Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between January, 1990 and May, 1991, we administered LAK immunotherapy using the intralymphatic route to 25 patients with metastatic cancer resistant to conventional therapies. In the preparation of the immunotherapy, we followed the technique described by Pizza G. et al. The age of our patients ranged between 50 and 75 years and their Karnofsky's indexes were above 70%. The histological type of the metastasis were determined by Rx, ECO and/or CAT before and after the administration of the immunotherapy. In the intralymphatic administration, we followed the technique described by Pizza G. et al. The immunological therapy was administered on days 1, 21, 90 and 111 and the clinical response was assessed by RC, RP, EE and F. The immunological behaviour of the host was assessed through the determination of lymphoid populations (CD2, CD4, CD5 and CD8) and cytolytic cells were studied with monoclonal antibodies CD and CD16. Such immunological study was carried out before the administration of each immunotherapy series. In 7 out of 25 patients (28%), we were able to administer the four LAK series. Such patients were subsequently studied, observing that, although tumoral lesions did not increase in size, they did not disappear and, thus, they were classified as clinically stable. Clinical and analytical toxicity was null. The immunological study did not show any statistically significant changes and the activity of cytotoxic cells (NK) was not modified.
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PMID:[Intralymphatic administration of adoptive (LAK) immunotherapy in the treatment of patients with metastatic cancer resistant to conventional therapies]. 150 2

A variant cell line (EL-4ad) which adhered to a tissue culture dish was isolated from highly metastatic EL-4 murine T-lymphoma. The experimental and spontaneous metastatic ability of EL-4ad was lower than that of the EL-4 parent cell line. The cell surface phenotypes of both cell lines were CD2+3+4-8-45+TCR alpha beta+TCR gamma delta-, but the level of CD2 expression of EL-4ad was much lower than that of EL-4. Furthermore, EL-4ad had higher binding ability to fibronectin and expressed more PNA receptors on the cell surface than EL-4. These differences indicated that either the maturation stage of the less metastatic variant was lower than that of the parent cell line or the activation state of the two cell lines differed. EL-4ad showed higher in vitro invasiveness and adhesiveness to liver cells, and these characters were not consistent with the reduced metastatic ability of this variant. Neuraminidase-releasable cell surface sialic acid levels did not differ significantly between the cell lines. Neither cell line was adhesive to laminin, type IV collagen or reconstituted basement membrane. These metastasis-related properties could not explain the decreased metastatic ability of EL-4ad. On the other hand, EL-4ad was more sensitive to NK activity than EL-4 in vivo, and this was thought to be a major cause of its decreased metastatic ability. The molecules or mechanisms involved in the differentiation or activation of T-cells may be responsible for the sensitivity of tumor cells to NK activity.
Clin Exp Metastasis 1992 Sep
PMID:Isolation and characterization of a low metastatic variant from EL-4 mouse T-lymphoma. 150 20

Frozen tissue sections obtained from human glioblastomas, brain tumor metastases and normal brain were examined for the expression of molecules known to be involved in lymphocyte activation and/or adhesion and migration. The molecules studied included CD3, CD45R, UCHL-1 (CD45RO), lymphocyte function-associated antigen 1 (LFA-1) (CD11a, CD18), intercellular adhesion molecule 1 (ICAM-1) (CD54), 4B4 (CD29), CD44, CD2, and LFA-3 (CD58). CD3+ lymphocytes infiltrating human glioblastomas and brain tumor metastases expressed LFA-1 alpha and beta. Many cells were also UCHL-1+ whereas only a small percentage were CD45R+. CD2+ lymphocytes were also present. Tumor-infiltrating lymphocytes (TIL) were found to be negative for CD29, which was, however, expressed on intratumoral vessels in addition to vessels found in normal brain. Glioblastoma cells and intratumoral vessels expressed ICAM-1 whereas no ICAM-1 was found on TIL or on normal brain. Glioblastoma cells also expressed high levels of both CD44 and LFA-3 whereas TIL were negative for these antigens. CD44 was also expressed on certain regions of normal brain. Antibodies to LFA-1 alpha and -beta and ICAM-1 could significantly block the binding of lymphokine-activated killer (LAK) cells or TIL to human glioblastoma cells suggesting that these molecules play a role in the binding and subsequent migration of lymphocytes into brain tumor tissue.
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PMID:Activation and adhesion molecule expression on lymphoid infiltrates in human glioblastomas. 169 16

