bromochloroacetic-acid and Neuroblastoma

Cytokeratin 1, an intermediate filament keratin, was isolated as a partner of the tyrosine kinase Src from neuroblastoma NMB7 cells. The cytokeratin 1-Src complex was found to be associated with the molecular scaffolder RACK1 (receptor for activated protein kinase C). Interestingly, the cytokeratin 1-Src-RACK1 complex was found to actively bind with membrane receptors such as integrin beta1. We are interested in using this complex to find downstream kinases and phosphatases that bind upon cytokine stimulation, especially during neurogenesis.

Topics: Cell Line, Tumor; Humans; Integrin beta1; Keratins; Neuroblastoma; Peptides; Protein Binding; Receptors for Activated C Kinase; Signal Transduction

Topics: Animals; Carcinoma; Cytoplasm; Digestive System; Embryonic and Fetal Development; Epidermal Cells; Female; Humans; Hyperplasia; Keratins; Male; Melanocytes; Neuroblastoma; Neurosecretory Systems; Rats; Skin; Skin Neoplasms

In most cell types intermediate or 10-mm filaments (IF) are a major cytoskeletal organization and, thus, directly or indirectly influence the structural appearance of the cytoplasm. In line with the cell type-specific expression patterns of different IF proteins in normal animal and human tissue, IF typing distinguishes the major tumor groups, as documented by results with several hundred human tumors classified by conventional histologic methods. Carcinomas are characterized by cytokeratins, sarcomas of muscle cells by desmin, nonmuscle sarcomas by vimentin, and gliomas by glial fibrillary acidic protein. Furthermore, certain tumors originating from the sympathetic nervous system, e.g., ganglioneuroblastoma, pheochromocytoma, and at least some neuroblastomas, are characterized by the presence of neurofilaments. Carcinomas can often be further subdivided with regard to their possible derivation by examining their cytokeratin profiles. The IF type characteristic of the cell of origin seems to be kept not only in the primary tumor but usually also in solid metastases. In general, tumors do not acquire additional IF types. Therefore, IF typing can provide an unambiguous and rapid characterization in certain cases, that are difficult to diagnose by conventional techniques. Some useful examples are the small cell tumors of childhood and the discrimination between undifferentiated carcinoma and lymphoma. IF typing of a few tumors has already led to a revision or reconsideration of the original light microscopic diagnosis. The combined results indicate that at least certain carcinomas, as well as certain other tumor types, seem to arise by the selective multiplication of a particular and identifiable cell type present in the normal tissue. The procedure is not restricted to tumor material. IF typing of Mallory bodies, Alzheimer's disease tangles, certain myopathies, and the cells of the amniotic fluid offers further interesting applications. Thus, IF typing should become a valuable new tool both in histology and surgical pathology.

Topics: Amniotic Fluid; Animals; Carcinoma; Cells, Cultured; Cytoskeleton; Desmin; Embryo, Mammalian; Fluorescent Antibody Technique; Ganglioneuroma; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filament Proteins; Keratins; Muscular Diseases; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Pheochromocytoma; Sarcoma; Vimentin

神经母细胞肿瘤是儿童最常见的颅外恶性实体肿瘤，通常认为不表达细胞角蛋白，借此可与上皮来源肿瘤相鉴别。该文报道1例5岁男孩发生的神经母细胞瘤伴有细胞角蛋白表达，描述其组织学特征、免疫表型及遗传学特点，旨在拓展对神经母细胞瘤免疫表型的认识。.

Topics: Diagnosis, Differential; Humans; Keratins; Neuroblastoma

Topics: Adult; Diagnosis, Differential; Follow-Up Studies; Humans; Infant; Keratins; Male; Mandibular Neoplasms; Melanoma; Neuroblastoma; Neuroectodermal Tumor, Melanotic; Rhabdomyosarcoma, Embryonal; Synaptophysin

Genetic, immunohistochemical, and histologic data has led to the reclassification of renal cell carcinoma in the last decade. Recent studies suggest that renal cell carcinomas in children and young adults may represent a distinct group of tumors. These tumors have unique genetic findings (most commonly t(x;1)(p11:q21)), a predominantly papillary architecture, numerous calcifications, granular cytoplasm, and a possible relationship with neuroblastoma.

