摘要:

Because tumors are composed of cells that are genetically unstable, tumor cell populations tend to become heterogeneous during the division and proliferation that occurs after the onset of carcinogenesis, even if a tumor is derived from a single transformed progenitor cell. As a result of this, and the process of host selection, the tumorigenic and malignant aggressiveness of tumor cells can increase with time. This is known as the concept of tumor progression. On the other hand, as we know, or can infer, from examples of the spontaneous regression of some human cancers, the tumorigenic capacity of tumor cells can sometimes actually decrease during the course of tumor growth. This is the concept of tumor regression. Based on this two dimensional concept of tumor growth, it seems reasonable to suppose that individual tumor cells may gradually enter into a state of either progression or regression. In this report, I review experimental models that have been designed to cause tumor regression through immunological mechanisms.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Interleukin-2 (IL-2) production following concanavalin A stimulation and the response of peripheral blood mononuclear cells (PBMC) to both IL-2 alone and IL-2 plus indomethacin, a prostaglandin synthetase inhibitor, were examined in 16 melanoma patients and 12 healthy controls. Mean IL-2 production by PBMC in 11 melanoma patients with metastatic disease (Stage III) was significantly decreased compared with controls and was moderately decreased compared with five patients with resected nodal disease (Stage II). Indomethacin restored IL-2 production in Stage III PBMC to levels equivalent to that produced by control PBMC. The PBMC of stage III patients also produced 40 times more prostaglandin E2than PBMC from controls or Stage II patients. Indomethacin plus IL-2, but not IL-2 alone, was capable of restoring the low blastogenic response of PBMC of Stage III patients to normal levels. Hence, these data emphasize the importance for using IL-2 along with indomethacin for in vivo immunorestoration in disseminated melanoma.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The capacity of a lipophilic derivative of synthetic muramyl dipeptide (MDP), B30-MDP, to induce morphological changes and functional alterations in the activity of resident peritoneal macrophages was studied. Macrophages incubated in vitro for 24 h with B30-MDP, but not with MDP or medium, showed rounding and extensive ruffling of the cell surface when examined by scanning electron microscopy. Transmission electron microscopy of B30-MDP-treated macrophages revealed the development of large cytoplasmic vacuoles. These structural changes did not affect the viability of macrophages. The Fc receptor-mediated phagocytosis of51Cr-labeled sheep red blood cells by adherent macrophages incubated with a high dose of MDP showed a modest response whereas even low doses of B30-MDP greatly enhanced the phagocytic activity. Adherent macrophages incubated with B30-MDP generated elevated levels of luminol-dependent chemiluminescence in response to stimulation by zymosan.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Because two of five patients with renal cell carcinoma in a Phase I study had partial response to recombinant a-2 interferon (IFN), we treated 26 patients with advanced renal cell carcinoma with a 3-month regimen of IFN. Patients were randomized to receive IFN either subcutaneously (2 ± 106IU/m23 times a week) or intravenously (3 ± 107IU/m2for 5 consecutive days every 2–3 weeks). Patients whose disease was responding or stable were treated further, while those with progressive disease on subcutaneous treatment were offered intravenous therapy. Sites of metastasis included lung (14 patients), bone (7 patients), soft tissue (7 patients) and liver (2 patients). Twenty patients were evaluable for response. One patient had a partial response at the end of the third course of intravenous IFN and subsequently had complete disappearance of a 12 ± 7 cm subcutaneous mass after the seventh course of treatment. The disease was stable in 13 patients including two minor responses, and six patients had progressive disease (5 with subcutaneous treatment; 1 with intravenous treatment) including one mixed response. All patients experienced early flu-like symptoms of fever, chills, and rigors during the first few days of treatment and most had mild to moderate fatigue. Three patients left the study because of fatigue, and one had an urticarial rash. From these results and our previous experience, it appears that IFN has activity against renal cell carcinoma with acceptable toxicity.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effects of recombinant interleukin-2 on resting T lymphocytes were examined in vitro. T cell enriched populations were isolated from the peripheral venous blood of three normal individuals by Ficoll-Hypaque gradient separation and standard sheep erythrocyte rosetting techniques. Interleukin-2 at concentrations of 100 and 1,000 U/ml stimulated tritiated thymidine incorporation, Tac antigen expression, interferon production, and blast transformation in T cell cultures. These changes were observed in the absence of cell proliferation. The effects of interleukin-2 at a concentration of 100 U/ml were substantially blocked by the addition of a 1:1,000 dilution of anti-Tac antibody to the culture medium indicating that the effects observed were mediated by the Tac receptor. These results indicate that recombinant interleukin-2 can have demonstrable functional and morphologic effects on unstimulated human T cells.