Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human melanoma-associated antigen was solubilized from fresh surgical specimens by 3 M KC1 extraction. The antigenicity of this extract was demonstrated by delayed cutaneous hypersensitivity responses and inhibition of complement fixation. Twenty-one of 33 melanoma patients had delayed cutaneous hypersensitivity responses to melanoma antigen, while only four of 28 reacted to autologous muscle. Although KC1 extracts did not fix complement directly, they reacted with antibody, thus inhibiting complement fixation by the autologous melanoma antigen extracted from tissue culture supernatants. The soluble antigenic moiety was then purified by fractionation on a G-150 Sephedex column and polyacrylamide gels, and the antigenic activity was monitored by delayed cutaneous hypersensitivity responses in melanoma patients. A 20-fold purification was achieved. Solubilization of tumor antigens with 3 M KC1 provides tumor-associated antigen of high activity which is amenable to further biochemical purification.
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PMID:Isolation of a soluble tumor-associated antigen from human melanoma. 124 46

An analysis of cell cycle-dependent expression of tumor-associated antigen was performed on a human neurosarcoma cell line (T2 cells). The expression of sarcoma-associated tumor antigen on T2 cells was detected using test sera obtained from sarcoma patients; control sera were from patients with nonsarcoma neoplasias and from normal donors. Results indicate a progressive increase in the antigenic expression beginning in late mitosis and early G1 with maximum expression in mid-G1. Antigenic expression declines to minimum levels in S and G2-phase. Mechanisms responsible for this cycle-dependent fluctuation are presently unknown.
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PMID:Cell cycle dependency of human sarcoma-associated tumor antigen expression. 126 Jul 55

The positive effect of an immunotherapy using tumor-associated antigens or tumor cells of ovarian carcinomas has not yet been proven. Although many unique tumor-associated antigens have been described and a tumor rejection could be seen in occasional cases, the failure of the immune system to destroy tumor cells is not clearly understood. An alternative approach is to initiate the idiotypic network utilizing antibodies (Ab1 or 2) against a tumor-associated antigen, which induces the production of anti-idiotypic-antibodies (Ab2 beta), mimicking the "internal image" of the tumor-associated antigen. These antibodies are able to induce a specific antitumor immunity in two ways: (1) the Ab2 can present the critical epitope in a different way and so modulates the immune system, or (2) it can induce the production of an Ab3, which by itself binds to the tumor antigen. Our first results on 22 patients with advanced ovarian carcinomas show that the induction of an anti-idiotypic antibody (Ab2 beta) against OC 125 mimicking the TAA Class III CA 125 leads to a prolongation of the survival rate also for extended stages. We see a beneficial role of the induction of the idiotypic network against a tumor-associated antigen showing delayed clinical courses of the disease after vaccination of the patients with antibody fragments of the OC 125.
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PMID:Immunotherapy of advanced ovarian carcinomas by activation of the idiotypic network. 130 94

Tumor-associated antigens that are expressed in tumor cells of cattle with enzootic bovine leukosis (EBL) were analyzed previously by use of 13 monoclonal antibodies. We biochemically identified one of the tumor-associated antigens, which is recognized by the c143 monoclonal antibody, as two glycoproteins, each having an apparent molecular weight of 32,000 or 34,000. These glycoproteins were found in the plasma membrane of peripheral blood lymphocytes of both bovine leukemia virus (BLV)-free normal and BLV-infected cattle. With the progression of EBL, the proportion and the absolute number of cells positive for the tumor-associated antigen increased. Moreover, the level of the M(r) 34,000 component, which was susceptible to cell-surface labeling, increased over the level of the M(r) 32,000 component. Partial proteolytic peptide mapping with V8 protease and deglycosylation analysis revealed that the two glycoproteins most likely have an identical M(r) 30,000 polypeptide portion but have different N-linked oligosaccharide portions. Both glycoproteins were found to be phosphorylated at serine residue(s) in EBL-derived B-lymphoid cell lines and in tumor cells and peripheral blood lymphocytes from cattle with EBL, but not in peripheral blood lymphocytes from BLV-free normal cattle and BLV-infected cattle without any evidence of tumor, suggesting that the phosphorylation of these glycoproteins is related to the transformed state of the BLV-infected B-lymphoid cells.
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PMID:Tumor-associated M(r) 34,000 and M(r) 32,000 membrane glycoproteins that are serine phosphorylated specifically in bovine leukemia virus-induced lymphosarcoma cells. 133 Feb 94

