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Biomedical subjects

E C Halperin

Publications and source records attributed to E C Halperin.

At least 127 records · Page 7Linked to original sources

Phenotypic and genotypic analysis of a human medulloblastoma cell line and transplantable xenograft (D341 Med) demonstrating amplification of c-myc.

D341 Med is a new continuous cell line and transplantable xenograft derived from a cerebellar medulloblastoma. This line grew in vitro in suspension culture with spontaneous macroscopic spheroid formation and demonstrated 20-fold amplification of c-myc. Cultured D341 Med cells injected subcutaneously into athymic mice grew as markedly cellular, highly invasive undifferentiated neoplasms. Intracranial tumors grew as markedly cellular mitotically active neoplasms largely located within the subarachnoid space or lining the ventricular system. Immunocytochemical analysis of the cell line and SQ tumors revealed the high (NFP-H) and middle (NFP-M) molecular weight (Mr) neurofilament proteins (NFPs). Immunoblots demonstrated the presence of molecular species that co-migrated with authentic human NFP-H and NFP-M. This cell line and transplantable xenograft may allow, in conjunction with the authors' other models of human medulloblastoma, analysis of the heterogeneous biologic properties and therapeutic sensitivity of this tumor.

Animals↗

Oligodendroglioma. An analysis of the value of radiation therapy.

The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.

Adolescent↗

The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model.

Immunosuppression generated by total lymphoid irradiation (TLI) may be of use in solid organ transplantation. We have investigated the use of TLI in the rat cardiac allograft model. Lewis rats received TLI from a cobalt-60 machine. The daily dose was 1.25 Gy and treatments were administered 4 days per week. We performed experiments to assess the effect of dose rate upon graft survival. The dose rate was varied by changing the source to animal distance and by using a lead attenuator. Cardiac allografts from each ACI donor rat were transplanted to the recipient Lewis rat's abdomen utilizing microvascular surgical technique. Heart graft survival times (GST) were monitored by direct palpation of the cardiac impulse. Immune function was measured by an activity index of the mixed lymphocyte reaction. In the absence of any immunosuppression there was a mean GST of 6.9 +/- 0.3 days. When a graft was placed the day following completion of TLI, there was an increase in GST as the total TLI dose was increased. Mean GST (+/- S.E.) following 5, 10, and 15 Gy were 12.3 +/- 1.3, 14.5 +/- 1.3, and 25.5 +/- 1.1 days, respectively. Following 20 Gy, GST decreased because of irradiation induced pulmonary toxicity and host death. When 3.5 weeks were allowed to elapse between the completion of TLI and transplantation, GST were less than those seen with equivalent doses of TLI and early transplantation. Mean GST following 5, 10, and 15 Gy and a delayed transplant were 7.2 +/- 0.1, 10.7 +/- 1.2, and 19.0 +/- 3.5 days, respectively. We tested the effect of dose rate upon GST.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hepatic metastasis from neuroblastoma.

Neuroblastoma is a common solid tumor of infancy and childhood. From 1967 to 1986 we evaluated and treated 58 children with neuroblastoma; in ten (17%) of these children, symptomatic hepatic metastasis developed. The ten children ranged in age from 2 days to 2 years 3 months. The most common symptoms attributable to hepatic metastasis were abdominal enlargement, abdominal pain, respiratory difficulty due to upward pressure on the diaphragm, and obstruction of the inferior vena cava. At the time of initial diagnosis, two children had stage III disease, three had stage IV disease, and five had stage IV-S disease. Six were initially given chemotherapy; all six of these patients required radiation therapy when hepatic enlargement progressed. In the other four cases, radiation therapy was used alone or in combination with chemotherapy. Irradiation or irradiation plus chemotherapy produced complete resolution of local symptoms in seven cases, and a partial response in one case. The seven children who had a complete response are alive without evidence of recurrent disease; the remaining three children died of their tumor. The roles of chemotherapy, surgery, and radiation therapy in the management of symptomatic hepatic metastasis from neuroblastoma are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine.

Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.

Animals↗

Medulloblastoma: the Duke University Medical Center experience.

We have reviewed the clinical experience in the treatment of medulloblastoma with radiotherapy at Duke University Medical Center. One hundred and twenty-seven patients treated between January 1, 1940 and December 31, 1983 were evaluated. The irradiation technique was reviewed and all irradiation doses were recalculated as minimum tumor doses in Gray (Gy). The mean follow-up was 24.4 years and the median follow-up was 26.5 years. The energy of the treatment machine was known in 102 cases. Sixty patients were treated with orthovoltage equipment and 42 patients were treated with megavoltage equipment. As a gross assessment of the impact of the details of radiotherapy treatment upon outcome, patients were grouped into excellent, good, fair, and poor treatment groups. Patients undergoing cranio-spinal axis (CSA) irradiation and receiving greater than or equal to 52 Gy to the posterior fossa and greater than or equal to 30 Gy to the clinically uninvolved remainder of the CSA were classified as having "excellent" technique. Patients undergoing CSA irradiation and receiving 40 to 52 Gy to the posterior fossa and greater than or equal to 20 Gy to the remainder of the CSA were classified as "good." Patients receiving 20 to 40 Gy to the posterior fossa and greater than or equal to 10 Gy to the spinal axis with or without prophylactic cranial irradiation were designated "fair." Any patient not fulfilling the above minimum criteria was categorized as "poor." The actuarial 5-year survival for the entire population was 33%. The 10-year survival was 21%. In 93 patients for whom records were detailed enough to allow categorization of treatment technique, 5-year actuarial survivals were: Excellent 37% (n = 17), Good 55% (n = 13), Fair 35% (n = 23), Poor 20% (n = 40). A complete surgical resection was not correlated with improved disease-free survival (DFS) in the excellent and good groups, but was correlated with an improved DFS in the fair and poor groups. The posterior fossa accounted for 62% of the failures in the 55 patients completing irradiation where the initial site of failure was known. An examination of patterns of failure in the spinal canal failed to demonstrate a dose response relationship above 10 Gy for spinal canal prophylactic irradiation. No patient developed recurrence beyond their period of risk as defined by "Collins' Law."(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984.

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Neoplasms↗

Pediatric brain stem tumors: patterns of treatment failure and their implications for radiotherapy.

There have been conflicting opinions regarding the correct volume to be used in radiotherapy fields for brain stem tumors of childhood. Whereas many clinicians recommend limited fields designed to cover the tumor volume with a margin, some have advocated whole brain radiotherapy. Using our clinical experience at Duke University Medical Center, we have made an attempt to determine the proper irradiation volume in this group of tumors. We have evaluated 38 patients with brain stem tumors in children less than 18 years of age. The most common presenting symptoms were headache, ataxia, and hemiparesis. Thirteen patients had a histologic diagnosis made prior to treatment or post-mortem. All had either an anaplastic astrocytoma or a glioblastoma multiforme. Tumors were located in the thalamus, hypothalamus, or midbrain in 9 patients and in the pons or medulla oblongata in the remaining 29 patients. All patients received a course of radiotherapy. The mean minimum tumor dose was 52.6 +/- 5 Gy given at 1.7 to 2.0 Gy/fraction. Twenty-three patients received radiation to a limited field and 14 received whole brain irradiation. In one patient, the field size could not be ascertained. The five year survival of the total group was 39%. The survival of patients with thalamic, hypothalamic, or midbrain tumors was 73% compared with 28% for those with tumors of the pons or medulla oblongata (p = 0.0159). Eighty-eight percent of the tumor recurrences in evaluable patients (22/25) occurred within the radiotherapy fields. Patients were stratified for tumor location and no difference was observed in survival or relapse-free survival among those individuals treated with limited irradiation fields or whole brain irradiation fields. When our results are examined in conjunction with previously published data, the bulk of existing evidence supports the use of limited fields for irradiation of brain stem tumors of childhood.

