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P M Zeltzer

Publications and source records attributed to P M Zeltzer.

At least 19 recordsLinked to original sources
PubMed1992

Choroid plexus tumors in childhood. Response to chemotherapy, and immunophenotypic profile using a panel of monoclonal antibodies.

Clinical and immunophenotypic (IP) data are presented on three children with choroid plexus (CP) tumors. Two children ages 0.2 and 2 years old with histologically proven malignant tumors had subtotal tumor resections and were treated with ten monthly cycles of eight-drugs-in-1-day chemotherapy without radiation therapy (XRT). Both are free of tumor 4 and 7 years later. The literature on survival of children with CP carcinomas after chemotherapy and XRT is reviewed. Monoclonal antibodies to 17 neuroectodermal, neuronal, glial, and leukocytic markers on frozen sections were used to IP the two malignant tumors and a CP papilloma. All tumors expressed two neuroectodermal markers (PI-153/3 and UJ 223.8), cytokeratin 19, and a neural and leukocyte marker (Thy-1). Two of three expressed neurofilament protein (NF-H) and glial fibrillary acidic protein (GFAP) and one expressed NF-M and common leukocyte antigen. None had strong expression for the panneuroectodermal antigen UJ13/A. There was variable expression of the other markers. The most common IP profile for CP tumors (cytokeratin 18+, PI-153/3+, Thy-1+, UJ 223.8+, and GFAP+ and UJ13A-, UJ 127.11-, and NF-L-) is discussed in the context of the current knowledge of the ontogenetic origin of the CP. It was concluded that chemotherapy for malignant CP tumors can be associated with long-term survival in young children and that the unique IP profile of CP tumors with coexpression of three intermediate filaments suggests new and provocative evidence of their cellular complexity and heterogeneity.

Antibodies, Monoclonal↗
PubMed1991

Prolonged response to carboplatin in an infant with brain stem glioma.

Adults and children with brain stem gliomas have a mean survival time of 15 months after radiation therapy (XRT). Infants with this tumor present additional complexities for treatment because of possible neurotoxicity of the radiation to the developing brain. We report a 15-month-old child with biopsy-proven brain stem glioma with clinical and radiographic evidence of disease progression. She was treated with 24 monthly courses of carboplatin without radiation therapy and has had a 39+ month response. The clinical response started after 3 months and the radiographic evidence was documented at 10 months by magnetic resonance imaging. The toxicity was minimal. Longitudinal neuropsychological assessment demonstrated continued improvement at 36 months post diagnosis but with some motor functioning below expected age levels. Cervico-medullary astrocytoma in a young patient may be the appropriate clinical setting for future trials of chemotherapy without XRT.

Brain Neoplasms↗
PubMed1991

Stroke as a late sequela of cranial irradiation for childhood brain tumors.

Cerebrovascular disease involving large and medium-size vessels is thought to be an uncommon sequela of treatment of childhood brain tumors. We reviewed 11 children who developed cerebrovascular disease manifested by strokes or transient ischemic attacks 6 months to 4 years after treatment of brain tumors, while their tumors were in remission. All had received radiation therapy, and seven had received chemotherapy. One child died of acute bilateral cerebral infarctions due to carotid occlusion on one side and marked stenosis on the other 2 years after receiving radiation therapy for an incompletely resected craniopharyngioma. Pathologically, there was marked subendothelial fibrosis of the vessels of the circle of Willis, with inflammatory changes surrounding some of the vessels. In addition to the widely recognized small-vessel damage caused by radiation and chemotherapy in children (mineralizing microangiopathy), damage to medium and large intracranial vessels may result in late sequelae, manifested by stroke or transient ischemic attacks.

Adolescent↗
PubMed1990

Immunophenotype profile of childhood medulloblastomas and supratentorial primitive neuroectodermal tumors using 16 monoclonal antibodies.

