New chemotherapy for malignant neoplasms of the nervous system.
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Arsenicals↗
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Results for “Nervous System Neoplasms”
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Veterinary oncology: a survey.
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Animals↗
The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors.
A simple classification system for central nervous system neoplasms occurring primarily in infancy and childhood and largely composed of undifferentiated neuroepithelial cells is proposed. Classification is based upon appearance of the tumor as determined by light microscopy, immunocytochemical techniques, and ultrastructural features without consideration for site of origin. This classification is based on the concept that neoplastic transformation of primitive neuroepithelial cells in subependymal zones at all levels of the central nervous system or pineal body may develop into tumors largely composed of similar cells. It therefore seems appropriate to call these neoplasms primitive neuroectodermal tumors and to use descriptive terms to indicate the direction of cellular differentiation, when it has occurred. Proposed terminology for the five subtypes of undifferentiated neuroepithelial round cell tumors is as follows: 1) Primitive neuroectodermal tumor, not otherwise specified (PNET, NOS), 2) PNET with glial differentiation, 3) PNET with ependymal differentiation, 4) PNET with neuronal differentiation, and 5) PNET with multi- or bipotential differentiation. If the tumor is located in the cerebellum, medulloblastoma may be added in parentheses; if in the pineal body, pineal parenchymal neoplasm may be added.
Cell Transformation, Neoplastic↗
Establishment and characterization of a human primitive neuroectodermal tumor cell line from the cerebral hemisphere.
The primitive neuroectodermal tumors (PNET) comprise a class of malignant nervous system neoplasms that afflict children. These tumors consist of cells that are morphologically identical to the primitive neuroepithelial cells normally seen in early stages of neural embryogenesis, supporting the notion that PNET result from a disturbance in the process of normal neuronal or glial differentiation. In the central nervous system, PNET occur most commonly in the cerebellum (medulloblastomas), but only occasionally in the cerebral hemispheres. We report here the establishment and characterization of a new human cell line (PFSK) derived from a PNET from the cerebral hemisphere of a child. The growth characteristics of PFSK cells were typical of an immortalized, transformed cell line. Cytogenetic and molecular genetic studies showed that three different sublines were present. In one of these sublines, sequences from chromosome 17 had been lost during establishment in culture. Immunocytochemical studies showed that PFSK cells expressed nestin, an intermediate filament protein normally expressed by neuroepithelial stem cells during neurulation. The PFSK cells did not express antigens typically found in terminally differentiated neurons or glia, indicating that this tumor cell line might represent neuroepithelial stem cells prior to commitment to a neuronal or glial lineage.
Brain Neoplasms↗
Neurofilament proteins and human nervous system tumors.
Neoplasms that arise in the peripheral (e.g., carotid body tumors, neuroblastomas, pheochromocytomas) or central (gangliocytomas, medulloblastomas) nervous system express a number of neuron-specific gene products. Presumably, these tumors are derived from precursor cells that are or have the potential to develop into neurons or neuron-like cells. This report provides a critical examination of the hypothesis that cytoskeletal proteins of normal neurons, in particular the neuron-specific class of intermediate filaments (neurofilaments), are present but are abnormal in neoplasms derived from neurons or neuron-like cells. The implications of these findings for understanding tumor promotion and progression, and for development of molecular probes for the diagnostic assessment of these neoplasms, are discussed.
Antibodies, Monoclonal↗
Phase I studies of treatment of malignant gliomas and neoplastic meningitis with 131I-radiolabeled monoclonal antibodies anti-tenascin 81C6 and anti-chondroitin proteoglycan sulfate Me1-14 F (ab')2--a preliminary report.
