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Biomedical subjects

J M Slater

Publications and source records attributed to J M Slater.

At least 55 records · Page 3Linked to original sources
PubMed1995

Concurrent radiation therapy and chemotherapy in the treatment of primary squamous cell carcinoma of the vulva.

BACKGROUND: Interest in combined modality treatment and in quality of life issues may affect the choice of radical vulvectomy as the treatment of choice in many vulvar carcinomas. To evaluate the potential role of combined radiation and chemotherapy with or without local excision as primary treatment for squamous cell carcinoma of the vulva, the outccomes of 19 patients with this disease treated with combination therapy were reviewed. METHODS: Nineteen patients were treated between September 1987 and October 1992. Fifteen patients had American Joint Committee on Cancer Stage III disease; 4 had Stage II. All had clinically negative inguinal lymph nodes with the exception of two patients who had positive ipsilateral inguinal nodes that were removed before treatment. The patients received 45-50 Gy to the pelvis and inguinal nodes with concurrent chemotherapy that consisted of 5-fluorouracil given as a 96-hour continuous infusion (1000 mg/m2/d) during weeks 1 and 5 of radiation. A single dose of mitomycin-C (10 mg/m2) during the first day of chemotherapy has been used since November 1991. Ten patients were boosted with implants or electrons and 6 others underwent local excision. RESULTS: The median follow-up was 34 months. Responses were determined clinically 1 month after completion of the radiation and chemotherapy. Clinically, complete responses were obtained in 10 patients (53%), partial responses in 7 (37%), and no response in 1; 1 patient progressed during treatment. The combined modality therapy (radiation/chemotherapy/with or without wide local excision) resulted in a local control rate of 74% (14/19). All five treatment failures occurred within 6 months of treatment. Four of these patients were rendered disease free by radical vulvectomy and/or exenteration, for an overall local control rate of 95% (18/19). CONCLUSION: Concurrent radiation therapy and chemotherapy with local excision performed as needed, appears to be a reasonable alternative to radical vulvectomy in patients with primary squamous cell carcinoma of the vulva. Radical surgery remains a viable option for patients in whom primary therapy has failed.

Adult↗
PubMed1995

Proton therapy for cranial base tumors.

Proton irradiation and other charged-particle modalities have demonstrated effectiveness in controlling cranial base tumors and other lesions. The combination of capabilities available with heavy charged particles makes for a desirable therapeutic option that offers the opportunity for tumor ablation while preserving normal tissue function, with obvious implications for quality of life.

Chondrosarcoma↗
PubMed1995

Effects of proton irradiation on radiolabeled monoclonal antibody uptake in human colon tumor xenografts.

A major limitation of radiolabeled monoclonal antibodies (MAbs) for cancer imaging and therapy is their low accumulation within solid tumors. We, and others, have previously shown that pretreatment of a tumor mass with gamma radiation can increase the level of radiolabeled MAb at the tumor site. Unlike that of conventional radiation, the dose distribution of protons allows for increasing the dose to the cancer volume while reducing the normal tissue dose. The Proton Radiation Therapy Facility at LLUMC treats patients and conducts research. In this study, we sought to determine if preirradiation with proton beam can enhance the localization of radiolabeled MAb within xenotransplanted human colon tumors. T380 colon tumors, implanted s.c. into athymic mice, were subjected to proton irradiation (10 Gy, single dose) when mean tumor volume was 125-135 mm3/group. 111In-ZCE025, a murine MAb directed against carcinoembryonic antigen, was injected i.p. 2 h later, and biodistribution studies were performed 38 h thereafter. Animals irradiated with 60Co and given either 111In-ZCE025 or 111In-MOPC21, an irrelevant MAb, served as controls. The mean percentage of injected radioactivity localized within tumors was highest in the group treated with protons + 111In-ZCE025 when expressed on a per gram basis (%ID/g = 19.3). Somewhat unexpectedly, higher radioactivity was also noted in the normal tissues of these animals compared to other groups. The mean %ID/g tumor values for those given 60Co + 111In-ZCE025 or the antibody alone were 12.5 and 9.0. Our data show that preirradiation of solid tumors increases the localization of tumor-specific radiolabeled MAb at the tumor site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Magnetic resonance imaging as a monitor of changes in the irradiated rat brain. An aid in determining the time course of events in a histologic study.

