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Biomedical subjects

W C Rose

Publications and source records attributed to W C Rose.

At least 91 records · Page 5Linked to original sources
PubMed1973

Enhanced toxicity for mice of pactamycin with bacterial endotoxin.

Combinations of pactamycin and Salmonella typhosa 0901 endotoxin, administered simultaneously, killed more BALB/c mice than comparable doses of either agent alone The slopes of the dose-response curves for combinations of endotoxin and pactamycin were parallel to both that for endotoxin alone and the antitumor drug alone; therefore, no new mechanism of toxicity has been evoked by the combination. The synergistic toxicity of endotoxin and pactamycin was due to an in vivo interaction rather than a direct reaction between the two agents. Phenobarbital pretreatment protected the mice from toxicity of the antitumor agent alone but not from the lethal action of the combination. Pretreatment with endotoxin increased the resistance of the mice to both endotoxin alone and the combination. Third agents unable to protect mice from the synergistic toxicity of endotoxin and pactamycin were alpha[p-(fluoren-9-ylidenemethyl)-phenyl]-2-piperidine-ethanol, neomycin, phenylbutazone, polymyxin B, and tybamate. Prednisolone pretreatment alleviated the toxicity of the combination. For the restricted series of killed bacteria and bacterial products tested for capability to enhance the toxicity of pactamycin, only gram-negative bacterial cells were potent. These results indicated that pactamycin rendered the mice more susceptible to endotoxin and that endotoxin was the causal lethal agent.

Animals↗
PubMed1972

Enhanced toxicity for mice of vincristine and other chemotherapeutic agents with Salmonella typhosa endotoxin and Pseudomonas aeruginosa.

The toxicity of Salmonella typhosa 0901 W endotoxin for BALB/c mice was potentiated by the administration of 375 mg of cyclophosphamide per kg, 16 mg of daunomycin per kg, 80 mg of methotrexate per kg, 8 mg of pactamycin per kg, 20 mg of polyinosinic-polycytidylic acid per kg, 1,000 mg of procarbazine per kg, and 1 or 4 mg of vincristine per kg. l-Asparaginase (20,000 units per kg) failed to potentiate endotoxin. Sedation following administration of 45 mg of pentobarbital per kg was prolonged in mice that had received 20,000 units of l-asparaginase per kg, 4 mg of daunomycin per kg, 120 mg of methotrexate per kg, 8 mg of pactamycin per kg, 10 mg of polyinosinic-polycytidylic acid per kg, 500 mg of procarbazine per kg, 2 mg of vincristine per kg, 2 mg of endotoxin per kg, or multiple doses of endotoxin. Mice pretreated with multiple endotoxin doses experienced a significant reduction in their lethal responses due to vincristine-endotoxin combinations; however, endotoxin-pretreated mice were more susceptible to vincristine alone than were normal mice. Simultaneous administration of 1 or 2 mg of vincristine per kg and 1 mg of endotoxin per kg produced greater lethality than sequential regimens. Pretreatment of mice with 65 mg of phenobarbital per kg on 4 consecutive days protected against vincristine-endotoxin combinations. Liver homogenates prepared from mice exposed previously to vincristine were capable of inactivating endotoxin. Vincristine lethality was increased by simultaneous administration of heat-killed cells of Pseudomonas aeruginosa isolated from mouse feces.

Animals↗
PubMed1971

Enhanced toxicity for mice of combinations of antibiotics with Escherichia coli cells or Salmonella typhosa endotoxin.

Enhanced lethality for BALB/c mice has been observed after the administration of Salmonella typhosa endotoxin with either actinomycin D, cycloheximide, or nogalamycin. The dose of actinomycin D required to kill half of the mice (LD(50)) was 0.8 mg/kg in normal animals, 0.35 mg/kg in mice administered 0.08 mg of endotoxin per kg, and 0.28 mg/kg in mice administered 0.2 mg of endotoxin per kg. The LD(50) of endotoxin in normal mice was 12 mg/kg and in mice given 0.4 mg of actinomycin D per kg was 0.067 mg/kg. The LD(50) of actinomycin D in mice administered 1.8 x 10(8) live Escherichia coli cells per kg or 1.8 x 10(9) heat-killed E. coli cells per kg was reduced to 0.4 mg/kg. The LD(50) of cycloheximide was 181 mg/kg in normal animals and 28 mg/kg in mice administered 4 mg of endotoxin per kg. The LD(50) of endotoxin in mice given 120 mg of cycloheximide per kg was 0.02 mg/kg. Enhanced lethality due to various combinations of cycloheximide and endotoxin was abolished by pretreatment of mice with endotoxin. The LD(50) of nogalamycin was 21 mg/kg in normal mice and 13 mg/kg in mice receiving 1 mg of endotoxin per kg.

Animals↗
PubMedDate not supplied

Transforming growth factor beta 1: lack of in vivo antitumor activity on A549 and Wehi 3BD+ tumors.

