Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Splenic CD4+ T cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 2 to 3 wk after the inoculation with CSA1M cells produced IL-2 and macrophage-activating factor upon in vitro cultures. This lymphokine production was achieved without stimulation of these T cells with exogenous stimulating tumor Ag. However, elimination of APC from spleen cells resulted in almost complete abrogation of the capacity of CD4+ T cells to produce IL-2/macrophage-activating factor. The lymphokine production was regained when APC from CSA1M-bearing mice were added back to cultures. APC from normal or another syngeneic tumor (Meth A)-bearing mice failed to regain the lymphokine production. These observations demonstrated that the lymphokines were produced by CD4+ T cells from CSA1M-bearing hosts through their collaboration with APC binding CSA1M tumor Ag in the tumor-bearing state. The lymphokine-producing capacity of whole spleen cells from tumor-bearing mice reached the maximal level around 2 to 3 wk after tumor implantation but gradually decreased with the progress of tumor-bearing stages. Importantly, tumor-bearing stage-related changes were observed in a different fashion in the capacities of anti-CSA1M CD4+ T cells vs CSA1M tumor Ag-binding APC. The capacity of APC increased with the progress of tumor-bearing stages as demonstrated by the stimulation of CSA1M-immunized T cells with APC from different CSA1M-bearing stages. In contrast, the reactivity of anti-CSA1M T cells to APC from a given CSA1M-bearing stage decreased with the tumor-bearing stage. These results demonstrate a stage-related increase tumor Ag-binding APC function, as well as a reciprocal reduction in tumor Ag-responsive CD4+ T cell activity.
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PMID:Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity. 134 22

The aim of this study was to investigate the influence of oral administration of OK-432 on the tumor growth of tumor-bearing mice. In addition, the changing pattern of the splenic lymphocyte subsets of tumor-bearing mice was evaluated by flow cytometry. OK-432 at a dose of 0.1, 1 or 10 KE was administered orally every 3 days or every other day for 30 days to subcutaneously Meth A tumor-inoculated mice. The tumor growth was significantly inhibited in the 1 KE every 3 days group, in the 1 KE every other day group and in the 10 KE every 3 days group. In the 10 KE every other day group, OK-432 inhibited the tumor growth on days 10 and 20, while the agent did not show a marked inhibitory effect on day 30. The percentages of splenic L3T4-positive cells and splenic asialo GM1-positive cells were significantly increased in the 1 KE every other day group, while the Lyt2+/Thy1.2+ ratio was decreased. On the other hand, in the 10 KE every other day group, OK-432 showed no effect on the percentages of splenic L3T4-positive cells and Lyt2+/Thy1.2+ ratio on days 20 and 30. Our results suggest that the antitumor effect of oral administration of OK-432 may be correlated with the changing pattern of L3T4-positive cells and Lyt2+/Thy1.2+ ratio.
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PMID:The changing pattern of the splenic lymphocyte subsets in tumor-bearing mice after oral treatment with OK-432. 135 56

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.
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PMID:Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy. 137 28

MY-1, which consists of DNA and RNA extracted and purified from Mycobacterium bovis strain BCG, causes the regression of various experimental syngeneic tumors when injected intratumorally. In order to identify the host cells involved in the antitumor mechanism(s) of MY-1, we examined Meth A tumors inoculated intradermally to BALB/c mice, which were given multiple injections of MY-1 following tumor inoculation. Histological and immunohistochemical examinations were performed at several time points. On day 4 after inoculation, the MY-1-treated tumors were heavily infiltrated with a heterogeneous population of mononuclear cells with low density nuclei. The MY-1-injected tumors contained asialo-GM1-positive cells and Mac-1-positive cells, which indicated that the infiltrating mononuclear cells were natural killer cells and macrophages. On day 14 after inoculation, the tumors were infiltrated with a large number of L3T4-positive cells and fewer Lyt-2-positive cells, both of which were more abundant in the MY-1-treated tumors than in the control tumors. The observed sequence of host cell infiltration corresponded well with our previous studies which have indicated that the antitumor mechanism of MY-1 is divided into two phases, i.e. the early phase when natural killer cells and macrophages inhibit tumor growth, and the late phase when L3T4-positive cells act to induce tumor regression via a delayed-type hypersensitivity against tumor cells.
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PMID:Changes of host cell infiltration into Meth A fibrosarcoma tumor during the course of regression induced by injections of a BCG nucleic acid fraction. 138 Sep 50

