Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methanesulfonamide, N-[4-(9-acridinylamino)-30methoxyphenyl]-(NSC-249992), an acridine derivative with significant antitumor activity in animal tumor systems, was administered to 29 patients in a phase I clinical trial. The dose ranged from 10 to 160 mg/m2 with a single dose given every 28 days. The toxic effects included moderate to severe leukopenia and mild thrombocytopenia. Myelosuppression was more severe in patients with prior whole abdominal or pelvic radiotherapy. Superficial phlebitis occurred when the drug was diluted in a volume of less than 500 ml of 5% dextrose in water. Antitumor activity was detected in one patient with ovarian carcinoma. Phase II studies are indicated with this compound since it has reproducible and reversible toxicity with some evidence of antitumor activity. The starting dose of the drug for phase II trials should be 120 mg/m2 as a single iv dose repeated at 4-week intervals.
 ...
PMID:Phase I study of methanesulfonamide, N-[4-(9-acridinylamino)-3-methoxyphenyl]-(m-AMSA) using a single-dose schedule. 36 Dec 22

The reactivity of lymphocytes in lymph nodes draining the site of a transplantable experimental bladder tumor (MBT2 in C3H/HeJ mice) has been measured in a multiparameter flow cytometry system. Acridine orange was used as a nucleic acid probe. This dye intercalates in helical DNA, emitting green (530 nm) fluorescence upon exposure to blue light; it stacks to single-stranded RNA, emitting red (640 nm) fluorescence. The relative magnitude of the increase of lymphocyte DNA and RNA has been evaluated simultaneously in tumor-draining nodes, in nondraining nodes of the same animal, and in untreated control animals. Stimulation of the regional node lymphocytes could be observed after 20 days but not after 10 days. It was uniformly high at 35 days. The transcriptive response (increased proportion of lymphocytes with high RNA) was more pronounced than the proliferative (increased proportion of lymphocytes with more than diploid DNA). The histological changes in the stimulated nodes resembled closely those described by others in human tumor-draining nodes. The described method has the advantage of being simple, rapid, and able to measure a representative part of the whole-cell population.
 ...
PMID:Regional lymph node reactivity in explanted bladder cancer of mice as measured by flow cytometry. 44 9

4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA, NSC 249992), an acridine derivative, was given to 28 patients with solid tumors and one patient with Hodgkin's disease in a Phase I clinical trial. The dose schedule used was a single dose given every 14 days for three doses. The amount given ranged from 10 to 120 mg/sq m/dose. Dose-limiting toxicity was moderate to severe leukopenia which occurred at and above 70 mg/sq m. Thrombocytopenia was infrequent and did not require transfusion. Nonhematological side effects were mild and included nausea, vomiting, local irritation, and fever. Antineoplastic activity was noted in liposarcoma, adenocarcinoma of unknown primary origin, and squamous carcinoma of unknown primary origin (one patient each). Pharmacokinetics studies were done in 19 patients. Total m-AMSA and free m-AMSA concentrations showed a biphasic distribution with an initial rapid phase of t1/2 = 10 to 15 min for both, and a second slow phase of t1/2 = 8 to 9 hr for total m-AMSA and 3 hr for free m-AMSA. Phase II studies with m-AMSA, in hematological cancers are warranted, since its most consistent effect is on leukocytes. The recommended dosages for solid-tumor Phase II studies are 70 mg/sq m for good-risk patients and 50 mg/sq m for poor-risk patients, given as a single dose every other week, or 120 mg/sq m for poor-risk patients for the single-dose every-3-week schedule.
 ...
PMID:Phase I clinical and pharmacological study of 4'-(9-acridinylamino)-methanesulfon-m-anisidide using an intermittent biweekly schedule. 47 24

Lymph node lymphocyte reaction to an explanted, transplantable mouse bladder tumor (MBT-2) was investigated by flow cytometry in animals previously immunized with irradiated tumor cells. Nodal lymphocytes in representative samples from four different lymph node sites were differentially stained for DNA and RNA with the fluorescent dye acridine orange; cell proliferation and the increase in RNA content were measured. Immunization abrogated tumor growth; one immunization reduced tumor take to 25 per cent of the animals, and two immunizations to 14 per cent. Lymphocyte reactivity to the tumor was reflected both by an increase of DNA synthesizing cells and by diploid cells with high RNA. The latter response was more pronounced and thus the more sensitive parameter for measuring immunologic lymph node reactivity. The juxtatumoral node displayed the most pronounced reactivity, but all node sites showed some degree of reaction.
 ...
PMID:Lymph node reactivity to experimental bladder tumor in preimmunized animals as measured by two parameter flow cytometry. 50 Mar 14

The synthesis and the characterization of a number of diacridines connected through the 9-amino position of the acridine rings by alkyl chains of varying lengths and with various substituents on the acridine ring are described. An interesting chemical property has been noted; whereas the 3-amino monoacridines cannot form stable dihydrochloride salts, the corresponding diacridines can form stable trihydrochloride salts. The biological activity of the diacridines encompasses a broad spectrum of action. Their antitumor activity (% ILS) and their toxicity have been correlated with their biological actions. The % ILS, as measured by inhibition of growth of P-388 ascites cells in BDF/1 mice, shows no significant correlation with their ability to inhibit the growth of P-388 cells in culture (I50). The toxicity of the diacridines does not correlate with the inhibition of DNA or RNA synthesis, the uptake of the diacridines by P-388 cells, or with % ILS. The only significant correlation that has been found to date between the antitumor effectiveness of the diacridines and their effects on intact cells occurs between % ILS and cell agglutination. These results emphasize that caution should be used in attributing the "antitumor activity" of a single compound or of a small number of congeners of a given chemical structure to a particular site of biological inhibition. Furthermore, the results suggest that effective antitumor drugs are those that affect the host-tumor interaction and that the toxicity of the drugs may not be essential to their antitumor properties.
 ...
PMID:Diacridines, bifunctional intercalators. Chemistry and antitumor activity. 72 54