RATIONALE AND OBJECTIVES: Optimal dose schedules and total dose of ionizing radiation for human central nervous system malignancy are not known. An animal model has been developed for the investigation of rat central nervous system response to proton irradiation using magnetic resonance imaging (MRI). A clinical MRI device was used to monitor the response of the rat brain after irradiation as a possible indicator for histologic injury as a function of time and dose. METHODS: Single-dose fractions of protons were delivered to the left brain of 25 adult Sprague-Dawley rats. T1- and T2-weighted images were obtained using a 1.5-T MRI device via a 12-cm diameter coil at 4- to 6-week intervals after irradiation. Coronal images were evaluated by visual inspection and relaxation maps comparing the control and irradiated hemispheres. Histologic review was conducted on all rats' brains after death. RESULTS: Proton irradiation was delivered successfully to only the left brain of the animals. Histologic review confirms the location and extent of tissue damage demonstrated on MRIs obtained in vivo. Statistically significant differences were seen in the T2-weighted relaxation times in the irradiated cerebral hemisphere compared with the unirradiated hemisphere. CONCLUSION: The proton hemibrain rat model can be used to test treatment schedules of irradiation for central nervous system response using MRI to noninvasively document early and late effects within the same animal.

Animals↗
PubMed1994

Effects of radiolabelled murine antibody infusion on TNF-alpha, IL-1 beta, and soluble IL-2 receptor in cancer patients.

This study evaluates the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and soluble IL-2 receptor (sIL-2R) in cancer patients infused with radiolabelled murine monoclonal antibodies (MAbs) for the purpose of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 with lung cancer) before and at 4 and 7 days after infusion of either conventional intact 111In-MAb or a bifunctional antibody delivery system. For all subjects, except one, this was the first exposure to murine MAb. Before infusion, higher levels of TNF-alpha, IL-1 beta, and sIL-2R than the average expected in the plasma of healthy individuals were found. A significant decrease was noted in TNF-alpha when preinfusion concentrations were compared to 4 day (P < 0.01) or to 7 day (P < 0.05) postinfusion values. A 50% or greater decrease in IL-1 beta was also observed in most individuals with time after infusion. In contrast, sIL-2R concentrations remained relatively stable during the 1 week follow-up period. However, strikingly different patterns in the IL-1 beta and sIL-2R levels were noted in the subject who had received two previous murine antibody infusions. Our data show that the administration of radiolabelled murine antibodies, either conventional or bifunctional, can significantly alter plasma levels of TNF-alpha and IL-1 beta. These cytokines are important in immunoregulation and, perhaps also, in modulation of neoplastic growth.

Adult↗
PubMed1994

Relative biological effectiveness and microdosimetry of a mixed energy field of protons up to 200 MeV.

We have studied radiation effects utilizing the new 250 MeV Synchrotron at Loma Linda University Medical Center. In this paper we present the data collected for the survival of Chinese hamster lung (V79) cells, that were irradiated with a beam of mixed energy protons up to 200 MeV. The RBE for protons, when compared to 60Co gamma rays, ranged from a low of 1.2 at the high energy portion of the field to 1.3+ at the low energy portion of the field. These results are consistent with the measured lineal energy (microdosimetric) spectra.

Animals↗
PubMed1994

Simple solid wire microdisc electrodes for the determination of vitamin C in fruit juices.

Five micrometre gold microwire encapsulated in a thin sheath of borosilicate glass produced by the Taylor wire process can be used in the fabrication of gold microdisc electrodes. By combining glass-coated wire with fluorinated ethylene propylene lined poly(tetrafluoroethylene) tubing, disposable, high quality electrodes suitable for a range of applications, can be fabricated easily. Chemical etching techniques were investigated as a means of finishing the electrode surface, and the resulting surfaces were studied using scanning electron microscopy and evaluated electrochemically using model redox compounds. The electrodes obtained by this fabrication method were used to determine L-ascorbic acid and the results were compared with values obtained using high-performance liquid chromatography and iodimetry. Measurements were taken in buffered solutions, fruit juices, and directly in fruit. Previous studies have shown that ascorbic acid fouls the electrode surface during voltammetric analysis; these problems were overcome by using potential cycling techniques.

Ascorbic Acid↗
PubMed1992

Role for proton beam irradiation in treatment of pediatric CNS malignancies.

The ability to vary the proton energy (depth of beam penetration) and modulate the dose distribution at the end of range permits delivery of an increased dose to the designated cancer-containing volume with a reduced dose to overlying normal brain tissue. The evolution of childhood CNS malignancy following therapy is reviewed to identify radiation response variables indicating where the proton dose distribution will improve the therapeutic ratio. The review documents that of the 1262 children expected to develop CNS malignancy in 1989, only 43% will survive 5 years. About 75% of those with medulloblastoma and over 90% with astrocytoma die from persistent (in-field) disease. When the patient has been treated with radiation, it is accepted that disease persistence indicates the cancer dose was insufficient. Potentially 536 children could show an improved incidence of local control and improved survival from an increased cancer dose available from proton irradiation. As the total dose and volume of brain irradiated is increased about 1800 cGy, brain dysfunction increases, producing a spectrum of functional and intellectual deficits which are age and volume related. About 900 irradiated patients would have fewer in-field histologic and functional changes if the dose to normal brain, or the volume of brain irradiated, is reduced by an improved dose distribution. A proton beam treatment plan, delivering a cancer dose of 7400 cGy, is simulated for a thalamic astrocytoma. The dose distribution of this plan is compared with an x-ray plan used to treat a patient, in which a dose of 5400 cGy was delivered to the astrocytoma. Comparative isodose distributions and dose-volume histograms indicate a decreased integral dose to normal brain and a decreased volume of normal brain irradiated, even as the cancer dose is boosted 2000 cGy with protons.

