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PubMed1993

Transforming growth factor-beta in neural embryogenesis and neoplasia.

The transforming growth factor-beta (TGF-beta) family of polypeptides includes three structurally and functionally related mammalian isoforms that influence cell proliferation, differentiation, and extracellular matrix production. Recent identification of these isoforms in the embryonic murine central nervous system suggests that these factors may regulate proliferation and differentiation of meningeal and neuroepithelial cells during development. Predominant expression of TGF-beta 1 in the leptomeninges compared with the brain of the murine and human central nervous system implicates this isoform in regulation of that mesodermal tissue. Thus, defective TGF-beta regulation may contribute to neoplastic transformation. Failure to activate latent TGF-beta s may contribute to the loss of autocrine regulation seen in meningiomas. Expression of TGF-beta 2 and TGF-beta 3 primarily in embryonic murine radial glia and adult human astrocytes suggests other roles for these isoforms, including glioblast differentiation and guidance of neuroblast migration. Although inhibitory to "normal" astrocyte proliferation, TGF-beta s demonstrate autocrine growth stimulation in vitro among hyperdiploid malignant gliomas, medulloblastomas, primitive neuroectodermal tumors, and anaplastic ependymomas. Hence, synthesis and release of active TGF-beta s by malignant brain tumors may create aberrant stimulatory autocrine loops. The mechanism of TGF-beta-induced growth stimulation is poorly understood. Future studies will likely clarify and identify additional roles for the TGF-beta isoforms in neuro-embryogenesis and neoplasia.

Animals↗
PubMed2004

Cytodiagnosis of neoplasms of the central nervous system in cerebrospinal fluid samples with an application of selective immunostains in differentiation.

In this study cytological findings in specimens of cerebrospinal fluid (CSF) of central nervous system (CNS) tumours (16 primaries, 57 metastatic and 12 suspicious) are presented, which were diagnosed over a period of 7 years in 85 patients (50 females and 35 males) with an age range of 2-76 years. The follow-up included information from clinicians and a review of medical charts, histological correlation and/or further investigations following cytodiagnosis. The patients clinically presented with signs and symptoms of meningeal involvement. The primary tumours included six medulloblastomas, eight gliomas (four glioblastomata multiforme, two anaplastic astrocytomas, and two ependymomas) and two germinomas. The metastatic tumours were 14 melanomas, 19 breast carcinomas, four leukaemias, six B-cell lymphomas, five adenocarcinomas of gastrointestinal origin, seven carcinomas of lung, one retinoblastoma and one neuroblastoma. Twelve cases were reported as suspicious. On further investigations, four of these were from a primary tumour (two glioblastomata multiforme and two anaplastic astrocytomas) while the other eight cases were of a metastasis (one B-cell lymphoma, three breast carcinomas, three melanomas and one adenocarcinoma of gastrointestinal origin). Using a panel of selective immunostains in some of the cases supported the cytological diagnosis and this was considered useful in furthering cytodiagnosis. In 75 of the patients the CSF samples were obtained on a spinal tap while in 10 patients the samples were received as ventricular CSF. There were no false-positive cases. The results of our study suggest that CSF cytology in the diagnosis of CNS tumours is quite reliable and reflects involvement of leptomeninges or the ventricles. Furthermore, the use of selective immunostains can be helpful in confirming the cytological impression and source of the tumour.

Adolescent↗
PubMed1984

Ultrastructural characterization of pulmonary neoplasms. I. The role of electron microscopy in characterization of the most common epithelial neoplasms.

We have attempted to summarize current concepts pertaining to the ultrastructural evaluation of epithelial pulmonary neoplasms, with an emphasis in potential clinicopathological correlations. Routine ultrastructural evaluation of the most commonly encountered pulmonary carcinomas seems to provide, in a significant number of cases, additional information that may be of help in patient management. Immunocytochemistry when employed as an adjunct to electron microscopic evaluation of pulmonary tumors also plays an important role in clarifying morphologic findings. With the advent of specific chemotherapy protocols and future development of monoclonal antibodies in the treatment of neoplasms, accurate tumor classification becomes crucial. The combined use of electron microscopy and immunocytochemistry seems to be extremely useful in providing accurate and reproducible criteria of great potential value in the overall assessment of pulmonary neoplasms. In part II of this study we will address the importance of the ultrastructural evaluation of less common epithelial and mesenchymal pulmonary neoplasms.

