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Biomedical subjects

V Levin

Publications and source records attributed to V Levin.

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

The role of neutrons in the treatment of soft tissue sarcomas.

Two-hundred twenty-one patients with soft tissue sarcoma were treated from 1978 to 1983. Treatment was nonrandomized and consisted of neutron irradiation in 94 cases with gross tumor. Treatment was nonrandomized and consisted of neutron boost irradiation after photon-irradiation or electron-irradiation in 127 cases with no gross tumor after surgery. Patient distribution according to UICC (1978) criteria was 15, 100, and 106 of T1, T2, and T3 respectively. Distribution by pathologic grade was 54, 107, and 60 for Grade 1, Grade 2, and Grade 3 tumors. Distribution by tumor residuum after surgery was 23 cases without microscopic disease (R0), 104 with microscopic disease (R1), and 94 with gross residuum (R2) or nonoperative disease. Five-year follow-up reveals a significant difference (P = 0.024) in disease-free survival (DFS) for T1 (60%), T2 (71%), and T3 (29%, P = 0.016) tumors. Similarly, there are significant DFS differences among G 1 (74%), G 2 (48%, P = 0.035), and G 3 lesions (22%, P = 0.024). The impact of tumor bulk or residuum on DFS after operation is significant when comparing R0 (87%) and R1 (65%) disease (P = 0.042). The 5-year survival of patients who had gross residuum (R2) after surgery was significantly worse (26%, P = 0.003). Ninety percent of patients failed treatment locally and distally within 2 years. The late morbidity rate was 27% for neutron and 7% for neutron-boost irradiation. In our series and reported photon data, local control rates for tumors 5 to 10 cm with neutrons were 76% and 53%, respectively. Low energy (d(14) + Be) neutrons are considered beneficial in the postoperative treatment of well-differentiated soft tissue sarcomas where gross tumor remains. Neutron-boost irradiation is of potential benefit in the treatment after operation of T2-3, and G 1-2 tumors if there is microscopic residual tumor.

Adult↗
PubMed1989

Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine.

Thirty-eight patients with primary recurrent anaplastic gliomas and glioblastomas, were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the polyamine inhibitor alpha-difluoromethylornithine (DFMO). There were 5 brain stem, 1 cerebellar, and 32 supratentorial glioma tumors. All had been treated with surgery (except in the case of 4 brain stem tumors for which biopsies were not obtained) and radiotherapy. Eight patients had received prior chemotherapy. Of the 21 patients with evaluable supratentorial anaplastic gliomas, 2 (9.5%) had a partial response and 10 (47.6%) had stable disease. The median time to tumor progression for the anaplastic gliomas has not been attained yet. However, median survival for these 12 patients was 119 weeks measured from the initiation of chemotherapy. Median survival for the entire anaplastic glioma group of 21 was 56 weeks. Minimal activity was seen against glioblastoma multiforme. The median time to tumor progression was 8 weeks with median survival of 21 weeks. Of the 5 patients with brain stem tumors, 3 are alive with stable disease at 77, 93, and 220 weeks. The combination was well tolerated with dose-limiting toxicity being myelosuppression and hearing loss. Further trials are warranted to compare the combination of BCNU and DFMO against BCNU alone in a prospective randomized trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Neuronal cell differentiation of human neuroblastoma cells by retinoic acid plus herbimycin A.

