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Biomedical subjects

V A Levin

Publications and source records attributed to V A Levin.

At least 109 records · Page 6Linked to original sources
PubMed1991

Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy.

Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.

Adolescent↗
PubMed1991

Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation.

A 360 residue region encoded by the neurofibromatosis type 1 (NF1) gene shows significant homology to the catalytic domains of both mammalian GTPase-activating proteins (GAP) and yeast IRA proteins. This GAP-related domain of the NF1 gene (NF1-GRD), like the GAP and IRA protein, has been reported to mediate hydrolysis of Ras-bound GTP to GDP, resulting in inactivation of Ras protein. In the present study, we identified two different types of NF1-GRD cDNA. One (type I) is identical to the previously reported sequence, and the other (type II) contained an additional 63 bp insertion that encodes for a region of 21 amino acids in the center of the NF1-GRD molecule. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. Our observations reveal that the type I transcript is predominantly expressed in undifferentiated cells, whereas the type II transcript predominates in differentiated cells. Furthermore, the expression pattern of type I and type II NF1-GRD mRNA immediately changed in SH-SY5Y neuroblastoma cells when neuronal differentiation programs were induced by retinoic acid treatment. We propose that the differential expression of type I and type II NF1-GRD transcripts might be an 'on/off' switch that regulates the catalytic activity of the NF1 gene product, which plays an important role in the regulation of neuronal differentiation.

Amino Acid Sequence↗
PubMed1990

Poorly differentiated gliomas of the cerebellum. A study of 18 patients.

Eighteen patients with poorly differentiated gliomas of the cerebellum were treated by the University of California San Francisco Neuro-Oncology Service between January 1977 and January 1987. Within this group pathologic diagnosis included five glioblastoma multiforme (28%), nine anaplastic astrocytomas (50%), and four mixed malignant gliomas (22%). The group included 13 male and five female patients with a median age at diagnosis of 23 years (range, 4-46 years). All patients underwent surgical resection, 16 of 18 received radiation therapy (12 limited-field irradiation and four whole-brain with or without a posterior fossa boost), and 16 of 18 received chemotherapy. Overall median survival was 31.5 months (range, 5-366 months). Ten patients (55%) died of recurrent disease with a median survival of 32 months (range, 5-128 months), two of whom manifested metastatic disease within the central nervous system (one parietal lobe and one cervical cord). Of the two extracerebellar metastatic recurrences, one patient failed at the junction of whole-brain irradiation and the cervical cord and one patient failed after inadequate posterior fossa irradiation. Eight patients (45%) are alive with a median follow-up of 27.5 months (range, 14-366 months). In this series recurrences of primary cerebellar anaplastic gliomas were locoregional failures. As a consequence, the authors suggest high-dose limited-field irradiation directed at the primary tumor as in their current strategy utilized for supratentorial gliomas.

Adolescent↗
PubMed1990

Adjuvant chemotherapy for primary lymphoma of the central nervous system.

Ten immunocompetent patients with primary non-Hodgkin's lymphoma of the central nervous system were treated by the neuro-oncology service at the University of California at San Francisco (UCSF). After undergoing surgery for biopsy or removal of their tumors, these patients (group 1) received irradiation with hydroxyurea followed by adjuvant chemotherapy with the combination of procarbazine, lomustine (CCNU), and vincristine. The outcome of treatment in this group was compared with that in three other groups of patients with primary CNS lymphoma: patients treated at the UCSF Cancer Research Institute who underwent surgery and radiation therapy (RT) (group 2); patients described in the literature who had surgery and RT (group 3); or patients described in the literature who had surgery, RT, and chemotherapy (group 4). Median and quartile survival times were greater in patients who received adjuvant chemotherapy (group 1, 30 and 50 months; group 4, 20 and 25 months) than in patients who did not receive chemotherapy after RT (group 2, 13 and 20 months; group 3, 15 and 24 months). These results suggest that adjuvant chemotherapy is useful in the treatment of primary CNS lymphoma.

Adolescent↗
PubMed1990

Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report.

Data from Northern California Oncology Group protocol 6G61, which was closed in February 1983, were reanalyzed in December 1988. The protocol called for a randomized trial that compared the effects of following 60 Gy radiation/oral hydroxyurea treatment with either carmustine (BCNU) or the combination of procarbazine, lomustine (CCNU), and vincristine (PCV) for two histologic strata: glioblastoma multiforme and other anaplastic gliomas. PCV produced longer survival and time to tumor progression than BCNU for both histologic groups, although the difference was statistically significant only for the anaplastic gliomas. With PCV treatment, time to progression and survival doubled for anaplastic glioma patients in the 50th and 25th percentiles.