Adenocarcinoma↗
PubMed2004

[Imaging neurological complications from bronchogenic carcinoma].

The natural history of bronchogenic carcinoma shows that 42% of patients are diagnosed with cancer-related neurological complications either at initial presentation or at follow-up that can be separated in 3 different categories: - locoregional involvement of cervicothoracic nerves (recurrent laryngeal nerves, phrenic and vagus nerves, brachial plexus and sympathetic cervical chains), - metastatic disease characterized by intracranial lesions (brain, meningeal, ependymal and pituitary metastases) and spinal (extradural, subarachnoid and medullary metastases) lesions, - paraneoplastic syndromes including limbic encephalitis, Lambert-Eaton syndrome and paraneoplastic cerebellar degeneration. These neurological disorders usually are associated with advanced cancer for which radical surgical management seldom is indicated. All imaging studies performed at the time of initial staging for bronchogenic carcinoma should therefore be carefully reviewed in order to detect signs that could suggest the presence of one or several neurological complications. The goals of this paper are to describe the clinical signs and to illustrate the imaging features of neurological complications related to bronchogenic carcinoma at conventional radiography, CT and MRI.

Carcinoma, Bronchogenic↗
PubMed1993

Lactotetraose series ganglioside 3',6'-isoLD1 in tumors of central nervous and other systems in vitro and in vivo.

Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuAc or NeuGc)alpha 2-6GlcNAc. The distribution of 3',6'-isoLD1 in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoLD1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV3NeuAcLcOse4Cer in vitro, expressed detectable levels. Expression of 3',6'-isoLD1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoLD1. The absence of 3',6'-isoLD1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoLD1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoLD1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoLD1 expression within the human central nervous system to periods of fetal-neonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.

Animals↗
PubMedDate not supplied

[Preliminary results of radiotherapy of children with neoplasms of the central nervous system].

42 children with diagnosis of neoplasm of the central nervous system have been treated in the Ist Teleradiotherapy Unit of the Oncology Center--Maria Skłodowska-Curie Institute in Warsaw in the years 1980-1985. The age of children has been within 16 months--16 years limits. In 38 cases brain tumors have been irradiated and in 4 spinal ones. The treatment consisted of megavoltage Co60 irradiation, and in part of the spinal tumors the irradiation with electrons of 13-17 MeV energy. The tolerance of the treatment has been in general very good. 25 children (60%) survived 3-8 years, without symptoms of the disease, including 15 (60%) in very good psychosomatic condition, 17 children died.

Adolescent↗
PubMed2000

Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors.

Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2, and PTEN genes were analyzed in addition. Our data point to several novel genetic loci associated with brain tumor development, demonstrate relationships between molecular changes and histopathological features, and further expand the concept of molecular tumor variants in neuro-oncology. This catalogue may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors.

Alleles↗
PubMed1997

Neuropathology of pediatric brain tumors.

Pediatric central nervous system neoplasms include a spectrum of both glial and nonglial tumors that differ significantly in location and biological behavior from those of adults. Brain tumors in infants and children most often arise from central neuroepithelial tissue, whereas a significant number of adult tumors arise from central nervous system coverings (e.g., meningioma), adjacent tissue (e.g., pituitary adenoma), or metastases. Most adult brain tumors are supratentorial malignant gliomas, whereas the most common malignant pediatric brain tumor is the cerebellar primitive neuroectodermal tumor (medulloblastoma). This article reviews neuropathological characteristics of the more common pediatric brain tumors. Entities, such as the brainstem glioma, and less common neoplasms like the desmoplastic infantile ganglioglioma and the central nervous system atypical teratoid/rhabdoid tumor are reviewed because they occur almost exclusively in children. Known cytogenetic and molecular characteristics of childhood brain tumors are also reviewed.

Brain Neoplasms↗