Biomedical subjects

V A Levin

Publications and source records attributed to V A Levin.

At least 181 records · Page 10Linked to original sources

PubMed1980

Heuristic modeling of drug delivery to malignant brain tumors.

It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the "breakdown" in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.

Animals↗

PubMed1980

Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability.

The rat brain capillary permeability coefficient was determined for 27 compounds. The relationship of permeability to octanol/water partition coefficient and molecular weight was found to be predictable for drugs with molecular weights less than 400.

Animals↗

PubMed1980

Chemotherapy of pediatric posterior fossa tumors.

Results of chemotherapy of recurrent posterior fossa tumors in children are presented. Cerebellar astrocytoma, ependymoma, and brain stem glioma have all shown objectively determined responses to treatment with nitrosourea compounds (BCNU or CCNU). Medulloblastoma has shown objectively determined response to various chemotherapeutic agents; but in our experience the best responses have been obtained with a combination of a nitrosourea (CCNU), vincristine, and procarbazine. Although chemotherapy after recurrence has significantly prolonged the life of the patients, cure has not been achieved. Theoretical considerations regarding the failure of initial therapy and the inadequacy of subsequent chemotherapy are discussed.

Astrocytoma↗

PubMed1980

Prognostic significance of the pretreatment CT scan on time to progression for patients with malignant gliomas.

Case histories of 61 patients receiving multimodality therapy for primary malignant brain tumors were reviewed for factors visible on the computerized tomography (CT) scan that correlated with the interval of time from diagnosis and pretherapy evaluation to the time of documented tumor progression. The initial pretreatment CT scan of each patient was reviewed. Midline shift, peritumor low density (edema), the greatest diameter of tumor enhancement, and the greatest diameter of the intratumor low-density area were measured prior to radiation therapy and chemotherapy. Using a Weibull survival probability model, time to tumor progression was most satisfactorily fitted using two covariates, the volume of enhancing tumor (for instance, contrast-enhancing tumor less intratumor low density), and the presence of a peritumor low-density area. Patients who exhibited a small amount of contrast-enhancing tumor with peritumor low density tended to have a longer time to progression than patients with large contrast-enhancing tumor volume and no peritumor low density. Midline shift was not as important a variable as the extent of tumor contrast enhancement or peritumor low density.

Brain Neoplasms↗

PubMed1980

Cysts in malignant gliomas. Identification by computerized tomography.

The clinical course, computerized tomography (CT) scans, and postmortem reports for 265 patients treated for malignant brain tumors were reviewed. Forty-one patients underwent reoperation for tumor recurrence and one had needle aspiration as a diagnostic procedure; of these patients, seven (3% of 265 and 17% of 42) were diagnosed as harboring tumor cysts and 10 (25% of 41) as having necrotic tumor centers. The CT scans on the 17 patients harboring tumors with surgically confirmed cysts and necrotic centers were reviewed; criteria for distinguishing between cysts and central necrosis are suggested. The relative benefits of repeated aspiration and surgical therapy for these cystic lesions are discussed.

Astrocytoma↗

PubMed1980

Cerebrospinal fluid polyamines in patients with Glioblastoma multiforme and anaplastic astrocytoma.

Eighteen cerebrospinal fluid polyamine determinations in 12 patients with glioblastoma multiforme and 76 determinations in 37 patients with anaplastic astrocytoma were evaluated. Cerebrospinal fluid polyamine levels showed no significant relationship to the degree of malignancy or to enhanced tumor volume or volume of tumor central low density as determined by contrast-enhanced computerized tomography. A significant correlation was found between polyamine levels and the proximity of the tumor to the cerebral ventricles. Polyamine levels were correlated with clinical status as determined by neurological examination, radionuclide scan, and computerized tomography. Compared with those of stable patients, cerebrospinal fluid polyamine levels were significantly elevated in patients with recurrent tumors; however, elevation of polyamine levels did not appear to precede tumor recurrence. A large fraction of the results were false-positive or false-negative results. In contrast to our findings in patients with medulloblastoma, it appears that cerebrospinal fluid polyamine levels determinations may be of little use for monitoring tumor progression in patients with glioblastoma multiforme and anaplastic astrocytoma.

Astrocytoma↗

PubMed1980

In situ drug delivery.

Drug delivery to tumours and the accessibility of tumour cells to drugs remains a problem of foremost importance and is affected by many factors. We will discuss models we have developed for drug delivery from tumour capillaries to tumour cells, and drug delivery from well perfused, well oxygenated tumour regions to less well perfused hypoxic regions in terms of computer simulation of drug delivery for the anticancer agent BCNU and the hypoxic cell radiosensitizer misonidazole.

Animals↗

PubMed1980

Brain tumor chemotherapy: an evaluation of agents in current use for phase II and III trials.

The reported English-language literature since 1969 on chemotherapy for malignant brain tumors has been collated, and reports of drugs or drug combinations used in phase II or III trials or with adjunctive therapies are reviewed. A significant fraction of the literature contained only anecdotal information, and even in the reports of more systematic trials, the criteria used to evaluate response were variable, ranging from subjective evaluation of clinical improvement to more stringent evaluations using one or more neurodiagnostic tests. A more consistent method of determining response is needed to facilitate comparison of different treatment protocols in the future, and guidelines for this are suggested. It appears that drugs of small molecular size (less than 450 daltons) and high lipid solubility have been the most effective. Single-agent chemotherapy using cell-cycle-specific drugs has, however, been disappointing. The nitrosoureas (especially BCNU) used either singly or in combination have consistently been the most effective agents in phase II and III trials. The combination of irradiation with adjunctive BCNU remains, for the present, the standard against which all other phase II and III protocols should be compared. New drugs for phase II evaluations are sorely needed. There is also need for new combination-drug and sequential-drug protocols for evaluation. The use of radiosensitizing agents with more novel radiation therapy fractionations and in combination with adjunctive drug therapies holds some promise for improving the disappointing results obtained thus far with chemotherapy for malignant brain tumors.

Antibiotics, Antineoplastic↗

PubMed1980

Lipophilic drugs and lipoproteins: partitioning effects on chloroethylnitrosourea reaction rates in serum.

Chloroethylnitrosoureas are anticancer agents that undergo chemical reactions in vitro and in vivo to form active alkylating agents. The rate at which lipophilic chloroethylnitrosourease decompose in serum is faster than in aqueous solution and comparable to in vivo clearance rates. The increase in reaction rate is known to be caused by a reaction catalyzed by protein. Addition of lipoproteins to serum stabilizes chloroethylnitrosoureas to degradation. A model is presented that correlates serum decomposition rates to lipoprotein concentrations. This model involves partitioning of lipophilic chloroethylnitrosoureas into the hydrophobic core region of the lipoproteins where the chloroethylnitrosourea is chemically stable and is not free to undergo protein binding nor aqueous chemical degradation reactions. Normal interindividual variations of serum lipoprotein concentrations and hence partitioning may be a significant factor affecting the tissue distribution and pharmacokinetics of lipophilic drugs.

Carmustine↗

PubMed1979