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)

Since 1968 we have been treating a patient, who has had a combination of pyoderma gangraenosum (dermatitis ulcerosa) and signs that may indicate early multiple myeloma. She also had carcinoma of the colon, which was successfully operated. The pyoderma healed later after intensive and successful cytostatic treatment of the "myeloma". The ulcers remain practically healed and the protein pattern is normal in May 1977. Such cases are rare and a search in the literature has not been very rewarding. In our own series of more than 200 cases with myeloma this combination is unique. The lieterature is discussed in detail with data on the follow-up on some of the patients.
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PMID:Pyoderma gangraenosum (dermatitis ulcerosa) and monoclonal (IgA) globulin healed after melphalan treatment. Case report and review of the literature. 64 42

Over the past 40 years, the American Cancer Society has led in large-scale, prospective studies of behavioral and environmental risk factors in association with cancer development. Through results of its 1952 study, cigarette smokers were found to have a 10-fold higher risk of lung cancer than nonsmokers. Cancer Prevention Study I (1959-1972) extended these results and also showed the relationship between age smoking began, depth of inhalation, smoking cessation, air pollution, body weight, etc., on all causes of death as well as specific cancer sites. Cancer Prevention Study II began in 1982 and after six years of follow-up has confirmed many earlier findings, and additionally has found: aspirin may be protective against colon cancer; persons reporting themselves to be heavy exercisers had higher standardized mortality ratios (SMR) for lung, colorectal, and pancreas cancer than moderate exercisers; more women who were long-term users of artificial sweeteners reported gaining weight during the past year than nonusers; diesel fume exposure elevated the risk of lung cancer among men ages 40-79; pesticide exposure was associated with an increased risk of multiple myeloma; and based on CPS II mortality rates, an estimated 250 million of the 1.25 billion persons living in developed countries will die because they smoke.
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PMID:Cancer Prevention Study II. The American Cancer Society Prospective Study. 147 48

Described herein are structure-activity studies of new antitumor agents based on the pyrrolo[1,2-a]benzimidazole (PBI) ring system. These compounds were designed as new DNA cross-linkers mimicking the mitomycin antitumor agents. Actually, the PBI derivatives were found to have anthracycline-like features: (i) shared cross resistance with doxorubicin in a human myeloma line, (ii) cardiotoxicity, and (iii) excellent DNA strand cleaving capability. The DNA strand cleavage is thought to result from reductive alkylation of DNA followed by the generation of reactive oxygen radicals. The best antitumor agent studied is 6-N-aziridinyl-3-hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo- [1,2-a]benzimidazole-5,8-dione 3-acetate (PBI-A), which possesses nanomolar IC50 values against various human ovarian and colon cancer cell lines.
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PMID:Structure-activity studies of antitumor agents based on pyrrolo[1,2-a]benzimidazoles: new reductive alkylating DNA cleaving agents. 192 Mar 49

Spleen cells from inbred Biozzi mice, immunized against the human breast cancer cell line T47D, were fused with murine myeloma SP2O cells to generate monoclonal antibodies. One of these, 1BE12, of IgM isotype, reacted with five of six human breast tumor cell lines, while no binding was detectable with normal lymphocytes, RBC, or fibroblasts. The antigen recognized by monoclonal antibody 1BE12 was localized on the surface of T47D and MCF7 cells and was detected in cell-free supernatants of cultures. The antigen was found also on the surface of milk secretory cells. Immunohistochemical staining of frozen and paraffin-embedded sections of human tissues showed apical polarized reactivity in normal breast glands, while in all breast cancers staining was either cytoplasmic or membranous and heterogeneously distributed. Immunostaining was also observed in some other normal epithelia, including salivary gland, gastroduodenal mucosa, exocrine pancreas, and cervix. The antigen was not detectable in secretory endometrium, whereas proliferative endometrium was strongly stained. Colon carcinoma, and cancers of the bladder and endometrium were strongly reactive. No staining was detected in melanoma, lymphoma, mesothelioma, non-small cell lung carcinoma, and thyroid, renal, and ovarian carcinomas. Lectin absorption of MCF7 membrane extracts reduced 1BE12 binding. A large reduction in 1BE12 reactivity was observed after digestion of T47D and MCF7 membrane extracts with proteases. Treatment with sodium periodate resulted in complete loss of antigenicity, while neuraminidase treatment did not affect 1BE12 binding. These findings suggest that the 1BE12 epitope is expressed on the carbohydrate moiety of a glycoprotein and does not contain sialic acid. Immunoblotting of the perchloric acid-soluble fraction of MCF7 membrane extracts after electrophoresis in 1% agarose detected the antigen as a high molecular weight species (Mr greater than 900,000). The antigen was purified by perchloric acid extraction of MCF7 membrane preparations followed by affinity chromatography on 1BE12 antibody coupled to Sepharose-4B and gel exclusion fast protein liquid chromatography. No reactivity of the purified material was found with monoclonal antibodies directed against human milk fat globule membrane-associated mucins HMFG1 and DF3.
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PMID:Characterization and distribution in human tissues of a glycoproteic antigen defined by monoclonal antibody 1BE12 raised against the human breast cancer cell line T47D. 222 61

