Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocyte subsets in the tumor nests of breast carcinoma were immunohistochemically investigated and a quantitative analysis was added. The majority of cases showed predominance of T cell and suppressor T cell (T8). A decrease in number of lymphocyte subsets and the helper T (T4)/T8 ratio in the stroma of tumor nests correlated well with the progression of clinical stage and the presence of metastasis. This correlation could not be found in the peripheral region of the tumor nests. Macrophages and NK cells were infrequently observed only in the peripheral region of ductal carcinoma. T cell infiltration was prominent in medullary carcinoma with lymphocyte infiltration (MC), and macrophages, NK cells, and T zone histiocytes were frequently encountered. For the purpose of knowing the activity of T cells, IL-2 receptor (Tac) and transferrin receptor were examined immunohistochemically. The fact that a few activated T cells were found only in the peripheral region of tumor nest suggested the local immune response in ductal carcinoma not to be so active as to reject the tumor cells. Since numerous activated T cells were recognized in the tumor nests of MC, this type of breast carcinoma was thought to have a higher immune reactivity. There was little evidence indicating NK cells to play a role for natural cytotoxicity in breast carcinoma.
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PMID:Immunohistochemical study on the distribution and significance of mononuclear cells in human breast carcinoma. 302 38

We report here experiments on the analysis of cellular signal transduction in a series of patients with chronic B cell disorders (B cell chronic lymphocytic leukemia [B-CLL] and prolymphocytic leukemia). We compared the response of the leukemic cells with primary external signals (interleukin 2 [IL-2] or B cell differentiation factors [BCDF or IL-6]) with their response to secondary inducers (the phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA] or the calcium ionophore A23187) that circumvent the first part of the signal transduction pathway by directly activating the key enzyme protein kinase C. One BCDF was synthesized by mitogen-activated peripheral blood B lymphocytes; a second BCDF was constitutively produced by the human bladder carcinoma cell line T24. Changes in morphology, Tac (IL-2 receptor) expression, RNA synthesis measured by 3H-uridine uptake, and immunoglobulin production tested by enzyme-linked immunosorbent assay were used as parameters of successful signal transduction. TPA alone and TPA plus A23187 (synergistically) effectively initiated differentiation in all the leukemia cases. Neither IL-2 nor BCDF (singly or in combinations) caused equivalent responses. On the other hand, IL-2 and BCDF produced a substantial differentiation effect on normal B lymphocytes. Our data suggest that (a) B-CLL cells are able to respond to direct stimulation of the second messenger pathway (through protein kinase C) but not to the physiological stimuli IL-2 or BCDF; (b) the defect in signal transduction appears to be located upstream of protein kinase C (a possible candidate is a G protein); (c) malignant B cells may spontaneously or after treatment with inducers express the IL-2 receptor (Tac antigen) in the absence of a functional differentiating response to IL-2; and (d) signs of proliferation/differentiation in B-CLL samples after incubation with IL-2 or BCDF might be due to contamination of the cell populations with residual normal B cells.
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PMID:Analysis of signal transduction in B chronic lymphocytic leukemia cells. 312 49

Disulfide-stabilized Fv's (dsFv's) are recombinant Fv fragments of antibodies in which the unstable variable heavy (VH) and variable light (VL) heterodimers are stabilized by disulfide bonds engineered at specific sites that lie between structurally conserved framework positions of VH and VL. We have recently described one example of a recombinant immunotoxin, B3(dsFv)-PE38KDEL, that is composed of such a dsFv connected to a truncated form of Pseudomonas exotoxin [Brinkmann, U., Reiter, Y., Jung, S.-H., Lee, B., & Pastan, I. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7538-7542]. This disulfide-stabilized immunotoxin has the same cytotoxic activity and specificity as its single-chain immunotoxin counterpart. To determine whether the stabilization of Fv's by disulfides at these positions is generally applicable, we made and analyzed two other dsFv-containing immunotoxins. One is made from the e23 antibody, which binds to the carcinoma-associated antigen erbB2; the other is made from the anti-Tac antibody, which binds to the p55 subunit of the IL-2 receptor. Comparison of the specificity and activity of these immunotoxins with those of their scFv counterparts revealed that e23(dsFv)-PE38KDEL was considerably more active than e23(Fv)-PE38KDEL, whereas anti-Tac(dsFv)-PE38KDEL was only somewhat more active than its single-chain counterpart. These results suggest that dsFv's have at least the same binding properties as scFv's, and in some cases they may have better binding. Thus, it should be feasible to use the positions we have identified in the conserved framework region to disulfide-stabilize many different Fv's.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stabilization of the Fv fragments in recombinant immunotoxins by disulfide bonds engineered into conserved framework regions. 791 34

