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)

Idarubicin is a 4-demethoxy-anthracycline analogue of daunorubicin which, when administered intravenously in combination with cytarabine, has therapeutic efficacy superior to that of standard induction and salvage treatment regimens in acute myelogenous leukaemia. Idarubicin alone or in combination regimens has also been effective in limited studies in patients with other acute leukaemias, advanced breast cancer, multiple myeloma and non-Hodgkin's lymphoma. Idarubicin is more lipophilic than its parent drug daunorubicin. It intercalates DNA, induces DNA strand breaks and delays cell cycle progression. Leucopenia is often dose-limiting in patients with solid tumours treated with idarubicin, and most other adverse effects are similar in incidence and severity to those experienced with other anthracycline cytotoxic agents, except for alopecia which appears to occur with a reduced incidence and severity. Cardiotoxic effects have been reported with idarubicin as with other anthracyclines, but animal data and preliminary clinical findings suggest the possibility of reduced cardiotoxicity with idarubicin--a potentially important advantage if confirmed on further study. A maximum cumulative dose of idarubicin beyond which the incidence of cardiotoxicity rapidly increases has not been determined. Thus, intravenous idarubicin is a useful alternative to other anthracyclines (particularly in combination with cytarabine) in the treatment of acute myelogenous leukaemia, and there is some evidence that it is less cardiotoxic than other anthracycline drugs. Further studies are required to establish the use of intravenous idarubicin as a replacement for other intravenous anthracyclines, especially its effect on response duration and survival, and to confirm the evidence of reduced cardiotoxic effects. The role of idarubicin as consolidation and maintenance therapy for various malignancies requires further investigation, as does the potential use of oral idarubicin which is currently under development.
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PMID:Idarubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. 172 69

28 patients with progressing painful bone metastases (18 breast cancer, 9 myeloma and 1 low grade lymphoma) received pamidronate 60 mg by 24 h continuous infusion for at least 2 courses (range 2-12). In patients urinary calcium and hydroxyproline excretion significantly decreased in relation to diminution of bone resorption. 9 of 18 breast cancer patients and 8 of 9 evaluable patients with myeloma had symptomatic improvement. Sclerotic areas of previously lytic lesions appeared in 8 breast cancer patients and in 1 myeloma patient. Transient fever developed in 1 patient and local phlebitis in 2. Among the 28 patients, 15 did not receive any anticancer treatment or have any change of the anticancer therapy during pamidronate administration. Of 7 with breast cancer, 4 had an improvement of symptoms and 4 sclerosis on radiographs. Impressive control of symptoms was the major feature of 8 myeloma patients, but only 1 had radiographic sclerosis.
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PMID:Treatment of bone metastases from breast cancer and myeloma with pamidronate. 182 38

Monoclonal antibodies which bind selectively to cancer cells are currently used for tumor localization and for targeting cytotoxic reagents. The success of these approaches depends on the specificity of the antibody and its reactivity to a majority of the tumor samples. Frequently, monoclonal antibodies are generated by immunizing mice with antigenic preparations from a single tumor cell line. Antibodies generated under these conditions often react to a narrow range of tumors. In the present study, mice were immunized with multiple ovarian cancer cell lines in a sequential manner to amplify the immune response against common antigenic determinants expressed in these cell lines. Spleen cells from the immunized mice were then fused with NS-1 myeloma cells to establish hybridomas. Two cell lines were selected on the basis of their selective reactivity to ovarian cancer cells after extensive screening. Monoclonal antibodies OVX1 and OVX2 bound to all 5 ovarian carcinoma cell lines tested and did not bind to normal fibroblast cells. These antibodies recognized a unique antigenic determinant present in ovarian and breast cancer cells. Cross-blocking studies showed that the binding of OVX1 and OVX2 is not displaceable by 10 other previously described anti-ovarian antibodies including OC125. In immunocytochemical studies, OVX1 reacted to a majority of ovarian cancer tissues (17 of 20) and did not bind to normal ovarian tissues. Preliminary results indicate that OVX1 and OVX2 antibodies are directed to a high molecular weight antigen. These antibodies could be used in the preparation of cytotoxic conjugates.
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PMID:Development of two new monoclonal antibodies reactive to a surface antigen present on human ovarian epithelial cancer cells. 185 17

