Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine type-2 receptor antagonists (H-2RA) have been used chronically to prevent dyspepsia in cancer patients subjected to immunotherapy with chronic indomethacin (Indo) and intermittent IL-2 in our cancer centre. We tested the effects of these agents during immunotherapy of C3H/HeJ mice transplanted s.c. with 5 x 10(5) C3L5 mammary adenocarcinoma cells. Tumor-transplanted mice were divided into groups receiving: (1) Indo (14 micrograms/ml); (2) H-2RA, i.e. (a) ranitidine at 28.6 micrograms/ml (Ran-lo) or 143 micrograms/ml (Ran-hi), or (b) famotidine (Fam) at 4.3 micrograms/ml, or (c) cimetidine (Cim) at 107 micrograms/ml, all in the drinking water on days 5-24; (3) IL-2 (1.5 x 10(3) Cetus U i.p. every 8 h on days 10-14 and 20-24); (4) combinations of H-2RA + Indo; or (5) combinations of H-2RA + Indo + IL-2. Animals were killed on day 24 for examination of primary s.c. tumor growth, secondary lung metastasis and splenocyte cytotoxicity against YAC-1 lymphoma cells (51Cr release assay). Results revealed: (1) primary tumor growth was reduced in mice treated with Fam + Indo, Indo + IL-2 and any of the H-2RA + Indo + IL-2 (no difference observed within the last two groups); (2) lung metastases decreased in mice treated with IL-2 alone, Indo + IL-2, and Indo + IL-2 + Ran-hi; (3) splenic cytotoxicity was suppressed in tumor-bearing controls, with partial restoration seen in Ran (both doses), Ran-lo + Indo, Ran-lo + Indo + IL-2, and Cim + Indo + IL-2 treated groups. Nearly complete restoration was seen in Cim, Cim + Indo, Indo + IL-2, Ran-hi + Indo + IL-2, and Fam + Indo + IL-2 groups. Thus, addition of H-2RA did not alter the overall therapeutic efficacy of the standard Indo + IL-2 tumor immunotherapy.
 ...
PMID:Effects of histamine type-2 receptor antagonists on indomethacin and IL-2 immunotherapy of metastasis. 809 42

Anti-CD3 x antitumor bispecific Ab can retarget T cell mediated lysis in an MHC-independent fashion and prevent tumor growth in animal models. Two bispecific Ab preparations that differ in the presence or absence of Fc were compared in the 38C13 immunocompetent murine lymphoma model to evaluate how functional Fc and T cell activation impact on response to bispecific Ab therapy. Bispecific (bs) IgG contained functional Fc and was purified from hybrid-hybridoma Ab product. Bsf(ab')2 lacked functional Fc, and was genetically constructed using the leucine zipper technique. In vitro, bsF(ab')2 induced tumor cell lysis by activated T cells more effectively than bsIgG. However, bsF(ab')2 failed to induce T cell activation in the absence of tumor cells, and did so more slowly than bsIgG when tumor cells were present. In vivo, bsIgG induced nonspecific T cell activation whereas bsF(ab')2 did not. In therapy experiments, bsIgG inhibited tumor growth in mice although a single dose of bsF(ab')2 had minimal antitumor effect. BsF(ab')2 was capable of preventing tumor growth and improving survival when mice were also treated with T cell activators (IL-2 or staphylococcal enterotoxin B), or given repeated bsF(ab')2 doses. We conclude that therapeutic response to bispecific Ab was not dependent on functional Fc, but did require T cell activation. The use of bifunctional constructs that lack functional Fc therefore allows for separate manipulation of T cell retargeting and T cell activation and deserves further evaluation as a potential immunotherapy for malignancy.
 ...
PMID:The role of T cell activation in anti-CD3 x antitumor bispecific antibody therapy. 813 49

Antitumor effects of interleukin-2 entrapped in liposomes (IL-2 liposomes) on Renca, murine renal cell carcinoma of spontaneous origin, were evaluated by in vivo and in vitro experiments. As a local treatment model, IL-2 liposomes at a dose of 1.0 x 10(4) units were for 7 days injected adjacent to the Renca tumors inoculated in the back of BALB/c mice. The treatment inhibited the tumor growth and prolonged the survival time of mice significantly compared to the control (p < 0.01). Serum IL-2 levels after subcutaneous administration of IL-2 liposomes confirmed its slow releasing mechanism into blood circulation. The spleen cells from mice following the IL-2 liposome treatment showed higher cytotoxicity in vitro than that of IL-2 alone using Renca, YAC-1, and P-815 cells, which was determined by 51Cr-release assay. Indirect immunoperoxidase staining of tumor-infiltrating lymphocytes (TILs) showed that accumulation of Lyt-2+ and L3T4+ cells were seen in the tumor treated with IL-2 liposomes. These results indicate that IL-2 liposomes have a long-acting cytotoxicity against renal cell carcinoma caused by a slow release mechanism generated through the efficient local immune response mediated by TILs.
 ...
PMID:Antitumor effect of interleukin-2 entrapped in liposomes on murine renal cell carcinoma. 818 79