Adult↗
PubMed1990

Management of hypothalamic gliomas in children: an analysis of 33 cases.

The cases of 33 children with hypothalamic-chiasmatic gliomas are reviewed. Radiation therapy produced clinical or radiographic improvement in 11 (46%) of 24 patients. Progression was documented in 18 patients (54%). Overall, the median time to tumor progression was 60 months; it was 70 months in patients who received radiation therapy and 30 months in those who did not (P less than 0.05). Chemotherapy, either given initially or at the time of progression, caused the tumor to respond or to stabilize in 10 patients. Partial resection of the tumor led to improvement in 3 of 12 patients, obviating the need for a shunt in 2 of them; there were no deaths and postoperative morbidity was transient and minimal (diabetes insipidus, intraventricular hemorrhage, and left hemiparesis in one patient each). The 5- and 10-year survival probabilities were 93 and 74%, respectively. Patients with neurofibromatosis had a better prognosis.

Adolescent↗
PubMed1989

Reevaluation of procarbazine for the treatment of recurrent malignant central nervous system tumors.

Ninety-nine patients with primary recurrent malignant tumors of the central nervous system were treated with procarbazine as a single agent. Procarbazine was not given as a specified protocol, but for patients who were ineligible or refused other protocols. All patients had been treated previously with radiotherapy and 96 patients had also received previous chemotherapy. Twenty-five patients were treated at the first progression of their tumor, 47 were treated at the second progression, and 27 were treated at the third progression of their tumor. For the aggregate, the response plus stabilization rate was 27% for glioblastoma multiforme with median time to tumor progression of 30 weeks, and 28% for other anaplastic gliomas with a median time to tumor progression of 49 weeks. With respect to the percent of patients who responded or stabilized to treatment, these results are inferior to those reported previously for patients treated with procarbazine at recurrence. With respect to duration of response and stabilization, the data are comparable.

Adolescent↗
PubMed1989

Chemotherapeutic treatment of the diencephalic syndrome. A case report.

Tumors of the hypothalamus present with a variety of clinical syndromes. Such syndromes appear to be both age and histology dependent. The diencephalic syndrome, an entity classically seen in infancy, presents as failure to thrive. In essentially all cases the pathologic substrate is a tumor with a predominance of gliomas. The traditional approach to treatment of the diencephalic syndrome has been surgery both for decompression and pathologic diagnosis followed by irradiation. Because of the tumor location, surgery is often confined to biopsy rather than radical extirpation. Furthermore, in infancy focal brain irradiation is not without significant morbidity. Within this context, we would like to present a case discussion regarding a 27-month-old boy with a hypothalamic-midbrain protoplasmic glioma treated with primary chemotherapy after surgical biopsy and pathologic documentation. The schedule of drugs utilized was based on the hypothesis of biochemical modulation of nitrosourea chemotherapy. Successful response to therapy was documented by sequential computed tomography (CT) studies and serial neurologic examinations beginning at age 5 months and every 2 months thereafter. The response of a single patient with the diencephalic syndrome treated primarily with chemotherapy makes extrapolation premature. Rather, the authors suggest chemotherapy as an alternative to focal brain irradiation. Such therapy could be utilized either in the event of recurrent tumor or as late consolidation after primary treatment with chemotherapy. The latter approach would allow a patient to have radiation therapy deferred until a later age at which time morbidity attending brain irradiation may be minimized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Pineocytomas.

Six cases of histologically proven pineocytoma are reported. The diagnosis was established by surgery in five cases and at autopsy in one. All patients received focal radiation therapy (4500 to 5400 cGy). Two patients had local recurrences at 1 and 48 months and subsequently died of tumor. A third patient died of Alzheimer's disease 29 years after the initial presentation. Three patients are alive with no evidence of disease at 21+, 52+, and 84+ months after treatment. Tumor dissemination occurred after a local recurrence in one patient. We found no evidence of recurrence outside the irradiated field unless there was an initial recurrence at the primary tumor site. We recommend postoperative staging for all patients with pineocytoma and focal radiation therapy if local disease alone is found. Craniospinal radiation therapy appears to be justified only if tumor dissemination is documented on staging tests.

Adolescent↗
PubMed1989

Phase I/II study of intraventricular and intrathecal ACNU for leptomeningeal neoplasia.

