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)

Differentiating agents have been used experimentally and clinically as an adjuvant in the treatment of cancer, but their role in chemoprevention is limited. We used 5% dimethylsulfoxide (DMSO), 1% and 4% methylsulfonylmethane (MSM), 0.3% N-methylformamide (NMF), and retinol acetate (RA) in the chemoprevention of rat mammary breast cancer. One hundred fifty 42-day-old Sprague-Dawley rats were randomized into six groups (control, RA, DMSO, 1% MSM, NMF, and 4% MSM) and received chemopreventive agents along with standard rat chow ad libitum. Eight days later, 15 mg of 7,12-dimethylbenzanthracene was given by oral gastric intubation. The animals were examined weekly for tumor incidence and size (biplanar analysis). Animals were followed up for 240 to 300 days. Tumor incidence was not statistically affected. Time to appearance (latency period) of both tumors and cancers were prolonged by NMF, DMSO, and 4% MSM. Doubling times of all cancers produced were prolonged by DMSO and RA. No group exhibited toxic reactions or significant weight loss. Polar solvents and differentiating agents, specifically NMF, DMSO, and 4% MSM, were effective in the chemoprevention of dimethylbenzanthracene-induced mammary cancers.
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PMID:Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer. 309 7

Substances known to inhibit mammalian NK cell activity during the first stage of lysis (i.e., effector cell-target cell binding) will also inhibit frog SK cell activity. We analyzed target cell lysis after conjugate formation between one target cell and at least one effector cell. Using frog SK effector cells and frog allogeneic and mammalian tumor target cells, we demonstrated that EDTA, the Ca+2 and Mg+2 chelating agent, but not EGTA, the Ca+2 chelating agent, inhibited binding. Thus, Mg+2 is required for conjugate formation. The inhibitory effects of EDTA were at least partially reversible following removal of EDTA. Binding also required membrane fluidity since pretreatment of targets with glutaraldehyde prevented effector cell binding. Adding glutaraldehyde after conjugate formation increased lysis. Modification of target cell surface proteins by DMSO and trypsin also inhibited binding of effector and target cells. Substances inhibiting binding decreased lysis as measured by 51Cr-release from target cells. Inhibition of binding between SK effector and target cells adds further support to our view that natural or spontaneous killing of foreign cells may be one of the most primitive immuno-defense mechanisms.
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PMID:Inhibition of frog SK effector-target cell binding. 310 69

The effects of differentiating agents on the activity and phosphorylation pattern produced by phospholipid- and Ca2+-dependent protein kinase (PL-Ca-PK) were examined in human promyelocytic leukemia cell line HL-60. Dimethyl sulfoxide (DMSO), retinoic acid (RA), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increased the appearance of mature myelocytic (DMSO and RA) or monocytic [1,25(OH)2D3] cells. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increased the appearance of adherent macrophage-like cells. Coincident with the appearance of differentiated cells induced by DMSO, RA, and 1,25(OH)2D3 was an increase in PL-Ca-PK activity. In contrast, TPA treatment resulted in the rapid disappearance of PL-Ca-PK and the induction of phospholipid- and Ca2+- (PL-Ca-) independent protein kinase activity. The phosphorylation pattern resulting from endogenous PL-Ca-PK in extracts from cells treated with DMSO, RA, or 1,25(OH)2D3 showed a prominent phosphorylated protein of molecular weight 37,000 (pp37) and 38,000 (pp38) which was related to the appearance of the myelocyte/monocyte phenotype. pp37 and pp38 were also present in TPA-treated cells, but their phosphorylation was no longer dependent on the presence of phospholipid and calcium. Cells treated with DMSO and RA also exhibited a PL-Ca-dependent pp21 which was barely evident in 1,25(OH)2D3-treated cells and thus represented a myeloid cell marker. Also present was a prominent PL-Ca-dependent pp19 which remained unchanged following treatment with DMSO, RA, and 1,25(OH)2D3, but which diminished markedly in TPA-treated cells. On the other hand, TPA-treated cells exhibited a characteristic pp130 which was antigenically related to the actin binding protein, vinculin. These results indicate that there are characteristic PL-Ca-dependent phosphorylated proteins indicative of mature myelocytic and monocytic cells, as well as PL-Ca-independent phosphorylated proteins characteristic of the macrophage-like phenotype.
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PMID:Phospholipid- and Ca2+-dependent protein kinase activity and protein phosphorylation patterns in the differentiation of human promyelocytic leukemia cell line HL-60. 316 11

