Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disulfide (S-S) bonds and sulfhydryl (-SH) groups in skin-limited and systemic amyloidoses in frozen and paraffin-embedded sections were examined with a thiol reagent, N-(7-dimethylamino-4-methyl-3-coumarinyl)-maleimide (DACM). In frozen sections, dermal amyloids of skin-limited amyloidoses contained a large number of S-S bonds but no -SH groups [macular amyloidosis (9 cases), lichen amyloidosis (4), and skin tumor-associated (seborrheic keratosis) amyloidosis (1)]. In contrast, amyloids of systemic amyloidoses contained no S-S bonds or -SH groups [primary and myeloma-associated amyloidoses (1 each)]. The identical results were obtained from paraffin-embedded sections in skin-limited amyloidoses [macular (31), biphasic (4), lichenoid (9) and skin tumor-associated Bowen's disease (3), seborrheic keratosis (2), solar keratosis (2), porokeratosis Mibelli (1), and basal cell epithelioma (1) amyloidoses], systemic amyloidoses [primary (3), myeloma-associated (2), and secondary (2) amyloidoses] and tumefactive amyloidoses of the tongue (2). Furthermore, amyloid-like deposits confirmed by various histochemical stainings were found in the epidermis in 27/67 cases of skin-limited amyloidoses in both frozen and paraffin sections. These intraepidermal amyloid-like deposits contained S-S bonds in all cases (27/27) and -SH groups in 10 of 27 cases. In contrast, an intraepidermal amyloid-like deposit was not observed in any systemic amyloidoses (0/9) or tumefactive amyloidoses of the tongue (2). These results showed that skin-limited amyloidoses could be differentiated from systemic amyloidoses by DACM methods (this appears to depend upon the differences of amino acid composition between skin-limited and systemic amyloidoses) and that paraffin-embedded sections were usable for DACM methods. Present study further suggests that amyloids ion skin-limited amyloidoses are, at least in part, derived from epidermal keratinocytes.
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PMID:Sulfhydryl and disulfide stainings in amyloids of skin-limited and systemic amyloidoses. 619 91

Specific germline activating point mutations in the gene encoding the tyrosine kinase receptor FGFR3 (fibroblast growth factor receptor 3) result in autosomal dominant human skeletal dysplasias. The identification in multiple myeloma and in two epithelial cancers-bladder and cervical carcinomas-of somatic FGFR3 mutations identical to the germinal activating mutations found in skeletal dysplasias, together with functional studies, have suggested an oncogenic role for this receptor. Although acanthosis nigricans, a benign skin tumor, has been found in some syndromes associated with germinal activating mutations of FGFR3, the role of activated FGFR3 in the epidermis has never been investigated. Here, we targeted an activated receptor mutant (S249C FGFR3) to the basal cells of the epidermis of transgenic mice. Mice expressing the transgene developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. We therefore screened a series of 62 cases of seborrheic keratosis for FGFR3 mutations. A large proportion of these tumors (39%) harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms. Our findings directly implicate FGFR3 activation as a major cause of benign epidermal tumors in humans.
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PMID:Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans. 1577 91

Germinal activating mutations of FGFR3 are responsible for several forms of dwarfism due to the inhibitory effect of FGFR3 on bone growth. Surprisingly, identical somatic activating mutations have been found at the somatic level in tumours: at high frequency in benign epithelial tumours (seborrheic keratosis, urothelial papilloma) and in low-grade, low-stage urothelial carcinomas, and at a lower frequency in other types of urothelial carcinoma, in cervix carcinoma, and in haematological cancer, multiple myeloma. FGFR3 exists as two isoforms, FGFR3b and FGFR3c, differs in ligand specificity and tissue expression. FGFR3b is the main form in epithelial cells and derived tumours, whereas FGFR3c is the main form in mesenchyme-derived cells and multiple myeloma. Several lines of evidence suggest that mutated FGFR3c has transforming properties. Although mutated FGFR3b is mostly found in benign epithelial tumours or carcinomas of low malignant potential, we present evidence here that mutated FGFR3b is oncogenic. All bladder tumours presenting FGFR3 mutations expressed this receptor more strongly than normal urothelium or non-mutated tumours. NIH-3T3 cells transfected with a mutated form of FGFR3b--FGFR3b-S249C, the most common mutation in bladder tumours--presented a spindle-cell morphology, grew in soft agar and gave rise to tumours when xenografted into nude mice. We identified one line of 17 bladder cell lines tested (MGH-U3) that expressed a mutated form of FGFR3b, FGFR3b-Y375C. We showed using siRNA and SU5402, an FGFR inhibitor, that the tumour properties of MGH-U3 depended on mutated receptor activity. Thus, in two different models, mutated FGFR3b presents oncogenic properties.
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PMID:Oncogenic properties of the mutated forms of fibroblast growth factor receptor 3b. 1633 52