#01#
Revisiones
(todas) *** Reviews (all)
AGENTES
INMUNOSUPRESORES *** IMMUNOSUPPRESSIVE COMPOUNDS
(Conceptos
/ Keywords: Immunosuppressive comp; Muromonab-cd3; Sirolimus; Tacrolimus;
Cyclosporine; Mycophenolic acid; Antilymphocyte serum; Immunosuppressive comp.
used in oncology, etc).
Enero /
January 2001 --- Marzo / March 2004
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documento sólo contiene artículos escritos en Castellano y/o Inglés.
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Only articles written in Spanish and/or English are included.
[1]
TÍTULO / TITLE: - Integration of growth
factor and nutrient signaling: implications for cancer biology.
REVISTA
/ JOURNAL: - Mol Cell 2003 Aug;12(2):271-80.
AUTORES
/ AUTHORS: - Shamji AF; Nghiem P; Schreiber SL
INSTITUCIÓN
/ INSTITUTION: - Harvard Biophysics Program, Harvard
University, 12 Oxford Street, Cambridge, MA 02138, USA.
RESUMEN
/ SUMMARY: - Signaling networks that promote cell
growth are frequently dysregulated in cancer. One regulatory network, which
converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting
protein synthesis. Here, we discuss how this network is regulated by both
extracellular signals, such as growth factors, and intracellular signals, such
as nutrients. We discuss how mutations amplifying either type of signal can
lead to tumor formation. In particular, we focus on the recent discovery that a
tumor suppressor complex whose function is lost in tuberous sclerosis patients
regulates the nutrient signal carried by the critical signaling protein TOR to
the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule
rapamycin, which inhibits TOR and thereby the activation of these effectors,
could be useful to treat tumors that have become dependent upon this pathway
for growth. N. Ref:: 80
----------------------------------------------------
[2]
TÍTULO / TITLE: - Dendritic cells:
emerging pharmacological targets of immunosuppressive drugs.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2004 Jan;4(1):24-34.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1256
AUTORES
/ AUTHORS: - Hackstein H; Thomson AW
INSTITUCIÓN
/ INSTITUTION: - Institute for Clinical Immunology and
Transfusion Medicine, Justus-Liebig University Giessen, Langhansstr. 7, D-35392
Giessen, Germany. holger.hackstein@immunologie.med.uni-giessen.de
RESUMEN
/ SUMMARY: - Immunosuppressive drugs have
revolutionized organ transplantation and improved the therapeutic management of
autoimmune diseases. The development of immunosuppressive drugs and
understanding of their action traditionally has been focused on lymphocytes,
but recent evidence indicates that these agents interfere with immune responses
at the earliest stage, targeting key functions of dendritic cells (DCs). Here,
we review our present understanding of how classical and new immunosuppressive
agents interfere with DC development and function. This knowledge might provide
a rational basis for the selection of immunosuppressive drugs in different
clinical settings and for the generation of tolerogenic DCs in the
laboratory. N. Ref:: 116
----------------------------------------------------
[3]
- Castellano -
TÍTULO / TITLE:La ruta de senalizacion
CA++/calcineurina/NFAT en activacion endotelial y angiogenesis: efectos de la
ciclosporina A. CA++/ calcineurin/NFAT signaling in endothelial activation and
angiogenesis: effects od cyclosporin A .
REVISTA
/ JOURNAL: - Nefrologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.aulamedica.es/nefrologia/
●●
Cita: Nefrologia: <> 2003;23 Suppl 3:44-8.
AUTORES
/ AUTHORS: - Quesada AJ; Redondo JM
INSTITUCIÓN
/ INSTITUTION: - Centro de Biologia Molecular Severo Ochoa,
Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid
y Centro Nacional de Investigaciones Cardiovasculares (CNIC), Sinesio Delgado,
4 28049 Cantoblanco, Madrid. jmredondo@cbm.uam.es N. Ref:: 31
----------------------------------------------------
[4]
TÍTULO / TITLE: - Identification of TOR
signaling complexes: more TORC for the cell growth engine.
REVISTA
/ JOURNAL: - Cell 2002 Oct 4;111(1):9-12.
AUTORES
/ AUTHORS: - Abraham RT
INSTITUCIÓN
/ INSTITUTION: - Program in Signal Transduction Research,
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road,
La Jolla, CA 92037, USA. abraham@burnham.org
RESUMEN
/ SUMMARY: - The Target of Rapamycin (TOR) proteins
function in signaling pathways that promote protein synthesis and cell growth.
In yeast, TOR signaling is regulated by nutrient availability, whereas in
metazoan cells TOR activities may be controlled by both nutrients and growth
factors. The recent identification of novel TOR-interacting proteins has
provided crucial insights into TOR regulation and function. N. Ref:: 20
----------------------------------------------------
[5]
TÍTULO / TITLE: - Interleukin-2 receptor
monoclonal antibodies in renal transplantation: meta-analysis of randomised
trials.
REVISTA
/ JOURNAL: - British Medical J (BMJ). Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://bmj.com/search.dtl
●●
Cita: British Medical J. (BMJ): <> 2003 Apr 12;326(7393):789.
