Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 6 (IL-6) is a major in vitro growth factor for tumoral cells in human multiple myeloma and myeloma cell lines, whose growth is completely dependent on exogenous IL-6, can be reproducibly obtained. IL-6 is overproduced in patients with active myeloma, mainly by the tumoral environment. Injection of anti-IL-6 antibodies to myeloma patients with terminal disease and extramedullary proliferation completely blocked myeloma-cell proliferation in vivo and completely inhibited the C-reactive protein production. Moreover, the serum CRP level is a strong prognostic factor in myeloma, increased serum CRP levels (reflecting an increased IL-6 production) being associated with a poor prognosis. Other cytokines control the IL-6 mediated myeloma cell proliferation. GM-CSF, IL-3 and G-CSF stimulate the IL-6 responsiveness of myeloma cells without affecting the endogenous IL-6 production. Interferon-gamma completely inhibits the IL-6 mediated myeloma-cell proliferation without affecting the endogenous IL-6 production and IFN alpha and TNF alpha stimulate the proliferation of our IL-6 dependent myeloma-cell lines by inducing an autocrine production of IL-6 in these cell lines.
 ...
PMID:[Cytokines and lymphoplasmocytic proliferations: essential role of interleukin 6]. 850 54

In two consecutive studies of a pilot study and a multicenter trial 16 patients and 61 patients, respectively, with multiple myeloma were treated with the combination chemotherapy (CMVM regimen; the same intermittent high dose dexamethasone as in VAD regimen, MCNU bolus injection of 1.2mg/m2 on day 1, melphalan 12mg/day on days 1-6) plus IFN alpha (HLBI 300MU every day or two) to assess the efficacy and the toxicity of this protocol. Both studies were achieved in the same regimen except for initial 12 days administration of IFN alpha in the multicenter trial. The treatment was repeated 3 times every 6-8 weeks. Complete remission (CR) in which serum and urine M protein disappeared and myeloma cells in bone marrow were eradicated was obtained in 6 in 16 patients (37.5%) in the pilot study and 16 in 61 patients (26.2%) in the multicenter trial. CR plus PR was 68.8% and 68.9% in two studies. The achievement of CR in such high proportion of patients may exhibit a significant advance in the myeloma therapy.
 ...
PMID:[New protocols for myeloma chemotherapy plus IFN alpha]. 851 Mar 33

In clinical trials with interferon alpha 2b (IFN-alpha 2b) as maintenance therapy for multiple myeloma, the therapeutic benefit is inconclusive. Although the mechanism(s) by which IFN-alpha 2b prolongs remission in some patients is unknown, 2',5'-oligoadenylate synthetase (2,5-A synthetase) has been used as an objective indicator that IFN-alpha 2b is active in vivo. The enzyme was assayed in cytosol preparations of peripheral blood mononuclear cells (MNCs) from 111 patients who were receiving IFN-alpha 2b and 54 patients who were not, using an assay which measures the conversion of [alpha-32P]ATP to triphospho(adenylyl 2',5')adenosine. 2,5-A synthetase activity was compared with response to intensive therapy and with duration of maintenance therapy. Seventy-three per cent of patients had measurable amounts of 2,5-A synthetase during the first 6 months of maintenance therapy. This percentage decreased with longer follow-up but not significantly. There was no difference between the magnitude of enzyme induction amongst patients who were in complete remission, partial response or who had no change in disease status following intensive therapy. Peripheral blood T cells were a major source of 2,5-A synthetase activity in patients receiving the cytokine. However, both T and B cells produced the enzyme following exposure to IFN-alpha in vitro. The data show that the level of 2,5-A synthetase in patients with multiple myeloma is not indicative of clinical response to IFN-alpha 2b.
 ...
PMID:2',5'-Oligoadenylate synthetase levels in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b do not correlate with clinical response. 851 71

The article reviews the therapeutic efficacy of alpha interferon (alpha IFN) in the management of myelomatosis. The data provided in the medical literature suggest that alpha IFN is a useful agent in the management of myelomatosis. In particular, its association to conventional induction therapies of previously untreated multiple myeloma (MM) patients may improve the overall response rate and probably increase the number of complete responders. On the other hand, even though alpha IFN alone, in some patients with previously untreated MM, may induce good objective responses, it remains certainly less effective than conventional chemotherapy. Moreover, in a small proportion of advanced MM patients, alpha IFN alone has induced objective responses. It is therefore possible that alpha IFN should be combined with other therapeutic modalities to improve the observed response rate in these patients. Finally, alpha IFN maintenance treatment seems to be one of the most promising therapies for patients with myelomatosis. However, the achievement of a "true" "plateau phase" after the induction treatment is certainly necessary to permit alpha IFN of prolonging the response duration as well as survival duration. The importance of the achievement of a "true" "plateau phase" is better emphasized by the good results obtained using alpha IFN after transplantation procedures.
 ...
PMID:Is alpha-interferon treatment in multiple myeloma worthwhile? 852 Apr 97

A 49-year-old man with the idiopathic hypereosinophilic syndrome (HES) and a unique chromosomal abnormality 46,XY,t(5;9)(q32;q33) is reported. Complete cytogenetic remission was induced by interferon alpha-2b (IFN-alpha). The beneficial action of IFN-alpha in different stem-cell disorders such as CML, HES, multiple myeloma and solid tumours such as hypernephroma or malignant melanoma suggests a common regulatory effect possibly by immunomodulation or other (immune-mediated) mechanisms, but the exact pathophysiological mechanisms remain hypothetic and unresolved. Since it has been known for some years that the genes encoding for GM-CSF, IL-3 and IL-5 reside on the long arm of chromosome 5, it could be possible that the chromosomal translocation in our patient resulted in excess production of these cytokines, hence causing the hypereosinophilia. This case report and the results obtained from the literature review support the growing body of evidence that IFN-alpha has a major place in the long-term treatment of HES, especially in those cases resistant to conventional treatment, with cytogenetic abnormalities, or presenting as a myeloproliferative variant of HES. In those cases IFN-alpha results in lower morbidity, lower mortality and long-term survival.
 ...
PMID:Further evidence for the clonal nature of the idiopathic hypereosinophilic syndrome: complete haematological and cytogenetic remission induced by interferon-alpha in a case with a unique chromosomal abnormality. 921

