Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A serum-free primary culture system has been developed which allows for three-dimensional growth and differentiation of normal rat mammary epithelial cells (RMECs) within an extracellular matrix preparation. RMECs were isolated from mammary glands of immature 50- to 60-d-old rats and the organoids embedded within a reconstituted basement membrane matrix prepared from the Engelbreth-Holm-Swarm sarcoma. Cells grown in a serum-free media consisting of phenol red-free Dulbecco's modified Eagle's medium-F12 culture medium containing 10 micrograms/ml insulin, 1 microgram/ml prolactin, 1 microgram/ml progesterone, 1 microgram/ml hydrocortisone, 10 ng/ml epidermal growth factor (EGF), 1 mg/ml fatty-acid-free bovine serum albumin (BSA), 5 micrograms/ml transferrin, and 5 microM ascorbic acid proliferated extensively (15- to 20-fold increase in cell number as quantitated using the MTT dye assay) over a 2- to 3-wk culture period and remained viable for months in culture. Several types of colonies were observed including the alveolarlike budding cluster which predominates at later times in culture, units with no or various degrees of ductal-like projections, stellate colonies, and two- and three-dimensional web units. Optimal proliferation required insulin, prolactin, progesterone, EGF, and bovine serum albumin. Hydrocortisone was not required for proliferation, but the colonies developing in its absence were morphologically altered, with a high frequency of colonies that formed an extensively branched network with many fine projections. Cell proliferation was also dependent on substratum, with significantly less growth and development occurring in RMECs grown within a type I collagen gel matrix compared to RMECs grown within the reconstituted basement membrane. In conjunction with other studies demonstrating extensive differentiation as well as proliferation, it is concluded that this model should prove to be an important tool to study the hormonal regulation of the growth and development of rat mammary cells.
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PMID:Primary culture of normal rat mammary epithelial cells within a basement membrane matrix. I. Regulation of proliferation by hormones and growth factors. 239 74

The cephalosporins are a family of semisynthetic antibiotics, some of which have structural features associated with substrates for the multidrug transporter, P-glycoprotein. The activity of a series of six cephalosporins in reversing multidrug resistance (MDR) was examined in MDR variants (Dx5 cells) of the human sarcoma line MES-SA. Dx5 cells express high levels of the mdr1 gene product P-glycoprotein and are 25- to 30-fold resistant to doxorubicin (DOX), etoposide (VP-16), and vinblastine (VBL). Cytotoxicity was measured by the MTT assay. Cefoperazone (1.0 mM) was the most effective modulator of MDR, lowering the IC50 for VP-16 by 29-fold (29x), for VBL by 16x, and for DOX by 14x. Ceftriaxone at 1.0 mM produced 10x modulation of VP-16 cytotoxicity, 8x for DOX, and 2x for VBL. The reversal of resistance was concentration dependent, decreasing to 4x and 5x, respectively, for DOX with 0.25 mM cefoperazone and ceftriaxone. No modulation of cytotoxicity was observed in the parental MES-SA cells, which do not express mdr1. Cefazolin, cefotetan, cephradine, and ceftazidime were ineffective, producing less than 5x modulation of DOX at 1.0 mM. Among these cephalosporins, cefoperazone and ceftriaxone were the most highly protein bound in the media (30 and 52%), and the most lipid soluble, with octanol/water partitioning coefficients of -0.49 and -0.60. Varying the serum concentration in medium from 5 to 50% had less than a two-fold effect on the modulation of MDR by ceftriaxone. The ability to reverse MDR among these agents is associated with lipid solubility, high protein binding, a polycyclic planar geometry, and the presence of the piperazine group in cefoperazone. These data and the potential for achieving high tissue concentrations indicate that cefoperazone merits further study as a modulator of MDR.
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PMID:Reversal by cefoperazone of resistance to etoposide, doxorubicin, and vinblastine in multidrug resistant human sarcoma cells. 258 32

We compared the colorimetric reactions between the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl 2H-tetrazolium bromide (MTT) assay and the succinate dehydrogenase inhibition (SDI) test, in order to evaluate the usefulness of the SDI test for in vitro chemosensitivity testing. The addition of sodium succinate enhanced the colorimetric absorbance at 565 nm in the MTT assay in a dose- and a time-dependent manner, in mouse sarcoma-180 (S-180) cells. At 10 microM of sodium succinate, a dose used in the SDI test, the absorbance of the MTT assay increased by about 2.5-fold in the S-180 cells and in 10 human tumor tissues. The absorbance in the SDI test correlated well with the viable cell number of S-180 cells (r = 0.9993). These results show that the SDI test, using MTT as a tetrazolium salt, has a higher sensitivity for predicting cell viability, compared to the MTT assay.
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PMID:Sodium succinate enhances the colorimetric reaction of the in vitro chemosensitivity test: MTT assay. 318 53