●●
Enlace al texto completo (gratuito o de pago) 1136/bmj.326.7393.789
AUTORES
/ AUTHORS: - Adu D; Cockwell P; Ives NJ; Shaw J;
Wheatley K
INSTITUCIÓN
/ INSTITUTION: - Department of Nephrology, Queen Elizabeth
Hospital, Birmingham, B15 2TH. dwomoa.adu@uhb.nhs.uk
RESUMEN
/ SUMMARY: - OBJECTIVE: To study the effect of
interleukin-2 receptor monoclonal antibodies on acute rejection episodes, graft
loss, deaths, and rate of infection and malignancy in patients with renal
transplants. DESIGN: Meta-analysis of published data. DATA SOURCES: Medline,
Embase, and Cochrane library for years 1996-2003 plus search of medical
editors’ trial amnesty and contact with manufacturers of the antibodies.
SELECTION OF STUDIES: Randomised controlled trials comparing interleukin-2
receptor antibodies with placebo or no additional treatment in patients with
renal transplants receiving ciclosporin based immunosuppression. RESULTS: Eight
randomised controlled trials involving 1871 patients met the selection criteria
(although only 1858 patients were analysed). Interleukin-2 receptor antibodies
significantly reduced the risk of acute rejection (odds ratio 0.51, 95%
confidence interval 0.42 to 0.63). There were no significant differences in the
rate of graft loss (0.78, 0.58 to 1.04), mortality (0.75, 0.46 to 1.23),
overall incidence of infections (0.97, 0.77 to 1.24), incidence of
cytomegalovirus infections (0.81, 0.62 to 1.04), or risk of malignancies at one
year (0.82, 0.39 to 1.70). The different antibodies had a similar sized effect
on acute rejection (test for heterogeneity P=0.7): anti-Tac (0.37, 0.16 to
0.89), BT563 (0.37, 0.1 to 1.38), basiliximab (0.56, 0.44 to 0.72), and
daclizumab (0.46, 0.32 to 0.67). The reduction in acute rejections was similar
for all ciclosporin based immunosuppression regimens (test for heterogeneity
P=1.0). CONCLUSIONS: Adding interleukin-2 receptor antibodies to ciclosporin
based immunosuppression reduces episodes of acute rejection at six months by
49%. There is no evidence of an increased risk of infective complications.
Longer follow up studies are needed to confirm whether interleukin-2 receptor
antibodies improve long term graft and patient survival.
----------------------------------------------------
[6]
TÍTULO / TITLE: - Progress in the
treatment of rheumatoid arthritis.
REVISTA
/ JOURNAL: - JAMA. Acceso gratuito al texto completo.
●●
Enlace a la Editora de la Revista http://jama.ama-assn.org/search.dtl
●●
Cita: JAMA: <> 2001 Dec 12;286(22):2787-90.
AUTORES
/ AUTHORS: - Pisetsky DS; St Clair EW
INSTITUCIÓN
/ INSTITUTION: - Division of Rheumatology, Allergy, and
Clinical Immunology, Duke University Medical Center, 1516 Durham Veterans
Affairs Medical Center, Box 151G, Durham, NC 27710, USA. dpiset@acpub.duke.edu N. Ref:: 27
----------------------------------------------------
[7]
TÍTULO / TITLE: - Novel therapeutic
molecular targets for prostate cancer: the mTOR signaling pathway and epidermal
growth factor receptor.
REVISTA
/ JOURNAL: - J Urol 2004 Feb;171(2 Pt 2):S41-3; discussion
S44.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.ju.0000108100.53239.b7
AUTORES
/ AUTHORS: - Tolcher AW
INSTITUCIÓN
/ INSTITUTION: - Director Clinical Research, Institute for
Drug Development Cancer Therapy and Research Center, San Antonio, Texas, USA.
RESUMEN
/ SUMMARY: - PURPOSE: The scientific rationale and
existing evidence for the use of novel molecular targets in the chemoprevention
of cancer are reviewed, with special attention to prostate cancer. MATERIALS
AND METHODS: A search for relevant literature on basic science and clinical
trials was conducted using PubMed/MEDLINE. RESULTS: The emergence of
molecularly targeted therapies for advanced malignancies creates an important
opportunity to examine these agents for the chemoprevention of prostate cancer.
Two critical targets in the proliferation and malignant transformation of
normal cells, the PI3/Akt signal transduction pathway and the epidermal growth
factor receptor, are currently the focus of several novel investigational
therapies that are in late stage phase II and phase III studies. CONCLUSIONS:
Research to date supports consideration of these novel molecular targets as
future agents in the chemoprevention of prostate cancer. N. Ref:: 28
----------------------------------------------------
[8]
TÍTULO / TITLE: - A randomized long-term
trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus
cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival,
function, and protocol compliance at 1 year.
