#03#
Revisiones-Clínica-Etiología
& Patología *** Reviews-Clinical-Etiology & Pathology
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
La
biblioteca del conocimiento biomédico© es un servicio GRATUITO. Toda la
información ha sido obtenida de fuentes públicas, de portales de internet que
no requieren registro alguno para su uso, que no requieren estar de acuerdo con
sus Términos de uso, que son de libre acceso a todo el mundo, y son a su vez
gratuitos. La biblioteca (revisiones, guías, protocolos, medicina basada en la
evidencia, etc...) se recopila en base a una patente que permite a Effiloop la catalogación
de los artículos por campos de interés así como por el orden de su importancia
(se proveen las primeras 200 revisiones). Toda la informacion se ampara en las
leyes de libre pensamiento-expresión, y de uso justo. Este documento sólo
contiene artículos escritos en Castellano y/o Inglés.
The
biomedical library© is a FREE service. All the information has been obtained
from public sources, from web sites that do not require registration for their
use, that do not require an agreement with their Terms of use, that provide
free access for all, and are free of charge. The library (reviews, guides,
protocols, medicine based medicine, etc) is arranged according to a patent that
warrants Effiloop to catalogue the articles by fields of interest as well as to
sort articles by true relevance (the first 200 reviews are provided). All the
information is provided according to the freedom of speech and fair use laws.
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: - 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.
----------------------------------------------------
[5]
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
----------------------------------------------------
[6]
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.
----------------------------------------------------
[7]
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
----------------------------------------------------
[8]
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
----------------------------------------------------
[9]
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
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
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.
----------------------------------------------------
[12]
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
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
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
----------------------------------------------------
[15]
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
----------------------------------------------------
[16]
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.
AUTORES
/ AUTHORS: - O’Garra A; Barrat FJ
INSTITUCIÓN
/ INSTITUTION: - Division of Immunoregulation, The National
Institute for Medical Research (NIMR), The Ridgeway, Mill Hill, NW7 1AA,
London, UK. N. Ref:: 40
----------------------------------------------------
[17]
TÍTULO / TITLE: - Risk for myopathy with
statin therapy in high-risk patients.
REVISTA
/ JOURNAL: - Arch Intern Med 2003 Mar 10;163(5):553-64.
AUTORES
/ AUTHORS: - Ballantyne CM; Corsini A; Davidson MH;
Holdaas H; Jacobson TA; Leitersdorf E; Marz W; Reckless JP; Stein EA
INSTITUCIÓN
/ INSTITUTION: - Center for Cardiovascular Disease
Prevention, Baylor College of Medicine, 6565 Fannin, Mail Station A601, Suite
A656, Houston, TX 77030, USA. cmb@bcm.tmc.edu
RESUMEN
/ SUMMARY: - Emerging data suggest that the
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
offer important benefits for the large population of individuals at high risk
for coronary heart disease. This population encompasses a sizable portion of
individuals who are also at high risk for drug-drug interactions due to their
need for multiple medications. In general, statins are associated with a very
small risk for myopathy (which may progress to fatal or nonfatal
rhabdomyolysis); however, the potential for drug-drug interactions is known to
increase this risk in specific high-risk groups. The incidence of myopathy
associated with statin therapy is dose related and is increased when statins
are used in combination with agents that share common metabolic pathways. Of
particular concern is the potential for interactions with other lipid-lowering
agents such as fibrates and niacin (nicotinic acid), which may be used in
patients with mixed lipidemia, and with immunosuppressive agents, such as
cyclosporine, which are commonly used in patients after transplantation.
Clinicians should be alert to the potential for drug-drug interactions to
minimize the risk of myopathy during long-term statin therapy in patients at
high risk for coronary heart disease. N.
Ref:: 128
----------------------------------------------------
[18]
TÍTULO / TITLE: - Renal transplantation:
can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol
biopsy findings.
REVISTA
/ JOURNAL: - J Am Soc Nephrol. Acceso gratuito al texto
completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.jasn.org/
●●
Cita: Journal of the American Society of Nephrology: <> 2003
Mar;14(3):755-66.
AUTORES
/ AUTHORS: - Gotti E; Perico N; Perna A; Gaspari F;
Cattaneo D; Caruso R; Ferrari S; Stucchi N; Marchetti G; Abbate M; Remuzzi G
INSTITUCIÓN
/ INSTITUTION: - Department of Medicine and
Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for
Pharmacological Research, Italy.
