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Biomedical subjects

W R Shapiro

Publications and source records attributed to W R Shapiro.

At least 91 records · Page 5Linked to original sources
PubMed1979

Human brain tumor transplantation into nude mice.

Seven human brain tumors were transplanted into the brains (6/7 takes) and subcutaneous tissues (7/7 takes) of athymic nude mice. Compared to experimental animal brain tumors, these tumors, taken directly from patients in the operating room and transplanted, grew more slowly in the mice; their growth rates following explant generally paralleled those in the patients. A rough correlation was seen between the degree of the tumor's malignancy and both successful take and rate of growth following explant. The tumors' growth rates increased during serial transplantation after explant. Two tumors developed into long-term serial lines; both came from gliosarcomas. Preliminary chemotherapy experiments with these two lines demonstrated different chemosensitivities. One line was very sensitive to the nitrosoureas and resistant to procarbazine; the other line was more sensitive to procarbazine than to the nitrosoureas. This model permits study of the biologic behavior of human brain tumors growing intracerebrally and subcutaneously in nude mice.

Animals↗
PubMed1979

Enhancement of CNS penetration of methotrexate by hyperosmolar intracarotid mannitol or carcinomatous meningitis.

Intracarotid (i.c.) hyperosmolar mannitol enhances central nervous system (CNS) penetration of intravenous (i.v.) methotrexate (MTX) in normal adult rats. A fivefold augmentation in the CSF:serum and ipsilateral brain:serum MTX concentration ratios was observed 1 hour after drug administration. Intravenous mannitol had no such effect. Rats with meningeal carcinomatosis have a partial defect in blood-brain barrier function, and the CSF:serum MTX concentration ratio was 4.6 times higher in these animals than in normal rats prior to mannitol therapy. Intracarotid hyperosmolar mannitol further augmented the blood-brain barrier permeability to intravenous MTX. Intracarotid mannitol increased the therapeutic effect of MTX, since rats with meningeal carcinomatosis that received i.v. MTX and i.c. mannitol experienced a slight enhancement in survival.

Animals↗
PubMed1977

Metastic tumor of the brain: development of an experimental model.

The injection of a suspension of Walker 256 carcinoma cells into the carotid artery of rats produced a model of hematogenously spread cerebral metastases. Most animals died from massive extracerebral tumors of the head and jaw; brain tumors were present in only one-quarter. External carotid artery ligation prior to tumor inoculation did not increase the incidence of fatal brain tumor. When cyclophosphamide, 15 mg/kg, was injected as a single dose on the fourteenth day after tumor inoculation, most of the extracerebral tumor disappeared. Fifty percent of the animals so treated were cured of tumor, but 90% of the remainder died of large intracerebral tumors. Severe cytopathic changes resulting from cyclophosphamide were present in extracerebral or choroid plexus tumors but were mild or nonexistent in intracerebral tumors. These selective effects of cyclophosphamide suggest that water-soluble agents are less effective against tumor in the brain than against extracerebral tumors despite the fact that metastatic tumor breaks down the blood-brain barrier.

Animals↗
PubMed1977

Experimental spinal cord compression by epidural neoplasm.

We have developed an experimental model of spinal cord compression in rats. Tumor injected anterior to the T-12 vertebral body grows through the intervertebral foramina to compress the cord and produces paraplegia in 3 to 4 weeks. Evidence for vasogenic edema in spinal cord compressed by tumor includes increased water content, leakage of horseradish peroxidase into gray matter, and histologic evidence of edema. The vascular supply to the cord overlying the tumor appears to be compromised. Both spinal cord edema and clinical symptoms are lessened by treating symptomatic animals with dexamethasone.

Acute Disease↗
PubMed1977

Treatment of experimental spinal cord compression caused by extradural neoplasms.

Epidural spinal cord compression was produced in rats by injection of Walker 256 carcinoma cell suspension anterior to the T-12 or T-13 vertebral body. The tumor grows through the intervertebral foramina to compress the spinal cord and produce paraplegia in 3 to 4 weeks. The effect of several treatments upon clinical signs was assessed. Dexamethasone caused a significant but transient improvement in neurological function. Radiation therapy likewise improved neurological function, and was more effective when given by a high-dose protracted course than when given either in a single dose or a low-dose protracted course. Laminectomy was not helpful in relieving neurological symptoms. Dimethyl sulfoxide did not relieve neurological symptoms. Cyclophosphamide was most effective in relieving neurological symptoms, and most of the animals that were treated with that drug when they were severely weak but still able to move their hind limbs recovered fully. Some animals that were totally paraplegic when treatment began recovered function after radiation therapy or cyclophosphamide treatment, but recovery was better if treatment was started when animals could still move their hind limbs. This animal model appears to be a useful way of studying the treatment of human spinal cord compression produced by epidural neoplasms.

Animals↗
PubMed1976

Treatment of malignant glioma. A controlled study of chemotherapy and irradiation.

Thirty-three patients with malignant glioma were randomly divided into two groups after extensive tumor resection. Those in group A received, every five to eight weeks, a course of chemotherapy consisting of intravenously administered carmustine, 80 mg/sq m/day for three days, and vincristine sulfate, 1.4mg/sq m on days 1 and 8. Patients in group B were treated identically and received radiation therapy (RT) as well, 4,500 rads whole brain plus 1,500 rads to the side of the tumor. The median survival time of group A was 30 weeks, while that of group B was 44.5 weeks, but the overall survival curves were not significantly different. The median survival times exceeded the 17 weeks reported elsewhere in comparable patients not receiving postoperative therapy. Estimates of the quality of survival suggested (1) the two groups were not comparable following randomization, possibly influencing the results; and (2) postoperative radiation and chemotherapy do not increase morbidity and offer a longer period than other treatments during which patients' conditions remain stable or improve.

Brain Neoplasms↗
PubMed1976

Comparison of 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine and cytosine arabinoside in the treatment of murine brain tumor.

2,2'-Anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine (anhydro-ara-FC) was compared with cytosine arabinoside (ara-C) in the treatment of ic implanted murine Glioma 261. Both drugs given in ip doses of 500 mg/kg immediately inhibited the uptake and incorporation of tritiated thymidine into the DNA of brain tumor, small intestine, and spleen. Inhibition of DNA synthesis in the tumor recovered within 12 hours of anhydro-ara-FC administration, yet it remained depressed greater than 50% of control 12 hours after ara-C administration. Inhibition in the small intestine recovered within 24 hours of drug administration with either agent while inhibition in the spleen remained depressed greater than 24 hours. Anhydro-ara-FC administered ip in single doses less than or equal to 1500 mg/kg or in multiple doses less than or equal to 200 mg/kg three times a week for ten doses failed to prolong the survival of tumor-bearing mice, and minimal increased survival followed drug administration of 200 mg/kg every 24 hours for five doses. In contrast, ara-C in doses of 50, 100, or 200 mg/kg three times weekly for ten doses significantly increased the survival of tumor-bearing animals between 17% and 36%.

Ancitabine↗