REVISTA
/ JOURNAL: - Transplantation 2004 Jan 27;77(2):252-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000101495.22734.07
AUTORES
/ AUTHORS: - Ciancio G; Burke GW; Gaynor JJ; Mattiazzi
A; Roth D; Kupin W; Nicolas M; Ruiz P; Rosen A; Miller J
INSTITUCIÓN
/ INSTITUTION: - Department of Surgery, Division of
Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA. gciancio@med.miami.edu
RESUMEN
/ SUMMARY: - BACKGROUND: In an attempt to reduce
chronic calcineurin inhibitor induced allograft nephropathy in first cadaver
and human leukocyte antigen non-identical living-donor renal transplantation,
sirolimus (Siro) or mycophenolate mofetil (MMF) was tested as adjunctive
therapy, with planned dose reductions of tacrolimus (Tacro) over the first year
postoperatively. Adjunctive Siro therapy with a similar dose reduction
algorithm for Neoral (Neo) was included for comparison. METHODS: The detailed
dose reduction plan (Tacro and Siro, group A; Tacro and MMF, group B; Neo and
Siro, group C) is described in our companion report in this issue of
Transplantation. The present report documents function, patient and graft
survival, protocol compliance, and adverse events. RESULTS: As mentioned (in
companion report), group demographics were similar. The present study shows no
significant differences in 1-year patient and graft survival but does show a
trend that points to more difficulties in group C by way of a rising slope of
serum creatinine concentration (P=0.02) and decreasing creatinine clearance
(P=0.04). There were more patients who discontinued the protocol plan in group
C. Thus far, no posttransplant lymphomas have appeared, and infectious
complications have not differed among the groups. However, a greater percentage
of patients in group C were placed on antihyperlipidemia therapy, with an
(unexpected) trend toward a higher incidence of posttransplant diabetes
mellitus in this group. Group A required fewer, and group B the fewest,
antihyperlipidemia therapeutic interventions (P<0.00001). CONCLUSIONS: This
1-year interim analysis of a long-term, prospective, randomized
renal-transplant study indicates that decreasing maintenance dosage of Tacro
with adjunctive Siro or MMF appears to point to improved long-term function,
with reasonably few adverse events.
----------------------------------------------------
[9]
TÍTULO / TITLE: - Early outcome after
sirolimus-eluting stent implantation in patients with acute coronary syndromes:
insights from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology
Hospital (RESEARCH) registry.
REVISTA
/ JOURNAL: - J Am Coll Cardiol 2003 Jun
4;41(11):2093-9.
AUTORES
/ AUTHORS: - Lemos PA; Lee CH; Degertekin M; Saia F;
Tanabe K; Arampatzis CA; Hoye A; van Duuren M; Sianos G; Smits PC; de Feyter P;
van der Giessen WJ; van Domburg RT; Serruys PW
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiology, Thoraxcenter,
Erasmus Medical Center, Dr Molewaterplein 40, NL-3015 GD Rotterdam, the Netherlands.
RESUMEN
/ SUMMARY: - OBJECTIVES: This study evaluated the early
outcomes of patients with acute coronary syndromes (ACS) treated with
sirolimus-eluting stents (SES). BACKGROUND: The safety of SES implantation in
patients with a high risk for early thrombotic complications is currently
unknown. METHODS: Sirolimus-eluting stents have been utilized as the device of
choice for all percutaneous procedures in our institution, as part of the
Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH)
registry. After four months of enrollment, 198 patients with ACS had been
treated exclusively with SES (64% of those treated in the period) and were
compared with a control group composed of 301 consecutive patients treated with
bare stents in the same time period immediately before this study. The
incidence of major adverse cardiac events (MACE) during the first month was
evaluated (death, nonfatal myocardial infarction [MI], or re-intervention).
RESULTS: Compared with control patients, patients treated with SES had more
primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting (13%
vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less
glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The
30-day MACE rate was similar between both groups (SES 6.1% vs. control patients
6.6%; p = 0.8), with most complications occurring during the first week. Stent
thrombosis occurred in 0.5% of SES patients and in 1.7% of control patients (p
= 0.4). In multivariate analysis, SES utilization did not influence the
incidence of MACE (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p =
0.97). CONCLUSIONS: Sirolimus-eluting stent implantation for patients with ACS
is safe, with early outcomes comparable with bare metal stents. N. Ref:: 25
----------------------------------------------------
[10]
TÍTULO / TITLE: - The target of rapamycin
(TOR) proteins.
REVISTA
/ JOURNAL: - Proc Natl Acad Sci U S A. Acceso gratuito
al texto completo a partir de los 6 meses de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.pnas.org/
●●
Cita: Proc Natl Acad Sci USA (PNAS): <> 2001 Jun 19;98(13):7037-44.
●●
Enlace al texto completo (gratuito o de pago) 1073/pnas.121145898
AUTORES
/ AUTHORS: - Raught B; Gingras AC; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry and McGill
Cancer Centre, McGill University, 3655 Promenade Sir-William-Osler, Montreal,
QC H3G 1Y6 Canada.
RESUMEN
/ SUMMARY: - Rapamycin potently inhibits downstream
signaling from the target of rapamycin (TOR) proteins. These evolutionarily
conserved protein kinases coordinate the balance between protein synthesis and
protein degradation in response to nutrient quality and quantity. The TOR
proteins regulate (i) the initiation and elongation phases of translation, (ii)
ribosome biosynthesis, (iii) amino acid import, (iv) the transcription of
numerous enzymes involved in multiple metabolic pathways, and (v) autophagy.
Intriguingly, recent studies have also suggested that TOR signaling plays a
critical role in brain development, learning, and memory formation. N. Ref:: 132
----------------------------------------------------
[11]
TÍTULO / TITLE: - Regulation of
translation initiation by FRAP/mTOR.
