Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of halogeno (chloro or fluoro) analogues of phospholipid precursors has been checked for their cytostatic activity both in vitro and in vivo. The compounds included monoacyl-, diacyl-, monoalkyldeoxyhalogenoglycerols and other acylhalogenoalkanols. Analogues of monoacylglycerols or monoalkylglycerols were found to have a strong inhibitory activity on the proliferation of Ehrlich ascites carcinoma cells in suspension culture. The compounds were also effective in vivo. Tolerable doses (e.g. 1/10 of the LD50) given i.p. only once on the first day after transplantation of EAC cells reduced the cell number on day 7 by 99% or increased the survival time about 4-fold. The in vivo efficacy or the ether derivatives was higher than that of the corresponding esters. However, most of the compounds so far investigated had no effect on the survival time or cell number after s.c. application. Moreover, there was no prolongation of the survival time of leukemia L1210 or L184 bearing mice. This shows that the systemic effects of most of the compounds are low and that they have to come into direct contact with tumour cells during application in order to be active. It is discussed whether theese compounds interfere more with the structure of the membrane than with membrane biosynthesis. However, at least in comparison to Tween 80 (which is of poorer cytostatic activity) they show only very low lytic effects on red blood cells.
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PMID:Inhibition of proliferation of Ehrlich ascites carcinoma cells in vitro and in vivo by halogeno analogues of long chain acyl- and alkylglycerols. 54 74

The action of two preparations (I and II) of antibiotic Wr 142 FPG on development of Ehrlich carcinoma, Nemeth-Kellner lymphoma and leukemias L 1210 and P 388 was studied. Preparation I injected s.c. daily during 14 days in doses of 10 mg/kg (1/25 LD50) inhibited growth of Ehrlich carcinoma and Nemeth-Kellner lymphoma subcutaneous tumors in R 3 mice by about 70%. The same preparation in a single i.p. injection (10 mg/kg) in FDF1 mice distinctly prolonged survival of mice inoculated with L 1210 leukemia, but was without effect on P 388 leukemia. Preparation II inhibited growth of solid tumors in doses as low as 0.1-0.2 mg/kg (about 65% inhibition), but in the same doses was ineffective against leukemias L 1210 and P 388 in CDF1 mice.
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PMID:Antibiotics produced by Streptomyces olivaceus 142. III. Influence of antibiotic Wr 142 FPG on development of transplantable tumors in mice. 56 28

The chemotherapeutic effects of 6-diazo-5-oxo-L-norleucine (DON) and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]6-diazo-5-oxo-norleucine (azotomycin) were evaluated in a spectrum of transplantable experimental tumor systems including xenografts of human tumors in athymic mice. Both drugs displayed remarkable activity against the murine leukemia L1210 and P388, the Colon Tumors C26 and C38 and the CD8F1 mammary tumor. No significant activity was observed against Lewis lung carcinoma, B16 carcinoma, B16 melanoma, and intracranial ependymoblastoma. DON and azotomycin also exhibited striking inhibitory effects on the growth of s.c. human tumor (MX-1 mammary, LX-1 lung and CX-1 and CX-2 colon) xenografts in athymic mice. With the exception of one colon xenograft (CX-1), all tumor lines were markedly responsive to both drugs. Tumor regressions below the initial tumor sizes of 100 to 300 mg, albeit temporary, were brought about by one course of treatment every 4 days for 3 doses (at optimal dose) with either drug. Although these drugs have been tested previously in the clinic and have shown only limited therapeutic effectiveness, they seem to worthy of a second and closer look in light of the recent laboratory results.
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PMID:Efficacy of 6-diazo-5-oxo-L-norleucine and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]-6-diazo-5-oxo-norleucine against experimental tumors in conventional and nude mice. 57 61

10-Chloro-5-(2-dimethylaminoethyl)-7H-indolo [2,3-c]-quinolin-6(5H)-one hydrochloride (CIQ) was shown to exert significant antitumor activity against the Ehrlich carcinoma and sarcoma 180 transplantable tumors in mice by the intraperitoneal (ip) or oral (po) routes and when incorporated into diet. A solid tumor induced in BALB/c mice by the subcutaneous (sc) implantation of nonproducer murine sarcoma virus-transformed BALB/3T3 cells was also inhibited by CIQ after ip or po treatment but there was no effect against leukemia L1210 ascites or a transplantable murine renal adenocarcinoma. When tested in rats, CIQ significantly reduced the growth of Flexner-Jobling carcinoma, Murphy-Sturm lymphosarcoma and Walker 256 carcinosarcoma when administered by the ip or po routes. Pretreatment, but not posttreatment, with CIQ slightly inhibited the humoral antibody response of mice to sheep red blood cells. CIQ therefore differs from immunosuppressive agents such as imuran, methotrexate, cytosine arabinoside, or 6-mercaptopurine which affect the antibody response of mice to sheep erythrocytes when administered after immunization.
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PMID:Activity of 10-chloro-5-(2-dimethylaminoethyl)-7H-indolo [2,3-c]-quinolin-6(5H)-one hydrochloride against experimental tumors in mice and rats. 57 26

The incidence of malignancy among patients with Graves' disease who were residents of one Minnesota county was examined in 342 patients between 1935 and 1967. During 4,736 person-years of observation, 32 malignancies were diagnosed; 24 cases were expected and the difference is not significant. Four cases of breast carcinoma were found vs five expected. Other tumor sites were cervix (five), uterus (two), rectosigmoid colon (three), stomach (two), larynx (two), and lung (two). There were three cases of leukemia, and in nine other sites one cancer each was recorded. There was a slightly higher than expected incidence of malignancy in patients who had received 131I therapy; this finding requires further study in a larger patient population. Among patients who received thyroid hormone, the observed incidence of breast cancer was not significantly different from the expected incidence in our population.
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PMID:Incidence of malignant neoplasms of all types of patients with Graves' disease. 58 May 55