The authors describe a case of multiple myeloma, with the typical aspects of bone marrow and with bone lesion, in presence of monoclonal IgM secretion. Polychemotherapy proved effective transitorily. The clinical period had, as complication, the occurrence of breast cancer. The terminal period was characterized by irreversible renal failure.
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PMID:[A case of IgM-secreting myeloma]. 194 12

Tumours which involve the skeleton do so by producing humoral factors which increase osteoclast and osteoblast activity. Increases in osteoclast activity lead to osteolytic bone destruction and sometimes to hypercalcaemia. Osteolytic metastases are common, and are found most often in patients with lung and breast cancer and in myeloma. The tumour-associated factors responsible are multiple and probably different in each case. Osteoblastic metastases occur most frequently in metastatic cancer of the prostate, and are due to osteoblast stimulating factors released by the tumour cells which have not, as yet, been identified. Agents such as bisphosphonates which inhibit osteoclastic bone resorption are useful in the prevention and treatment of patients with osteolytic metastases, although the precise mechanisms by which these agents work are not yet understood.
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PMID:Mechanisms of osteolytic bone destruction. 195 46

Neoplasia affecting the skeleton is an important cause of morbidity, which includes hypercalcaemia, bone pain and fracture. In most instances these events are mediated by an increase in the resorption of bone which decreases bone density and disrupts skeletal architecture, either at focal sites or generally throughout the skeleton. Neoplastic activation of bone resorption in heterogeneous, but there is now good evidence that this is due to the increased activation of osteoclasts, the cells which mediate bone resorption in health. Bisphosphonates are specific inhibitors of osteoclast-mediated bone resorption and are capable of inhibiting osteoclastic activation independent of the mechanism of its stimulation. This provides the rationale for the use of bisphosphonates in the hypercalcaemia of malignancy. Despite refinements in the use of endocrine therapy, chemotherapy and radiotherapy these interventions have had relatively little impact on the skeletal morbidity or mortality of common malignancies affecting the skeleton, particularly breast cancer and myelomatosis. In addition, there is good evidence that skeletal disease is progressive in many patients despite the use of chemotherapy and radiotherapy. Since accelerated bone resorption can be inhibited by long-term treatment with bisphosphonates, their use is likely to decrease skeletal complications such as bone pain and fracture. The bisphosphonates, therefore, hold great promise as agents to improve the quality of life of such patients.
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PMID:Rationale for the use of bisphosphonates in bone metastases. 195 47

Monosomy 7 as the sole cytogenetic abnormality was detected in five of 310 consecutive adult patients with acute leukaemia who were characterized by morphological, immunophenotypic and cytogenetic analyses. Morphologically, blast cells were myelomonocytic (FAB M4) in three and lymphoid (FAB L2) in two patients. By immunophenotyping, two M4 patients expressed terminal transferase (TdT) in 15-90% of myelomonoblasts (patients 3 and 1, respectively), and in the third M4 patient (no. 2), a 10% TdT+ component was present distinct from the bulk of myelomonoblasts. In one L2 patient (no. 4), the blast cells had an undifferentiated phenotype only expressing TdT and HLA-DR but lacking specific lymphoid and myeloid antigens, and patient 5 was typed as CD10+ ALL. Two patients had developed leukaemia following radiotherapy and/or chemotherapy for multiple myeloma or breast cancer. In two patients, induction chemotherapy induced a lineage switch in the immunophenotype without change in karyotype. These observations support the concept that monosomy 7 leukaemia results from the transformation of a multipotential stem cell.
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PMID:Monosomy 7 in multilineage and acute lymphoblastic leukaemia. 195 71

