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Biomedical subjects

J A Belli

Publications and source records attributed to J A Belli.

At least 37 records · Page 2Linked to original sources
PubMed1989

Interaction between radiation and drug damage in mammalian cells. IV. Radiation response of adriamycin-resistant V79 cells.

Adriamycin-resistant variants derived from V79 Chinese hamster cells were examined for their radiation response properties. A stable resistant cell line (77A) demonstrated a significant reduction in the extrapolation number of the single-dose radiation survival curve. Second-step mutants from 77A cells exhibited a spectrum of radiation response states including decreased D0 values and large extrapolation numbers. A highly Adriamycin-resistant line (LZ) was found to be radiation sensitive with increased capacity for the accumulation of sublethal radiation injury. LZ cells are known to contain double-minute chromosomes and an amplified gene for the multidrug phenotype and to exhibit multidrug resistant properties. These cells require the presence of Adriamycin in their growth medium to maintain their pleiotropic characteristics. LZ cells became more resistant to radiation following reversion to an intermediate Adriamycin response as the consequence of growth in Adriamycin-free medium. Reverted cells also lost their large capacity for sublethal damage. It is suggested that detailed study of these mutants may provide insight into the identification of radiation-sensitive sites and their relationship to the genetic changes characterizing Adriamycin-resistant cell lines.

Animals↗
PubMed1988

Enhancement of radiation sensitivity by postirradiation hypoxia: time course and oxygen concentration dependency.

We have recently demonstrated that postirradiation hypoxia during colony formation in vitro enhanced the radiation sensitivity of murine tumor cells irradiated and maintained at 0.1% O2. The effect of postirradiation hypoxia was expressed by a significant reduction in the oxygen enhancement ratio. We now demonstrate that this enhancement of radiation sensitivity by postirradiation hypoxia is also observed in a human tumor cell line. The effect was observed at [O2] less than or equal to 0.1%, but was not present at [O2] greater than or equal to 0.5%. Time-course experiments suggested that this enhancement of cell killing by X rays required prolonged exposure to hypoxic conditions.

Animals↗
PubMed1987

2,000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis.

Because toxicity with the use of 3,000 centiGray (cGy) of total lymphoid irradiation (TLI) was observed in an earlier study, 2,000-cGy treatments were delivered in a 2-portal format to 7 patients and in a modified 3-portal fashion to 6 patients, as part of a randomized, investigator-blinded trial of TLI treatment for refractory rheumatoid arthritis. Analysis of combined data from the 13 patients revealed statistically significant improvement in 5 clinical indicators of disease activity at the end of TLI and 6 and 12 months later, accompanied by T4-specific immunosuppression. Management considerations resulted in the introduction of prednisone therapy in 5 patients, methotrexate in 4, and azathioprine in 1 during the interval of 8-12 months post-TLI. Herpes zoster occurred in 5 patients prior to the initiation of this additional therapy. These data indicate that, in patients with rheumatoid arthritis, a TLI dose of 2,000 cGy is sufficient to produce measurable benefit that lasts for 6 months, and that the improvement can be maintained at 12 months by the use of prednisone and methotrexate.

Adult↗
PubMed1987

Radiation therapy of tumors of the brainstem and midbrain in children: experience of the Joint Center for Radiation Therapy and Children's Hospital Medical Center (1971-1981).

Between 1971 and 1981, 79 previously untreated children with proven or presumed gliomas of the brainstem or midbrain were seen and treated at the Joint Center for Radiation Therapy and Children's Hospital Medical Center in Boston. Twenty-seven patients had tumors of the thalamus and midbrain (Group I) and 52 had lesions of the pons or medulla (Group II). Overall 5- and 10-year survivals were 50% and 41% respectively. Eighty percent of deaths occurred within 2 years of treatment. Eighty-six percent of the children (69/79) had clinical improvement or stabilization of disease after treatment. Group I patients had a 5-year survival of 73% which was significantly greater than that of Group II patients (38%) (p = 0.007). Children who presented with hypothalamic tumors in association with a diencephalic syndrome or other growth abnormality appeared to have had a better prognosis with 6/6 (100%) surviving without evidence of disease. Age at presentation was not correlated with prognosis. Of 10 children less than 3 years of age at presentation and treatment, 6 are alive (60%) at 2, 3, 7, 9, 10, and 12 years after treatment. The functional results in this group have been good--all six are leading apparently normal lives in regular schools with minor or no apparent neurologic deficits. Although these children will require long term follow-up to determine whether cures have actually been achieved, it appears that the majority achieve some benefit, that a significant proportion enjoy long term survival, and that very young children may be treated successfully with minimal radiation-induced neurologic sequela.

Adolescent↗
PubMed1986

Enhancement of radiation sensitivity by postradiation hypoxia.

