Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of angiostatic steroids on pulmonary metastasis was investigated using mice treated with such a steroid before or after intravenous inoculation with Lewis lung carcinoma; cortisone acetate and tetrahydro S, of which the former possesses glucocorticoid activity, and the latter lacks it, were used as the angiostatic steroids. In the presence of heparin, both types of steroids prevented angiogenesis in chick embryo and also pulmonary metastasis in mice when the administration started after cell lodgement. On the other hand, one-shot cortisone treatment before cell inoculation increased the weight of lung colonies to twice that seen in the controls, while tetrahydro S pretreatment did not enhance metastasis. These results revealed that both angiostatic steroids with and without glucocorticoid activity in the presence of heparin inhibited tumor growth in the lungs, and further indicated that cortisone acetate affected the steps of metastasis after the invasion of tumor cells into the blood stream until angiogenesis in the secondary foci, and consequently promoted metastasis, whereas tetrahydro S (which has no glucocorticoid activity) did not affect the steps before angiogenesis. It was thus indicated that the inhibitory effect of angiostatic steroids against tumor growth due to an anti-angiogenic activity was not dependent at all on the metastasis promotion by these steroids having glucocorticoid activity.
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PMID:Effect of angiostatic steroid with or without glucocorticoid activity on metastasis. 244 51

We have used several transplantable experimental murine tumors to evaluate the potentiation of antitumor activity by a combination of human recombinant interleukin 2 (rHIL2) and recombinant interferons (rIFNs). The combination of rHIL2 and either human hybrid recombinant alpha-interferon A/D (rIFN-alpha A/D) or mouse recombinant beta-interferon (rIFN-beta) induced the s.c. adenocarcinoma 755, which had been established for 8 days, to regress, although rHIL2 or the rIFNs alone hardly inhibited the tumor's growth. Eight injections of the rHIL2-rIFN-alpha A/D combination cured 38% of the tumor-bearing mice. The rHIL2-rIFN-beta combination achieved a complete cure only when given in more than 13 injections. The administration of rHIL2 and mouse recombinant gamma-interferon (rIFN-gamma) markedly inhibited tumor growth of the s.c. established adenocarcinoma 755, but did not cure any of the mice. Other tumors, B16-F10 melanoma, and colon tumors 38 and 26 responded almost as well to a rHIL2-rIFN-alpha A/D or -beta combination, but not to a rHIL2-rIFN-gamma combination. The growth of Lewis lung carcinoma was inhibited to a lesser extent by all combinations, for which there were no long-term survivors. The combination therapy of rHIL2 and rIFN-beta produced a marked regression of the tumor in beige mice which have low natural killer activity, suggesting the activated natural killer cells not to be responsible for the therapeutic effect. And T-cell immunity may be important in the regression of s.c. established tumors, because of the lesser potentiation of antitumor activity in athymic mice. These results demonstrate that combination therapies of rHIL2 and rIFN-alpha A/D or -beta can function synergistically in the various s.c. established murine tumor systems and give further evidence in support of their clinical potential.
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PMID:In vivo antitumor activity of multiple injections of recombinant interleukin 2, alone and in combination with three different types of recombinant interferon, on various syngeneic murine tumors. 244 44