Blood lymphocytes of cancer patients lysed autologous, freshly isolated tumor cells. The autologous tumor-killing (ATK) activity is strongly associated with postoperative clinical course, indicating that ATK is a meaningful prognostic indicator and provides evidence for immunological control of tumor growth and metastasis. Large granular lymphocytes (LGL) with ATK activity released a soluble cytotoxic factor(s), termed LGL-CF (LGL-derived cytotoxic factor) during interaction with autologous tumor cells. The cytotoxic factor lysed autologous and allogeneic freshly isolated human tumor cells, while they were resistant to any of recombinant cytokines, including tumor necrosis factor (TNF), lymphotoxin (LT), interferon (IFN) alpha, IFN gamma, interleukin (IL)-1 alpha and IL-2. Biological activity of LGL-CF was not abrogated by monoclonal and polyclonal antibodies against these cytokines. LGL-CF also exhibited lysis of a variety of tumor cell lines, but not of nonmalignant cells. Actinomycin D augmented the lysis of LGL-CF. LGL-CF was stable at 56 degrees C, but was destroyed at 100 degrees C. Treatment of LGL-CF with trypsin or proteinase K reduced or abrogated the lytic effect, respectively, while it was resistant to papain, catalase, and superoxide dismutase. These results indicate that LGL produce a novel cytotoxic factor in response to autologous tumor cells that mediates lysis of fresh human tumor cells.
 ...
PMID:Role of NK cell cytotoxic factor against fresh human tumors. 825 31

The state of the art with regard to the employment of various cytokine-based tumor immunotherapy strategies and their mechanisms of action are critically reviewed. As matters now stand, adoptive transfer of LAK cells or tumor infiltrating lymphocytes together with high doses of IL-2 constitutes the only immunologic way to hinder tumor growth in advanced stages of cancer. On the other hand, many experimental data show that the local presence of cytokines, either injected repeatedly at tumor site or released by cytokine-gene engineered tumor cells, arouses immunogenicity in apparently nonimmunogenic spontaneous tumors. By strengthening the notion that most tumors are potentially immunogenic, these findings offer substantial evidence to stress the potential use of cytokines as a component of new tumor vaccines.
 ...
PMID:Strategies for cytokine utilisation in tumor therapy. 825 96

Interleukin-2 and hyperthermia have been used individually to treat a variety of tumors in both experimental and human trials. Combined adoptive immunotherapy and hyperthermia is an exciting new line of investigation. Previous work in our laboratory has shown that combined local hyperthermia and rIL-2 therapy can significantly decrease the rate of tumor growth. In this study, we investigated the effect of combined whole-body hyperthermia (WBHT) and rIL-2 on the growth of subcutaneous MCA-105 murine tumors in C57BL/6 mice. Treatment of both microscopic (day 3) and macroscopic (day 10) tumors was evaluated. In the treatment of microscopic tumors, animals received either no treatment; rIL-2 (3 x 10(5) IU ip tid) on days 3-7; plus WBHT (41 degrees C for 30 min) on days 3, 5, and 7; or WBHT only days 3, 5, and 7. In treating macroscopic tumors, animals received either no treatment; rIL-2 on days 10-14; plus WBHT on days 10, 12, and 14; or WBHT only on days 10, 12, and 14. While combined treatment and WBHT alone had no significant effect on the growth of microscopic tumors, combined IL-2 and WBHT significantly reduced the rate of tumor growth of macroscopic tumors. These results suggest that the tumor microenvironment plays a critical role in combined WBHT and rIL-2 therapy, and may be due to effects of WBHT on the tumor vasculature.
 ...
PMID:Immunotherapy and whole-body hyperthermia as combined modality treatment of a subcutaneous murine sarcoma. 833 40

The feedsideward phenomenon is the interaction of three or more rhythmic physiological entities by a diversified spectrum of rhythms that constitute a rhythmic network. These rhythmic units are: a) the modulator, b) the actor, c) the reactor and d) the integrative unity. Rhythmic interactions are characterized by an alternating sequence of algorithmically predictable effects of attenuation, no effect, and stimulation occurring in different frequencies. The basis of this phenomenon was determined from experimental evidence derived from cephalo-adrenal ex vivo studies. Internal phase-shift studies allow the demonstration ex vivo of a collateral hierarchy of rhythmic neuro-endocrine interactions as alpha, beta, gamma and delta rhythms. Linear least squares analyses describe and quantify circadian (alpha, beta and gamma) and infradian (delta) rhythms in the original series and the differences in responses [beta-alpha] and [gamma-delta]. These spontaneous and response rhythms reveal a collateral neuro-endocrine hierarchy and validate a pineal feedsideward phenomenon. Circadian-infradian murine rhythmic intermodulations are demonstrated in the epithelial corneal mitosis; brain neurosteroids and pineal melatonin content. A circadian rhythm in pineal melatonin content in female B6D2F1 mice and the chronomodulating action of melatonin + ACTH upon adrenal corticosterone production are confirmed. A chronopilot ex vivo study "suggests" that melatonin chronomodulates mouse aldosterone production. In a second chronopilot study, HrIL-2 chronomodulates rat corticosterone production ex vivo. Feedsidewards in vivo were seen in the chronomodulation of tumor-host balance occurring after melatonin, IL-2, cefodizime, and cyclosporine treatments that enhanced or delayed tumor growth and survival time of tumor-bearing mice.
 ...
PMID:The feedsideward of cephalo-adrenal immune interactions. 835 98