REVISTA
/ JOURNAL: - Genes Dev. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.genesdev.org/
●●
Cita: Genes & Development: <> 2001 Apr 1;15(7):807-26.
●●
Enlace al texto completo (gratuito o de pago) 1101/gad.887201
AUTORES
/ AUTHORS: - Gingras AC; Raught B; Sonenberg N
INSTITUCIÓN
/ INSTITUTION: - Department of Biochemistry, McGill
University, Montreal, Quebec H3G 1Y6, Canada.
N. Ref:: 236
----------------------------------------------------
[12]
TÍTULO / TITLE: - Rapamycin plays a new
role as differentiator of vascular smooth muscle phenotype. focus on “The
mTOR/p70 S6K1 pathway regulates vascular smooth muscle differentiation”.
REVISTA
/ JOURNAL: - Am J Physiol Cell Physiol. Acceso gratuito
al texto completo.
●●
Enlace a la Editora de la Revista http://ajpcell.physiology.org/contents-by-date.0.shtml
●●
Cita: Am J Physiol Cell Physiol: <> 2004 Mar;286(3):C480-1.
●●
Enlace al texto completo (gratuito o de pago) 1152/ajpcell.00526.2003
AUTORES
/ AUTHORS: - Lucchesi PA N. Ref:: 12
----------------------------------------------------
[13]
TÍTULO / TITLE: - CD3-specific antibody-induced
active tolerance: from bench to bedside.
REVISTA
/ JOURNAL: - Nat Rev Immunol 2003 Feb;3(2):123-32.
●●
Enlace al texto completo (gratuito o de pago) 1038/nri1000
AUTORES
/ AUTHORS: - Chatenoud L
INSTITUCIÓN
/ INSTITUTION: - Centre de l’Association Claude Bernard sur
les Maladies Autoimmunes and Hopital Necker Enfants Malades IRNEM, 161 Rue de
Sevres, 75015 Paris, France. chatenoud@necker.fr
RESUMEN
/ SUMMARY: - Although they were used initially as
non-specific immunosuppressants in transplantation, CD3-specific monoclonal
antibodies have elicited renewed interest owing to their capacity to induce
immune tolerance. In mouse models of autoimmune diabetes, CD3-specific
antibodies induce stable disease remission by restoring tolerance to pancreatic
beta-cells. This phenomenon was extended recently to the clinic—preservation of
beta-cell function in recently diagnosed patients with diabetes was achieved by
short-term administration of a CD3-specific antibody. CD3-specific antibodies
arrest ongoing disease by rapidly clearing pathogenic T cells from the target.
Subsequently, they promote long-term T-cell-mediated active tolerance. Recent
data indicate that transforming growth factor-beta-dependent CD4+CD25+
regulatory T cells might have a central role in this effect. N. Ref:: 117
----------------------------------------------------
[14]
TÍTULO / TITLE: - Neuroimmunophilins:
novel neuroprotective and neuroregenerative targets.
REVISTA
/ JOURNAL: - Ann Neurol 2001 Jul;50(1):6-16.
AUTORES
/ AUTHORS: - Guo X; Dillman JF 3rd; Dawson
VL; Dawson TM
INSTITUCIÓN
/ INSTITUTION: - Department of Neurology, The Johns Hopkins
University School of Medicine, Baltimore, MD 21287, USA.
RESUMEN
/ SUMMARY: - Cyclosporin A (CsA) and FK506 (tacrolimus)
are immunosuppresants that are widely used in organ transplantation. CsA is an
11-member cyclic peptide, whereas FK506 is a macrolide antibiotic. Recently,
these powerful and useful compounds have become of great interest to
neuroscientists for their unique neuroprotective and neuroregenerative effects.
These drugs and nonimmunosuppressive analogs protect neurons from the effects
of glutamate excitotoxicity, focal ischemia, and
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell
death. They also stimulate functional recovery of neurons in a variety of
neurologic injury paradigms. These drugs exert their effects via immunophilins,
the protein receptors for these agents. The immunophilin ligands show
particular promise as a novel class of neuroprotective and neuroregenerative
agents that have the potential to treat a variety of neurologic disorders. N. Ref:: 102
----------------------------------------------------
[15]
TÍTULO / TITLE: - Preliminary guidelines
for diagnosing and treating tuberculosis in patients with rheumatoid arthritis
in immunosuppressive trials or being treated with biological agents.
REVISTA
/ JOURNAL: - Ann Rheum Dis 2002 Nov;61 Suppl 2:ii62-3.
AUTORES
/ AUTHORS: - Furst DE; Cush J; Kaufmann S; Siegel J;
Kurth R
INSTITUCIÓN
/ INSTITUTION: - UCLA Medical School, Los Angeles, USA
Presbyterian Hospital, Dallas, USA.
----------------------------------------------------
[16]
TÍTULO / TITLE: - Drug-eluting stents in
vascular intervention.
REVISTA
/ JOURNAL: - Lancet 2003 Jan 18;361(9353):247-9.
