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

Th cells are stimulated by peptide Ag presented in the context of MHC class II molecules. We have reasoned that immune responses against tumors may be more efficient if tumor cells were class II Ag positive, and thereby able to directly function as APC to stimulate tumor-specific Th cell proliferation. We have tested this hypothesis by using DNA-mediated gene transfer to generate syngeneic MHC class II Ag-expressing mouse Sal sarcoma cells (Sal/Ak transfectants). Autologous A/J mice challenged i.p. or s.c. with Sal/Ak transfectants do not develop tumors, whereas A/J mice challenged with the class II negative parental Sal tumor have a high tumor incidence. Furthermore, immunization of the autologous host with Sal/Ak transfectants completely protects against subsequent challenge with wild-type Sal cells. MHC class II-expressing tumor cells, therefore, stimulate an improved tumor-specific immune response, and the immunity is cross-reactive with the class II negative tumor. Inasmuch as the transfected MHC class II gene product is not functioning as a target molecule for autologous tumor rejection, the improved immunogenicity of the Sal/Ak cells is probably due to stimulation of a tumor-specific Th cell population. The increased immunogenicity of Sal/Ak cells is, therefore, probably the result of direct presentation of Sal tumor-associated Ag in the context of tumor cell MHC class II molecules to Th lymphocytes. These studies demonstrate that induction of tumor cell MHC class II Ag expression is a potential strategy for tumor-specific immunotherapy, and suggest that tumor immunity may be enhanced by improved Th cell generation.
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PMID:Rejection of mouse sarcoma cells after transfection of MHC class II genes. 233 39

We found that three tumor patients treated with mouse mAbs have T cells that recognize processed mouse Ig on autologous APC in a class II-restricted fashion, and we have shown that mouse mAbs directed against various cell surface molecules can be used as antigens to focus these T cells on an MHC class II-positive target of choice.
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PMID:Antibodies as antigens. The use of mouse monoclonal antibodies to focus human T cells against selected targets. 245 Jan 58

The present study investigates the role of APC in inducing tumor-specific in vivo protective immunity. Thy-1+ cell-depleted, Mac-1+ cell-enriched fraction of normal BALB/c spleen cells were used as a source of APC. These APC were cultured in vitro with the membrane fraction isolated from CSA1M fibrosarcoma derived from BALB/c strain. The administration of such APC into naive BALB/c mice generated the capacity of these animals to reject the subsequently challenged viable CSA1M tumor cells. Although the induction of anti-CSA1M in vivo protective immunity required three consecutive immunizations with more than 10(5) APC which had been pulsed in vitro with 200 to 300 micrograms protein of CSA1M membrane fraction, the immunity was induced irrespective of whether APC were administered via s.c., i.v., or i.p. route. This immunity was tumor-specific, inasmuch as the inoculation of CSA1M or Meth A fibrosarcoma membrane component-pulsed APC resulted in the selective immunity against the challenge with homologous types of tumor cells. The CSA1M-specific in vivo protective immunity was also induced by injecting APC pulsed with solubilized CSA1M membrane components. Moreover, it was demonstrated that the efficiency for inducing anti-CSA1M immunity was much higher in the utilization of tumor Ag-pulsed APC than in the immunization with tumor Ag emulsified in CFA. These results indicate the critical role of APC in generating tumor rejection immunity in vivo and this model presents a novel approach to induce tumor-specific immunity without using tumor cells themselves.
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PMID:Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells. 246 22

The present studies were undertaken to characterize Ag presentation by cultured human melanoma cell lines. Cell lines established from "biologically early" lesions of malignant melanoma were able to present the soluble Ag tetanus toxoid (TT) to autologous and HLA-DR-matched allogeneic, TT-immune T cell clones. Proliferation of T cell clones in response to Ag presented by primary melanoma peaked on day 2 of culture with Ag. Ag presentation was blocked by pretreatment of TT-pulsed and fixed melanoma cells with mAb against HLA-DR, but not HLA-DQ, HLA-DP, or HLA-ABC. Ag processing and presentation were inhibited by treating the melanoma cells with ammonium chloride. In parallel with previous findings from this laboratory demonstrating the inability of cell lines cultured from "advanced" primary or metastatic melanoma to induce autologous T cell proliferation, such cell lines also failed to present this exogenous Ag despite the presence of cell-surface HLA-class II molecules. Thus, in contrast to the finding in biologically early melanoma, none of the multiple TT-immune, T cell clones from autologous patients or HLA-DR matched donors was able to respond to TT presented by melanoma cells cultured from advanced disease. Co-incubation studies revealed that metastatic melanoma cells did not secrete inhibitory substances during the APC assay, however, they were able to process TT, rendering it "immunogenic" in the presence of fixed, autologous non-T cells. When fixed, autologous melanoma cells were assayed for their ability to present processed Ag; fixed cells of early but not advanced disease were able to present Ag in this setting, indicating that the presenting limb becomes flawed in the evolution of the metastatic phenotype. Finally, studies of chloroquine inhibition of the capacity of melanoma cells derived from early primary disease to stimulate autologous peripheral blood T cells suggest that such cells process and present tumor-associated Ag in the same fashion as the "model" Ag TT.
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PMID:Defective antigen presentation by human melanoma cell lines cultured from advanced, but not biologically early, disease. 246 32

