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)

We have made monoclonal antiidiotypic antibodies (Ab2) relating to the p97 antigen of human melanoma. This was accomplished by immunizing BALB/c mice with 96.5, a monoclonal antibody (MAb) specific for epitope p97a, hybridizing their spleen cells with NS-1 myeloma cells, and selecting for hybridomas making antibody binding to Fab fragments prepared from MAb 96.5 (Fab 96.5). The Ab2 were tested for binding to Fab 96.5, as well as for their ability to inhibit the binding between MAb 96.5 and p97. Three monoclonal Ab2 were identified which competitively inhibited the binding between p97 and MAb 96.5 when injected into either BALB/c or C3H/HeN mice; two of them induced Ab3 which expressed the same idiotype as MAb 96.5 and which were specific for p97. These two Ab2 thus appear to functionally mimic p97. They were, however, unable to induce delayed-type hypersensitivity to p97 and to protect mice against transplants of p97-positive mouse melanoma cells, suggesting that the epitope recognized by MAb 96.5 may not be a target for cell-mediated rejection of tumors.
 ...
PMID:Monoclonal antiidiotypic antibodies related to the p97 human melanoma antigen. 247 May 2

The lymphocytes from lymph nodes of six patients with metastatic mammary carcinomas were hybridised by fusion with a non-secreting variant of murine myeloma cells. Hybrid cells producing human immunoglobulin were detected by screening of culture supernatants using a solid-phase enzyme-linked immunosorbent assay for human IgG or IgM. Reactivity of human immunoglobulins to breast tumour cells was assessed by an indirect immunoperoxidase staining of fresh-frozen breast carcinoma sections. In the initial screening, the tissues used were those removed from the patients who acted as source of lymphocytes for fusion. The hybrid-cells, after repeated cloning, were stable for secretion of immunoglobulins. A total of 14 immunoglobulin G and 51 immunoglobulin M human monoclonal antibodies, showing variable reactivity to mammary carcinoma cells in tissue sections by an indirect immunoperoxidase staining method, were obtained. Two immunoglobulin G monoclonal antibodies (designated HMA-29 and HMA-31) were selected on the basis of their strong reactivity to the tumour cells and utilised to identify their corresponding antigens. The antibodies quantitatively discriminated, as expressed by the degree of staining, malignant from normal or benign mammary epithelia in freshly frozen or formalin-fixed breast tissues. The antibodies also showed reactivity to malignant cells of colon, stomach and lung and to normal cells lining the renal tubules and surface epithelium of colon. As revealed by blocking experiments, the epitopes recognised by these antibodies were not expressed on carcinoembryonic antigens, erythrocytes, lymphocytes, glycoproteins from milk-fat-globule membrane or keratins. The antibody HMA-29 immunoprecipitated a phosphoprotein (Mr = 29,000), and antibody HMA-31 two protein components (Mr = 31,000 and 34,000), from lysates of intrinsically labelled human mammary carcinoma cell line (MCF7). Neither of these proteins were present in detectable amounts in an intrinsically labelled melanoma cell line. Immunoblocking and immunoprecipitation experiments suggested that epitopes recognised by these two antibodies are dissimilar and are expressed on different molecules. The antibodies appear to be useful for functional characterisation of those antigens which are present in elevated levels in malignant compared with normal mammary epithelia.
 ...
PMID:Biochemical and immunological characterizations of antigens recognised by human monoclonal antibodies. 247 67

