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)

One class of genes coding for the acute-phase proteins (acute-phase genes) is induced by interleukin 6 (IL-6) through the human transcription factor NF-IL-6 and its rat homolog IL-6-DBP/LAP. A second class, represented by the rat alpha 2 macroglobulin gene, utilizes a different IL-6 response element (IL-6-RE) and different DNA-binding proteins interacting with this element, the so-called IL-6-RE binding proteins (IL-6 RE-BPs). Human Hep3B and HepG2 hepatoma, U266 myeloma, and CESS lymphoblastoid cells contain IL-6 RE-BPs that form complexes, with the IL-6-RE, with gel mobilities indistinguishable from those of the corresponding complexes of rat liver cells. The ability to form these complexes was induced by IL-6 in human hepatoma cells with a maximum reached after 4 h and required ongoing protein synthesis. Multiple copies of an 18-bp element containing the IL-6-RE core were sufficient to confer both induction by IL-6 and a synergistic induction by IL-6 plus glucocorticoids to minimal promoters. The synergism was blocked by the receptor antagonist RU486 and thus was dependent on the glucocorticoid receptor (GR). However, the 18-bp element contained no consensus GR-binding site, and recombinant GR did not bind at this sequence. Therefore, the synergism was probably achieved by an indirect effect of a glucocorticoid-activated intermediate gene on the IL-6 RE-BPs. The rat IL-6 RE-BP had a molecular weight of 102 +/- 10 kDa and was thus distinct from NF-IL-6 and IL-6-DBP/LAP. Therefore, IL-6 must activate two different classes of liver acute-phase genes through at least two different nuclear DNA-binding proteins: NF-IL-6/IL-6-DBP/LAP and the IL-6 RE-BP.
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PMID:Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene. 137 12

The present experiment was undertaken to study what types of human cancers are responsive to the antiproliferative effects of suramin. The human malignant cells used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), in vitro transformed fibroblasts (KMST-6, SUSM-1, VA-13), five myeloma cell lines (KMM-1, KMS-5, KMS-11, KMS-12, RPMI 8226), Burkitt's lymphoma (Raji), acute promyelocytic leukemia (HL-60), chronic myelocytic leukemia (K562), Epstein-Barr virus nuclear antigen positive lymphoblastoid cells (KMS-9). The cells were treated with 25 to 100 micrograms/ml suramin for 72h. Proliferation of HuH-7 and two human myeloma cells (KMS-11 and KMS-12) was remarkably inhibited, and that of PA-1, PLC/PRF/5, KMST-6, two other myeloma cell lines (KMM-1 and KMS-5), Raji and HL-60, was moderately inhibited. In order to confirm part of the results obtained from in vitro experiments, in vivo experiments were also undertaken. The growth of HuH-7 cells transplanted subcutaneously into nude mice was significantly suppressed by intravenous injection of suramin. We discussed the possibility that certain types of human cancers, the growth of which seemed to be more or less dependent on polypeptide growth factors, might be sensitive to the antiproliferative effects of suramin.
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PMID:Antiproliferative effects of suramin on human cancer cells in vitro and in vivo. 148 40

Monoclonal antibodies that bound to 3 human hepatocellular carcinoma cell lines (PLC/PRF/5, SK-SF and Mahlavu) and snap-frozen sections of a patient's tumour were raised by immunising mice with PLC/PRF/5 membrane preparations. The monoclonals designated RF-HCC 1 and RF-HCC 2 were of IgG1 and IgM subclasses respectively. Binding of the antibodies to surface epitopes present on Mahlavu cells in vitro took place in a biphasic fashion, with initial rapid binding of each antibody during the first 15 minutes of incubation followed by a plateau after this period. It was found that the commercially available MOPC 21 myeloma IgG1 (Sigma) monoclonal antibody used a control also bound to a surface antigenic determinant expressed on Mahlavu cells.
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PMID:Production of monoclonal antibodies against human hepatocellular carcinoma by immunisation with a cell membrane preparation. 169 62

