Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We have synthesized a promising class of bis-naphthalimide anti-tumor agents. A representative compound in this series, XB596, exhibits potent in vitro growth inhibitory activity against several human and murine leukemic and solid tumor lines in culture, with IC50 values ranging from 7.2 to 147.5 nM. XB596 was almost as equally growth inhibitory against three doxorubicin-resistant cell lines compared with their parental lines. Using a human tumor colony-forming assay, XB596 demonstrated cytocidal activity against fresh human tumors taken directly from patients, with 23 of 25 evaluable tumors responding to a continuous exposure of 1 microgram/ml of XB596. When L1210 cells were incubated with XB596 for 1 h, the incorporation of uridine and thymidine into RNA and DNA, respectively, was inhibited with IC50 values of 0.14 microM. DNA single-strand breaks, but not double-strand breaks, were detected in XB596-treated L1210 cells. XB596 bound to DNA with guanine-cytosine sequence selectivity as shown by an indirect ethidium bromide displacement assay. XB596 was shown to interact with DNA by a spectrophotometric titration assay, with an estimated binding constant of 4.7 +/- 2.2 +/- 10(6) M-1. XB596 unwound supercoiled DNA as measured by agarose gel electrophoresis. These data are consistent with XB596 being a DNA intercalator. In vivo, XB596 demonstrated good anti-tumor activity against two human solid tumors (DLD-2 colon adenocarcinoma and MX-1 mammary carcinoma) xenografted in nude mice, but has not demonstrated anti-leukemic activity. In summary, XB596 is a pre-clinical anti-cancer agent which interacts with DNA and demonstrates good in vivo anti-tumor activity against human solid tumor xenografts.
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PMID:XB596, a promising bis-naphthalimide anti-cancer agent. 840 Mar 47

Bistratene A is a polyether which was isolated from the marine ascidian Lissoclinum bistratum Sluiter. The hypothesis has been tested that the cytostatic effect of bistratene A is mediated by modulation of protein kinase C (PKC). Human-derived A549 lung and MCF-7 breast adenocarcinoma cells are extremely sensitive to growth inhibition induced by activators of PKC. Therefore, the effect of bistratene A on these cell lines was compared with that of the known PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA). The ability of bistratene A to modulate PKC activity in cellular cytosol was assessed to determine the involvement of PKC in the induction of cytostasis. Bistratene A inhibited the growth of both cell lines and initial seeding density determined its cytostatic potency. IC50 values were between 1.0 and 2.9 nM. Bistratene A also had a profound effect on the colony forming ability of A549 cells, preventing clonal growth at 5 nM. Using the incorporation of [3H]thymidine into cells to assess DNA synthetic activity and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to define cytotoxicity, the compound was found to have both cytostatic and cytotoxic properties. Bistratene A decomposed by 50% after only 2.8 hr in cell culture medium. TPA induced rapid motility and the formation of a network of branched colonies in both cell lines grown on Matrigel, whereas bistratene A did not cause the same effect. Cell cytosol was analysed for phorbol ester binding sites after treatment with bistratene A or TPA. Incubation with TPA (10 nM) caused a reduction in binding sites to 57% of binding in control cells after 30 min and to 35% after 24 hr. Bistratene A did not cause a significant change in binding sites. Assays of PKC activity in cellular cytosol revealed that bistratene A was unable to activate or inhibit the enzyme at concentrations of up to 10 microM. The results suggest that bistratene A is an exquisitely potent cytostatic agent in the two cell lines studied, but modulation of PKC is not involved in the mode of action by which it elicits this effect.
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PMID:Cytostatic and cytotoxic properties of the marine product bistratene A and analysis of the role of protein kinase C in its mode of action. 849 33

Mechanisms of intracellular pH (pHi) regulation seem to be involved in cellular growth and cell division. Little is known about how extracellular acidosis, known to occur in central regions of solid tumors, or alkaline conditions affect pHi regulation in colonic tumors. pHi changes in the colonic adenocarcinoma cell-line SW-620 were recorded by spectrofluorimetric monitoring of the pH-sensitive, fluorescent dye BCECF, and proliferative activity was assessed by [3H]thymidine uptake. Resting pHi in Hepes-buffered solution was 7.53 +/- 0.01 (n = 36). Both 1 mM amiloride and Na(+)-free solution inhibited pHi recovery from acidification and decreased pHi in resting cells. In HCO3-/CO2-buffered media resting pH1 was 7.42 +/- 0.01 (n = 36). Recovery from acidification was Na(+)-dependent, CI(-)-independent, and only partially blocked by 1 mM amiloride. In the presence of amiloride and 200 microM H2DIDS pHi recovery was completely inhibited. In Na(+)-free solution pHi decreased from 7.44 +/- 0.04 to 7.29 +/- 0.03 (n = 6) and no alkalinization was observed in CI(-)-free medium. Addition of 5 microM tributyltin bromide (an anion/OH-exchange ionophore) caused pHi to decrease from 7.43 +/- 0.05 to 7.17 +/- 0.08 (n = 5). The effects of pH0 on steady-state pHi, pHi recovery from acidification and proliferative activity after 48 h were investigated by changing buffer [CO2] and [HCO3-]. In general, increases in pH0 between 6.7 and 7.4 increased pHi recovery, steady-state pHi and growth rates. In summary, SW-620 cells have a resting pHi > 7.4 at 25 degrees C, which is higher than other intestinal cells. Acid extrusion in physiological bicarbonate media is accomplished by a pHi-sensitive Na+/H+ exchanger and a pHi-insensitive Na(+)-HCO3-cotransporter, both of which are operational in control cells at the resting pHi. No evidence for activity of a CI-/HCO3- exchanger was found in these cells, which could account for the high pHi observed and may explain why the cells continue to grow in acidic tumor environments.
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PMID:Effects of extracellular pH on intracellular pH-regulation and growth in a human colon carcinoma cell-line. 867 50