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The survival-enhancing capabilities of particulate (P) and soluble (F) glucan, a B-1,3 polyglycan biological response modifier, were assayed in60Co irradiated mice. Although glucan-P was slightly more effective than glucan-F, both glucans significantly enhanced survival in otherwise lethally irradiated (9.0–11.0 Gy) C3H/HeN mice. Following 9.0 Gy, 60% of the glucan-P treated and 53% of the glucan-F treated mice exhibited long-term survival as opposed to 0% of the radiation control mice. The survival-enhancing effects of glucan-P and glucan-F decreased as the radiation dose increased to 11.0 Gy. At higher radiation doses (e.g., 12.0 Gy) neither glucan preparation was capable of enhancing survival. Both glucan-P and glucan-F enchanced the recovery of peripheral blood white cell numbers, platelet numbers, and hematocrit values. In addition, both agents increased endogenous pluripotent hemopoietic stem cell numbers in sub-lethally irradiated mice. Taken together, these results demonstrate that both glucan-P and glucan-F can significantly enhance survival in lethally irradiated mice. However, these agents appear to function specifically by enhancing hemopoietic recovery and are not effective at radiation doses also known to induce gastrointestinal damage.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Highly purified interleukin-2 (IL-2) induced proliferation of fresh human peripheral blood mononuclear leukocytes (PBML) in the absence of identifiable exogenous mitogenic or antigenic stimuli. Dose dependent proliferation was observed with three IL-2 preparations, including two preparations purified from natural sources and a preparation produced by recombinant DNA techniques. Both T and non-T cells proliferated. Purified helper/inducer and suppressor/cy-totoxic T cells cultured in the absence of non-T cells proliferated only weakly; the proliferative response to IL-2 was restored by the addition of irradiated non-T cells. Proliferation to IL-2 was not blocked by the monoclonal antibody anti-Leu 4, which reacts with a component of the T-cell receptor complex for antigen and blocks mitogen and antigen-induced T-cell responses. Monoclonal antibody to HLA-DR also failed to significantly block the proliferation of resting cells to IL-2. The IL-2 induced proliferative response thus appears to be dependent on interactions between different subpopulations of PBML but probably does not simply reflect augmentation by IL-2 of antigen-driven or autoreactive processes.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Toxicity was assessed during and following 186 infusions of various murine monoclonal antibodies (MoAbs) in 82 patients afflicted with 10 different malignancies. Doses ranged from 0.5 to 500 mg per infusion and were administered over 0.25–24 h. Reactions of varying degrees were noted in 27 patients (33%) during or following 57 (31%) infusions. For antibodies that reacted with circulating cells, toxicity was seen in 20/82 of the first infusions compared with 0/55 for patients receiving antibodies that did not react with circulating cells. A 25% decrease in white blood cells (WBC) was associated with side effects in 40/ 66 courses whereas only 9/81 courses were associated with any sort of toxicity when the WBC decreased by less than 25%. Fevers, rigors, chills, and diaphoresis were observed in 21–23% of patients, but only in association with removal of circulating cells that bound the antibody. Presumed hypersensitivity reactions, including urticaria, pruritis, bronchospasm, and anaphylaxis occurred in 15 patients (18%). The two episodes of bronchospasm and single episode of anaphylaxis occurred in patients treated more than once, at least 2 weeks after a previous treatment. There was no clear relationship between dose or rate of infusion and toxicity for these antibodies. We conclude that murine MoAbs can be given with an acceptable frequency of serious allergic reactions and that the biologic effects of specific antibody-antigen reactions may be a more significant source of toxicity for such antibodies.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Six lymphoid human interleukin-2s (nIL-2s) [four from peripheral blood mononuclear cells (PBMC) and two from JURKAT cells] and six recom-binant IL-2s (rIL-2s) were obtained for comparative evaluation. The main issues addressed were possible differences among the preparations in potency in T cell growth assays and other functional assays, and the possible presence of other cytokine activities or contaminants. Each preparation was assigned a standardized IL-2 activity in reference units (RU) by comparing its T cell growth promoting activity against the Biological Response Modifiers Program IL-2 (JURKAT) reference reagent. Relative to the IL-2 unitage indicated by the suppliers, the RU varied from 110-fold less to 38.5-fold more for the various preparations. Two nIL-2s and two rIL-2s contained significant levels of endotoxin. One nIL-2 contained low levels of both alpha and gamma interferon (IFN), and one nIL-2 had a high level of gamma IFN. All other IL-2s were negative for IFN activity. All IL-2 preparations significantly augmented human natural killer (NK) activity, although the amount of RU required varied from 0.1 to 50 RU. Four nIL-2s and three rIL-2s induced human PBMC to produce gamma IFN, whereas two nIL-2s and one rIL2 did not. All nIL-2s had substantial amounts of B cell growth factor activity, whereas none of the rIL-2s consistently displayed this activity. All IL-2s stimulated the tritiated thymidine [3H]TdR incorporation of human PBMC in the absence of other stimuli, in addition to augmenting the response to mitogen or alloantigens. Some nILs and IL-2s had effects on human monocytes such as inhibiting migration, inducing cytotoxic or growth inhibitory activity against tumor cells, and causing changes in cell surface markers. The IL-2s were also tested for activity in vitro and in vivo in mice. Although there was a 12-fold variation in activity among the preparations, all but one of the IL-2s showed augmentation of the mixed lymphocyte reaction activity and all IL-2s tested stimulated mac.

ISSN:0732-6580    

出版商:OVID    

年代:1986

数据来源: OVID