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Biomedical subjects

R G Selker

Publications and source records attributed to R G Selker.

At least 37 records · Page 2Linked to original sources
PubMed1990

Response of malignant glioma cell lines to epidermal growth factor and platelet-derived growth factor in a serum-free medium.

The use of a serum-free culture system for assessing the growth factor responsiveness of malignant glial cells is described. The mitogenic properties of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were examined in three human malignant glioma cell lines (T98G, U87, and U138). Each of the three had high-affinity EGF receptors and all responded in a dose-dependent fashion to physiological concentrations of EGF. These cell lines also showed a pronounced mitogenic response to PDGF which equaled or exceeded that achieved with EGF. Simultaneous stimulation with both factors produced an additive response, which approximated that obtained in medium supplemented with 10% fetal calf serum. The authors conclude that functional EGF and PDGF receptors were present in the human malignant glial tumors studied. The response of the human glioma lines to these growth factors in many respects parallels the response seen in fetal astrocytes tested under similar conditions. In contrast, the behavior of two chemically induced rat gliomas (9L and C6) differed significantly from that seen in the human lines, suggesting that the rat lines may not be entirely acceptable as models for studying the growth characteristics of human malignant glial tumors.

Brain Neoplasms↗
PubMed1989

Results of a randomized trial comparing BCNU plus radiotherapy, streptozotocin plus radiotherapy, BCNU plus hyperfractionated radiotherapy, and BCNU following misonidazole plus radiotherapy in the postoperative treatment of malignant glioma.

In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30-35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma.

Adolescent↗
PubMed1989

Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001.

Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

In vitro generation and antitumor activity of adherent lymphokine-activated killer cells from the blood of patients with brain tumors.

A procedure for enrichment in recombinant interleukin-2 (rIL2)-activated natural killer (NK) cells was developed and used for in vitro generation of antitumor effector cells from the peripheral blood of 20 patients with central nervous system (CNS) tumors. In comparison to the patients' unseparated mononuclear cells and nonadherent lymphocytes cultured in the presence of 1000 U/ml of rIL2 for up to 3 weeks, interleukin-2-stimulated lymphoid cells, when purified by adherence to plastic, proliferated better (up to 6,720-fold expansion) and achieved up to five times higher levels of antitumor activity against K562 cell targets and NK-resistant glioblastoma cell targets. Two-color flow cytometry analysis showed that cultures of cells purified by adherence to plastic which had the best proliferation contained 10% or less of CD3+Leu19- T-lymphocytes, while the unseparated lymphokine-activated killer cell cultures which proliferated poorly contained up to 85% of CD3+Leu19- T-cells. Cultures of adherent lymphocytes which reached the highest antitumor cytotoxicity were enriched in CD3+Leu19+ effectors (60-80%); the proportion of CD3-Leu19+ NK-cells was not greater than 25% in these cultures. Thus, using the technique of 24- or 48-h activation in rIL2 and adherence to plastic, and in contrast to the results obtained with cells from normal donors, it was not possible to enrich in activated NK cells from the blood of patients with CNS tumors. Instead of activated NK cells, a population enriched in non-major histocompatibility complex-restricted cytotoxic T-cells (CD3+Leu19+) was obtained in cultures from most but not all patients. Low NK cell activity and elevated numbers of circulating CD3+Leu11+ cells seen in the blood of these patients, previously treated by surgery/radiation/chemotherapy and maintained on steroids, could be responsible for the preferential adherence and subsequent expansion to plastic of IL2-activated non-major histocompatibility complex restricted cytotoxic T-lymphocytes.

Antigens, Differentiation↗
PubMed1986

On a method of dosimetry planning and implantation of 125I for interstitial irradiation of malignant gliomas.

Utilizing a treatment concept geared to the cell cycle of the glioma, a CT determined tumor volume and boundaries, 125I dosimetry data and a reference probe template system, it is now feasible to produce a volume implant of an intracranial mass based on prospective planning with accurate postimplant correspondence. The cell cycle oriented treatment plan is felt perhaps to be more beneficial in the treatment of the highly malignant glioblastoma, considering its wide range of cell cycle times, large irregular volumes and large dormant segment, than would be a similar isotope source delivering a high-dose rate, but short-term course irradiation. Seeds are contained within Lexan tubes, thereby allowing accurate assessment of postoperative dosimetry planning, negating seed migration and possible 'cold spots' within a volume implant as would be noted with unrestrained seeds. The implant described in this communication is designed to remain in place for approximately 20 months, a period of time well beyond the life expectancy of any group of failed glioma patients. Although ultimately the system may prove most beneficial in newly diagnosed glioblastomas, the current trial in patients having previously undergone 5-6000 rads of external beam therapy is not considered hazardous to surrounding brain.