A survey of in vitro cytotoxic effects of camptothecin in human epitheliod sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma (PNET) cell lines, was done. We chose the MTT assay to measure survival and observed that 24 h exposures to camptothecin caused consistently greater toxicity than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range. There was a 10-fold range of growth rates measured by OD after 5 days exposure and varied expression of MDR1 in these cell lines--none of which could be correlated with tumor sensitivity to drug. The most sensitive cell lines were colon and glioblastoma, and the most resistance were ovarian, breast and epithelioid sarcoma.
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PMID:Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose. 757 68

The four kinds of plant polysaccharides, i.e., pachyman polysaccharides (PPS), Acanthopanax senticosus polysaccharides (ASPS), polysaccharides of tremella fuciformis (TF) and lentinan, have obviously inhibitory action against the animal tumor growth and have been applied to the treatment of cancer. The mechanism was that they could enhance the body immune function, but whether the tumor cells were killed is not clear. In this paper, the effects of the four plant polysaccharides on cell proliferation in mice sarcoma (ascitic type) S180 and human chronic myelogenous leukemia K562 cells were studied with MTT chromometry. Tt was found That TF and lentinan had no effect on both cell line, but PPS and ASPS could obviously inhibit the proliferation of them, the IC50 of PPS was 1.5mg/ml in both cell line, that of ASPS was 0.38 mg/ml (S180 cells) and 0.28mg/ml (K562 cells) respectively. This result indicated that the PPS and ASPS were able to kill the tumor cell directly. To investigate the mechanism of antitumor action of PPS and ASPS, the sialic acid (SA), phospholipid (PI) and cholesterol (Ch) contents of S180 cell membrane were examined after the PPS or ASPS application for 24 hours. No significant changes were observed for the Ch and Ch/Pl ratio, the amount of SA increased and that of PI lowered respectively (P < 0.05). The results suggested that the antitumor action of PPS and ASPS not only related to the action of enhancing the body immune function but also related to the changes of cell membrane.
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PMID:[Effects of plant polysaccharides on cell proliferation and cell membrane contents of sialic acid, phospholipid and cholesterol in S 180 and K 562 cells]. 784 57

The chemosensitivity of 43 human sarcoma tissues, including 18 osteosarcomas, 16 leiomyosarcomas and 9 liposarcomas, was compared with that of 28 adenocarcinomas of the stomach, using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues were exposed for 3 days to each antitumor drug, including adriamycin (ADM), 5-fluorouracil (5-FU), mitomycin C (MMC), cisplatin (CDDP), aclacinomycin A (ACR) and carboquone (CQ), them the cell viability was estimated based on the succinate dehydrogenase (SD) activity, determined using [3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H tetrazolium bromide] (MTT). SD activity was significantly lower in the osteosarcoma as compared to that in the adenocarcinoma, for ADM, MMC, CDDP, ACR and CQ (p < 0.01), and was higher for ADM (p < 0.05) in cases of leiomyosarcoma and for CDDP (p < 0.01) and ACR (p < 0.05) in cases of liposarcoma. The sensitivity rate was higher in osteosarcoma than in adenocarcinoma for ADM, MMC and CDDP. These findings suggest that patients with osteosarcoma will probably show a fairly good response to antitumor drugs, and that when liposarcoma or leiomyosarcoma tumors show resistance to antitumor drugs, then resection at the time of initial exploration and combined modalities, including radiation and hyperthermia, should be considered.
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PMID:Antitumor chemosensitivity differs between clinical sarcoma and adenocarcinoma tissues. 816 44

The effects of heat on intracellular accumulation of anthracyclines were investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME-2303 (ME) and KRN-8602 (KRN) at 37 degrees C and at higher temperatures. There was a dose-dependent increase in the fluorescence intensity of all drugs at 37 degrees C, but heat varied the fluorescence intensity of each drug. At 43 degrees C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but for DM the increase was 110-130%. The cellular fluorescence of THP and ME was little affected by heat, and heat reduced that of KRN to 80-90%. Each drug showed was unique in the relationship between drug exposure time and the fluorescence intensity at 37 degrees C and 43 degrees C. Cytotoxicity determined by the MTT assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP, ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities when given in combination with hyperthermia.
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PMID:Laser flow cytometric studies on the intracellular accumulation of anthracyclines when combined with heat. 830 10