Inoculation of P815 tumor cells (DBA/2 origin) into the anterior chamber of eyes of BALB/c mice normally produces anterior chamber-associated immune deviation (ACAID) whereby delayed hypersensitivity (DH) responses to the minor H alloantigens of the tumor cells are suppressed. Based on our previous work showing an association of Langerhans cell infiltration into central cornea with the abrogation of ACAID, we have hypothesized that the induction of ACAID may depend upon the avoidance of local antigen processing within the anterior chamber. In this study, we have examined whether various putative antigen-presenting cells coinjected with allogeneic P815 cells into the anterior chamber could alter the course of the subsequent systemic alloimmune response. BALB/c recipients of intracameral P815 cells admixed with BALB/c spleen cells, B cells, or A20 B lymphoma cells developed ACAID. However, recipients of tumor cells admixed with cutaneous epidermal cells containing LC, and those receiving intracameral P815 cells admixed with purified LC developed vigorous DBA/2-specific delayed hypersensitivity responses. We conclude that avoidance of antigen processing and presentation by specialized APC such as dendritic LC within the anterior chamber is a condition for the induction of ACAID. Since under normal circumstances the anterior chamber is lined by tissues that are devoid of LC and contain very few class II MHC-expressing cells, this immunologically privileged site appears to be designed physiologically to avoid the unique form of local antigen presentation offered by dendritic LC--a condition that favors induction of selective immunologic incompetence.
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PMID:Induction of delayed hypersensitivity to alloantigens coinjected with Langerhans cells into the anterior chamber of the eye. Abrogation of anterior chamber-associated immune deviation. 249

Using separated epithelium (SVE) and fibromuscular stroma (SVM) of guinea pig seminal vesicle, the antihormonal effects of daily subcutaneous administration (14 and 28 days) of the benzothiophene keoxifene (LY156758; [6-hydroxy-2-(4-hydroxyphenyl)benzo(b) thien-3-yl] [4-(2-1-piperidinyl) ethoxyl] phenyl) methanone hydrochloride) in intact, castrate, and androgen/estrogen-maintained castrate animals was evaluated. The compound was devoid of agonist activity in castrated males, in that the compound had no stimulatory effect on SVM wet weight or DNA content. In vitro cytosolic binding of [3H]estradiol (E2) in the SVM was decreased in a concentration-dependent manner by keoxifene, but the compound did not perturb the binding of [3H]dihydrotestosterone (DHT) in the SVM or SVE. Likewise, keoxifene administration to castrated males treated with exogenous steroids antagonized the estrogen-induced hyperplastic response of the SVM, whereas no interference with androgen-induced growth of the SVM or SVE was observed. Keoxifene treatment of intact male guinea pigs produced regression of the androgen-sensitive SVE as well as the androgen/estrogen-sensitive SVM. Keoxifene-induced decreases in guinea pig serum testosterone levels were associated with this activity. Histological analysis of the seminal vesicle under these conditions suggests androgen deprivation. These findings indicate that keoxifene is a physiological antagonist of androgen action in the intact male guinea pig. The pure estrogen antagonist properties of keoxifene and its ability to decrease accessory sex organ epithelium and fibromuscular stroma in vivo suggest potential applications of the benzothiophenes in the medical management of prostatic neoplasia.
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PMID:Antagonism of androgen and estrogen effects in guinea pig seminal vesicle epithelium and fibromuscular stroma by keoxifene (LY156758). 253 83

