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Biomedical subjects

V A Levin

Publications and source records attributed to V A Levin.

At least 91 records · Page 5Linked to original sources
PubMed1993

Imaging patterns of multifocal gliomas.

We reviewed the imaging characteristics of 51 consecutive cases of cerebral glioma with multiple foci of involvement. In 26 patients, multifocality was present at the initial diagnosis, whereas in 25, it developed at a later stage. Thirty-two patients were studied with MRI, 13 with CT, and six with both imaging techniques. In 14 cases, no apparent dissemination route was identified; these tumors were presumed to be true multicentric gliomas. In the rest of the cases, various patterns of spread from a primary site were evident or suggested, and the tumors were denoted as multifocal. The most frequent dissemination route in the latter group was the meningeal-subarachnoid space, followed by the subependymal, intraventricular route and direct brain penetration. Multifocal gliomas are more frequent than generally believed and, therefore, multiple cerebral masses should be thoroughly evaluated and not always presumed to be of metastatic origin.

Brain↗
PubMed1993

The treatment of anaplastic oligodendrogliomas and mixed gliomas.

We evaluated the treatment outcome of 17 patients with anaplastic oligodendroglioma and 17 patients with anaplastic mixed oligodendroglioma-astrocytoma. In the anaplastic oligodendroglioma group, eight patients were treated at the time of the initial admission with radiotherapy and adjuvant chemotherapy, and nine patients were treated at the time of recurrence with salvage chemotherapy. Three patients for whom adjuvant chemotherapy was not successful were also treated with chemotherapy at the time of recurrence. In the initial group, one patient had complete response, three had partial responses, and 4 had stable disease (response and stable disease, 100%), but all except one progressed within 10 months. Of the 12 patients who received chemotherapy during recurrence, there was 1 complete response, 2 partial responses, and 6 stable disease (response and stable disease, 75%), with long response duration and long survival (15-132+ mo). In the anaplastic mixed oligodendroglioma-astrocytoma group, 12 patients were treated at the time of the initial admission and 6 patients treated at the time of recurrence. The initial treatment resulted in two complete responses, three partial responses, and seven stable disease (response and stable disease, 100%), with most responses lasting longer than 12 months. The treatment of the patients with recurrent disease resulted in one partial response and five stable disease (response and stable disease, 100%), with a median time to progression of 6 months. These results suggest that aggressive treatment is beneficial for recurrent anaplastic oligodendrogliomas and mixed gliomas as well as initial mixed gliomas but may offer only minimal advantage over conventional radiotherapy for the initial treatment of anaplastic oligodendrogliomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Management of brain metastases from breast carcinoma.

Brain metastases occur clinically in about 10% of patients with stage IV breast cancer, in the setting of widespread extracranial metastases. Prognosis is poor and management is aimed at relieving acute symptoms and improving neurologic status, as well as controlling the metastatic disease. Therapies include surgery, radiotherapy, chemotherapy, and hormonal therapy, used alone or in combination. Performance status is the single most important factor determining treatment choice. In selected patients, surgery can improve survival and performance status. Radiotherapy is the palliative treatment of choice, providing rapid relief of symptoms, especially headache. Recent innovations include accelerated split courses of radiotherapy given in two or three daily fractions, use of radiosensitizers, brachytherapy, and radiosurgery. Systemic therapy remains controversial, but studies show that cytotoxic agents can be palliative against brain metastases if the primary tumor is sensitive to the drug or drugs used.

Brain Neoplasms↗
PubMed1992

Treatment of recurrent gliomas with eflornithine.