RESUMEN
/ SUMMARY: - How to combine antirejection drugs and
which is the optimal dose of steroids and calcineurin inhibitors beyond the
first year after kidney transplantation to maintain adequate immunosuppression
without major side effects are far from clear. Kidney transplant patients on
steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol
biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA
were discontinued or reduced on the basis of biopsy to establish effects on
drug-related complications, acute rejection, and graft function over 3 yr of
follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal
clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were
monitored yearly. At the end, patients underwent a second biopsy. Per-protocol
biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA
nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n =
12, standard therapy). Reducing the drug regimen led to overall fewer side
effects related to immunosuppression as compared with standard therapy or
no-biopsy. Steroids were safely stopped with no acute rejection or graft loss.
Complete CsA discontinuation was associated with acute rejection in the first
four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led
to acute rejection or major renal function deterioration. Biopsy patients on
conventional regimen had no acute rejection, one graft loss, no significant
change in GFR, and significant RPF decline. No-biopsy controls: no acute
rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy
analysis, severe lesions did not develop in patients with steroid
discontinuation in contrast to patients on standard therapy over follow-up. CsA
reduction did not adversely affect histology. Per-protocol biopsy more than 1
yr after kidney transplantation is a safe procedure to guide change of drug
regimen and to lower the risk of major side effects.
----------------------------------------------------
[19]
TÍTULO / TITLE: - Drug immunosuppression
therapy for adult heart transplantation. Part 1: immune response to allograft
and mechanism of action of immunosuppressants.
REVISTA
/ JOURNAL: - Ann Thorac Surg 2004 Jan;77(1):354-62.
AUTORES
/ AUTHORS: - Mueller XM
INSTITUCIÓN
/ INSTITUTION: - Department of Cardiovascular Surgery,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. xavier.mueller@usherbrooke.ca
RESUMEN
/ SUMMARY: - In the early days of transplantation,
immunosuppression therapy was rather broad and nonspecific, mainly using
high-dose corticosteroids and azathioprine. Thereafter we progressively
narrowed the target of immunosuppressive strategy starting with polyclonal
antibodies. The introduction of cyclosporine, OKT3, and tacrolimus further
narrowed the target on the T-cell pathways. More recently mycophenolate mofetil
progressively took the place of azathioprine with its higher lymphocyte
specificity and sirolimus and interleukin-2 receptor antibodies were
introduced. In this field in constant movement the aim is to find a drug or a
regimen that provides optimal immunosuppression therapy with minimal side
effects, in other words to find the right balance between overimmunosuppression
and underimmunosuppression therapy. This review is divided into two parts. The
first part will provide a basic understanding of the immunologic response to
allograft and explain how conventional and recently introduced immunosuppressive
agents work. The second part will describe the clinical application of
immunosuppressive drugs to provide practical information for those in charge of
heart transplant recipients. N.
Ref:: 68
----------------------------------------------------
[20]
TÍTULO / TITLE: - Longstanding
obliterative panarteritis in Kawasaki disease: lack of cyclosporin A effect.
REVISTA
/ JOURNAL: - Pediatrics 2003 Oct;112(4):986-92.
AUTORES
/ AUTHORS: - Kuijpers TW; Biezeveld M; Achterhuis A;
Kuipers I; Lam J; Hack CE; Becker AE; van der Wal AC
INSTITUCIÓN
/ INSTITUTION: - Emma Children’s Hospital, Academic Medical
Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.w.kuijpers@amc.uva.nl
RESUMEN
/ SUMMARY: - Kawasaki disease is a childhood vasculitis
of medium-sized vessels, affecting the coronary arteries in particular. We have
treated a therapy-resistant child who met all diagnostic criteria for Kawasaki
disease. After the boy was given intravenous immunoglobulins and salicylates,
as well as several courses of pulsed methylprednisolone, disease recurred and
coronary artery lesions became progressively detectable. Cyclosporin A was
started and seemed clinically effective. In contrast to the positive effect on
inflammatory parameters, ie, C-reactive protein and white blood cell counts, a
novel plasma marker for cytotoxicity (granzyme B) remained elevated. Coronary
disease progressed to fatal obstruction and myocardial infarction.