AUTORES
/ AUTHORS: - Fattori R; Piva T
INSTITUCIÓN
/ INSTITUTION: - Department of Radiology, Cardiovascular
Unit, University Hospital S Orsola, 40138, Bologna, Italy. ross@med.unibo.it
RESUMEN
/ SUMMARY: - CONTEXT: Restenosis is the most important
long-term limitation of stent implantation for coronary artery disease,
occurring in 15-60% of patients. In-stent restenosis, a refractory coronary
lesion resulting from neointimal hyperplasia, challenges both vascular
biologist and interventional cardiologist. Various drugs and devices have been
used tried to overcome restenosis but are not particularly successful. Over
1500000 percutaneous coronary interventions are done annually. Restenosis is
not only important clinically but also for its impact on health-care costs.
STARTING POINT: Growth and migration of vascular smooth-muscle cells result in
neointimal proliferation after vascular injury and are the key mechanism of
in-stent restenosis. The rationale of the most recent approaches to restenosis
(eg, brachytherapy and immunosuppressive agents) arises from the similarity
between tumour-cell growth and the benign tissue proliferation which
characterises intimal hyperplasia. Several immunosuppressants have been tested for
their potential to inhibit restenosis, with the novel strategy of administering
the drug via a coated stent platform. Local drug delivery achieves higher
tissue concentrations of drug without systemic effects, at a precise site and
time. The first multicentre trial with stents coated with sirolimus was by
Marie-Claude Morice and colleagues (N Engl J Med 2002; 346: 1773-80). In a
trial of 238 patients, restenosis of 50% or more at 6 months was 0% and 27%
with sirolimus or normal stents (p<0.001), respectively, after percutaneous
revascularisation. Muzaffer Degertekin and colleagues (Circulation 2002; 106:
1610-13) present data on 2-year follow-up of 15 patients who had been implanted
with the sirolimus stent in another study, and confirm persistent inhibition of
restenosis and an absence of unexpected adverse events. WHERE NEXT? Local
application of antiproliferative agents is a promising technique and research
is developing. Other agents with potential benefits (eg, statins, local
gene-therapy, adenovirus-mediated arterial gene-transfer, L-arginine,
abciximab, angiopeptin, recombinant pegylated hirudin, and hiloprost) as well
as improvements in polymer technology (biodegradable smart polymers, coatings
for multiple-drug release) are under evaluation. The clinical impact of the
elimination of restenosis may influence the approach to coronary artery
disease, the future of cardiac surgery, and health-care economics in
cardiology. N. Ref:: 22
----------------------------------------------------
[17]
TÍTULO / TITLE: - Nephrotic syndrome in
childhood.
REVISTA
/ JOURNAL: - Lancet 2003 Aug 23;362(9384):629-39.
AUTORES
/ AUTHORS: - Eddy AA; Symons JM
INSTITUCIÓN
/ INSTITUTION: - Department of Pediatrics, University of
Washington, Children’s Hospital and Regional Medical Center, Seattle, WA 98105,
USA. allison.eddy@seattlechildrens.org
RESUMEN
/ SUMMARY: - Childhood nephrotic syndromes are most
commonly caused by one of two idiopathic diseases: minimal-change nephrotic
syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). A third distinct
type, membranous nephropathy, is rare in children. Other causes of isolated
nephrotic syndrome can be subdivided into two major categories: rare genetic
disorders, and secondary diseases associated with drugs, infections, or
neoplasia. The cause of idiopathic nephrotic syndrome remains unknown, but
evidence suggests it may be a primary T-cell disorder that leads to glomerular
podocyte dysfunction. Genetic studies in children with familial nephrotic
syndrome have identified mutations in genes that encode important podocyte
proteins. Patients with idiopathic nephrotic syndrome are initially treated
with corticosteroids. Steroid-responsiveness is of greater prognostic use than
renal histology. Several second-line drugs, including alkylating agents,
ciclosporin, and levamisole, may be effective for complicated and
steroid-unresponsive MCNS and FSGS patients. Nephrotic syndrome is associated
with several medical complications, the most severe and potentially fatal being
bacterial infections and thromboembolism. Idiopathic nephrotic syndrome is a
chronic relapsing disease for most steroid-responsive patients, whereas most
children with refractory FSGS ultimately develop end-stage renal disease.
Research is being done to further elucidate the disorder’s molecular
pathogenesis, identify new prognostic indicators, and to develop better
approaches to treatment. N.
Ref:: 140
----------------------------------------------------
[18]
TÍTULO / TITLE: - Overcoming restenosis
with sirolimus: from alphabet soup to clinical reality.
REVISTA
/ JOURNAL: - Lancet 2002 Feb 16;359(9306):619-22.
AUTORES
/ AUTHORS: - Poon M; Badimon JJ; Fuster V
INSTITUCIÓN
/ INSTITUTION: - Mount Sinai School of Medicine, 1 Gustav L
Levy Place, Box 1030, New York, NY 10029, USA.
N. Ref:: 34
----------------------------------------------------
[19]
TÍTULO / TITLE: - New agents in acute
myeloid leukemia and other myeloid disorders.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 1;100(3):441-54.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.11935
AUTORES
/ AUTHORS: - Ravandi F; Kantarjian H; Giles F; Cortes J
INSTITUCIÓN
/ INSTITUTION: - Department of Leukemia, The University of
Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. fravandi@mdanderson.org
RESUMEN
/ SUMMARY: - Over the past several decades,
improvements in chemotherapeutic agents and supportive care have resulted in
significant progress in treating patients with acute myeloid leukemia (AML).