1. Hyperpolarization-activated Cl- currents (ICl,hyp) were investigated in the T84 human adenocarcinoma cell line, using the patch-clamp whole-cell configuration. 2. During whole-cell recording with high-chloride and ATP-containing internal solutions, hyperpolarizing jumps from a holding potential of 0 mV elicited slow inward current relaxations, carried by Cl- and detected at membrane potentials more negative than -40 mV. Analysis of the relative permeabilities to monovalent anions gave the following sequence: Cl- > Br- > I- > glutamate. 3. ICl,hyp was partially inhibited by 1 mM diphenylamine-2-carboxylic acid or 0.1 mM 5-nitro-2-(3-phenylpropylamino)-benzoate, and was completely blocked by Cd2+ (> 300 microM). It was insensitive to 1 mM external 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid or 1 mM Ba2+. 4. ICl,hyp was inhibited by external application of 500 microM cptcAMP (8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate) or 500 nM of the protein kinase C activator, phorbol 12-myristate, 13-acetate. 5. (i) Omission of ATP from the pipette solution, (ii) ATP replacement by the non-hydrolysable ATP analogue 5'-adenylylimidodiphosphate, and (iii) inhibition of protein kinase C by staurosporine or calphostin C accelerated the activation kinetics of the current and increased its amplitude, but did not alter its pharmacological properties. 6. We conclude that hyperpolarization-activated Cl- channels similar to those of ClC-2 channels (mammalian homologue of Torpedo chloride channel ClC-0) are present in T84 cells, and that their gating properties are modulated by phosphorylation.
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PMID:Modulation of the hyperpolarization-activated Cl- current in human intestinal T84 epithelial cells by phosphorylation. 874 82

We established a sensitive and accurate method for screening of anti-adenovirus agents using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. MKN-28 cells, which are well-differentiated stomach adenocarcinoma cells, were used for adenovirus (ADV) infection and examined for the anti-ADV activities of several established anti-herpes virus agents. ADV-11 is the causative agent of respiratory and urinary infections. It frequently causes hemorrhagic cystitis in immunocompromised hosts. One laboratory strain and 4 clinical isolates of ADV-11 were examined, and found susceptible (in order of decreasing activity) to 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S-2242), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine[(S)-HPMPA ], and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine[(S)-HPMPC++ +]. On the other hand, ganciclovir and iododeoxyuridine were only weakly effective and dextran sulfate was ineffective. Our findings indicate that the MTT assay using MKN-28 cells is applicable to anti-ADV screening. The anti-ADV activity of (S)-HPMPA and (S)-HPMPC was confirmed, and, furthermore, S-2242 emerged as a highly potent and selective inhibitor of ADV-11.
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PMID:Application of a gastric cancer cell line (MKN-28) for anti-adenovirus screening using the MTT method. 881 Dec

The effect of illumination on intracellular free calcium concentration, [Ca2+]i, was studied in a cell line (WiDr cells) derived from a primary adenocarcinoma of the rectosigmoid colon. In these cells the biosynthesis of protoporphyrin IX was stimulated by 5-aminolevulinic acid to reach levels of 600-700 pmol of protoporphyrin IX per mg cell protein. A brief (1-min) exposure of the cells to light (70% of light energy at 340-380 nm) resulted in an increase in [Ca2+]i. This increase was not reversible over a period of at least 20 min following illumination. Elevation of [Ca2+]i most probably represented an influx of calcium ions from the medium to the cell, since it was completely abolished in the presence of extracellular EGTA. The increased [Ca2+]i did not reflect general membrane damage, as determined by trypan blue staining as well as measurement of the intercalation of ethidium bromide into cellular DNA, and neither did the sustained elevation of [Ca2+]i lead to any substantial loss of clonogenicity following illumination of protoporphyrin-containing cells. Together these results indicate that an increased [Ca2+]i level is not per se a cause of cell death during photodynamic therapy.
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PMID:The effect of brief illumination on intracellular free calcium concentration in cells with 5-aminolevulinic acid-induced protoporphyrin IX synthesis. 898 53