N1-Acyl derivatives of the tumor inhibitory 4'-(9-acridinylamino)methanesulfonanilide agents act as prodrugs undergoing deacylation to liberate the core agents on incubation with pH 7.5 buffer or mouse blood. Against L1210 tumor implanted remotely from the drug administration site, lower acyl derivatives often provide enhanced effects over that obtained with nonacylated precursor alone. In certain homologous series of acyl derivatives, toxicity first increased with increasing lipophilic character, until greater than that of the core agent alone, and then at higher lipophilic levels decreased. Tumor inhibitory properties of the acyl derivatives in such series appeared inversely related to their toxicity. Several 3-(3,3-dialkyl-1-triazeno)acridine-substituted congeners provided excellent L1210 activity. Contrasting with most other tumor-active triazenes, one alkyl group need not be a methyl group of antileukemic activity to be observed. 3-Methyl-3-propyl-1-triazene and 3,3-diethyl-1-trazene analogues had comparable lipophilic-hydrophilic balance, toxicity, and antileukemic effectiveness; usual metabolic activation of the triazene N-methyl group may make little contribution to antitumor properties in the examples presented. Prepared as a nonalkylated triazene analogue, a 3-azidoacridine congener had high L1210 activity.
 ...
PMID:Potential antitumor agents. 22. Latentiated congeners of the 4'-(9-acridinylamino)methanesulfonanilides. 85 Feb 38

From structure--anti-L1210 relationships developed earlier for the 4'-(9-acridinylamino)alkanesulfonanilides it was predicted that congeners bearing both lipophilic 3-acridine substituents and compensatory hydrophilic function(s), together providing an overall molecular lipophilic--hydrophilic balance close to optimum, should have augmented antitumor properties. The acceptability of a variety of hydrophilic functions, and optimum positioning of these, has now been investigated. A variety of sterically demanding, hydrophilic functions may be acceptably appended to the acridine 4(5) position suggesting considerable site bulk tolerance. A variant with both a lipophilic 3-acridine substituent (3-iodo) and a hydrophilic 5-(2,3-dihydroxypropoxy) function is markedly more active than previous examples in the early treated, intraperitoneally (ip) dosed, ip implanted L1210 system, the assay system employed in the structure--activity analyses. However, this latter compound, on ip administration, failed to significantly inhibit subcutaneously implanted L1210 whereas earlier variants, under the same conditions, provided significant tumor inhibition. In this drug series the observed order of relative drug effectiveness alters with changing site of tumor implantation.
 ...
PMID:Potential antitumor agents. 23. 4'-(9-Acridinylamino)alkanesulfonanilide congeners bearing hydrophilic functionality. 89 84

A series of 87 L1210 active 4'-(9-acridinylamino)alkanesulfonanilides has been screened against L1210 cells (10(5)) implanted at various sites (ip, sc, ic) employing early ip drug administration for a limited time. With each implantation site a different most active congener was selected. For good activity against tumor implanted remotely from the ip drug administration site, an agent should be more lipophilic than that found optimal for ip implanted tumor. An acridine 4-CH3 group appears to assist drug translocation, possibly by sterically hindering binding to nonproductive sites. An unprotected NH2 group on the acridine ring system is incompatible with activity against sc implanted tumor. Agents in which NH2 is shielded by N-acetylation, N-monomethylation, or ortho substitution with a bulky group can inhibit sc implanted tumor.
 ...
PMID:Potential antitumor agents. 20. Structure-activity-site relationships for the 4'(9-acridinylamino)alkanesulfonanilides. 100 26

Tumors of the central nervous system were stained with acridine orange. Photographs were taken during observation through ultraviolet light. Cellular detail was not recognizable but malignant tumors fluoresced more than benign tumors.
 ...
PMID:Fluorescence microscopy in tumors of central nervous system: a method of recognizing malignancy with acridine orange. 118 65

Binding of the fluorochrome acridine orange (AO) to nucleic acids in situ is studied by automated cytofluorometry in two differentiating cell systems: Friend virus-transformed murine erythroleukemia induced to differentiate by dimethyl sulfoxide, and phytohemagglutinin-stimulated human lymphocytes. The specificity of the stain for deoxyribonucleic acid is discussed on the basis of data obtained by cell treatment with nucleases. Evidence is presented that in the case of Friend leukemia cells, but not phytohemagglutinin-stimulated lymphocytes, a significant change in the number of AO-intercalating sites in DNA occurrs during differentiation. These results suggest that changes in nuclear chromatin occurring during cell differentiation may be correlated, in some but not all systems, with changes in accessibility of DNA in situ to intercalating dyes. The role of divalent cations, especially Mg2+, in the conformation of nuclear chromatin and in modulation of the accessibility of nucleic acids to AO is discussed. The method provides a tool for the study of nucleic acid-protein interaction in situ, and in some cell systems it may be applicable as a marker for recognition of cell transformation, differentiation or neoplasia.
 ...
PMID:Cytofluorometric studies on conformation of nucleic acids in situ. I. Restriction of acridine orange binding by chromatin proteins. 125 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>