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)

With a direct in vitro tumor-colony assay developed to measure sensitity of human-tumor stem cells to anticancer drugs, we performed 32 retrospective or prospective clinical studies in nine patients with myeloma and nine with ovarian cancer treated with standard agents that were tested in vitro. The results were clearly correlated (P is less than 0.00001). Unique patterns of sensitivity and resistance to the six drugs tested were observed for individual patients. In eight cases of myeloma and three of obarian carcinoma in vitro sensitivity corresponded with in vivo sensitivity whereas in one case of myeloma it did not. In vitro resistance correlated with clinical resistance in all five comparisons in myeloma and all 15 in ovarian cancer. We conclude that this assay shows sufficient promise to warrant larger-scale testing to determine its efficacy for selection of new agents and individualized cancer chemotherapy regimens.
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PMID:Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. 7 75

An increase in the serum copper (Cu++) level has been described as a sensitive index of disease activity in several hematologic and nonhematologic malignancies. In order to explore the diagnostic value of Cu++ compared to other hematochemical parameters frequently abnormal in malignancies, Cu++, serum alpha2 globulin (alpha2), plasmatic fibrinogen (Fibr), the erythrocyte sedimentation rate (ESR), and serum iron (Fe++) have been detected and evaluated in 267 patients affected with the following diseases: Hodgkin's lymphoma (HL), non-Hodgkin's Lymphomas (NHL), Acute Leukemias (AL), Chronic Myeloid Leukemia (CML), Chronic Lymphocytic Leukemia (CLL), Myeloma (MM), and Breast Cancer (BC). The best correlation between Cu++ increase and disease activity has been found in HL, NHL, AL, and BC. In these diseases, when the considered parameters were compared, Cu++ and ESR showed a similar pattern, i.e., a high frequency of abnormalities in active disease. It is concluded that Cu++ represents a good complement to some other aspecific parameters in evaluating the activity and diffusion of neoplasias and the therapeutic results, particularly in HL, NHL, AL and BC.
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PMID:The diagnostic value of serum copper levels and other hematochemical parameters in malignancies. 7 79

Twenty-seven patients with far-advanced multiple myeloma, resistant to standard agents, were treated with either adriamycin (eight patients) or bleomycin (19 patients). Adriamycin was given iv at a dose of 60 mg/m2 every 3 weeks and bleomycin was administered im at a dose of 15 mg/m2 weekly. Drug toxicity was modest. One partial response was seen with each agent, both occurring in "good-risk" patients.
Cancer Treat Rep 1978 Sep
PMID:Phase II study of adriamycin and bleomycin in patients with multiple myeloma. 8 Feb 75

Radial immunodiffusion assay was used to measure fetal hemoglobin (HbF) concentrations in 312 patients with various malignancies. In 305 of these, alpha-fetoprotein (AFP) was measured by radioimmunoassay. The concentration of HbF exceeded 3 SDs above the normal mean in 68 of 312 patients, most notably in patients with leukemia, multiple myeloma, lymphoma, bladder carcinoma and testicular tumors. HbF was correlated with total hemoglobin concentration and with serum AFP concentration in hepatoma and bladder carcinoma.
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PMID:Fetal proteins in various tumors. 8 98

Eleven patients with advanced multiple myeloma refractory to standard chemotherapy were treated with a regimen of sequential hemi-body radiotherapy consisting of 800 rad midplane in a single dose to each half. 9/10 patients experienced significant relief of skeletal pain and there were 5/11 objective tumor responses with one complete remission. Treatment-related morbidity was significant and consisted primarily of nausea and emesis, bone marrow suppression, and pneumonitis. This therapy is helpful in the management of advanced myeloma, and should be studied earlier in the course of the disease.
Cancer 1979 Jan
PMID:Sequential hemi-body radiotherapy in advanced multiple myeloma. 8 3

Electrofocusing patterns of plasma fucosyltransferases provide information concerning marrow status of patients with myeloproliferative disorders. Three enzymes were detected in normal plasmas using an acceptor terminating in the sequence N-acetylglucosamine-galactose. The enzyme which focused at pH 4.7 was elevated during rapid proliferation of myeloid cells, e.g., acute myelogenous leukemias and certain infectious diseases. Activity at pI = 5.1 was decreased in acute myelogenous leukemia patients, and from other observations, appears related to the level of erythropoietic activity. Acceptor studies show this enzyme to be specified by the H gene. A third enzyme focused at pH 5.5 and appeared to be correlated with a later step in granulocytes maturation. Two other plasma fucosyltransferases (pl = 5.6 and 8.3) were detected with a high-molecular-weight acceptor terminating in N-acetylglucosamine. This activity was markedly elevated during regeneration of a normal marrow population during drug-induced remission of acute myelogenous leukemia. Additional isoenzymes were detected, using this acceptor, in plasma of patients with certain solid tumors and multiple myeloma. However, the new isoelectric points observed (pH 6.0, 6.9, and 7.8) suggest these enzymes are probably not derived from hematopoietic tissues.
Cancer Res 1979 Sep
PMID:Electrofocusing patterns of fucosyltransferases in plasma of patients with neoplastic disease. 8 96

IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.
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PMID:Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation. 9 18

In this analysis, I have concentrated on advances in immunology, kinetics, and clinical oncology which have provided a substantial basis for identifying major common features in the natural history and pathophysiology of B-cell neoplasia as diverse as MM, MG, BMG, and NL. Observations on the natural history of both experimental and clinical myeloma as well as studies of kinetics of proliferation of MM and BMG in man provide the basis for reasonable hypotheses. Firstly, malignant variants of B-cell neoplasms may result from a two-hit evolution. In this scheme, the first hit is a triggering by specific antigen which leads to a required monoclonal expansion, while the second hit is the oncogenic event. Some cases of BMG seem to be examples of an unusually prolific response to the first hit, while others appear to be minimal deviation malignancies after the second hit. In this latter circumstance, the neoplastic clone in BMG usually retains a significant degree of sensitivity to tumor mass-related feedback inhibition. This may occasionally be lost during subsequent subcloning. Significant future testing of these hypotheses may prove feasible through the application of the in vitro tumor colony-forming assay system as it lends itself to study of a number of the salient features of these disorders.
Recent Results Cancer Res 1978
PMID:Neoplastic proliferation and natural history of B-cell neoplasia. 10 71

1. Nine patients in whom acute non-lymphoblastic leukemia (ANLL) developed following prolonged alkylating agent therapy are described. Five of the patients received no radiotherapy. The conditions treated were: Hodgkin's disease (four patients), primary amyloidosis, primary macroglobulinemia, malignant lymphoma, multiple myeloma, and carcinoma of the tonsil. 2. Prior to the advent of chemotherapy, this complication was not observed in large series of patients with lymphoproliferative disorders and multiple myeloma. However, the medical literature now contains at least 125 other detailed reports of ANLL developing after prolonged cytotoxic agent therapy. 3. Multiple myeloma and Hodgkin's disease, both of which commonly have good responses to chemotherapy, predominate as the underlying diseases. However, 35% of the case reports involve patients with other illnesses, including 12 patients who did not have neoplasms. 4. More than half of the patients developing ANLL have received chemotherapy alone without radiotherapy. 5. At least half of the patients developing ANLL experienced long periods of significant cytopenia during therapy, often with documentation of bone marrow dysplasia. 6. The wide variety of drugs associated with this complication suggests that any cytotoxic agent may be leukemogenic. However, alkylating agents overwhelmingly predominate as the class of compounds which are most often associated with terminal ANLL. 7. The vast majority of patients reported in the literature with ANLL complicating underlying malignancies have received cytotoxic drugs for prolonged periods (median 3 1/2 years) and leukemia developed most commonly 3 to 5 years after the diagnosis of the underlying disease. Most of these patients benefited from therapy and survived longer (median 5 years) than historical control of untreated patients. 8. The leukemogenic potential in man of prolonged cytotoxic agents therapy, especially with alkylating agents, seems to be well established. This evidence admonishes against the prolonged use of these drugs in non-fatal disorders. 9. More accurate assessment of risk: benefit ratios awaits the results of prospective controlled studies. The results of these studies could also lead to significant modifications in recommendations for long-term maintenance therapy with cytotoxic agents.
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PMID:Acute leukemia following prolonged cytotoxic agent therapy. 10 27

Attempts were made to find prognostic factors in myeloma. In 16 deceased patients, urinary light chains, skeletal lesions, and the quantity of the monoclonal protein fraction in the serum were correlated to prognosis, in contrast to the electrophoretic mobility of the monoclonal fraction, the hemoglobin, the serum creatinine value, the serum calcium, or the intestinal calcium absorption. Skeletal calcium uptake was only numerically higher in mild myeloma than in advanced myeloma. Since these findings partially agreed with the staging procedure previously proposed by Salmon, a modification of this procedure was used to stage 50 myeloma patients. Survival was statistically significantly shorter in stage III than in stage I. A differentiated treatement with melphalan-prednisone in stage I, cytoxan infusions in stage II, and vincristine-cytoxan-prednisone in stage III is proposed. A preliminary comparison of nine patients in stage II-III given intensive treatment with 23 given melphalan-prednisone suggests a numerically, but not as yet a statistically significant increase in survival in the intensively treated group, which seems to have an 80% 2-year survival.
Recent Results Cancer Res 1978
PMID:Staging of myeloma. A preliminary study of staging factors and treatment in different stages. 10 48


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