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)

An investigation was made of 17 patients with multiple myeloma using the method of alkaline filter elution for the detection of DNA damage and the determination of sister chromatid exchange (SCE) frequency in peripheral lymphocytes during a course of chemotherapy with melphalan and prednisone. We were able to detect elevated SCE frequencies in pretreated patients that approximately doubled during the therapeutic cycle. An appreciable level of DNA cross-linking was detected by alkaline filter elution; DNA cross-linking scarcely increased during a course of chemotherapy. The increase in the SCE frequency during the first therapy cycle was even greater in the case of patients with newly diagnosed multiple myelomas. The results obtained by alkaline filter elution and measuring SCE frequencies suggest that these techniques are suitable as methods in molecular epidemiology, especially if applied to persons who are chronically exposed to cytostatic drugs. Whether or not the methods could be valuable in evaluating therapy response needs further investigation.
Carcinogenesis 1992 Nov
PMID:Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of patients with multiple myeloma undergoing cytostatic therapy with melphalan and prednisone. 142 93

Flow cytometry (FCM) is a useful method for clinical research of oncogene products since it can analyze proteins quantitatively which are located at cell surfaces or inside of cells. Oncogene products are now under study by FCM not only as tumor markers but also as functioning proteins in carcinogenesis. The examples of oncogene products analyzed by FCM are ras, myc, p53, myb and fos; those of cell-proliferation-related proteins are Ki-67, PCNA and DNA polymerase alpha. In some diseases the relationship between these proteins and disease classification, stage, pathophysiology, or prognosis have been clarified. Using dual color FCM of H-ras p21 and DNA, we analyzed the expression of H-ras p21 in human multiple myeloma and leukemias and found that H-ras p21 levels in multiple myeloma strongly correlated to the prognosis of patients (p = 0.03). When AML cells were stimulated by adding G-CSF, it was found that many cells proliferated but some were dying. The percentage of dying cells was small in one AML case whose myeloblasts showed increased expression of H-ras p21 by G-CSF stimulation. Together with other papers reviewed, it is conceivable that H-ras p21 expression is related to cell proliferation and inhibition of cell autolysis. Thus FCM is useful in the classification of the role of oncogene products in carcinogenesis in clinical cases.
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PMID:[Application of flow cytometry to the study of hematologic disorders: analysis of oncogene products]. 214 49

7-(2-Hydroxyethyl)guanine (7HEG) is of biological interest because it is formed in vivo by reaction of DNA with ethylene oxide (EO). Furthermore, the major DNA adduct of vinyl chloride, 7-(2-oxyethyl)guanine, can be converted to this adduct by reduction. Two monoclonal antibodies (9E2, 4A5) recognizing 7HEG have been developed from BALB/c mice immunized with the adduct coupled to keyhole limpet hemocyanin. In addition, another antibody (8E10) was developed against the imidazole ring-opened form of the adduct (ro-7HEG). ELISAs were used to determine the sensitivity and specificity of these antibodies. With antibody 9E2, 50% inhibition of antibody binding in the competitive ELISA was at 54 pmol of the modified base 7HEG/well and 67 pmol 7HEGR/well, while with antibody 4A5, the values were 3.6 pmol 7HEG/well and 6.7 pmol 7HEGR/well. Antibody 8E10 gave 50% inhibition at 48 pmol ro-7HEGR/well. Neither antibody 9E2 nor 8E10 cross-reacted with unmodified DNA or with the normal nucleosides at the highest concentration tested. However, antibody 4A5 had a low affinity for deoxyguanosine (50% inhibition at 31,000 pmol). Sensitivity of adduct measurement can be increased 3- to 10-fold using an ELISA with fluorescence endpoint detection. These antibodies have been used to determine the level of adducts in DNA modified in vitro with [3H]- or [14C]EO. Because of the cross-reactivity of the most sensitive antibody, 4A5, with deoxyguanosine, a combined HPLC/immunoassay method was developed to quantitate 7HEG in DNA. The limit of sensitivity of this method is dependent upon the amount of DNA available for analysis. Using 30 fmol as the lowest detectable amount (20% inhibition) in the fluorescent ELISA with antibody 4A5 and 100 micrograms of DNA assayed per well, adduct levels of 1/10(7) nucleotide can be determined. This method was applied to DNA adduct detection in EO-treated myeloma cells and whole blood. Antibody 8E10 was also used in immunohistochemical studies to visualize ring-opened adducts in cells treated with EO followed by high pH. These antibodies will be used for the detection and quantitation of adducts in human samples.
Carcinogenesis 1990 Oct
PMID:Development of monoclonal antibodies recognizing 7-(2-hydroxyethyl)guanine and imidazole ring-opened 7-(2-hydroxyethyl)guanine. 220 83

