Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DBA/2 (H-2d) mice bearing a transplanted highly metastatic lymphoma (ESb) in a state of widely disseminated disease could be successfully treated by a combination of surgery (removal of the local tumour), irradiation (5 Gy) and adoptive immunotherapy. The immunotherapy was achieved by transfer of anti-ESb-immune spleen cells from B10.D2 mice, which express the same major histocompatibility complex (MHC) molecules as DBA/2. In contrast, anti-ESb-immune cells from MHC-disparate C57BL/6 mice did not confer protective immunity. The B10.D2 anti-ESb-immune T cells contain two types of cytolytic specificity as detected by limiting-dilution analysis: (1) clones with specificity for the ESb-tumour-associated transplantation antigen (TATA) (at low frequency), and (b) clones with specificity for minor DBA/2 histocompatibility (H) antigens (at high frequency). Immune B10.D2 cells raised against different tumour lines or against TATA-ESb tumour variants did not confer the 100% protection seen with immune cells against ESb TATA+ cells. Finally we demonstrate that the allogeneic immune cells are more potent in terms of protective immunity than corresponding syngeneic immune cells. The data suggest that the strong graft-versus-leukemia effect with immune T cells from allogeneic MHC-identical but not from MHC-disparate mice was due to T cells with MHC-restricted specificity for an ESb-associated TATA. A graft-versus-host reactivity that developed much later and could not be prevented was most likely due to T cells sensitized against normal minor H antigens of the host. Our results are of potential relevance for allogeneic bone marrow transplantation and adoptive immunotherapy protocols.
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PMID:Specific eradication of micrometastases by transfer of tumour-immune T cells from major-histocompatibility-complex congenic mice. 182 94

The antitumor activity of the immunomodulator, Nocardia rubra cell wall skeleton (N-CWS), was investigated using syngeneically transplanted P388 leukemia cells in a solid form. The s.c. growth of P388 tumors in DBA/2 mice was significantly suppressed by systemically administered N-CWS, and the effect was dose dependent. The antitumor effect of N-CWS was partially but significantly abrogated in splenectomized mice but not in T-cell or natural killer cell-deficient mice. Although spleen cells from mice treated with 1600 micrograms N-CWS contained no cytolytic activity, they exerted a significant cytostatic effect on P388 cell growth both in vitro and in vivo. Splenic cytostatic activity did not reside in T- or natural killer cells, but in plastic adherent cell population, macrophages. The response to N-CWS immunotherapy appeared to be associated with the number of macrophages infiltrating into the tumor lesions, and this was confirmed by histological analysis showing that P388 tumors from N-CWS-treated mice were intensively and dominantly infiltrated by macrophages. Furthermore, these were shown to be strongly tumor necrosis factor-positive by immunohistochemical analysis. These findings indicate that macrophages are the main effector cells playing a critical role in the suppression of P388 tumor growth in DBA/2 mice, and that tumor necrosis factor produced by these cells may be involved in the macrophage-mediated cytostatic effect induced by N-CWS. The fact that N-CWS suppressed the growth of weakly immunogenic P388 cells in syngeneic DBA/2 mice even when it was systemically injected would support the clinical potential of this agent.
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PMID:Antitumor effect of Nocardia rubra cell wall skeleton on syngeneically transplanted P388 tumors. 185 18

Myeloproliferative syndrome was induced in adult DBA/2 mice by inoculation with myeloproliferative sarcoma virus (MPSV) and Friend murine leukemia virus (F-MuLV) as a helper virus. On day 26 after infection, the spleen weighed a maximum of 2.0 g (about 30 times the control weight). Assay of multipotent stem cells in vitro showed that the more enlarged spleens contained an increased number and concentration of mixed colony-forming units (CFU-mix) (at maximum, 11 times higher than the control). When the supernatant of cultured spleen cells was added to a serum-free bone marrow cell culture with or without erythropoietin (Epo) for detection of burst-promoting activity (BPA), it enhanced erythroid mixed colony (E-mix) formation only in the presence of Epo (p less than 0.05). Even when addition of Epo was delayed, it still induced a significant number of E-mix (p less than 0.05). These findings rule out a mimic effect of Epo resembling BPA and indicate the presence of BPA in the spleen. The culture supernatant also supported the proliferation of interleukin 3 (IL-3)-dependent 32Dcl cells. Therefore, although purification of the BPA substance has not yet been accomplished, BPA in the supernatant seems to depend on the presence of IL-3, which is known to be one of the factors stimulating multipotent hemopoietic stem cells. The presence of BPA- or CFU-mix-stimulating activity in the spleen after infection might be responsible for the development of panmyelosis, which is a characteristic of MPSV-induced myeloproliferative syndrome.
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PMID:Detection of burst-promoting activity in spleens of myeloproliferative sarcoma virus-infected mice using serum-free cultures. 186 6