A large number of reports have described the potential of transforming growth factor beta 1 (TGF-beta 1) as an antitumor agent on the basis of its antiproliferative action on a wide variety of tumor types in culture. In this report we now extend the assessment of TGF-beta 1's antitumor potential by evaluation in vivo versus the mouse monomyelocytic leukemia, Wehi 3BD+, and the human lung adenocarcinoma, A549. In culture both Wehi 3BD+ and A549 cells, sampled from in vivo, were sensitive to inhibition (greater than or equal to 50%) by TGF-beta 1 (greater than or equal to 1 ng/ml) in a 6 day proliferation assay. Despite their sensitivity to TGF-beta 1 in culture, in vivo the growth of neither tumor was reproducibly altered following treatment with various doses, routes and schedules of TGF-beta 1. For example, the median lifespan of mice inoculated with Wehi 3BD+ cells (10(3) or 10(5) cells, ip) was not increased by TGF-beta 1, given as 9 daily ip injections or 7 days of continuous ip infusion. Dose levels in these studies ranged over greater than 2 logs and were escalated to include those frankly lethal (28 micrograms/mouse by injection or 7 micrograms/mouse/day by infusion). Furthermore, the growth of A549 tumors implanted sc in athymic mice was not inhibited by iv injection (every 3 days for 5 injections or 6 consecutive daily injections), sc treatment distal to the tumor (every 3 days for 5 injections or continuously infused for 14 days), or even sc injection adjacent to the tumor (every 3 days for 5 injections), although dose levels of TGF-beta 1 covered a wide range including those which produced lethalities. On the basis of cumulative dose, continuous infusion of TGF-beta 1 by both ip and sc routes was more toxic than frequent injections given by the same routes. These studies indicate lethality is reached without a meaningful tumor inhibition being produced following ip, sc, or iv injections, and sc or ip infusions of TGF-beta 1.

Adenocarcinoma↗
PubMedDate not supplied

Experimental tumor inhibitory and toxic properties of the mitomycin A analogue 7-(2-hydroxyethoxy) mitosane (BMY-25551).

BMY-25551, 7-(2-hydroxyethoxy)mitosane, was selected from a series of mitomycin A (MMA) analogues for more detailed study. As with other members of this class, it was shown to be 8 to 20 times more potent than mitomycin C (MMC) in cytotoxicity to murine and human tumor cell lines in vitro, in causing DNA cross links in vitro, and in dose levels for tumor inhibition in vivo. BMY-25551 appeared to be more effective in tumor inhibition than MMC against P388 leukemia and B16 melanoma in mice and comparable to MMC against L1210 leukemia and Madison 109 lung carcinoma. BMY-25551 was also comparable to MMC in hematologic depression in mice. Factors affecting its possible utility in humans are discussed.

Animals↗
PubMedDate not supplied

In vivo model development of cisplatin-resistant and -sensitive A2780 human ovarian carcinomas.

The human ovarian carcinoma, A2780, and a derived cisplatin-resistant subline, A2780 cDDP, were developed as in vivo sc models in athymic mice. The tumor volume doubling time (TVDT) of both lines was calculated for tumors of between 250 mg and 1 gm, determined in both unselected (unstaged) tumor-bearing mice as well as mice whose tumors were (staged) between 50 and 200 mg when selected for observation. Similar mean TVDT (+/- SD) of 2.3 (+/- 0.5) and 2.7 (+/- 1.1) days for unstaged A2780 and A2780/cDDP tumors, respectively, and 2.2 (+/- 0.5) and 2.5 (+/- 0.7) days for staged A2780 and A2780/cDDP tumors, respectively, were observed. Each of the tumor settings just described was used to assess cisplatin's antitumor activity following ip and iv injections. Antitumor activity was expressed predominantly as gross log cell kill (LCK) and occasionally as percent inhibition. The staged tumor models used with iv cisplatin therapy evolved as the preferred system. Against staged A2780, the mean maximum LCK (+/- SD) associated with iv cisplatin therapy was 2.5 (+/- 1.0) based on 9 experiments, whereas with iv cisplatin versus staged A2780/cDDP yielded 0.5 (+/- 0.3) mean maximum LCK in 16 experiments. The sensitive and cisplatin-resistant staged tumor models were also used to evaluate three platinum analogs, carboplatin, iproplatin, and tetraplatin. All three cisplatin analogs were active (greater than or equal to 1 LCK) versus A2780 but not A2780/cDDP. Thus, the A2780 and A2780/cDDP tumor models demonstrated reproducible sensitivity and resistance, respectively, to cisplatin, and provide an in vivo system for evaluating cisplatin analogs.

Animals↗
PubMedDate not supplied

An in vivo human tumor xenograft model of etoposide resistance.

HCT-116 and HCT-116/E represent human colon carcinoma lines characterized in vitro as sensitive and resistant, respectively, to etoposide. Using both subrenal capsule (src) and sc implants, we sought to develop in vivo tumor models of these cell lines. Src implantation of tumor fragments into athymic mice yielded reproducible growth (165-271%) for both tumor models during the 10-day assay period. The maximum therapeutic effects for etoposide on the preferred schedule (Days 1 and 5, ip) were (mean +/- SD) 78% +/- 10% tumor inhibition versus src HCT-116 compared to 45% +/- 14% tumor inhibition versus src HCT-116/E (p less than 0.001). The modest but significant differential sensitivity toward etoposide seen in the src tumor setting was not observed in the sc tumor models. Principally, this was due to the insensitivity of sc HCT-116 to etoposide, even when treatment was initiated one day post-implant. Interestingly, mitomycin C, included as a positive reference drug, was more active versus sc HCT-116/E than sc HCT-116. In summary, src tumor models for etoposide sensitivity and resistance have been developed as in vivo counterparts for cell lines with characterized differential sensitivity to etoposide in vitro.

Adenocarcinoma↗