Late tumor bearers (LTB), that is, mice that had tumors 3 weeks or longer, can have a selective immune dysfunction and fail to respond to target antigens expressed by the cancer cells. Such mice, however, do respond to nonmalignant cells engineered to express the rejection antigen, and they can be vaccinated with such cells to reject growing tumors. In this study, we compared the efficacy of passive immunization with that of active immunization using the engineered vaccine. An allogeneic MHC class I molecule was used as model tumor antigen. We found that active immunotherapy was only effective for small tumors in early stages of growth. In a later stage of tumor growth, active immunotherapy did not cure any mice, whereas passive immunotherapy was successful in all animals. Reasons for the failure of these LTB to respond to active vaccination with the engineered vaccine may be related to the decreased primary or secondary response we observed in these mice after active immunization. It is suggested that normal antigen-presenting cells expressing the tumor rejection antigen can elicit, in the presence of IL-2, antigen-specific T-cell responses by LTB, and that such T cells may be curative when used in adoptive therapy. We also suggest that the stage of tumor growth and the immune status of LTB more closely simulate the conditions observed in cancer patients.
 ...
PMID:Genetically engineered vaccines. Comparison of active versus passive immunotherapy against solid tumors. 836 42

We investigated the ability of bispecific anti-T-cell receptor x anti-tumor antibodies, destined for the study of T-cell retargeting in a rat colon carcinoma model, to enhance tumor neutralization by polyclonally activated CD8+ T lymphocytes in hepatic subcapsular Winn type assays against syngeneic CC531 colon carcinoma cells. Attempts to improve on initially unsatisfactory results were guided by a 3-day in vitro cocultivation assay, demonstrating that recombinant IL-2 (rIL-2) at concentrations as low as 1 U/ml would promote tumor neutralization by retargeted effector cells. Accordingly, we found that a nontoxic regimen of rIL-2 administration, 200,000 U subcutaneously every 8 h for 3 days, strongly enhanced natural killer-like as well as retargeted anti-tumor activity in Winn assays and enabled retargeted effector cells to prevent tumor growth in the majority of animals. These results back up and direct future attempts to treat established tumor lesions.
 ...
PMID:T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model: IV. Tumor neutralization in Winn type assays. 839 65

Transfection of tumor cells with a vector containing the entire coding sequence of human interleukin-2 (hIL-2) was previously shown to convert the tumorigenic murine fibrosarcoma line CMS-5 into a non-tumorigenic line. The failure of the IL-2-secreting tumor to grow in conventional (immunocompetent) mice was attributed to the activation of CD8+ T cells that exhibited tumor specificity and memory. In order to determine whether or not the IL-2 produced by the tumor may be activating tumor cytotoxic effector cells other than B or T cells we have repeated this study using immunodeficient SCID and SCID-beige mice as syngeneic tumor recipients. In contrast to the rapid growth of the wild-type tumor, the hIL-2-transfected cells (N2A/IL2/CMS5) did not grow, or grew more slowly and regressed, in the mice that lack functional B and T cells. The inhibition of tumor growth associated with the local release of IL-2 was reversed in mice treated with antiasialo-GM1 antibodies specific for natural killer (NK) lineage cells. In contrast to the studies with conventional mice, the IL-2-dependent effector cells in the immunodeficient mice exhibited no evidence of memory. In vitro analysis of spleen cells from tumor-bearing mice revealed the presence of effector cells able to lyse YAC-1 target cells as well as the wild-type CMS-5 and the IL-2-transfected variant tumor lines but unable to lyse P815 cells. The pattern of selective target cell killing and the kinetics of killing were indistinguishable from those observed using tumor necrosis factor alpha (TNF alpha) the mediator associated with natural cytotoxicity cell killing of tumor cells. Histopathology of the IL-2-secreting tumors in SCID mice reveals the presence of infiltrating lymphoid cells and macrophages that were not observed in the CMS-5 tumors. Consistent with the notion that the tumor killing in the SCID mice was mediated by TNF alpha, mice bearing IL-2-secreting tumors had elevated levels of serum TNF alpha and little or no effector cell activity, or TNF alpha was found in tumor-bearing mice treated with anti-asialo-GM1 antibody. The results indicate that the cytokine-induced tumor regression observed in the IL-2-transfected tumors is a more complex phenomenon than previously recognized and one that is mediated by effector cells of the NK cell and/or monocyte/macrophage lineages, in addition to CD8+ T cells.
 ...
PMID:Antitumor response independent of functional B or T lymphocytes induced by the local and sustained release of interleukin-2 by the tumor cells. 850 Jan 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>