D and L isomers of aspartic acid beta-hydroxamate (respectively DAH and LAH) were compared for their in vitro and in vivo activity against the murine leukemia L5178Y and their tolerance in vivo in DBA/2 mice. DAH and LAH displayed comparable cytotoxic activity against L5178Y leukemia in vitro. Death of leukemia cells was observed at concentrations above 1.2 mM for both DAH and LAH. High concentrations of L-asparagine partially reversed the growth-inhibitory effects of DAH and LAH on L5178Y cells for concentrations of DAH and LAH lower than 0.6 mM. Intraperitoneal administration of DAH and LAH to mice showed that the LD10, LD50 and LD90 of DAH was 3- to 4-fold greater for DAH than for LAH. DAH was able to eradicate L5178Y tumors in mice without inducing toxic deaths, whereas LAH at comparable doses killed all the animals treated.
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PMID:Anti-tumoral activity of L and D isomers of aspartic acid beta-hydroxamate on L5178Y leukemia. 191 41

We have implicated histamine as a mediator of proliferation through its binding to novel intracellular receptors (HIC), closely associated with antiestrogen binding sites (AEBS) in microsomes and nuclei. N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), is a potent ligand for AEBS/HIC. We now demonstrate that DPPE stimulates in vivo tumor growth (DMBA-induced mammary cancer in Sprague-Dawley rats and L5178Y leukemia in DBA/2 mice) and synergizes with phorbol-12-myristate-13-acetate (PMA) to induce inflammation and mitotic activity in mouse epidermis. Thus, ligands for intracellular histamine receptors may represent a new class of tumor promoting agents; this finding lends new credence to an important role for histamine in growth.
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PMID:Stimulation of in vivo tumor growth and phorbol ester-induced inflammation by N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine HCl, a potent ligand for intracellular histamine receptors. 193 Jan 76

We previously developed a mathematical model to describe the emergence and dynamic growth of a drug-resistant subpopulation in a tumor. In the present study, our objective was to test the model's ability to mimic two strategies for reversal of drug resistance. We present data from one in vitro cell proliferation assay with drug-resistant LS174T human colon carcinoma variants and one in vivo assay of survival after treatment of female (C57BL/6 x DBA/2)F1 mice inoculated with doxorubicin-resistant P388/ADR leukemia cells. The in vitro assay examined the effects of inhibiting the biosynthesis of glutathione in cells resistant to alkylating agents or cisplatin. The in vivo assay compared the effects on cell survival of low-level continuous infusion versus high-intensity bolus dosing, with or without coadministration of the drug efflux pump blocker verapamil. Results in vitro and in vivo were comparable for qualitative accuracy and predictability to results with the model. Both the in vitro study and the model showed that, for resistant cells with high levels of glutathione, short-term cell survival was dose dependent and that even high doses of drug did not eliminate all of these cells. Addition of an inhibitor of glutathione biosynthesis did, however, augment elimination of the resistant cells. Resistant cells with low levels of glutathione could be eliminated with high drug doses or coadministration of drug and a glutathione synthesis inhibitor. In vivo, coadministration of doxorubicin with verapamil increased animal survival when either continuous infusion or bolus dosing regimens were used. The effectiveness of the blocker is crucial; when a partially (50%) effective blocker is used, continuous infusion achieves better elimination of resistant cells, but a completely (100%) effective blocker is efficacious in both dosing scenarios. Careful interpretation of these findings is necessary because the pharmacokinetics of drug in the small populations of cells in the model are not easily extrapolated to those in large tumors. This model may be useful in determining resistance mechanisms, their levels of effectiveness, and concentrations of compounds required at target sites to overcome them.
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PMID:Drug resistance-reversal strategies: comparison of experimental data with model predictions. 196 Jul 54

The 3' half of the env gene of the dualtropic Friend mink cell focus-forming virus was modified by replacing the restriction enzyme fragment of the genome DNA with the corresponding fragment of the acutely leukemogenic, polycythemia-inducing strain of Friend spleen focus-forming virus (F-SFFVP) genome DNA. Replacement with the fragment of F-SFFVP env containing the 585-bp deletion, the 6-bp duplication, and the single-base insertion converted the resulting chimeric genome so that the mutant had a pathogenic activity like that of F-SFFVP. Replacement with the fragment containing only the 585-bp deletion did not result in a pathogenic virus. However, when this virus pseudotyped by Friend murine leukemia virus was passaged in newborn DBA/2 mice, we could recover weakly pathogenic viruses with a high frequency. Molecular analysis of the genome of the recovered virus revealed the presence of a single-base insertion in the same T5 stretch where the wild-type F-SFFV env has the single-base insertion. These results provided evidence that the unique genomic structures present in the 3' half of F-SFFV env are the sole determinants that distinguish the pathogenicity of F-SFFV from that of Friend mink cell focus-forming virus. The importance of the dualtropic env-specific sequence present in the 5' half of F-SFFV env for the pathogenic activity was evaluated by constructing a mutant F-SFFV genome in which this sequence was replaced by the ecotropic env sequence of Friend murine leukemia virus and by examining its pathogenicity. The results indicated that the dualtropic env-specific sequence was essential to pathogenic activity.
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PMID:Conversion of Friend mink cell focus-forming virus to Friend spleen focus-forming virus by modification of the 3' half of the env gene. 198 93