Age-specific worldwide trends in cancer mortality were reviewed, with emphasis on cancer sites where increases have been reported in the USA. Cancer rates vary by factors as high as 30 between all countries, and 5-fold within and between industrialised countries. In Italy, Japan, Federal Republic of Germany, England and Wales, and the USA, patterns of cancer mortality have shifted uniformly over the past two decades. Stomach cancer continues to decline, while brain and other central-nervous-system cancer, breast cancer, multiple myeloma, kidney cancer, non-Hodgkin lymphoma, and melanoma have increased in persons aged 55 and older. Cancer of the lung is starting to decline for men under age 85 and women under age 60 in England and Wales and men under age 45 in the USA, but is still rising for men and women in other countries. All forms of cancer are increasing in persons over age 54 except lung and stomach (which together comprise between 20% and 43% of all cancer in males in these countries). Studies of the quality of ascertainment and enumeration indicate that these increases are not attributable solely to diagnostic artifacts or to increased access to health care, although both these factors may be involved. These recorded increases in cancer should be assessed in greater detail to provide better projections of health care needs and to identify causal factors that may be controlled. The changes in cancer other than lung are so great and rapid that their causes demand intensive investigation.
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PMID:International trends in cancer mortality in France, West Germany, Italy, Japan, England and Wales, and the USA. 197 9

We retrospectively analyzed thirty-three patients (21 males, 12 females) with malignancy induced spinal cord compression (SCC). The mean age of the patients was 42.8 years and almost half (51%) of them presented with SCC. Mean duration of symptoms was 4.5 months and the mean interval between the original diagnosis of cancer and the development of SCC was 14.6 months. Back pain was the most frequent (97%) symptom with an equal number of patients having subjective or objective evidence of lower limb weakness. Majority (73%) of the patients were non-ambulatory at the time of diagnosis. Spinal level involvement was mostly thoracic (62%) followed by lumber (38%). Breast cancer was the commonest underlying malignancy (21%). Lung (12%), prostrate (12%), multiple myeloma (9%), and carcinoma with unknown primary (12%) were also frequently encountered. There was an overall response rate of 22% to the therapeutic interventions: mostly observed in the ambulatory patients. Only 7% of the non-ambulatory patients regained ability to walk. None of the responders had bladder or bowel dysfunction. Twenty-two percent of the responders are still ambulatory with a mean follow-up of six months.
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PMID:Epidural spinal cord compression from metastatic cancer: clinical features and management. 203 83

Interleukin-3 (IL-3) is a T-cell-derived colony-stimulating factor (CSF) whose primary targets include relatively early, multipotential, hematopoietic progenitor cells. In this trial, we treated 24 patients with recombinant human IL-3 given by a daily 4-hour intravenous infusion for 28 days. The dose levels were 30, 60, 125, 250, 500, 750, and 1,000 micrograms/m2/d. At least three patients were entered at every dose level. Each participant suffered from bone marrow failure, with the underlying diagnosis being myelodysplastic syndrome (13 patients), aplastic anemia (eight patients), or aplasia after prolonged high-dose chemotherapy (three patients) for multiple myeloma, breast cancer, or acute myelogenous leukemia. Most patients tolerated therapy well, with the most frequent side effects being low-grade fever and headaches. Hematopoietic changes included modest increases in neutrophil counts (eight patients), eosinophil counts (six patients), platelet counts (three patients), and reticulocyte counts (two patients). An increase in blasts occurred in one patient who had refractory anemia with excess blasts in transformation and was reversible once IL-3 was discontinued. In addition, one patient with chronic myelomonocytic leukemia showed an increase in monocytes (and granulocytes). Progression to acute leukemia did not occur. Pharmacokinetic analyses showed a rapid clearance with a mean half-life of 18.8 minutes at the 60 micrograms/m2/d dose, and 52.9 minutes at the 250 micrograms/m2/d dose. Serum concentrations of 10 to 20 ng/mL of IL-3 were achievable at the 250 micrograms/m2/d dose. Our observations indicate that recombinant human IL-3 can be given safely at doses of 1,000 micrograms/m2/d or less. In addition, on the basis of preclinical data and the biologic activity observed in this study, further trials of this molecule, alone and in combination with other growth factors, are warranted in patients with pancytopenia.
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PMID:Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. 204 65


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