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

The tumoricidal properties of an anti-human colon carcinoma monoclonal antibody (MAb), designated D612 (IgG2a), alone and in combination with IL-2-activated human lymphocytes were investigated in athymic mice bearing LS-174T colon tumor xenografts. Treatment of mice bearing LS-174T tumors (1 day, s.c.) with a single i.v. dose of 400 micrograms of D612 alone resulted in a significant inhibition of tumor growth. Lower doses of D612 had an intermediate effect on tumor growth. Similar inhibition of tumor growth was obtained when D612 was administered in three doses of 400 or 800 micrograms each during the first week after tumor implantation. Mouse macrophages but not splenocytes mediated antibody-dependent cellular cytotoxicity with D612, suggesting that tumor inhibition was due to the participation of host macrophages with D612. Human lymphokine-activated killer (LAK) cells were generated by incubating human peripheral blood mononuclear cells (PBLs) from normal donors with 100 U/ml of IL-2 for 24 h. An administration of human LAK cells did not significantly inhibit the growth of the human xenograft tumor. Adoptive transfer of a single dose of human LAK cells (2 x 10(7), i.v.) into mice treated with a suboptimal dose of D612 (200 micrograms) significantly inhibited tumor growth compared to that obtained with either D612 or LAK cells alone. Similar results were obtained with three doses of D612 plus human LAK cells although there was a tendency for multiple doses of LAK cells alone to show some antitumor effects. LAK cells or PBLs had similar antitumor activities when used in conjunction with D612. When larger established tumors were treated, single or multiple doses of D612 or LAK cells alone were without effect; however, LAK cells plus D612 elicited significant growth inhibition. These results demonstrate that the tumoricidal properties of LAK cells and the D612 MAb can be augmented when used together in the immunotherapy of human colon cancer xenografts.
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PMID:Human lymphokine-activated killer cells augment immunotherapy of human colon carcinoma xenografts with monoclonal antibody D612. 201 97

Specific antitumor effects of lymphokine-activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of IL-2 were studied. Inbred C57BL/6 mice bearing syngeneic tumor (B16,3LL) were used. After intratumoral consecutive injection of recombinant human IL-2 (rhIL-2), the splenocytes of these mice were cultured with rhIL-2 and the effector cells were obtained. Specific antitumor effects of the effector cells against B16 and 3LL were studied in vitro and in vivo. Surface antigens of them were also analysed. The results were as follows: 1) 51Cr-release test under coculture with rhIL-2 showed that cytotoxicity against the host tumor cells with the effector cells became specifically augmented. 2) Winn assay showed specific inhibition of the host tumor growth with the effector cells. 3) Adoptive transfer of te effector cells specifically diminished the size of the host tumor and prolonged the life span of the mice. 4) The lymphokine-activated lymphocytes obtained from normal and non-treated tumor-bearing mice had no specific antitumor effect. 5) The analysis of the surface antigens indicated that Thy1.2+L3T4+ T cells increased in the effector cells as the specific cytotoxicity of them were augmented, while in the effector cells from normal and non-treated tumor-bearing mice, Thy1.2+L3T4+ T cells decreased and Thy1.2+Lyt2+ T cells increased.
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PMID:[Specific antitumor effect of lymphokine-activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of interleukin-2 (IL-2)]. 205 76

Lymphokine-activated killer (LAK) cells were generated from splenocytes of rats bearing a weakly immunogenic Dunning prostate tumor (R-3227 AT-3) and activated with recombinant interleukin-2 (rIL-2). The maximal LAK activity was obtained from splenocytes of rats bearing tumors for 10 to 14 days after incubation with 1000 U/ml./day of rIL-2 for five to eight days. The majority of these LAK cells expressed high levels of asialo GM1 (89%), laminin (83%), OX-19 (80%) and OX-8 (88%) surface markers. LAK cells exhibited higher cytotoxicity to rat prostate tumor cells and mouse lymphoma in vitro than to other non-prostate tumor cells or normal rat splenocytes and thymocytes. Splenocytes of rats bearing prostate tumors have higher LAK activity than normal splenocytes. The Winn type assay showed that Dunning prostate tumor growth was inhibited effectively by LAK cells at a tumor cell:LAK cell ratio of 1:50. The therapeutic efficacy of LAK cells in the treatment of primary solid prostate tumors and pulmonary metastases of Dunning rats was evaluated. LAK cells in combination with rIL-2 showed a greater therapeutic benefit in 1) prevention of prostate tumor metastases to lung, 2) retardation of the primary tumor growth, 3) regression of spontaneously established pulmonary metastases, and 4) prolongation of survival as compared to untreated controls or those groups treated with LAK cells or rIL-2 alone. The results of this study indicate that the conjunctive therapeutic approach of using surgical therapy to remove primary solid tumors followed by adoptive immunotherapy with LAK cells plus in vivo administration of IL-2 may be potentially valuable in the treatment of prostate tumors, particularly for the spontaneous pulmonary metastases.
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PMID:Adoptive immunotherapy using lymphokine-activated killer cells and recombinant interleukin-2 in preventing and treating spontaneous pulmonary metastases of syngeneic Dunning rat prostate tumor. 205 87