It has previously been demonstrated that decarboxylation of ornithine in tumors, and the oxidative splitting of N1-acetylspermidine in tumor and normal tissues, are important sources of putrescine. Both these sources are utilised by tumors and other tissues with a high demand for polyamines to ensure their polyamine requirement. Consequently, combined treatment of tumor-bearing animals with an inhibitor of ornithine decarboxylase (e.g. alpha-difluoromethylornithine) and polyamine oxidase (e.g. N,N'- bis-allenylputrescine) has an antitumoral effect superior to that of either drug alone. In the present work, it was demonstrated that the alimentary tract is a third important source of polyamines which maintains tumor growth. Gastrointestinal polyamines are of alimentary origin, and are also formed by aerobic and anaerobic microorganisms. They can be reduced by feeding a polyamine deficient diet together with antibiotics that are suitable for decontaminating the gastrointestinal tract. This treatment combined with the administration of the mentioned inhibitors of ornithine decarboxylase and polyamine oxidase completely prevents Lewis lung carcinoma from growing, and prolongs considerably the average life span of L1210 leukemia mice. The results of the polyamine analyses of tumors, leukemia cells and tissues are compatible with the notion that the effective blocking of the three main putrescine sources (intracellular decarboxylation of ornithine, formation of putrescine from N1-acetylspermidine, and the gastrointestinal tract) produces a very strong cytostatic effect. It is expected that the clinical efficacy of polyamine antimetabolites can be considerably improved by measures analogous to those applied in this pilot study.
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PMID:The gastrointestinal tract as polyamine source for tumor growth. 249 54

Creation of an amino acid imbalance, particularly curtailment of L-methionine, at the tumor cell level is thought to have a favorable effect on the inhibition of tumor growth. In the present study, we examined the influence of a specially-formulated amino acid mixture, avoid of sulfur-containing amino acids (L-methionine and L-cysteine), on the growth and amino acid fraction of Sato lung carcinoma (SLC) and the host metabolism in SLC-bearing rats. The rats were treated by total parenteral nutrition containing the above amino acid mixture, plus other nutrients (methionine-deprived TPN) for 10 days. Tumor growth began to decrease 4 days after the start of this treatment and the size was significantly less at the end of the treatment than in rats receiving conventional TPN with general purpose Vuj-N type amino acid solution as a protein source. The tumor-to-carcass weight ratio also showed a similar trend. In biochemistry, the albumin level and albumin-to-globulin ratio were significantly lower than in the rats receiving conventional TPN but other parameters such as total protein, glucose, GOT and GPT were not affected by the treatment. In the amino acid fraction of the tumor tissue extraction, both L-methionine and L-tyrosine were decreased and L-serine was increased significantly compared with the control group.
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PMID:Influence of L-methionine-deprived total parenteral nutrition on the tumor tissue and plasma amino acids fraction and the host metabolism: experimental study with Sato lung carcinoma-bearing rats. 249 79

We have previously established that type I interferon (IFN), a mixture of alpha- and beta-IFN, augments the antitumor activity of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, against B16 melanoma. The objective of the present investigation was to extend these earlier observations to metastatic Lewis lung carcinoma and to determine specifically which component(s) of type I IFN potentiates the antitumor activity of DFMO. Furthermore, we wanted to determine whether type II (gamma) IFN can also potentiate the antitumor activity of DFMO. Treatment of animals bearing Lewis lung carcinoma with DFMO, 2% in drinking water (3 g/kg/day), or IFN-alpha/beta (1000 units/mouse) given subcutaneously on alternate days for a total of ten doses alone resulted in 42 and 5% inhibition of tumor growth, respectively. A combination of DFMO and interferon brought about complete elimination of tumors in 12 of the 18 animals, and 94% inhibition of tumor growth in the remainder. DFMO or type I IFN administered alone caused 94 and 26% inhibition of metastasis, respectively. Combination treatment with these two agents resulted in complete elimination of visible metastases. Treatment of mice bearing B16 melanoma with DFMO resulted in 81% inhibition of tumor growth compared to controls. The administration of interferons alone resulted in tumor growth inhibition of 15, 3, 1, and 43% for type I, alpha-, beta-, and gamma-interferons, respectively. Treatment of animals with combination of DFMO and various interferons resulted in inhibition of 94, 93, 86, and 94% of B16 tumor growth for type I, alpha-, beta-, and gamma-interferons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of murine alpha-, beta-, and gamma-interferons in combination with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on the tumor growth and metastasis of B16 melanoma and Lewis lung carcinoma in mice. 249 64