Echocardiography, electrocardiograms, and myocardial creatine phosphokinase did
not predict impending death. At autopsy an obliterative panarteritis was
observed resulting from massive fibrointimal proliferation, affecting the aorta
and several large and medium-sized arteries. Immunophenotypic analysis of the
inflammatory infiltrates in arteries revealed mainly granzyme-positive
cytotoxic T cells and macrophages in the intima and media, as well as nodular
aggregates of T cells, B cells, and plasma cells in the adventitia of affected
arteries. These findings further endorse the role of specific cellular and
humoral immunity in Kawasaki disease. Unremitting coronary arteritis and
excessive smooth muscle hyperplasia resulted in coronary occlusion despite the
use of cyclosporin A. N.
Ref:: 37
----------------------------------------------------
[21]
TÍTULO / TITLE: - Mammalian target of
rapamycin inhibition as therapy for hematologic malignancies.
REVISTA
/ JOURNAL: - Cancer 2004 Feb 15;100(4):657-66.
●●
Enlace al texto completo (gratuito o de pago) 1002/cncr.20026
AUTORES
/ AUTHORS: - Panwalkar A; Verstovsek S; Giles FJ
INSTITUCIÓN
/ INSTITUTION: - Section of Developmental Therapeutics,
Department of Leukemia, University of Texas M. D. Anderson Cancer Center,
Houston, Texas, USA.
RESUMEN
/ SUMMARY: - The mammalian target of rapamycin (mTOR)
is a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt
(protein kinase B) signaling pathway, which mediates cell survival and proliferation.
mTOR regulates essential signal-transduction pathways, is involved in the
coupling of growth stimuli with cell cycle progression, and initiates mRNA
translation in response to favorable nutrient environments. mTOR is involved in
regulating many aspects of cell growth, including membrane traffic, protein
degradation, protein kinase C signaling, ribosome biogenesis, and
transcription. Because mTOR activates both the 40S ribosomal protein S6 kinase
(p70s6k) and the eukaryotic initiation factor 4E-binding protein 1, its
inhibitors cause G1-phase cell cycle arrest. Inhibitors of mTOR also prevent
cyclin dependent kinase (CDK) activation, inhibit retinoblastoma protein
phosphorylation, and accelerate the turnover of cyclin D1, leading to a
deficiency of active CDK4/cyclin D1 complexes, all of which may help cause
G1-phase arrest. It is known that the phosphatase and tensin homologue tumor
suppressor gene (PTEN) plays a major role in embryonic development, cell
migration, and apoptosis. Malignancies with PTEN mutations, which are
associated with constitutive activation of the PI3K/Akt pathway, are relatively
resistant to apoptosis and may be particularly sensitive to mTOR inhibitors.
Rapamycin analogs with relatively favorable pharmaceutical properties,
including CCI-779, RAD001, and AP23573, are under investigation in patients
with hematologic malignancies. N.
Ref:: 116
----------------------------------------------------
[22]
TÍTULO / TITLE: - Cholesteryl ester
transfer protein facilitates the movement of water-insoluble drugs between
lipoproteins: a novel biological function for a well-characterized lipid
transfer protein.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2002 Dec
15;64(12):1669-75.
AUTORES
/ AUTHORS: - Kwong M; Wasan KM
INSTITUCIÓN
/ INSTITUTION: - Division of Pharmaceutics and
Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British
Columbia, 2146 East Mall Avenue, Vancouver, BC, Canada V6T 1Z3.
RESUMEN
/ SUMMARY: - This review article addresses the recently
discovered finding that cholesteryl ester transfer protein (CETP) can
facilitate the transfer of water-insoluble drugs between different lipoprotein
subclasses. This protein, which is often referred to as lipid transfer protein
I (LTP I), is involved in the lipid regulation of lipoproteins. It is
responsible for the facilitated transfer of core lipoprotein lipids,
cholesteryl ester and triglycerides, and approximately one-third of the coat
lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins.
