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Biomedical subjects

J M Collier

Publications and source records attributed to J M Collier.

10 recordsLinked to original sources
PubMed1992

Ellagic acid protects rat embryos in culture from the embryotoxic effects of N-methyl-N-nitrosourea.

Ellagic acid is a naturally occurring plant phenol that has demonstrated anticarcinogenic and antimutagenic activity in several test systems. Given the common proposed etiopathogenic processes of mutagenesis, carcinogenesis, and teratogenesis induced by genotoxic chemicals, the present study was initiated to determine whether ellagic acid would protect rat embryos in culture from the teratogenic effects of N-methyl-N-nitrosourea (MNU). Ellagic acid alone (as used in these experiments; 50 microM in DMSO) was not embryotoxic. Ellagic acid (50 microM) significantly (P less than 0.01) prevented MNU (75 microM)-induced effects including mortality (absence of heart beat), abnormal formation of the cephalic neural tube derivatives, and delayed differentiation as assessed by a morphological scoring system. These embryoprotective effects were dose responsive. Sequential treatment of embryos with ellagic acid followed by MNU in fresh media also was embryoprotective with no diminution of effect. The site at which ellagic acid interrupts the critical teratogenic events induced by MNU is apparently within the embryo and/or placenta. This model of chemical embryoprotection may be useful in determining the role of cell death and/or mutation in the teratogenic mechanism of action of methylating agents.

Abnormalities, Drug-Induced↗
PubMed1992

Clinical gain from improved beam delivery systems.

The feasibility of dynamic conformal heavy charged particle radiotherapy has been investigated at UCLBL, and shows high promise of: 1. an improved therapeutic ratio and 2. reduction in the number of treatment portals required for efficient treatment delivery. Assessment of dose to tumor and critical structures for several anatomical sites have been carried out using a normal tissue complication algorithm developed at LBL. For high-LET charged particle treatment delivery, dynamic conformal therapy using a raster scanned beam with variable modulation and multileaf collimator appears to be the optimal technique for treatment delivery.

Energy Transfer↗
PubMed1992

Charged particle radiotherapy of paraspinal tumors.

Between 1976 and 1987, 52 patients with tumors adjacent to and/or involving the cervical, thoracic, or lumbar spinal cord were treated with charged particles at the University of California Lawrence Berkeley Laboratory. The histologies included chordoma and chondrosarcoma (24 pts), other bone and soft tissue sarcoma (14 pts), and metastatic or unusual histology tumors (14 pts). Radiation doses ranged from 29 to 80 Gray-equivalent (GyE), with a median dose of 70 GyE. Twenty-one patients received a portion of their treatment with photons. Median followup was 28 months. For 36 previously untreated patients, local control was achieved in 21/36 patients and the 3-year actuarial survival was 61%. Of 16 patients treated for recurrent disease, 7/16 were locally controlled and the 3-year actuarial survival was 51%. For patients treated for chordoma and chondrosarcoma, probability of local control was influenced by tumor volume (less than 100 cc or greater than 150 cc) and whether disease was recurrent or previously untreated. Complications occurred in 6/52 patients, including one spinal cord injury, one cauda equina and one brachial plexus injury, and three instances of skin or subcutaneous fibrosis. Charged particle radiotherapy can safely deliver high tumor doses to paraspinal tumors with good local control.

Adolescent↗
PubMed1992

Recurrent locally advanced nasopharyngeal carcinoma treated with heavy charged particle irradiation.

Between June 1981 and May 1990, 11 patients with recurrent locally advanced nasopharyngeal carcinoma were treated with heavy charged particle radiation at Lawrence Berkeley Laboratory. All patients had previously undergone full course radiotherapy to a median dose of 70.2 Gy [range 61-81 Gy]. Median time to recurrence was 18.2 months. At the time of heavy charged particle radiotherapy treatment, all had evidence of invasion of the base of skull and 7 of 11 had cranial nerve deficits. None of the patients were candidates for brachytherapy because of tumor extent or poor geometry. The tumor histology was squamous cell carcinoma in 10 patients and lymphoepithelioma in one patient. Ten of the 11 patients had received chemotherapy prior to re-irradiation. The heavy charged particle tumor dose delivered ranged from 31.80 GyE to 62.30 GyE (average 50.25 GyE, median 50 GyE). Local control was achieved in 45%. Median survival was 42 months. Actuarial survival was 59% at 3 years and 31% at 5 years (Kaplan-Meier). There were no fatal complications. The results in treating locally advanced recurrent nasopharyngeal carcinoma with heavy charged particles appear superior to those reported by others using photon therapy.

Carcinoma, Squamous Cell↗
PubMed1992

Preliminary results in heavy charged particle irradiation of bone sarcoma.

Between 1979 and 1989, 17 patients with unfavorable bone sarcoma were treated wholly or in part with heavy charged particle irradiation (helium and/or neon ions) at the University of California Lawrence Berkeley Laboratory. The majority of tumors were located near critical structures such as the spinal cord or brain. Gross tumor was present in all but two patients at the time of irradiation. Six patients were treated for recurrent disease. Histologies included osteosarcoma, Ewing's sarcoma, and recurrent osteoblastoma. Four of the osteosarcomata were believed to have been induced by previous therapeutic irradiation for various tumors. Follow-up time since initiation of radiation ranged from 7 to 118 months (median 40 months). The 5-year Kaplan-Maier local control rate was 48%; the corresponding survival rate was 41%. Over half the patients succumbed to distant metastases despite the majority of patients receiving chemotherapy. In this preliminary study, we have shown that heavy charged particle irradiation can be effectively used for control of bone sarcoma. A Phase II trial is warranted to determine optimal treatment for unresectable or gross residual disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Flow cytometric analysis of thymic lymphosarcoma induced by N-methyl-N-nitrosourea in C57B1/6J mice.

