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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of concanavalin A and ricin (RCAII, Mr 65,000) on [3H]thymidine incorporation into human neuroblastoma IMR-32 DNA showed reduction of total DNA synthesis to 50% and 70% of control, respectively. Two DNA polymerase (DNA nucleotidyltransferase, EC 2.7.7.7.) activities (alpha and beta) involved in the biosynthesis in vitro of DNA were separated by sucrose density gradient centrifugation from IMR-32 cell homogenate. The DNA polymerase alpha activity was also purified by selective precipitation with polyethylene glycol (Mr 6000) followed by agarose-concanavalin A column chromatography. The activities of both DNA polymerases were examined at various concentrations of mutagenic and nonmutagenic plant agglutinins and the toxin ricin. Concanavalin A and ricin specifically inhibited DNA polymerase alpha activity (activity reduced to 19% and 10%, respectively), whereas DNA polymerase beta activity was inhibited (reduced to 16%) by red kidney bean agglutinin (PHA-P).
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PMID:Inhibition of human neuroblastoma DNA polymerase activities by plant lectins and toxins. 28 62

Children with localized and metastatic neuroblastoma were studies to determine their immune status at the time of diagnosis and while they were receiving intensive intermittent chemotherapy; Investigations included leukocyte and differential counts, delayed hypersensitivity response, quantitative serum immunoglobulins, percentages of T and Fc receptor lymphocytes, PHA-induced mitogenesis, and antibody-and PHA-dependent cellular cytoxicity. Abnormalities related to the neoplasm at diagnosis were limited to depressed leukocyte and lymphocyte counts and increased concentrations of serum IgM in patients with metastases to bone marrow and other sites. No abnormalities were observed in those with localized tumors. Intermittent chemotherapy of metastatic neuroblastoma caused immunosuppression. Effects were most marked during five-day courses of chemotherapy; they included abrogation of DH and decreased leukocyte and lymphocyte counts and percentages of Fc receptor lymphocytes. Recovery of DH with partial recovery of leukocyte and lymphocyte counts was observed three weeks, later, prior to the next course, We conclude that both metastatic tumor and chemotherapy cause abnormalities of the immune system in children with neuroblastoma.
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PMID:Abnormalities of the immune system in children with neuroblastoma related to the neoplasm and chemotherapy. 32 Feb 98

Two human melanoma lines, RPMI-7931 and HS-294, respond to mitogenic stimulation by PHA. A dose-response curve for these lines can be demonstrated with maximal stimulation at 16 and 32 micrograms per ml and inhibition at 75 to 250 micrograms per ml PHA. The mitogenic effects of PHA were inhibited by N-acetyl-D-galactosamine. Neuroblastoma cells also exhibits a similar but less important dose-response to PHA. These data indicate that human melanomas and neuroblastomas may have PHA receptors or mechanisms for mitogenic stimulation which are analogous to those observed with normal lymphocytes.
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PMID:Phytohemagglutinin effects on cultured human neural crest tumors. 51 Dec 4

