t(11;14) involving the bcl-1 major translocation cluster (bcl-1 MTC) was evaluated by analyzing DNA from 33 patients with mantle cell lymphoma, 14 patients with other non-Hodgkin's lymphomas, and five patients with reactive lymphoid hyperplasia. The polymerase chain reaction (PCR) assay was performed using a consensus immunoglobin heavy-chain joining region primer in conjunction with a chromosome 11 specific oligonucleotide primer flanking the translocation site. The sensitivity and specificity of the assay were confirmed by correlation of the (PCR) assay data with restriction analysis. Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis. Amplicons were detectable by PCR in 85% (11 of 13) of the cases shown to be bcl-1 rearranged by restriction analysis. Failure to detect amplification products in DNA samples from non-mantle cell lymphomas and reactive follicular hyperplasia further confirmed the specificity of the assay. Sequential hybridization of the PCR products with oligonucleotide probes 3' to the bcl-1 MTC primer revealed that the breakpoints in the bcl-1 MTC were clustered around an Sst I restriction site over a range of 170 base pairs. The study demonstrates that PCR-mediated assay for the detection of the t(11;14) at the bcl-1 MTC is specific and sensitive and can be used as an adjunct to restriction analysis in routine diagnostics.
Diagn Mol Pathol 1995 Mar
PMID:Polymerase chain reaction detection of the t(11;14) translocation involving the bcl-1 major translocation cluster in mantle cell lymphoma. 773 55

Constitutional mutations of the RET proto-oncogene have been identified in multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) families. We sequenced RET exons 10 and 11 in 86 unrelated patients with an inherited predisposition to MTC (excluding MEN 2B). Germ-line mutations were identified in 93% of the MEN 2A families and 67% of the FMTC families tested. All were missense mutations affecting one of three cysteines in the extracellular domain of the RET tyrosine kinase receptor. The prevalence of phaeochromocytoma and hyperparathyroidism was significantly higher in families with a mutation of cysteine 634. These data confirm the preferential localisation of MEN 2A and FMTC associated mutations and the strong correlation between clinical manifestations and the position of RET mutation. Although direct sequencing of RET exons 10 and 11 allows the identification of a constitutional mutation in a large proportion of MEN 2A and FMTC families, our data sustain the existence of other MTC predisposing mutations elsewhere in RET coding or regulating region.
Hum Mol Genet 1994 Nov
PMID:RET proto-oncogene mutations in French MEN 2A and FMTC families. 787 9

The susceptibility loci for the three multiple endocrine neoplasia (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosine kinase. The majority of MEN 2A and familial medullary thyroid carcinoma results from missense mutations within one of five cysteine codons in the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonine for a methionine at codon 918 in the tyrosine kinase catalytic domain, in the germline of 26 of 28 apparently distinct families with MEN 2B. DNA from five of 13 apparently sporadic MTC and one of 12 apparently sporadic phaeochromocytomas harboured a similar mutation, but the corresponding germline DNA was wildtype in each case.
Hum Mol Genet 1994 Feb
PMID:Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. 791 97

In this study, the alterations (amplification/rearrangement) of 3 D-type cyclins loci were analyzed by Southern blot in 5 dysplastic head and neck lesions and 79 primary head and neck squamous cell carcinoma (HNSCC) of Indian patients to understand the role of the cyclins in development of the disease. No alteration was found in the dysplastic lesions. Overall, 54% of alterations were found in bcl-1/CCND1 locus, whereas amplification was only found in CCND2 and CCND3 loci in 12% and 2% samples, respectively. In bcl-1/CCND1 locus amplification was the major type of alteration; however, rearrangement as well as coalterations had been seen in some samples indicating the common mechanism of activation of this locus in different types of tumors. In bcl-1 region, the breakpoint clustered in the MTC (major translocation cluster) region, whereas in CCND1 the breakpoint located near 3' end of the gene. The coamplification of CCND2 locus with bcl-1, bcl-1/CCND1, and CNND3 loci suggests cumulative effect of these genes in this tumor. The significant association was seen between bcl-1/CCND1 locus alteration with HPV prevalence and poor patient outcome indicating its importance as prognostic marker. This indicates that the genetic instability caused due to HPV infection may induce the alterations in the bcl-1/CCND1 locus, which will provide selective growth advantage to the specific malignant clones resulting poor prognosis of the disease.
Diagn Mol Pathol 2006 Mar
PMID:Genetic alterations (amplification and rearrangement) of D-type cyclins loci in head and neck squamous cell carcinoma of Indian patients: prognostic significance and clinical implications. 1653 63