The human body appears to recognize exogenous water-insoluble drugs as
lipid-like particles, which suggests that these compounds may interact with
lipoproteins just like endogenous plasma lipids, and thus their transfer
between lipoproteins may be facilitated by plasma CETP. Patients with a variety
of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or
hypercholesterolemia and triglyceridemia, commonly referred to as
dyslipidemias, which result in changes in their plasma lipoprotein-lipid composition
and concentration. The interaction of water-insoluble drugs with these
dyslipidemic lipoproteins may be responsible for the differences seen in the
pharmacokinetics and pharmacodynamics of the drug within different diseased
patient populations. It is possible that these differences may be linked to the
ability of CETP to transfer these compounds from one lipoprotein to another.
This review examines the current understanding of the relationship between CETP
activity and the lipoprotein distribution of a number of compounds (e.g.
amphotericin B and cyclosporine A). It further suggests that additional
research will expand our understanding of the role of CETP to explain other
functions in lipophilic drug distribution and metabolism. N. Ref:: 45
----------------------------------------------------
[23]
TÍTULO / TITLE: - Advances in
transplantation tolerance.
REVISTA
/ JOURNAL: - Lancet 2001 Jun 16;357(9272):1959-63.
AUTORES
/ AUTHORS: - Yu X; Carpenter P; Anasetti C
INSTITUCIÓN
/ INSTITUTION: - Human Immunogenetics Program, Fred
Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
RESUMEN
/ SUMMARY: - Immunosuppressive drugs developed in the
past two decades have improved the short-term survival of organ allografts, but
tolerance has not been achieved and almost all transplant recipients continue
to require drugs throughout life. Graft rejection arises from the cognate
interaction of T cells with antigen-presenting cells, the recognition of
alloantigen through the T-cell receptor, and the delivery of accessory
stimulation signals. Once activated by the specific antigen, replicating T
cells die if they are re-exposed to the same antigen. Since depletion of
antigen-activated T cells is one critical mechanism of transplantation
tolerance, drugs such as ciclosporin that interfere with activation-induced
T-cell death could inhibit tolerance, whereas drugs such as mycophenolate
mofetil, that induce the death of activated T cells, could facilitate
tolerance. Other tolerance mechanisms depend on inactivation rather than
elimination of allograft reactive T cells. When antigen recognition occurs
without costimulation through the CD28 and CD154 accessory receptors, or in
absence of cell division, T cells become unresponsive. Thus, inhibitors of CD28
and CD154, and inhibition of T-cell division by rapamycin promotes
transplantation tolerance. N.
Ref:: 54
----------------------------------------------------
[24]
TÍTULO / TITLE: - Clinical development of
mammalian target of rapamycin inhibitors.
REVISTA
/ JOURNAL: - Hematol Oncol Clin North Am 2002
Oct;16(5):1101-14.
AUTORES
/ AUTHORS: - Dancey JE
INSTITUCIÓN
/ INSTITUTION: - Cancer Treatment Evaluation Program,
Division of Cancer Treatment and Diagnosis, Investigational Drug
Branch/CTEP/DCTD/NCI, 6130 Executive Boulevard, EPN 7131, Rockville, MD 20854,
USA. danceyj@ctep.nci.nih.gov
RESUMEN
/ SUMMARY: - Rapamycin and CCI-779 have significant in
vitro and in vivo anti-proliferative activity against a broad range of human
tumor cell lines, justifying the clinical evaluation of this class of agent in
cancer patients. Preliminary results from phase I studies of CCI-779 suggest
that the agent is well tolerated and has anti-tumor activity. The challenge to
investigators is to efficiently determine what role this class of agent will
play in the treatment of cancer patients.
N. Ref:: 69
----------------------------------------------------
[25]
TÍTULO / TITLE: - Effects of
immunosuppressive drugs on dendritic cells and tolerance induction.
REVISTA
/ JOURNAL: - Transplantation 2003 May 15;75(9
Suppl):37S-42S.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000067950.90241.1D
AUTORES
/ AUTHORS: - Lagaraine C; Lebranchu Y
INSTITUCIÓN
/ INSTITUTION: - EA 3249, Cellules hematopoietiques,
hemostase et greffe, Laboratoire d’immunologie, Faculte de medecine, Tours,
France.