We investigated the effect of retinoic acid (RA) and herbimycin A (herb-A) on cell growth, cell differentiation, and colony formation of human neuroblastoma cell lines. The neuroblastoma line SK-N-SH expressed both neuroblast and nonneuronal phenotypes, whereas its subclone SH-SY5Y and the Kelly cell line were predominantly neuroblastic. Both herb-A and RA, given alone, moderately reduced cell growth and colony formation of the neuroblastic cell lines. Growth curve analyses with SK-N-SH suggested that herb-A greatly reduced the number of initially growing cells, whereas RA slightly enhanced initial cell growth. Morphological changes were determined with the use of rhodaminephalloidin staining of actin. Retinoic acid caused an increase in the fraction of neuroblast cell in SK-N-SH, and conversely of nonneuronal cells in SH-SY5Y and Kelly cell lines. Both drugs also caused partial differentiation towards a neuronal phenotype, and herb-A induced selective lysis of nonneuronal cells of SK-N-SH. Because of their discrepant effects, RA (10 microM) and herb-A (236 nM) were tested in combination at a concentration that had only moderate effects when given alone. The combination further reduced cell growth and colony formation and dramatically enhanced differentiation towards a neuronal morphology. The Kelly cell line with amplified N-myc genome, which correlates with clinical progression of neuroblastoma, was also sensitive to RA plus herb-A. These results recommend the combination of RA and herb-A for differentiation therapy of neuroblastoma.

Anti-Bacterial Agents↗
PubMed1988

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine.

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.

Adolescent↗
PubMed1987

Malignant supratentorial gliomas in childhood.

In this review, we try to review concisely the incidence, genetic predilections, classification, and diagnosis of supratentorial gliomas (astrocytomas, oligodendrogliomas, and mixed gliomas) in children. While surgery and irradiation present the most commonly used and valuable modes of treatment, chemotherapy is a valuable adjunctive therapy. Used either with surgery and radiation in primary untreated patients or at recurrence (progression), chemotherapy can increase useful life. The late effects of treatment are primarily endocrine deficiencies and intellectual impairment; nevertheless, they are not of a degree to preclude aggressive therapy. In order to improve therapy, and because of the small number of patients with supratentorial tumors, collaborative multi-institutional trials should be encouraged.

Adolescent↗
PubMed1986

Induction of progesterone receptor by androgens in the mouse uterus.

The comparative abilities of 3 naturally occurring androgens to compete for [3H]estradiol-17 beta ([3H]E2)-binding sites in uterine cytosol and to induce uterotrophic responses in immature female mice have been investigated. 5 alpha-Androstane-3 beta,17 beta-diol (3 beta-diol), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and 5-androstene-3 beta,17 beta-diol (delta 5-diol) are all effective at diminishing cytoplasmic [3H]E2 binding. Their relative effectiveness are in the order of 3 beta-diol greater than delta 5-diol = 3 alpha-diol. When these steroids were injected intramuscularly (two 100-200 micrograms injections) into immature female mice (21 days old), they induced similar elevations of uterine dry weight, water content, cytosolic estrogen (ER) and progesterone (PR) receptor contents, and nuclear ER content as did estradiol-17 beta (E2). 3 beta-Diol was the most effective steroid at inducing cytosolic and nuclear ER, and PR production in mouse uterus. Followed in effectiveness was delta 5-diol and 3 alpha-diol. Unexpectedly, 3 beta-diol was found to be more potent than E2 in stimulating uterine ER and PR increases. Nonetheless, the androgens are poorer stimulators of uterine dry weight increase and water retention than E2 is. These results indicate that the androgens may interact with the ER system in the uterus to bring about the uterotrophic responses and 3 beta-diol is a more estrogenic steroid than delta 5-diol and 3 alpha-diol in the mouse uterus.

Androgens↗
PubMed1986

Computerized tomography in the prognosis of malignant cerebral gliomas.

