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)

N-heterocyclic aromatics are environmentally important carcinogenic pollutants produced by incomplete combustion of organic material. 7H-Dibenzo-(c,g)carbazole (DBC), is a potent skin and systemic carcinogen, whereas dibenz(a,j)acridine (DBA), is a carcinogen with local effects. Therefore, the overall objective of these studies was to determine the initiating ability of DBC and DBA in mouse skin using an initiation-promotion protocol. Acetone-, TPA- or BaP-treated animals were used as negative and positive controls, respectively. DBC, DBA or BaP (200 nmol) dissolved in acetone was applied once to the backs of thirty shaved Hsd:(ICR)Br female mice, followed 2 weeks later with 2 micrograms of TPA in 50 microliters of acetone applied twice a week for up to 24 weeks. Skin tumors developed in 26, 17 and 27 animals, respectively. DBC plus TPA produced a significant influx of dermal macrophages similar to that seen for BaP. Initiation with BaP, DBC or DBA moderated the effect of TPA on most other dermal parameters, particularly neutrophils. These data indicate that, DBC, with apparently different activation pathways than BaP shows similar tumor initiating ability and morphological changes as BaP.
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PMID:Comparative tumor-initiating ability of 7H-dibenzo(c,g)carbazole and dibenz(a,j)acridine in mouse skin. 173 15

The patterns of in vitro intracellular and in vivo intratumoral localization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AlPCS4) in human melanoma LOX were studied by means of computer-enhanced video fluorescence microscopy (CEVFM). The hydrophobic drug P-II localized diffusely in the perinuclear fraction of the cytoplasm of the LOX cells cultivated in vitro. Light exposure did not result in any observable change in the localization pattern. The hydrophilic dye AlPCS4 was distributed as granular and grain patterns in the cytoplasm before light exposure, in exactly the same pattern as that of acridine orange incubated in the same cells, which is known to emit red fluorescence from lysosomes, thus indicating that AlPCS4 was also primarily localized in the lysosomes of the LOX cells. After light exposure the distribution of the intracellular AlPCS4 fluorescence was altered and the intensity increased. In vivo, P-II had a combined cellular localization pattern (i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern) and an extracellular distribution pattern in the tumor tissue, while the AlPCS4 fluorescence was seen mainly in the stroma of the tumor. The total fluorescence intensity of P-II and AlPCS4 in the LOX tumor tissue at different times after injection was quantitatively determined by means of CEVFM.
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PMID:Location of P-II and AlPCS4 in human tumor LOX in vitro and in vivo by means of computer-enhanced video fluorescence microscopy. 182 13

We have used derivatized antisense oligodeoxynucleotides both in vitro and in vivo specifically to inhibit translation of the activated human oncogene Ha-ras. The oligonucleotides (5'-CCACACCGA-3') were targeted to a region of Ha-ras mRNA including the point mutation G----T at the 12th codon which leads to a Gly----Val substitution in the ras p21 protein. They were linked to an intercalating agent and/or to a hydrophobic tail, both to increase their affinity for their mRNA target and to enhance their uptake by tumor cells. A cell-free translation system was used to demonstrate an RNase H-dependent specific inhibition of activated ras protein synthesis. 50% inhibition was observed at a concentration of 0.5 microM of the most efficient oligonucleotide (5'-substitution with an acridine derivative and 3'-substitution by a dodecanol chain). This inhibitory effect stems from a point mutation-sensitive cleavage of the mRNA and it mirrors the growth inhibition obtained with T24 bladder carcinoma cells, which carry activated Ha-ras. The proliferation of HBL100 cells (non tumorigenic human mammary cell line) which carry two copies of normal Ha-ras was unaffected. This study shows that it is possible to design antisense agents that will inactivate the mutated oncogene but not the protooncogene which is generally essential to cell survival.
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PMID:Short modified antisense oligonucleotides directed against Ha-ras point mutation induce selective cleavage of the mRNA and inhibit T24 cells proliferation. 185 Jun 94

