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)

In this survey for rheumatoid factor (RF) seropositivity on patients with neoplasms, an 85% rate of positive screening tests was recorded under certain circumstances. This high rate of RF seropositivity occurred after irradiation and/or chemotherapy of breast and lung cancers. Treated patients with breast cancers who had no evidence of residual tumor had an 89% rate of positive RF tests. Conversely, the incidence of RF seropositivity was low among untreated patients with similar tumors and treated patients with glioblastomas or multiple myeloma. The administration of cytotoxic drugs (e.g., azathiprene) was not itself associated with RF production even in renal allograft recipients. The data indicate that RF production occurs frequently after therapy of certain tumors and suggest that in these circumstances RF may be an expression of tumor-host interaction.
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PMID:Rheumatoid factor and tumor-host interaction. 106 77

We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma. 168 31

Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 x 10(6) cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotype-matched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse.
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PMID:Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen. 176 Aug 21

The junctional sequences corresponding to the complementarity determining region 3 (CDR3) of rearranged heavy chain Ig genes can provide allele-specific markers in the detection of B-lymphoid malignancies. Consensus oligonucleotide primers were used to amplify CDR3 regions of rearranged heavy chain alleles in clinical samples from myeloma, acute lymphocytic leukemia, and chronic lymphocytic leukemia patients. From the sequence of the amplified products, allele-specific primers were synthesized and used directly in polymerase chain reaction (PCR) amplification to detect the malignant clone. This method was both highly specific and sensitive to 1 malignant B-cell in a background of 10(5) normal cells. In addition, parameters that affect the linearity of PCR detection were determined and, by using titrations of malignant target cells to generate standard curves, quantitations of residual malignancies were determined. The application of this method is shown in an analysis of myeloma patients whose marrows were analyzed sequentially during therapy. Allele-specific oligonucleotide-PCR provided a rapid, highly specific and quantitative measure of residual disease, even in patients with clinical parameters indicating complete remission.
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PMID:Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: a technique for sequential quantitation of residual disease. 195 87

The effectiveness of ex vivo chemotherapy with drugs, such as vincristine, etoposide, and Adriamycin (doxorubicin, Adria Labs, Columbus, OH) for elimination of residual tumor cells from human bone marrow grafts could be undermined by the presence of multidrug-resistant tumor cells in the bone marrow. Therefore, to supplement chemoseparation, we investigated whether MRK-16, a monoclonal antibody (MoAb) to the surface moiety of multidrug resistance-associated P-glycoprotein antigen, can eliminate drug-resistant tumor cells in the presence of rabbit complement (RC). Two doxorubicin (DOX)-resistant human myeloma tumor cell line, 8226/DOX40 (resistant to 4 x 10(-7) mol/L DOX) and 8226/DOX6 (6 x 10(-8) mol/L DOX) with high and low amounts of cell surface P-glycoprotein, respectively, and the drug-sensitive parent cell line 8226/S were used as tumor models in this study. Using the limiting dilution assay, we have shown that three cycles of treatment with 25 micrograms/mL of MRK-16 MoAb and a 1:4 final dilution of RC eliminated 2.90 +/- 0.10 logs of 8226/DOX40 cells and 1.94 +/- 0.18 logs of 8226/DOX6 cells. One and two cycles of treatment were less effective, eliminating 0.47 +/- 0.40 and 1.94 +/- 0.36 logs of 8226/DOX40 and 0.12 +/- 0.20 and 1.63 +/- 0.58 logs of 8226/DOX6 cells, respectively. The 8226/S cell growth was unaffected by one to three cycles of treatment. The cell kill was not impaired when the antibody plus complement treatment was carried out on a mixture of 8226/DOX40 or 8226/DOX6 cells with a ninefold excess of irradiated bone marrow mononuclear cells (MNCs). The three cycles of treatment with antibody plus complement did not adversely affect granulocyte-macrophage colony-forming unit (GM-CFU) survival in hematologically normal marrows (92.5% to 104% survival) or in myeloma patient marrows (85% to 100%). These results show that it is possible to eliminate drug-resistant myeloma tumor cell lines from the admixed human bone marrow by treatment with MRK-16 MoAb plus RC. This method could prove to be effective for elimination of other drug-resistant tumor cell lines including those of leukemia and solid tumors, and will be further useful for supplementing chemopurging, and immunopurging of bone marrow with other antitumor cell antibodies.
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PMID:Elimination of drug-resistant myeloma tumor cell lines by monoclonal anti-P-glycoprotein antibody and rabbit complement. 257 83

