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At least 19 recordsLinked to original sources
PubMed1978

[Action of aureolic acid and dactinomycin group antibiotics on human brain tumors in culture].

The cytotoxic effect of antitumour antibiotics, such as dactinomycin, mithramycin, variamycin and olivomycin on the cells of the human brain tumours (multiform glyoblastoma, arachnoidendotelioma and astrocytoma) grown by the method of the primary plasmic culture was studied. Dactinomycin was superior to the antibiotics of the aureolic acid group in the rate and level of the cytotoxic effect on the tumour cells: 76 per cent of the above tumours were sensitive to dactinomycin, 56 per cent to mithramycin and 52 per cent to variamycin and olivomycin. Among the total number of the tumours sensitive to the drugs the number of the highly sensitive tumours amounted to 57.9 per cent for dactinomycin and 30.8--38.5 per cent for the antibiotics of the aureolic acid group. Definite differences in the efficiency of the antibiotics of the aureolic acid group with respect to different types of the brain tumours were observed.

Antibiotics, Antineoplastic↗
PubMed1979

Late treatment of murine lupus erythematosus with dactinomycin (actinomycin D). I. Course and longevity.

Dactinomycin treatment a of group of (NZB X NZW)F1 hybrid female mice was delayed until the age of 6-6 1/2 months, by which time the immune complex disease was well established. Three animals of the original twenty-eight had already died, ten had heavy proteinuria and a few were oedematous. The dactinomycin dose was 3.5 microgram per day, which was suspended when significant weight loss occurred. Twelve of the thirteen experimental mice were alive at 12 months of age, eleven at 15 months, but only eight by 20 months, whereas all twelve control animals had died by the age of 11 months. These results and the supporting data on body weight and renal function indicate that dactinomycin can at least arrest the disease process and may improve it. The mechanism is not known, but it may be the result of a reduced availability of DNA or an alteration in its properties following combination with dactinomycin.

Animals↗
PubMed1976

Effects of dactinomycine (actinomycine D) on budless hydra and during its budding process.

The effect of dactinomycine (actinomycine D) is manifested in various ways, which depends upon its concentration and animal condition at the time of treatment. Dactinomycine is citotoxic in stronger concentations so hydra dies quickly. In thinner concentrations it stops the mitotic activity of the cell, but the basic metabolic processes continue as before. Interstitial cells differenciate into cnidoblasts for some time, the cnid production is not halted, but all of these cells disappear as well as zimogen cells which dedifferentiate into gastrodermal interstitial and into mucous cells. Such animals live longer but die eventually. The effect of dactinomycine is generally milder on animals with a larger cell mass, in hydras with the budding tendency where exist such reserves and in those hydras in which the budding process has begun. In these a part of mobile undamaged zimogen cells can remain. They keep their reproduction ability. These animals can survive and keep on growing normally.

Animals↗
PubMed1977

Combination chemotherapy with bleomycin, cyclophosphamide and dactinomycin for the treatment of osteogenic sarcoma.

Thirteen patients with osteogenic sarcoma were treated with multiple drug chemotherapy consisting of bleomycin, cyclophosphamide and dactinomycin. The dosage schedule used was: bleomycin 12 mg/m2/day, cyclophosphamide 600 mg/m2/day, and dactinomycin 450 microgram/m2/day. All drugs were given intravenously for two consecutive days. Treatment was repeated every 2 weeks. Toxicity included severe nausea and vomiting (managed with antiemetics and intravenous hydration) and manifestations of bone marrow depression. Of 13 patients, eight were previously treated with high dose methotrexate with citrovorum factor rescue, cyclophosphamide and Adriamycin. Of these eight, three patients had objective evidence of tumor regression (37.5%). Five of five previously untreated patients had objective evidence of tumor regression. The overall response rate in osteogenic sarcoma patients to BCD was 61.5%. The combination of BCD appears to be more active against osteogenic sarcoma than cyclophosphamide alone or Adriamycin alone. The relative safety with which BCD can be administered makes this combination a valuable adjunct to high dose methotrexate with citrovorum factor rescue and Adriamycin in the treatment of osteogenic sarcoma.

