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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As described in this review, both partially purified and recombinant interferons are potent modulators of differentiation in diverse cell culture systems (Table 2). Depending on the target cell, interferon exerts either an inhibitory or an inductive effect on cell differentiation. In certain myeloid leukemic cells, such as HL-60, interferon by itself is growth suppressive but does not induce cell maturation, whereas in combination with inducers of differentiation, such as DMSO, TPA or retinoic acid, interferon potentiates their ability to stimulate differentiation in both sensitive and resistant cell populations (Grant et al., 1982, 1983; Tomida et al., 1982). Interferon also interacts synergistically with phorbol ester tumor promoters in inhibiting melanogenesis in murine B-16 cells (Fisher et al., 1981a, 1984a) and adipocyte formation in 3T3 cells (Cioe et al., 1980), whereas the combination is synergistic in inducing differentiation in human melanoma cells (Fisher et al., 1984b,c). In contrast, interferon and TPA display antagonistic effects on differentiation in human skeletal muscle cultures, i.e. interferon induces and TPA inhibits myogenesis (Fisher et al., 1982, 1983). Recent studies have demonstrated the presence of high affinity saturable cell membrane receptors for mouse and human interferons (Aguet, 1980; Branca and Baglioni, 1981, 1982; Mogensen et al., 1981; Branca et al., 1982; Anderson et al., 1982; Joshi et al., 1982; Faltynek et al., 1983; Yonehara et al., 1983; Langer and Pestka, in preparation). Similarly, specific membrane receptors have been identified for phorbol esters and mezerein (Driedger and Blumberg, 1980; Shoyab and Todaro, 1980; Horowitz et al., 1981; Fisher et al., 1981b). These findings suggest that the plasma membrane may be a primary target for mediating the biochemical effects induced by both interferon and phorbol esters. Although the mechanism by which interferon and phorbol esters transmit the necessary membrane signal(s) required for altering differentiation are not known, a possible component of this transmembrane signaling process may involve changes in the physical dynamics of the plasma membrane. It is therefore of interest that both interferon and TPA induce early changes in the fluidity of the plasma membrane (Fisher et al., 1979, 1981b, 1984d; Castagna et al., 1979; Kuhry et al., 1983).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of interferon on differentiation of normal and tumor cells. 241 43

The volume of a tumour is the difference between the integrals of cell production and cell loss. Cell production depends on mitosis. Cells are lost by detachment from external surface, loss into blood vessels and lymphatics and into body cavities. Immunological lysis, macrophagia and apoptosis take place, and there is necrosis due to hypoxia. Cell birth can be measured, cell loss must be calculated. Tumour cells differentiate and mature to varying degrees. An inverse relationship between maturation and proliferation exists. DNA synthesis inhibitors often also induce differentiation. Retrodifferentiation does not take place. Immature tumours are undifferentiated because of a population change, not because of retrodifferentiation. The oncogene theory assumes that proto-oncogenes are part of the normal genome. They can be activated to oncogenes by mutation or by loss of regulatory factors. Oncogenes code for important membrane proteins: growth factors or receptors. It has been proposed that anti-oncogenes also exist, coding for inhibitory growth factors like chalones. Much attention has hitherto been directed to attempts at arresting the birth rate of cells by cytostatic drugs. There is a trend in modern research to find substances that can force the cells into maturation. Lithium, DMSO, vitamin-analogues, human post-endotoxin serum, TPA, 4 NQO, hormones and acetamide have been shown to induce maturation in experimental systems. This area of research is presently gaining considerable impetus.
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PMID:What's new in proliferation and differentiation in malignant tumours? 242 Dec 77

