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)

Recent reports suggest that recombinant interleukin-2 may be effective in the treatment of cancer patients with low tumor burden. Considering the poor long-term survival, 11 ovarian cancer patients with minimal residual disease at second-look have so far been selected for rIL-2 intravenous continuous infusion therapy: two induction courses (3 x 10(6) U/m2/day: 120 h + 108 h) followed by three maintenance courses (3 x 10(6) U/m2/day: 120 h) and third-look laparotomy. At present, three patients are still on treatment, three have completed it, and five have discontinued treatment. Sixty-seven per cent of the planned dose was administered in 49 cycles of which 42 (86%) required dose modifications due to hypotension (greater than or equal to grade III) and nephrotoxicity (greater than grade I). CNS and GI toxicity, allergies and fever, even though requiring dose modifications in a few cases, significantly affected patient compliance. The rebound lymphocytosis was clearly dose-related and a significant percentage increase after rIL-2 was detected only for IL-2 receptor positive cells. To date, four patients are evaluable for response after a median follow-up of 7 months, two progressed during the maintenance period, while one CR and one progression were detected in the two patients so far submitted to third-look laparotomy.
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PMID:Recombinant interleukin-2 continuous infusion in ovarian cancer patients with minimal residual disease at second-look. 278 2

This study was undertaken to explain the molecular basis for the diverse pathology and clinical behavior of postthymic T cell malignancies. Total cellular RNAs were extracted from four HTLV-1 positive and ten HTLV-1-negative T cell lymphomas and cell lines, and investigated for homology with cloned DNA probes specific for interleukin-2 (IL-2), IL-2 receptor (IL-2R), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and epidermal growth factor receptor (EGF-R). Tumor cells associated with clinically high grade HTLV-1-positive adult T cell leukemia (ATL) and large cell morphology (T immunoblastic lymphomas) were found to have higher levels of expression of IL-2 and TGF-beta genes than low grade T cell neoplasms (mycosis fungoides and Sezary's syndrome). High expression of IL-2R gene was restricted to Ki-1-positive lymphomas and to one ATL. Cell lines corresponding to the advanced stage of a cutaneous T cell lymphoma (CTCL) showed enhanced expression of PDGF. Therefore, high grade T cell malignancies had consistently elevated expression of growth factor/receptor (GF/R) genes. Expression of EGF-R was negligible in all T cell malignancies. An inverse relationship was found between the expression of T cell antigen receptor (differentiation antigen) and GF/R (activation antigen) genes, accounting for the frequent aberrant expression of T cell antigens in high grade T cell lymphomas. The results suggest that post-thymic T cell malignancies derived from activated T cells produce and secrete GF, conferring a growth advantage on neoplastic T cells, and correlating well with their histologic subtype and clinical behavior.
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PMID:Expression of growth factor/receptor genes in postthymic T cell malignancies. 278 74

Human T-cell leukemia/lymphoma virus I (HTLV-I) is known to be associated with adult T-cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in IL-2 production and its receptor (Tac antigen) expression based on the experimental observations of IL-2-dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T-cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of IL-2 to the culture medium. Cell-surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and IL-2 binding assays revealed that one of the ATL cell lines, HPB-ATL-2, expresses only a minimal amount of IL-2 receptor (IL-2-R) on the cell surface and binds less radiolabelled human recombinant IL-2 than the other highly Tac-positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by IL-2, anti-Tac MAb or the tumor-promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no IL-2 activity toward Con-A-stimulated human peripheral blood lymphocytes, and their growth was not affected by additional IL-2 in cultures. IL-2-independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of IL-2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV-I. Trans-activation of the PX40 gene product of HTLV-I for activation of IL-2-R gene might not be coincidentally associated with stimulation for cell proliferation.
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PMID:IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients. 287 15

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.
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PMID:Interleukin 1 gene expression in adult T cell leukemia. 288 87

Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/- SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s-IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL-2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s-IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex-matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture.
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PMID:Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers. 290 Feb 31

From one colonic carcinoma chemically induced in the rat, 2 sublines of tumor cells have been cloned, one (PROb) inducing progressive tumors, the other (REGb) generating tumors that regress a few weeks after s.c. injection into syngeneic hosts. Our study was aimed at comparing cellular immunity between animals bearing PROb or REGb tumors. Spleen cells were first tested for in vitro proliferation in response to mitomycin-treated PROb or REGb cells. Only spleen cells from rats injected with REGb cells proliferated significantly when mixed with PROb or REGb cells. The proliferative response induced by REGb cells was considerably higher than the response to PROb cells. When spleen cells from rats bearing REGb tumors were cultured with a mixture of REGb and PROb cells at various PROb/REGb cell ratios, PROb cells significantly suppressed the strong proliferative response generated by the same number of REGb cells alone. REGb-immune spleen cells, after in vitro stimulation by PROb or REGb cells, were not cytotoxic for either cell variant. REGb-immune spleen cells did not differ in their content of T lymphocytes expressing CD4 or CD8 markers when they were stimulated by PROb or REGb cells in vitro, but REGb cells induced a larger number of activated lymphocytes expressing the IL-2 receptor. Our results indicate that, compared to REGb cells, PROb cells are poorer stimulators of proliferation of tumor-immune spleen cells, and that they are able to suppress the proliferative response induced by REGb cells.
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PMID:In vitro proliferative responses of spleen lymphocytes from rats bearing progressive or regressive tumors induced by cell variants of a syngeneic colon carcinoma. 291 5