To study tumor-associated antigens that are immunogenic to humans, we have generated human monoclonal antibodies by fusing lymph node lymphocytes of a melanoma patient with a mouse myeloma cell line. We examined in detail the reactivity of one IgG antibody, termed 2-139-1. Immunostaining was performed with purified antibody conjugated to biotin. Binding was visualized by the avidin-biotin-peroxidase complex. With cultured cells, 2-139-1 stained 12 of 12 melanomas and 12 of 16 carcinomas. Reactivity was not detectable in seven neural crest tumors, six sarcomas, and 45 lymphomas and leukemias. This spectrum of reactivity was confirmed with sections of human tissues. The human monoclonal antibody 2-139-1 reacted against melanomas and not banal nevi. While the antibody reacted strongly to adenocarcinomas of the colon, prostate, rectum, and pancreas, it did not stain all the carcinomas tested. Furthermore, reactivity was not seen against sarcomas. Interestingly, 2-139-1 did not bind to the majority of the cells in normal tissues, including fetal tissues. The reactivity of 2-139-1 may be representative of the humoral immune response found in the regional lymph nodes of cancer patients. The distribution of this epitope in various tumors was fairly limited and appeared to be associated with malignant transformation.
 ...
PMID:Tumor-reactive human immunoglobulin G monoclonal antibody from a melanoma patient. 247 81

The interferons are the first of a new class of biologic response modifiers that include, among others, the interleukins, colony-stimulating factors, erythropoietin, additional growth factors, and monoclonal antibodies. Interferons have exhibited important clinical activity in hematologic malignancies, lymphomas, and solid tumors. Specific diseases responding to interferons include hairy-cell leukemia (HCL), chronic myelogenous leukemia (CML), low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, multiple myeloma, superficial bladder carcinoma, malignant carcinoid, acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma, ovarian carcinoma, renal cell carcinoma, and malignant melanoma. The potentially antigenic nature of the recombinant interferons can result in the formation of antibodies. These antibodies have been associated with the abrogation of some of the clinical responsiveness of some patients treated with interferons. It is hoped that the controversy existing over the role of antibody formation in treatment efficacy can be resolved by prospective trials using standardized methodology in such areas as assay type, sampling time, route of drug administration, treatment schedule, cumulative dose, and duration of treatment.
 ...
PMID:Biotherapy in clinical practice. 247 4

Incubation of peripheral blood mononuclear cells with interleukin-2 (IL-2) results in the release of a factor which is cytostatic and cytotoxic both to tumor cell lines (A375M, A375P, C480, MCF-7, Hey) and fresh tumor cells (in the human tumor cloning assay), including breast cancer, colon cancer, melanoma, myeloma and ovarian cancer. The factor cannot be detected in a 4-h chromium-release assay, but is best demonstrated after tumor cells have been to it for exposed 3 days. The factor is not cytotoxic to normal peripheral blood leukocytes or normal fibroblasts, and is not toxic to certain targets sensitive to lymphokine-activated killer (LAK) cells, such as K562 and Daudi cells. The factor is diffusible, non-dialyzable, relatively stable to heat and acid and does not contain appreciable amounts of targets resistant to interferon-alpha and beta, tumor necrosis factor beta and interleukin-1. The data suggest that there are several mechanisms of LAK cell activity against tumor cells including one which requires direct interaction of LAK and tumor cells and one which is mediated by LAK cell supernatant. The former is detected by 4-h chromium release while the latter is not.
 ...
PMID:Cytostatic and cytotoxic activity of lymphokine-activated killer cell supernatants. 248 Aug 43

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposi's sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Unusual malignant tumours in 49 patients with HIV infection. 250 49

The authors collected and analyzed cancer incidence data for Alaska Natives (Indians, Eskimos, and Aleuts) for the 15-year period 1969-83 by ethnic and linguistic groups. Compared with U.S. whites, observed-to-expected ratios are high in more than one ethnic group for cancer of the nasopharynx, salivary gland, liver, gallbladder, and cervix. Low ratios were found for cancer of the breast, uterus, bladder, and melanoma. In Alaska, Eskimos have the highest risk for cancer of the esophagus and liver and the lowest risk for breast and prostate cancer. Risk for multiple myeloma in Indian men in Alaska exceeds not only those of other Native groups in Alaska but that in U.S. whites as well. Despite the short period studied, increases in cancer incidence over time can be documented for lung cancer in Eskimo men and women combined, and for cervical cancer, especially in Indian women.
 ...
PMID:Cancer in Alaskan Indians, Eskimos, and Aleuts, 1969-83: implications for etiology and control. 251 2