A total of 27 patients with leptomeningeal neoplasia were treated with the water-soluble nitrosourea ACNU given intraventricularly or intrathecally in a phase I/II study. Patients were entered in the study if they showed evidence of either a positive CSF cytology or neurodiagnostic evidence of leptomeningeal disease, or both. Patients were evaluated for toxicity and efficacy; additionally, in 13 patients ACNU pharmacokinetic studies were carried out. A variety of tumor types were represented in the study group, including primary and metastatic CNS tumors. Toxicity was mild and included pain at the injection site (four patients), transient radicular symptoms at a short distance from the injection site (three patients), and nausea and vomiting (one patient). No myelotoxicity was seen. Of 21 patients who presented with positive cytology, 8 (38%) had a conversion from positive to negative cytology, with a range of response durations from 1 to 20+ months. Of the remaining six patients with negative cytology but other neurodiagnostic evidence of leptomeningeal disease, one patient showed an improvement seen on the myelogram and one underwent a brief reduction in CSF protein. ACNU elimination from the ventricular system is rapid, with a beta slope of 0.028 min-1 and a computed elimination constant, Ko of 13 min. The mean clearance was 3.8 ml/min (range, 1.0-6.2 ml/min). Peak ACNU levels varied between 108 and 620 micrograms/ml, with the AUC being 1.4-14.7 mg.min/ml. The total dose of ACNU given was between 9 and 104 mg, and the single dose range was 4-16.5 mg. We conclude that ACNU can be given safely with minimal toxicity as intra-CSF therapy, that it demonstrates efficacy in some patients with leptomeningeal disease, and that further studies are warranted to evaluate more fully alternative dosing and drug delivery approaches.

Arachnoid↗
PubMed1989

Hyperfractionated radiation therapy for brain-stem glioma: a phase I-II trial.

Fifty-three patients (19 adults and 34 children) harboring brain-stem glioma were treated with hyperfractionated radiation therapy (100 cGy twice a day, 5 days/wk, to a total dose of 7200 cGy). For the entire group, the median time to tumor progression (TTP) was 59 weeks (adults 66 weeks, children 44 weeks) and the median survival time was 74 weeks (adults 92 weeks, children 64 weeks). Statistically significant prognostic factors associated with a decrease in TTP and median survival times (adults less than children) were: patient's age, a clinical history of less than 2 months, widespread brain-stem dysfunction, and a diffuse tumor as seen on magnetic resonance imaging. A finding of glioblastoma multiforme at histological analysis was associated with a statistical trend toward poorer survival, but in general tumor histology was not predictive of outcome. No evidence of an increase in acute or delayed radiation toxicity was seen with this fractionation schedule and total dose. This study suggests that hyperfractionation prolongs the TTP and survival time for many patients with brain-stem glioma. However, there remains a group of patients who are only moderately helped by this technique and for whom more aggressive treatment is warranted.

Adult↗
PubMed1988

Protein-tyrosine kinase activity and pp60v-src expression in whole cells measured by flow cytometry.

The expression and phosphotyrosine activity of pp60v-src were measured in the B31 avian sarcoma virus-transformed rat cell line by flow cytometry using monoclonal antibodies against pp60v-src (EB7) and phosphotyrosine (1G2). Although the immunocytochemical staining was markedly heterogeneous, binding of both antibodies was significantly greater to B31 cells than to untransformed Rat 1 cells. Binding of 1G2 to phosphotyrosine residues was specific; it was entirely inhibited by adding excess phenylphosphate but was not affected by phosphoserine or phosphothreonine. The relationship between the amount of phosphorylated tyrosine measured by our FCM technique and total cellular phosphotyrosine measured by phosphoamino acid analysis was linear in vanadate-treated BALB/c 3T3 cells. Treatment of B31 cells for 48 h with herbimycin A, a benzenoid ansamycin antibiotic, to decrease the expression and tyrosine kinase activity of pp60v-src caused reductions of 42% in anti-pp60v-src and 58% in anti-phosphotyrosine antibody immunofluorescence. DNA staining with the fluorescent dye propidium iodide showed no cell cycle specificity in the binding of either antibody. Herbimycin A also caused the transformed cell line to revert to the morphology, actin configuration, and growth behavior of untransformed cells; these changes were reversed within 12 h after removal of the drug. Flow cytometric evaluation of tyrosine kinase expression and activity was fast and easy, and the results correlated well with other measures of cell phenotype. This technique can be used to quantitate the effects of drugs on oncogenic proteins such as pp60v-src and their associated tyrosine kinase activity.