The purpose of our study was to develop new biologic systems for the treatment or diagnosis of patients with ovarian carcinoma through expansion of T-cell lines from the tumor-infiltrating lymphocytes of patients with ovarian carcinoma in low-dose recombinant interleukin-2 in sufficient numbers for treatment and human monoclonal antibodies that recognize cell-surface tumor-associated antigen determinants on ovarian carcinoma cells. Technologic advances in tumor immunology and new data presented in relation to ovarian carcinoma were used to develop T-cell lines for the treatment of advanced ovarian carcinoma patients. Logarithmic expansion of T-cell lines was performed in a hollow-fiber bioreactor, and a pilot clinical trial was initiated to treat ovarian carcinoma patients with intraperitoneal tumor-infiltrating lymphocytes plus low-dose recombinant interleukin-2. Human hybridomas were produced by fusion of regional lymph node B cells with a heteromyeloma cell line SPATZ 4. Two ovarian carcinoma patients have been treated with tumor-infiltrating lymphocytes expanded to 1 x 10(10) to 1 x 10(11) with manageable side effects and evidence of biologic activity. Human monoclonal antibodies have been developed that recognize tumor-associated antigen determinants. Recombinant interleukin-2-expanded tumor-infiltrating lymphocytes and human monoclonal antibodies recognize different molecular entities on tumor cells and act by different mechanisms. These approaches may be complementary to one another in future treatment strategies for ovarian carcinoma.
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PMID:Novel immunologic strategies in ovarian carcinoma. 133 80

Because tumor size has been shown to influence the specific accumulation of radiolabeled anti-tumor-associated antigen monoclonal antibodies (mAb), the present study has investigated the effect of the tumor size on the enhancement by gamma interferon (IFN-gamma) of the accumulation of radiolabeled mAb in malignant lesions. Intercellular adhesion molecule-1 (ICAM-1) has been used as a marker because of its high susceptibility to modulation by IFN-gamma. F(ab')2 fragments of anti-ICAM-1 mAb CL207.14 have been selected to visualize malignant lesions, because they had been shown to be more sensitive probes for our experiments than whole IgG. Administration of IFN-gamma to human colon carcinoma-bearing nude mice increased the expression of ICAM-1 in the xenografts and the specific accumulation of 125I-F(ab')2 fragments of anti-ICAM-1 mAb CL207.14. The latter effect is influenced by the size of the lesions, because it was observed only in tumors with an approximate diameter of 8 mm and an approximate weight of 250 mg. If these results obtained in an animal model system are applicable to patients with malignant diseases, the present investigation suggests that administration of IFN-gamma enhances the sensitivity of immunoscintigraphy and the efficacy of immunotherapy with radiolabeled mAb which recognize tumor-associated antigens that are susceptible to modulation by IFN-gamma. However, the effect of IFN-gamma is not a general phenomenon but is influenced by the size of the malignant lesions.
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PMID:Effect of tumor size on the enhancement by gamma interferon of the localization of radiolabeled F(ab')2 fragments of anti-intercellular adhesion molecule-1 monoclonal antibodies in human colon carcinoma cells grafted in nude mice. 134 88

