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)

The mouse monoclonal antibody, m30.6 (IgG2b), detects an antigenic determinant expressed predominantly on the surface of colorectal adenocarcinoma cells and has been shown previously to be a potentially useful therapeutic and diagnostic reagent for human colon cancer. We report the production and characterization of a mouse/human chimeric antibody, c30.6, with potent in vitro and in vivo antitumor activity. The genes encoding the variable domains for heavy and light chains were amplified by thermal cycling using degenerate oligonucleotide primers complementary to conserved immunoglobulin framework sequences. The gene segments were sequenced, subcloned into eukaryotic expression vectors containing human constant region genes (IgG1 and kappa), and cotransfected into nonsecreting Sp2/0 mouse myeloma cells. There were significant differences in the biological activities of the murine and chimeric antibodies. The i.p. administration of c30.6 but not of m30.6 produced a marked growth inhibition of s.c. 30.6+ COLO 205 tumors in scid/scid mice (approximately 40% reduction in tumor size, measured 21 days after tumor inoculation). Reduced tumor growth was not due to altered binding characteristics of c30.6 because: (a) the chimeric antibody was shown by flow cytometry to bind exclusively to cell lines that expressed the 30.6 determinant; (b) c30.6 was able to completely inhibit the binding of m30.6 on 30.6+ cells; and (c) the affinity of binding of the two antibodies was the same (Ka, approximately 1.50 x 10(8)). Up to 15% of the total injected antibody dose/g tissue was localized in 30.6+ tumors at 24 h, approximately 13% was present in the tumors at 48 h, and approximately 10% was present at 72 h. Furthermore, c30.6 demonstrated a shorter circulating half-life (53 h; m30.6, 72 h) when given i.p. to C57BL6 x BALB/cF1 mice. Unlike m30.6, c30.6 was also strongly active in antibody-dependent cell-mediated cytotoxicity against a range of 30.6+ tumor target cells in vitro. Up to 80% specific 51Cr release was achieved using either freshly isolated human peripheral blood mononuclear cells or 2-day-old interleukin 2-stimulated human peripheral blood mononuclear cells as effectors. The enhanced antitumor activity of c30.6 suggests that it might be a useful immunotherapeutic reagent for colorectal carcinoma.
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PMID:Chimeric (mouse/human) anti-colon cancer antibody c30.6 inhibits the growth of human colorectal cancer xenografts in scid/scid mice. 795 62

Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 6 kinds of mucin core proteins, MUC1-6, have thus been performed. Among them, the entire structure was revealed on MUC1 and 2. MUC 1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. To date, some of the MoAbs to adenocarcinoma which were prepared for the last decade have been shown to react with the tandem repeat of MUC1(MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We could also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in a HLA-unrestricted manner, and may be of use as an adoptive immunotherapy. In addition, we have found antibody against MUC1 epitope in patients with ulcerative colitis or colon cancer. EB virus-transformed B-cell clone producing antibody against MUC1 epitope has been established from a cancer patient. Thus, MUC1 is now considered as a targeting molecule for immunotherapy. Indeed, Longenecker's group in Canada has recently tried the basic evaluation for immunotherapy using synthetic peptides of MUC1.
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PMID:[Molecular biological analyses of mucin core proteins and their clinical application]. 831 84