This study was undertaken to investigate the pathways involved in the interleukin 2 (IL-2)-driven growth of tumour-infiltrating lymphocytes (TILs). For this purpose, TIL lines and freshly isolated TILs obtained from 16 patients with solid cancer (three melanoma, seven primary colorectal carcinoma, four hepatic metastases from colorectal cancer and two lung cancer) were evaluated for (a) expression of IL-2 receptor (IL-2R) both at the RNA level and on the cell surface by flow cytometric analysis and (b) their proliferative activity in response to IL-2 and the role of IL-2R subunits in the IL-2-driven TIL growth. Northern blot analysis showed that TILs express a strong message for both the p55 and the p75 IL-2R. Accordingly, flow cytometric analysis demonstrated that TILs bear both IL-2R chains. TILs cultured in vitro in the presence of rIL-2 were able to proliferate in response to different concentrations of this cytokine. Monoclonal antibodies (MAbs) specifically recognising the p55 and p75 IL-2R chains (anti-Tac and TU27 respectively) exhibited a marked inhibitory effect on IL-2-driven growth when added individually or in appropriate combinations. Our results demonstrated that TILs are equipped with a fully functional IL-2 receptor system, thus suggesting the involvement of this structure in the activation and expansion of TILs following immunotherapy with IL-2.
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PMID:Functional role of IL-2 receptors on tumour-infiltrating lymphocytes. 819 69

Perioperative blood transfusions have been shown to enhance recurrence rates in patients with operable solid tumors, perhaps by inducing immunosuppression through unknown mechanisms. Since the surgical treatment per se has been proven to induce immune alterations, the present study was carried out to evaluate the immune effect of blood transfusions on surgery-induced immune variations. The study included 27 patients with resectable colorectal carcinoma, 18 of whom received no transfusion, while the other 9 received blood transfusions in the perioperative period. Total lymphocytes, total T lymphocytes (CD3) and soluble IL-2 receptor serum levels (SIL-2R) were measured on venous blood samples collected from each patient either before or 7 days after surgery. Both in non transfused and in transfused patients, SIL-2R mean levels were significantly higher after than before surgery. Their increase was associated with a significant decrease in both lymphocytes and CD3 cells in non-transfused patients, while in the transfused ones lymphocytes and CD3 cells did not show significant changes with surgery. This study shows that blood transfusions modify the relation between changes in SIL-2R and those in lymphocyte number induced by major surgery. It remains to be understood which relation exist between these immune effects and the promoting action of blood transfusion on relapse frequency in cancer.
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PMID:Influence of blood transfusions on surgery-induced immune changes in colorectal carcinoma. 832 79

The serum levels of soluble IL-2 receptor (sIL-2R) were determined in 30 patients with esophageal carcinoma and in 32 normal subjects. In addition, the ability of PBMC to express IL-2 receptor (IL-2R) and release sIL-2R following PHA stimulation were studied in vitro. sIL-2R concentrations in sera derived from patients were significantly higher than in sera derived from healthy controls (P < 0.001). The expression of IL-2R by PBMC were decreased in patients, but no difference was demonstrated between the patients and healthy controls in the sIL-2R release. The increased levels of sIL-2R and decreased IL-2R expression by PBMC in patients might reflect the immunologic abnormalities in patients with esophageal carcinoma.
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PMID:[Soluble interleukin 2 receptor (sIL-2R) in patients with esophageal carcinoma]. 833 35