Adolescent↗

Total lymphoid irradiation as an immunosuppressive agent for transplantation and the treatment of 'autoimmune' disease: a review.

Total lymphoid irradiation (TLI) is a powerful immunosuppressive agent. This immunosuppression has the potential for clinical application in certain selected situations. In this review, the immunological changes produced by TLI and its potential applications in organ transplantation and the treatment of certain 'autoimmune' diseases are discussed.

Anemia, Aplastic↗

Establishment and characterization of the human medulloblastoma cell line and transplantable xenograft D283 Med.

A new continuous cell line and transplantable xenograft, D283 Med, was derived from the peritoneal implant and ascitic fluid of a child with metastatic medulloblastoma and grew in vitro in suspension culture with spontaneous macroscopic spheroid formation. The in vitro population doubling time was 52.55 hours. Mean colony forming efficiency in an agarose medium was 1.83 +/- 0.56%. The cell line, D283 Med, grew in athymic mice as serially transplantable intracranial and subcutaneous xenografts. Intracranial tumors grew as masses of small cells with scant cytoplasm and abundant mitotic figures and prominent anuclear zones resembling neuroblastic rosettes. Subcutaneous (SQ) tumors were markedly cellular neoplasms but did not contain rosettes. They expressed glutamine synthetase, neuron-specific enolase and neurofilament protein. Glial fibrillary acidic protein and S-100 protein were not detected. The SQ tumors grew to 500 mm3 with a latency of 52.55 +/- 12.5 days and a doubling time of 9.33 +/- 2.39 days. The stemline karyotypes of the peritoneal implant and ascitic fluid cells contained an extra copy of chromosome number 11 and three marker chromosomes (8q+, 17p+, 20q+). The cultured cell line and subcutaneous and intracranial xenografts retained the three marker chromosomes and differed from the original karyotype only in that they lacked the additional copy of chromosome number 11. This cell line and transplantable xenograft may allow further analysis of the biological properties and therapeutic sensitivity of human medulloblastoma.

Animals↗

Conventional external beam radiotherapy for central nervous system malignancies.

Fractionated external beam photon radiotherapy is an important component of the clinical management of malignant disease of the central nervous system. The practicing neurologist or neurosurgeon frequently relies on the consultative and treatment skills of a radiotherapist. This article provides a review for the nonradiotherapist of the place of conventional external beam radiotherapy in neuro-oncology.

Adenoma↗

Sarcoma of bone and soft tissue following treatment of Hodgkin's disease.

Intensive chemotherapy and radiotherapy of Hodgkin's Disease has resulted in improved survival rates. With long-term follow-up, however, a risk of secondary malignancy in these individuals is now appreciated. The authors of this report have encountered five patients who developed bone or soft tissue sarcomata more than 5 years after treatment of Hodgkin's Disease. The four males and one female ranged in age from 14 to 74 years at the time of diagnosis of Hodgkin's disease. Two had received radiotherapy alone for treatment of Hodgkin's disease, two were treated with radiation and chemotherapy, and one received only chemotherapy. The latent period prior to diagnosis of sarcoma ranged from 6 to 11 years. There was one case each of neurofibrosarcoma, fibrosarcoma, osteosarcoma, liposarcoma and leiomyosarcoma. Four patients died within 1 year of the diagnosis of sarcoma. One is alive with no evidence of disease 2 years following diagnosis and surgical excision of the sarcoma. On the basis of the Massachusetts General Hospital experience in the treatment of Hodgkin's Disease, the authors calculate a risk of 0.9% of sarcoma occurring in five year survivors of Hodgkin's disease. Previously reported cases of sarcoma following treatment of Hodgkin's disease are summarized. The pertinent literature is reviewed.

Adult↗