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)

In a phase II study 28 patients with advanced multiple myeloma were treated with a five drug regimen consisting of vincristine, BCNU, adriamycin, melphalan and dexamethasone. 11 out of 13 patients without prior chemotherapy showed significant remissions (greater than 25% tumor cells mass reduction), 7 of them had more than 75% TCM reduction. Out of 15 additional patients resistant to previous chemotherapy, 13 had significant remissions, including 9 patients with greater than 75% TCM reduction. No tumor progression was observed in either group of patients. The median follow-up of all patients was 12.75 months. 4 patients relapsed. Toxicity mainly related to the bone marrow was observed in 14 patients. This regimen might offer a promising alternative for the treatment of advanced multiple myeloma, but still has to be tested in a prospective randomized trial.
 ...
PMID:VBAMDex chemotherapy in advanced multiple myeloma. 335 40

Thirty-five previously untreated patients with multiple myeloma were treated with a 60-week course of alternating, potentially non-cross-resistant chemotherapy combinations (melphalan and prednisone; vincristine, cyclophosphamide, doxorubicin, and prednisone; and carmustine, melphalan, and prednisone), alternating every 15 weeks in an attempt to prevent the development of drug resistance. The overall objective response rate (greater than 50% decrease in M protein) was 60% and six patients (17%) had a complete disappearance of the M protein. After 60 weeks, chemotherapy was discontinued in 17 responding or stable patients until relapse occurred from 4 to 39 months later (median, 12 months). Patients relapsing late (greater than 12 months after discontinuation of therapy) responded more frequently than those relapsing earlier to the reinstitution of the same chemotherapy program. The overall response rate and the actuarial median survival of 26 months in the 35 patients do not differ from the results reported recently with nonalternating combinations given until clinical tumor progression. The failure of this study to prolong survival by using alternating regimens may be due to (a) the likely possibility that the initial two regimens are not actually non-cross-resistant in most myeloma patients, and (b) the long interval between the alternating regimens, particularly in the face of the low response rate to the initial regimen of melphalan and prednisone.
 ...
PMID:Therapy for multiple myeloma with alternating non-cross-resistant chemotherapy combinations: heterogeneity of tumor responsiveness. 639 62

Criteria were defined for recognizing 29 patients with a localized plasmacytoma of bone and 20 patients with an indolent variety of multiple myeloma in order to justify long-term follow-up without chemotherapy. All patients with indolent myeloma were asymptomatic from their low tumor mass disease, had a hemoglobin greater than 10 g/dl, and showed no more than 3 lytic bone lesions. The presence of more than 200 mg/day of Bence Jones protein was usually followed by disease progression within 2 yr. Serial assessments of myeloma protein level provided a useful index of changing tumor load and the need for chemotherapy. In patients with localized disease, radiotherapy usually reduced myeloma proteins markedly with subsequent disease control for many years, even though small serum peaks persisted. Chemotherapy for multiple myeloma was not required for a median of 8 yr in patients presenting with localized disease and of 3 yr in those with indolent myeloma. The additional survival from the start of drug treatment was similar to that of comparable patients treated promptly for overt multiple myeloma. The delay of chemotherapy until evidence of tumor progression did not affect the long-term outcome of patients with localized or indolent myeloma.
 ...
PMID:Localized and indolent myeloma. 740 16

N- and K-ras oncogene mutations represent the most frequent molecular lesions in plasma cell dyscrasias. They are not randomly distributed since they are detectable in multiple myeloma (MM) (9-31%) and plasma cell leukemia (PCL) (30%), and not in monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma (SP). Codons 12, 13 and 61 of N- and K-ras genes have been found mutated. Mutations affecting codon 61 of N-ras gene are the most frequent finding. A heterogeneous pattern of mutations is described with a prevalence of purine-pyrimidine transversions. Ras gene mutations have been predominantly detected in myelomas characterized by an advanced stage disease, and adverse prognostic parameters. These findings suggest that ras mutations represent a late molecular lesion and may be implicated in tumor progression rather than tumor initiation.
 ...
PMID:N- and K-ras oncogenes in plasma cell dyscrasias. 785 96

The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.
 ...
PMID:p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy. 841 84