Adolescent↗
PubMed1978

Dactinomycin treatment of murine lupus erythematosus. I. Renal disease and longevity.

Three groups of female (NZB X NZW)F1 hybrid mice were treated with an intermittent regimen of dactinomycin (actinomycin D), 3.5 microgram. daily. Median survival was doubled in two of the groups and increased by more than 75 per cent in the third. Most of the treated animals never had significant proteinuria. When kidneys from 14 treated mice, which died between the ages of 11 and 20 months, were examined by light and fluorescence microscopy, most showed the lesions of normal aged CBA and C57BL/6 mice, some expansion of the mesangial matrix and increased cellularity, consistent with deposition of immunoglobulins and complement components in the mesangium, generally sparing the capillary loops. Four of the 14 animals, three of them long-lived, had advanced renal glomerular disease. These data indicate that dactinomycin, by whatever therapeutic mechanism, permits very extended survival of B/W female mice, the large majority of them without significant renal disease.

Animals↗
PubMed1978

[Experimental study of the organotropic properties of dactinomycin].

Dactinomycin was studied pharmacologically on experimental animals. When dactinomycin was administered to the test-animals in doses close to the therapeutic ones for humans, suppression of the bone marrow blood formation was registered in spite of some increase in the number of the reticulocytes and thrombocytes in the peripheral blood and acceleration of the process of blood coagulation. In addition, the urea nitrogen blood levels increased. When the drug was administered in higher doses, suppression of the bone marrow blood formation was pronounced and the number of the leucocytes, reticulocytes and thrombocytes in the peripheral blood decreased. The rate of the blood coagulation decreased, while the biochemical values of the blood were indicative of impairement of the liver and kidney functions.

Animals↗
PubMed1978

Treatment of malignant ovarian germ cell tumors: response to vincristine, dactinomycin, and cyclophosphamide (preliminary report).

From November 1971 to November 1975, 27 patients with malignant germ cell tumors of the ovary (excluding pure dysgerminoma and tumors containing trophoblastic elements) were treated with vincristine, dactinomycin, and cyclophosphamide; 12 patients received other therapy. Fourteen tumors were pure endodermal sinus tumors, two were embryonal carcinomas, 11 were mixed germ cell tumors and 12 were immature teratomas. Of 23 patients with surgically resected disease (Stages I-IIA) only seven have failed. Median follow-up for 16 patients remaining free of disease is 24.5 months. Restaging (second-look) laparotomies were done in 15 patients. Eight were negative. Fifteen of the patients had tumors with endodermal sinus elements. Six of these have failed. Of 16 patients with advanced disease (Stage IIB, III and recurrent), eight have responded to chemotherapy, eight have failed. Median follow-up period for those remaining free of disease is 26.5 months. Six have had negative second-look surgery and one had mature teratoma. Four of eight cases which contained endodermal sinus elements responded to chemotherapy and remain disease-free. Grade 3 hematologic toxicity was seen in eight patients, dose-limiting gastrointestinal toxicity in five patients, dose-limiting neurotoxicity in five patients.

Adolescent↗
PubMed1975

Effects of intratracheal instillation of dactinomycin on pulmonary edema and phosphatase activity of the lung lavage fluid in rats.

Intratracheal (i.t.) administration of protein synthesis inhibitors produced pulmonary edema. Of those inhibitors studied, dactinomycin (act. D) was the most potent. Severity of lung damage due to act. D was dose- and almost age-related. Maximal intensity of pulmonary edema was reached on the 3rd day following administration and remained constant for 14 days. Histopathological studies revealed confluent edema of the entire lung. Pretreatment with act D induced tolerance to an LD100 edematogenic dose of thiourea. The effects of i.t. instillation of act. D appear to be localized in the pulmonary tissue. Lung lavage fluid collected from drug-treated rats had higher acid and alkaline phosphatase activities, higher protein content and more leukocyte infiltration than that of control.

Animals↗
PubMedDate not supplied

Mobilization of leucocytes and subsequent release of histamine and lysosomal enzymes into the peritoneal and pleural cavities of rats by actinomycin D (dactinomycin).

