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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a model system which can be utilized for characterizing both the molecular basis of natural killer (NK):tumor interactions and the consequences of these interactions on tumor growth in vivo. This model system consists of several tumor lines which were derived from the murine lymphoma ASL1w under conditions which permitted the isolation of clonal lines that differ in their susceptibility to NK-mediated lysis. The NK-resistant clones used in this study (AW5J and AW5E) were susceptible to cytotoxic T-lymphocyte-mediated lysis and thus appear to be resistant to lytic processes utilized uniquely by NK cells. In competitive (cold target) inhibition assays, the AW5J clone did not inhibit NK recognition as well as the NK-sensitive clones. Thus AW5J may not be efficiently recognized by NK cells. The AW5E clone, on the other hand, competitively inhibited NK recognition as efficiently as the NK-sensitive clones; therefore, AW5E appears to evade a post-recognition event which is required for NK-mediated lysis. The susceptibility of these clones to killing by NK cells directly correlated with their lethality, suggesting that NK cells regulated the growth of these tumors in vivo. The level of host NK activity was also an important determinant of the level and site of tumor localization. Two-step immunofluorescence assays and flow cytometric analysis were used to quantitate the number of tumor cells in the bone marrow, spleen, and lymph nodes of mice with augmented or depleted NK activity. Increasing host NK activity decreased the number of tumor cells in each organ which could support the growth of the particular tumor tested. Furthermore, the extent of NK regulation was dependent, in part, upon the susceptibility of the particular tumor to NK-mediated lysis and the site of tumor growth. Thus, the data presented here demonstrate the utility of the ASL1w-derived clones as a model system which can be used to delineate the requirements and consequences of NK:tumor interactions.
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PMID:Development of a murine lymphoma model system for the characterization of natural killer:tumor cell interactions. 163 30

Histopathology and scan findings of hot nodule on 99mTcO4- and/or 123I were correlated in 34 patients with thyroid nodules. In a series of 30 hot nodular lesions, 29 were either adenomas or benign nodules; however, one was proved follicular carcinomas histopathologically. And four patients were chronic thyroiditis without nodular lesions in the thyroid lobes, which were diagnosed pathologically and clinically. In 6 patients with palpable thyroid nodules, thyroid scans performed with both 99mTcO4- and 123I were compared. A discrepancy of the two types of scan existed in only one case. Subsequent surgery revealed no malignancy in this patient. From the results of 201T1 imaging of the thyroid gland in 30 patients with cold or hot nodules on either 99mTcO4- or 123I thyroid scanning, we found no distinct difference between the degrees of 201T1 malignant and nonmalignant tumors. It appears that 201T1 accumulation demonstrates only tumor volume and tumor cell viability in these subjects. From these results, it is confirmed that the functional heterogeneities exist in thyroid adenoma tissues as well as in thyroid cancerous tissues. Therefore, the development of the reliable techniques used to distinguish a benign from malignant lesion is indispensable.
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PMID:[Clinical evaluation of the hot nodule on 99mTcO4- and 123I thyroid scintigraphy: correlation of scan appearance and histopathology]. 164 1