Aflatoxin B1 (AFB1) had a reversible inhibitory effect on the assembly of porcine brain tubulin in vitro. The 30%-inhibition concentration was 0.3 mM AFB1. The 8 tumor promoters showed different effects. Five of them, anthralin, cholic acid, gamma-hexachlorocyclohexane (lindane, gamma-HCH), lithocholic acid and phenobarbital (PB), enhanced the in vitro assembly. The effect was reversible in the case of PB and anthralin, only partially reversible in the case of cholic acid and gamma-HCH, whereas the stimulating effects of lithocholic acid led to an irreversible modification of the tubulin structure, as shown by the insolubility of the microtubules at 0 degrees C. This could be confirmed by an electron microscopic study. The doses necessary for a 30% enhancement of the steady-state level were 3 mM (PB), 0.2 mM (anthralin), 6 mM (cholic acid), 0.7 mM (gamma-HCH) and less than 0.2 mM (lithocholic acid). The other 3 tumor promoters tested - diethylstilbestrol (DES), 4,4'-dichloro-diphenyl-trichloro-ethane (DDT) and saccharin - inhibited the assembly. The concentrations necessary for a 30% inhibition varied within a wide range: 0.025 mM, 0.4 mM and 7.5 mM for DES, DDT and saccharin, respectively. Five of the 9 miscellaneous compounds, namely asbestos (crocidolite), bavistan, colchicine, chloropropham and ethylacetate, showed inhibitory effects, whereas Fe2+ (a constituent of asbestos) and 5-azacytidine did not influence the assembly process. The 30%-inhibition concentrations for colchicine, ethylacetate and asbestos were 10 microM, 0.153 M and 0.19 mM, respectively. For bavistan and chloropropham the 30%-inhibition values were 0.7 mM and 2.0 mM, respectively. The inhibitory effects of chloropropham and asbestos were reversible. For colchicine and bavistan the reversibility of the effects was not assayed. In agreement with published data, dimethylsulfoxide (DMSO) and acetone enhanced the in vitro assembly of porcine brain tubulin. The doses needed for a 30% enhancement by DMSO and acetone were 0.4 mM and 0.136 M, respectively. The effect of DMSO was irreversible whereas acetone led to a reversible stimulation. Some compounds were tested for their influence on preformed microtubules (interaction with the equilibrium between assembly and disassembly). Anthralin, cholic acid, PB and DMSO showed no effect on the steady-state plateau. A slight reduction was induced by DDT and bavistan, whereas DES, colchicine and chloropropham led to a pronounced reduction.
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PMID:The in vitro porcine brain tubulin assembly assay: effects of a genotoxic carcinogen (aflatoxin B1), eight tumor promoters and nine miscellaneous substances. 317 78

Freshly isolated and cultured hepatocytes were analyzed by two-parameter flow cytometry. The combined analysis of DNA and cellular protein content allowed the contribution of ploidy classes and of subpopulations within a ploidy class to be defined. Analysis of hepatocytes during exposure to dimethylsulfoxide (DMSO), phenobarbital (PB), low oxygen tension (4% O2) or fetal calf serum (FCS), provided insight into the dynamic response of individual ploidy classes as a function of culture time. By analogy with the age-dependent ploidy shifts in vivo, hepatocyte-cultures shift towards adult animals during exposure to DMSO and towards young animals when cultured at low pO2 (4% O2). FCS and phenobarbital disturb this constitutive ploidy balance. FCS increased the 2 N cell population, where stem cells probably respond to the proliferative stimuli provided by growth factors in the serum. Phenobarbital affects the liver-specific 4 N hepatocytes, which agrees with effects seen in liver after exposure in vivo. It is suggested that drug-induced pathological alterations in ploidy in hepatocyte cultures could serve as indicators of compounds, such as liver tumor promoters, which interfere with cell differentiation in liver. The heterotypic cell-cell interaction of freshly isolated hepatocytes with isolated, in vitro cultured, rat liver epithelial cells in co-cultures proved to be a valuable concept in toxicity testing: aldrin epoxidase, an enzyme system involved in xenobiotic metabolism, was stabilized for more than two weeks. After exposure to the three chemicals, 2-acetylaminofluoren, procarbazine and cyproterone-acetate, a preferential toxicity for each compound and cell population was established. Thus heterotypic cell cultures can considerably increase the amount of information available from in vitro studies. The final concept, combining monitoring of cellular DNA (ploidy) and protein content in hepatocyte cultures during and after exposure to a given test compound at tissue oxygen tension with the heterotypic cell-cell interaction, would create a more in vivo-like culture system. This would enhance the predictability of hepatocyte cultures and contribute to a more widespread use of the test system and as a result help to reduce the number of whole-animal tests.
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PMID:Development of in vitro toxicity tests with cultures of freshly isolated rat hepatocytes. 318 68

The purpose of the experiments was to establish whether individual cells of a tumor cell population, or clonal lines derived from its express the differentiated phenotype, or respond heterogeneously following treatment with inducers of differentiation or with cytostatic drugs. The human cell lines used in this study were: HL-60 promyelocytic leukemia, K562 erythroleukemia, BHM-97 and A2058 melanoma, and A-1, A-2, A-4 and A-6 clones of A2058 line. Inducers of differentiation were phorbol myristate acetate (PMA), dimethylsulfoxide (DMSO) and retinoic acid (RA); cytostatics: adriamycin (ADM), 5-fluorouracil (5-FU), dacarbazine (DTIC), cis-platin (platidiam, PD) and arabinosyl cytosine (ara-C). Expression of the differentiated phenotype was shown by cell attachment (HL-60), hemoglobin production (K562), dendrit formation (A2058, BHM-97). Individual cells expressed the differentiated phenotype heterogeneously in all types of cell populations. Clone A-4 was the most, and clone A-6 the least sensitive to PMA. The drug sensitivity of the clones was different and drug-dependent. It is concluded that induction of differentiation as another approach to therapy of cancer, similar to anticancer drug therapy, also implies disadvantages due to population heterogeneity. Combinations of cytostatics with differentiation inducers might result in improved therapeutic effects.
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PMID:Heterogeneity of the response to inducers of differentiation and to cytostatics of tumor cell populations. 323 68