The causes of mortality of 3,649 white and 397 non-white male U.S. embalmers and funeral directors, who had died between 1975 and 1985, were examined in a proportional mortality study. Non-significant excesses were found for malignancies of the buccal cavity and pharynx (PMR = 120) and for nasopharyngeal cancer (PMR = 216). No sinonasal cancers were observed, while 1.7 were expected. A statistically significant excess of colon cancer (PMR = 127) was found and a non-significant excess of brain and other CNS cancer was noted among whites only (PMR = 123). Statistically significant excesses of malignancies of the lymphatic and hematopoietic systems were found in whites (PMR = 131) and non-whites (PMR = 241). Myeloid leukemia (PMR = 157) and leukemia of other and unspecified cell types (PMR = 228) were in excess, while no excess of lymphatic leukemia was noted. Elevations in risk were also found for non-Hodgkin's lymphoma, polycythemia vera, and myelofibrosis. Non-whites showed a marked excess of multiple myeloma (PMR = 369). Chronic nephritis was in excess among whites (PMR = 215) and non-whites (PMR = 257). No excess of cirrhosis of the liver was found. Excesses of malignancies of the lymphatic and hematopoietic systems could not be directly related to job held in the funeral industry. Further case-control studies are planned to rule out the possibility that the observed associations are artifactual, by assessing the association between specific work practices and disease risk.
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PMID:Mortality of U.S. embalmers and funeral directors. 178 18

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

Highly specific anti-human colorectal carcinoma monoclonal antibody(A7) was developed by fusion of mouse myeloma cells with mouse spleen cells immunized by colon cancer cells. Neocarzinostatin (NCS) was bound to A7 preserving both antibody and drug activities. This conjugate (A7-NCS) was applied for clinical trial. No serious side effects were reported, and half of the eight patients with metastatic liver tumor responded to A7-NCS well. To overcome the variety in the expression of tumor-specific antigen on tumor cells, new types of conjugates were developed. Mitomycin C(MMC) was bound to Dextran sulphate. And this conjugate (M MC-Dex) was bound to A7 with the expectation that MMC would release from Dextran that was delivered to the surface of the cancer cells. This type of conjugate would be effective not only against cancer cells that express antigens detected by A7 but also against any cells around cancer cells detected by A7. The possibility and problems in cancer therapy using immunotoxin are discussed.
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PMID:[Application of immunotoxin in cancer therapy; its usefulness and problems in the future]. 247 54

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.
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PMID:Cytostatic and cytotoxic activity of lymphokine-activated killer cell supernatants. 248 Aug 43

Two tumor-associated cellular proteins, 82k/6.3 (MW/pI) and 61k/7.5, which were detected by two-dimensional gel electrophoresis, were studied by biochemical and immunological methods. In two-dimensional gel electrophoresis, 82k/6.3 and 61k/7.5 were rich in colon cancer tissue compared with normal colon mucosa, and they were also detected in fetal intestines. This shows that both proteins might be involved in category of oncofetal proteins. The localization of 82k/6.3 and 61k/7.5 was investigated by subcellular fractionation. They were rich in microsomal fraction, but not found in both nuclear and mitochondrial fractions. In binding reaction with seven kinds of lectins, 82k/6.3 reacted with RCAI, DBA and WGA, where 61k/7.5 reacted with RCAI, DBA, WGA, UEAI and SBA. Transferrin reacted with only RCAI. Each hybrid producing monoclonal antibody against 82k/6.3 or 61k/7.5 was generated by fusing spleen cells of BALB/c mice immunized by the two proteins and mouse myeloma cells. Each monoclonal antibody was specified in enzyme-linked immunoassay. In indirect immuno-fluorescent studies, monoclonal antibodies against 82k/6.3 and 61k/7.5 reacted with cytoplasma and membrane of human cancer cells. This result strongly suggests the localization of the two proteins demonstrated by subcellular fractionation.
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PMID:[Biological and immunological studies on human tumor-associated cellular proteins detected by two-dimensional gel electrophoresis]. 268 83

The mouse monoclonal antibody 17-1A (gamma 2a, kappa) recognizes a tumor-associated antigen expressed on human gastrointestinal malignancies and has been used in Phase I and II clinical trials. Chimeric genetic constructs have been produced using 17-1A variable region genes (VL and VH) and the constant region genes for human kappa light chains and gamma 1 heavy chains (C kappa and gamma 1). The chimeric gene constructs were transfected into mouse myeloma cells for antibody production. The secreted mouse/human chimeric antibody contains the antigen-binding domain of 17-1A and the human (gamma 1, kappa) constant regions. Native mouse 17-1A and the chimeric antibody (chIgG1) were analyzed for binding to two human colon cancer cell lines and for the mediation of cancer cell line antibody-dependent cellular cytotoxicity by normal human peripheral blood lymphocytes and monocytes in 4 h 51Cr-release assays. The 17-1A and chIgG1 gave similar results in these in vitro biologic assays. This study demonstrates the feasibility of using mouse/human chimeric antibodies in human therapeutic applications.
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PMID:Human lymphocyte and monocyte lysis of tumor cells mediated by a mouse/human IgG1 chimeric monoclonal antibody. 336 51


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