BACKGROUND: Oral eflornithine in combination with intravenous mitoguazone (methylbisguanylhydrazone) has shown activity against recurrent anaplastic gliomas. Eflornithine alone, however, has not been evaluated against recurrent gliomas. PURPOSE: This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas. METHODS: During the 1st year of therapy with eflornithine alone, the drug was given at a dose of 3.6 g/m2 on days 1-14, 22-35, and 43-56 every 8 hours; cycles were repeated every 63 days until progression. For the 2nd year, the drug was given on days 1-14, 29-42, and 57-70, with 84 days between cycles. For the 1st and 2nd years of eflornithine-mitoguazone therapy, eflornithine was given at 1.8 g/m2 on the same schedule. Mitoguazone was given intravenously at 200 mg/m2 on the final day of each 2-week sequence of eflornithine therapy. Response was determined by evaluating changes in the size of contrast-enhanced neuroimages. RESULTS: Because of two cases of lethal hepatic necrosis, the initial random allocation of patients to the eflornithine-mitoguazone arm was stopped after 23 patients had been accrued. Ninety-eight patients were entered in the eflornithine arm; 80 patients (36 glioblastoma multiforme patients and 44 anaplastic glioma patients) were assessable for response. Antitumor activity (partial response, minor response, and stable disease) was seen in 45% of the patients with anaplastic gliomas, for a median of 49 weeks, but in only 17% of patients with glioblastoma multiforme (median not attained). Twenty-one (20%) of the patients with anaplastic glioma and 33% of the patients with glioblastoma multiforme were removed from the study before completing the first 8-week course of therapy because of neurological deterioration and tumor progression by the 5th week of treatment. CONCLUSION: This study suggests that eflornithine alone is an effective palliative therapy for recurrent anaplastic gliomas. Additional studies are needed to confirm our finding.

Adolescent↗
PubMed1992

Alternative splicing of neurofibromatosis type 1 gene transcript in malignant brain tumors: PCR analysis of frozen-section mRNA.

The neurofibromatosis type 1 (NF1) gene encodes a 360-residue region showing significant homology to the catalytic domains of both mammalian GTPase-activating protein (GAP) and yeast IRA protein. The product of the GAP-related domain of the NF1 gene (NF1-GRD) has been shown to stimulate ras GTPase and consequently to inactivate ras protein. We previously reported that the NF1-GRD has two types of transcripts, type I and type II, which are generated by an alternative splicing mechanism, and that the differential splicing of the NF1-GRD may be related to differentiation of neuroectodermal cells. Here we examined the differential expression of type I and type II transcripts of NF1-GRD in clinical samples of supratentorial malignant brain tumors by the RNA-polymerase chain reaction (PCR) method using frozen tissue sections. Our observations revealed that normal cerebrum predominantly expressed the type II NF1-GRD transcript, whereas primitive neuroectodermal tumors predominantly expressed the type I transcript. Additionally, although the type I/type II ratio in astrocytomas varied widely among tissue samples, all glioblastomas showed higher type I/type II ratios than adjacent brain samples. The RNA-PCR analysis using frozen tissue sections is a useful and sensitive method for detecting genetic markers in clinical tissue samples.

Astrocytoma↗
PubMed1992

Primary central nervous system lymphoma: a role for adjuvant chemotherapy.

Sixteen immunocompetent patients, 10 of whom were previously reported, with primary non-Hodgkins lymphoma of the central nervous system (PCNSL) were treated and followed longitudinally by the Neuro-oncology Service at the University of California, San Francisco (UCSF) and the University of California, San Diego (UCSD). After undergoing surgery (biopsy or resection), these patients received radiation therapy (RT) with hydroxyurea (HU) followed by adjuvant chemotherapy with the combination of procarbazine, CCNU, and vincristine (PCV) as previously reported. All patients ultimately died of progressive recurrent PCNSL. Toxicity using the HU + RT followed by PCV schedule was tolerable. Median and quartile survival data (41 and 65 months, respectively) suggest efficacy for this chemotherapy schedule and further emphasizes a role for adjuvant chemotherapy in the primary treatment of PCNSL.

Adolescent↗
PubMed1992

Opioid-dopaminergic mechanisms in the potentiation of d-amphetamine discrimination by interferon-alpha.

In rats trained to discriminate 0.8 mg/kg IP d-amphetamine from 1 ml/kg saline, 4 x 10(6) U/kg of recombinant human interferon-alpha (rIFN-alpha) given intramuscularly 1 h prior to tests potentiated responses elicited by 0.4 mg/kg d-amphetamine. Coadministration of the opioid receptor antagonist naloxone (1 mg/kg IP) with rIFN-alpha suppressed the potentiation of d-amphetamine by the cytokine. Opioid-dopaminergic mechanisms are proposed to explain the action of rIFN-alpha.

Animals↗
PubMed1992

Hyperfractionated radiation therapy for gliomas of the brainstem in children and in adults.

