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)

Porphyria cutanea tarda (PCT) may be associated with various neoplasma. Two additional cases are reported here. In the first case, a 58-year old alcoholic man had been presenting for two years with clinical signs of PCT. The diagnosis was confirmed by porphyrin assays in the urine. He also had cirrhosis of the liver. During a routine fibroscopy in search of oesophageal varices, a gastric adenocarcinoma was discovered by chance. Following partial gastrectomy the skin lesions of PCT improved dramatically within a few weeks, leaving only moderate cutaneous fragility. Urinary porphyrin assays performed 18 and 40 months after gastrectomy gave normal results, although no specific treatment had been prescribed. The second case concerns a 67-year old man, also alcoholic, with clinical and biochemical PCT. For the previous 12 months he had received chemotherapy (Adriamycin, then BCNU combined with melphalan, vincristine and prednisone) for multiple IgA K myeloma. The myeloma was active when PCT was diagnosed with, in particular, chronic anaemia. Treatment with chloroquine improved the cutaneous signs of PCT but had no effect on urinary porphyrins after 5 months. Comments PCT has been reported to be associated with cancers. The best known of these cancers is primary carcinoma of the liver (4, 27, 32), but its frequency is diversely evaluated depending on the diagnostic methods (e. g. patient autopsied or not) and on the selection of patients (age, duration of the disease).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Porphyria cutanea tarda and neoplasms. Apropos of 2 cases]. 380 Feb 18

Impressive results have recently been reported in 29 cases of advanced refractory myeloma treated with 4-d infusions of Vincristine and Adriamycin (VAD). We report our own experience with this protocol in 13 cases of myeloma and related lymphoproliferative disorders. In 2 of these cases, VAD was used as first line treatment. Objective responses were seen in two-thirds of cases and the major complication of therapy was infection, predominantly bacterial in nature.
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PMID:The efficacy and toxicity of VAD in the treatment of myeloma and related disorders. 381 40

The effects of eight different drug combinations were evaluated in 256 patients with multiple myeloma. The response rate and time to remission were superior from regimens that added both vincristine and Adriamycin (doxorubicin) to an alkylating agent-prednisone combination. There was no improvement in response rate or survival time from two alternating drug combinations evaluated in an attempt to achieve more marked tumor reductions and to delay the emergence of resistant subclones. The addition of levamisole during remission maintenance did not improve survival time. Results supported the utility of unmaintained remission follow-up in selected patients with marked reductions in myeloma cell mass.
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PMID:Chemotherapy for multiple myeloma. 636 19

A total of 151 patients with myeloma who had relapsed with or were resistant to melphalan and/or cyclophosphamide (Cytoxan) with prednisone received vincristine, carmustine (BCNU), doxorubicin (Adriamycin), and prednisone (VBAP) at 21-day intervals; 39 patients (25%) responded. Of the 123 patients with relapsing myeloma, 37 (30%) responded. Only two (7%) of the 28 patients with resistant myeloma responded. The regimen was well-tolerated in patients who had not had prior extensive irradiation. Thrombocytopenia was the most frequent form of toxicity. Survival was significantly longer in those patients responding to VBAP (median, 78 weeks) than in those not responding (median, 33 weeks) (P = 0.002). VBAP is a safe, effective regimen for patients with myeloma who relapse with alkylating agents.
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PMID:Vincristine, BCNU, doxorubicin, and prednisone (VBAP) combination in the treatment of relapsing or resistant multiple myeloma: a Southwest Oncology Group study. 704 34

Sixty-five patients with multiple myeloma resistant to melphalan were randomized to receive cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP) (30 patients) or carmustine (BCNU), doxorubicin, and prednisone (BAP) (35 patients). Objective responses occurred in two patients in the CAP group and in seven in the BAP group. Indirect responses were noted in seven additional patients in the CAP group and in six additional patients in the BAP group. Toxic effects consisted mainly of leukopenia and thrombocytopenia. Median survival did not differ between the two treatment groups (CAP, 8.4 months; BAP, 7.7). Objective responders had a longer survival than nonresponders (14.5 vs 7.7 months).
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PMID:Multiple myeloma resistant to melphalan: treatment with doxorubicin, cyclophosphamide, carmustine (BCNU), and prednisone. 706 34

A current southeastern cancer study group protocol for the treatment of multiple myeloma involves induction with BCNU, cyclophosphamide, and prednisone (BCP) and maintenance with either melphalan and prednisone (MP), prednisone, Adriamycin, imuran, and vincristine (PAIV), or delayed treatment of relapsed cases following induction. These combinations of drugs are used as induction regimens to establish their chemotherapeutic effects and hematological toxicity in the murine MOPC 104E plasmacytoma model. The three combinations of drugs produce rapid, reliable, and reproducible tumor regressions. However, MP is the only combination which consistently gives long-term disease-free survivors. This particular regimen has least toxicity and is considered to be most effective. BCP produces complete remission with no relapses; however, long-term survivors are not observed with this combination due to early deaths because of drug toxicity. Most of the mice on the PAIV regimen die due to drug toxicity. This combination is considered least effective. With the different drug regimens, toxic events and regressions are noted to occur at different time periods, indicating that perhaps tumor cells in different stages are being destroyed. Toxic events as measured by hematocrit and body weight changes always precede regression by several days. This disparity between rapid drug effects on the host and a delayed effect on the tumor remains unexplained but may possibly be used to advantage in designing future trials.
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PMID:Assessment of myeloma maintenance regimen of prednisone. Adriamycin, imuran, and vincristine in a murine plasmacytoma model. 724 51