Immunophenotype analysis of 17 childhood medulloblastoma (MED) and supratentorial primitive neuroectodermal tumors (SPNET) was performed on frozen sections using 16 monoclonal antibodies (MoAb) with the biotin-streptavidin alkaline phosphatase immunohistochemical technique. Neuroectodermal associated antigens, reacting with MoAb UJ13/A, UJ127.11, UJ167.11, and UJ223.8 were detected on greater than 10% of the cells in 15 of 17 MED/SPNET. Thy-1 was present on 14 of 17 tumors and absent on two of three SPNET. Neuronal (NF) and glial (GFAP) differentiation markers were evaluated. NF-H was demonstrated in 15 of 17, NF-M in six of 17 and NF-L in one of 17 tumors; GFAP was positive in nine of 17 patients. In nine of 17 MED/SPNET both proteins were present within the same tumor. Common leukocyte antigen was demonstrated on greater than 50% of the cells in four of 14 tumors as were shared tumor/leukocyte markers using monoclonal antibodies Thy-1, PI153/3, UJ308. The most frequent MED immunophenotype analysis was UJ 13/A+, UJ 127.11+, UJ 167.11+, UJ223.8+, PI 153/3+, A2B5+, GFAP+, NF-H+, and CLA-, NF-M-, NF-L-, 215-, 275-, 282.1-. The authors conclude that MED and SPNET are heterogeneous for expression of 16 markers and have similar immunophenotype analysis profiles, supporting the concept of their common, neuroectodermal origin. Common leukocyte antigen on both tumor cells and leukocytes precludes identification of tumor infiltrating leukocytes using monostaining techniques.

Adolescent↗
PubMed1990

Immunophenotyping of childhood astrocytomas with a library of monoclonal antibodies.

Immunophenotype (IP) analysis of 14 childhood glial tumors was performed with a library of 16 monoclonal antibodies (MAbs) using biotin-streptavidin-alkaline phosphatase immunohistochemical detection technique. Presence of glial or neuronal differentiated cells within the tumors was evaluated with MAbs against cell-lineage-specific markers: high-, medium- and low-molecular-weight neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP). Intense expression of GFAP was demonstrated in 14/14 astrocytomas. The three NFs were detected in 10-50% of the cells in 6/14 cases. The pan-neuro-ectodermal antigen defined by MAb UJ 13/A was present in 7/14 astrocytomas on more than 10% of the cells. Thy-1 was expressed in 14/14 tumors on more than 50% of their cells. The GQ ganglioside antigen detected by MAB A2B5, was found in 12/14 tumors. Shared antigens exist among morphologically benign and malignant glial tumor cells and leukocytes detectable with the following four MAbs: Thy-1, PI 153/3, UJ 308 and anti-HLe, common leukocyte antigen (CLA). CLA-expressing cells were demonstrated in 8/12 astrocytomas, and in 4/12 cases more than 90% of the cells were positive. We have shown that cells within childhood astrocytomas can express neuronal IP. The most common expressed phenotype for glial tumors was: GFAP+, Thy-1+, A2B5+, UJ 167.11+, UJ 223.8+, NF (H,M)+, UJ 13/A+, UJ 127.11-, and NF (L)-.

Adolescent↗
PubMed1989

Current neurosurgical treatment of medulloblastomas in children. A report from the Children's Cancer Study Group.

To determine the current neurosurgical treatment of children with medulloblastomas, we reviewed the operative reports and neurosurgical report forms from 141 children with posterior fossa medulloblastomas treated on two current Children's Cancer Study Group (CCSG) protocols, CCG-921 for high-stage and CCG-923 for low-stage medulloblastoma. Most medulloblastoma operations were performed in major medical centers: 61% of the operations were performed in CCSG member institutions, 23% in CCSG affiliates and 16% in other institutions. The tumor T stage distribution was as follows: T1-4%, T2-15%, T3A-35%, T3B-36%, and T4-10%. Tumors infiltrated the brainstem in 38% of cases and were associated with hydrocephalus in 91% of cases. Hydrocephalus was managed by external ventricular drains in 50% and by shunts in 60%. Adjunctive instruments (e.g., microscope, ultrasonic aspirator) were used in 93% of the operations. Tumor removals were as follows: biopsy only 3%, partial removals 13%, subtotal removals 13%, near total removals 41% and gross total removals in 40%; 90% or more of the tumor was removed in 81% of the operations. Forty-seven percent of the operations were performed by pediatric neurosurgeons. Near total and gross total removals were performed significantly more often (p less than 0.05) by pediatric neurosurgeons than by general neurosurgeons. Postoperative morbidity was reported in 46% of cases, including neurologic morbidity in 26% of cases. There was no significant difference in patient morbidity between pediatric and general neurosurgeons.