1. The effects of intraperitoneal injections of actinomycin D on the temporal characteristics of the accumulation of the inflammatory exudate and cells into the peritoneal and pleural cavities were studied in male Sprague Dawley rats. 2. A measurable quantity of the exudate appeared in both cavities within 24 h and reached maxima in the peritoneal and pleural cavities on the fourth and third days, respectively. Thereafter, the accumulated volume of liquid decreased progressively in the peritoneal cavity but stayed more or less at about the same level in the pleural cavity until the sixth day. 3. The pooled peritoneal and pleural exudates contained neutrophils, macrophages, mast cell and eosinophils. The leucocyte infiltration occurred in two phases, the maximum cell numbers being found on the third and fifth days. A precipitous fall in the number of leucocytes occurred on the fourth day. Neutrophils and macrophages accounted for 85-95% of the total number of leucocytes. 4. The supernatant of the inflammatory exudate after centrifugation at 3,000 g contained histamine and the soluble lysosomal enzyme proteins, acid phosphatase and beta-glucuronidase until the sixth day following the initial dose of actinomycin D. 5. It is suggested that the release of lysosomal enzymes in the exudate, subsequent to leucocyte mobilization and the release of histamine from the mast cells, are probably involved in the genesis of inflammatory conditions induced by actinomycin D.

Acid Phosphatase↗
PubMed1977

Regeneration of proximal and distal part of hydra body cut in the middle of gastral cavity and treated with dactinomycine.

Hydras were cut in the middle of the gastral part of the body. The part with the hypostome is marked as H, and the one with the foot as P. Both parts were treated with actinomycine D in 0,5 mg : 200 ml water solution. H-parts are much more sensitive to the effect of actinomycine than P-parts, and P lives considerably longer. It is supposed that such reaction are the result of specificity of H and P cell composition, and of the growth direction which is characteristic of hydra in general. H-part has a proportionally greater number of differentiated cells and this relatively smaller number of non-differentiated cells is spent in it quicker than in P-part in which they are more numerous. The growth direction has a decisive influence on further life of H- respectively P-part. Namely, H- in growth direction does not have any damaged body regions (hypostome and tentacles are intact) and it lacks the amputated P-part i.e. gastral region with foot: the region which is on the opposite side of growth direction of hydra. H-part has all the characteristic cells of this body region, so after amputation mostly it does not change. Unfavourable effect of citostatic manifests sooner and H-part desintegrates quicker. On the contrary, P-part lacks the hypostome with tentacles, and these are the body parts in the growth direction. Zimogen cells can dedifferentiate and differentiate. The hypostome and tentacles regenerate as far as is allowed by actinomycine.

Animals↗
PubMed1975

The influence of selected cytostatics on human trophoblast in vitro.

The effect of cytostatics (Methotrexate, Oncovin and Dactinomycin) on early human trophoblast in vitro was studied by the tissue (organ) culture technique according to Trowell and by brief incubation with thymidine 3H. The cytostatics were tested by the method of Tanneberger in clinical and tenfold higher doses. The criteria for cytostatic efficacy were based an activity of DNA, histologic and histochemical changes, and secretion of hormonal chorionic gonadotropin. In vitro cultures of trophoblast were found to be a good model for evaluation of cytostatics, and the tested chemotherapeutics were effective chemotherapeutically. Upon addition to in vitro cultures they changed the structure and function of trophoblastic cells, resulting in depression of DNA resynthesis, histologic changes, changes in enzyme activities assessed histochemically, and impaired HCG secretion. The most pronounced effects were obtained with Dactinomycin or with a combination of Dactinomycin and methotrexate. Methotrexate alone had the weakest effect on DNA resynthesis and structure of the trophoblastic cells. The effect achieved with methotrexate after 120 hours was equal to the effect of Dactinomycin after 48 hours. Comparison of the histologic and hormonal results with DNA activity showed concordance between the intensity of morphologic and hormonal changes and impairment of nucleic acid functions.

Acid Phosphatase↗
PubMed1977

Focal chemotherapy of brain tumours using semipermeable membranes.