By fusion of mouse NS1 myeloma cells with splenocytes from a BALB/c mouse immunized with human melanoma cells, an IgG1 monoclonal antibody, designated as 140.72, was produced. By the mixed hemadsorption antibody binding assay, 140.72 was shown to react with 17 of 20 melanoma cell lines and with 5 of 14 carcinoma cell lines. This antibody also reacted with 3 of 3 normal melanocyte cultures in much lower titers. It did not react with any of 35 other normal and malignant lines, including neuroblastoma, glioblastoma, sarcoma, teratoma, fibroblast, and lymphoid cell lines. Absorption with fresh melanoma and carcinoma homogenates confirmed the results of direct tests. Fetal reactivity of antibody 140.72 was determined by positive absorption with 10 of 11 tissue homogenates derived from different fetuses of 10-16 weeks' gestation. The reactivity of this antibody was completely removed by absorption with a highly purified preparation of carcinoembryonic antigen (CEA) derived from a colon carcinoma. The antigenic activity was detected in the culture medium of reactive cell lines. Immunoprecipitation analyses of melanoma and carcinoma cells indicated that the antigenic determinant recognized by antibody 140.72 is on a glycoprotein with an apparent molecular weight of 95,000-150,000 common to both serologically reactive cell types. Additionally, a 200,000-molecular-weight glycoprotein corresponding to the CEA molecule was detected only on the reactive carcinoma cells. These data confirmed previous findings obtained with polyclonal anti-CEA antisera for the existence of shared CEA-related antigenic determinants on human carcinomas and melanomas and provided additional molecular characterization of these glycoproteins. Further characterization of the molecules bearing the antigenic determinant recognized by antibody 140.72 should be performed with a view to exploring its potential in the immunodiagnosis and immunotherapy of patients with melanoma.
 ...
PMID:Monoclonal antibody recognizing human melanoma-carcinoma cross-reacting oncofetal antigen epitopically associated with carcinoembryonic antigen. 258 73

Hybridization with murine myeloma cells P3-X63-Ag8.653 of splenocytes from BALB/c mice immunized with syngeneic anti-human high molecular weight melanoma-associated Ag (HMW-MAA) mAb 149.53, 225.28, 763.74, and TP41.2 has resulted in the formation of antiidiotypic antibody-secreting hybridomas with a frequency ranging between 1.2% and 5.2%. No marked difference was detected in the frequency of antibody secreting hybridomas in the fusions generated from mice immunized with the four anti-HMW-MAA mAb, suggesting that the idiotopes expressed by each of them display similar immunogenicity in a syngeneic combination. The number of antiidiotypic mAb that did not inhibit the binding of immunizing mAb to melanoma cells was higher than that of those that died, suggesting that idiotopes not associated with the Ag-combining site are more immunogenic than those that are. The idiotopes recognized by mAb were not detected on a large panel of anti-HLA Class I mAb, anti-HLA Class II mAb, and anti-human melanoma-associated Ag mAb. The latter included also mAb that cross-inhibit the immunizing anti-HMW-MAA mAb. The idiotopes recognized by mAb were not detected on the isolated H and L chain of the immunizing anti-HMW-MAA mAb. Cross-blocking experiments with a selected number of antiidiotypic mAb identified three distinct idiotopes on mAb 149.53, 225.28, and TP41.2 and two on mAb 763.74. Three, 5, 2, and 5 antiidiotypic mAb to idiotopes within the Ag-combining site of mAb 149.53, 225.28, 763.74, and TP41.2, respectively, were tested for their ability to induce anti-HMW-MAA antibodies. Serological and immunochemical assays detected anti-HMW-MAA antibodies only in sera from BALB/c mice immunized with mAb MK2-23. Therefore, mAb MK2-23 can be classified as beta, while the remaining 14 can be classified as gamma.
 ...
PMID:Characterization of syngeneic antiidiotypic monoclonal antibodies to murine anti-human high molecular weight melanoma-associated antigen monoclonal antibodies. 258 21


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