Brachytherapy↗
PubMed1986

Brain-tumor cell kinetics correlated with survival.

In a review of 38 glioblastoma patients for whom fresh tissue kinetic data were available before any therapy was instituted, no correlation between the labeling index and survival time could be statistically determined. This relationship seems entirely consistent with the published theoretical determinants of tumor behavior: that is, altered ability for growth arrest and differentiation, constantly evolving mutant sublines, genetic instability, and an ever-changing metabolic and vascular environment.

Brain Neoplasms↗
PubMed1985

Immunobiology of primary intracranial tumors. Part 10: Therapeutic efficacy of interferon in the treatment of recurrent gliomas.

Human lymphoblastoid alpha-interferon was administered intravenously or intramuscularly to 19 patients with recurrent gliomas. Each patient had previously undergone surgery and radiation therapy. The treatment course consisted of 8 weeks of therapy with an escalating daily dosage and number of days of treatment per week to a total dose of 900 X 10(6) U/sq m. Response to treatment was determined by serial computerized tomography (CT) scans. Seven of the 17 evaluable patients were determined to be treatment responders at 12 weeks (1 month after completion of treatment), and the other 10 patients exhibited tumor progression during this period. Median survival time was 511 days for the responders versus 147 days for the non-responding patients. Interferon appears to be efficacious in the treatment of recurrent anaplastic gliomas as defined by CT brain scan responses following therapy.

Adult↗
PubMed1984

Effects of induced total-body hyperthermia on phosphorus metabolism in humans.

The effects of total-body hyperthermia on phosphorus homeostasis are controversial. To evaluate the problem, 10 clearance studies were performed in seven patients undergoing total-body hyperthermia as an adjunct to the treatment of solid malignant tumors. Total-body hyperthermia was associated with significant reduction in plasma phosphorus concentration from a baseline value of 3.51 +/- 0.18 to 0.6 +/- 0.1 mg/dl (p less than 0.001), returning to baseline following cessation of total-body hyperthermia. The clearance of phosphorus increased from 15.2 +/- 2.5 to 26.1 +/- 3.1 ml per minute (p less than 0.01), and the fractional excretion of phosphorus increased from 11.37 +/- 2.2 to 47.68 +/- 9.7 percent (p less than 0.01). The reduction in plasma phosphorus during total-body hyperthermia was also associated with a significant reduction in the renal threshold phosphorus concentration from 3.17 +/- 0.16 to 0.38 +/- 0.08 (p less than 0.001). The changes in phosphorus homeostasis during total-body hyperthermia were independent of changes in circulating parathyroid hormone level, urinary cyclic AMP excretion, and arterial carbon dioxide tension.

Bicarbonates↗
PubMed1983

Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma.

Within 3 weeks of definitive surgery, 609 patients with histologically demonstrated, supratentorial malignant glioma were randomized to receive, in addition to 6000 rads of radiotherapy, one of four treatment regimens: carmustine (BCNU), high-dose methylprednisolone, procarbazine, or BCNU plus high-dose methylprednisolone. We analyzed the data for the total randomized population and for the 527 patients (87% with glioblastoma multiforme) in whom the initial protocol specifications were met (the valid study group). Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone. No other pairwise comparisons demonstrated differences significant at the 0.05 level. However, the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis. This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma. In addition, future protocols may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose. More effective regimens for the treatment of malignant glioma should be sought.

Adolescent↗
PubMed1982

Pathological correlation of CT ring in recurrent, previously treated gliomas.