With the objective of developing human T-T cell hybrids producing B-cell growth factor, we fused concanavalin A-activated T lymphocytes with cells of the Jurkat T cell line. The hybrids were selected on the basis of their ability to form colonies in soft agar, whereas the parent Jurkat T cell line did not. T-T cell hybrids were HLA-typed, screened by functional tests, and recloned by limiting dilution. In addition to obtaining B-cell growth factor-producing hybrids, we also obtained certain other T-T cell hybrids (as determined by HLA-typing) producing suppressor factors inhibiting proliferative responses and antibody production by human lymphocytes. Subsequently, a suppressor factor with similar inhibitory properties was identified in supernatants of the Jurkat T cell line. However, the Jurkat factor exhibited different biochemical and functional properties than the hybridoma-derived suppressor factors. Using two-parameter cell cycle analysis and the metachromatic fluorochrome acridine orange, we found that the hybridoma-derived 160 and 169 suppressor factors arrested phytohemagglutinin-induced proliferative of peripheral blood mononuclear cells in the G0/G1 phase of the cell cycle, whereas the Jurkat suppressor factor arrested proliferation in the S phase. Incubation of peripheral blood mononuclear cells with the 160, 169, or Jurkat suppressor factors for 24 hr at 37 degrees C, followed by washing, did not alter their cell cycle progression (or RNA content) in response to stimulation with phytohemagglutinin. The hybridoma-derived 160 and 169 suppressor factors and the Jurkat factor inhibited the growth but not the viability of cells from the following human tumor cell lines: A673 sarcoma cell line, SK-LC-6 and SK-LC-14 lung cell lines, SB, Raji, and Daudi lymphoblastoid cell lines, and FARR malignant melanoma cell line. In contrast, it did not affect the growth of murine L1210 cells and FS-4 normal human diploid fibroblasts. The hybridoma-derived 160 suppressor factor was selected to investigate its effect on cell-mediated cytotoxicity. The 160 suppressor factor did not inhibit natural killer cytotoxicity or its augmentation by interferon alpha or interleukin 2 or the generation of lymphokine-activated killer cells. However, this factor partially inhibited the generation of specific T cell-mediated cytotoxicity.
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PMID:Hybridoma-derived human suppressor factors: inhibition of growth of tumor cell lines and effect on cytotoxic cells. 187 5

Fluorimetric techniques were used to examine accumulation of fluorescent probes by the P388 murine leukemia and an anthracycline-resistant subline, P388/Adriamycin(ADR), which expresses the multidrug-resistant phenotype. P388 could be differentiated from P388/ADR on the basis of fluorescence intensity measurements using 3 classes of cationic dyes that are sensitive to membrane potential differences: rhodamine esters, cyanines, and styrylpyridinium dyes. But fluorescence intensity differences were also observed with potential-insensitive dyes: zwitterionic rhodamines and an acridine orange derivative. In all cases, fluorescence intensity differences were caused by impaired dye accumulation, and could be eliminated by treatment of P388/ADR cells with verapamil. Moreover, fluorescence signals from 2 anionic potential-sensitive dyes, merocyanine 540 and a bis-oxonol, were identical in P388 and P388/ADR. None of these dyes could be used to delineate CCRF-CEM, a lymphoblastic leukemia of human origin from the CEM/VM-1 subline that exhibits a markedly atypical drug resistance pattern not based on an enhanced outward transport. But accumulation of both neutral and cationic dyes was impaired in CEM/VLB100, a subline of CCRF-CEM expressing mdr. These studies show that many cationic and neutral fluorescent probes are substrates for the enhanced outward drug transport system associated with P388/ADR cells, and cannot be used to probe membrane-potential differences in cells expressing the mdr phenotype. With several dyes, differences in fluorescence intensity were sufficient so that flow cytometry could be used to delineate P388 from P388/ADR and CCRF-CEM from CEM-VLB100. The latter technique may be useful for identifying malignant cell populations expressing multidrug resistance in patients with neoplastic disease.
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PMID:Characterization of multidrug resistance by fluorescent dyes. 187 11

Flow cytometric cellular DNA-RNA content analysis by acridine orange staining was conducted on surgical fresh specimens of primary lung carcinomas from 66 patients (31 squamous cell carcinomas, 34 adenocarcinomas and 1 large cell carcinoma). The frequency of aneuploid tumors was 84.6% among the tumors. RNA content (RNA Index) in the DNA aneuploid tumor much more significantly (p less than 0.05) increased than the DNA diploid tumor. Tumor doubling time in the DNA aneuploid tumor was significantly (p less than 0.05) shorter than in the DNA diploid tumor. In the patients with lung cancers that recurred within 1 years, recurrence of the DNA aneuploid tumor was higher than the DNA diploid tumor. It is evident from the above results that proliferative activity in the DNA aneuploid tumor increases much more than in the DNA diploid tumor. This in turn may induce early recurrence in patients with lung cancer.
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PMID:[Proliferative activity assessed on the basis of DNA ploidy patterns in primary lung cancer]. 187 1