Doxorubicin (Dox) was coupled by four published methods to a murine monoclonal antibody (MAb) developed against human pulmonary adenocarcinoma. Dox immunoconjugates made with this murine IgG1 MAb, 44-3A6, were evaluated for anti-tumor activity against the human lung cancer cell line, A549. Dox was attached to the MAb (1) by an oxidized dextran T40 intermediate, (2) using dilute glutaraldehyde cross-linking, (3) with an acid-sensitive linker using cis-aconitic anhydride and EDCI, a water-soluble carbodiimide, and (4) using EDCI alone. The biological activity of the different conjugates was compared in vitro by antigen binding (whole-cell RIA) versus serial dilutions of unconjugated MAb cytotoxicity (dye exclusion/viability) versus long dilutions of the various Dox conjugates, Dox and mixtures of Dox and MAb. Preincubation of antigen-expressing tumor cells (A549) for 2 h with excess (250 micrograms/ml) unconjugated MAb prior to conjugate exposure was attempted in order to block the cytotoxic effect. The number of Dox molecules conjugated to 44-3A6 (molar incorporation ratio or MIR) ranged from 3 to 10/1 for carbodiimide linkage and up to 63/1 using the dextran intermediate. Cis-aconityl-derivatized Dox conjugates contained an average of 22 mol Dox/mol immunoglobulin, but drug incorporation was quite variable from experiment to experiment. Dilute glutaraldehyde cross-linking produced an average MIR of 10/1. After repeated attempts to minimize drug and/or MAb precipitation, the percentage decrease (versus MAb) in immunoreactivity of the drug conjugates ranged from 2 to 42% and was dependent on the coupling method and extent of aggregate formation in the preparation. Loss of biological activity (antigen binding and cytotoxicity) was significant when aggregation and precipitation occurred. There were additional losses (17-25%) after sterile filtration through low protein-binding (0.22 microns) filters. Immunoconjugates produced by glutaraldehyde cross-linking were reproducibly 5-10 times more potent against antigen-bearing tumor cells than Dox, and showed selectivity for inhibiting the viability of antigen-positive A549 cell line. Noncovalent mixtures of 44-3A6 and Dox were slightly more potent than Dox. Immunoconjugates produced by the aconityl method and the dextran intermediates were less effective than Dox, the glutaraldehyde-mediated conjugates or Dox and 44-3A6 mixtures. The unconjugated MAb was not cytotoxic when tested at concentrations up to 500 micrograms/ml. Blocking studies using 'cold', unlabeled MAb were of limited success.(ABSTRACT TRUNCATED AT 400 WORDS)
Tumour Biol 1991
PMID:Monoclonal antibody 44-3A6 doxorubicin immunoconjugates: comparative in vitro anti-tumor efficacy of different conjugation methods. 165 54

Postoperative mortality and morbidity are determined by intraoperative stress calculated by changes in arterial ketone body ratio (AKBR) during hepatectomy. In this report, we introduced two types of operative procedure which aims not to decrease AKBR during operation. One is total vascular exclusion (HVE) for liver resection using venovenous bypass which improved the deleterious effects of portal pooling and decreased return of blood to heart. The other is the hepatic resection applying the technique used in the transplantation from the living related donor. In this procedure, the remnant liver works for decreasing the intraoperative stress. The tumor involving lobe is removed under cold perfusion and the tumor is removed on the back table. Then, the tumor free liver is transplanted to the same position.
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PMID:[Extensive liver resection according to redox theory]. 165 89

In March 1989, ultrasonography revealed a hepatic mass in a 40 year old nulliparous woman who was then referred to the University of Southern California--Los Angeles (UCLA) Liver Unit. She exhibited no symptoms of a liver condition. From 19-28 years old, she took the combined oral contraceptive (OC) Ovulen 21 for irregular menses. After a brief period of taking Ortho Novum 1/80, she took Demulen 1/35-24 between ages 28-34. Her physician diagnoses endometriosis at 34. He stopped OC therapy and prescribed the progestin Norlutate. She had no history of hepatitis, toxin exposure, and previous liver disease. Further no one in her family had had liver disease or neoplasms. Computer tomography identified a 6.5 cm x 3.5 cm mass in the right lobe of the liver which matched a cold defect on a liver scan using technetium Tc 99m sulfur colloid. The mass selectively took up gallium. Arteriography revealed the mass to be a vascular tumor, but it did not exhibit a typical vascular pattern of an adenoma or the neovascularity of hepatocellular carcinoma. Physicians at UCLA used peritoneoscopy to take percutaneous needle biopsies of the right lobe which confirmed a hepatic adenoma. they then removed the right lobe of the liver. The remaining part of the liver was normal. Histologic examinations of the removed section showed features of a well differentiated hepatocellular carcinoma. Further tumor cells had invaded normal hepatic parenchyma. The physicians believed that hepatic adenoma was in the process of transforming into hepatocellular carcinoma in this patient. They thought that long term OC use, and possibly long term progestin use, may have contributed to the formation of the liver neoplasms. They emphasized the need for a pilot study to develop guidelines on surveillance ultrasonography of women taking OCs over a long period.
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PMID:Hepatocellular carcinoma coexisting with hepatic adenoma. Incidental discovery after long-term oral contraceptive use. 166 98