The interleukin-2 (IL-2) receptor, the leukocyte-specific membrane glycoprotein, T200, and the class I major histocompatibility antigens (HLA) have been identified as substrates for protein kinase C in vitro. IL-2 receptors on normal human T lymphocytes and the leukemic cell line, HUT102B2, are rapidly phosphorylated in vivo in response to the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). Tryptic peptide analysis showed that the in vitro and in vivo 32P-labeled IL-2 receptors were phosphorylated on the same sites. A synthetic peptide corresponding to the carboxyl-terminal cytoplasmic tail of the IL-2 receptor was shown to be phosphorylated in vitro by protein kinase C. Tryptic digestion of the peptide generated the same 32P-labeled species as those found for the IL-2 receptor. From these studies, it was concluded that Ser-247 is the major site of phosphorylation in the IL-2 receptor and that Thr-250 is a minor site. These results also provide direct evidence that the in vivo phosphorylation of the IL-2 receptor stimulated by TPA is catalyzed by protein kinase C. The sites phosphorylated in the HLA antigens in vitro by protein kinase C or in vivo after TPA stimulation were also localized to the carboxyl-terminal cytoplasmic domain of the heavy chain by limited proteolysis.
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PMID:Identification of lymphocyte integral membrane proteins as substrates for protein kinase C. Phosphorylation of the interleukin-2 receptor, class I HLA antigens, and T200 glycoprotein. 294 17

We have analyzed the effects of high doses of cyclophosphamide (Cy) on primary and secondary antitumor immune response against immunogenic (tum-) variants of Lewis lung carcinoma (3LL) treated in vitro with UV light. Normal mice and mice previously immunized with tum- clones wer inoculated i.p. with Cy (200 mg/kg body weight) and 24 h later challenged intrafootpad with tum- or parental 3LL cells. Cy treatment suppressed the primary immune response of normal animals and allowed the growth of tum- cells. In contrast, Cy-treated immune mice rejected the tumor challenge. The in vivo treatment with Cy decreased the total number of lymphoid cells in the spleens, as well as the proportion of B lymphocytes; however, it increased the percentage of both Lyt2+ and L3T4+ lymphocytes. Thus, the immunosuppressive effects of Cy on the primary antitumor response could not be attributed to elimination of major T lymphocyte subpopulations. Although the treatment of immune mice with Cy did not significantly impair their antitumor resistance, nor the proportion of Lyt2+ and L3T4+ lymphocytes in their spleens, the in vitro generation of cytotoxic T lymphocytes (CTL) was markedly reduced. After Cy treatment, the proliferative ability of spleen cells in response to interleukin-2 (IL-2) was substantially impaired. Using monoclonal antibodies to the IL-2 receptor, we found that Cy-treated T lymphocytes failed to fully express the IL-2 receptor following in vitro stimulation with irradiated tumor cells. In line with these findings, the in vitro generation of CTL was not restored by addition of recombinant IL-2 to the cultures. In vivo experiments using purified functional subsets of immune T cells showed that Lyt1+, but not Lyt2+ lymphocytes were able to transfer antitumor immunity in normal irradiated recipients. Therefore, since Ly1+ T lymphocytes were responsible for the antitumor resistance in vivo, the Cy-induced impairment of CTL generation did not affect the ability of immune mice to reject a secondary tumor challenge.
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PMID:In vivo resistance of secondary antitumor immune response to cyclophosphamide: effects on T cell subsets. 294 33

We constructed a series of MAb heterodimers consisting of the J5 (anti-common acute lymphoblastic leukemia antigen [CALLA]) antibody and antibodies to a variety of structures present on the surface of activated human T cells, including CD3 antigen (T cell receptor-associated glycoproteins), CD2 antigen (T11/E-rosette receptor), CD25 antigen (IL-2 receptor), and the transferrin receptor. We tested the ability of these heterodimers to direct a CD2 + CD3 + CD8 + CD4 - CD25 + transferrin receptor + MHC-restricted human cytolytic T lymphocyte (CTL) clone to lyse a CALLA + human tumor in vitro. Only heterodimers containing an anti-CD3 antibody or activating antibodies to CD2 could direct the clone to lyse these human tumor targets, even when the clone was additionally activated with anti-CD3 or anti-CD2 antibodies. Our findings may have implications in the design of strategies for the use of such reagents in the treatment of human neoplasia.
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PMID:Requirements for the construction of antibody heterodimers for the direction of lysis of tumors by human T cells. 296 15

Our method of adoptive immunotherapy (AIT) using autologous IL-2-cultured lymphocytes differs from so-called LAK therapy in several points. We (1) obtain cultured lymphocytes from effusion lymphocytes (EL) or regional lymph-node lymphocytes (RLNL), when possible, rather than peripheral blood lymphocytes (PBL), (2) use crude IL-2 to induce T cell proliferation and to maintain killer activity, (3) use sonicated autologous tumor extract as antigen (Ag) to stimulate proliferation of cytotoxic T cells, and (4) pretreat the patients with local administration of OK-432 before AIT to induce effector cells that act synergistically with transferred killer cells. Surface marker analysis showed that OKT3, IL-2 receptor, Leu 2+15- cells were elevated while Leu 11a and Leu 3+8+ cells were decreased. Culture of RLNL augmented the expression of Leu 3+8- marker. Both of PBL and RLNL responded to Ag, and their auto-tumor killing activities were augmented in about half of the patients while rarely decrease by the addition of Ag. Response rates of patients with pleural effusion due to breast cancer and those with liver metastasis of breast cancer were 94% and 60%, respectively. Moreover, the survival was prolonged in the treated patients with pleural effusion or gastric cancer patients with peritoneal dissemination.
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PMID:[Clinical therapeutic effect of adoptive immunotherapy using IL-2-cultured autologous lymphocytes]. 297 6


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