Ninety-seven patients with supratentorial malignant gliomas who received postoperative radiation therapy and chemotherapy at the University of California, San Francisco, from 1977 through 1984 showed improvement in their follow-up computerized tomography (CT) scans. Twenty-one of these 97 "CT responders" were designated "complete responders" because on serial CT scans they had complete disappearance of the tumor mass and contrast enhancement, which had been present postoperatively. In the remaining 76 patients, CT scans showed reduction in the size, but not disappearance, of the lesions, and these were designated "partial responders." Fifty-eight partial responders had glioblastoma multiforme (GM); their median survival time was 72 weeks. The median survival time for the 11 complete responders with GM has not yet been achieved, but survival at the 53rd percentile is 172 weeks. Among patients with highly anaplastic astrocytoma, the median survival time was 211 weeks for the 10 complete responders and 125 weeks for the 18 partial responders. Eleven of the 21 complete responders are alive at a median postoperative follow-up time of 163 weeks (range 114 to 470 weeks). Eighteen of these patients had subtotal resection of tumor; three patients had gross total tumor resections, but postoperative CT scans showed evidence of residual or possibly recurrent tumor within 1.5 to 4.5 months. Resolution of the tumor mass and contrast enhancement took 9 to 151 weeks; the time to resolution did not depend upon the configuration of the remaining tumor mass and contrast enhancement after surgery. In this study, patients with malignant gliomas whose CT scans eventually showed sustained complete disappearance of the tumor mass and contrast enhancement had a more favorable prognosis than did patients whose CT scans showed improvement, but not complete disappearance, of the tumor. These CT findings may prove useful in determining the prognosis of patients with malignant gliomas.

Adolescent↗
PubMed1980

Cyclic GMP system in the epidermis.

A great deal of knowledge has been gained concerning the activation of adenylate and guanylate cyclase in epidermal cells. Adenylate cyclase is activated by 4 different independent receptors-responding respectively to catecholamine (beta), to prostaglandins (E), to histamine (H2), and to adenosine and it phosphorylated derivatives. Upon activation, each of these receptors becomes unresponsive to further stimulation by its specific stimulator. Guanylate cyclase, on the other hand, is activated by histamine (H1) and epidermal growth factor (EGF). Unlike EGF, the histamine activation is extremely rapid (less than 5 minutes). Epidermal cells are permeable (leak) to cyclic GMP but not cyclic AMP. When the skin is traumatized or injured in any way (even by intradermal injection) there is a sudden catastrophic change in the intracellular levels of the cyclic nucleotides (and of ATP). Cyclic AMP rapidly rises to perhaps 5-10 times its normal resting level while cyclic GMP falls to 10-20% of its level in vivo. The rise in cyclic AMP is due to activation of adenylate cyclase while the fall in cyclic GMP is due in major part to activation of cyclic GMP phosphodiesterase (and perhaps the fall in ATP is due to activation of ATPase). The changes in ATP and cyclic AMP can be reversed by incubating the tissue in a buffered salt solution containing glucose, but this does not normalize the cyclic GMP content. The fall in cyclic GMP can be prevented by a phosphodiesterase inhibitor (IBMX ). This series of events has been called the "ischemia effect." However, it implies that a lack of oxygen is at fault, and that has not been shown to be the case. Its underlying cause and possible physiologic significance are not known. Do these changes in cyclic nucleotides have effects on epidermal proliferation? And does EGF? Agents which increase cyclic AMP do inhibit the epidermal outgrowth and mitotic activity of explant cultures of pig skin. Cyclic GMP does increase outgrowth at a particular concentration. Histamine, which elevates both cyclic nucleotides, has a biphasic action depending on its concentration. These findings imply that these nucleotides do act as one of the controls of epidermal proliferation. The action of cyclic GMP is not accompanied by detectably increased phosphorylation of epidermal proteins. On the other hand, EGF action which also enhances epidermal outgrowth is characterized by an increased protein phosphorylation that precedes any increase in cellular cyclic GMP. We conclude that the action of EGF is independent of the cyclic nucleotide system.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1978

Computed tomography in the follow-up of medulloblastomas and ependymomas.