Biopsy↗
PubMed1986

Serum neuron-specific enolase in children with neuroblastoma. Relationship to stage and disease course.

Serum neuron-specific enolase (NSE) was measured in 61 children at diagnosis with all stages of neuroblastoma. The median serum values for Stages I, II, III, IV, and IV-S were 13, 23, 40, 214, and 40 ng/ml, respectively. Mean serum levels were different between groups I versus IV, (P = 0.0004) II versus IV (P = 0.0001) and IV-S versus IV (P = 0.004). The prognostic value of serum NSE for disease-free survival was determined in 54 patients at risk for relapse 2 or more years after diagnosis. The disease-free survival rate of all patients with levels of less than 100 ng/ml was 27/34 (79%), whereas it was 2/20 (10%) for those with higher levels. In 28 patients with lower stage disease and a good prognosis (Stages I, II, and IV-S) NSE levels were not predictive of relapse. Only 1 of these 28 patients had a raised level (greater than 100 ng/ml) and survived without relapse, whereas 4 patients who relapsed had serum NSE less than 100 ng/ml at diagnosis. In patients with Stages III and IV disease, a raised serum NSE level was associated with poor outcome: only 1/19 (5%) survived with NSE levels greater than 100 ng/ml, whereas survival was 5/8 (63%) with values below 100 ng/ml. Serial samples were analyzed on 17 patients; all 8 patients with initial NSE levels greater than 100 ng/ml achieved near normal levels during remission (median, 21 ng/ml). However, in only 4/10 patients studied at time of relapse, did the levels rise coincident with relapse. The sera of 47 patients with other forms of cancer and 19 siblings of cancer patients were at or near the normal limits (0-15 ng/ml), with three exceptions: acute lymphoblastic leukemia (286 ng/ml), hepatoblastoma (176 ng/ml), and primitive neuroectodermal tumor (105 ng/ml). Serum NSE is a useful marker for patients with advanced neuroblastoma in whom elevated levels were associated with a poor outcome; the raised NSE levels returned to near normal after therapy. In patients with Stage IV-S disease serum NSE levels were significantly lower than those in Stage IV despite their extensive tumor burden. Serum NSE estimation may confirm Stage IV-S status and suggest a more benign clinical course.

Carcinoma, Hepatocellular↗
PubMed1986

Normal and malignant neural cells: a comprehensive survey of human and murine nervous system markers.

Tumor-associated neural markers are finding increased application in diagnostic histopathology and in the development of brain tumor therapy. The major cell-type-specific markers and monoclonal antibodies that identify murine and human neural cells are reviewed in this study. Monoclonal antibodies, raised against fetal and adult neural tissue, neuroectodermal tumor tissue, or cell line immunogens which recognize epitopes on brain tumors are comprehensively described including antigens common to the nervous, hematopoietic, and immune systems. The clinical application of neural cell markers and monoclonal antibodies for the diagnosis, localization, and treatment of neuroectodermal tumors is reviewed.

Animals↗
PubMed1986

Cloning of pediatric malignancies for drug sensitivity testing in the human tumor cloning assay.

In a 4-year period 168 tumor specimens received from 119 pediatric patients were plated in a soft agar cloning system. Overall, 47 or 28% of the tumor specimens had growth adequate enough for drug sensitivity testing. Drug sensitivity testing was performed using a variety of standards as well as investigational anticancer agents. Overall, 129 evaluable in vitro drug sensitivity tests were performed with 33 (26%) of the tests showing sensitivity to an agent. The most active drugs in vitro included the standard agents doxorubicin and cis-platinum as well as the investigational agents mitoxantrone and m-AMSA. From these data it is clear the cloning assay can be used to study pediatric malignancies. However, before the cloning assay can be applied to clinical pediatric oncology practice, the assay must be improved in terms of tumor growth and validated with prospective clinical trials.

