AMD473 (ZD0473) exhibits marked in vitro anticancer activity in human tumor specimens taken directly from patients.

AMD473 (ZD0473; cis-amminedichloro[2-methylpyridine]platinum [II]) is a new generation anticancer agent that, in preclinical studies, shows evidence of an extended spectrum of antitumor activity and overcomes platinum resistance mechanisms. Here we evaluate the activity of AMD473 (ZD0473) in a panel of 120 human tumor specimens using a soft agar cloning assay (human tumor colony-forming assay). When tumor cells were treated with 1.

Acute behavioral toxicity of pyridostigmine or soman in primates.

Effects of a peripherally active carbamate (pyridostigmine bromide) and a centrally active organophosphate (OP) nerve agent (soman) on performance by rhesus monkeys of a compensatory tracking (primate equilibrium platform, or PEP) task were measured using a balanced Latin-square design to determine the ED50 for pyridostigmine (0.66 mg/kg) and the up-and-down (titration) method to determine the ED50 for soman (2.50 micrograms/kg).

Evaluation of domperidone as a modifier of gamma-radiation-induced emesis.

The D2 antidopaminergic drug domperidone was evaluated, singly and in combination with synthetic adrenocorticoid and an H2 antihistamine, for its ability to reduce the acute emetic effects of 60Co whole-body radiation. Random-source adult male dogs were fasted 12 hr, fed a standard meal, injected 44 min later, and irradiated 47 min after that. Four groups of dogs were irradiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim + Thi), and dexamethasone + domperidone + cimetidine (Dex + Dom + Cim).

Surgical treatment of endometriosis in 50 rhesus monkeys.

Surgical treatment of endometriosis was attempted in 50 female rhesus monkeys (Macaca mulatta). Endometriosis was clinically staged as minimal (8% of the monkeys), moderate (18%), or massive (74%). Elective euthanasia was performed in 15 (30%) of the monkeys.

Animal studies of life shortening and cancer risk from space radiation.

The U.S. Air Force study of the delayed effects of single, total body exposures to simulated space radiation in rhesus monkeys is now in its 21st year.

Occurrence of brain tumors in rhesus monkeys exposed to 55-MeV protons.

Twenty-year observation of monkeys exposed to single doses of high energy protons simulating solar particles revealed that the most prevalent fatal cancers were brain tumors in the group of animals exposed to 55-MeV protons. Of 72 animals (50 males and 22 females) receiving 0.25 to 8.

Performance following a 500-675 rad neutron pulse.

A three-light, three-lever discrete avoidance behavioral task was initiated to study the effects of a 500-675 rad neutron pulse upon performance. Eight primates performed the task for 4 h (3.5 h postexposure) on exposure day and for 4 h on each of 3 d postexposure.

Seventeen-year mortality experience of proton radiation in Macaca mulatta.

This is an interim report on the lifetime study of chronic mortality and its causes under investigation in 31 control (20 males, 11 females) and 217 survivors (124 males, 93 females) of an acute 90-day experiment in rhesus monkeys. Single acute whole-body exposures were made using 32-, 55-, 138-, 400-, and 2300-MeV protons in 1964-1965. Doses ranged from 25 to 800 rad and dose rates from 12.

Prevention of radiation emesis in dogs by combinations of drugs.

Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H2 antihistamine, Pro as an H1 antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were: 167 mg/m2 i.

Proton irradiation and endometriosis.

Female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was 7 years after exposure. The doses and energies of the radiation received were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event, leading to the conclusion that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crewmembers.

Effects of benactyzine on an equilibrium and multiple response task in rhesus monkeys.

Five Macaca mulatta were tested for performance changes following exposure to benactyzine HCl (intramuscular) at four doses ranging from 0.054 mg/kg to 1.7 mg/kg.

The value of estrogen and progesterone receptors in the treatment of breast cancer.

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50 to 60 percent are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of clinical relapse.

Modern approaches to the treatment of breast cancer.

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease.

Steroid hormone receptors in the management of human breast cancer.

Recent insight into the mechanism of steroid hormone receptors in human breast cancer has led to new approaches in treatment strategy. Estrogen receptor (ER) has now replaced clinical criteria in the selection of patients for endocrine therapy. Patients whose tumors do not contain ER should not be subjected to hormonal manipulation.

Protracted radiation-stressed primate performance.

An experimental investigation has been made of the effects of nuclear radiation on the behavior of four trained primates (rhesus monkeys) proficient in control of the primate equilibrium platform during a hypothetical 72-h aircraft mission. The radiation exposure was assumed to result from a radioactive cloud penetration at the start of the mission, with subsequent low dose rate exposure resulting from radioactive debris in and on the aircraft. Minor performance changes were detected in three of four subjects; all experienced emesis.

Performance in a 12-hour, 300-rad profile.

A discrete behavioral task was initiated to study the effects of a 300-rad variable dose rate exposure profile upon positively (food reward) and negatively (mild shock) reinforced groups of primates. Animals performed the task for 12 h. Performance decrements were readily apparent in 2 of 8 shock and 2 of 7 food animals, while delayed reaction times were found in 3 of 8 shock and 3 of 7 food animals.

Regional planning of maternity services.

Analysis of utilization data from maternity units in a ten-county region in New York indicates that more small rural maternity units exist in that region than are needed. A mathematical model is used to ascertain optimal unit sizes, and criteria are developed by which units could be combined for more efficient use of facilities.