A 60-year-old female, who was exposed to the Nagasaki atomic bomb at 18 years old, had renal cancer and subsequently was found to have multiple myeloma (IgG kappa). She underwent the left mastectomy for breast cancer at 43 years old but was not given chemotherapy and radiotherapy. The karyotype of bone marrow cells was 46, XX. The estimated radiation dose was under 10 rads. While the effect of such a low-dose of radiation is considered to be almost negligible, there would be a possibility that in this case the risk of carcinogenesis was enhanced as her age advanced.
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PMID:[Occurrence of breast cancer, renal cancer and multiple myeloma in a Nagasaki atomic bomb survivor]. 221 84

A rapid and simple scheme has been developed for the isolation and purification of two of the major mutagenic heterocyclic amines formed in heated beef products by affinity chromatography using monoclonal antibodies which recognize 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Two cell lines producing IgG antibodies were established following fusion of Sp2 or P3x.63 myeloma cells with spleen cells of immunized BALB/cby mice. The antigen was bovine gamma globulin haptenized with 2-(3-carboxypropylthio)-3-methylimidazo-[4,5-f]quinoline. The antibodies were immobilized on CNBr-activated Sepharose 4B. IQ and MeIQx formed in heated beef products were partially purified by XAD-2 chromatography and then applied to the affinity columns. Purification by affinity chromatography was adequate for subsequent quantitative analysis by HPLC with UV detection. With this purification scheme as little as 1 g of beef extract or 15 g of fried beef could be assayed for IQ and MeIQx at the part per billion level. Both antibodies had similar affinity constants for IQ (9.3 X 10(6) and 6.7 X 10(6) M-1) and for MeIQx (7.1 X 10(5) and 2.7 X 10(5) M-1) and both were suitable for immunoaffinity purification of IQ from complex mixtures. MAb2 could be used as well to selectively remove MeIQx from meat products after partial purification by XAD-2. MAb1, despite having a 3-fold higher affinity than MAb2 for MeIQx, could not be used for affinity chromatography for this mutagen.
Carcinogenesis 1989 Jan
PMID:Purification of the food-borne carcinogens 2-amino-3-methylimidazo [4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in heated meat products by immunoaffinity chromatography. 264 49

Over the past two decades, marked shifts have occurred in cancer mortality in the United States, the United Kingdom, and the Federal Republic of Germany. Stomach cancer mortality has declined sharply, while brain cancer and multiple myeloma increased nearly twofold for persons ages 75 to 84. Total cancer incidence in the United States, excluding lung cancer, has risen 27% since 1950, adjusted to the aging of the population. The origins of these trends are not known. The diet in the developed countries includes a number of naturally occurring, powerful anticarcinogens and carcinogens. To evaluate the role of these substances in the prevention and causation of human cancer, this paper reviews existing toxicologic and epidemiologic data. These data indicate that naturally occurring substances in food influence cancer initiation, promotion, progression, and demotion by a number of mechanisms, including (1) covalent binding to DNA of naturally occurring anticarcinogenic compounds to block the initiation of carcinogenesis; (2) induction of biotransforming enzymes such as cytochrome P450 and mixed-function oxidase (MFO) which can reduce carcinogenicity; (3) inhibition of tumor promotion by compounds such as retinol, tocopherol, and organosulfates found in garlic, onions, fruits, and vegetables; and (4) physical alteration of carcinogens by food constituents or by food preparation and handling so as to alter carcinogenicity. Systems have been proposed for estimating the relative ranking for humans of individually tested, experimental carcinogens, including some constituents of food. While qualitatively useful, such systems as the HERP Index do not take into account important interactions among naturally occurring and synthetic constituents in foods, nor do they permit examination of the possible role of evolved resistance. Common mixtures in food must be tested for carcinogenicity in human tissue cultures and in long-term rodent bioassays. Such studies need to examine whether the action of synthetic organic carcinogens may be inhibited by potent naturally occurring anticarcinogens.
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PMID:Natural anticarcinogens, carcinogens, and changing patterns in cancer: some speculation. 268 27