More recently, advances in understanding the biology of AML have resulted in
the identification of new therapeutic targets. The success of
all-trans-retinoic acid in acute promyelocytic leukemia and of imatinib
mesylate in chronic myeloid leukemia have demonstrated that targeted therapy
may be more effective and less toxic when well defined targets are available.
At the same time, understanding mechanisms of drug resistance and means to
overcome them has led to modification of some of the existing cytotoxic agents.
Rational design and conduct of clinical trials is necessary to ensure that the
full potential of these new agents is realized. N. Ref:: 140
----------------------------------------------------
[20]
TÍTULO / TITLE: - High-dose immune
suppression and autologous hematopoietic stem cell transplantation in
refractory Crohn disease.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2003 Mar 1;101(5):2064-6. Epub 2002 Oct 10.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-07-2122
AUTORES
/ AUTHORS: - Burt RK; Traynor A; Oyama Y; Craig R
INSTITUCIÓN
/ INSTITUTION: - Division of Immunotherapy, Northwestern
University Medical School, Chicago, IL 60611, USA. rburt@nwu.edu
RESUMEN
/ SUMMARY: - Two patients with severe Crohn disease,
defined by a Crohn Disease Activity Index (CDAI) higher than 250 despite
anti-tumor necrosis factor alpha (TNF-alpha), were treated by intense immune
suppression and autologous hematopoietic stem cell transplantation (HSCT). Stem
cells were mobilized from the peripheral blood using cyclophosphamide (2.0
g/m2) and granulocyte colony-stimulating factor (G-CSF; 5 micro g/kg/d),
enriched ex vivo by CD34+ selection, and reinfused after immune conditioning
with cyclophosphamide (200 mg/kg) and equine anti-thymocyte globulin (ATG; 90
mg/kg). Patients have remained in remission (CDAI < 100) for 1 year since
HSCT. We conclude that further HSCT studies for severe Crohn disease appear
warranted. N. Ref:: 13
----------------------------------------------------
[21]
TÍTULO / TITLE: - Immunosuppressive and
cytotoxic therapy for pulmonary sarcoidosis.
REVISTA
/ JOURNAL: - Cochrane Database Syst Rev
2003;(3):CD003536.
●●
Enlace al texto completo (gratuito o de pago) 1002/14651858.CD003536
AUTORES
/ AUTHORS: - Paramothayan S; Lasserson T; Walters EH
INSTITUCIÓN
/ INSTITUTION: - Respiratory Medicine, Kingston Hospital
NHS Trust, Galsworthy Rd, Kingston Upon Thames, Surrey, UK, KT2 7QB.
RESUMEN
/ SUMMARY: - BACKGROUND: Immunosuppressive and
cytotoxic agents have been used as both an alternative to oral corticosteroids,
and as a means of maintaining a low dose of steroids in the treatment of
pulmonary sarcoidosis. OBJECTIVES: To determine the efficacy of
immunosuppressive and cytotoxic agents in the treatment of pulmonary
sarcoidosis. SEARCH STRATEGY: The Cochrane Airways Group trials register was
searched for possible randomised trials. Bibliographies were searched for other
potentially relevant trials. Searches were current as of February 2001.
SELECTION CRITERIA: Randomised controlled trials comparing an immunosuppressive
or cytotoxic therapy with a control in patients with pulmonary sarcoidosis were
included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers
independently extracted data for entry in to the Review Manager statistical
package (MetaView 4.1). Pharmaceutical companies and study investigators were
contacted for unpublished trials. MAIN RESULTS: Four studies were included in
the review. Trials comparing methotrexate, chloroquine and cyclosporin A were
identified. No data could be combined for a meta-analysis. Data on lung
function, chest x-ray scores and dyspnoea were largely inconclusive. Adverse
effects were associated with methotrexate, cyclosporin A and chloroquine. In
one small study, methotrexate was associated with a steroid sparing effect
after 12 months of therapy, but no difference was observed at 6 months.
REVIEWER’S CONCLUSIONS: The current body of evidence supporting the use of
immunosuppressive agents and cytotoxic therapies is limited. Side-effects
associated with some of the therapies were severe. N. Ref:: 46
----------------------------------------------------
[22]
TÍTULO / TITLE: - Treatment of chronic
granulomatous disease with myeloablative conditioning and an unmodified
hemopoietic allograft: a survey of the European experience, 1985-2000.
REVISTA
/ JOURNAL: - Blood. Acceso gratuito al texto completo a
partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.bloodjournal.org/
●●
Cita: Blood: <> 2002 Dec 15;100(13):4344-50. Epub 2002 Aug 8.