Actins↗
PubMed1988

A phase I/II study of 24 hour intravenous AZQ in recurrent primary brain tumors.

This study was undertaken to determine the maximum tolerated dose of aziridinylbenzoquinone (AZQ) given as a 24-hour intravenous infusion every 21-28 days. Thirty-four patients with recurrent or progressive gliomas received AZQ at a dose of 25, 30, 35, 40, or 45 mg/m2. At a dose of 45 mg/m2, leukopenia and thrombocytopenia of grade 3 or greater was observed in 42% and 25% of patients respectively; no patient required transfusion or antibiotics for fever. For administration of AZQ at a 24-hour intravenous infusion, we recommend a starting dose of 40 mg/m2 for patients without previous exposure to cytotoxic agents, and 35 mg/m2 for patients treated with such agents. In 14 patients with glioblastoma, tumor regression was observed in 1 patient (14%) and stabilization of disease was demonstrated in 7 patients (50%). In 17 patients with anaplastic astrocytomas there were no responses, but 8 patients (47%) stabilized. Of two patients with an oligodendroglioma, one continues without progression at 34 weeks after initial response. One patient with malignant ependymoma stabilized and had not progressed at 39 weeks. The median time to tumor progression in patients who stabilized and responded was 18 weeks for those with glioblastoma multiforme and 16 weeks in those with anaplastic astrocytomas.

Antineoplastic Agents↗
PubMed1988

A phase II trial of oral melphalan in recurrent primary brain tumors.

Thirty-seven patients with recurrent primary brain tumors were treated with oral melphalan at a dose of 8 mg/m2/day for 5 days every 4-6 weeks. All patients had failed prior nitrosourea-based chemotherapy. Oral melphalan had no activity against glioblastoma, and minimal activity against other anaplastic astrocytomas. One recurrent medulloblastoma did have a clinical and radiographically sustained response that continued for greater than 14 months. We concluded that oral melphalan was not effective in the treatment of recurrent astrocytomas, but might have efficacy in medulloblastoma.

Administration, Oral↗
PubMed1988

Absence of contrast enhancement on CT brain scans of patients with supratentorial malignant gliomas.

The medical records of 229 consecutive patients with supratentorial malignant gliomas were reviewed with respect to histology, age at diagnosis, tumor location, and enhancement pattern on the CT obtained after the administration of contrast material at the time of operation. Nonenhancing tumors were identified in four (4%) of 93 patients with glioblastoma multiforme (GM), three (30%) of ten with gemistocytic astrocytoma (GA), 23 (31%) of 74 with highly anaplastic astrocytoma (HAA), and 28 (54%) of 52 with moderately anaplastic astrocytoma (MoAA). The age-related incidence of the various glioma histiotypes (both enhancing and nonenhancing) was reflected by the median age at diagnosis: 50 years in GM, 52 years in GA, 40 years in HAA, and 34 years in MoAA. The age and CT contrast enhancement pattern were similar in patients with GM, GA, and MoAA; patients with nonenhancing HAAs tended to be younger at presentation. The tumor location and the frequency of enhancing and nonenhancing lesions were similar for all groups except MoAA, in which nonenhancing tumors were most often frontotemporal and enhancing tumors were usually frontoparietal. Our results demonstrate that it is important to obtain histologic confirmation of the diagnosis in patients with supratentorial gliomas regardless of the presence or absence of contrast enhancement of the tumor on CT, because neither of these characteristics correlates with the tumor histology.

Adolescent↗
PubMed1988

Treatment of extraneural metastatic medulloblastoma with a combination of cyclophosphamide, adriamycin, and vincristine.

Seven patients with extraneural metastases from medulloblastoma were treated with a combination of cytoxan, adriamycin, and vincristine (CAV). None of the patients had evidence of active neural axis disease. All patients with bone metastases responded with a reduction in bone pain and improvement on the radionuclide bone scan. One patient presenting with lymph node metastases showed initial reduction in the size of the palpable nodes. In this group, the median time to the development of extraneural metastasis was 18 months from the time of original diagnosis of central nervous system medulloblastoma. The median duration of response to CAV, after extraneural metastasis, was 17 months (4-65 months). Four of seven patients died of disease-related causes, one patient presumed well was lost to follow-up, and two of seven are still without evidence of active disease at 37 and 65 months. The combination of CAV is well tolerated and provides reasonably good palliation for extraneural medulloblastoma.

Adolescent↗