Between February 1984 and September 1990, 60 patients with brainstem gliomas were treated with hyperfractionated radiotherapy in the Department of Radiation Oncology at the University of California, San Francisco. Forty-one children (< or = 18 years) and 19 adults were treated with 100 cGy twice daily with 4-8 hr between doses. Thirty-one patients (21 children and 10 adults) received total doses of 66-72 Gy and 29 patients (20 children and nine adults) received 74-78 Gy. Median follow-up was 208 weeks for all patients (214 weeks for children, 157 weeks for adults). Twenty-three patients (14 children and nine adults) were alive at the time of analysis, surviving 59-359 weeks following treatment. Median actuarial survival was 73.6 weeks overall (72 weeks for children, 190 weeks for adults; p = 0.43). Survival at 12 and 24 months was 65% and 38%, respectively (63% and 32%, for children; 68% and 53% for adults). All patients had pretreatment magnetic resonance imaging by which tumors were classified as either focal or diffuse. No significant pretreatment prognostic factors for adults were identified. In children, significant favorable prognostic factors on univariate analysis were older age (p = 0.001), tumor location in thalamus or midbrain (p = 0.002), focal appearance on MRI scan (p < 0.001) and duration of symptoms > 2 months prior to treatment (p < 0.001). Thirty-five patients had tumor biopsies, leading to a diagnosis in 33 (22 children and 11 adults). Children with moderately anaplastic astrocytomas survived significantly longer than those with glioblastoma multiforme or unbiopsied tumors (p < 0.001). Only duration of symptoms > 2 months remained significant as a favorable prognostic indicator for children on multivariate analysis (p < 0.001). Survival was not significantly different for patients receiving < or = 72 Gy and those receiving > 72 Gy (p = 0.18). No subgroup of patients showed significantly better survival with the higher dose. These findings indicate that hyperfractionated radiotherapy is effective treatment for adults and a subgroup of better prognosis children with brainstem gliomas. There is a subgroup of pediatric patients with extremely poor prognosis for whom even this aggressive treatment does little to extend survival. We conclude that there is no benefit to increasing total dose above 72 Gy for any of the groups analyzed.

Adolescent↗
PubMed1992

Biology and treatment of gliomas.

This review discusses some of the recent advances in glioma research and treatment. Our understanding of the characteristics of these tumors has been strengthened by the application of molecular biologic and genetic techniques to pathologic grading and therapy outcome. Newer attempts to correlate imaging modalities to pathologic grading are also discussed. It is anticipated that these developments will strengthen our ability to design improved treatment strategies, an essential goal inasmuch as current treatment schemes have limited benefit. More work needs to be done to understand the biology of these tumors especially the complex interactions of their cytokine expression, multiplicity of genetic abnormalities, and their local environment. Only then will be able to develop improved therapeutic interventions.

Biomarkers, Tumor↗
PubMed1992

Analgesic activity of anticancer agent suramin.

Suramin exhibited morphine-like analgesic activity in mice. It antagonized both thermal (hot-plate) and acetic acid-evoked writhing responses with ED50 values 1/100 and 1/68, respectively, that of morphine. The suramin- and morphine-induced hot-plate analgesia was suppressed by administration of 0.5 mg/kg naloxone. However, lower doses (5-30 micrograms/kg) of naloxone produced dose-related potentiation or suppression of suramin and morphine analgesia. This potentiation effect may be due to the inhibition of writhing by naloxone itself rather than be a direct antagonism of the morphine effect.

Analgesia↗
PubMed1992

Treatment of recurrent gliomas and metastatic brain tumors with a polydrug protocol designed to combat nitrosourea resistance.

PURPOSE: The study was undertaken to evaluate a chemotherapy protocol against recurrent malignant gliomas that was designed to combat presumed chloroethyl-nitrosourea (NU) resistance. PATIENTS AND METHODS: All patients had malignant gliomas and had failed prior therapy. Patients were stratified as having either glioblastoma multiforme (GM) or anaplastic gliomas (AG) and as having failed radiotherapy (RT) only or both RT and chemotherapy. Chemotherapy consisted of six drugs: before lomustine (CCNU), thioguanine (TG), dibromodulcitol (mitolactol; DBD), and procarbazine (PCB) were given to enhance CCNU-induced tumor-cell kill and to reduce alkyltransferase repair of ethylated DNA. A fluorouracil-hydroxyurea (FUHU) combination was given 2 weeks later to kill cells that began to cycle after the challenge of the first four drugs (TPDC-FUHU chemotherapy). RESULTS: Of the 88 assessable patients, 37 had GM, 38 had AG, and 13 had other primary and metastatic brain tumors. For GM patients, 61% had a partial response (PR) or stable disease (SD) for a median of 9.3 months if RT only failed, and 58% had a PR or SD for a median of 5.1 months if they had previously been treated with an NU. For AG patients, 92% had a PR or SD for a median of 15 months if RT only had failed, but only 38% had a PR or SD for a median of 10.6 months if they had been previously treated with a NU. Activity was also seen against other recurrent or progressive primary and metastatic brain tumors. CONCLUSIONS: TDPC-FUHU chemotherapy is a highly effective form of chemotherapy for both recurrent GM and AG patients. This study suggests but does not prove that this combination may be superior to other NU-based treatments for recurrent malignant glioma patients who fail RT. Because of the activity of this chemotherapy, we intend to evaluate more fully this approach in a randomized study.

