Linked Life Data

2564428

Source:http://linkedlifedata.com/resource/pubmed/id/2564428

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-5-8
pubmed:abstractText
The B-cell neoplasms, multiple myeloma and non-Hodgkin's lymphoma, frequently become drug resistant, despite initial responses to chemotherapeutic drugs. Tumor cells from eight patients with clinically drug-refractory disease were evaluated by immuno-histochemical staining for monoclonal immunoglobulin (Ig) expression, nuclear proliferation antigen, P-glycoprotein (P-gly) expression, and other cellular antigens. P-gly was detected on tumor cells from six of eight patients with drug-resistant disease. Of the six patients with P-gly-positive tumors, five patients had advanced multiple myeloma and one had a drug-refractory non-Hodgkin's lymphoma. Cellular RNA analysis confirmed the over-expression of P-gly. In an effort to overcome drug resistance, a pilot study evaluated possible verapamil enhancement of chemotherapy in these eight patients. All patients had developed progressive disease while receiving a regimen containing vincristine and doxorubicin, and seven of eight patients had previously received continuous infusion vincristine and doxorubicin plus oral dexamethasone (VAD). At the time of progressive disease, continuous infusion verapamil was added to the VAD regimen. Three of the eight patients who were refractory to vincristine and doxorubicin alone responded when verapamil was added to VAD. The three patients who responded had P-gly-positive tumors. Verapamil increased the intracellular accumulation of doxorubicin and vincristine in vitro for both a P-gly-positive myeloma cell line and tumor cells from two patients with end-stage myeloma which over-expressed P-gly. The dose-limiting side effect associated with the addition of verapamil to chemotherapy was temporary impairment of cardiac function, manifest as hypotension and cardiac arrhythmia. We conclude that P-gly expression occurs in drug-refractory B-cell neoplasms and may contribute to the development of clinical drug resistance. However, other factors, such as the proliferative activity of the tumor, may also play a role in determining response to chemotherapy. The administration of verapamil along with VAD chemotherapy may partially circumvent drug resistance in patients whose tumors over-express P-gly.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0732-183X
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
415-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy.
pubmed:affiliation
Department of Medicine, University of Arizona, College of Medicine, Tucson.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.