Chorea associated with a subdural hematoma in a child with leukemia.
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Child↗
Biomedical subjects
S Ladisch
Publications and source records attributed to S Ladisch.
Proceedings: Immunologic similarities between fetal cell antigens and tumor cell antigens in guinea pigs.
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Animals↗
p53 expression in Langerhans cell histiocytosis.
PURPOSE: Langerhans cell histiocytosis (LCH) is a disorder of unknown etiology involving the proliferation and accumulation of cells with the phenotype of a bone marrow-derived antigen-presenting cell of the skin, the Langerhans cell. We have studied p53 expression, an element in the control of cell proliferation, to determine whether it plays a role in the pathogenesis of LCH. PATIENTS AND METHODS: LCH lesions from 10 patients with either localized (n = 5) or multisystem disease (n = 5) were studied. p53 protein expression was assessed by immunohistochemistry, and p53 gene mutation by the single strand conformation polymorphism (SSCP) technique. RESULTS: p53 protein expression was detected in all 10 LCH biopsy specimens examined. It was restricted to Langerhans cells (LCH cells), absent from adjacent cells, and localized to the cell nuclei. No mutations of the p53 gene were detected, nor was there abnormal expression of the p53 binding protein, mdm2. CONCLUSIONS: p53 is readily detectable in LCH cells but not in normal cells. This is either caused by an unusual mechanism (given the absence of mutations in the p53 gene and of mdm2 expression in LCH cells) or by overexpression or posttranslational changes of normal p53 in response to an as yet unidentified cellular stress. Stabilization and inactivation of p53 could lead to the uncontrolled proliferation of LCH cells, or the abnormality could lead to the induction of programmed cell death.
Adolescent↗
Antisense to integrin alpha v inhibits growth and induces apoptosis in medulloblastoma cells.
BACKGROUND: Integrin alpha v promotes brain microvessel endothelium survival, yet its role in brain tumor cells is unknown. MATERIALS AND METHODS: Alpha v synthesis in medulloblastoma cells Daoy, D341Med, and D283Med, was inhibited with antisense oligonucleotides (ASODN) to test the effect on growth and survivaL RESULTS: ASODN reduced alpha v surface expression 75% in a dose- and time-dependent manner (2 microM, 72 hours). Alpha v-deficient cells grown with vitronectin demonstrated reduced cell spreading, G0-G1 growth arrest, decreased proliferation and increased apoptosis compared to controls or alpha v-deficient cells grown with collagen. Furthermore, insulin-like growth factor-I (IGF-I) suboptimally stimulated proliferation and survival of alpha v-deficient cells, suggesting that alpha v-IGF-I interactions potentiate medulloblastoma growth. Finally, treatment with alpha v-blocking antibody induced caspase-8 and caspase-3 expression, while apoptosis of alpha v-deficient cells was associated only with increased caspase-3. CONCLUSION: Alpha v integrin supports medulloblastoma growth by activating adhesion-dependent and -independent survival pathways and thus may serve as a novel therapeutic target in this tumor.
Antigens, CD↗
[Stable transfection of DAOY cells with a GM3 synthase antisense construct and transient reduction in ganglioside content].
Tumor cell gangliosides are bioactive molecules involved in tumor-host interactions. To investigate their role in tumor formation and angiogenesis, we sought to develop an inhibitory model targeting human GM3 synthase, an essential enzyme in the ganglioside synthesis pathway, by antisense transfection. We prepared a number of transfectants from DAOY human medulloblastoma cells and isolated clones that stably expressed a 560-bp fragment of human GM3 synthase cDNA, in either sense or antisense orientation, as well as clones transfected with an empty vector. Both sense and antisense clones permanently incorporated mammalian expression vectors into their genomes. The DAOY cell clones were screened for ganglioside content using total lipid extraction, ganglioside isolation, and HPTLC. One antisense-transfected clone, 7.2A, in which total ganglioside content was reduced by 70%, was selected for further study. All sense- and sham-transfectants had ganglioside levels not different from that of untransfected DAOY cells. After 10 passages however, while antisense mRNA expression was fully maintained, the ganglioside content of 7.2A cells had reverted to normal levels. Antisense RNA transfection can sometimes have a reversible effect on the expression of a target. Possible regulatory mechanisms of this previously unrecognized process of reversion to wild type phenotype are discussed.
Cell Line, Tumor↗