Topics: Adolescent; Adrenal Gland Neoplasms; Biomarkers; Carcinoma, Renal Cell; Child; Child, Preschool; Chromosome Aberrations; Female; Humans; Karyotyping; Keratins; Kidney Neoplasms; Mucin-1; Neuroblastoma; Vimentin

B-myb gene is expressed in neuroblastoma cells and down-regulated during differentiation. We used B-myb-transfected LAN-5 cells, which constitutively express high level of B-myb, to detect changes at phenotypic and morphological levels in basal and differentiation conditions. Our results demonstrate that the overexpression of B-myb markedly affects the cytoskeletal composition, the pattern of neurotransmitter enzymes and the extracellular matrix expression. In general, B-myb transfected neuroblastoma cells show a broad potentiality without a direction toward a specific neuroectodermal differentiation pathway. On the other hand, we confirm inhibition of the neuronal differentiation upon retinoic acid (RA) treatment of B-myb transfected cells. Furthermore, the ultrastructural analyses are supportive of a change in the metabolism in B-myb transfected cell treated with RA. Our data suggest that B-myb expression is compatible with an early phase of differentiation of neuroectodermal cells, but must be down-regulated for the completion of the differentiative programme.

Topics: Cell Cycle Proteins; Cell Differentiation; Cytoskeleton; DNA-Binding Proteins; Extracellular Matrix; Gene Expression Regulation, Neoplastic; Glial Fibrillary Acidic Protein; Immunohistochemistry; Keratins; Microscopy, Electron; Neuroblastoma; Neurofilament Proteins; Phenotype; RNA, Messenger; Trans-Activators; Transcription Factors; Transfection; Tumor Cells, Cultured; Vimentin

During apoptosis, one of the first membrane changes that can be detected is exposure of phosphatidylserine residues at the outer plasma membrane leaflet, while early apoptosis is also accompanied by changes in the cytoskeletal organization. In this study we investigated the relationship between these two phenomena during olomoucine- and roscovitin-induced apoptosis in human lung cancer and neuroblastoma cell lines. Loss of membrane asymmetry was detected by biotin-labeled or FITC-labeled annexin V binding to negatively charged phosphatidylserine, while cytoskeletal components were visualized by immunocytochemistry. The apoptotic, annexin V-positive, cells were analyzed by flow cytometry, confocal scanning laser microscopy, and Western blotting. We report that cytokeratin and vimentin aggregation in early apoptosis occurs simultaneously with phosphatidylserine exposure and chromatin condensation. In contrast to these intermediate filament proteins, which were disassembled and proteolytically cleaved in early apoptosis, microfilaments and microtubuli were not proteolytically degraded but were found to be present as aggregated filaments in the apoptotic bodies. We also show that loss of membrane asymmetry and cytokeratin aggregation are independent processes, since N-ethylmaleimide-induced phosphatidylserine exposure does not cause cytokeratin disassembly. Vice versa, phorbol 12-myristate 13-acetate-induced cytokeratin filament aggregation does not result in phosphatidylserine exposure.

Topics: Actins; Annexin A5; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Membrane; Chromatin; Cytoskeleton; Ethylmaleimide; Humans; Keratins; Kinetin; Lung Neoplasms; Neuroblastoma; Phosphatidylserines; Purines; Roscovitine; Tetradecanoylphorbol Acetate; Tubulin; Tumor Cells, Cultured; Vimentin

We report three cases of neuroblastoma arising within the thymus of elderly patients. All tumors consisted of primitive neuroblasts showing focal gangliocytic differentiation within nests of neuropil. All stained for neuroendocrine markers but were negative for cytokeratins and for the MIC2 gene product. One tumor was associated with the syndrome of inappropriate secretion of antidiuretic hormone, an endocrinopathy we found in three of five case reports of thymic neuroblastoma in adults. Immunohistochemical stains confirmed production of antidiuretic hormone by this tumor. One patient died of progressive disease, one patient is disease free at 18 months, and the other patient died of unrelated causes, a spectrum that reflects the variable clinical behavior others have reported. The possible histogenesis of these purely neural tumors includes malignant transformation of a mediastinal teratoma, aberrantly located sympathetic ganglia, neuroectodermal cells native to the normal thymus, and precursors of thymic epithelial cells that have differentiated along neural lines.