Kinetic events associated with the dimethylsulfoxide (DMSO)-induced inhibition of hepatic tumor cell proliferation were studied using established lines of murine liver tumor cells (BW77-2 and Hepa-1/A1) and conditions of polar solvent treatment (1-3% final concentration in the culture medium for a period of 4 days) previously shown to increase the expression of differentiated functions in BW77-2 cells. Cell-cycle substrates of exponentially growing and DMSO-treated liver tumor cell populations were compared by flow cytometric techniques employing recently developed cytochemical criteria to identify hepatocyte cell cycle compartments based on individual cellular RNA and DNA contents (Higgins, 1985). Suppression of hepatic tumor cell proliferation by DMSO (in non-cytotoxic concentrations) persisted only for the duration of the exposure period. Resumption of cell division was readily observed following removal of the polar solvent from the culture medium. During DMSO treatment, BW77-2 and Hepa-1/A1 cells accumulated in the G1 phase of the cell division cycle (low-population-density 3% DMSO-treated cultures were composed of 88% G1 cells compared to only 48% G1 DNA content cells in control cultures of similar population density) and exhibited a substantial shift to lower mean cellular RNA content. The relatively few S- and G2 + M-phase cells in DMSO cultures also possessed lower RNA contents compared to the corresponding cell cycle compartments in exponentially growing cultures. The mean RNA contents for the G1, S, and G2 + M compartments of DMSO-treated cells approximated 63.8, 78.6, and 74.4%, respectively, of the amounts observed in control cultures. Low-RNA G1 cells in DMSO cultures expressed a continuum of RNA distributions similar in range variation to (but at lower mean cellular RNA content levels than) cycling G1 cells in log-phase growth. Thus, G1 cells in 1% DMSO-treated populations had a mean cellular RNA content of just 25 (arbitrary RNA) units compared to over 40 units for G1 cells in exponential phase growth. Low RNA content, non-replicating, hepatic tumor cells in polar solvent-treated cultures were designated as being in the "Qi" substate (DMSO-induced quiescent-type cells). Release of BW77-2 cells from Qi, after replacement of the DMSO-containing growth medium by medium without the polar solvent, was characterized by an increase in mean G1 RNA content and recruitment into log-phase growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization of the growth inhibited substate induced in murine hepatic tumor cells during in vitro exposure to dimethylsulfoxide. 243 18

Two sublines of HL-60 cells differing markedly in their ability to undergo differentiation to granulocytes after treatment with retinoic acid (RA), dimethyl sulfoxide (DMSO) and the pyrimidine analog, 5-aza-2'-deoxycytidine (azadCyd) were studied. The sensitive subline (HL-60 S) responded well to 1 microM RA, 1% DMSO and 1 microM azadCyd, showing 89 +/- 5%, 46 +/- 5% and 29 +/- 6% mature nitroblue tetrazolium (NBT)-positive cells, respectively. However, the resistant subline (HL-60 R) showed only modest maturational effects (12 +/- 3%, 11 +/- 2% and 9 +/- 2%, respectively) after treatment with the same agents. Using the HL-60 R as a model for resistance to differentiation induction in the HL-60 cell line, studies were carried out to determine whether the combined use of RA, DMSO and azadCyd could reverse the resistance of these tumor cells to the induction of maturation expressed by the individual agents. When these agents were given in any combination of 2, a minor increase in differentiation induction was detected (13 +/- 6% or less NBT-positive cells). However, when all 3 agents were combined (RA + DMSO + azaCyd), resistance was completely reversed (89 +/- 7% mature NBT-positive cells). In addition, different degrees of concentration-dependence of each agent in the combination were observed. The RA + DMSO + azadCyd combination caused a maximal accumulation of NBT-positive cells after 72 to 96 hr of incubation. These results show that the lack of competence for induction of differentiation in resistant HL-60 cells can be completely reversed by the above ternary drug combination. However, the mechanism responsible for this synergistic effect must await further elucidation of the molecular mechanisms by which such agents act.
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PMID:Resistance of HL-60 promyelocytic leukemia cells to induction of differentiation and its reversal by combination treatment. 244 60

In order to elucidate the mechanism by which HLA antigens expression is induced or enhanced on the injured or transformed hepatocytes, we have made in vitro studies using human hepatic tumor-derived cell lines as a model system. In the present study, PLC-PRF-5 cells that have the integrated form of hepatitis B virus genome in DNA were treated with 5-azacytidine (5-azaC) in combination with gamma-interferon (IFN-gamma) or dimethyl sulfoxide (DMSO). HLA antigens on the cell surface were quantitated by using a modified cell-ELISA method. As a result, it was demonstrated that DMSO- or IFN-gamma-treatment enhanced expression of HLA class I antigens on the cell surface. In addition, enhanced expression of the antigens on PLC-PRF-5 cells treated with 5-azaC in combination with IFN-gamma or DMSO represented a synergistic effect of these inducers on HLA class I antigens expression although no changes in HLA antigens expression were induced after 5-azaC-treatment alone in short-term experiments. Furthermore, an indirect immunofluorescent analysis of hepatitis B surface antigen on the cells demonstrated increased expression of the antigen after 5-azaC-treatment alone. HLA class II antigens and hepatitis B core antigen were not induced even after those treatments and also not after a long-term experiment. These results might indicate possible modulation of HLA class I and hepatitis B virus antigens expression on the cultured cells by a DNA hypomethylating agent, 5-azaC.
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PMID:Synergistic effect of 5-azacytidine and gamma-interferon or dimethyl sulfoxide on expression of HLA class I antigens by PLC-PRF-5 cells. 246 98