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over ten years. Although the antitumor mechanism of PSK is not fully understood, host-mediated antitumor activity has been claimed to play a significant role. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. To clarify the potential immunomodulating activities of PSK, we examined the direct effect of PSK on cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC) in vitro. As determined by Northern blotting, PSK was a potent inducer of gene expression for IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha) and monocyte chemotactic and activating factor (MCAF), but not for IL-2 and lymphotoxin (LT). Expression of mRNA occurred at 1-3 hr in a dose dependent manner using from 5-400 micrograms/ml of PSK. Furthermore, these cytokines were also produced in response to PSK as detected by ELISA, RIA or bioassays. We speculate that these cytokines may mediate immunoenhancing actions of PSK in vivo.
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PMID:Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. 209 Aug 74

Meth A sarcoma, growing in the subcutaneous tissue of syngeneic BALB/c mice, regressed completely after an intraperitoneal (ip) injection of proteose peptone (PP) (on day 6) followed by 2 ip administrations (on days 7 and 8) of human recombinant interleukin-2 (IL-2, 25 micrograms/day), whereas one such treatment alone had little effect on the tumor growth. While this combination treatment was effective in anti-asialo GM1 antibody-treated mice, no such effect was noted in T cell-depleted ATXFL (thymectomized, irradiated and fetal liver cell-reconstituted) mice. These results show that T cells are mainly responsible for this antitumor effect. Treatment with a combination of PP and IL-2, but not with either PP or IL-2 alone, resulted in a marked increase in the T cell population in the peritoneal cavity after the treatment. At an early stage after the combination treatment, both peritoneal exudate cells (PEC) and spleen cells exhibited killing activity with a promiscuous specificity. However, at a later stage, 7 days after the treatment, Meth A-specific killer activity was observed in both PEC and the spleen. Meth A rechallenge was rejected by the mice in which the tumor had regressed, but the antigenically different Meth 1 was accepted by them. A similar result was obtained in Winn's neutralization test. These results suggest that this combination treatment, which is effective in the generation of lymphokine-activated killer cells in the peritoneal cavity, finally resulted in the induction of tumor-specific killer cells in the periphery. These results clearly show the anti-tumor efficacy of combination treatment with PP and rIL-2.
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PMID:Combination treatment with irritant and recombinant interleukin 2 in the peritoneal cavity for evoking effective anti-tumor activity: generation of lymphokine-activated killer cells and tumor-specific killer cells. 211 94

We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.
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PMID:Antitumor effect of combination of murine recombinant interferon beta, murine recombinant interferon gamma and human recombinant interleukin-2 in MethA-bearing mice. 212 86

The autologous mixed lymphocyte reaction (AMLR) is an in vitro measure of autoreactivity, a key mechanism in immune homeostasis. In this system, macrophages (M phi) act as accessory cells to autoreactive L3T4+ T cells by presenting self-Ia and releasing soluble modulators. During tumor growth, changes occur in M phi and T cells. Tumor-bearing host (TBH) M phi have a reduced ability to act as accessory cells. In fact, TBH M phi suppressed autoreactivity by 60-70%. The decrease in TBH M phi or T-cell abilities was not due to differences in cell numbers or incubation time. Because tumor growth causes increased prostaglandin E2 (PGE2) production by M phi, indomethacin was used to assess the contribution of prostaglandins. Normal and TBH T-cell reactivity increased nearly 50% when stimulated by normal host M phi, while normal and TBH T-cell reactivity increased nearly 100% when stimulated by TBH M phi. Thus increased prostaglandin production is partly responsible for the increased TBH suppressor M phi activity and in the normal host, suppressor M phi may be responsible for maintaining immune regulation. To assess the direct role of prostaglandins in T-cell hyporesponsiveness, PGE2 was titrated into the cultures. PGE2 suppressed normal and TBH T-cell responsiveness in a dose-dependent manner. Normal host T cells were suppressed to a greater extent than TBH T cells by PGE2 (66% versus 42% suppression, respectively). Reduced Ia expression and active suppressor mechanisms are not the only mechanisms mediating hypoautoreactivity during tumor growth. TBH autoreactive L3T4+ T cells were less responsive to self-Ia; they were only 60-80% as reactive as their normal counterparts. To address whether the helper T (TH)-cell defect involved cytokines, T cells were treated with interleukin (IL)-1, IL-2, and IL-4. In all cases, the TBH T-cell response to the factors was decreased (only 60-75% as reactive as normal T cells). Because TBH M phi-mediated suppression can override the addition of IL-1, IL-2, and IL-4, indomethacin was also added with the exogenous interleukins. This coaddition significantly enhanced normal host autoreactivity above control levels while TBH autoreactivity (the combination of TBH T cells and TBH M phi) only returned to normal host unstimulated levels. Tumor growth modulates the immune response at least by (i) decreasing the accessory cell abilities of TBH M phi through decreased Ia expression and increased production of suppressive molecules such as prostaglandins; and (ii) decreasing the responsiveness to immune enhancing factors by TH cells.
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PMID:Tumor modulation of autoreactivity: decreased macrophage and autoreactive T cell interactions. 213 15

