Linked Life Data

8724701

Source:http://linkedlifedata.com/resource/pubmed/id/8724701

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-10-29
pubmed:abstractText
The paucity of effective cytotoxic agents for the treatment of steroid resistant multiple myeloma explains the ongoing search for alternative substances for chemotherapy of this disease. In the present study, the purine antagonist 2-chlorodeoxyadenosine (2-CdA, cladribine) and the pyrimidine antagonist 2',2'-difluorodeoxycytidine (gemcitabine) were tested on four myeloma cell lines (i.e., U 266, OPM 2, RPMI 8226, IM 9), one plasma cell leukemia cell line (HS Sultan) and a myeloid control cell line (HL 60), all of which are resistant to 10-6 M dexamethasone. Gemcitabine has been found to be promising in the chemotherapy of other tumors with low proliferative activity, but its effectiveness against myeloma cells has not been analyzed so far. In our tests, gemcitabine induced a significant degree of apoptosis in all cell lines investigated. After incubation for 48 h with 10 microM gemcitabine, the median numbers of apoptotic cells were in the range of 45% in the OPM 2 and 79% in the U 266 cell line. All of the investigated cell lines were responsive to concentrations of 10 microM gemcitabine even after an exposure of only 30 min, three of them (U 266, HS Sultan, IM 9) also responded to a concentration of 10 nM. Higher concentrations and longer exposure times were necessary to suppress the growth of normal hematopoietic bone marrow progenitor cells. In contrast to gemcitabine, standard concentrations of 2-CdA (i.e., 30 and 300 nM) failed to induce a significant degree of apoptosis in the cell lines investigated but inhibited the growth of myeloid progenitor cells. The results suggest that gemcitabine induces apoptosis in myeloma and plasma cell leukemia lines resistant to steroids and 2-CdA. The fact that tumor cell apoptosis was achieved at concentrations clinically achievable and tolerable, which at the same time do not inhibit the growth of normal CFU-GM progenitor cells, favors the initiation of phase I trials with this drug for the treatment of multiple myeloma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1066-5099
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-62
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8724701-2-Chloroadenosine, pubmed-meshheading:8724701-Antimetabolites, Antineoplastic, pubmed-meshheading:8724701-Apoptosis, pubmed-meshheading:8724701-Biotin, pubmed-meshheading:8724701-DNA Damage, pubmed-meshheading:8724701-Deoxyadenosines, pubmed-meshheading:8724701-Deoxycytidine, pubmed-meshheading:8724701-Deoxyuracil Nucleotides, pubmed-meshheading:8724701-Dexamethasone, pubmed-meshheading:8724701-Drug Resistance, pubmed-meshheading:8724701-Glucocorticoids, pubmed-meshheading:8724701-Hematopoietic Stem Cells, pubmed-meshheading:8724701-Humans, pubmed-meshheading:8724701-Multiple Myeloma, pubmed-meshheading:8724701-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:8724701-Sensitivity and Specificity, pubmed-meshheading:8724701-Staining and Labeling, pubmed-meshheading:8724701-Steroids, pubmed-meshheading:8724701-Tumor Cells, Cultured
pubmed:year
1996
pubmed:articleTitle
2',2'-Difluorodeoxycytidine (gemcitabine) induces apoptosis in myeloma cell lines resistant to steroids and 2-chlorodeoxyadenosine (2-CdA).
pubmed:affiliation
Department of Internal Medicine, University of Innsbruck, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't