Tat (transactivator of transcription) is essential for HIV-1 replication in vivo and in vitro. Tat-(65-80), an RGD containing domain, has been shown to regulate proliferative function of a variety of cell lines, including a human adenocarcinoma cell line, A549. The exact cellular and molecular mechanisms by which these effects are mediated, remain unknown. To evaluate the hypothesis that Tat-(65-80) modulates the expression of immediate early genes (IEG) c-jun, c-myc, c-fos and the tumor suppressor gene p53, serum starved A549 cells were incubated with Tat-(65-80) or heat-inactivated Tat-(65-80) at 10 ng/ml. Total cellular RNA was isolated from the cells at various time points (0-24 hours). In each case, 5 micrograms of RNA was reverse transcribed in 20 microliters of reaction volume. Equal amounts of cDNA were subjected to polymerase chain reaction (PCR) and analyzed by electrophoresis. The photographic negatives of the ethidium bromide stained gels were quantitated by densitometric scanning and normalized to corresponding beta-actin PCR products. Treatment with Tat-(65-80) showed a twofold induction of c-jun at 0.5 h. Peak expression occurred at 60 minutes and remained above baseline at 24 hours (h). c-myc was increased at 0.5 h, reached a twofold increase at 2 h and remained above baseline at 24 h. c-fos increased seven fold at 0.5 h and declined subsequently to baseline at 8 h. p-53 gene was reduced fivefold at 0.5 h and remained downregulated thereafter. These results show that Tat-(65-80) can modulate growth related genes in human lung epithelial cells.
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PMID:An RGD containing peptide from HIV-1 Tat-(65-80) modulates protooncogene expression in human bronchoalveolar carcinoma cell line, A549. 912 88

The ability of anti-inflammatory agents to modulate cellular sensitivity to anticancer drugs was investigated for pulmonary carcinoma cells in vitro. We examined the drug sensitivity of two pulmonary adenocarcinoma cell lines (76-2, 77-4) in the presence of two drugs, an anticancer drug and an anti-inflammatory agent, for 72 hr by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with 96 well plates. Anticancer drugs used for screening test were cyclophosphamide (CPM), mitomycin C (MMC), adriamycin (ADR), 5-fluorouracil (5FU), vindesine (VDS), cisplatin (CDDP), cytarabine (Ara C), methotrexate (MTX), etoposide (VP-16), and vincristine (VCR). Anti-inflammatory agents examined as modulators to anticancer drugs were aspirin, mefenamic acid, ibuprofen, sulindac, piroxicam, phenacetin, dicrofenac, ketoprofen, tolmetin and indomethacin. Screening tests showed indomethacin to be the most effective modulator, resulting in more than a 3-fold increase in cytotoxicity of VCR as compared with that produced by VCR alone. Study of each of the ten anticancer drugs in combination with indomethacin showed VCR to be the most effective anticancer drug in this combination. In 76-2 cells, the concentration of VCR producing 50% growth inhibition (IC50) for VCR alone and VCR in combination with 2 micrograms/ml indomethacin were 1.58 +/- 0.16 and 0.52 +/- 0.1 ng/ml respectively, which represents a 3-fold decrease. In 77-4 cells, the IC50 for VCR alone and VCR in combination with 2 micrograms/ml indomethacin were 2.86 +/- 0.2 and 0.52 +/- 0.11 ng/ml respectively, which represents a 3.8-fold decrease. Our studies indicate that clinically achievable concentrations of indomethacin may be useful in modulating VCR resistance in human pulmonary adenocarcinoma cells, so that combined use of VCR and indomethacin may be of potential clinical significance in the treatment of lung cancer.
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PMID:Indomethacin enhances the cytotoxicity of VCR and ADR in human pulmonary adenocarcinoma cells. 916 51

Thick cell clusters are a common finding in reactive and malignant effusions. In order to arrive at a diagnosis, clusters are evaluated for certain cytomorphologic features including size, shape, smooth vs. scalloped borders, and three-dimensional (3-D) configuration. By conventional microscopy, the image of these clusters is often blurred due to limitations in resolution. Consequently, the exact internal structure and cellular arrangement within these clusters cannot be adequately determined. Utilizing confocal laser scanning microscopy (CLSM), we examined serous fluids from a variety of conditions. Cases included mesothelioma, adenocarcinoma, and papillary adenocarcinoma. Smears were stained with 0.01% ethidium bromide and 1% eosin Y, followed by analysis with an ACAS 570 image analyzer (Meridian Instruments, Inc. Okemos, MI). Serial confocal fluorescence images were acquired, which allowed 3-D reconstruction of the clusters. Mesothelioma clusters (excluding those with obvious central collagen cores by light microscopy) appeared to be formed of the following configurations: 1) randomly coiled cords of cells, 2) small papillae encompassing central cores, and 3) tissue fragments with pseudoacinar formation. In contrast, adenocarcinomas had a more orderly pattern, with tightly cohesive cells and true acinar formation.
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PMID:Confocal laser scanning microscopy and three-dimensional reconstruction of cell clusters in serous fluids. 931 83


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