In multiple myeloma (MM), low-cost maintenance treatment has some attractions, since maintenance of a small tumor is usually compatible with a fairly healthy state. However, the great majority of the studies of maintenance treatment have failed to show any clinical benefit. Based on simple theoretical consideration, it is shown that in MM response duration and survival are affected primarily by the residual tumor mass after primary treatment, and by the kinetics of the tumor. Continuation of maintenance treatment is likely to have a moderate effect. The main cause of that is identified in the presence or in the development of a substantial proportion of drug-resistant cells. Preliminary data suggest that only alpha-interferon can be useful for maintenance, and that it can act by slowing down the kinetics of the tumor.
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PMID:Maintenance treatment of multiple myeloma. 269 86

Serum beta-2-microglobulin (B2m) levels were measured in 78 patients with multiple myeloma (MM) and were compared with values for normal individuals and patients with benign monoclonal gammopathies (BMG). Serum B2m levels and values corrected for renal function were significantly higher in patients with MM at time of diagnosis than in normal individuals (P less than 0.001) and were highly correlated with the total body burden of myeloma cells as derived from the staging system of Durie and Salmon. However there were no significant differences between values for BMG and low-mass MM. For patients evaluated following induction chemotherapy, there was also a clear correlation between serum B2m levels and the magnitude of tumor regression or progression (P less than 0.05). During the plateau-phase, serum B2m levels remained very stable and highly correlated with the residual tumor mass (P less than 0.001). It was concluded that (1) B2m was not a reliable marker to distinguish between BMG and low-mass MM and (2) B2m was a valuable marker for assessing initial tumor mass of patients with MM and response to chemotherapy (especially the plateau-phase), above all in patients with urine or low-serum monoclonal component levels.
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PMID:Serum beta-2-microglobulin in multiple myeloma: relation to presenting features and clinical status. 617 35

We performed the first successful syngeneic bone marrow transplantation (BM Txp) in a patient with multiple myeloma. The patient and his normal identical twin are 50-year-old physicians. Prior to BM Txp, a partial remission was achieved with 1 year of continuous low dosage melphalan and prednisone therapy. Immediately before BM Txp, high dose cyclophosphamide and total body irradiation were administered in an attempt to eradicate the residual tumor. For 17 months after BM Txp, the patient was asymptomatic and hematologically normal although a low concentration of serum monoclonal IgGK persisted. In the 18th month, recurrence of bone pain and increase in the monoclonal IgG signalled exacerbation of the disease. Chemotherapy was resumed and again produced objective and subjective evidence of response. This study demonstrates the feasibility and potential usefulness of syngeneic BM Txp in myeloma.
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PMID:Identical twin marrow transplantation in multiple myeloma. 621 15

Previous reports have shown that serum beta-2-microglobulin (S beta2M) is a reliable marker of presenting tumor mass, response to chemotherapy, and prognosis of patients with multiple myeloma (MM). In order to more thoroughly evaluate the optimal use of S beta2M in plasma cell dyscrasias (PCD), S beta2M levels were serially measured in 160 patients with MM, in comparison with 37 normal controls (NC) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS). In MGUS, S beta2M did not differ significantly from that of NC, but was significantly lower than that of MM (p less than 0.001), including low cell mass MM (p less than 0.02). In MM, S beta 2M was highly correlated with the total body burden of myeloma cells as derived from the staging of Durie and Salmon, both at diagnosis and in remission (residual tumor mass) (p less than 0.001). During the plateau phase, S beta 2M remained very stable and was always within the normal range for patients with greater than or equal to 75% tumor regression. The most striking finding was that S beta 2M gave an extremely reliable fit for survival prediction at (1) diagnosis, (2) remission, and (3) early relapse, with higher S beta 2M levels in each instance being in favor of poorer prognosis. We conclude that S beta 2M is an extremely useful marker in initial stratification and follow-up of patients with MM.
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PMID:Beta-2-microglobulin in myeloma: optimal use for staging, prognosis, and treatment--a prospective study of 160 patients. 636 53

To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [3H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [3H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [3H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity.
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PMID:Correlation of proliferative and clonogenic tumor cells in multiple myeloma. 674 29


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