Antitumor activity of Hypsizigus marmoreus, one of the most popular Japanese edible mushrooms, was investigated. The aqueous and methanol extracts were tested against allogeneic tumor, solid sarcoma 180 and syngeneic tumor, Meth A fibrosarcoma. The aqueous extract was highly active in inhibiting growth of solid sarcoma 180, but not as much for Meth A fibrosarcoma. Fractionation of antitumor substances of the aqueous extract isolated four polysaccharides. Chemical analysis revealed one of them to be beta-(1-3)-glucan with a remarkable inhibitory effect against tumor-growth of sarcoma 180.
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PMID:Antitumor activity of Hypsizigus marmoreus. I. Antitumor activity of extracts and polysaccharides. 139 18

Treatment of human carcinoma xenotransplants in athymic mice with recombinant human tumor necrosis factor (rh TNF) causes necrosis mainly in the central parts of the tumors, while peripheral sections remain mitotically active. As tumors are known to be supplied with adequate glucose exclusively in their periphery, the influence of the lack of glucose on the cytotoxic activity of rh TNF was studied. The absence of glucose enhanced the killing of tumor cell lines by rh TNF in tissue culture. Meth-A, a cell line known to be resistant to TNF in vitro but highly sensitive to it in vivo, was readily killed in tissue-culture medium lacking glucose. All non-transformed cell lines tested were found to be resistant to rh TNF, regardless of the presence or absence of glucose. In tumor-bearing mice a reduction of the blood glucose content augmented by insulin led to increased anti-tumor efficiency of rh TNF. The enhanced anti-tumor activity was reflected both in histological sections of the tumor xenotransplants, by extensive central necroses, and by reduction of the tumor volumes.
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PMID:Glucose depletion enhances the anti-tumor effect of TNF. 139 14

Biologically active mutant p53 from Balb/c mouse tumor cells (Meth A) was analysed for its specific interaction with DNA. Restricted phage lambda DNA, representing DNA of high complexity with regard to sequence and secondary structure, was used to probe for such an activity in a target-bound DNA-binding assay, using doubly immunopurified p53. A single lambda DNA fragment was specifically retained with very high affinity (KD = 10(-10) M). Specific DNA binding was shown to be an intrinsic property of p53, as it could be blocked with p53-specific monoclonal antibodies PAb122 and PAb421. The characteristics of the DNA binding of p53 to this lambda DNA fragment, as well as the structural properties of this fragment, suggested the possibility that p53 might be able to interact with nuclear matrix attachment region (MAR) DNA. Indeed, established genomic MAR elements were specifically bound by Meth A p53, whereas no binding was observed to an AT-rich control DNA. The interaction of p53 with MAR elements in vitro is compatible with the idea that p53 in vivo is involved in the regulation of replication and/or expression of cellular DNA. Complex DNA interactions were not restricted to mutant p53 from Meth A cells. Mutant p53 of a different conformational phenotype (PAb246+ 'wild-type' as opposed to PAb246- 'mutant' for p53 from Meth A cells) from minimally transformed T3T3 cells, as well as genotypic wild-type p53 expressed by a recombinant baculovirus in insect cells, exhibited similar DNA-binding properties.
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PMID:Specific and complex interactions of murine p53 with DNA. 140 33

