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

Tumor infiltrating lymphocytes (TIL) play an important role in the host immune response to cancer. When these cells are reinfused into cancer patients after in vitro expansion with lymphokines such as interleukin 2 (rIL-2), they often induce regression of tumor metastases. We obtained TIL of enzymatic digestion of 7 human solid tumors and then cultured them with rIL-2 and interleukin 4 (IL-4) at different concentrations for about 36 days. Immunophenotypic analysis was performed at the end of the second and fourth week; cytotoxic activity against autologous and heterologous targets was assessed on the 30th day of culture. The best lymphocytic growth was observed when we used rIL-2 and IL-4 for the first two weeks of culturing and then continued with rIL-2 alone. CD3 and CD56 cells formed the majority of TIL in all cultures. In 4 cases CD4 cells predominated at the initial stage of culturing, with CD8 cells gradually increasing and finally inverting the CD4/CD8 ratio. Autologous cytotoxicity (3/4 cases) appeared to be better in those patients in whom the CD4/CD8 ratio was inverted. These data enable identification of the combination of lymphokines that will will best provide expansion of live TIL active against tumoral cells. This procedure must be followed before in vivo reinfusion of expanded lymphocytes is carried out.
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PMID:[Analysis of growth, phenotype and cytotoxic activity of tumor infiltrating lymphocytes expanded in vitro with interleukin-2 and interleukin-4: preliminary results]. 138 39

Cell adhesion molecules (CAMs) of the immunoglobulin supergene family may play important roles in tumorigenesis and the development of metastatic disease. In a variety of human malignancies, tumor progression has been observed to be associated with changes in CAM expression. An early event in colorectal tumorigenesis appears to be the down regulation of a normally expressed CAM, DCC. Over-expression of a second CAM, carcinoembryonic antigen, is associated with colorectal tumors which have a high risk for metastasis development. Several tumors, including Wilms tumors and neuroblastoma, have been found to express a developmentally regulated form of NCAM which inhibits a variety of cell-cell interactions. Malignant cells not only show aberrations in the expression of their CAMS and thus their normal cell-cell interactions, but establish new adhesive interactions. The development of metastatic potential in cutaneous melanoma is associated with the de novo expression of two CAMs, one of which is ICAM-1, a molecule mediating adhesion between the tumor cells and leukocytes.
Cancer Metastasis Rev 1991 May
PMID:Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. 168 May 75

The neural cell adhesion molecule, NCAM, plays an important role in cell-cell adhesion. Therefore, we have studied NCAM expression in the glioma cell lines BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic ability; while BT4C cells have a very low capacity for producing experimental metastases, that of BT4Cn cells is high. In BT4C cells NCAM is synthesized as 4 polypeptides with Mr's of 190,000, 140,000, 115,000 and 97,000. The 140,000, 115,000 and 97,000 polypeptides are glycosylated and for the 140,000 and 115,000 polypeptides sulfatation is observed. Conversely, no NCAM protein synthesis is observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of an increased metastatic capacity is accompanied by the disappearance of NCAM protein expression in this model system. The functional importance of NCAM expression was studied by a cell-substratum binding assay in which the binding of BT4C and BT4Cn cells to NCAM immobilized to glass was assessed. We found that BT4C cells adhere specifically to NCAM, and that adhesion is inhibited by anti-NCAM Fab'-fragments, while no specific binding of BT4Cn cells to NCAM was observed. The BT4C and BT4Cn cell lines thus constitute an important new model system for the study of tumor invasion and metastasis and of the role of cell adhesion molecules in these processes.
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PMID:Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells. 198 68

To identify molecules which may be functionally associated with the development of metastasis in human melanoma, monoclonal antibodies which discriminate between benign and malignant melanocytic lesions in situ were selected. Biochemical studies and cDNA cloning identified the antigens HLA-DR, ICAM-1 and MUC18 which showed an expression pattern on primary tumors correlating with vertical tumor thickness, the most predictive parameter for the development of metastasis in melanoma. ICAM-1 and MUC18 show sequence similarity to a family of cell adhesion molecules which include the neural cell adhesion molecule NCAM. Both HLA-DR and ICAM-1 can be induced on melanoma cells by lymphokines, suggesting a role of the mononuclear cell infiltrate in the control of tumor cell phenotype. Knowledge of the normal function of these molecules allows one to hypothesize how they may contribute to the successful development of metastases.
Invasion Metastasis 1989
PMID:Functional aspects of three molecules associated with metastasis development in human malignant melanoma. 257 17

Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-alpha, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-alpha at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-alpha was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreatment using rIL-2, rIL-2 and rIFN-alpha, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific to rIL-2.
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PMID:Low-dose interleukin-2 in combination with interferon-alpha effectively modulates biological response in vivo. 768 66