Geraniol, an acyclic end product of a plant isoprene pathway and a pyrophosphorylated intermediate in plant and animal pathways, caused a concentration-dependent increase in the population doubling time of murine P388 leukemia cells in suspension culture and of B16 melanoma cells in monolayer culture. The suppression of the growth of P388 cells by geraniol (0-0.9 mM) and by mevinolin (0-0.25 microM), a competitive inhibitor of mevalonate biosynthesis, was reversed by the addition of 0.5 mM mevalonolactone to the growth medium. Flow cytometry of asynchronous B16 cells grown with geraniol (0-0.15 mM) revealed a population characterized by larger cells with altered nuclear characteristics. Over the course of four studies, dietary geraniol increased the 50% survival time of mice by 10, 29, 33, and 50% following the i.p. transfer of P388 cells. The results of the latter study showed that, following the i.p. transfer of 1 x 10(5) P388 cells, the control group of female C57BL x DBA/2 F1 mice had a 50% survival time of 24 days and a maximum survival of 27 days. Mice fed a diet containing 0.1% geraniol for 14 days prior to and following the P388 cell transfer had a 50% survival time of 36 days, and 20% of the mice remained free of tumors during the 50-day trial. These studies support the possibility that monoterpenes and other isoprenoid products of plant metabolism are in part responsible for the anticarcinogenic actions of diverse fruits, vegetables, and cereal products.
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PMID:Concentration-dependent increase of murine P388 and B16 population doubling time by the acyclic monoterpene geraniol. 198 98

DBA/2 mice infected with lethal dosages of Friend virus complex (FVC) can be 100% cured by split-dose total body irradiation (TBI) at 150 cGy, an effect associated with the restoration of the cellular immunity which is compromised by the virus. The exact mechanism underlying the curative effect is unknown, but it may involve the interferon (IFN) system and interleukin-2 (IL-2) production. Initial studies indicated that TBI did not directly inactivate the virus, suggesting that irradiation either acted on the target cells for virus replication or on other cells mediating the effect. We have now examined the effect of this relatively low dose TBI on replication, transcription, and protein expression of the Friend virus. Northern blot analysis revealed that in FVC infected mice treated with curative low dose TBI, no spleen focus-forming virus (SFFV)-specific mRNA species were detected. Southern blot analysis revealed that a 6.0 kb SFFV fragment could be detected in infected, untreated spleen cells, but not in cells from FVC-infected mice treated with TBI, or in uninfected spleen cells. Western blot analysis revealed that the SFFV envelope glycoprotein was expressed in the spleen cells from untreated FVC infected mice, but not in the cells from TBI treated FVC infected mice. These results, consistent with our previous findings of greatly reduced spleen focus forming units in mice with FVC which had been treated with this regimen of TBI, suggest the possibility of using such treatments in other retroviral associated disorders.
Leukemia 1991 Mar
PMID:Effect of split low dose total body irradiation on SFFV mRNA, genomic DNA and protein expression in mice infected with the Friend virus complex. 201 81

We investigated whether the proliferating cell nuclear antigen (PCNA) protein takes part in cis-diamminedichloroplatinum (II) (CDDP) resistance, using a murine leukemia cell line P388 and its CDDP resistant cell line. P388/CDDP was 4 times more resistant to CDDP than P388. The cell lines were maintained in the DBA/2 female mouse peritoneal space. In total cells, the amount of the PCNA protein decreased to 90% in P388 after 1 h CDDP treatment, but that of P388/CDDP increased to 127%. The difference was statistically significant (p = 0.012, n = 5). As for G2/M phase cells, the difference was also significant at 1 h (p = 0.016, n = 5) and at 2 h (p = 0.036, n = 5) after treatment. In P388 the amount of the PCNA protein decreased in accordance with the inhibited cell proliferation, whereas in P388/CDDP, the amount of the PCNA protein increased in spite of the inhibited cell proliferation. This increase of the PCNA protein suggests that the PCNA protein is involved in CDDP resistance of P388/CDDP through enhanced DNA repair synthesis.
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PMID:The relationship of the proliferating cell nuclear antigen protein to cis-diamminedichloroplatinum (II) resistance of a murine leukemia cell line P388/CDDP. 202 4


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