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

Novel islet cell, duct cell, and acinar cell markers have been identified by monoclonal autoantibodies (Maab) derived from prediabetic BB rats. Spleen cells from two rats that both developed diabetes after splenectomy were fused with mouse myeloma cells. A cellular immunoradiometric assay for differential reactivity toward the surface of two closely related, insulin- and non-insulin-producing rat islet tumor cell lines was used to select and clone several IgM-producing hybridomas. The supernatants were finally characterized by two-color immunofluorescence with islet hormone antisera on frozen sections of human, monkey, and rat pancreas. Maab EB52 stained PP cells, but also few A cells on rat pancreas. Maab CA812 identified a subpopulation of islet D cells on rat, human and monkey pancreas. Although the CA812-reactive antigen and somatostatin were coexpressed in most D cells in adult rat pancreas, only a few islet D cells were stained in the newborn pancreas. The CA812-reactive antigen was not detected in somatostatin-producing cells in the duct epithelium. Maab H37 and IF5 selectively stained acinar cells in rat, human, and monkey pancreas, whereas Maab DA39 identified the rat ductal epithelium including the scattered endocrine cells of the ducts. In summary, B lymphocytes producing autoantibodies to pancreatic endocrine, exocrine, and ductal markers are present in prediabetic BB rats and can be detected by use of transformed pluripotent islet cells as target. Such B lymphocytes can be immortalized to produce monoclonal antibodies to study their role in insulin-dependent diabetes mellitus pathogenesis and to clarify the development of the pancreas.
Pancreas 1990 Sep
PMID:Novel islet, duct, and acinar cell markers defined by monoclonal autoantibodies from prediabetic BB rats. 212 46

A series of 12 cell fusions of BALB/c mice spleen cells with the SP2/O-Ag14 mouse myeloma cell line were performed after immunizations with normal human pancreas to generate monoclonal antibodies (mAbs) with high affinity against antigens of the exocrine pancreas. The immunohistologic tissue screening resulted in the selection of 14 clones that were further characterized on frozen tissues, tumor cell lines, and lectin binding assays. Four mAbs reacting with pancreatic acini detected granular antigens and three mAbs reacted with acinar cell membrane antigens. Six other clones reacted with pancreatic ducts; among these were three clones positive with antigens in both acini and ducts. Among the clones reactive with secretory products, there was one pair of mAbs identified as pancreas specific (P78C9/P79D4); the other secretory antigens (identified by P97F3 and P109H1) were also detectable in other exocrine organs, but were absent from the gastrointestinal mucosa. Two clones reactive with acinar cell membranes (P96H2 and P100H1) were also positive with hepatocytes. All but four antigens were detectable in pancreatic cancer cell lines Capan-1, Capan-2, and DAN-G. On the whole, immunizations were more effective using whole pancreatic tissues (eight clones selected) compared with single-cell suspensions as immunogen (four clones) or cell membrane preparations (two clones). Therefore, the immunization and screening strategies used in this study resulted in the generation of new mAbs against specific substructures of the exocrine pancreas. The shared expression of some of these antigens with other exocrine organs and pancreatic adenocarcinoma cell lines suggests that these mAbs detect antigens that are characteristic for the exocrine system and could therefore be useful for the study of the exocrine pancreas and pancreatic adenocarcinomas.
Pancreas 1993 May
PMID:Characterization of new monoclonal antibodies directed against normal human exocrine pancreas and pancreatic adenocarcinomas. 848 69

Analysis of familial cancer risks between discordant sites provides etiologic understanding on genetic and environmental risks factors of site-specific cancers. We used the Swedish nation-wide Family-Cancer Database to analyze familial risks in discordant cancers of offspring and parents. Familial risk ratios (FRRs) were calculated for cancer in offspring aged 15 to 53 years at 22 sites, discordant from parental sites. We confirmed many reported associations. Consistent novel findings associated parental-offspring sites of pancreas-breast, breast-testis and uterus-nervous system. For these, the FRRs were modest, 1.2 to 1.5 in the whole Database, but the FRRs increased in those whose parents were diagnosed before age 50. Pancreas and liver cancers showed FRRs of 2.5 to 3.3 in offspring of women and of 1.3 in offspring of men. One or both of these cancers was/were associated with cancers of stomach, colon, breast, uterus, ovary and prostate. Melanoma was associated with pancreas, breast, skin and nervous-system cancers and with leukemias. Myeloma showed a concordant FRR of about 4.0 and was associated with prostate cancer and non-thyroid endocrine-gland cancers. Mutations in known cancer-related genes may explain some of these findings, but new susceptibility genes are yet to be found. For melanoma, pancreatic and liver cancer, environmental factors are important etiologic factors and may contribute to the familial effects observed.
...
PMID:Familial cancer risks in offspring from discordant parental cancers. 1007 45