N-Methyl-N-nitrosourea (MNU) induces thymic lymphosarcoma in numerous mouse strains. We determined the neoplastic phenotype induced by MNU in 20 C57B1/6J mice. Eleven neoplasms were composed of cells that were CD4-CD8+, four neoplasms were composed of cells that were CD4+CD8+, two neoplasms were mixtures of CD4+CD8+ and CD4-CD8+ cells, and three neoplasms were made up of cells that expressed neither CD4 nor CD8. Expanded populations of CD4+CD8- cells were observed within individual neoplasms. Of 10 neoplasms that were further classified, all were composed of cells that were J11d+, indicating immaturity. CD3 expression was generally negative, while IL2R expression was variable in these neoplasms. These data from C57B1/6J mice, a strain with a low incidence of spontaneous (viral-associated) thymic lymphosarcoma, indicate that a continuous spectrum of immature phenotypes are produced by MNU. The finding that each immature cell population can be expanded in this model system differs from previous reports. Our data do confirm the general finding in AKR mice, a strain with a high incidence of spontaneous thymic lymphosarcoma, that cells with immature phenotypes, particularly CD4-CD8+J11d+, make up MNU-induced thymic lymphosarcomas.

Animals↗
PubMed1991

A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments.

The ability of normobaric oxygen and carbogen (95% O2 + 5% CO2) combined with nicotinamide to enhance the radiosensitivity of two rodent adenocarcinomas and of mouse skin and kidneys, using a 10 fraction radiation schedule, was compared with the effect of radiation in air with and without the drug. Tumour response was assayed using local control and regrowth delay, and compared with acute skin reactions, decreased renal 51Cr-EDTA clearance and reduction in haematocrit. Nicotinamide increased the radiation sensitivity of CaNT tumours under all three different oxygen concentrations tested (21, 95 and 100% oxygen). The effect was statistically significant for oxygen and carbogen but not for air; the combination of nicotinamide with carbogen gave the greatest increase in tumour radiosensitivity. Relative to treatments in air without the drug, the enhancement ratios (ER) at the TCD50 level were 1.17, 1.65 and 1.83 for CaNT tumours irradiated in air, oxygen or carbogen and injected with nicotinamide 1 h before each fraction. The ER in CaRH tumours irradiated in carbogen plus the drug was 1.83, which was greater, but statistically not significantly different, to that seen with carbogen alone (ER = 1.68). In skin, relative to air without the drug, the increase in radiosensitivity by nicotinamide was greater in oxygen and carbogen than in air (1.29, 1.36 and 1.08, respectively). The ERs for both assays of renal damage were similar and lower than those in skin: less than or equal to 1.07, less than or equal to 1.13 and less than or equal to 1.16 for irradiations done in air, oxygen and carbogen plus nicotinamide, relative to air alone. A comparison of these results in the tumours and normal tissues showed that a significant therapeutic benefit was obtained with normobaric oxygen and carbogen combined with nicotinamide. This benefit is greater than observed with other radiosensitizers tested so far. Toxic side effects of the treatment are unlikely in a clinical situation, since prolonged administration of nicotinamide is well tolerated in man. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumour radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment.

Adenocarcinoma↗
PubMedDate not supplied

The effect of patient motion on dose uncertainty in charged particle irradiation for lesions encircling the brain stem or spinal cord.

A specialized charged-particle radiotherapy technique developed at Lawrence Berkeley Laboratory (LBL) is applied to patients with lesions abutting or surrounding the spinal cord or brain stem. This technique divides the target into two parts, one partially surrounding the critical structure (brain stem or spinal cord) and a second excluding the critical structure and abutting the first portion of the target. Compensators are used to conform the dose distribution to the distal surface of the target. This technique represents a novel approach in treating unresectable or residual tumors surrounding the spinal cord or brain stem. Since the placement of the patient with respect to beam-shaping devices is critical for divided-target treatments, a method for calculating dose distributions reflecting random patient motion is proposed, and the effects of random patient motion are studied for two divided-target patient examples. Dose-volume histograms and a normal-tissue complication probability model are used in this analysis. For the patients considered in this study, the normal-tissue-complication probability model predicts that random patient motion less than or equal to 0.2 cm is tolerable in terms of spinal cord complications.

Central Nervous System Neoplasms↗
PubMedDate not supplied

Design of beam-modulating devices for charged-particle therapy.

The computer modeling program used to design beam-modulating devices for charged-particle therapy at Lawrence Berkeley Laboratory has been improved to allow a more realistic description of the beam. The original program used a single calculated Bragg peak to design the spread Bragg peak. The range of this curve was shifted so that Bragg curves of varying ranges could be superimposed. The new version of the program allows several measured Bragg curves with different ranges to be used as input, and interpolates between them to obtain the required data for the superposition calculation. The experimental configuration for measuring these input curves simulated therapy conditions. Seven beam-modulating propellers with spread Bragg-peak widths ranging from 2.2 to 14.4 cm were designed and constructed for a 215-MeV/u helium beam using this new design program. Depth-dose distributions produced by these new propellers were in good agreement with predicted distributions, and these propellers are currently being used clinically.

Equipment Design↗