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

Twenty renal cell carcinomas were cultured in the presence of 200 IU/ml of recombinant interleukin-2; tumour-infiltrating lymphocytes (TIL) developed in 70% of cases; the phenotypic profile was heterogeneous in 11 TIL tested on day 30: 4 were mostly CD8 positive, 4 mostly CD4 and 3 showed CD4-CD8-CD56 mixed phenotypes. The cytotoxic activity was also heterogeneous, and no TIL developed a tumour-specific cytotoxic activity. The phenotypic profile and cytotoxic activity were also tested after thawing, and this study demonstrated that TIL can be frozen at the time of the nephrectomy, then thawed and cultured for the purposes of therapeutic trials when metastases appear. The differences between TIL derived from renal cell carcinoma and TI1 derived from melanoma are discussed.
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PMID:Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with renal cell carcinoma. 813 57

The cytotoxicity against neuroblastoma cells of IL-2-activated peripheral blood (PBL) and tumor-infiltrating lymphocytes (TIL) was evaluated in seventeen patients with neuroblastoma. Regional lymph node lymphocytes (LNL) were similarly studied in some patients. Three allogeneic neuroblastoma cell lines, LA2D2, LA2B4 and SIFA, established from the different metastases of the same patient were used as targets. Of the three neuroblastoma lines, LA2D2, with low CD56 expression, was the most susceptible to IL-2-activated lymphocytes, while SIFA, with high CD56 expression, was resistant in the greatest degree. LA2B4 showed moderate susceptibility. Although TIL (73.9 +/- 2.1%), LNL (81.0%) and PBL (76.2 +/- 3.1%) revealed similar cytotoxic activity to K562, they demonstrated distinct cytotoxic activities to each neuroblastoma cell line, as follows: against LA2D2: TIL 56.3 +/- 4.2%, LNL 52.1%, PBL 33.6 +/- 4.9% (P < 0.01); against LA2B4: TIL 47.3 +/- 3.3%, LNL 37.8%, PBL 33.7 +/- 4.8% (P < 0.05); against SIFA: TIL 27.0 +/- 6.2%, LNL 20.7%, PBL 13.9 +/- 2.4% (P = 0.056). TIL always showed higher cytotoxic activity against neuroblastoma cells than those of LNL and PBL, whereas LNL were more cytotoxic than PBL. This data showed that TIL from neuroblastoma patients preferentially killed neuroblastoma cells. It was suggested that lymphocytes in the tumor site and regional lymph node could have been sensitized with neuroblastoma-related antigens and exert preferential killing activity against neuroblastoma cells. Phenotypical analysis revealed that TIL had a larger population of CD56+ cells than PBL. Conversely, PBL had a higher population of CD16+ cells than TIL. The cytotoxic activity of TIL significantly decreased by the depletion of CD56+ cells (10.9 +/- 6.2 from 49.9 +/- 5.9% against LA2D2, P < 0.001). These results indicated that CD56+ cells were most responsible for the killing of neuroblastoma cells, and that TIL, with a high proportion of CD56+ cells with strong activity, would be the best source for the immunotherapy of neuroblastoma. Additionally, since neuroblastoma cell lines used in the present study were derived from the different metastases of the same patient, heterogeneity in the susceptibility to lymphocytes might result from the differential expression of tumor-related antigens on these cell lines.
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PMID:Distinct cytotoxicity against neuroblastoma cells of peripheral blood and tumor-infiltrating lymphocytes from patients with neuroblastoma. 840 93

We studied the relationship of natural killer cell activity from peripheral blood mononuclear cells with the clinical and pathologic stage of disease in 23 male patients with previously untreated carcinoma of the larynx and 22 healthy male control subjects. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of stage, tumor size, and clinical cervical adenopathies. Natural killer cell activity, however, was significantly decreased in patients with pathologic cervical lymph node involvement. The number of natural killer cells, as estimated by CD16 and CD56 monoclonal antibodies, was similar in all groups of subjects. We conclude that in patients with laryngeal carcinoma, there is a correlation between deficient natural killer cell activity and nodal metastases, which may represent a prognostic indicator in these patients.
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PMID:Natural killer cell activity in laryngeal carcinoma. 841 47

The status of natural killer (NK) cell activity in peripheral blood, based on number and functional state, was studied in relation to the clinical and histopathologic stage of 52 patients with laryngeal carcinoma and in 23 healthy controls. The number of NK cells, estimated using CD16 and CD56 monoclonal antibodies, was similar in patients and controls and showed no relation to tumor size and nodal involvement. NK cell function did not show significant differences in spontaneous cytotoxic activity either overall or in relation to tumor size and the presence of palpable lymph nodes. However, cytotoxic activity was significantly lower in patients who had histologically confirmed nodal involvement. NK activity under 36% (the percentage of specific lysis at an effector:target dilution of 50:1) was suggested the probable presence of nodal metastases and was a highly sensitive and specific test. In patients with laryngeal carcinoma, NK-cell cytotoxic activity may be an independent prognostic parameter for evaluating cervical lymph node involvement.
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PMID:[Study of spontaneous cytotoxic activity in laryngeal carcinoma: prognostic value]. 855 23


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