We demonstrate that postradiation hypoxia during colony formation in vitro enhances radiation sensitivity when cells are irradiated in severely hypoxic states. The presence and magnitude of this phenomenon, if it occurs in vivo, raise questions about the importance of the oxygen effect in the radiation response of tumor cells in vivo and suggest that hypoxia may not be an important factor in the probability of tumor control following radiation therapy.

Animals↗
PubMed1985

Treatment of craniopharyngiomas in children: 1972-1981.

Between 1972 and 1981, 37 children with craniopharyngioma were cared for at Children's Hospital, Boston. In this paper, the results of treatment with radiation therapy after conservative operations are compared with those following an initial attempt to excise the tumor. Radiation therapy was equally, if not more, effective than attempted excision in controlling subsequent tumor growth. Although this was not a controlled study, the complications of each approach are indicated, and it is inferred that conservative operations combined with radiation therapy offer less risk for psychosocial impairment than does attempted tumor excision when patients are considered as a group. The ultimate effect that either approach might have on quality of life remains to be defined, and therapy must still be individualized to the particular clinical problem.

Child↗
PubMed1984

Total lymphoid irradiation therapy in refractory rheumatoid arthritis. Fifteen- to forty-month followup.

Twelve patients with refractory rheumatoid arthritis were treated with total lymphoid irradiation (TLI) to a total cumulative dose of 3,000 rads. Post-TLI morbidity/mortality included 8 patients with xerostomia, 4 with weight loss of greater than 10 kg, 3 with loss of 4 or more teeth, 3 with herpes zoster, 4 with bacterial infection that was fatal in 2, 3 with hypothyroidism, 1 with cutaneous vasculitis, and death from myocardial infarction in 1 patient and cardiorespiratory arrest in another. Ten of the patients were reevaluated 15-40 months (mean +/- SE, 30 +/- 2) after completion of TLI, and significant improvement was noted in several disease parameters including number of swollen joints, duration of morning stiffness, and 50-foot walking time. Blood lymphopenia and a decrease in helper T cells (T4) were also noted. These data suggest that changes in immunoregulation induced by TLI can produce longlasting alterations in rheumatoid arthritis, although adverse effects may limit its efficacy.

Adult↗
PubMed1984

A rational clinical staging system for childhood rhabdomyosarcoma.

There is a need for a rational and useful staging system for childhood rhabdomyosarcoma that predicts prognosis based on the biology and natural history of the disease. Important factors to consider are age, histology, tumor volume, extent of invasion, and lymphatic involvement. A clinical staging system based on a classical tumor/node/metastasis status, and which accounts for natural history as a function of site of primary, local invasion, and lymphatic or hematogenous metastases is presented. This staging system eliminates the requirement that stage is assigned following an initial therapeutic strategy and removing the implication that prognosis is determined by that strategy.

Adolescent↗
PubMed1984

High-level, unstable adriamycin resistance in a Chinese hamster mutant cell line with double minute chromosomes.

An Adriamycin-resistant Chinese hamster V79 line was isolated previously in this laboratory. There was about a 5-fold increase in Adriamycin resistance in this mutant as determined from survival curve measurements. Using this low-level Adriamycin-resistant mutant, a cell line with a high level of resistance was isolated after a multistep selection process culminating in continuous growth of the cells in medium containing 5.0 micrograms Adriamycin/ml. These cells are about 3000 times more resistant towards the cytotoxic effects of Adriamycin than is the parental V79 line. This high-level resistance phenotype is unstable and lost upon culture in the absence of drug. The highly resistant cells also showed increased cross-resistance to actinomycin D, Colcemid, and vincristine compared to the low-level resistant cells. Cytogenetic studies showed that these mutant cells contained increased numbers of double minute chromosomes and that the number of double minutes decreased proportionately with the reduction of Adriamycin resistance in cultures changed to drug-free medium. Adriamycin uptake assays demonstrated that there was a further decrease in net uptake relative to the low-level resistant mutant.

Animals↗
PubMed1983

Correlations between cell-cycle perturbations and survival levels after exposure to adriamycin for two Chinese hamster cell lines.

The cell-cycle perturbation and cell inactivation after adriamycin (ADR) exposure were measured in two Chinese hamster cell lines differing in ADR sensitivity. Based on DNA distribution analysis, it was found that the rate of G1 fraction depletion following low-dose ADR treatment was related to the level of cell inactivation. The results indicate that gross cellular sensitivity to ADR can be predicted rapidly by this approach.

Animals↗
PubMed1983

Neurological and psychophysiological sequelae following different treatments of craniopharyngioma in children.