The antitumor activity of "blastolysin", a preparation that consisted mainly of glycopeptide fragments of the cell wall of Lactobacillus bulgaricus, was studied. Blastolysin was found to exert a specific antitumor effect on sarcoma S-180, leukemia P-388, plasmacytoma MOPC-315, adenocarcinoma AKATOL, melanosarcoma B-16, carcinoma LIC, and spontaneous tumors in mice. It is of low toxicity, does not inhibit hemopoiesis, and its action on tumor tissue differs considerably from that of the known antitumor chemotherapeutic agents.
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PMID:[Antitumor effect of glycopeptides from the cell wall of Lactobacillus bulgaricus]. 59 7

From the time of its inception in 1955, the Drug Development Program of the National Cancer Institute has relied primarily on transplanted rodent tumor systems in vivo for the evaluation and selection of potential antitumor agents. Although greater emphasis has been placed in recent years on rationally designed drugs, the major effort throughout the history of the program has involved the empirical screening of a wide variety of chemical structures and natural products of varying sources. The initial screening spectrum consisted of three mouse tumors, Sarcoma 180, Carcinoma 755 and Leukemia 1210, based on the retrospective analysis presented in the GELLHORN-HIRSCHBERG Report. As a result of further expermental studies and analyses, the screens changed successively to (1) L1210 plus a spectrum of mouse, rat and hamster tumors, (2) L1210 plus the rat tumor, WALKER 256, (3) L1210, plus P388 for natural products and B16 melanoma and LEWIS lung carcinoma for special studies, and finally (4) P388 as a pre-screen followed by a panel of transplanted tumors and xenografts representing the major tumor sites. The rationale underlying each of the successive changes, and results obtained with each approach, will be discussed.
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PMID:Antitumor screening procedures of the National Cancer Institute. 61 10

Macromomycin is a protein isolated from the culture filtrate of Streptomyces macromomyceticus. It is an antibiotic and also cytotoxic to a broad spectrum of carcinoma cells, the ID50 for P388 leukemia cells being 1 X 10(-9) M. Macromomycin binds rapidly and tightly to the P388 cell membrane and the eventual death of the cell cannot be reversed by either washing the toxin away or treating the cell with trypsin. The cytotoxicity does not appear to be specific for any phase of the P388 cell cycle. Macromomycin is a single polypeptide, pI 5.38, devoid of methionine and arginine residues and contains 4 cysteine residues joined by two intramolecular disulfide bonds. The cytotoxicity results in inhibition of DNA, RNA, and protein synthesis in P388, the latter inhibition occurring a few hours after the inhibition of nucleic acid synthesis. The antibiotic and antitumor activities are destroyed rapidly by ultraviolet light, which gives a product that differs little in amino acid composition, molecular weight, and antigenic property, but can be separated from the native macromomycin by ion exchange chromatography. It is proposed that macromomycin has an ultraviolet-sensitive prosthetic group upon which much of the biological activity is based.
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PMID:Studies on macromomycin, an antitumor protein. 64 Oct 69

Except for oral administration, there was no grossly observed toxicity from carefully administered high doses of amygdalin in the experimental systems used. The compound in high doses was ineffective against the DMBA-induced rat mammary carcinoma and the following transplanted experimental tumors: Sarcoma 180, plasma cell tumor LPC-1, leukemia L1210, Mecca lymphosarcoma, Ridgway osteogenic sarcoma, sarcoma T241, mammary carcinoma E0771, Taper liver tumor, Ehrlich carcinoma (solid and ascites), and Walker carcinosarcoma 256. Amygdalin did not noticeably influence the toxicity or impair the efficacy of these chemotherapeutic agents in their respective systems: Cytosine arabinoside, methotrexate, cytoxan, or 5-fluorouracil in L1210; the latter two in LPC-1; 6-mercaptopurine in Ridgway osteogenic sarcoma; estradiol-17beta or 2alpha-methyldihydrotestosterone propionate in the DMBA-induced rat mammary carcinoma.
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PMID:Antitumor tests of amygdalin in transplantable animal tumor systems. 64 16

Human tissues contain ferritin molecules with a range of isoelectric points but immunoassays for detecting serum ferritin have generally employed antibodies to the more basic liver or spleen proteins. To study the distribution of more acidic ferritins in tissues and serum acidic ferritin has been isolated from normal human heart and a two-site immunoradiometric assay for this protein developed. This assay gives little cross-reaction with spleen ferritin. Tissue ferritins have been fractionated by anion exchange chromatography and assayed with both spleen and heart antibodies. The spleen ferritin assay detects the more basic ferritin and the heart ferritin assay the more acidic ferritin. Acidic ferritins were found in heart, kidney, reticulocytes and HeLa cells. In sera from normal subjects and patients with iron overload, myocardial infarction, leukaemia and carcinoma only low concentrations of heart ferritin were found, although in the pathological sera spleen ferritin concentrations were generally raised. Circulating ferritin contains only a small proportion of molecules with the immunological characteristics of acidic heart ferritin.
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PMID:An immunoradiometric assay for the acidic ferritin of human heart: application to human tissues, cells and serum. 64 67


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