During a 10-year period, 17 patients with segmentally destructive bone lesions of the humeral diaphysis in disseminated malignancies resulting in impending fracture (8 patients), pathologic fracture (6 patients), or failure of attempted internal fixation techniques (3 patients) were treated with resection of the involved diaphyseal segment and reconstruction with a cemented modular intercalary humeral spacer. Fourteen patients had metastatic cancer, 2 had multiple myeloma, and 1 had lymphoma. Breast and renal carcinoma were the most common pathologic diagnoses. The involved site was within the middle 1/3 in 8 patients, in the proximal-middle junction in 5, in the middle-distal junction in 2, and within the proximal and distal 1/3 in 1 patient each. Early pain relief was successful in 88% of patients. Early in the postoperative hospital course, patients generally were able to use the ipsilateral hand to assist feeding. Radiographic analysis revealed that the limited selection of stem lengths led to 76% of the distal stems and 47% of the proximal stems being shorter than the ideal length. The complication rate independent of disease progression was 29%. The most common complication was temporary radial nerve injury (3 patients). There were 3 implant failures, most commonly due to disengagement of the male-female junction. Two periprosthetic fractures occurred, 1 proximally (due to tumor progression) and 1 distally. Suggestions are given for modification of the implants to improve the major problems of limited versatility in intramedullary stem length and inadequate mating at the junction.
 ...
PMID:Intercalary spacers in the treatment of segmentally destructive diaphyseal humeral lesions in disseminated malignancies. 859 62

CD3 engagement has been used as a surrogate for antigen-specific stimulation to trigger T cell effector functions. Exogenous IL-2 has been used to prolong and amplify CD3-induced T cell activation. Previous studies have been shown that CD3 reactivity is increased in cancer patients with preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In this study, we report 9 courses of a single infusion of anti-CD3 mAb (OKT3) followed by continuous infusion of intermediate dose IL-2 in 4 cancer patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metastatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells in the peripheral blood. An increase of lymphocytes, equally distributed between CD4+ and CD8+ subsets, was observed during treatment. Activation was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including proliferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL-2 infusions were well tolerated and no limiting toxicity was observed. The treatment did not revert tumor progression in the 2 patients with progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequential administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for treatment because of an increased number of HLA-DR+ T cells in the peripheral blood. A discrepancy was observed between the emergence of CD25+ T cells and the clinical outcome.
 ...
PMID:Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2. 872 15

The Neural Cell Adhesion Molecule NCAM is a membrane glycoprotein and belongs to the immunoglobulin superfamily. It is expressed on neural cells as well as on various neuroendocrine tumors and can be detected in sera of patients with small cell lung cancer. Its role is attributed to tumor invasion and formation of metastases. Malignant plasma cells and a subset of plasma cells from patients with monoclonal gammopathy exhibit surface expression of NCAM whereas normal plasma cells do not express NCAM. Expression as measured by flow cytometry using anti-CD56 antibodies does not seem to correlate with clinical course, however leukemic myelomas and myeloma cell lines tend to loose NCAM surface expression. An isoform of NCAM which is rich in polysialic acids and characteristic for embryonal NCAM (eNCAM) has been shown to be elevated in sera of patients with multiple myeloma using a chemiluminescence immunoassay. Patients with progressive myeloma tend to have high serum NCAM levels above the normal range of 20 U/ml. Analysis of 125 myeloma patients suggest that serum NCAM is a valuable parameter for tumor progression rather than tumor mass. Increase in serum NCAM may be associated with loss of adhesive function.
 ...
PMID:The neural cell adhesion molecule NCAM in multiple myeloma. 883 94

Mouse myeloma cell line VKCK/RM4-IFN-gamma secreting the bifunctional fusion protein RM4/IFN-gamma was used to study the relationship between IFN-gamma secretion of tumor cells and its tumorigenicity and to study the potential mechanism responsible for the immune response. IFN-gamma secretion of VKCK/RM4-IFN-gamma tumor cells was estimated at 90 U/ml using an antiviral assay. To evaluate tumorigenicity, 5 x 10(5) viable IFN-gamma-secreting VKCK/RM4-IFN-gamma and non-IFN-gamma-secreting VKCK tumor cells were injected s.c. into syngeneic BALB/c mice and VKCK/RM4-IFN-gamma-immunized or T cell subset-depleted BALB/c mice, respectively. Tumor progression or regression was evaluated 2 weeks after tumor inoculation. Our animal studies showed that RM4/IFN-gamma secretion by VKCK/RM4-IFN-gamma tumor cells curtailed its tumorigenicity in BALB/c mice and induced a persistant protective immune response against a subsequent graft of parental VKCK tumor. This protective immunity is long term and tumor specific as measured in a 51Cr-release assay. In addition, our animal studies in T cell subset-depleted BALB/c mice showed that CD8 CTL play a major role in the reduction of tumorigenicity. This study thus highlights the potential advantages of localized IFN-gamma in tumors to induce potent antitumor immunity and further suggests that the bifunctional fusion protein RM4/IFN-gamma may be useful in cancer immunotherapy because of its capacity of targeting IFN-gamma to human tumors expressing the human tumor-associated TAG72 antigen [corrected].
 ...
PMID:Mouse myeloma cell line secreting bifunctional fusion protein RM4/IFN-gamma [corrected] elicits antitumor CD8 MHC class I-restricted T cells that are cytolytic in vitro and tumoricidal in vivo. 891 Jul 61

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.
 ...
PMID:Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression. 896 Jan 9


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