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.
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PMID:Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family. 170 Oct 20

The authors describe 2 patients with chronic active hepatitis accompanied for many years by stable monoclonal immunoglobulinopathy. In addition to the formation of liver cirrhosis, these patients were diagnosed to have multiple myeloma. Analysis of the authors' and reported data (including those on transformation of liver cirrhosis associated with monoclonal immunoglobulinopathy to hepatocellular carcinoma) makes it possible to regard patients suffering from chronic diffuse liver diseases associated with monoclonal immunoglobulinopathy as a group at risk for paraproteinemic hemoblastosis and hepatocellular carcinoma. The pathogenesis of the development of paraproteinemic hemoblastoses and hepatocellular carcinoma in the indicated group of patients is under discussion.
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PMID:[The development of multiple myeloma in chronic diffuse liver diseases with a long course of monoclonal immunoglobulinopathy (a description of 2 cases)]. 179 3

The sternum is known as a common site of bone metastasis in a variety of neoplasms. Sternal metastasis is usually visualized as hot spot on bone scintigraphy. However, photon deficiency in the sternum on bone scintigraphy is reported in few cases with malignancy. We undertook a retrospective analysis to clarify the clinical significance of photon deficiency in the sternum in 12 patients with malignancy. Twelve patients (five breast cancer, two multiple myeloma, one lung cancer, one renal cell cancer, one hepatocellular carcinoma, one malignant lymphoma, and one thyroid cancer) showing cold sternal metastasis on bone scintigraphy were identified among 9,430 patients in whom bone scintigraphy was performed. Except for two cases with pathologically confirmed sternal metastasis, all patients showed lytic change in the sternum on tomography or CT scan. Six cases of solitary sternal metastasis showed partial effect of systemic therapy (chemotherapy, humoral therapy, and radiation therapy) and surgical treatment. It is necessary to keep in mind that this type of lesion may occur as a manifestation of metastatic disease.
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PMID:Photon-deficient finding in sternum on bone scintigraphy in patients with malignant disease. 207 33

The chimeric toxin IL6-PE40, which is composed of interleukin 6 (IL6) fused to a mutant form of Pseudomonas exotoxin (PE) devoid of its native cell recognition domain, can kill myeloma and hepatoma cells which express high levels of IL6 receptors. To enhance the usefulness of IL6-PE40 on potential target cells, we have attempted to develop more potent IL6-PE derivatives. We have developed nine new IL6-PE derivatives and assessed their cytotoxicity on human myeloma cells. Two of these new forms, IL6-domain II-PE40 and IL6-PE664Glu were more toxic to myeloma cells bearing IL6 receptors than was IL6-PE40. These two chimeric toxins were compared with IL6-PE40 for cytotoxicity toward a variety of tumor cell lines. We found that most tumor cell lines which are sensitive to IL6-PE40 are more sensitive to IL6-domain II-PE40 and IL6-PE664Glu. Cells with as few as 200-600 IL6 receptors/cell could be killed. The specificity of these chimeric toxins was shown through competition with recombinant IL6. Toxicity studies in mice demonstrated that the two new molecules had an LD50 of 10-20 micrograms/mouse. This compares to an IL6-PE40 LD50 of 20 micrograms/mouse. The new IL6-toxins could be detected in the serum up to 8 h after intraperitoneal administration with a peak at 1 h. These data suggest that IL6-domain II-PE40 and IL6-PE664Glu may be more useful than IL6-PE40 in killing IL6 receptor-bearing tumor cells in animals.
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PMID:Cytotoxicity of IL6-PE40 and derivatives on tumor cells expressing a range of interleukin 6 receptor levels. 211 4