The meaning of the enhancing ring commonly seen on computerized tomographic (CT) scans in patients with recurrent, treated glioblastoma has long been of concern. Does the ring represent radiation necrosis, pseudocapsule formation, compressed adjacent brain, or, in fact, a peripheral zone of viable tumor? We employed a multiple intratumoral biopsy technique at the time of reoperation to investigate this ring. Pathological evidence is presented documenting the content of the ring to the viable tumor. It is suggested that perhaps treatment failure may be determined on sequential CT examinations by comparing the volume and degree of contrast enhancement.

Brain Neoplasms↗
PubMed1982

Potentiation of carmustine-cranial irradiation-induced myelosuppression by cimetidine.

In nine patients with glioblastomas, the histamine H2-receptor antagonist cimetidine was found to augment the myelosuppressive activities of carmustine and cranial irradiation. The nadir in neutrophil cell counts in this group averaged 650 +/- 220/microL. In a comparable series of 31 patients who did not receive cimetidine, the lowest neutrophil cell count averaged 2,160 +/0 240/microL. Further, marked suppression of these cells in the patients receiving cimetidine extended through day 42 of the treatment cycle. By contrast, the patients treated with carmustine and cranial irradiation alone did not experience significant neutropenia. This suggests that cimetidine may enhance the myelosuppressive effects of cytotoxic therapy.

Adult↗
PubMed1981

Intracranial pencil injuries.

A case of delayed central nervous system manifestations of intracranial penetration by a pencil is presented. Twenty-one additional cases of cerebral injury by pencils are reviewed and discussed. A high index of suspicion, liberal use of the computed tomographic scan, and early operative intervention in cases with cranial perforation are important points in the management of these injuries.

Brain Injuries↗
PubMed1980

Prediction of BCNU pulmonary toxicity in patients with malignant gliomas: an assessment of risk factors.

Symptomatic pulmonary disease occurred in 20 per cent of 93 patients with anaplastic gliomas being treated with carmustine (BCNU). An analysis of the variables has revealed a relation between the occurrence of pulmonary toxicity on the one hand, and the total cumulative dose of BCNU, the number of cycles over which the BCNU was administered, the history of lung disease, the patient's age, and the platelet-count nadir after the first course of BCNU on the other. An equation has been generated that allows prediction of pulmonary toxicity during the course of therapy with BCNU with 80 per cent accuracy. Pretreatment analysis of individual cases should allow safe use of BCNU and prevention of most of the serious pulmonary complications caused by this drug.

Adult↗
PubMed1980

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced pulmonary fibrosis.

Clinical data are presented on 14 patients undergoing BCNU therapy for a primary intracranial glioma (11 biopsied, 3 suspected) in whom pulmonary fibrosis developed as a consequence of the therapy. Pulmonary diffusion abnormalities, dry hacking cough, and chest x-ray changes herald the onset of the process. Microscopic evaluation of lung specimens revealed a wide spectrum of change including hyaline membrane formation, alveolar septal thickening, interstitial fibrosis, and granuloma formation. It is concluded that BCNU causes pulmonary fibrosis that is primarily but not necessarily dose-related and may not be reversible.

Adolescent↗
PubMed1979

Effect of total body temperature on toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

One hundred eighty-two rats were divided into groups to test the effect of three different total body temperature levels on the toxic effect of three different dose levels of 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and to assess the effect of delayed total body temperature elevation on BCNU breakdown products. Results were tabulated on the basis of life survival figures. At depressed total body temperatures (28 degrees C), normally expected toxicity was avoided. Elevated body temperatures, on the other hand, enhanced the toxic effect of BCNU. Delayed total body temperature elevation (3 and 6 days after BCNU administration) created similar toxicity. This finding was not observed when total body temperature elevation was delayed 10 days. The results point toward an interesting interaction between BCNU and heat (immediate and delayed) on the basis of an elevated metabolic rate of tissue, a synergistic effect of two therapeutic modalities, interference with normal reparative processes by the combination, or an enhancement of retained serum protein-bound breakdown products of BCNU.

Animals↗
PubMed1979

Prolonged cerebral "luxury perfusion" after removal of a convexity meningioma.

Following total removal of a convexity meningioma, serial computerized tomographic scans disclosed massive hemispheric contrast enhancement compatible with "luxury perfusion". Maximum enhancement occurred one month following the operation and resolved two months postoperatively. Luxury perfusion appeared to be associated with slowly resolving cerebral edema.

Brain↗