The glomus tumor, characterized by the classic trio of tumefaction, acute pain on palpation, and sensitivity to cold, is localized most commonly in the hand and quite rarely in the knee. It occurs most frequently in subjects between the ages of 20 and 40, and its cause is unknown. Masson divided glomus tumors into 4 main types: angiomatous, stromal, nervous, and myxoid, according to the histo-pathological features present. The authors believe that the histological appearance may be affected by the functional phase of the tumor at the moment of surgery: with sphincters closed, meaning very little dilatation of the venous collection areas, or with sphincters open, meaning considerable dilatation of the venous collection areas due to increased hematic flow.
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PMID:[Rare localization of a glomus tumor in the knee]. 166 94

Autologous melanoma-specific CTL recognize a common tumor-associated Ag (TAA) in the context of HLA class I antigens. We have demonstrated that HLA-A2 can be a restricting Ag and, in T cell lines homozygous for HLA-A2, that CTL can be generated by stimulation with HLA-A2 allogeneic melanomas. In the current study, we have investigated T cell lines from patients who are heterozygous at HLA-A region locus, to determine the relative importance of each A-region allele in this MHC-restricted recognition of tumor. We have shown that HLA-A1 can be a restricting Ag, and that allogeneic melanomas expressing HLA-A1 can substitute for the autologous tumor in the generation of HLA-A1-restricted CTL. However, when T cell lines express both HLA-A1 and HLA-A2, the HLA-A2 allele governed restriction of the melanoma TAA. Three autologous-stimulated HLA-A1, A2 CTL lines all demonstrated restriction by the HLA-A2 allele, when examined in cytotoxicity assays, cold-competition assays, and proliferation assays. There was no evidence of restriction by the second HLA-allele, HLA-A1. Although the autologous-stimulated CTL use a single A-region allele for tumor recognition, the autologous HLA-A1, A2 tumors are lysed by both HLA-A1-restricted and HLA-A2-restricted CTL. The dominance of restricting alleles was further demonstrated when HLA-matched allogeneic melanomas were used as the stimulating tumor to generate tumor-specific CTL. Stimulation of the heterozygous (HLA-A1, A2) lymphocytes with HLA-A2-matched allogeneic melanomas resulted in CTL specific for the autologous tumor, and restricted by the HLA-A2 Ag. However, stimulation with an HLA-A1-matched allogeneic melanoma failed to induce tumor-specific CTL restricted by the HLA-A1 Ag. The data suggest there is a dominance of HLA-A region Ag at the level of the T cell, such that only one is restricting in the recognition of the autologous melanoma. At the level of the tumor, however, the TAA is expressed in the context of both HLA-A region alleles. We can generate specific CTL from lymph node cells or PBL and HLA-A region matched allogeneic melanomas; however, because most patients are heterozygous at the HLA-A region locus, an understanding of the dominant restricting alleles must be obtained so that an appropriately matched allogeneic melanoma can be selected.
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PMID:MHC-restricted recognition of autologous melanoma by tumor-specific cytotoxic T cells. Evidence for restriction by a dominant HLA-A allele. 167 80

We have previously shown that thrombospondin (TSP) is synthesized and secreted by human MG-63 osteosarcoma cells. In this study, the secretion and cell surface expression of TSP by two different human osteosarcoma cell lines (MG-63 and TE-85) as well as the involvement of TSP in the platelet-aggregating activity of these tumor cells were studied. Using a sandwich enzyme-linked immunosorbent assay, MG-63 cells secreted 3-fold as much TSP as TE-85 cells at 48 h (0.17 +/- 0.01 (SD) versus 0.06 +/- 0.006 micrograms/10(6) cells, P = 0.007). Binding of exogenous 125I-TSP to MG-63 and TE-85 cells in monolayer indicated that binding was time and concentration dependent, saturable, and inhibited by excess cold TSP. However, despite a similar affinity, MG-63 cells had 10-fold more TSP-binding sites than TE-85 cells (402,394 +/- 130,346 versus 36,748 +/- 7,708 TSP-binding sites/cell; P = 0.002). Similar binding differences of 125I-TSP were observed with both osteosarcoma cell lines in suspension. A fluorescence-activated cell-sorting analysis was used in conjunction with an anti-TSP polyclonal antibody, and binding of endogenous TSP to MG-63 and TE-85 cells in suspension was investigated. Addition of an anti-TSP antibody to MG-63 and TE-85 cells in suspension increased the mean fluorescence intensity 50-fold when compared to an irrelevant antibody. Moreover, the fluorescence intensity of MG-63 cells with an anti-TSP polyclonal antibody was increased by 40% when compared to TE-85 cells. Since TSP was expressed on the surface of osteosarcoma cells, the involvement of this glycoprotein in the platelet-aggregating activity of MG-63 and TE-85 cells was therefore investigated using an anti-TSP polyclonal antibody and two monoclonal antibodies (P10 and MA-II), the epitopes of which lie within the Mr 140,000 non-heparin-binding fragment and the Mr 25,000 heparin-binding fragment of TSP, respectively. Preincubation of MG-63 cells (1 x 10(6) cells/ml) with either an anti-TSP polyclonal antibody (100 micrograms/ml) or monoclonal antibody P10 (15 micrograms/ml) inhibited by 80% other platelet-aggregating activity of these tumor cells, while anti-TSP monoclonal antibody MA-II (15 micrograms/ml) had no effect. In sharp contrast, the anti-TSP polyclonal antibody (100 micrograms/ml) only exhibited a slight inhibitory effect on platelet aggregation induced by TE-85 cells when using a low concentration of tumor cells (0.6 x 10(6) cells/ml).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thrombospondin binds to the surface of human osteosarcoma cells and mediates platelet-osteosarcoma cell interaction. 170 97