The authors present neurological findings and data from psychophysiological tests administered during the follow-up period of 35 patients with craniopharyngioma. Group I patients who were treated by irradiation alone or by radiotherapy and conservative surgical procedures (including biopsy, cyst aspiration, and shunting), showed significantly less frontal lobe and visual perceptual dysfunction than Group II patients, in whom radical tumor resection was attempted by a subfrontal exposure. Frontal lobe dysfunction was demonstrated in sorting tests by perseverative responses, inflexibility of behavior, and lack of inhibitory control, while intelligence quotients remained relatively unaffected. Immediate memory defects and decreased manual dexterity were present, to different degrees, in both treatment groups. On the basis of these preliminary data and a maximum follow-up period of 10 years, the authors conclude that primary irradiation of a craniopharyngioma appears associated with a lower morbidity rate and may avoid the frontal lobe disorders seen in the patients with extensive tumor resection.

Adolescent↗
PubMed1983

Efficacy and morbidity of central nervous system "prophylaxis" in childhood acute lymphoblastic leukemia: eight years' experience with cranial irradiation and intrathecal methotrexate.

Between 1972 and 1979, 214 children with acute lymphoblastic leukemia and no evidence of central nervous system (CNS) disease prior to CNS prophylaxis were treated with 2400 rad cranial irradiation and concurrent intrathecal methotrexate. Only nine children developed CNS leukemia; five of them in the CNS only and four concurrently in the CNS and another site. Major acute effects of CNS prophylaxis were seizures in seven patients (3%). Sixty-nine children who had a minimum follow-up of 4 yr were evaluable for late effects of therapy. Small cataracts, incomplete regrowth of hair, and learning disabilities were noted. The latter occurred in 18% of patients, an incidence similar to that encountered in a normal community of school-age children. However, the incidence of learning disabilities in patients who were under 5 yr of age at the time of diagnosis was much higher, 35%. We conclude that the combination of cranial irradiation and intrathecal methotrexate was highly efficacious. The incidence and severity of neuropsychologic abnormalities, the principal late morbidity of this treatment program, varies among reporting institutions. Prospective longitudinal studies of neuropsychologic function are necessary to better define the incidence of abnormalities. Future programs should attempt to decrease late morbidity, but must also assure equal efficacy and improve overall disease-free survival.

Brain Neoplasms↗
PubMed1982

Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis.

Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease.

Animals↗
PubMed1982

The effect of dose rate and adriamycin on the tolerance of thoracic radiation in mice.

Radiation damage to the lung may be a predisposing factor in the development of interstitial pneumonitis in patients undergoing total body radiation and subsequent bone marrow transplantation in the treatment of leukemia. Adriamycin has been used in conjunction with bone marrow transplantation, and has also been shown to interact with radiation. This experiment was designed to study the effects of pre-administration of adriamycin on the radiation tolerance of the lung and esophagus. Since total body radiation is usually administered at low dose rates in order to spare the gastrointestinal tract preferentially as compared to the bone marrow, we investigated whether such a dose rate effect was present for the lung and if so, whether this pulmonary and esophageal dose rate effect would be ameliorated by pre-treatment with adriamycin. Mice were irradiated at 5 rad; 15 rad or 70 rad per minute to the upper body, 24 hours or 7 days after adriamycin. Oral esophageal death occurred within one month; thus deaths within 30 days were ascribed to this mechanism. In comparison, deaths because of pulmonary toxicity occurred later. Those between 30 and 160 days were ascribed to this mechanism. In the absence of adriamycin, a dose rate effect was found for the lung and confirmed for the upper gastrointestinal tract. The dose of radiation necessary to give pulmonary and gastrointestinal toxicity was markedly reduced when adriamycin was administered 24 hours before radiation. If seven days were allowed between adriamycin and radiation there was still an effect seen only at the high dose rate for the esophagus while for the lung at the high dose rate and for both systems at low dose rate no significant drug effects were noted. The dose rate effect is still seen after the drug, but it is reduced. These studies indicate that adriamycin given shortly before can significantly increase the oral esophageal and pulmonary toxicity of radiation and can practically abrogate the sparing effect of dose rate. This must be considered when clinically using total body radiation and adriamycin in preparation for bone marrow transplantation.

Animals↗
PubMed1981

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

Aged↗
PubMed1981

Tolerance of brain to multiple courses of radiation therapy. I. Clinical experiences.

Patients with recurrent brain tumours years after initial radiation therapy pose a difficult management decision. Should retreatment be performed with irradiation, which carries a risk of necrosis, or should retreatment be with less effective agents but without unnecessary risks? We present the results of retreatment of 32 patients at the Mayo Clinic and the Joint Center for Radiation Therapy. Clinical improvement was seen in all retreated patients. The median survival was 36 months after completion of the second course of irradiation. Eight patients (25%) were alive, free of disease, from 22 to 315 months after retreatment. Of the 11 patients alive at the time of analysis, eight were experiencing productive lives and three were suffering from severe neurological damage. Evidence of brain necrosis was observed in two patients (6%); however, only 10/21 patients underwent autopsy examinations. Reirradiation of patients with late recurrences of brain tumours may offer neurological improvement and prolonged survival without excessive risk of necrosis.

Adolescent↗