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the RET proto-oncogene. Three distinct clinical subtypes of MEN 2 have been characterized: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The specific RET mutation may suggest a predilection toward a particular phenotype and clinical course, with strong genotype-phenotype correlations. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on classification of RET mutations into risk levels according to genotype-phenotype correlations. The excellent prognosis for MTC diagnosed at its earliest stage underscores the importance of prospective screening (calcitonin screening) for sporadic MTC and early diagnosis by RET-mutation analysis for hereditary MTC. MEN 2 provides a unique model for early prevention and cure of cancer and for the roles of stratified mutation-based diagnosis and therapy of carriers.
Mol Cell Endocrinol 2010 Jun 30
PMID:Molecular genetics and phenomics of RET mutations: Impact on prognosis of MTC. 2008 56

The introduction of PET(-CT) has brought about a major paradigm shift in the management of thyroid carcinoma, especially from the diagnostic standpoint. From the viewpoint of patient management, the areas where it has made significant impact include the following: (1) the detection of disease focus in patients with differentiated thyroid carcinoma with elevated Tg levels and negative radioiodine scan. When localized disease is identified with F-18 FDG-PET-CT, surgery or focused radiotherapy could be utilized to eradicate the tumor; (2) the localization of disease in patients of MTC with elevated serum calcitonin levels; (3) the detection of unsuspected focal F-18 FDG uptake in the thyroid in patients undergoing whole body F-18 FDG PET for a different indication. This would prompt a workup to rule out thyroid carcinoma. The use of I-124 is evolving at this time and has been of great promise with regard to (a) its better efficacy of lesion detection and (b) the ability to provide lesion-specific dosimetry. In addition, F-18 FDG PET appears to be of potential value in patients with thyroid lymphoma in making the initial diagnosis, monitoring therapeutic response, and assessing for residual disease and/or recurrence.
Methods Mol Biol 2011
PMID:PET and PET/CT in the management of thyroid cancer. 2133 36

We analyzed the in vitro effects of celecoxib, a COX-2 inhibitor, and determined if celecoxib can sensitize a human MTC-derived cell line (TT) to chemotherapeutics. We found that celecoxib induced apoptosis in TT cells and decreased drug efflux by reducing the expression of MDR-1 mRNA, which codes for the drug efflux pump P-gp. We also observed that TT cells were 10-fold more resistant to doxorubicin than to vinorelbine, mimicking what can be observed in clinical practice. In addition, we found that the combination of celecoxib and vinorelbine, but not doxorubicin, induced a significant reduction in cell viability and a significant increase in apoptosis. In conclusion, we showed that celecoxib was able to enhance the chemotherapeutic effect of vinorelbine. A clinical trial exploring the in vivo activities of celecoxib in MTC patients who cannot benefit from available treatments would be desirable, taking into account the possible risks of cardiovascular effects of this drug.
Mol Cell Endocrinol 2012 May 15
PMID:Celecoxib, a cyclooxygenase-2 inhibitor, potentiates the chemotherapic effect of vinorelbine in the medullary thyroid cancer TT cell line. 2230 71

Medullary thyroid carcinoma is a rare malignant tumor originating in parafollicular C cells. It accounts for 5 to 8% of all thyroid cancers. MTC develops in either sporadic (75%) or hereditary form (25%). Genetic and molecular studies have demonstrated the involvement of the RET proto-oncogene in hereditary MTC and, less often, in its sporadic form. Although a strong genotype-phenotype correlation has been described, wide clinical heterogeneity is observed among families with the same RET mutation or even in carriers of the same kindred. In recent years, several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. Some studies have reported associations between the presence of polymorphisms and development or progression of MTC. Nonetheless, other studies failed to demonstrate any effect of the RET variants. Differences in the genetic background of distinct populations or methodological approaches have been suggested as potential reasons for the conflicting results. Here, we review current knowledge concerning the molecular pathogenesis of sporadic and hereditary MTC. In particular, we analyze the role of RET polymorphisms in the clinical presentation and prognosis of MTC based on the current literature.
Int J Mol Sci 2012
PMID:Molecular basis of medullary thyroid carcinoma: the role of RET polymorphisms. 2231 49


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