Brain Neoplasms↗
PubMed1992

Carcinoma of the tonsillar region: potential for use of proton beam therapy.

An investigation of treatment results in tonsillar region carcinomas was conducted, with particular attention to local control and morbidity from current therapy. The purpose of the investigation was to identify problems that might be resolvable with a superior treatment modality. A search was made of the National Library of Medicine's MEDLINE database, covering local control, survival, and morbidity from current therapies; dose-response relationships; and prognostic indicators. Three-dimensional radiotherapy plans were developed for representative cases, comparing photon-beam plans with proton-beam plans. Locoregional control is a major problem, and morbidity from standard therapy is high. Comparative treatment plans reveal that proton beams can deliver higher doses to the tumor volume, with significantly reduced radiation to salivary glands and mandible, than can photon-beam irradiation. The absorption and distribution characteristics of protons provide the radiation oncologist with a superior tool for treating patients with tonsillar region carcinomas. The therapeutic advantage accrues from these superior characteristics, not from an inherent biologic advantage.

Humans↗
PubMed1992

The potential for proton beam therapy in locally advanced carcinoma of the cervix.

Advanced cervix cancer has a local failure rate of 40-45% when treated with a combination of external beam irradiation and intracavitary implants, and approximately 60-65% when treated by external beam irradiation alone. Because of the absorption characteristics of protons, there is the potential for improved dose distributions and delivery of greater total doses to cervical neoplasms. Using computer-modelled examples, this theoretical advantage has been tested and the results have been extrapolated to show a therapeutic advantage in local control and morbidity. The first example shows the use of protons and intracavitary implants in advanced cervix tumors. Larger tumor doses are possible with protons than with photons, while the dose-volume to normal structures is decreased. In the second example, external proton beam treatment alone also reveals significantly higher tumor doses and lower normal tissue doses, compared to photon irradiation. With new proton therapy facilities being designed and built in the United States and overseas, protocols are being designed to evaluate the therapeutic potential of proton therapy in locally advanced cervix cancer.

Female↗
PubMed1992

The proton treatment center at Loma Linda University Medical Center: rationale for and description of its development.

Proton radiation, a continuation of radiation oncology's historic search for an optimum dose distribution, offers superior characteristics for clinical radiation therapy. A complete facility for clinical proton radiation therapy has been designed for and constructed at Loma Linda University Medical Center. To bring about this achievement, a consortium of engineers, physicists, and physicians interested in the clinical applications of protons was necessary. The accelerator, the beam transport and delivery systems, the building, and the personnel who operate the system were all brought together to fully exploit the properties of protons for patient treatments, which are now underway.

Academic Medical Centers↗
PubMed1990

Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients.

This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients.

Aged↗
PubMed1990

Proton beam therapy: a promising method of locoregional cancer control.

Proton beams offer superior characteristics for clinical radiation therapy, including the capability to localize precisely the dose to the desired target volume. Such precision enables the radiation therapist to give higher doses to the tumor while avoiding intolerable doses to adjacent normal tissues. Locoregional control is thus increased, and treatment morbidity and side effects are decreased. When it opens in late spring 1990, Loma Linda University Medical Center's proton treatment facility will feature the world's first accelerator and proton therapy system designed for patient care. During the next decade, other similarly-designed proton therapy systems will be built in Canada, England, France, Belgium, Germany, Japan, and South Africa, as well as at Massachusetts General Hospital in the United States.

Facility Design and Construction↗
PubMed1990

Radioisotopic pulmonary lobectomy: feasibility study in dogs.