Two citrus limonoids, limonin and nomilin, were tested for their effects on the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced buccal pouch epidermoid carcinomas. Forty-five female Syrian hamsters were divided into three equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of dimethylsulfoxide (DMSO) (group I), a 2.5% solution of limonin dissolved in DMSO (group II) or a 2.5% solution of nomilin dissolved in DMSO (group III). After this initial treatment, 11 hamsters from each group were selected. The left buccal pouches of these animals were painted 2 or 3 times weekly with a 0.5% solution of DMBA in mineral oil. On alternate days the pouches were painted with DMSO (I), the 2.5% solution of limonin (II) or the 2.5% solution of nomilin (III). The 12 remaining hamsters were used as controls and were painted with mineral oil and DMSO (I), mineral oil and the 2.5% solution of limonin (II), or mineral oil and the 2.5% solution of nomilin (III). After 15 weeks the hamsters were killed, the pouches were excised and the tumors were counted and measured. Tumors of variable size were common in the animals treated with DMBA. However, the animals receiving topical applications of limonin exhibited a 60% reduction in tumor burden. Further comparisons between groups I and II showed that this reduction in tumor burden was due to a 20% decrease in tumor number and a 50% decrease in tumor mass. The results for group III showed that nomilin was considerably less effective as an inhibitor of DMBA-induced neoplasia.
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PMID:The effect of citrus limonoids on hamster buccal pouch carcinogenesis. 250 23

A s.c. experimental model of Wilms' tumor in rats was used to compare the effects of intratumoral treatment with vincristine plus actinomycin D to i.v. treatment with these chemotherapeutic drugs. The Wilms' tumor model is a fast-growing solid tumor that has been shown to be resistant to traditional clinical treatment procedures used for Wilms' tumor in man. Injection of the chemotherapeutic drugs directly into the tumor mass was found to be more effective than i.v. therapy in causing long-term remission of the tumor. Intratumoral therapy was also less toxic to the animals than i.v. therapy when measured by post-treatment survival rates and weight loss during the 1st week following treatment. However, intratumoral treatment caused an initial fibrosis of the tumor tissue, which resulted in a slower rate of absorption of the resultant fibrotic tumor mass than was seen in tumors treated i.v. Also, intratumoral injection resulted in necrosis of the overlying skin, which healed as the fibrotic tumor tissue was absorbed. Intratumoral treatment of a cervical tumor was found to cause the remission of a second major tumor mass located at some distance from the initial injection (i.e., in the lumbar region). No significant benefits were noted when dimethylsulfoxide (DMSO) was used in place of aqueous mannitol as a vehicle to deliver the chemotherapeutic agents. There was a significant correlation between the drug dose-to-tumor-size ratio (D/T ratio) and the effectiveness of the chemotherapy. When this ratio was high enough, a single treatment with a combination of vincristine and actinomycin D usually resulted in total remission of the experimental Wilms' tumor in response to either intratumoral or i.v. therapy.
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PMID:Regional chemotherapy in an experimental model of Wilms' tumor in rats. 253 93