The poly(ADP-ribose) polymerase (PADPRP) gene (13q33-qter) depicts a two-allele (A/B) polymorphism. In the noncancer population, the frequency of the B allele is higher among blacks than among whites. Since the incidence of multiple myeloma and prostate and lung cancer is higher in the U.S. black population, we have analyzed the B-allele frequency in germ-line DNA to determine whether the PADPRP gene correlates with a polymorphic susceptibility to these diseases. For multiple myeloma and prostate cancer, an increased frequency of the B allele appeared to be striking only in black patients. In contrast, the distribution of the B allele in germ-line DNA did not differ among white patients with these diseases, when compared with the control group. An elevated B-allele frequency was also found in germ-line DNA in blacks with colon cancer. These observations suggest that the PADPRP polymorphism may provide a valid marker for a predisposition to these cancers in black individuals. To determine the genomic structure of the polymorphic PADPRP sequences, a 2.68-kb HindIII clone was isolated and sequenced from a chromosome 13-enriched library. Sequence analysis of this clone (A allele) revealed a close sequence similarity (91.8%) to PADPRP cDNA (1q42) and an absence of introns, suggesting that the gene on 13q exists as a processed pseudogene. A 193-bp conserved duplicated region within the A allele was identified as the source of the polymorphism. The nucleotide differences between the PADPRP gene on chromosome 13 and related PADPRP genes were exploited to develop oligonucleotides that can detect the difference between the A/B genotypes in a PCR. This PCR assay offers the opportunity for analyzing additional black cancer patients, to determine how the PADPRP processed pseudogene or an unidentified gene that cosegregates with the PADPRP gene might be involved with the development of malignancy.
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PMID:A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer. 843 80

We have established three kinds of monoclonal antibodies against gangliosides containing N-glycolylneuraminic acid (NeuGc) by immunization of BALB/c mice with the purified gangliosides inserted into liposomes comprising Salmonella minnesota R595 lipopolysaccharides, and fusion of spleen cells with a mouse myeloma cell line. One monoclonal antibody, SHS-1, which was generated by immunizing mice with purified i-active ganglioside(NeuGc), reacted specifically with the i-active ganglioside(NeuGc) used as an immunogen. Structurally related gangliosides, such as GM3(NeuGc), sialosylparagloboside (SPG) (NeuGc), or I-active ganglioside(NeuGc), corresponding gangliosides [GM3 containing N-acetylneuraminic acid (NeuAc), SPG(NeuAc), i-active ganglioside(NeuAc), and I-active ganglioside(NeuAc)], other gangliosides, or neutral glycosphingolipid (GSL) were not recognized by the monoclonal antibody. These findings indicate that the SHS-1 monoclonal antibody may be specific for NeuGc-containing i-active ganglioside. On the other hand, the other two monoclonal antibodies, MSG-1 and SPS-20, which were generated by immunizing mice with purified ganglioside GM3(NeuGc) and SPG(NeuGc), respectively, showed cross-reactivity to structurally related gangliosides. The MSG-1 monoclonal antibody exhibited reactivity to ganglioside GM3(NeuAc). The SPS-20 monoclonal antibody also cross-reacted with SPG(NeuAc), i-active ganglioside(NeuGc), and i-active ganglioside(NeuAc). Neither MSG-1 nor SPS-20 reacted with corresponding gangliosides, other gangliosides, or neutral GSLs tested. Using the SHS-1 antibody specific for i-active ganglioside(NeuGc), we studied the expression of NeuGc-containing antigen in human colon cancer tissue. An NeuGc-containing glycoconjugate was detected in the colon cancer tissue.
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PMID:Production of monoclonal antibodies directed to Hanganutziu-Deicher active gangliosides, N-glycolylneuraminic acid-containing gangliosides. 858 20

The occurrence of multiple malignancy was studied in 674 patients with hematologic malignancies who were admitted to this department during the past 10 years. Of the 674 patients, 205 were aged 65 years or older, and 56 (8.3%) had another cancer. The frequency of multiple malignancy was significantly higher in older patients than in younger patients: 44 (21.5%) vs. 12 (2.6%). The major hematologic conditions in patients with multiple malignancy were multiple myeloma, myelodysplastic syndromes, non-Hodgkin's lymphoma, and chronic myelogenous leukemia. The major sites of cancers other than hematological malignancies were the stomach, colon, breast, and esophagus. Many of the older patients had gastric cancer or colon cancer, and gastric cancer was common in the younger patients. The multiple malignant neoplasms were synchronous in as many as 20 of the 44 older patients. There was only one such case among the younger patients. Of the 56 patients, nine had received alkylating agents, and one has received etoposide. In brief, elderly patients with hematologic malignancies are likely to have multiple malignant neoplasms. If they are synchronous, the patient's prognosis may be adversely affected, because simultaneous management of multiple malignant neoplasms is not easy.
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PMID:[Double cancer in elderly patients with hematologic malignancies]. 875 14