●●
Enlace al texto completo (gratuito o de pago) 1182/blood-2002-02-0583
AUTORES
/ AUTHORS: - Seger RA; Gungor T; Belohradsky BH;
Blanche S; Bordigoni P; Di Bartolomeo P; Flood T; Landais P; Muller S; Ozsahin
H; Passwell JH; Porta F; Slavin S; Wulffraat N; Zintl F; Nagler A; Cant A;
Fischer A
INSTITUCIÓN
/ INSTITUTION: - European Group for Blood and Marrow
Transplantation (EBMT) and the European Society for Immunodeficiencies (ESID),
Division of Immunology/Hematology, University Children’s Hospital, Zurich,
Switzerland. reinhard.seger@kispi.unizh.ch
RESUMEN
/ SUMMARY: - Treatment of chronic granulomatous disease
(CGD) with myeloablative bone marrow transplantation is considered risky. This
study investigated complications and survival according to different risk
factors present at transplantation. The outcomes of 27 transplantations for
CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant
Registry for primary immunodeficiencies were assessed. Most transplant
recipients were children (n = 25), received a myeloablative busulphan-based
regimen (n = 23), and had unmodified marrow allografts (n = 23) from human
leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative
conditioning, all patients fully engrafted with donor cells; after
myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or
4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9
with pre-existing overt infection, 1 of 2 with acute inflammatory disease.
Exacerbation of infection during aplasia was observed in 3 patients;
inflammatory flare at the infection site during neutrophil engraftment in 2:
all 5 patients belonged to the subgroup of 9 with pre-existing infection.
Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2
years). Survival was especially good in patients without infection at the
moment of transplantation (18 of 18). Pre-existing infections and inflammatory
lesions have cleared in all survivors (except in one with autologous
reconstitution). Myeloablative conditioning followed by transplantation of
unmodified hemopoietic stem cells, if performed at the first signs of a severe
course of the disease, is a valid therapeutic option for children with CGD
having an HLA-identical donor. N.
Ref:: 30
----------------------------------------------------
[23]
TÍTULO / TITLE: - The transplantation of
hematopoietic stem cells after non-myeloablative conditioning: a cellular
therapeutic approach to hematologic and genetic diseases.
REVISTA
/ JOURNAL: - Immunol Res 2003;28(1):13-24.
AUTORES
/ AUTHORS: - Maris M; Storb R
INSTITUCIÓN
/ INSTITUTION: - Fred Hutchinson Cancer Research Center,
and University of Washington, Seattle, WA, USA. mmaris@fhcrc.org
RESUMEN
/ SUMMARY: - Originally, allogeneic hematopoietic stem
cell transplantation (HSCT) was viewed as a form of rescue from the marrow
lethal effects of high doses of chemo-radiotherapy used to both eradicate malignancy
and to provide sufficient immunosuppression to ensure allogeneic engraftment.
Clear evidence of a therapeutic graft-versus-tumor (GVT) effect mediated by
allogeneic effector cells (T cells) has prompted the exploration of HSCT
regimens that rely solely upon host immunosuppression (non-myeloablative) to
facilitate allogeneic donor engraftment. The engrafted donor effector cells are
then used to accomplish the task of eradicating host malignant cells. The
non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation
(TBI) before transplant followed by postgrafting cyclosporine (CSP) and
mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host
chimerism in all patients with hematologic malignancies and genetic disorders
who received HLA-matched sibling allografts. The 17% incidence of graft
rejection was reduced to 3% with the addition of fludarabine, 30 mg/m2/day on d
-4, -3, and -2. The non-myeloablative combination of fludarabine/TBI has also
been successful at achieving high engraftment rates in recipients of 10 of 10
HLA antigen matched unrelated donor HSCTs in patients with hematologic
malignancies. By reducing acute toxicities relative to conventional HSCT, most
patients have received their pre- and post-HSCT therapy almost exclusively as
outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the
incidence and severity appear less compared to conventional HSCT. As in
conventional transplants, immune dysregulation from GVHD and its treatment and
delayed reconstitution of immune function continue to present risks to patients
who have otherwise undergone successful non-myeloablative HSCT. Cellular
therapeutic effects have been observed after non-myeloablative HSCT such as
correction of inherited genetic disorders, and eradication of hematologic
malignant diseases and renal cell carcinoma via GVT responses. N. Ref:: 52
----------------------------------------------------
[24]
TÍTULO / TITLE: - Immunosuppressive
agents in childhood nephrotic syndrome: a meta-analysis of randomized
controlled trials.
REVISTA
/ JOURNAL: - Kidney Int 2001 May;59(5):1919-27.
AUTORES
/ AUTHORS: - Durkan AM; Hodson EM; Willis NS; Craig JC
INSTITUCIÓN
/ INSTITUTION: - Centre for Kidney Research, The Children’s
Hospital at Westmead, New South Wales, Australia.
RESUMEN
/ SUMMARY: - BACKGROUND: Many children with
steroid-sensitive nephrotic syndrome (SSNS) relapse frequently and receive
immunosuppressive agents. In this systematic review of randomized controlled
trials (RCTs), the benefits and harms of these immunosuppressive agents are
evaluated. METHODS: RCTs with outcome data at six months or more that evaluated
noncorticosteroid agents in relapsing SSNS were included. A summary relative
risk for relapse at 6 to 12 months was calculated using a random effects model.
RESULTS: Seventeen trials involving 631 children were identified.