IL6-PE40 is a chimeric toxin composed of human interleukin-6 (IL6) linked by a peptide bond to PE40, a form of Pseudomonas exotoxin (PE) devoid of its cell recognition domain. To identify cancer cell lines with high numbers of IL6 receptors and to assess the usefulness of IL6-PE40 as a possible anticancer agent, we evaluated the toxicity of IL6-PE40 on a variety of tumor cell lines and demonstrated that certain human myeloma and hepatoma cell lines were particularly sensitive. IL6 binding to selected hepatoma and myeloma cell lines were determined by using [125I]IL6. IL6 receptor mRNA levels were measured by polymerase chain reactions. When comparisons were made among different hepatoma cell lines, the sensitivity to IL6-PE40 correlated with the number of IL6 receptors. However, the hepatoma line PLC/PRF/5, which contains 2,300 IL6 receptors, was more sensitive to IL6-PE40 (amount of protein required to inhibit protein synthesis by 50% was 5 ng/ml) than both the myeloma cell lines U266 and H929 (for both cell lines, the 50% inhibitory dose was 8 ng/ml), which contain 15,500 and 16,500 IL6 receptors, respectively. RNA analysis confirmed that the sensitivity of these cells to IL6-PE40 and the amount of IL6 receptor RNA detected did not correlate. These data suggest that factors in addition to the number of IL6-binding sites contribute to the sensitivity of cells to IL6-PE40.
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PMID:Cell-specific toxicity of a chimeric protein composed of interleukin-6 and Pseudomonas exotoxin (IL6-PE40) on tumor cells. 216 May 79

We studied the antitumor activity of newly synthesized bis(1-acyloxymethyl) derivatives of 4,4'-(1,2-ethanediyl)bis(2,6-piperazinedione) using i.p.-i.p. models of P388 leukemia and B16 myeloma. As a result, we found 4,4'-(1,2-ethanediyl)bis(1-isobutoxycarbonyloxymethyl-2,6-piperazi nedione) (MST-16) to possess considerable therapeutic activity. MST-16 showed not only marked life-prolonging effects in both P388 leukemia- and B16 melanoma-bearing mice but also a greater therapeutic ratio than did its parent compounds, ICRF-154 and ICRF-159. Further studies revealed that MST-16 has considerable therapeutic activity against a number of other tumors such as ascitic forms of L1210 leukemia, colon 26 adenocarcinoma, and MH-134 hepatoma and solid forms of B16 melanoma, Lewis lung carcinoma, colon 38 adenocarcinoma, and M5076 fibrosarcoma. These results suggest that MST-16 is very promising as an antitumor agent.
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PMID:Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models. 235 66

Sixteen tumor markers are reviewed, and measured to the ideal: produced by the tumor cell alone absent in health and in benign disease present in all patients with a given malignancy level in the blood representative of tumor mass detectable in occult disease. The only marker that approaches the ideal is human chorionic gonadotropin (HCG) in gestational trophoblastic tumors. In this malignancy, the HCG level suggests the diagnosis and stage, confirms response to therapy, and predicts relapse. The three most widely used and intensely studied tumor markers are carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and HCG. CEA cannot be used in screening for cancer, but in carcinoma of the colon its elevation preoperatively increases the likelihood of advanced disease and postoperative recurrence. Postoperatively, elevated titers are often but not invariably associated with recurrent disease. AFP and HCG are useful in the management of nonseminomatous germ cell testicular tumors. Like CEA, they cannot be used for screening. They are more likely to be increased with advancing stage, and after therapy rising levels almost always mean recurrent disease. Some markers are valuable in specific circumstances, such as calcitonin in screening for familial medullary carcinoma of the thyroid. In multiple myeloma, immunoglobulins are useful in determining the tumor mass and response to therapy. In neuroblastoma, catecholamine metabolites are useful primarily in making the diagnosis. In some malignancies, the absence of effective therapy lowers the value of the marker, as for AFP in hepatoma. The remaining markers are too unreliable or too little studied to be useful in the management of an individual patient with cancer. The purpose of this paper is to provide the clinician with an understanding of the limitations of the present tumor markers that will lead to wiser use of the tests, and to provide standards to which future tumor markers should be measured.
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PMID:Tumor markers: value and limitations in the management of cancer patients. 241 41


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