Social class differences in cancer mortality among New Zealand men aged 15-64 years are examined for the period 1984-7. Age-standardised rates are presented for all cancer deaths, and for 23 specific cancer sites. The strongest social class mortality gradients were found for cancers of the larynx, liver, buccal cavity/pharynx, oesophagus, lung and for soft tissue sarcoma. On the other hand, rectal cancer, malignant melanoma, colon cancer, brain/nervous system cancers, and multiple myeloma showed higher death rates for the more advantaged socioeconomic groups. Lung cancer accounted for 54.1% of the overall social class gradient, and the major smoking related cancers (these include buccal/pharynx, oesophagus, larynx, lung and bladder, although it should be stressed that not all cases of these cancers are caused by smoking) accounted for 77.6% of the overall gradient.
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PMID:Social class and male cancer mortality in New Zealand, 1984-7. 921 1

We evaluated epidemiologic evidence pertaining to the human carcinogenic potential of triazine herbicides in general and of atrazine, the most common triazine. Cancers for which data are available included non-Hodgkin's lymphoma, Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer. The investigations had methodologic limitations, including lack of in-depth exposure measurements and small numbers of subjects with heavy exposure and/or with many years since starting exposure, possibly required for the induction of cancer. The relation between triazines and non-Hodgkin's lymphoma has been assessed in four independent population-based case-control studies, reporting odds ratios ranging from 1.2 to 2.5. However, chance and/or confounding by other agricultural exposures may have produced these weak statistical associations. Furthermore, a pooled analysis of three of the case-control studies and the combined analysis of two retrospective follow-up studies did not demonstrate the types of dose-response or induction time patterns that would be expected if triazines were causal factors. The epidemiologic data pertaining to Hodgkin's disease, leukemia, multiple myeloma, soft tissue sarcoma, colon cancer, and ovarian cancer were inadequate for determining whether associations with atrazine or triazines exist in humans. For each of these cancers, only one or two studies evaluating the relationship were available, and the results of the studies typically were imprecise.
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PMID:A review of epidemiologic studies of triazine herbicides and cancer. 940 33

The first tumor marker (TM) described in Oncology was the Bence-Jones protein in 1847 in patients with multiple myeloma. However, it was not until the early 60s that the first useful TM in gastrointestinal (GI) cancer was recognized, alpha fetoprotein. The development of TM has achieved enormous progress over the last years and its definition includes not only tumor products but elements inherent to the tumor such as oncogenes. A review is presented of the most important TM in GI tumors according to anatomic location. Emphasis is made in colon cancer and the clinical usefulness of carcinoembryonic antigen throughout the different stages in the management of such patients.
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PMID:[Tumor markers in cancer of the digestive system]. 948 May 20

A proportional cancer incidence analysis is reported, based on 6,563 cases of cancer diagnosed in Israel between 1972 and 1991 among migrants from the former Soviet Union who arrived in Israel between 1972 and 1986. For digestive system cancers, there is evidence of a marked reduction in the risk of stomach cancer among the migrants with time since migration, and an increase in the proportion of colon cancer, although little change in cancer of the rectum. For most of the smoking-related cancers, there is little evidence of any meaningful change in proportions with time since immigration. For multiple myeloma, proportions decreased substantially in both men and women over the 20-year period. Among women, there is a small, statistically significant increase in breast cancer, and a marked decrease in cancer of the cervix. Among younger immigrants, the proportion of malignant melanoma has increased substantially since migration. A number of the changes in cancer patterns are consistent with various etiologic hypotheses including those based on possible dietary and other lifestyle changes among the migrants.
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PMID:Cancer incidence patterns (1972-91) among migrants from the Soviet Union to Israel. 948 57

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.
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PMID:Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States). 948 66


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