Bloom's syndrome (BS) is an autosomal recessive disease characterized by short stature, sensitivity to sunlight, and telangiectasic malar erythema. It is associated to chromosomal breakage, to primary combined immunodeficiency, and to a high incidence of neoplasias. The authors report the case of two siblings with BS and associated immunodeficiency. Both patients were male and 5 (A) and 4 (B) years old at the time of diagnosis. Chronic diarrhea, recurrent otitis media, purulent rhinitis, conjunctivitis and pyodermatitis were reported by patient A. Patient B was admitted with diagnosis of bilateral neuroblastoma and had the tumor resected. Later on, he presented with oral moniliasis, herpetic stomatitis, and skin abscesses. This patient did not have recurrent infections. Immunological evaluation showed normal serum levels of CH50, C3, and C4 for both patients. Serum IgG, IgA, IgM, and salivary IgA levels were: 455 mg/dl, 15mg/dl, 20mg/dl, 0.6mg/dl for A, and 400mg/dl, 15mg/dl, 20mg/dl, and 0.2mg/dl for B, respectively. Serum antipolio antibodies (1, 2, and 3) were normal, and low levels of isohemagglutinins were observed in both patients. T cells subset determination showed: patient A--OKT3 = 66%, OKT4 = 33%, OKT8 = 32%, and 4/8 ratio = 1.0; patient B--OKT3 = 70%, OKT4 = 32%, OKT8 = 34%, and 4/8 ratio = 1.0. In vitro cellular immune response to PHA was depressed only in patient B. Patients karyotype showed chromosomal breaks with sister chromatid exchanges. Neither patient had abnormal alphafetoprotein and carcinoembryonic antigen serum levels. The rarity of such associations justifies the presentation of the cases.
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PMID:[Familial Bloom's syndrome associated with neuroblastoma]. 221 4

Human neuroblastoma is an immunogenic tumor for which therapy directed in an immunologic context may offer some advantage over conventional treatment. This study examines the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. In vivo studies of primary tumor growth characteristics after treatment demonstrated no superiority of either therapeutic modality in control of local tumor or prolongation of host survival. However, irradiated hosts showed an increased ability to reject a secondary tumor challenge, compared to their surgical counterparts. That this phenomenon may be immune-related is suggested by in vitro studies of T lymphocyte function utilizing mixed lymphocyte-tumor cell cultures and PHA lymphoblastogenesis.
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PMID:Selection of optimal therapy for neuroblastoma: a study of the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. 294 17

The cellular immune response in A/J mice inoculated with in vitro cultured neuroblastoma (NB) cells is completely different from the response obtained after inoculation of in vivo passaged NB cells. Indeed, inoculation of in vivo grown tumor cells leads to a strongly decreased MLC and PHA response of the host spleen cells. This depressed response is not reversed by in vitro addition of indomethacin, but correlates with a low IL-2 production by the spleen cells. In addition, non-specific suppressor cells are present in the spleen and in the peritoneal cavity. The splenic suppressor cells are of low specific gravity and they are nylon wool adherent. The suppressor capacity is not reduced by anti-Thy plus rabbit complement treatment. Another effect of in vivo maintained NB cells is that the natural killer (NK) activity of the spleen cells of the host is increased 4-5 fold 2 days after inoculation of the tumor cells. On the contrary, in vitro passaged NB cells do not induce a reduced MLC and PHA responsiveness, and the IL-2 production of the host spleen cells remains nearly normal. No non-specific suppression can be demonstrated and the NK activity is not augmented 2 days after inoculation. We can conclude that it is very important in which condition tumor cells are maintained when used to study anti-tumor immunity.
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PMID:Immune response to murine neuroblastoma: effects of in vitro culture of the tumor. Mitogen and mixed lymphocyte culture responses, interleukin-2 production, suppression and natural killer activity. 295 23

Retinoic acid (RA) decreased growth and increased morphologic differentiation of human neuroblastoma LA-N-1 cells. These phenomena correlated with a specific enhancement of PHA-E lectin binding to a glycoprotein of MW 67 kDa (gp67). Gp67 was found susceptible to N-glycanase and displayed BSA binding by affinity chromatography analysis. The chemotherapeutic agent methotrexate (MTX) also reduced growth and induced differentiation of LA-N-1 cells. In addition, the cells responded to MTX as well as to doxorubicin by a marked increase in PHA-E binding to gp67. We conclude that reduced growth and induction of morphological differentiation of LA-N-1 cells correlates with increased binding of PHA-E to gp67.
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PMID:Retinoic acid and methotrexate specifically increase PHA-E-lectin binding to a 67-kDa glycoprotein in LA-N-1 human neuroblastoma cells. 754 81