In this review article some novel immunotherapeutic models as well as some new concepts concerning the unspecific and specific T-cell stimulation are discussed briefly. Some of these immunotherapeutic models are restricted to bladder cancer; the others have a generalized meaning. One model, restricted to bladder cancer, is based on the enzymatic++ pretreatment of effector-cells (macrophages, NK-cells), followed by their instillation in the patient's bladder. The other bladder tumor restricted model includes the direct in situ activation of effector cells by proteases and lipases. A third model for the treatment of bladder tumor implies a presensitization of patient's TD/TDTH-cells, followed by the treatment of patient's bladder tumor cells by some, common haptenic group. In addition, some novel ways of immune stimulation, partly by circumventing the (tumor-specific) immune tolerance, based on the cross-linking of crucial membrane structures on T4- and T8-cells or on a managed, controlled APC: T-cell interaction, are discussed. The details inclusively the comprehensive special literature can not be brought in this review article; they should be dealt with in special papers being in preparation.
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PMID:[Novel immunotherapeutic models for neoplastic diseases of the urogenital tract with special attention to bladder carcinoma]. 257 84

After immunization of B6 mice with the syngeneic retrovirus-induced T cell leukemia/lymphoma FBL-3, two major tumor-specific proliferative T cell clonotypes were derived. T cell clones derived from long-term lines propagated by in vitro culture with irradiated tumor cells and syngeneic spleen cells were exclusively of the Lyt-2+ phenotype. Such clones were cytolytic, retained their proliferative phenotype indefinitely when expanded by repeated cycles of reactivation and rest, and recognized a tumor-specific cell surface antigen in association with class I MHC molecules. This tumor cell antigen was not present on nontransformed virus-infected cells. Class II MHC-restricted MT4+ clones specific for the viral antigen gp70 were derived from lymph node T cells of FBL-3 tumor-immune mice only by in vitro culture with purified Friend virus in the presence of syngeneic splenic APC. Once derived, however, such clones could be stimulated in the presence of FBL-3 tumor cells and syngeneic spleen cells, demonstrating the reprocessing of tumor-derived gp70 antigen by APC in the spleen cell population. In contrast, no reprocessing of the tumor cell surface antigen by splenic APC for presentation to the class I MHC-restricted T cell clones could be demonstrated. Evidence is presented that FBL-3 T leukemia/lymphoma cells function as APC for Lyt-2+ class I MHC-restricted clones, and that no concomitant recognition of Ia molecules is required to activate these clones. Both Lyt-2+ and MT4+ clones were induced to proliferate in the presence of exogenous IL2 alone, but this stimulus failed to result in significant release of immune interferon. In contrast, antigen stimulation of both clones resulted in proliferation as well as significant immune interferon release. Immune interferon production is not required for the generation of MHC-restricted cell-mediated cytolytic function.
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PMID:Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen. 258 53

The growth-inhibitory activity of recombinant human tumor necrosis factor (rH-TNF: PAC-4D) against 32 human cultured cell lines derived from leukemias and lymphomas (7 T cell, 11 B cell, 5 non-T,non-B cell and 9 myeloid cell lines) was measured quantitatively by in vitro regrowth assay. The growth of two non-T,non-B-cell lines (Reh, P30/OHK) and six myeloid cell lines (ML-1, U937, THP-1-0, P31/FUJ, P39/TSU, HEL) was found to be significantly inhibited by a 72 hr treatment with PAC-4D. Although the levels of sensitivity of these cell lines to PAC-4D were different, it was common to all these cell lines that increasing the dose of PAC-4D did not augment the growth-inhibitory action above a certain level. Neither dose-dependent nor time-dependent growth-inhibitory action was observed, namely, exposure to 100 U/ml of PAC-4D for 48 hr was sufficient to exhibit maximum growth-inhibitory action. Furthermore U937 cells were found to become completely resistant to PAC-4D during a continuous 12-day exposure to it. This resistance, however, was lost on culture of the cells with PAC-4D-free growth medium for 15 days. These results suggested that some non-T,non-B acute lymphoblastic leukemias and acute myelogenous leukemias might show an initial response to PAC-4D therapy, but prolonged administration might induce resistance to PAC-4D rather than increase the anti-tumor effect.
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PMID:Potential limitation of growth-inhibitory action of recombinant human tumor necrosis factor (PAC-4D) due to easy induction of resistance: evidence in vitro. 282 76

A dilated cardiomyopathy picture has been produced by rapid atrial and ventricular rates sustained for a long period of time in some patients. The ventricular tachycardias have in some instances been associated with ventricular tumors as the cause of the tachycardia. Once the tumor is removed, the tachycardia stops and the heart function improves. Atrial ectopic tachycardias also produce a similar picture, but have not been associated with atrial tumors. Such a case is presented with an atrial rhabdomyoma producing atrial ectopic tachycardia and a dilated, poorly contracting myocardium. The tumor was resected and the tachycardia was immediately abolished. Cardiac function quickly returned to normal.
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PMID:Atrial automatic ectopic tachycardia due to an atrial tumor. 334 60


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