A number of polyclonal antibodies specific for DNA modified with (+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyre ne (BPDE) were obtained from the sera of New Zealand white rabbits immunized with BPDE-DNA, complexed with methylated bovine serum albumin (mBSA). Monoclonal antibodies were developed by fusion of mouse myeloma cells with spleen cells isolated from BALB/c mice immunized with the same complex of BPDE-DNA and mBSA. These antibodies have been characterized for specificity in a highly sensitive, enzyme-linked immunosorbent assay (ELISA). All antibodies showed a very high affinity for single-stranded BPDE-DNA, but had lower affinity towards native BPDE-DNA. The affinity for the free mononucleoside BPDE-dG was at least 100-fold lower than that for BPDE-DNA, and no affinity was detected for BP tetrols or DNA modified with N-acetoxy-N-acetyl-2-aminofluorene. A high cross reactivity was observed with DNA modified with (+/-)-trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydrochrysene++ +. Using five different antibodies, monoclonal or polyclonal, we observed that the antibody affinity for BPDE-DNA was dependent on the level of modification; in the competitive ELISA as little as 4 fmol BPDE-DNA (50 pmol/micrograms) was sufficient for 50% inhibition with our best antisera, but 17 fmol of the adduct was required when [3H]BPDE-DNA of low modification (1-10 fmol/micrograms) was used as inhibitor. When samples of [3H]BP-DNA isolated from the livers of mice, treated i.p. with different doses of [3H]BP were examined by competitive ELISA and calibrated with [3H]BPDE-DNA of low modification (1-10 fmol/micrograms), binding values calculated from the immunoassay were in good agreement with those obtained from radioactivity measurements. In contrast, when this DNA was quantitated in competitive ELISA using highly modified BPDE-DNA as standards, values by ELISA were 20-40% of those obtained by radioactivity. These results indicate that the use of serially diluted BPDE-DNA of high modification as standard competitor in the ELISA will lead to erroneous results in the measurement of adducts in DNAs modified to a low extent (biological samples). The property of antisera specific for BP-DNA, recognizing highly modified DNA more efficiently than DNA modified to a low extent, may be common to all antisera elicited against highly modified DNA immunogens. Therefore we conclude that antibody affinity must be tested also with DNA samples of low modification, obtained either in vitro or in vivo.
Carcinogenesis 1987 Sep
PMID:The binding efficiency of polyclonal and monoclonal antibodies to DNA modified with benzo[a]pyrene diol epoxide is dependent on the level of modification. Implications for quantitation of benzo[a]pyrene-DNA adducts in vivo. 311 53