Topics: Aged; Aged, 80 and over; Carcinoid Tumor; Chromogranins; Female; Humans; Immunohistochemistry; Inappropriate ADH Syndrome; Keratins; Male; Mediastinal Neoplasms; Microscopy, Electron; Neuroblastoma; Phosphopyruvate Hydratase; Synaptophysin; Thymus Gland; Thymus Neoplasms

Ultrasound-guided percutaneous needle biopsy proved to be a reliable and safe method to obtain material for histopathological and immunohistochemical diagnosis prior to treatment in childhood malignancies. A principal tumour identification could be obtained by a combined morphological and phenotypic examination of 38 small-sized tumour biopsy specimens using a fairly limited panel of immunological reagents, including antibodies to leucocyte common antigen (CD 45), certain B- and T-cell markers, various intermediate filaments (cytokeratin, desmin and vimentin), and neuroblastoma cells (UJ 167.11, A2B5, and UJ 13A; the latter recognizes NCAM). Five undifferentiated neuroblastomas were all positive with the neuroblastoma antibodies but negative for the other markers, including vimentin. The negative reactivity for desmin and vimentin was the major immunohistochemical distinction between neuroblastomas and rhabdomyosarcomas. In addition, limited reactivity with the neuroblastoma antibodies was seen in blastematous parts of Wilms' tumour, duct-like structures in a hepatoblastoma, and in tumour cells in a few undifferentiated myelo- and lympho-proliferative lesions. This study shows the importance of a combined evaluation of morphology and the pattern of immunoreactivity employing multiple markers.

Topics: Antibodies, Monoclonal; Antigens, CD; Biomarkers, Tumor; Biopsy, Needle; Child; Child, Preschool; Desmin; Diagnosis, Differential; Fluorescent Antibody Technique; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoproliferative Disorders; Neuroblastoma; Rhabdomyosarcoma; Vimentin; Wilms Tumor

Twenty-eight malignant olfactory neural tumors representative of the histologic spectrum commonly designated as olfactory neuroblastoma were subdivided into two groups: Group I closely resembling classical neuroblastoma (20 cases), and Group II exhibiting neuroendocrine features (eight cases). Immunohistochemically, the tumors were analyzed by using antibodies to keratin, neurofilament protein, S-100, and neuron specific enolase. Neuron specific enolase was the most consistently positive in both groups. Single S-100 positive cells, within or at the edges of tumor nests, often corresponded ultrastructurally to Schwann cells at the tumor-stroma interface. Keratin and neurofilament proteins were expressed singly or together by a small number of cases in both groups. All 11 tumors examined ultrastructurally exhibited neuronal processes containing dense-core granules. The results indicate the following: (a) the reliable diagnostic utility of electron microscopy; (b) the frequent occurrence of Schwann cells in these tumors despite their inconspicuousness by light microscopy; and (c) the unexpected expression of keratin by tumors in both groups. The single or coexpression of keratin-neurofilament protein may define a subset of these tumors for which the clinical significance is presently unclear.

Topics: Cranial Nerve Neoplasms; Humans; Immunologic Techniques; Keratins; Microscopy, Electron; Neuroblastoma; Olfactory Nerve; Phosphopyruvate Hydratase; S100 Proteins; Schwann Cells

Two cases of olfactory neuroblastoma mixed with other neoplastic elements are reported. One tumor contained foci of adenocarcinoma and of ganglioneuroblastoma in addition to an undifferentiated small cell component consistent with neuroblastoma; the other tumor histologically resembled small cell undifferentiated carcinoma with foci of squamous differentiation, but was shown by electron microscopy to be neuroblastoma. The histogenesis and treatment of mixed tumors of this type are discussed.

Topics: Adenocarcinoma; Aged; Carcinoma; Carcinoma, Small Cell; Cytoplasm; Humans; Keratins; Male; Nasopharyngeal Neoplasms; Neuroblastoma; Nose Neoplasms

Topics: Cauda Equina; Child; Glioma; Humans; Keratins; Male; Medulloblastoma; Meningitis; Myelography; Neuroblastoma; Physical Examination; Retinoblastoma; Spinal Cord Neoplasms; Spinal Puncture; Steroids