In a companion paper (Gillies et al.: J. Cell. Physiol. 139:124-129, 1989) we show that phorbol esters (PEs) are unable to stimulate Na+/H+ exchange in BALB/c-3T3 cells under a wide variety of conditions. The Na+/H+ exchangers of a number other cell types are also not responsive to PEs yet have been rendered responsive by treatment with agents such as dimethylsulfoxide (DMSO). We undertook the present study to evaluate whether or not the treatment of BALB/c-3T3 cells with DMSO will induce modifications in the sensitivity of these cells to activation by PEs. The present study indicates that a 3-5 day exposure of BALB/c-3T3 cells to 1.25% DMSO leads to changes in the sensitivity of these cells to the activation of Na+/H+ exchanger by PEs. These changes in sensitivity were apparent at day 3 and maximal at day 5. Non-tumor-promoting analogues of PEs do not activate Na+/H+ exchange, suggesting that the effect is mediated through kinase C. Sphingosine prevents PE-, but not serum-induced alkalinization. However, the half-time of the intracellular pH (pHin) response to serum was increased by sphingosine, suggesting that kinase C participates in, but is not required for, the serum induced activation. Since DMSO does not induce any apparent morphological change, the change in sensitivity of Na+/H+ exchange to PEs is not likely to be related to differentiation, but may be associated with structural changes in the Na+/H+ exchanger and/or changes in isoforms of kinase C which recognize the exchanger as a substrate.
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PMID:Dimethylsulfoxide modifies the sensitivity of BALB/c-3T3 cells to the activation of Na+/H+ exchange by phorbol esters. 254 Feb 8

n-Butyrate and dimethyl sulfoxide (DMSO) are known to promote differentiated characteristics in certain cells, including hepatocytes. We have previously reported that butyrate up-regulates the surface expression of hepatocyte epidermal growth factor (EGF) receptors and preserves a high-affinity receptor subpopulation. In the present study, culturing of hepatocytes with DMSO dose-dependently (0.5-2%) increased EGF binding and maintained a high-affinity binding component which was otherwise down-regulated during culturing. Although butyrate was more effective than DMSO in most experiments, the two agents caused qualitatively the same alteration in hepatocyte EGF receptor status. The high-affinity component of the EGF binding present in cells treated with butyrate or DMSO was reduced by treatment (10 nM-1 microM, 1 h) with the phorbol ester tumor promoter TPA, an activator of protein kinase C. Butyrate- or DMSO-treated hepatocytes were more susceptible to this response to TPA than were untreated hepatocytes. The present data indicate that in hepatocytes both butyrate and DMSO preserve a high-affinity EGF receptor subpopulation which is otherwise down-regulated during hepatocyte culture, and that this effect particularly comprises receptors that are sensitive to modulation by the tumor promoter TPA.
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PMID:Regulation of hepatocyte epidermal growth factor receptors by n-butyrate and dimethyl sulfoxide: sensitivity to modulation by the tumor promoter TPA. 262 13

The mutagenic activities in Salmonella typhimurium and tumorigenic activities in newborn mice of 6-nitrochrysene (6-NC), 5-methyl-6-nitrochrysene (5-Me-6-NC), 11-methyl-6-nitrochrysene (11-Me-6-NC) and 5-methylchrysene (5-MeC) were compared. In S. typhimurium TA100 in the absence of rat liver 9000 g supernatant, 11-Me-6-NC was the most active compound followed by 6-NC; 5-Me-6-NC and 5-MeC were inactive. In the assays conducted in the presence of rat liver 9000 g supernatant, the order of activity was 11-Me-6-NC greater than 6-NC greater than 5-Me-6-NC approximately 5-MeC. In S. typhimurium TA98 a similar trend was observed. For the tumorigenicity studies, groups of mice were treated with the appropriate compounds in DMSO by i.p. injections on the 1st, 8th and 15th day of life. At a dose of 100 nmol/mouse 6-NC induced significantly more lung tumors than 5-MeC, which in turn was more active than 11-Me-6-NC and 5-Me-6-NC. All compounds induced significant numbers of liver tumors in treated males compared to controls; the order of activity was the same as that observed for lung tumor induction. The results of this study clearly indicate that bay region methyl substitution can either inhibit (5-position) or enhance (11-position) the mutagenic activity of 6-NC. In contrast, bay region methyl substitution (5- and 11-positions) inhibited the tumorigenic activity of 6-NC in newborn mice. Since ring oxidation and nitroreduction are involved in the metabolic activation of 6-NC in newborn mice, bay region methyl substitution may either inhibit the nitroreduction pathway or hinder the formation of the appropriate bay region diol epoxide. Steric factors may be important in determining the tumorigenicity of methylated nitrochrysenes.
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PMID:The effects of bay-region methyl substitution on 6-nitrochrysene mutagenicity in Salmonella typhimurium and tumorigenicity in newborn mice. 267 Mar 5


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