The advent of monoclonal antibody (MAb) technology has made Ehrlich's postulate of the 'magic bullet' an attainable goal. Although specific localization of polyvalent antibodies to human gliomas was demonstrated in the 1960s, the lack of specific, high affinity antibody populations and of defined target antigens of sufficient density precluded therapeutic applications. Not until the identification of operationally specific tumor-associated antigens (present in tumor tissue but not normal central nervous system tissue); production of homogeneous, high affinity MAbs to such antigens; and the use of compartmental administration (intrathecal or intracystic), has the promise of passive immunotherapy of primary and metastatic central nervous system neoplasms been recognized. We report here preliminary data from Phase I studies of the compartmental administration of the anti-tenascin MAb 81C6 and F(ab2)2 fragments of MAb Me1-14, which recognizes the proteoglycan chondroitin sulfate-associated protein of gliomas and melanomas, to patients with primary central nervous system tumors or tumors metastatic to the central nervous system. Phase I dose escalation studies of intracystically administered 131I-labeled anti-tenascin MAb 81C6 to either spontaneous cysts of recurrent gliomas or surgically created cystic resection cavities have resulted in striking responses. Of five patients with recurrent cystic gliomas treated, four had partial responses, clinically or radiographically. Similarly, in patients with surgically created resection cavities, a partial response at the treatment site and extended stable disease status has been obtained following intracystic administration of 131I-labeled 81C6. No evidence of hematologic or neurologic toxicity has been observed in either patient population, with the exception of transient exacerbation of a pre-existing seizure disorder in a single patient. Dosimetry calculations indicated high intracystic retention for four to six weeks with little or no systemic dissemination; estimated total doses intracystically ranged from 12,700-70,290 rad. Intrathecal administration of labeled MAbs to patients with neoplastic meningitis is more difficult to assess in terms of clinical responsiveness. Of patients so treated with either 131I-labeled 81C6 or 131I-labeled Me1-14 (F(ab)2, cerebrospinal fluid and radiographic responses have been achieved, and survival prolongation through maintenance of stable disease has been observed in several cases. Initial results from pHase I dose escalation trials are encouraging in terms of the proportion of cases of disease stabilization and partial and complete responses obtained. Importantly, neurotoxicity has been virtually nonexistent, and hematologic toxicity rare and rapidly responsive to treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting.
Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases. Therefore, the authors propose that synaptophysin antibodies be used for the positive identification of metastatic NE tumors, notably in differential diagnosis. The possible implications of these findings for tumor diagnosis are discussed.
Endocrine System Diseases↗
Primary reticuloses of the central nervous system in dogs.
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Animals↗
Tumor-like multiple sclerosis (MS) lesions: neuropathological clues.
The neuroradiological evidence of a single, large white matter lesion with mass effect, clinically revealed by signs of endocranial hypertension, is highly suspicious for central nervous system neoplasm. In rare cases, a demyelinating disorder can start with atypical features suggestive of a brain tumor; in these cases a brain biopsy is often carried out. We report our experience regarding cases of multiple sclerosis (MS) with atypical tumor-like presentation. None of our patients underwent biopsy. Serial magnetic resonance imaging performed during steroid treatment, together with other paraclinical data, were sufficient for the final diagnosis of MS. These cases are characterized by a severe clinical course and a rapid clinical deterioration, only partially modified by medical treatments. Atypical severe cases, misdiagnosed as MS, can be indeed due to primary CNS vasculitis.
Adult↗
Experimental and human brain neoplasms: detection with in vivo sodium MR imaging.
Elevations of intracellular sodium concentration have been observed in rapidly proliferating cells and malignant neoplasms. Sodium magnetic resonance (MR) imaging (with repetition times of 133 msec and echo times of 13, 26, 39, and 42 msec) was performed in ten patients and three dogs with central nervous system neoplasms. In all instances the neoplasms were associated with an increased sodium signal compared with that of normal brain. Unfortunately, the available echo times did not enable discrimination of intracellular sodium from extracellular sodium, which was present in high concentrations in adjacent vasogenic edema fluid. Further study is necessary to establish the utility of sodium MR imaging for the investigation of malignant neoplasms.
Animals↗
Intracranial neoplasms in children with neurofibromatosis 1.