Using monoclonal antibodies (MoABs) against blood group determinants and related carbohydrate sequences, it is now possible to clarify their carcinoma-associated modulation at a molecular level. In the present study a panel of MoABs against different type 1 chain derived blood group antigens, comprising A, B, H type 1, Le(a), sialyl-Le(a) (CA 19-9), sialyl type 1 structure (CA 50), and Le(b) was used to investigate their immunoreactivity in 38 medullary carcinomas of the thyroid (MTC) and in normal thyroid tissue. The antigens were not expressed in normal follicular or C-cells but were expressed to a various extent in MTC. The studies revealed some characteristic anomalies in the frequency and patterns of tumor-associated antigen expression. The MoAB C 50 stained 32 of the 38 tumors, H type 1 (Le(d)) was demonstrated in 21 and the Le(b) antigen in 27. The Le(a)- and the A antigen were detected in 10 and 12 tumors and the B antigen in one. From the results some rules about the pathways for tumor-associated re-expression of these antigens can be deduced. Le(a) antigen expression was significantly correlated with the CA 50 and Le(b) antigens. The significant relation observed between A-, H1-, and Le(b) antigen formation in MTC suggests the existence of a carcinoma-associated fucosyltransferase committing the type 1 precursor chain along the H1-antigen pathway, and by further glycosylation to an A-, B-, or a Le(b) antigen. Comparative studies of tumor-associated H type 1 and H type 2 antigen expression revealed that H type 2 antigen synthesis was significantly related to a blood type 0 in the host. On the other hand, H1 antigen reactivity was independent of the AB0 blood type of the hosts and was also detected in H type 2 antigen-negative tumors. These findings support the proposal that even in tumor tissue, H antigen expression is still determined by the interaction of at least two different genes. Despite the occurrence of the precursor substance (CA 50) and the formation of the Le(a)- and Le(b) antigens, indicating the presence of a alpha 1,4-fucosyl-transferase (Lewis-enzyme), only two tumors showed the formation of CA 19-9. In conclusion, the investigations demonstrated the dominant re-expression of three type 1 chain-derived structures in MTC, namely H type 1, Le(b), and CA 50. These findings support the general concept demonstrated in other carcinomas, that fucosyl- and sialyltransferases are preferentially activated in MTC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Blood group antigen expression in medullary carcinoma of the thyroid. An immunohistochemical study on the occurrence of type 1 chain-derived antigens. 135 24

Two new human cholangiocarcinoma (CC) cell lines (CC-SW-I and CC-LP-I) were established and maintained in culture for 2 years. Histologically, both original liver tumors were adenocarcinomas, and the cell lines exhibited morphologic features of moderately differentiated adenocarcinoma. Immunohistochemistry showed that both cell lines were strongly positive for cytokeratin AEI but negative for carbohydrate tumor-associated antigen, CA19-9. Ultrastructural analysis of both cell lines showed the presence of tight junctional complexes and focally formed microvilli. Both CC cell lines were tumorigenic in nude mice. Cytogenetic analysis showed that both cell lines expressed highly aneuploid karyotypes with numerous structural and numerical deviations. CC-SW-I was hypodiploid with numerous chromosome losses and structural rearrangements, while CC-LP-I was hyperdiploid and displayed multiple additional chromosomes. Doubling times for the CC-SW-I and CC-LP-I cell lines in the presence of 15% fetal bovine serum were 72 hr and 180 hr, respectively. Growth of the CC-SW-I cell line was significantly stimulated in the presence of insulin, while that of the CC-LP-I cell line was significantly augmented by epidermal growth factor (EGF). In contrast, dexamethasone strongly inhibited proliferation of both cell lines in a dose-dependent manner. Among various recombinant cytokines examined for effects on growth or surface antigen expression on CC cell lines, only interleukin I-beta (ILI-beta) strongly inhibited growth of the CC-LP-I cell line, while interferons (IFNs) or tumor necrosis factor-alpha (TNF-alpha) were mildly inhibitory. Both tumor cell lines were resistant to natural killer (NK) cells but sensitive to lymphokine-activated killer (LAK) cells. Preincubation of tumor cells with IFN-gamma, IFN-alpha or TNF-alpha significantly decreased the susceptibility of each tumor cell line to lysis by LAK cells, and the change in sensitivity did not correlate with the expression of HLA antigens or intercellular adhesion molecule-I (ICAM-I) on the surface of tumor cells. These 2 CC cell lines are expected to provide valuable information about cell biology of human CC.
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PMID:Two new human cholangiocarcinoma cell lines and their cytogenetics and responses to growth factors, hormones, cytokines or immunologic effector cells. 135 57