The course of 36 patients with medulloblastoma and ependymoma was evaluated prospectively by clinical examination, radionuclide (RN) studies and computed tomography (CT). Seventeen of the 36 patients (47%) had tumor recurrence. Twelve (41%) of the 29 patients with medulloblastoma had recurrent tumors of which 7 of 12 (58%) were at the primary site and 2 of 12 (17%) were within the ventricles while 10 of 12 (83%) were in the subarachnoid space. Five of the 7 patients with ependymoma had recurrent tumors. In 4 of the 5 patients tumor recurred at the primary site while subarachnoid seeding occurred in 2 of 5 patients (40%) and intraventricular metastases were found in 4 of 5 patients (80%). Progressive ventricular enlargement often accompanied subarachnoid seeding, presumably secondary to obstruction of cerebrospinal fluid (CSF) flow in the subarachnoid pathways. CT and RN scans were frequently complementary in detecting tumor recurrence.

Brain Neoplasms↗
PubMed1978

Quantitative aspects of contrast enhancement in cranial computed tomography.

The temporal relationship of blood iodine levels to tumor enhancement in cranial computed tomography was studied in a series of patients. Both the bolus and biphasic techniques were evaluated. Peak tumor intensity may not develop immediately, but may be more pronounced on a 20-minute scan. The low-density centers seen in malignant gliomas show delayed enhancement. These low-density centers represent a second compartment which equilibrates with the intravascular and interstitial contrast material at a much slower rate. Patients with malignant gliomas can be scanned up to one hour following contrast injection without significant loss of information.

Blood-Brain Barrier↗
PubMed1977

Brain tumors: criteria of response and definition of recurrence.

The criteria for determining response to therapy and establishing brain tumor recurrence are presented. Basing their conclusions on a series of more than 500 patients, the authors contend that serial scintiscans and computerized axial tomograms can be used to determine accurately the response to therapy and recurrence or tumor regrowth. The problems in evaluating response and tumor recurrence are discussed, with emphasis on those relating to concurrent glucocorticoid therapy and medical conditions such as infection, hematomas, and drug side-effects.

Antineoplastic Agents↗
PubMed1975

Phase II study of procarbazine, CCNU, and vincristine combination chemotherapy in the treatment of malignant brain tumors.

Forty-eight patients with primary or metastatic malignant tumors of the central nervous system (CNS) were treated with combination chemotherapy, consisting or procarbazine (100 mg/m2 X 14 days), CCNU (75 mg/m2), and vincristine (1.4 mg/m2 X 2, 1 week apart) (PCV) every 4 weeks. Most patients had undergone initial resection of primary tumors, postoperative radiotherapy, and a post irradiation interval of 3 months or more. Other patients harbored unbiopsied, newly-discovered primary or metastatic tumors. All patients were deteriorating neurologically when treatment began. Overall response rate for PCV combination therapy was 44%, no better than results obtained with single agent procarbazine or BCNU, the most effective drugs used alone in previous brain tumor chemotherapy studies.

Brain Neoplasms↗
PubMed1972

A compartmental analysis of 24 Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid.

1. The kinetics of (24)Na exchange in rat cerebrospinal fluid, brain and sciatic nerve were studied during steady-state plasma isotope conditions. The entrance of (24)Na into brain and sciatic nerve was found to fit a three compartmental model. Using newly derived equations for compartmental analysis, the first compartment (24)Na space of brain was found to be about 22% and the second compartment space about 6%; the corresponding sciatic nerve spaces were 26 and 11%, respectively. In the discussion, arguments are presented that suggest that the first compartment is the extracellular space (ECS) and the second compartment is the intracellular space. The t((1/2)) for compartmental equilibration between plasma and brain ECS was 2 hr and from ECS to intracellular space 14 hr; in nerve the respective t((1/2))'s were (2/3) hr and 10 hr.2. A third compartment of 18% was found in sciatic nerve which was interpreted to be anatomically confined to the epi- and perineurium; in brain the corresponding space was 2% and was felt to be anatomically and kinetically an inactive closed compartment in parallel with the blood.3. There were two t((1/2))'s for plasma-c.s.f. (24)Na equilibration of less than 10 min and 2 hr.4. Profiles of brain, from cortex to ventricle, at 6 min, demonstrated a gradient of decreasing (24)Na radioactivity from ventricle to cortex.

Animals↗