We have previously reported that 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), a derivative of 5-fluorouridine (5-FUR), and 1-(6-[N-(2-n-propyl-n-pentanoyl)-glycyl]amino-n-hexylcarbamoyl)-5- fluorouracil (UK-25), a derivative of 5-fluorouracil (5-FU), exert their antitumor activity in mice bearing Meth A or EL4 tumor, while their immunosuppressive effects are mild. In the present study, we examined the effects of these compounds on Sarcoma-180 (S-180), P388, L1210, and Lewis lung carcinoma (LLC) in mice by p.o. administration and i.p.-administration. UK-21 given p.o. showed an antitumor effect against S-180, but it showed virtually no antitumor effects against P388, L1210 and LLC. UK-21 given i.p., on the other hand, strongly inhibited the growth of Meth A tumor at a far lower dose than that for oral administration. The bioavailability of UK-21 given p.o. was suspected to be poor. UK-25 given p.o., in contrast, showed the antitumor effect on all of the tumors employed. The bioavailability of UK-25 given p.o. seemed to be comparable to those of other drugs. These results suggest that UK-21 has the potential for development as a parenterally applicable anticancer drug, and UK-25 has the potential as an oral one.
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PMID:Antitumor activity of two novel low immunosuppressive fluoropyrimidines UK-21 and UK-25. 143 42

We have previously reported that the lethal toxicity of 5-fluorouracil (5-FU) in specific-pathogen-free mice is due to an indigenous infection with Escherichia coli (K. Nomoto, T. Yokokura, Y. Yoshikai, et al. Can. J. Microbiol. 37:244-247, 1991). In the present study, we demonstrate that nonspecific immunostimulation augments host resistance against the lethal toxicity of 5-FU in tumor-bearing mice. Intravenous administration of a preparation of heat-killed Lactobacillus casei (LC 9018), a nonspecific immunostimulant, at a dose of 20 mg/kg to BALB/c mice augmented their resistance against the lethal toxicity of 5-FU if the preparation was injected into the mice 10-40 days before administration of 5-FU. Injection of LC 9018 into BALB/c mice bearing Meth A fibrosarcoma also enhanced their resistance against the lethality of 5-FU. Systemic infection with E. coli was induced in all of the 5-FU-treated tumor-bearing mice 10 days or more after administration of the drug at a lethal dose of 500 mg/kg, and it was accompanied by an overgrowth of the bacteria in the intestine. Treatment of tumor-bearing mice with LC 9018 resulted in decreased rates of occurrence of systemic infection with E. coli and inhibition of overgrowth of the bacteria in the intestine after administration of 5-FU. A single administration of either LC 9018 or 5-FU significantly inhibited the growth of Meth A cells in vivo, and a combined antitumor effect was shown in the mice treated with both 5-FU and LC 9018.
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PMID:Prevention of 5-fluorouracil-induced infection with indigenous Escherichia coli in tumor-bearing mice by nonspecific immunostimulation. 145 70

The combined effects of the synthetic glucosaminylmuramyl dipeptide (GMDP) on the antitumor activity of chemically synthesized lipid A analogs, compound A-103 (glucosamine-4-phosphate with (R)-3-tetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), Escherichia coli-type lipid A (506), Salmonella typhimurium LT-2 lipopolysaccharide (LPS) against Meth A fibrosarcoma in mice were examined. Meth A fibrosarcoma cells (5 x 10(5) were inoculated intradermally into BALB/c mice on day 0, and compound A-103 and/or GMDP was administered intravenously (i.v.) on days 7 and 9. Two i.v. injections of A-103 (50 micrograms) alone or GMDP (10 micrograms) alone induced 42.8 or 51.8% inhibition of the rate of tumor growth, however, A-103 (100 micrograms) with GMDP (10 micrograms) exhibited a high 68.7% inhibition rate 19 days after tumor inoculation. The inhibition of the tumor growth rate by the combination A-103 (100 micrograms) or 506 (50 micrograms) with GMDP (10 micrograms) was stronger than that of A-103 or 506 with MDP (10 micrograms). The combination of LPS (1 or 10 micrograms) with GMDP (10 micrograms) exhibited a higher inhibition rate than that of LPS with MDP, and three or four tumor-free mice out of five mice were observed, suggesting that the combined effect of GMDP is more potent than that of MDP. With the addition of GMDP, A-103 did not enhance the production of tumor necrosis factor (TNF) on the basis of L929 cell lysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combined effects of synthetic lipid A analogs or bacterial lipopolysaccharide with glucosaminylmuramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice. 146 73


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