Multiple myeloma (MM) remains incurable. Despite many chemotherapy programs for large numbers of patients, there has been little improvement in outcome during the past 25 years. For many years, intermittent courses of melphalan and prednisone have represented the standard chemotherapy for newly diagnosed symptomatic MM. Many other drug combinations have been assessed, including regimens using multiple alkylating agents, and programs with vincristine, or an anthracycline, and have failed to show any superiority to melphalan-prednisone. Interferon alpha (IFN alpha) inhibits plasma cell growth and has induced responses in approximately 15% of previously untreated patients. This cytokine may have a role when used in those patients who have reached a good "plateau phase" with low tumor burden at the end of a chemotherapeutic program or after a transplantation procedure. The results of myeloablative therapy with allogenic or autologous marrow transplantation are promising and suggest possibility of a cure in some patients. Important problem in the management of MM patients is the treatment of complications, especially bone destruction, hypercalcemia, anemia and infections. Experimental modalities, especially immunotherapy, hold promise for use in humans and may also provide further insights into the pathogenesis of MM.
 ...
PMID:[Treatment of multiple myeloma--present status and perspectives]. 862 44

Plasma cell tumors (plasmacytomas-PCT) of the bone, or extramedullary PCT, may be diagnosed in patients with or without the diagnostic criteria for systemic multiple myeloma (MM). The reason for the local development of these tumors is not clear. Recent reports emphasize the contribution of CT and MRI in the detection of bone lesions and their expansion into the soft tissues. We report the development of PCT in nine patients with MM under maintenance treatment with alpha-IFN, of whom six had no evidence of systemic relapse and three had indications of early relapse. The PCT were located in the pelvis (4), thoracic (3), cervical (1), and lumbar (2) spine and in 8/9 cases were not demonstrable on plain X-rays. These observations suggest that frequent screening with advanced imaging techniques may detect local disease expansion in asymptomatic patients. Early application of radiochemotherapy may improve prognosis.
 ...
PMID:Development of plasma cell tumors during treatment of multiple myeloma. 864 44

The c-cbl proto-oncogene product (p120cbl) forms a stable complex with the Tyk-2 protein tyrosine kinase in various human cell lines of diverse hematopoietic origin. In U-266 myeloma and 293T embryonic kidney cells, p120cbl is rapidly phosphorylated on tyrosine in an IFN alpha-dependent manner. p120cbl also acts as a specific substrate for the Tyk-2-associated SHP-1 phosphatase in vitro, suggesting that this phosphatase plays a regulatory role on the phosphorylation of the protein. These data provide evidence that p120cbl interacts with the functional Type I IFN receptor complex, and suggest its involvement in IFN alpha signaling.
 ...
PMID:Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase. 878 Jun 98

Haematopoietic stem cell-supported myeloablative therapy appears to be a promising treatment modality for MM. It yields increased overall response and CR rates when compared with conventional chemotherapy, and seems to prolong the duration of survival. These conclusions, while encouraging, have mostly been drawn from uncontrolled studies carried out in select groups of patients and, obviously, need to be confirmed in controlled clinical trials. While the results of these studies are still awaited, the wider application of BMT should probably be encouraged. As in other malignancies, the best candidates appear to be those less heavily pre-treated, with chemosensitive disease, low tumour cell mass and other favourable prognostic features, for example low beta 2-microglobulin levels. Under these conditions, the chance of entering CR following BMT, be it autologous or allogeneic, is currently estimated to be of at least 50%, and the long-term probability of survival averages approximately 30%. However, while it appears that a plateau for progression-free survival cannot be ascertained following a single ABMT, reported observations of patients with continued disease-free survivals up to and beyond 10 years after allografting suggest that this latter procedure may be curative. It seems likely therefore that the higher mortality related to allogeneic BMT (which in recent years decreased from 50% to approximately 30% as the results of a better selection of patients and increasing experience in their management) may be offset by more durable control of the disease and cure in a certain proportion of patients. Recurrence of underlying malignant disease remains, however, a major problem and is the most common cause of treatment failure following BMT. For this reason, attempts to improve the impact of transplantation are warranted. Options currently under investigation include the development of more effective conditioning regimens, as applied in double auto-transplant or with targeted therapy using antibody-radionuclide conjugates, as well as post-transplant immunomodulation with either IFN-alpha, interleukin-2 or idiotype vaccines. In addition, many other problems regarding BMT for MM are still unresolved and could be properly addressed only in future clinical trials. The most important of these issues include the choice of the best conditioning regimen and the optimal source of haematopoietic stem cells, the nature of relapse after autografting, the need to purge or not to purge the autologous marrow, the existence of a 'graft-versus-myeloma' effect and its role in prolonging the duration of disease control and, finally, the likelihood of cure, especially for patients with molecularly-defined CR.
 ...
PMID:The role of haematopoietic stem cell-supported myeloablative therapy for the management of multiple myeloma. 884 73

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.
 ...
PMID:The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma. 884 74


<< Previous 1 2 3 4 5 6 7 8 9 10