Melphalan (Alkeran) is an alkylating agent commonly used in the treatment of multiple myeloma and other neoplasia. We have isolated melphalan-resistant (MelR) Chinese hamster ovary cells in vitro. Stably resistant clones were observed with a frequency of about 10(-7) after a single drug exposure. Two clones, MelR1 and MelR6, were studied in detail, and their phenotypes were compared to a colchicine-resistant membrane permeability mutant (CHRC5) isolated previously by Ling and Thompson (J. Cell Physiol., 83: 103-116, 1974), which was cross-resistant to melphalan. The MelR cones were cross-resistant to the nitrogen mustard class of alkylating agents, such as melphalan, nitrogen mustard, and chlorambucil, but not to alkylating agents, such as methanesulfonic acid:ethyl ester or mitomycin C. The MelR clones differed from CHRC5 in their lack of cross-resistance to puromycin and Adriamycin. Studies with [14C]melphalan showed CHRC5, but not the MelR clones, to be defective in drug accumulation into whole cells. The mechanism of melphalan resistance in CHRC5 is attributed to reduced drug accumulation due to a plasma membrane alteration. In the MelR clones, investigation of drug distribution into cell subfractions revealed reduced accumulation into the nucleus compared to the parental cell line. We therefore propose that the mechanism of resistance in the MelR cells results from a nuclear alteration(s) specific to a subclass of alkylating agents.
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PMID:Selection and characterization of Chinese hamster ovary cell mutants resistant to melphalan (L-phenylalanine mustard). 744 83

Multiple myeloma is basically an incurable cancer. Most patients respond initially to chemotherapy with reduction in bone marrow (BM) plasma cells and monoclonal Ig levels, but the disease nearly always recurs and becomes refractory to therapy. The objective of this study was to characterize the expression of the multidrug transport pump, P-glycoprotein 170 (P-gp), in myeloma. The great majority of B cells from peripheral blood mononuclear cells (PBMCs) in myeloma express P-gp, detected by the monoclonal antibody MRK-16. P-gp+ blood B cells exhibit extensive DNA hyperdiploidy, suggesting replicative abnormality characteristic of malignant growth. We speculate these represent a stem cell population in myeloma. The proportion of B cells expressing P-gp was comparable among untreated myeloma patients and those treated with chemotherapy, biologic response modifiers, or off treatment. Among BM cells, P-gp was absent or low in untreated myeloma patients but was expressed at high levels on BM cells from patients previously treated with chemotherapy. For untreated patients the majority of B/plasma cells expressing P-gp are located in PBMCs, not the BM cells. Flow cytometric analysis of rhodamine 123 dye efflux indicated a functional P-gp that was efficiently blocked by verapamil or cyclosporin A (CsA). Both the CD11bhi CD19+ B cells and the T cells in myeloma PBMCs had active CsA-inhibited dye efflux, but monocytes lacked the ability to efflux dye. Nearly all CD38hi plasma cells from myeloma BM cells retained dye, indicating their lack of a functional transport pump. Thus, PBMC B cells may be the predominant set of drug-resistant tumor cells. Myeloma PBMC B cells were cultured with Adriamycin with or without CsA and drug toxicity evaluated by the induction of apoptosis, using flow cytometry to quantitate DNA disruption. No apoptosis was detectable at 0.01 microgram/mL adriamycin, the in vivo steady-state level, with or without CsA. With 0.1 microgram adriamycin, no apoptosis was detectable in the absence of CsA, but with CsA, 66% of B cells initiated DNA disruption, whereas most T cells were spared. This work suggests that currently used drug dosages are too low to effect P-gp+ B-cell death, even in the presence of CsA. We suggest that blood B cells comprise a highly drug-resistant subset of the myeloma B lineage that escapes conventional chemotherapy and may underlie the almost uniform fatal relapse in myeloma patients.
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PMID:Circulating monoclonal B cells expressing P glycoprotein may be a reservoir of multidrug-resistant disease in multiple myeloma. 750 31

The effect of in vitro exposure to vincristine, Adriamycin, and glucocorticoids was studied in 4 human myeloma cell lines. The drug concentrations tested approximated the steady-state plasma level achievable clinically. Marked growth inhibition was seen in all 4 cell lines with vincristine, but in only 2 with Adriamycin. Glucocorticoids were only minimally inhibitory. The inhibition by glucocorticoids was reversible after drug removal, but that by vincristine and Adriamycin was sustained except the vincristine inhibition of ARH-77 cells. The degree of cell growth inhibition paralleled the reduction in tumor cell 3H-thymidine uptake. Cell cycle distribution analysis showed an arrest of myeloma cells at M/G2 phase by vincristine and Adriamycin and an inhibition of myeloma cells from entering into S phase by dexamethasone. Dose-response analysis with ARH-77 cells, a cell line that appeared the most chemoresistant, showed that the growth-inhibitory effect of Adriamycin and vincristine was roughly proportional to the product of drug concentration and exposure time. However, in contrast to Adriamycin, an effective vincristine concentration and exposure time that totally inhibited cell growth was unable to prevent cell regrowth after drug removal. A higher vincristine concentration appeared to be more effective in preventing cell regrowth.
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PMID:Effect of vincristine, adriamycin and glucocorticoids on myeloma cells in vitro. 850 45

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.
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PMID:BCL-X expression in multiple myeloma: possible indicator of chemoresistance. 944 2


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