The use of recombinant tumour necrosis factor (TNF) in the treatment of solid tumours has been limited by life threatening toxicity. In addition TNF may be a major mediator of the effect of endotoxins. Recent evidence suggested that a synergism between endotoxin (at the picogram level) and TNF may contribute to this toxicity. The use of the anti-endotoxin taurolidine may reduce TNF toxicity by interfering with this synergy. C57/BL6 mice (n = 140) received toxic doses (12 micrograms/mouse IV) of TNF. Four groups were studied. Group A received taurolidine 200 mg/kg IV 30 minutes before TNF, group B received TNF followed 30 minutes later by taurolidine 200 mg/kg IV, group C received an identical volume (0.5 ml) of normal saline 30 minutes prior to TNF, and group D taurolidine 200 mg/kg IP 45 minutes before TNF. The mortality rate of those mice receiving intravenous taurolidine 30 minutes prior to TNF was 8.8%. This was significantly less (P < 0.005) than the mortality rate achieved in groups B, C and D (33% vs 39.4% vs 50%). Further experiments employing an MTT (3-(4,5-dimethylthinzol-2-microliters)-2,5-diphenyl tetrazolinm bromide) assay showed that this was not due to direct interaction of taurolidine with TNF but is likely to be due to interference with the synergistic effects of endotoxin and TNF. It was also demonstrated in cotherapy studies in a murine model that taurolidine did not reduce the anti-tumour efficacy of TNF against the TNF sensitive mouse fibrosarcoma cell line Meth-A sarcoma.
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PMID:Taurolidine inhibits tumour necrosis factor (TNF) toxicity--new evidence of TNF and endotoxin synergy. 831 79

We have previously described the synthesis of a cytotoxic polymeric conjugate of spermine (Poly-SPM) which is able to inhibit the transport of polyamines (spermine, spermidine, and putrescine) into normal and malignant cells. Recent studies examining the toxicity of Poly-SPM in parental and multidrug resistant (MDR) cancer cells have revealed a cross-resistance in the MDR variant Dx5 to the toxic effects of the conjugate in the MDR-positive cells. There were also differences in spermine and putrescine uptake rates between parental and MDR-positive with the MDR-positive cells having a lower Vmax and a higher Km. The ability of this Poly-SPM to reverse MDR was examined in MDR variants (Dx5 cells) of the human sarcoma cell line MES-SA. The cells express high levels of the mdr1 gene product, P-glycoprotein, and are 25-to 60-fold resistant to doxorubicin (DOX), etoposide (VP-16), vinblastine (VBL), and taxol (TAX). Cytotoxicity was measured by the MTT [3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Poly-SPM (50 microM) lowered the drug concentration IC50 values in the Dx5 cells by 37-fold with VBL, 42-fold with DOX, 29-fold with VP-16, and 25-fold with TAX when compared to the control IC50 values without Poly-SPM. This reversal of resistance was concentration dependent, decreasing 17-fold with DOX, 6.1-fold with VBL, 19-fold with VP-16, and 5-fold with TAX when 25 microM Poly-SPM was used. No modulation was observed in the parental cell line MES-SA, which does not express the mdr1 gene. Poly-SPM had no influence on the IC50 of non-MDR chemotherapeutic agents such as cisplatin. The modulation studies correlated with the ability of Poly-SPM to reverse the cellular accumulation defect of [3H]-VBL and [3H]-TAX in the Dx5 but not MES-SA cells. Pretreatment of the Dx5 cell with alpha-difluoromethylornithine (DFMO at 2 and 5 microM) for 24 h increased the function of the MDR transporter to further decrease the cellular accumulation of VBL and TAX when compared to untreated cells. DFMO pretreatment is known to upregulate the polyamine transporter(s). These findings show that, in addition to inhibiting polyamine transport, Poly-SPM reverses MDR in Dx5 cells, suggesting a potential relationship between the polyamine influx transporter and the MDR efflux pump. This potential functional link between the polyamine influx transporter(s) and the MDR efflux transporter (P-glycoprotein) offers a novel approach to inhibiting this form of drug resistance.
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PMID:Reversal of doxorubicin, etoposide, vinblastine, and taxol resistance in multidrug resistant human sarcoma cells by a polymer of spermine. 861 15

We have examined the use of the LDH (lactate dehydrogenase) assay for chemosensitivity testing in established and primary cultures of sarcoma, leukaemia and ovarian cancer in parallel with the MTT assay. The method we describe is rapid, sensitive and ideal for 96-well plate assays using adherent or suspension cultures. Excellent agreement between the two methods was observed (r = 0.936) using a variety of antitumour agents, with some notable exceptions. In the Bax (human synovial sarcoma) cell line MTT colour production by control cells was very low, thus MTT-->formazan production could not be relied upon as a definitive end point equating with cell number. In contrast, colour production of control cells using the LDH assay was significantly greater and all cultures tested were suitable for titration of chemosensitivity. There was a discrepancy between IC50 values obtained either by cell counting or MTT in the HTB88 (human leiomyosarcoma) line treated with 5-FU (59.9 microM vs > 200 microM, respectively). However, cell counting agreed well with the LDH assay (IC50 47.3 microM). Whilst the MTT assay remains a reliable method for chemosensitivity testing, the LDH assay may prove more appropriate in certain experimental settings.
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PMID:Chemosensitivity testing of fresh and continuous tumor cell cultures using lactate dehydrogenase. 906 57


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