Between January 1990 to December 1993, we administered LAK immunotherapy using intralymphatic route to 50 patients with metastatic cancer resistant to conventional therapies. In the preparations of the immunotherapy, followed the technique described by Pizza G. et al. The age of our patients ranged between 50 to 75 years and their Karnosfsky's indexes were above 70%. The histological type of the metastasis was determined by cytology and the size by Rx, ECO and/or TAC before and after the administration of the immunotherapy. In the intralymphatic administration, we followed the technique described by Pizza G. et al. The immunological therapy was administrated on days 1, 21, 90 and 111 and the clinical responses were assessed by RC, RP, SD and F. The immunological behaviour of the host was assessed through the determination of lymphoid populations (CD2, CD3, CD4, CD5 and CD8) and natural killer cells were studied with monoclonal antibodies CD3 and CD16. Such immunological study was carried out before the administration of each immunotherapy series. In 12 out of 50 patients (24%), we were able to administer the four LAK series. Such patients were subsequently studied, observing that although tumoral lesions did not increase in size, they did not disappear and, thus, they were classified as clinical stables. Clinical and analytical toxicity were null. The immunological study showed changes in immunological parameters, however these changes were not statistically significant.
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PMID:[The intralymphatic administration of adoptive immunotherapy (LAK) in the treatment of patients with metastatic cancer and resistant to conventional therapies. Apropos 50 patients]. 762 60

CD59 (protectin) and CD46 (membrane cofactor protein, MCP) are membrane-bound complement regulator proteins which inhibit complement-mediated cytolysis of autologous cells. CD59, a phosphatidyl-inositol-anchored glycoprotein, inhibits the formation of the terminal membrane attack complex (MAC) of complement and was found to be a second ligand for CD2 contributing to T-cell activation. In 20 colorectal normal mucosa samples, in ten adenomas, 71 carcinomas and in ten liver metastases derived thereof, CD59 was inconsistently expressed in the epithelial compartment. In carcinomas CD59 expression in the whole neoplastic compartment was more often found in well- and moderately differentiated tumours. By contrast, focal expression or even complete lack of CD59 was more often found in poorly differentiated tumours (P = 0.021). In addition, carcinomas without metastases at the time of operation (Dukes A/B) more often expressed CD59 in the entire neoplastic population compared to those carcinomas which had already metastasised (P = 0.018). There was no correlation between the mode of CD59 expression in colorectal carcinomas and the tumour type or location. CD46 has C3b/C4b binding and factor-I dependent cofactor activity and is broadly expressed in various cells and tissues. In the epithelial compartment of normal colorectal mucosa, of all adenomas, carcinomas and their liver metastases, CD46 was expressed throughout the epithelial compartment. Since CD46 was consistently expressed in colorectal carcinomas the low expression or even lack of CD59 in a subset of tumours might not lead to critical complement-mediated attack of CD59-negative tumour cells. Regarding CD59 as a natural T-cell ligand involved in cognate T-cell-target-cell interaction, however, loss of CD59 might well be a selection advantage, provided that tumour antigen-mediated T-cell toxicity in colorectal carcinoma exists.
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PMID:Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium. 769 19

We evaluated the expression of the cell-adhesion molecules (CAM) that might be involved in liver-associated lymphocyte (LAL) contacts with other sinusoidal cells and/or be responsible for natural-killer(NK)- and lymphokine-activated killer(LAK) activity in patients with liver metastasis. The LAL population was isolated by sinusoidal high-pressure lavage from partial hepatectomies obtained from patients operated for metastases (n = 13) and benign liver tumors (n = 9). Surface expression of the beta-2-integrin chains (CD11a, CD11b, CD11c and CD18), and the beta-I-integrin chains (CD49b, CD49d, CD49f and CD29), as well as that of members of the immunoglobulin superfamily (CD2, CD54, CD56 and CD58), were analyzed by one- or two-color flow cytometry. Quantitative and qualitative differences were observed in both groups of patients in the expression of CAM between LAL and peripheral blood lymphocytes (PBL). LAL were characterized by an increase in the percentage of CD11b-, CD49b-, CD49d-, CD54-, CD56- and CD58-positive cells in comparison with PBL. Fluorescence values for CD2, CD11a, CD18 and CD56 were higher in LAL than in PBL. Moreover, the population expressing these antigens of differentiation presented a bimodal distribution (dim and bright): in LAL, as opposed to PBL, the percentage of cells with a bright phenotype was greater than of those with a dim one. The increase in CAM expression on LAL could be due to the influence of the liver sinusoidal micro-environment. Results were more unexpected for the comparison between benign and malignant tumors. No difference was found in CAM expression on LAL between these 2 categories. Consequently, it cannot be this factor that explains the decrease in LAK activity of LAL in patients with metastasis.
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PMID:Variations in the expression of cell-adhesion molecules on liver-associated lymphocytes and peripheral-blood lymphocytes in patients with and without liver metastasis. 775 52

T cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T-cell receptors (TCR). In the present study, further characterization of modulations in CD3- and CD16-associated zeta chain in peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA-DR was found. As previously reported, we found significantly reduced levels of the CD3- and CD16-associated zeta chain in TIL and, to a lesser extent, also in patients' PBL. Levels of zeta chain in T and NK cells from non-cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal-transducing molecule and the distance from the tumor. In addition, zeta levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph-node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 zeta than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell-surface and cytoplasmic CD3 epsilon. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti-CD3 epsilon-immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the zeta chain, either on TIL or on PBL or on lymphocytes from non-cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin-2 and phytohemagglutinin, anti-CD3 or anti-CD2 monoclonal antibodies (MAbs), levels of CD3 zeta chain as well as of cell surface CD3 epsilon were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal-transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas.
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PMID:Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. 779 Jan 9

Patients with malignant thymoma rarely may also have a peripheral T-cell lymphocytosis. "Lymphocyte spillover" from the thymus into the peripheral blood as well as a second, associated neoplasm (ie, T-cell chronic lymphocytic leukemia) are two hypotheses that have been proposed to explain this clinical phenomenon. We describe another patient with a lymphocyte-rich malignant thymoma associated with peripheral T-cell lymphocytosis. At the time of initial diagnosis, the patient's complete blood cell count was unremarkable. However, subsequent to the development of pulmonary metastases, the patient developed persistent lymphocytosis. The total leukocyte count ranged from 20 to 30 x 10(9)/L, 80% of these cells being lymphocytes. Immunophenotypic analysis of peripheral blood specimens from this patient proved that the circulating cells were mature, polyclonal T cells. The cells expressed the alpha/beta T-cell receptor and the pan-T-cell antigens CD2, CD3, CD5, and CD7, and were negative for both terminal deoxynucleotidyl transferase (TdT) and the CD1 antigen. A mixture of T-helper (CD4+) and T-suppressor (CD8+) cells were present in a ratio of 1:1.6. Gene rearrangement studies revealed that the T-cell receptor beta chain and the immunoglobulin heavy-chain genes were in the germline configuration. Serum samples from this patient were also analyzed for thymic hormones; the level of thymosin alpha 1 was markedly elevated, while that of thymosin beta 4 was decreased. These results effectively exclude the hypothesis that the lymphocytosis represents a second, associated neoplasm. The lymphocyte spillover hypothesis also seems unlikely (although not excluded), since the lymphocytes in lymphocyte-rich thymomas usually have an immature thymic cortical immunophenotype. Furthermore, one might expect nonspecific elevation of all thymic hormone levels with lymphocyte spillover. Thus, we suggest that the lymphocytosis results from a poorly defined immunoregulatory disorder, related to the presence of thymoma, and perhaps secondary thymic hormone imbalance.
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PMID:Malignant thymoma associated with T-cell lymphocytosis. A case report with immunophenotypic and gene rearrangement analysis. 797 8

Targeting of spontaneous liver metastases of the ESb.MP murine lymphoma was achieved with anti-CD2 monoclonal antibody (MAb) 12-15A, which does not react with normal liver tissue. Using quantitative autoradiography on whole body sections of animals that had received a standard dose of 1.1 MBq of 125I-labelled monoclonal antibody, metastases accumulated up to > 90% of the injected dose per gram (id/g). The average uptake of primary tumour lesions was at a low level of 24 Bq/mg (corresponding to 2.2% id/g) because of highly non-uniform accumulation, while metastatic lesions were all above 50 Bq/mg. Uptake was particularly pronounced in animals tested after resection of the primary tumour: 85% of metastases showed levels above 300 Bq/mg, which was the upper limit of uptake in metastases of non-resected animals. These findings demonstrate the potential of the antibody approach with regard to attacking residual metastatic lesions after debulking.
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PMID:Preferential antibody targeting to small lymphoma metastases in the absence of the primary tumour. 842 86

A DNA vaccine encoding human carcinoembryonic antigen (CEA) broke peripheral T-cell tolerance toward this tumor self-antigen expressed by Lewis lung carcinoma stably transduced with CEA in C57BL/6J mice transgenic for CEA. This vaccine, delivered by oral gavage with an attenuated strain of Salmonella typhimurium (SL7207), and boosted with an antibody-IL2 fusion protein, induced tumor-protective immunity mediated by MHC class I antigen-restricted CD8(+) T cells, resulting in eradication of subcutaneous tumors in 100% of mice and prevention of experimental pulmonary metastases in 75% of experimental animals. Both CTL and antigen-presenting dendritic cells were activated as indicated by a decisive increase in their respective activation markers CD2, CD25, CD28 as well as CD48 and CD80. The antitumor effects of this CEA-based DNA vaccine obtained in prophylactic settings, suggest that this approach could lead to the rational design of effective treatment modalities for human lung cancer.
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PMID:An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth and dissemination of Lewis lung carcinoma in CEA transgenic mice. 1167 5


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