Tumour cells possess a cell surface protease referred to as guanidinobenzoatase (GB). The active centre of GB binds the fluorescent probe 9-amino acridine (9-AA) and this binding enables cells possessing active GB to be located by fluorescent microscopy. GB binding of 9-AA was inhibited by prior treatment of sections of tumour tissue with a specific polyclonal antibody recognising the tumour associated protease tissue plasminogen activator (t-PA). GB binding of 9-AA was also inhibited by prior treatment of sections of tumour tissues with PAI-I, a protein inhibitor of plasminogen activatory. We conclude from these studies and kinetic analyses that GB and t-PA are very similar both in structure and function.
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PMID:Evidence for the functional similarity between tumour cell surface guanidinobenzoatase and tissue type plasminogen activator. 190 3

Pyrazoloacridine is a rationally synthesized acridine derivative with in vitro activity against solid tumor cell lines, noncycling and hypoxic cells, and tumor cell lines that exhibit the multidrug resistance phenotype. The pharmacokinetic behavior of pyrazoloacridine after a 1- or 24-h i.v. infusion was studied in 5 rhesus monkeys that received a total of 10 courses of pyrazoloacridine at 300 or 600 mg/m2. Pyrazoloacridine levels in plasma and cerebrospinal fluid were measured by high-pressure liquid chromatography. For 1-h infusions, the plasma disappearance was biexponential with a t 1/2 alpha of 31 min and t 1/2 beta of 11 h. The mean volume of distribution at steady state was 1380 liters/m2. The clearance was 1660 ml/min/m2. For the 300 mg/m2 dose, the mean area under the concentration-time curve was 759 microM.min, and the mean peak concentration was 1.3 microM. For the 600 mg/m2 dose, the area under the concentration-time curve was 1330 microM.min, and the peak concentration was 2.5 microM. The steady-state plasma concentrations during the 24-h continuous infusions were 0.27 microM for the 300 mg/m2 dose and 0.45 microM for the 600 mg/m2 dose. The mean clearance calculated from these steady-state concentrations was 2420 ml/min/m2. Cerebrospinal fluid levels were less than 0.1 microM for all doses and schedules. There was no evidence of toxicity at any dose or schedule. These results contrast strikingly with those obtained in mice and dogs in which, despite a more rapid clearance of pyrazoloacridine, significant toxicities were observed at doses that were nontoxic in the monkey. These interspecies differences in the pharmacokinetic and pharmacodynamic behavior of pyrazoloacridine have important implications for the design of Phase I trials in humans.
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PMID:Pharmacokinetics of pyrazoloacridine in the rhesus monkey. 191 66

Tumour cells possess the cell surface protease guanidinobenzoatase (GB) which can be located by the fluorescent probe 9-amino acridine (9-AA). Frozen sections and formaldehyde fixed sections of tumour tissue were used to demonstrate the interactions between GB, 9-AA and two protein inhibitors of GB. A cytoplasmic extract from the tumour tissue, and a purified inhibitor of plasminogen activator (PAI-1) were shown to be exchangeable components of the enzyme-inhibitor complex on the fixed tumour cell surfaces. The evidence suggests that GB is functionally very similar to plasminogen activator and that this enzyme can be regulated by protein inhibitors in vivo and also by changes in the redox potential at the cell surface.
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PMID:The inhibitor reacting with a tumour cell surface protease can be exchanged with plasminogen activator inhibitor (PAI-1). 203 70

An acridine orange cytofluorometric analysis was used to study the DNA-RNA contents of bladder washing exfoliated cells from 109 patients with transitional cell carcinoma of the urinary bladder. DNA and RNA measurements were performed in each of 200-300 cells/sample, and DNA index (DI) and RNA index (RI) were calculated from the distributions of these values. Presence of aneuploid stem cell line and/or increased mean DNA contents were observed in 83 (76.1%) of the 109 patients. Elevated RNA content in a diploid cell population, was of no additional diagnostic significance. Histologically diagnosed high grade and high stage bladder carcinoma apparently showed an aneuploid stem cell line with high DI and high RI. Thirty patients with superficial bladder cancer (Ta and Tl) who had tumor recurrence within 2 years after surgical interventions showed a significantly increased RI in contrast to 10 patients who had no recurrence for more than 2 years. RNA content measurement was thought to be useful for prediction of tumor recurrence after surgical interventions. Six patients who had a progression from superficial to invasive carcinoma were with high histological malignancy, lamina propria invasion, high DI and high RI. However, there was no significant difference in RI between the 6 patients and the other patients with superficial bladder cancer. Eight patients who had distant metastasis within one year after radical cystectomy also showed a significant increase in RI in contrast to 8 patients who had no metastasis for more than 1 year. Increased RI may be said to be an important risk factor in predicting the development of distant metastasis and recurrent tumor after surgical interventions.
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PMID:[Studies of biological malignancy in bladder cancer using two parameter DNA-RNA cytofluorometric analysis]. 205 91


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