The antitumor properties of (E)-2-(fluoromethyl)dehydroornithine methyl ester (delta-MFMO-ME) and of (E)-2-(fluoromethyl)dehydroornithine ethyl ester (delta-MFMO-EE), the prodrugs of delta-MFMO, an irreversible inhibitor of mammalian L-ornithine decarboxylase (ODC) 14 times more potent than alpha-difluoromethylornithine (DFMO) and equipotent to (2R,5R)-6-heptyne-2,5-diamine (MAP) in vitro, have been investigated in L1210 leukemia- and Lewis lung carcinoma-bearing mice. The anticancer properties of these esters have been compared with those of DFMO and MAP as a function of the dose, the route of administration, and the stage of the lewis lung carcinoma development in mice. The two esters, administered i.p. shortly after cell inoculation at one-fifth the dose of DFMO, prolonged the survival of mice-bearing leukemia to the same extent as DFMO and MAP. When administered orally to leukemia-bearing mice the two esters were equipotent at prolonging survival. The methyl ester appears, however, to be slightly, but not significantly, more effective than the ethyl ester against leukemia when given i.p., maximum prolongation of the mice survival (79%) occurring at 0.5 g/kg methyl ester every 12 h. The two esters achieve at one-sixth to one-twelfth the dose, antitumor effects similar to DFMO in the Lewis lung carcinoma model, the ethyl ester being slightly, but not significantly, more effective than the methyl ester when administered orally. Moreover, the ethyl ester causes greater reduction of tumor growth than DFMO (P less than 0.05) and MAP (P less than 0.01) in this model. Inhibition of tumor growth is correlated with spermidine depletion and an increase of decarboxylated-S-adenosylmethionine, the aminopropyl donor in the spermidine and spermine synthase reactions. All ODC inhibitors, however, lose most of their antitumor properties when administered at late stage of Lewis lung carcinoma development. Finally, this study demonstrates the advantage of using prodrugs of delta-MFMO, an inhibitor of ODC, since they possess longer duration of action, higher potency, and in some cases better antitumor efficiency than the parent direct inhibitor of ODC. Moreover, and as already noticed for DFMO or MAP, no sign of overt toxicity is caused by the highest effective antitumor doses of the esters.
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PMID:Comparative antitumor properties in rodents of irreversible inhibitors of L-ornithine decarboxylase, used as such or as prodrugs. 250 Oct 26

Combination of an ip injection of Nocardia rubra cell wall skeleton (N-CWS) and 3 daily sc injections of human recombinant interleukin 2 (rIL 2) into C3H/HeN mice resulted not only in a significant increase in the number of peritoneal cells (PC) but also in a potent induction of their lymphokine-activated killer (LAK) activity, compared with results obtained with N-CWS or rIL 2 alone. The augmented LAK activity of PC was mediated by nonadherent, nonphagocytic, Thy-1.2+(-)- and asialo GM1+ cells. Nonadherent PC induced by an ip injection of N-CWS bound more 125I-labeled rIL 2 than did normal, nonadherent PC, and generated high LAK activity when cultured overnight with rIL 2. In contrast, normal, nonadherent PC responded only weakly to the overnight stimulation with rIL 2. The phenotype of N-CWS-induced PC with an elevated IL 2 responsiveness was Thy-1.2+(-)-, Lyt-1.1-, Lyt-2.1- and asialo GM1+, suggesting that the N-CWS-stimulated LAK precursors were derived mainly from the NK cell lineage. However, mature T cells may also be involved in this mechanism, because N-CWS failed to augment the IL 2 responsiveness of nonadherent PC in BALB/c nu/nu mice. Treatment of C57BL/6N mice bearing solid Lewis lung carcinoma (3LL) tumors with an intratumoral injection of N-CWS followed by 6 daily sc injections of rIL 2 resulted in the apparent suppression of tumor growth, while N-CWS or rIL 2 alone produced no such suppression. These results suggest that N-CWS augments the antitumor effect of rIL 2 by accumulating LAK precursors and elevating their responsiveness to rIL 2 at the injection site.
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PMID:Synergy of Nocardia rubra cell wall skeleton and interleukin 2 in the in vivo induction of murine lymphokine-activated killer cell activity. 251 71