Semipermeable silastic rubber membranes can be used to diffuse focally a variety of chemicals including antitumour drugs. Of the eight drugs tested, in vitro tests showed the best diffusion with dactinomycin, mithramycin, and oncovin, and the poorest diffusion with bleomycin, fluorouracil, and thiotepa. Biological testing was performed with mithramycin, dactinomycin, and oncovin using tissue cultures of human glioblastoma and subcutaneous implants of mouse ependymoblastoma. All three drugs caused rapid tissue culture cell death with direct injection, and impeded tumour growth when given intraperitoneally. Dactinomycin by silastic diffusion proved more effective than mithramycin against tissue cultures, but neither drug had a significant effect against local tumours treated with implanted drug capsules. Silastic diffusion of oncovin reduced tumour sizes significantly ipsilateral to the implant, compared to contralateral implants and to untreated controls.

Animals↗
PubMed1975

[Possibilities and limits of pre-therapeutic neoplasm sensitivity cytostatics tests under short-term conditions].

The following cytostatic agents were tested for activity in vivo and in vitro inWalker carcinosarcoma 256 of the rat: cyclophosphamide, triaziquon, 5-fluorouracil, methotrexate, adriamycin, dactinomycin, daunorubicin, hydroxyurea, procarbazin and vincritine. With the exception of vincristine, the results of therapy in vivo could be predicted by using a rapid in vitro test system. This involved, for cyclosphosphamide, triaziquon, adriamycin, and daunorubicin, the measurement of 3H-uridine or 3H-thymidine incorporation. The activities of methotrexate and 5-fluorouracil could be determined from 3H-deoxyuridine incorporation and that of dactinomycin from 3H-uridine incorporation. The results of short-term tests (uring adriamycin, daunorubicin, and dactinomycin) in roughly 100 human tumors were compared with data in the literature on therapy with the same cytostatic agents. Good agreement was found between the results of in vitro tests and the literature data on clinical therapy.

Animals↗
PubMed1977

Effect of inline filtration on the potency of drugs administered intravenously.

The binding of cephalothin sodium, phenobarbital sodium, dexamethasone sodium phosphate, isoproterenol hydrochloride, digoxin, dactinomycin and phenytoin sodium to three intravenous inline filters--a 5-micrometer stainless steel depth filter, a 0.2-micrometer cellulose ester membrane and a 0.2-micrometer polycarbonate membrane--was studied. The experiments were conducted simulating inline i.v. filtration of these drugs in three i.v. solutions--lactated Ringer's, 5% dextrose and normal saline. Cephalothin was assayed colorimetrically, phenobarbital and phenytoin spectrophotometrically, and the other drugs by radiotracer technique. Binding of the drugs to the filter was found to be insignificant from a therapeutic standpoint, except for dactinomycin which bound to the 0.2-uicrometer filters. The binding of dactinomycin was approximately 13% of the amount administered through cellulose ester and polycarbonate membranes, respectively. The binding occurred during the initial period of filtration of the drug solution. It was concluded that inline filtration of drugs administered in relatively high does should not present any problem concerning the reduction of the therapeutic potency because of filtration.

Cephalothin↗
PubMed1975

Single and combination chemotherapy for primary murine bladder cancer.

Single and combination chemotherapy was evaluated for antitumor activity against N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT)-induced bladder carcinoma in syngeneic mice. Two hundred fifty C3H/He mice having ingested FANFT for 10 months were randomly divided into groups of 30, and the following regimens initiated: cyclophosphamide (Cy), cis-diam-minedichloroplatinum (cis-Pt-II), dactinomycin, adriamycin, Cy plus cis-Pt-II, Cy plus 5-fluorouracil, and Cy plus adriamycin. The drugs were administered for 3 weeks. Each regimen was capable of producing a significant reduction in the mean bladder weight (MBW) when compared to a groups not receiving therapy (108.3 mg). Adriamycin (MBW equal 69.5), dactinomycin (49.6), and cyclophosphamide (42.9) were the best single agents, but the greatest inhibition of tumor growth was achieved by the combination of cyclophosphamide with 5-fluorouracil (38.3) or adriamycin (37.3). These combination chemotherapeutic regimens were able to effect a significant reduction in the number of bladders with Stage C tumors. It is hoped that information gained from this new animal model which allows evaluation of many antitumor drugs within a relatively short period of time will lead to therapeutic trials in patients with locally advanced or metastatic bladder cancer.

Animals↗