We show that expression of the p34cdc2 and cyclin A genes is induced by interleukin-2 in normal human T cells and present evidence to support the idea that these genes are deregulated in leukemic T cells. Our DNA sequencing data indicate that the promoter region of the p34cdc2 gene contains putative E2F-like binding sites which are recognized by Rb and binding sites for c-myb, Sp1, and ATF, and that the promoter region of the cyclin A gene contains binding sites for p53, Sp1, and ATF. In this study we focus on the effect of p53 and Rb on these cell cycle-regulatory genes. Cotransfection of Y79 human retinoblastoma cells with a p34cdc2 promoter-luciferase expression vector and a plasmid expressing the retinoblastoma gene (RB) indicated that RB suppresses p34cdc2 expression. Cotransfection of B104 rat neuroblastoma cells with a cyclin A promoter-luciferase expression vector and a plasmid expressing the normal or mutant p53 indicated that only the normal p53 suppresses cyclin A expression. In normal T cells, PHA stimulation reduces the amount of complexes in the p34cdc2 promoter between the E2F-like binding site and the RB gene product. These complexes were not detected in leukemic T cells. Our data support the idea that tumor suppressors modulate the expression of cell cycle-regulatory genes: RB regulates p34cdc2 expression and p53 regulates cyclin A expression.
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PMID:Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression. 827 2

Effects of organotin compounds were studied on voltage-gated K+ current in whole-cell voltage clamped lymphocytes and in N1E-115 neuroblastoma cells. In human peripheral blood lymphocytes the immunotoxic compounds dibutyltinchloride (DBT, 2.5 microM) and triphenyltinchloride (TPhT, 2.5 microM) decrease the peak amplitude of the K+ current and prolong time to peak. Tributyltinchloride (TBT, 2.5 microM) decreases the K+ current to a greater extent than DBT and TPhT, without affecting the time to peak. The neurotoxic organotin compound trimethyltinchloride (TMT, 2.5 microM) does not affect the voltage-gated K+ current in lymphocytes. Similar effects of DBT were observed in freshly isolated and PHA-activated human lymphocytes and with rat thymocytes. On the other hand, in mouse N1E-115 neuroblastoma cells, none of the organotin compounds altered the voltage-dependent K+ current. In human lymphocytes DBT affects both the peak amplitude and the time to peak of the K+ current in a concentration-dependent manner. At the maximum concentration of 10 microM tested, the peak amplitude of the K+ current was reduced to 22 +/- 4% of the control current. The IC50 and slope factor for block of the peak outward current by DBT amounts to 6.7 +/- 0.4 microM, and 2.7 +/- 0.4, respectively. The delay in K+ current activation does not saturate. At 10 microM DMT increases the time to peak to 332 +/- 12% of the control value. The present results suggest that the effects by DBT originate from two separate interactions with the voltage-gated K+ channel at the extracellular site of the membrane: a direct effect on the closed K+ channel causing a delay in current activation and a membrane-related effect causing inhibition of the K+ current. The differential effects of the organotin compounds may relate to their differential toxicological action.
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PMID:Differential effects of organotin compounds on voltage-gated potassium currents in lymphocytes and neuroblastoma cells. 871 53

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the development of several human cancers and, as a result, is a recognized target for the development of small-molecule inhibitors for the treatment of ALK-positive malignancies. Here, we present the crystal structures of the unphosphorylated human ALK kinase domain in complex with the ATP competitive ligands PHA-E429 and NVP-TAE684. Analysis of these structures provides valuable information concerning the specific characteristics of the ALK active site as well as giving indications about how to obtain selective ALK inhibitors. In addition, the ALK-KD-PHA-E429 structure led to the identification of a potential regulatory mechanism involving a link made between a short helical segment immediately following the DFG motif and an N-terminal two-stranded beta-sheet. Finally, mapping of the activating mutations associated with neuroblastoma onto our structures may explain the roles these residues have in the activation process.
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PMID:Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors. 2069 22


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