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1.
Antineuroblastoma activity of desferoxamine in human cell lines 总被引:3,自引:0,他引:3
That ferritin, an iron storage protein, can be produced by neuroblastoma cells raises the possibility that iron may have some role in promoting tumor cell growth. To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neuroblastoma cell lines. Cells (5 X 10(4)) were incubated with graded amounts of desferoxamine or ferrioxamine, an iron-saturated analogue of desferoxamine. Within 5 days of exposure to 60 microM desferoxamine, approximately 90% of cells from each of these cell lines were dead. This effect was dose dependent, was not seen with ferrioxamine, and could be prevented by coincubation with greater than stoichiometric amounts of ferric citrate. As determined by binding of OK-T9, desferoxamine also resulted in increased expression of receptors for transferrin, an iron transport protein. Desferoxamine had only minimal effects on viability of several non-neuroblastoma cell lines. These results suggest that iron is required for growth of neuroblastoma and that desferoxamine has potent, specific, antineuroblastoma activity in vitro. 相似文献
2.
Hua Tan Jena Derrick Jin Hong Corneliu Sanda William M Grosse Howard J Edenberg Milton Taylor Scott Seiwert Lawrence M Blatt 《Journal of interferon & cytokine research》2005,25(10):632-649
A role for type II interferon (IFN-gamma) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-gamma-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-gamma1b and a potent, consensus type I IFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-gamma1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-gamma1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (Th1) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state. 相似文献
3.
Leonidas JC; Berdon WE; Valderrama E; Neveling U; Schuval S; Weiss SJ; Hilfer C; Godine L 《Radiology》1996,198(2):377
4.
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6.
J S Miser J Roloff J Blatt G H Reaman M D Krailo G D Hammond 《American journal of clinical oncology》1992,15(6):490-493
Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A). 2'-Deoxycoformycin is an inhibitor of adenosine deaminase (ADA), an enzyme found in relatively high amounts in malignant lymphoid cells. Ara-A inhibits DNA polymerase and DNA synthesis. Because its efficacy in vivo as an anticancer agent is limited by its rapid inactivation by ADA, ara-A was combined with dCF to produce cytoreductive levels of ara-A. Twenty-four patients were assigned to receive dCF alone and 25 to receive the combination. No patient responded to dCF alone, and one patient developed a complete remission after treatment with the combination. The toxicity of dCF alone was minimal, except for one patient who became obtunded on day 5 following the first cycle of therapy. In contrast, five patients developed severe toxicity with the combination, including renal failure (three patients), hepatic failure (three patients), and neurologic toxicity (two patients). These results indicate that, at the doses and schedule used in this study, the combination of dCF and ara-A has significant toxicity and minimal activity against recurrent ALL in children. 相似文献
7.
Deferoxamine previously has been shown to have potent activity in vitro against human neuroblastoma cells, activity that results from its ability to chelate iron. To further understand the mechanism of deferoxamine-induced cytotoxicity, we looked at its effects on cell cycling and on DNA, RNA, and protein synthesis by CHP 126, a cell line that is derived from tumor tissue of a patient with a neuroblastoma and that is known to be drug sensitive. After 24 hours of exposure to 60 mumol/L deferoxamine, there was a 35% increase in the percent of cells in the nonproliferating and prereplicative phases of the cell cycle and a corresponding decrease in the percent of cells in the DNA synthesis, postreplicative, and mitotic phases of the cell cycle, results that are consistent with a block of cell cycle progression at the early DNA synthesis phase. The inhibitory effects of deferoxamine on DNA synthesis were confirmed by demonstration of a 60% decrease in thymidine incorporation into DNA in short-term cultures of CHP 126. Effects on RNA and protein synthesis were minimal. Equivalent effects on growth were seen by using several chelators that interact with different iron pools, suggesting that both intracellular and extracellular iron are required for growth of neuroblastoma cells. 相似文献
8.
Kaufmann SJ; Sharif K; Sharma V; McVerry BA 《Human reproduction (Oxford, England)》1998,13(2):498-499
The patient was diagnosed in childhood as having severe congenital
neutropenia and had recurrent admissions with severe infections. In 1987,
prior to getting married, she was sterilized. She continued to require i.v.
antibiotics when she contracted a severe infection. On one occasion, she
was treated with growth colony stimulating factor (G- CSF). Her increased
neutrophil count was sustained following this treatment. In June 1993, she
wished to start a family and underwent in- vitro fertilization (IVF)
treatment. G-CSF was given prior to oocyte retrieval. She conceived on her
first cycle and an ultrasound scan revealed a singleton pregnancy.
Throughout the course of the pregnancy, her white cell count was monitored
closely and remained at <1.0x10(9)/l. The pregnancy progressed
uneventfully and at 37 weeks gestation she was admitted for G-CSF
injections. At 38 weeks she was delivered of a boy weighing 3350 g, by
elective Caesarean section. His white cell count was normal. This is the
first case of G-CSF being used before conception and during pregnancy in a
patient with congenital neutropenia. It shows that advances in cytokine
therapy and close interdisciplinary liaison can lead to a successful
outcome and help patients, who would otherwise remain childless, to achieve
a family.
相似文献
9.
Silber SJ; Nagy Z; Devroey P; Tournaye H; Van Steirteghem AC 《Human reproduction (Oxford, England)》1997,12(11):2422-2428
The aim of the study was to determine whether a prior diagnostic testicle
biopsy can predict success or failure of testicular sperm extraction (TESE)
with intracytoplasmic sperm injection (ICSI) in patients with
non-obstructive azoospermia caused by testicular failure, and what is the
minimum threshold of sperm production in the testis which must be surpassed
for spermatozoa to reach the ejaculate. Forty- five patients with
non-obstructive azoospermia caused by testicular failure underwent
diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure.
The diagnostic testicle biopsy was analysed quantitatively, and correlated
with the quantitative findings of spermatogenesis in patients with normal
spermatogenesis, as well as with the results of subsequent attempts at
TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure
had a mean of 0-6 mature spermatids/seminiferous tubule seen on a
diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in
men with normal spermatogenesis and obstructive azoospermia. These findings
were the same for all types of testicular failure whether Sertoli cell
only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia.
Twenty-two of 26 men with mature spermatids found in the prior testis
biopsy had successful retrieval of spermatozoa for ICSI, 12 of their
partners became pregnant, and are either ongoing or delivered. The study
suggests that 4-6 mature spermatids/tubule must be present in the testis
biopsy for any spermatozoa to reach the ejaculate. More than half of
azoospermic patients with germinal failure have minute foci of
spermatogenesis which are insufficient to produce spermatozoa in the
ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for
the presence of mature spermatids) can predict subsequent success or
failure with TESE-ICSI. Incomplete testicular failure may involve a sparse
multi-focal distribution of spermatogenesis throughout the entire testicle,
rather than a regional distribution. Therefore, it is possible that massive
testicular sampling from many different regions of the testes may not be
necessary for successful TESE-ICSI.
相似文献
10.
β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis. 相似文献