Adolescent↗
PubMed1978

Alpha fetoprotein in the differentiation of neonatal hepatitis and biliary atresia: current status and implications for the pathogenesis of these disorders.

Neonatal hepatitis (NH) and biliary atresia (BA) are disorders of early infancy that may be difficult to differentiate. Since surgical therapy can be curative if performed early in the disease course of BA, accurate diagnosis is of great importance. Elevated levels of serum alpha fetoprotein (AFP) do occur in many cases of NH and may be helpful in differentiating this condition from BA. Evidence is presented which suggests that initially BA and NH may be the same disease. The individual host response determines the final clinical outcome and AFP could be the immunoregulatory substance which affects pathological progression from NH to BA.

Bile Ducts↗
PubMed1978

Microassay for immunoglobulin G antibodies to Treponema pallidum with radioiodinated protein A from staphylococcus aureus: immunoglobulin G response in experimental syphilis in rabbits.

Radioiodinated staphylococcal protein A (SpA) was used to detect the immunoglobulin G (IgG) antibody response to Treponema pallidum in experimental syphilis. This solid-phase assay is based on the principle that SpA binds avidly to the Fc portion of mammalian IgG. The optimal number of organisms for detection of antibody was 10(5) per microwell. Of eight fixatives, 10% ethanol gave an optimum immune binding ratio of infected to normal rabbit serus at a 1:100 serum dilution. Kinetic studies demonstrated maximum binding and the highest immune binding ratio (15:1) with a 60-min incubation each for antibody and (125)I-SpA, respectively. The IgG response in rabbits intratesticularly infected with live T. pallidum and bled at -1, 9, 30, 90, 180, and 480 days was detected first at 9 days, reached a peak at 30 days, and remained elevated for 480 days. Absorption studies with an extract of T. phagedenis biotype reiterii demonstrated that 65 to 85% of the total antitreponemal IgG response was specific for T. pallidum throughout the course of infection. The microassay was quantitative and detected less than 2 ng of antibody.

Animals↗
PubMed1977

Microassay using radioiodinated protein A from Staphylococcus aureus for antibodies bound to cell surface antigens of adherent tumor cells.

A new microassay which utilizes radioiodinated staphylococcal protein A (SpA) to detect antibodies bound to cell surface antigens (CSA) was developed for monolayers of viable cultured tumor cells. Optimal detection of bound antibodies occurred at 37 degrees C with incubation periods of one hour each for antiserum and 131I-SpA. Labelling target cells with 125I-iododeoxyuridine facilitated expression of results relative to tumor cell number or protein concentration. Quantitation of antibody depended on CSA (tumor cells) and 131I-SpA being in excess of antibody; under these conditions, 0.25 ng of cell surface bound antibody could be detected readily. Initial studies utilized cultured human neurobodies in human serum which bound to CSA were removed by absorption with glutaraldehyde-insolubilized fetal calf serum (FCS) suggesting that FCS or FCS-like determinants can be CSA. Rabbit antisera, after extensive absorption, bound to cultured neuroblastoma and lung adenocarcinoma cells in a cell type specific pattern. These experiments demonstrated the value of this assay in quantitating anti-CSA antibodies and in serological analysis of tumor CSA.

Adenocarcinoma↗
PubMed1977

Inhibition of antibody-dependent cellular cytotoxicity by protein A from Staphylococcus aureus.

Protein A, a cell wall constituent of several strains of Staphylococcus aureus, binds strongly to the Fc portion of immunoglobulins. This investigation demonstrated that such binding can inhibit antibody-dependent cellular cytotoxicity (ADCC). The degree to which ADCC was inhibited depended upon the relative concentrations of protein A and anti-target cell antiserum. Protein A also inhibited the formation of rosettes between antibody-coated sheep red blood cells and lymphoid cells with Fc receptors. We, therefore, conclude that protein A inhibits ADCC by preventing the binding of antibody-coated target cells to Fc receptors on cytotoxic effector cells.

Antibodies↗