A population of tumor-reactive cytotoxic T-cells can be propagated from tumor-draining lymph nodes of patients with breast adenocarcinoma. These T-cells specifically recognize breast and pancreatic tumor cells in a major histocompatibility complex (MHC)-unrestricted fashion but not other tumors of epithelial origin or the natural killer target K562. The tumor-specific but MHC-unrestricted lytic activity of these cytotoxic T-lymphocytes (CTLs) is mediated through the alpha/beta T-cell receptor. The molecule recognized by these CTLs is ductal epithelial mucin produced by breast and pancreatic adenocarcinomas. The protein core of the mucin consists of multiple tandem repeats of a 20-amino acid sequence. Antibody SM3, directed against a determinant on the mucin protein core preferentially expressed on malignant cells is able to significantly inhibit lysis of tumor cells by the CTL, while other antibodies binding to different core epitopes are not. Normal breast epithelial lines, which also express mucin but not the SM3 epitope, are not lysed by these tumor-reactive CTLs or act as cold target inhibitors of lysis of tumor lines. The data suggest that the highly repetitive nature of the mucin allows cross-linking of the T-cell receptor on mucin-specific T-cells and therefore accounts for the lack of MHC restriction seen in this system. They further suggest that the mucin core epitope recognized on tumor cells is not expressed on normal epithelial cells in a manner that can be recognized by tumor-reactive CTLs. These findings support the role of mucins as important tumor-associated antigens mediating the cellular response to certain human cancers and suggest that epithelial mucin core sequences might form the basis for an effective vaccine to augment the antitumor immune response.
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PMID:Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. 170 86

Cold agglutinins are human autoantibodies, usually of the IgM class, which agglutinate RBC at low temperature. The major subset recognizes the I/i carbohydrate Ag, and many of these antibodies bear cross-reacting idiotypic determinants. An anti-idiotypic mAb that is specific for one of the idiotopes largely confined to cold agglutinins has been used to identify and monitor tumor cells that secrete these molecules in two patients. The tumor cells were immortalized with EBV and the idiotope-positive lines used to investigate the utilization of the VH and VL genes by these antibodies. Nucleotide sequence analysis of the two cold agglutinins (FS-1 and FS-2) revealed the utilization of a single common gene segment, VH4-21. Serologic analysis documented that only human antibodies utilizing the VH4-21 gene segment were reactive in the idiotope assay, other VHIV antibodies as well as a panel of antibodies derived from other VH families being negative. The DH, JH, VK, and JK gene segments of FS-1 and FS-2 were structurally distinct. These data suggest that the structural basis for the cross-reactive idiotope as well as cold agglutinin activity is the VH4-21 gene segment. A nucleotide change in H chain CDR1 of both cold agglutinins results in the substitution of an aspartic acid residue for glycine at position 31, suggesting that this amino acid might be critical to recognition of the red cell Ag.
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PMID:Nucleotide sequence analysis of the V regions of two IgM cold agglutinins. Evidence that the VH4-21 gene segment is responsible for the major cross-reactive idiotype. 171 Feb 50


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