RESUMEN
/ SUMMARY: - Dendritic cells, the most effective
antigen-presenting cells for priming naive T cells and initiating immune
responses, are also able to induce tolerance. This balance between immunity and
tolerance depends on the functional stage of dendritic cells (DC). Activation
of naive T cells by immature DC can induce tolerance. It is therefore of
interest to summarize the effects of immunosuppressive agents on DC maturation
and functions. In contrast to glucocorticosteroids, mycophenolate mofetil, and
vitamin D(3) analogs, calcineurin inhibitors do not seem to inhibit DC
maturation in in vitro culture systems. However, these molecules all appear to
interfere with DC functions. N.
Ref:: 44
----------------------------------------------------
[26]
TÍTULO / TITLE: - Donor-specific
tolerance in fully major histocompatibility major histocompatibility
complex-mismatched limb allograft transplants under an anti-alphabeta T-cell
receptor monoclonal antibody and cyclosporine A protocol.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec 27;76(12):1662-8.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000105343.49626.6F
AUTORES
/ AUTHORS: - Siemionow MZ; Izycki DM; Zielinski M
INSTITUCIÓN
/ INSTITUTION: - Department of Plastic Surgery, Cleveland
Clinic Foundation, A60, 9500 Euclid Avenue, Cleveland, OH 44195, USA. siemiom@ccf.org
RESUMEN
/ SUMMARY: - BACKGROUND: Recent studies have
demonstrated that treatment with alphabeta-T-cell receptor (TCR) monoclonal
antibody and cyclosporine A (CsA) can extend survival in composite tissue
allografts (CTA). The purpose of this study was to induce tolerance in fully
major histocompatibility complex (MHC)-mismatched rat limb allografts under 7
days of a combined alphabeta-TCR-CsA protocol. METHODS: The authors performed
30 hind-limb allotransplantations across the MHC barrier between Brown Norway
donors (BN; RT1n) and Lewis recipients (LEW; RT1l). Isograft and allograft
controls received no treatment. The experimental groups received monotherapy of
alphabeta-TCR and CsA or a combination of alphabeta-TCR and CsA for 7 days
only. Donor-specific tolerance and immunocompetence were determined by standard
skin grafting in vivo and mixed lymphocyte reaction (MLR) in vitro. The
efficacy of immunosuppressive therapy and the level of donor-specific chimerism
were determined by flow cytometry. RESULTS: Long-term survival (>350 days)
was achieved in allograft recipients (n=6) under the 7-day protocol of combined
alphabeta-TCR-CsA. Donor-specific tolerance and immunocompetence of long-term
chimeras were confirmed by acceptance of skin grafts from the donors and
rejection of the third-party alloantigens (AxC Irish). At day 120, MLR
demonstrated unresponsiveness to the host and donor antigens but strong
reactivity against third-party alloantigens. Flow cytometry confirmed the high
efficacy of immunosuppressive treatment and the development of donor-specific
chimerism (7.6% of CD4+-RT1n+ cells, 1.3% of CD8+-RT1n+ cells, and 16.5% of
CD45RA+-RT1n+ cells) in the periphery of tolerated recipients. CONCLUSIONS:
Combined therapy of alphabeta-TCR-CsA for 7 days resulted in tolerance
induction in fully MHC-mismatched rat hind-limb allografts. Tolerance was
directly associated with stable, donor-specific chimerism.
----------------------------------------------------
[27]
TÍTULO / TITLE: - Dimerizer-regulated
gene expression.
REVISTA
/ JOURNAL: - Curr Opin Biotechnol 2002
Oct;13(5):459-67.
AUTORES
/ AUTHORS: - Pollock R; Clackson T
INSTITUCIÓN
/ INSTITUTION: - ARIAD Gene Therapeutics, 26 Landsdowne
Street, Cambridge, MA 02139, USA. roy.pollock@ariad.com
RESUMEN
/ SUMMARY: - Control of gene expression using small
molecules is a powerful research tool and has clinical utility in the context
of regulated gene therapy. Use of chemical inducers of dimerization, or
dimerizers, for this purpose has several advantages, including tight
regulation, modularity to facilitate iterative improvements, and assembly from
human proteins to minimize immune responses in clinical applications. Recent
developments include the use of the rapamycin-based dimerizer system to
regulate the expression of endogenous genes, the generation of new chemical
dimerizers based on FK506, dexamethasone and methotrexate, and progress towards
the clinical use of adeno-associated virus and adenovirus vectors regulated by
rapamycin analogs. N.
Ref:: 40
----------------------------------------------------
[28]