Familial Head and Neck Cancer: Molecular Analysis of a New Clinical Entity
摘要:
AbstractObjective The tumor suppressor gene p16 encodes a cyclin‐dependent kinase inhibitor that normally inhibits cell proliferation by causing a G1 cell cycle arrest. The p16 gene is frequently mutated in a variety of somatic tumors, as well as in familial melanoma and familial pancreatic carcinoma. We identified a family with a high incidence of head and neck squamous cell carcinoma (HNSCC) and melanoma. Molecular analyses of the p16 gene locus in blood and tumor DNA from this family was performed to determine whether an association between germline p16 gene mutation and HNSCC exists.Study Design Molecular pedigree analyses.Methods Exon 2 of p16 was polymerase chain reaction amplified from blood, tumor, or nontumor DNA isolated from affected and unaffected members, then directly sequenced and compared with consensus p16 sequence. Cell cycle position of cells expressing wild‐type or mutant p16 was determined by flow cytometry.Results Molecular analyses revealed a nonfunctional germline point mutation within exon 2 of the p16 gene that encodes a mutant p16 protein substituting proline at amino acid position 87 for the wild‐type arginine (p16R87P). Relative to wild‐type p16, p16R87P lost ability to cause a growth arrest following ectopic expression. The mutant (p16R87P) allele segregated with cancer predisposition in tested family members, and analyses of HNSCC tumor tissues demonstrated universal loss of wild‐type allele.Conclusions Significance of the mutant p16 (p16R87P) in HNSCC tumorigenesis is strongly suggested by its loss of cell cycle arrest activity and its retention in tumor tissue with simultaneous loss of the wild‐type allele. Further, the germline p16 mutation segregated with cancer predisposition within the family. In aggregate, these data suggest that there is a direct causal relationship between the germline p16 mutation in this family and HNSCC tumorigenesis. Based on our observations, the spectrum of familial cancers associated with p16 mutations should include a new clinical entity, familial HNSCC.
Non-toxic corrosion-protection pigments based on manganese
申请人:——
公开号:US20040011252A1
公开(公告)日:2004-01-22
Corrosion-inhibiting pigments based on manganese are described that contain a trivalent or tetravalent manganese/valence stabilizer complex. An inorganic or organic material is used to stabilize the trivalent or tetravalent manganese ion to form a compound that is sparingly soluble, exhibits low solubility, or is insoluble in water, depending upon the intended usage. Specific stabilizers are chosen to control the release rate of trivalent or tetravalent manganese during exposure to water and to tailor the compatibility of the powder when used as a pigment in a chosen binder system. Stabilizers may also modify the processing and handling characteristics of the formed powders. Manganese/valence stabilizer combinations are chosen based on the well-founded principles of manganese coordination chemistry. Many manganese-valence stabilizer combinations are presented that can equal the performance of conventional hexavalent chromium or tetravalent lead systems. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.
Non-toxic corrosion-protection pigments based on rare earth elements
申请人:——
公开号:US20040104377A1
公开(公告)日:2004-06-03
A corrosion-inhibiting pigment comprising a rare earth element and a valence stabilizer combinded to form a rare earth/valence stabilizer complex. The rare earth element is selected from cerium, terbium, praseodymium, or a combination thereof, and at least one rare earth element is in the tetravalent oxidation state. An inorganic or organic material is used to stabilize the tetravalent rare earth ion to form a compound that is sparingly soluble in water. Specific stabilizers are chosen to control the release rate of tetravalent cerium, terbium, or praseodymium during exposure to water and to tailor the compatibility of the powder when used as a pigment in a chosen binder system. Stabilizers may also modify the processing and handling characteristics of the formed powders. Many rare earth-valence stabilizer combinations are presented that can equal the performance of conventional hexavalent chromium systems.