In search for an alternate treatment for inoperable cancer of the lung in humans, we investigated the possibility that introduction of radioactive material into a selected lobe of the canine lung would effectively destroy that lobe without systemic effects or radiation injury to adjacent organs. Ten million ion exchange microspheres labeled with 740 MBq of phosphorus-32 (32P) were injected through a catheter placed in a selected lobar branch of a pulmonary artery in 12 anesthetized dogs. Six additional dogs served as controls and received 10 million microspheres not labeled with 32P. Organs were harvested from 1 wk to 12 mo after injection and examined grossly and histologically. There was progressive organization and contraction of each necrosed 32P treated lobe which was reduced to a scarred remnant by 12 mo, whereas only minimal inflammatory changes occurred in controls. Of the 32P injected dose, 94% remained in injected lobe, 4%-5% in nontargeted lobes and less than 0.08% in blood. Radioactivity in liver, kidneys, spleen, heart, and bone marrow was less than 0.1% for each organ. Thus, large doses of radiation in the order of 1,500 Gy can be effectively delivered to a selected lobe to produce a "radioisotopic pulmonary lobectomy."

Animals↗
PubMed1989

Age as a prognostic factor in carcinoma of the cervix.

The influence of age on prognosis for carcinoma of the cervix was evaluated for a population of 218 patients treated at Loma Linda University between 1972 and 1982. Treatment methods were consistent over this time interval and were tailored according to age and extent of disease. Minimum follow-up is 5 years. The age groups were less than 35, 35-55, 55-75, and greater than or equal to 75. There was a significantly higher percentage of stages IIB and III in the older (greater than 55) age groups. The age groups were subdivided by stage for analysis of local-regional and distant failures. No significant age differences in local-regional or distant failures were found. Actuarial analysis of disease-free survival demonstrated no significant difference by age group. Age could not be verified as a prognostic factor in this study population.

Adult↗
PubMed1989

Effects of monoclonal antibody, recombinant interferon-gamma, and tumor necrosis factor-alpha in the treatment of human melanoma xenografts.

ZME-018 monoclonal antibody (MAb, IgG2a subclass, 0.04 mg), recombinant human tumor necrosis factor-alpha (rHuTNF-alpha, 10(4) units), and recombinant human interferon-gamma (rHuIFN-gamma, 10(6) units) were injected intravenously into athymic nude mice bearing human malignant melanoma (Brown C5513) xenografts. Sixty-four animals were injected subcutaneously with 0.2 ml tumor chunks 4 days prior to administration of one or more of the treatments. The mice were randomized into eight groups so that mean tumor volume/group before initiation of treatment was similar (212-360 mm3); (a) saline, 2X; (b) rHuTNF-alpha, 1X; (c) rHuIFN-gamma, 1X; (d) ZME-018, 1X; (e) rHuIFN-gamma + rHuTNF-alpha, 1X each; (f) rHu-IFN-gamma + ZME-018 + rHuTNF-alpha, 1X each; (g) rHuTNF-alpha + ZME-018, 2X each; (h) rHuTNF-alpha + ZME-018, 3X each. The order of administration of the agents in those groups given more than one modality is as shown above and each injection was separated by a 24 h period. Tumor volume was measured daily for 9 days after the beginning of treatment. Compared to control mice, minimal suppression of tumor growth was noted when ZME-018, rHuTNF-alpha, or rHuIFN-gamma was used singly, but significantly (p less than or equal to 0.05) slower tumor progression occurred in animals given rHuIFN-gamma + rHuTNF-alpha or ZME-018 + rHuTNF-alpha when compared to controls. Histopathologic analyses of tumor biopsies obtained at 1 and 4 days after the last treatment for each group indicated that 15-95% necrosis was present. Necrosis was most striking in the animals given rHuIFN-gamma + rHuTNF-alpha or the ZME-018 MAb alone. However, the group receiving all three agents exhibited a tumor growth rate similar to that seen in the controls and demonstrated minimal necrosis. These results suggest that ZME-018, rHuIFN-gamma, and rHuTNF-alpha may be useful in the treatment of human melanoma. However, the effects of administration of all three of these agents in a single host needs to be evaluated further.

Animals↗
PubMed1988

Development of a hospital-based proton beam treatment center.

Radiation oncologists recognize a continuing need to improve the radiation dose distribution between a cancer and the surrounding normal tissue. A most promising method of accomplishing this goal is the use of charged particle beam irradiation, the clinical use of which has been investigated for the past 40 years. Since the first clinical studies began at the Lawrence Berkeley Laboratory in 1954, more than 5,000 patients have been treated with protons, using accelerators designed for physics laboratories. Superior results are reported for the control of selected diseases by the ten facilities which are currently investigating proton radiation therapy. The findings have resulted in expansion plans in several of these facilities, and in the formulation of plans for two new facilities. We report on the planned development of a new facility at Loma Linda University, which has contracted with Fermi National Accelerator Laboratory for the design and fabrication of a 250 MeV synchrotron and its beam transport and delivery systems. This facility will be the first in the world to employ a proton accelerator dedicated to medical service and research. As such, it will be available as an international resource to develop and improve the modality.

California↗