Adolescent↗
PubMed1992

The place of hydroxyurea in the treatment of primary brain tumors.

Hydroxyurea has been used since the early 1970s to potentiate the effects of radiation in the treatment of primary gliomas. In the only randomized study, a statistically significant increase in time to tumor progression for glioblastoma patients was noted for those receiving hydroxyurea. In other studies, hydroxyurea has been used as a cell-cycle phase-specific agent to improve survival in patients with recurrent gliomas and, in combination with 5-fluorouracil, to increase cell kill and as a potential DNA polymerase inhibitor. Other protocols have used hydroxyurea during radiation therapy in medulloblastoma and in combination chemotherapy for metastatic brain tumors as well. While widely used in the treatment of primary and secondary brain tumors, hydroxyurea trials usually have not been randomized or otherwise controlled; most have been nonrandomized, phase II activity studies. With the conclusion of some current trials, it is conceivable that the use of hydroxyurea may be more clearly defined in the treatment of tumors affecting the nervous system.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Low-dose craniospinal radiation therapy for medulloblastoma.

At the University of California, San Francisco, 65 children with medulloblastoma of the posterior fossa were treated postoperatively with craniospinal irradiation; the dose to the posterior fossa was 54 Gy. The 26 children initially treated had only radiation therapy, receiving 30 to 40 Gy to the spine and 40 to 50 Gy to the brain. Subsequently, 39 children were treated with low-dose craniospinal irradiation and chemotherapy; 24 to 30 Gy was directed to the whole brain and 24 to 26 Gy to the spinal axis. Chemotherapy generally consisted of procarbazine just before, and hydroxyurea during, radiation therapy. Poor-risk and good-risk patients (defined by tumor resection less than 75% or greater than 75%, positive or negative myelogram, positive or negative cerebrospinal fluid analysis, age less than or greater than 2 years, respectively) were evenly distributed between the low-dose and high-dose craniospinal radiation therapy groups. Median follow-up was 51 months (range, 24 to 228 months). Kaplan-Meier actuarial survival for all patients was 73% at 5 years, 70% at 10 years. Freedom from disease progression was 68% at 5 years, 65% at 10 years. Whereas poor-risk patients treated with low-dose craniospinal irradiation and chemotherapy had a 5-year survival of 58% and a 5-year freedom from disease progression of 39%, those figures in the comparable good-risk patients were 83% and 77%, respectively. For both good-risk and poor-risk patients, the posterior fossa was the primary site of recurrence. Tumors recurred in the frontal region, probably under blocks, in three patients receiving low-dose irradiation and in two receiving the higher dose. Reducing the dose of whole-brain and spinal irradiation and giving chemotherapy did not result in a higher rate of recurrence in the brain or spinal cord. Intellectual and social function appeared better in patients receiving the lower dose. We did not study whether chemotherapy benefitted good-risk patients. Craniospinal axis irradiation at a lower dose than conventionally used does not compromise local control or survival in patients with medulloblastoma, and may reduce toxicity.

Adolescent↗
PubMed1991

External irradiation followed by an interstitial high activity iodine-125 implant "boost" in the initial treatment of malignant gliomas: NCOG study 6G-82-2.