By use of phase contrast microscopy, transmission and scanning electron microscopy the cytomorphological effects of different known tumor promoters (TPA, teleocidin, mezerein and anthralin) were studied and compared to the cytomorphological effects of a variety of non- or weak promoting irritants (ethylphenylpropiolate (EPP), phorbol, acetone, ethanol and dimethyl sulfoxide (DMSO]. The studies were conducted in cultures of stratifying rat tongue epithelial cells. It was demonstrated that the tumor promoters induce characteristic cytomorphological alterations, the most striking changes being elongation of the cells and formation of long cytoplasmic extensions together with induction of so-called "dark cells". The non-promoting irritants exerted well-known cytotoxic reactions like cell rounding and cell sloughing. It is suggested that the characteristic tumor promotor induced cytomorphological effects partly reflects a block of the intercellular communication and thus should be paid more attention as an important characteristic event among the pleiotropic effects exerted by tumor promoters.
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PMID:Chemically unrelated tumor promoters induce identical morphological changes in cultured rat oral epithelium. 329 12

Five human tumor reference cell lines were tested in vitro against 0 percent, 5 percent, and 10 percent DMSO; four antineoplastic agents; and combinations of 5 percent or 10 percent DMSO plus each antineoplastic agent. Synergistic cytotoxicity between DMSO and antineoplastic agents against each cell line were demonstrated. We have concluded that delivery of standard doses of antineoplastic agents in 5 percent or 10 percent DMSO may be useful in the treatment of some tumors because of the marked increase in tumoricidal effect seen with some DMSO and drug combinations. Alternatively, lower doses of antineoplastic agents might be delivered in DMSO, producing the same cytotoxic effect as a full dose of drug without DMSO but with less systemic toxicity.
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PMID:Cytotoxicity of dimethyl sulfoxide and antineoplastic combinations against human tumors. 336 22

In this study DMSO (dimethylsulphoxide) was used as a tool to test the significance of in vitro modifications of procoagulant and fibrinolytic activity of tumor cells for their in vivo metastatic ability. B16 melanoma cells were chosen as the experimental model. After four days' treatment DMSO increased both the procoagulant and fibrinolytic (plasminogen activator) activity of B16 melanoma cells in a dose-related manner. DMSO treated cells showed significantly greater lung colonizing ability than untreated cells. Our results indicate that DMSO treatment in vitro can modulate procoagulant and fibrinolytic activity and the metastatic ability of B16 melanoma cells; however a direct causal relationship between these in vitro and in vivo effects remains to be established.
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PMID:DMSO-induced changes in the procoagulant and fibrinolytic activity of B16 melanoma cells: influence on lung colony formation. 337 75

In the present investigation we have determined the effects of the differentiation-inducing chemicals dimethyl sulfoxide (DMSO) and sodium butyrate on the growth and tumorigenicity of a highly malignant/metastatic cell line (RAW117-H10) and its less tumorigenic parental lymphoma cell line (RAW117-P). Both of these agents at doses shown to be nontoxic slowed the growth of these cells in suspension culture and significantly lengthened the doubling time while reducing colony formation in the agar tumor stem cell assay. Corresponding to these observations, the in vivo tumorigenicity of the highly malignant RAW117-H10 line was reduced by both chemicals but particularly by butyrate treatment. In addition, both agents increased the expression of some glycoproteins and the glycolipid asialo GM1. There was also a corresponding increase in the NK susceptibility of the normally NK resistant RAW117-H10 cells. To determine if the decreased malignancy of the highly malignant cells following treatment with the chemical agents was primarily due to the alteration in cell surface glycoconjugates or merely due to concomitant decreased growth potential, we transplanted highly glycosylated membrane fragments from normal syngeneic thymocytes to both RAW117-P and RAW117-H10 cells using a Sendai virus mediated membrane fusion technique. The in vivo tumorigenicity of the membrane altered RAW117-H10 cells was significantly decreased. These results strongly suggest that the decreased in vivo malignancy of RAW117-H10 cells resulting from treatment with chemical differentiation agents is caused by their increased susceptibility to NK cell mediated lysis which in turn results from cell surface changes involving altered, primarily increased, expression of certain glycosylated surface molecules. The cell surface glycoconjugates, such as receptors for certain lectins and glycolipid asialo GM1, can be used as markers for malignant potential and NK sensitivity of malignant lymphoid cells.
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PMID:Effects of differentiation inducing chemicals on in vivo malignancy and NK susceptibility of metastatic lymphoma cells. 339 Aug 59


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