Neurofibromatosis 1 is associated with an increased risk for the development of benign and malignant tumors involving neural and non-neural tissues. Children as well as adults with neurofibromatosis 1 are affected. Central nervous system neoplasms represent a significant portion of these malignancies and appear primarily in children less than 10 years of age. Optic pathway gliomas and brainstem gliomas are the most common intracranial neoplasms found in neurofibromatosis 1, although there also is an increased incidence of other brain tumors in this population. The majority of these intracranial neoplasms are benign pilocytic astrocytomas, which may behave in a less aggressive manner than histologically identical tumors in non-neurofibromatosis 1 patients. Owing to the indolent nature of these tumors, conservative management with close follow-up is recommended. When intervention is required, conventional treatment with surgery, radiation, or chemotherapy has been used with variable results. The current challenge lies in understanding the pathogenesis of gliomas in neurofibromatosis 1, which may lead to the development of biologically directed therapies with less associated morbidity and mortality for neurofibromatosis 1 as well as non-neurofibromatosis 1 children.
Brain↗
[Cylindromatous epithelioma of the palate; unilateral paralytic syndrome of the cranial nerves; hodotropic tumoral propagation along the medullar pia mater and the spinal roots and ganglia].
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Cranial Nerves↗
Synaptophysin staining in normal brain: importance for diagnosis of ganglioglioma.
Neuronal and mixed glioneuronal tumors traditionally have comprised a very small percentage of intrinsic central nervous system neoplasms, although they are somewhat more common among juvenile brain tumors and in the temporal lobe. Neuronal differentiation increasingly is recognized in pleomorphic xanthoastrocytoma, intraventricular neurocytoma, and subependymal giant cell astrocytoma. However, the diagnostic distinctions between subtle ganglioglioma (with rare neurons) and infiltrating glioma with entrapped neurons and between infiltrating oligodendroglioma and parenchymal neurocytoma are problematic but may be clinically important. Recently, it was proposed that perisomatic synaptophysin immunostaining in the human central nervous system reliably and selectively discriminates neoplastic from nonneoplastic neurons. Using this criterion, the number of brain stem and spinal cord gangliogliomas could be increased substantially. We canvassed synaptophysin immunostaining patterns in the normal brain stem, cerebellum, and forebrain, and found that synaptophysin-positive neurons are distributed broadly in the normal human brain. In disturbed neocortical tissue, such as near vascular malformations, synaptophysin-positive neurons and irregular white-matter synaptophysin immunostaining are visualized. Although synaptophysin-positive neurons are found in gangliogliomas and archipelagos of synaptophysin reactivity are found in neurocytomas, these patterns clearly are not pathognomonic for glioneuronal tumors and must be interpreted with caution whenever other histologic or ultrastructural evidence of neuronal differentiation is lacking.
Adult↗
The clinical and radiological evaluation of primary brain tumors in children, Part I: Clinical evaluation.
In Part I of this article, we present our data collected over the past 8 years on the clinical evaluations of pediatric brain tumors with an emphasis placed on the more common neoplasms. Our data consists of 385 children ranging in age from newborn to 18 years. The majority of children presented with signs of raised intracranial pressure (including nausea, vomiting, and headaches), seizures or other focal neurologic deficits. Five percent of our children presented to outlying hospitals with symptoms that retrospectively turned out to be due to brain neoplasms but were misdiagnosed as "gastroenteritis," "viral upper respiratory tract infection," or even viral meningitis. These delays in diagnosis can cause serious negative outcomes for these patients and can be avoided through more careful neurologic and ophthalmologic examination at the time of first presentation. Central nervous system neoplasms are not uncommon in children and any child presenting with nausea, vomiting, and headaches should raise the suspicion of a primary brain tumor and should receive both a thorough neurologic exam and screening for papilledema. If papilledema is present, these children should be referred for proper neuroradiologic evaluation (which will be addressed in Part II.