Between January 1982 and January 1990, 107 patients with unifocal, circumscribed malignant gliomas participated in a non-randomized trial testing brachytherapy in their initial treatment. Focal external irradiation (6000 cGy) was combined with an implant of high-activity iodine-125 (5000-6000 cGy) and six courses of procarbazine, lomustine, and vincristine. Of the 101 evaluable patients, 63 received implants. Of these, 29 had non-glioblastoma anaplastic gliomas, and 34 had glioblastoma multiforme. The other 38 did not receive implants, in most cases because radiation therapy failed to reduce the size of the tumor. The median survival was 165 weeks for all evaluable patients with non-glioblastoma anaplastic gliomas, 157 weeks for those with implants, 67 weeks for all evaluable glioblastoma patients, and 88 weeks for those with implants. Of the glioblastoma patients with implants, nine were alive after 2 years, and three were alive after 3 years. In each of the groups, nearly half the patients underwent reoperation for clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site after 46.1 weeks (median) for glioblastoma multiforme and 41.3 weeks for non-glioblastoma patients. Karnofsky Performance Scores showed only a small decline in performance after brachytherapy. Patients receiving implants for non-glioblastoma anaplastic gliomas had a mean Karnofsky Performance Score of 91% (range 90-100%) after 1 month and 78% (range 60-100%) 30 months after brachytherapy. Those treated for glioblastoma multiforme had a mean Karnofsky Performance Score of 86% (range 60-100%) at 1 month and 75% (range 60-100%) at 24 months. The quality of life of treated patients appears to be satisfactory. On the basis of comparisons with previous studies, we conclude that a brachytherapy "boost" after external irradiation may be valuable for some patients with glioblastoma multiforme but not for those with non-glioblastoma anaplastic gliomas.

Adult↗
PubMed1991

Evaluation of bromodeoxyuridine in glioblastoma multiforme: a Northern California Cancer Center Phase II study.

In a study activated in 1983 and closed in 1987, the Brain Tumor Research Center of the University of California and the Northern California Cancer Center evaluated the effect of bromodeoxyuridine in the treatment of glioblastoma multiforme. A total of 160 patients were evaluable of 173 entered. Patients were to receive a bromodeoxyuridine infusion of 0.8 g/m2 daily over 24 hours for 4 days of each of 6 weeks of radiotherapy directed to the tumor plus a margin delivering a total of 60 Gy. Eligibility requirements included Karnofsky performance status greater than or equal to 70, biopsy or resection and central pathology review by one of the authors. Following radiotherapy patients were to receive chemotherapy with procarbazine, CCNU, and vincristine for 1 year. Median survival was 55.7 weeks and time to failure, 34.5 weeks for the evaluable group of 160 patients. In a univariate analysis the variables that influence survival and time to failure were: age, Karnofsky performance status, bromodeoxyuridine dose and the delivery of at least one procarbazine, CCNU, and vincristine cycle following radiotherapy. In multivariate analysis, age, Karnofsky performance status, and bromodeoxyuridine dose remain significant for time to failure; age and Karnofsky performance status remain significant for survival.

Adult↗
PubMed1991

Inhibition of adenylate cyclase by tetraplatin.

In the investigation of effects of platinum-containing compounds on dopamine (DA)-activated adenylate cyclase system, tetraplatin and cisplatin were found to suppress the increase of enzyme activity by various activators. However, tetraplatin was a much more potent inhibitor than cisplatin, with its I50 values being 1/25, 1/45, and 1/130 that of cisplatin in the presence of DA/Gpp(NH)p, NaF/AlCl3, and forskolin/Gpp(NH)p respectively.

Adenylyl Cyclase Inhibitors↗
PubMed1991

Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: a phase I/II study.

A multicenter phase I/II trial of a human recombinant interferon beta (Betaseron; Triton Biosciences, Alameda, CA) was conducted in patients with recurrent glioblastoma and anaplastic astrocytoma in six centers between 1986 and 1988. Betaseron was given intravenously three times per week, starting at 90 x 10(6) IU per dose and escalating by 90 x 10(6) IU every 2 weeks up to a maximum dose of 540 x 10(6) per treatment. All patients had failed prior radiotherapy, and most had failed one or more courses of chemotherapy. Of the 72 patients entered into the protocol, 65 were considered assessable. Of 65 patients, 41 had glioblastoma, and 24 had anaplastic astrocytoma. Of the 65 assessable patients, 15 (23%) had an objective response (R), and 18 (28%) had stable disease (S), with a combined R and S rate of 51%. The Kaplan-Meier median time to progression was 24 weeks for the responders, 10 weeks for the nonresponders, and 23 weeks for the whole group. These results suggest that Betaseron has definite activity in recurrent gliomas, with an R + S rate of 51%. The maximum-tolerated dose (MTD) is between 180 and 360 x 10(6) IU, with neurotoxicity being the most troublesome toxicity at higher doses. Two patients died of treatment-related complication. Since most responders showed responses at the 180 x 10(6 IU dose range, further studies using a lower dose of Betaseron aimed at decreasing toxicity and allowing chronic maintenance therapy are merited.

Adult↗