The antitumor activity of calcium gluconate in combination with mitomycin C and 5-fluorouracil was examined against subcutaneously implanted Lewis lung carcinoma-bearing C57BL/6 mice. The mice were divided into four groups: group 1 received mitomycin C (2 mg/kg) and 5-fluorouracil (50 mg/kg) intraperitoneally once a week for four weeks beginning from the day after implantation of tumors, as well as calcium gluconate (155 mg/kg) twice a week for the same four weeks; group 2 received only mitomycin C and 5-fluorouracil; group 3 received only calcium gluconate; group 4 received a vehicle (physiological saline). Significantly enhanced inhibition of tumor growth was observed neither in a comparison between groups 3 and 4, nor in a comparison between groups 1 and 2 (expect on day 20 post implantation). Thus calcium gluconate given alone or in combination with antitumor agents hardly appeared to possess effective antitumor activity.
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PMID:Antitumor activity of calcium in combination with antitumor agents against Lewis lung carcinoma. 251 48

The human lung carcinoma H2981, was characterized as a preclinical model for evaluating immunoconjugates consisting of monoclonal antibody (MAb) L6 and drugs of the mitomycin (MMC) chemotype. The H2981 tumor, implanted subcutaneously in athymic, mice grew progressively in greater than 95% of recipients. Spontaneous regressions of established tumors were not observed. The administration of tolerated doses of MMC resulted in dose-dependent delays in tumor growth. The incidence of tumor regressions was low indicating the potential to observe increased efficacy with immunoconjugates. The antitumor effects of MMC were independent of the schedule and route of administration. MAb L6 delayed the outgrowth of tumors when administered 24 h after tumor implant. Antitumor activity was not observed when MAb L6 was administered to mice bearing established tumors. The efficacy of mixtures of MAb L6 and optimal doses of MMC was not significantly better than that of optimal doses of MMC given alone.
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PMID:Development of a human xenograft model for the evaluation of monoclonal antibody L6-mitomycin immunoconjugates. 251 72

The effects of a fish oil diet on the myelopoietic and immunological parameters of normal mice and of mice bearing metastatic Lewis lung carcinoma (LLC-C3) tumors were compared to the effects of a corn oil or a mixed-fat rodent chow diet. This was studied soon after tumor appearance, on Day 17, when immune suppression was mediated by prostaglandin E2 (PGE2)-producing suppressor cells, and late in tumor development, on Day 28 when immune suppression was associated with myelopoiesis and the appearance of bone marrow-derived suppressor cells whose activity was not dependent on PGE2. Feeding a fish oil diet from Days 10 to 17 of tumor growth partially restored splenic T-cell blastogenesis, reduced spleen cell secretion of PGE2, and alleviated splenic suppressor activity. When fed from Days 21 to 28 of tumor growth, a fish oil diet neither restored T-cell blastogenesis nor alleviated suppressor cell activity. The fish oil diet increased the frequency of myeloid progenitor cells in normal mice and in mice bearing small or large tumors. Concurrently, the fish oil diet stimulated the appearance of bone marrow-derived suppressor cells. When administered after the establishment of palpable primary tumors, a fish oil diet also increased the formation of pulmonary lung nodules. In contrast to the fish oil stimulation of myelopoiesis and the associated suppressor cells, feeding a corn oil diet to tumor-bearing mice during Days 21 to 28 after tumor implantation reduced myelopoiesis and the presence of the associated bone marrow suppressor cells. These data show that a fish oil diet can minimize the immune suppression in tumor bearers when suppression is mediated by PGE2-producing suppressor cells, but can also induce myelopoietic stimulation leading to the appearance of bone marrow-derived suppressor cells and increased tumor metastasis.
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PMID:Effects of fish oil and corn oil diets on prostaglandin-dependent and myelopoiesis-associated immune suppressor mechanisms of mice bearing metastatic Lewis lung carcinoma tumors. 252 13


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