Adolescent↗
Altered expression of ganglioside phenotypes of human gliomas in vivo and in vitro.
A library of epitope-defined antiganglioside monoclonal antibodies has been used to analyze the ganglioside phenotype of human glioma cell lines, rodent xenografts derived from them, and a separate panel of human glioma biopsies by multiple quantitative and qualitative assays. We have shown that the ganglioside phenotypes of cultured cell lines differ from the ganglioside phenotypes in the xenografts grown from the parent lines. The lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 are expressed in the majority of primary human central nervous system neoplasms and xenografts derived from glioma cell lines, whereas glioma cell lines themselves express 3'-isoLM1 and 3',6'-isoLD1 in only 2/15 and 0/15 cases, respectively. Examination of the ganglioside profiles of serially passaged xenografts established from the glioma cell line D-54 MG, which does not express the lacto series, revealed the appearance of these gangliosides within one to two passages in vivo. The presence of these defined gangliosides in the majority of human gliomas and their absence in normal brain supports their application in compartmental therapy of primary central nervous system tumors.
Animals↗
Neurologic features as initial presentations of childhood malignancies.
Thirty patients were examined initially because of neurologic problems and later were diagnosed as having systemic malignant disorders. Acute leukemia was the most common malignancy (36.6%), followed by neuroblastoma (33.3%), non-Hodgkin lymphoma (13.3%), rhabdomyosarcoma (10%), Ewing tumor (3.3%), and Hodgkin lymphoma (3.3%). Four of the 11 acute leukemia patients had nervous system involvement due to meningeal, orbital, or cerebellar infiltration. The complaints of the remaining patients included back pain, weakness, and difficulty in walking, all of which were caused by anemia or bone pain. Neurologic involvement in systemic malignancies, other than acute leukemia, mainly appeared as spinal cord compression (7 with neuroblastoma, 3 non-Hodgkin lymphoma, 1 rhabdomyosarcoma, 1 Ewing tumor), orbital or cavernous sinus infiltration (3 with acute leukemia, 1 rhabdomyosarcoma), and VIIth cranial nerve involvement (2 with rhabdomyosarcoma). One patient had skull infiltration without any neurologic deficit. Cerebellar signs were caused by the remote effects of cancer. It is concluded that acute leukemia is the first and neuroblastoma is the second most common malignancy among childhood systemic malignancies presenting with neurologic involvement; however, neuroblastoma is the most common cause of spinal cord compression.
Acute Disease↗
Hsp27 as a prognostic and predictive factor in cancer.
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Biomarkers, Tumor↗
Macrophages in experimental and human brain tumors. Part 2: studies of the macrophage content of human brain tumors.
The authors have analyzed 47 tumors of the central nervous system (11 glioblastomas, nine meningiomas, three medulloblastomas, 12 assorted primary neural tumors, and 12 brain metastases) for their content of macrophages. Cell suspensions were prepared by enzymatic digestion and macrophages were quantitated by IgGEAC rosette formation. Adsorption of sensitized indicator cells (EA) to sections of tumor was used as a measure to determine the distribution of IgGFc receptor-positive cells within the tumors and to serve as a control for selective release of IgGFc receptor-positive cells by enzyme digestion. The 11 glioblastomas had a mean macrophage content of 45% (range: 8% to 78%), the nine meningiomas had a mean of 44% (range: 5% to 81%), the three medulloblastomas a mean of 6% (range 2% to 15%), and the metastatic tumors a mean of 24% (range: 4% to 70%). Adsorption of EA demonstrated that IgGFc receptor-positive cells were distributed throughout the tumor mass, although different types of patterns were observed. There was an excellent correlation between the percent of IgGEAC positive cells in suspensions and the extent of EA adsorption to the tumor sections. Compared to systemic neoplasms, most nervous system tumors have a high macrophage content. It is possible that the high macrophage content of brain tumors is related to their immunogenicity, and may be a partial explanation for tha rarity of brain-tumor metastases.
Brain Neoplasms↗