Cyclophosphamide [3 trials; relative risk (RR) 0.44, 95% confidence interval
(CI), 0.26 to 0.73] and chlorambucil (2 trials; RR 0.13, 95% CI, 0.03 to 0.57)
significantly reduced the relapse risk at 6 to 12 months compared with
prednisone alone. In the single chlorambucil versus cyclophosphamide trial,
there was no observed difference in relapse risk at two years (RR 1.31, 95% CI,
0.80 to 2.13). Cyclosporine was as effective as cyclophosphamide (1 trial; RR
1.07, 95% CI, 0.48 to 2.35) and chlorambucil (1 trial; RR 0.82, 95% CI, 0.44 to
1.53), but the effect was not sustained when cyclosporine was ceased. During
treatment, levamisole (3 trials; RR 0.60, 95% CI, 0.45 to 0.79) was more
effective than steroids alone, but the effect was not sustained. CONCLUSIONS:
Cyclophosphamide, chorambucil, cyclosporine, and levamisole reduce the risk of
relapse in children with relapsing SSNS compared with prednisone alone.
Clinically important differences in efficacy among these agents are possible,
and further comparative trials are still needed. Meanwhile, the choice between
these agents depends on physician and patient preferences related to therapy
duration and complication type and frequency.
----------------------------------------------------
[25]
TÍTULO / TITLE: - “Stepping-up” from
methotrexate: a systematic review of randomised placebo controlled trials in
patients with rheumatoid arthritis with an incomplete response to methotrexate.
REVISTA
/ JOURNAL: - Ann Rheum Dis 2001 Nov;60 Suppl 3:iii51-4.
AUTORES
/ AUTHORS: - Hochberg MC; Tracy JK; Flores RH
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine, University of
Maryland School of Medicine, Baltimore 21201, USA. N. Ref:: 20
----------------------------------------------------
[26]
TÍTULO / TITLE: - Drug immunosuppression
therapy for adult heart transplantation. Part 2: clinical applications and
results.
REVISTA
/ JOURNAL: - Ann Thorac Surg 2004 Jan;77(1):363-71.
AUTORES
/ AUTHORS: - Mueller XM
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiovascular Surgery,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca
RESUMEN
/ SUMMARY: - This review describes the clinical
application of classical immunosuppressive drugs as well as that of more recent
drugs. All current immunosuppressive drugs target T-cell activation, and
cytokine production and clonal expansion, or both. Immunosuppressive protocols
can be broadly divided into induction therapy, maintenance immunosuppression,
and treatment of acute rejection episodes.
N. Ref:: 82
----------------------------------------------------
[27]
TÍTULO / TITLE: - Treatment of idiopathic
nephrosis by immunophillin modulation.
REVISTA
/ JOURNAL: - Nephrol Dial Transplant. Acceso gratuito
al texto completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://ndt.oupjournals.org/
●●
Cita: Nephrology Dialysis Transplantation: <> 2003 Aug;18 Suppl
6:vi79-86.
AUTORES
/ AUTHORS: - Meyrier A
INSTITUCIÓN
/ INSTITUTION: - Service de Nephrologie, Hopital Europeen
Georges Pompidou, 20 rue Leblanc, F-75015 Paris, France. alain.meyrier@brs.ap-hop-paris.fr
RESUMEN
/ SUMMARY: - Until 1985, glucocorticoids and cytotoxic
drugs were the only treatments available for idiopathic nephrotic syndrome
(nephrosis), that is, minimal change disease (MCD) and focal segmental
glomerulosclerosis (FSGS). Trials of cyclosporine (CsA) treatment of nephrosis,
the rationale of which was based on pathophysiologic considerations, have shown
that this immunophillin modulator is effective in inducing and maintaining
remission in patients suffering from idiopathic nephrotic syndrome. It appears
that the best results, in the order of 80% remission rate, are obtained in
steroid-sensitive cases, essentially MCD, and that in steroid-resistant FSGS
the drug obtains remission in no more than 20% of the cases. Addition of
glucocorticoids increases the success rate to approximately 30% of cases. Renal
toxicity is proportional to previous impairment of renal function, primary
renal disease (FSGS vs MCD) dosage >5.5 mg/kg/day and duration of treatment.
The better bioavailability of the new formulation of CsA (Neoral), implies that
the former dosage recommendations be reconsidered for distinctly lower figures.
Repeat renal biopsy after 1 year of continuous CsA treatment is advisable, as
stable serum creatinine levels may be falsely reassuring. CsA dependency is the
rule during the first year of treatment. However, in some 25% of cases stable
remission may be maintained after slow tapering off following 3-4 years of
treatment. Other immunophillin modulators have been tried in the treatment of
idiopathic nephrotic syndrome. Despite few preliminary reports indicating some
success of tacrolimus the effects of this drug do not seem convincingly
superior to CsA in terms of remission rate, toxicity and dependency. Rapamycin
has not been tried in the treatment of nephrosis. Anecdotal cases of de novo
FSGS induced by rapamycin in transplanted patients might indicate that this
drug is in fact contraindicated in the treatment of nephrosis. N. Ref:: 36
----------------------------------------------------
[28]
TÍTULO / TITLE: - In vitro generation of
IL-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs
and inhibited by Th1- and Th2-inducing cytokines.
REVISTA
/ JOURNAL: - Immunol Lett 2003 Jan 22;85(2):135-9.