Previous results obtained in our laboratory suggested that natural antibodies reactive with L5178Y lymphoma cells play a role in the induction of lung tumors by the chemical carcinogen urethane. In order to characterize some of the naturally-occurring L5178Y reactive antibodies we prepared hybridomas that secreted natural monoclonal IgM antibodies reactive with L5178Y lymphoma cells. In the present study we characterized some of these antibodies and provided further proof as to their role in urethane carcinogenesis. One hybridoma secreted a cytotoxic antibody that reacted only with mouse lymphoma cell lines. Other non-cytotoxic monoclonal L5178Y-reactive antibodies showed various degrees of cross-reactivity with syngeneic, allogeneic and xenogeneic cells of normal or malignant origin. One of these antibodies reacted much better with activated T cells than with resting ones. Four groups of mice were treated with urethane. Three groups were injected twice a week during 5 months with different IgM preparations of natural monoclonal antibodies. The mice in the fourth group were not treated with IgM and served as controls. Five months after the urethane treatment the mice were sacrificed and the number of tumor foci in the lungs of each mouse was determined. The results show that the group treated with the cytotoxic monoclonal antibody 1.80 had a significant decrease, while the group treated with the IgM myeloma protein 104E had a significant increase in the number of tumor foci compared to urethane-treated mice that did not receive any IgM treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The immune system during the precancer period: naturally-occurring tumor reactive monoclonal antibodies and urethane carcinogenesis. 316 48

Using the human liver cancer DNA transfected NIH/3T3 cell line, the human N-ras oncogene and the over expression of the oncoprotein P21ras was demonstrated, BALB/C mice were immunized. The spleen cells from the immunized mice were fused with SP2/0 myeloma cells. After the HAT medium selection and screening, two hybridoma cell lines, SCI-Oncogema 1 and 2, were established. In the immunoprecipitation test, the molecular weight of the protein reacting to Oncogema 1 was 21,000. This M.W 21,000 protein possessed the capability to bind with GTP, i.e. the character of P21ras. These data indicate that the Oncogema 1 is the monoclonal antibody against P21ras. Using Oncogema 1, specimens from 6 liver cancer patients were studied by immunopathology. With ABC stain, it was observed that the malignant cells in all the samples showed dark staining; the P21ras revealed over expression. Although the staining was heterogeneous, it implied that the ras oncogene was involved in the carcinogenesis of these six samples. No over expression was seen in the normal liver cells even in those around the cancerous lesion. However, dysplastic cells were moderately stained which means that the ras oncogene was activated and P21ras over expressed in these cells. The results suggest that the ras oncogene and P21ras play an important role in the early stage of liver cancer carcinogenesis.
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PMID:[Localization of oncoprotein P21ras in the human liver cancer]. 330 83

Human CCRF-CEM ('T' cell), EB3p ('B' cell) and RPMI-8226 (myeloma cell) lymphocytic cell lines were an order of magnitude more sensitive to melphalan (MEL) than Chinese hamster, V-79-753B, cells even though the amount of [14C]MEL they incorporated was less than 50% of that incorporated into the rodent cells: the D0 values were 0.16, 0.20 and 0.30 microgram/ml respectively compared with 1.6 micrograms/ml. Furthermore, MEL sensitivity was not related to the total thiol content of the cells. DNA-DNA cross-linking was not detectable in lymphocytic cells using the alkaline elution technique at doses of MEL used for clonogenic survival, whereas in Chinese hamster cells both parameters were assessable within the same dose range. At high concentrations of MEL there was a direct relationship between DNA-DNA cross-linking and drug dose in each lymphocytic cell line. Changes in the amounts of DNA-DNA cross-linking, at different MEL concentrations, increased directly with the sensitivity of the cells, viz. CCRF-CEM greater than EB3p greater than RPMI-8226. Calculated survival values for doses of MEL which produced measurable DNA-DNA cross-linking showed that there was a similar relationship between these parameters for the three lymphocytic cell lines which was different from that for Chinese hamster cells. It is concluded that the contribution of DNA-DNA cross-links in determining cell survival after MEL treatment is both quantitatively and possibly qualitatively different in human and rodent cells and that DNA-DNA cross-linking cannot be used as an indicator of MEL sensitivity in human lymphocytic cells unless parallel clonogenic survival studies are also undertaken.
Carcinogenesis 1987 Sep
PMID:Comparison of melphalan toxicity in human lymphocytic cells and Chinese hamster cells in vitro: the relationship between DNA-DNA cross-link formation and clonogenic survival. 362 62


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