In the present study we have analyzed the effect of a synthetic protein kinase C (PKC) activator 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol (ADMB) and the natural PKC-activating tumor-promoting agents 12-O-tetradecanoylphorbol 13-acetate (TPA) and mezerein on the antigenic phenotype of T47D human breast carcinoma cells. All three agents increased the surface expression of the tumor-associated antigen BCA 225 and various cellular antigens, including HLA class II antigens, intercellular adhesion molecule 1 (ICAM-1) and c-erbB-2. Expression of the same antigens was also upregulated to various extents in T47D cells by recombinant fibroblast (IFN beta) and immune (IFN gamma) interferon. Shedding of BCA 225 from T47D cells was induced by TPA, mezerein, IFN beta and IFN gamma, whereas ADMB did not display this activity. The ability of ADMB, TPA and mezerein to modulate the antigenic phenotype of T47D cells appears to involve a PKC-mediated pathway, since the PKC inhibitor, H-7, eliminates antigenic modulation. In contrast, the ability of IFN beta and IFN gamma to enhance the synthesis, expression and shedding of BCA 225, as well as to enhance HLA class II antigens, c-erbB-2 and ICAM-1 expression, was either unchanged or modestly reduced by simultaneous exposure to H-7. Analysis of steady-state mRNA levels for HLA class I antigens, HLA class II-DR beta antigen, ICAM-1 and c-erbB-2 indicated that the ability of H-7 to inhibit expression of these antigens in TPA-, mezerein- and ADMB-treated cells was not a consequence of a reduction in the steady-state levels of mRNAs for these antigens. The results of the present investigation indicate that the biochemical pathways mediating enhanced antigenic expression in T47D cells induced by TPA, mezerein and the synthetic PKC activator ADMB are different from those induced by recombinant interferons. Furthermore, up-regulation of antigenic expression in T47D cells can occur by a PKC-dependent or a PKC-independent pathway.
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PMID:Modulation of the antigenic phenotype of human breast carcinoma cells by modifiers of protein kinase C activity and recombinant human interferons. 135 26

A tumor-associated antigen detected by monoclonal antibody UM-A9 raised against a cultured cell line from a patient with an aggressive SCC of the oral cavity has been defined. The A9 antigen is abnormally expressed in squamous cancers, with loss of basal polarization and increased intensity of expression distinguishing malignant from normal cells. A minority of cultured SCC cell lines and about one third of fresh tumors exhibit polarized A9 expression. The increased intensity and loss of polarized expression of A9 antigen in recurrent and metastatic tumor cell lines when compared with primary or early tumor cell lines from the same patients indicated an association of altered expression with tumor progression. When A9 expression was evaluated in frozen tumor sections, three patterns of expression representing increasing intensity and loss of polarization were observed. Patients whose tumors exhibited the most intense A9 antigen expression had a higher rate of early relapse than patients whose tumors exhibited low intensity and polar expression. Loss of blood group antigen expression was also associated with poor prognosis, and together high A9 antigen expression and loss of blood group defined a group of patients at high risk of early relapse. The A9 antigen is immunologically and biochemically identical to the alpha 6 beta 4 integrin. The association of high expression of the A9/alpha 6 beta 4 integrin as a prognostic factor is supported by similar findings with a mouse model system. The mouse tumor-associated antigen, TSP-180, which is also an alpha 6 beta 4 integrin, distinguishes highly metastatic tumor cells from nonmetastatic variants of the same tumor line. In SCC, the alpha 6 beta 4 integrin contributes to attachment to laminin since anti-alpha 6 subunit specific antibody blocks cell attachment and only the beta 4 subunit is found in association with the alpha 6 subunit in these cells. Similar findings were obtained in colon carcinomas. Antibodies and peptides that block laminin attachment may lead to the development of antimetastatic agents for squamous carcinomas. The beta 4 subunit is unique from other integrins in that it has an unusually long cytoplasmic domain, the function of which is not known. The beta 4 subunit is heavily phosphorylated under conditions that favor anchoring and terminal differentiation in normal keratinocytes. Paradoxically the beta 4 subunit is also heavily phosphorylated in tumor cells, which are highly migratory and immortalized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Overexpression of the A9 antigen/alpha 6 beta 4 integrin in head and neck cancer. 138 8


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