The effects of the oral administration of 100 mg/kg/day egg-white lysozyme (EWL) on the expression of CD3, CD4, CD8 and CD25 antigens of lymphocytes harvested from IEL and mesenteric lymph nodes (MLNL) were tested in mice bearing MCa mammary carcinoma. Lysozyme, after oral administration, retains its enzymatic activity along the entire small bowel and almost 10% of the administered dose is recovered 1 hr after treatment in the middle of the jejunum. Correspondingly, the number of cells expressing the test antigens in MLNL is greater than in controls after a few days of treatment and is maintained high up to the end of treatment but returns to control values after treatment withdrawal; CD4:CD8 ratio is decreased by EWL in favour of CD8 positive cells. Treatment with EWL does not modify the ratio between CD4+ and CD8+ cells vs controls in IEL nor does it change the % of CD3 positive cells or the expression of IL-2 receptor at this level. These data support the existence of the induction of an immunity communication by EWL along the axis GALT-mesenteric lymph nodes which is in agreement with the reported effects of the oral administration of EWL on tumour growth in experimental systems and on host immunity in humans.
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PMID:Cytofluorimetric analysis of gut-intraepithelial and mesenteric lymph node lymphocytes of tumour bearing mice fed with egg-white lysozyme. 861

Induction of growth inhibition in human colorectal carcinoma cell lines by interleukin (IL)-4 and IL-13 was associated with the neophosphorylation of a 170 kDa cellular protein, identified as insulin receptor substrate-1 (IRS-1) by immunoprecipitation. Tyrosine phosphorylation of IRS-I was also induced by insulin and insulin-like growth factor I. Sublines of colorectal carcinoma cells unresponsive to growth modulation by IL-4, IL-13 or insulin-like growth factor I-induced growth did not phosphorylate IRS-1. A functional, multimeric IL-4 receptor complex was present on all carcinoma cell lines with a subunit composition of 65 kDa, 75 kDa and the previously characterized 130 kDa band as demonstrated by affinity cross-link with 126I labelled IL-4. The 65 kDa subunit is novel whereas the 75 kDa band represents the common IL-2 receptor gama-chain the novel 65 kDa receptor was present as a double band and bound primarily 125I-labelled IL-13. The present study demonstrates the involvement of a novel chain other than the gama-chain in the receptor complexes of IL-4 and IL-13 and and post-receptor tyrosine phosphorylation of IRS-1. The association of IRS-1 with growth inhibitory signals in carcinoma cells suggests a novel mechanism of tumour growth control.
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PMID:Growth inhibition signalled through the interleukin-4/interleukin-13 receptor complex is associated with tyrosine phosphorylation of insulin receptor substrate-1. 864 56

The expression of cytokine receptors by a variety of solid tumour tissues was examined, using an immunofluorescence procedure optimized for sensitivity. Several cytokines generally considered as relevant only to the immune and haematopoietic systems were shown to be expressed by solid tumours. For example, breast carcinoma frequently expressed both chains of the IL-3 receptor, the beta chain of the IL-2 receptor, the TNF type two receptor, the signal-transducing chain CD130, and c-kit. The broad expression of cytokine receptors suggests that the receptor profile of individual tumours should be determined before the application of therapy that involves the administration of cytokines.
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PMID:Cytokine receptor expression by solid tumours. 872 78

Metastasis is a critical problem in the treatment of human lung cancer. Thus, a suitable animal model of metastasis of human lung cancer is required for in vivo biological and preclinical studies. In this study, we tried to establish a suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x 10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells, an in vivo-selected variant line, formed significant numbers of lymph-node metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice depleted of NK cells by treatment with TM-beta 1 showed different patterns of metastasis when inoculated intravenously with the 2 different human lung cancer cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases mainly in the liver and kidneys, with only a few in lymph nodes. A histopathological study showed that the metastatic colonies consisted of cancer cells. The numbers of metastatic colonies formed by the 2 cell lines increased with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently removed NK cells from peripheral blood for at least 6 weeks, whereas, after treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within 9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a model in biological and pre-clinical studies on metastasis of human lung cancer.
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PMID:Novel metastasis model of human lung cancer in SCID mice depleted of NK cells. 876 May 90


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