Various strategies for local immunotherapy performed by using lymphokines and lymphocytes are presented. In experimental mice models, the antitumor reaction elicited through the injection of little amounts of IL-2 and gamma-IFN at the tumor growth site is significantly enhanced by the concurrence of lymphocytes from tumor bearing mice artificially admixed to challenging tumor cells. These lymphocytes act as initiator or helper cells that elicit both a local and a systemic long lasting immune reaction by the release of additional lymphokines. The reaction activated mostly involves draining lymph nodes, where multiple reaction mechanisms are induced. The local injection of cocktails of molecularly defined lymphokines can also mimic the helper action of lymphocytes and trigger a similarly effective anti-tumor reaction. A set of pilot clinical trials with IL-2 or gamma-IFN injected perilymphatically were initiated in patients with advanced primary or recurrent localized tumors of the head and neck and the bladder. This treatment appears to elicit a local reaction by activating a few pathways of patients immunoreactivity, whose efficiency may well be high, as shown by the tumor inhibition often observed.
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PMID:Perilymphatic injections of cytokines: a new tool in active cancer immunotherapy. Experimental rationale and clinical findings. 215 Nov 8

Beside their therapeutic effects, cytokines are involved in pathologies such as IL-6 in myeloma tumor growth and bone resorption, BCGF in the proliferation of hairy cell leukemic cells, IL-2 in the capillary leak syndrome. For biotherapy to develop, it is necessary to understand both the beneficial and the deletorious effects of cytokines.
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PMID:Pathophysiology of cytokines. 220 18

Our laboratory has previously reported that the adoptive transfer of highly purified lymphokine-activated killer cells (adherent-LAK, A-LAK) into Fischer 344 (F344) rats bearing established lung or liver micrometastases effectively reduced the resultant tumor growth more than 90%, leading to significant increases in animal survival (Cancer Res. 49, 1441, 1989). To begin to investigate the mechanism(s) by which A-LAK cells mediate this anti-tumor effect, we studied their migration patterns in F344 rats bearing experimentally induced lung and liver metastases as well as subcutaneous tumors. A-LAK cells which were phenotypically 95 to 100% natural killer cells/large granular lymphocytes were labeled with either 51Chromium or fluorescein diacetate (so as to be visualized microscopically). Intravenous injection of such labeled A-LAK cells did not show significant differences in their tissue distribution patterns in tumor-bearing versus normal rats, even when high levels of exogenous recombinant interleukin-2 (rIL-2) was administered. A-LAK cells first migrated to the lungs and then subsequently migrated to the liver and spleen as early as 2 to 6 hr following iv injection. The kinetics of exit of A-LAK cells from the pulmonary capillary beds was not significantly different in rats bearing 3-day micrometastases or 14-day macrometastases compared to normal rats. Moreover, the presence of metastases in the liver did not alter the extent or kinetics of entry of A-LAK cells into the liver even in the presence of exogenously administered rIL-2. Finally, in rats bearing subcutaneous tumors, no evidence could be obtained that A-LAK cells were selectively localized to the tumor site. Tissue sections of livers from metastases-bearing animals injected with fluorescein diacetate labeled A-LAK cells did not demonstrate significant numbers of A-LAK cells infiltrating tumor nests with or without the administration of exogenous IL-2. These data suggest that A-LAK cells may mediate tumor regression in vivo by direct and indirect mechanisms, possibly through the secretion of cytokines and/or the recruitment of secondary effector cells.
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PMID:In vivo migration and tissue localization of highly purified lymphokine-activated killer cells (A-LAK cells) in tumor-bearing rats. 238 92


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