#11#
Revisiones-Ciencias
Básicas-Eventos celulares *** Reviews-Basic Sciences-Cellular events
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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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: - 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
----------------------------------------------------
[7]
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
----------------------------------------------------
[8]
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
----------------------------------------------------
[9]
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
----------------------------------------------------
[10]
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
----------------------------------------------------
[11]
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
----------------------------------------------------
[12]
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
----------------------------------------------------
[13]
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
----------------------------------------------------
[14]
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
----------------------------------------------------
[15]
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.
----------------------------------------------------
[16]
TÍTULO / TITLE: - Composite tissue
allotransplantation in chimeric hosts part II. A clinically relevant protocol
to induce tolerance in a rat model.
REVISTA
/ JOURNAL: - Transplantation 2003 Dec 15;76(11):1548-55.
●●
Enlace al texto completo (gratuito o de pago) 1097/01.TP.0000085288.12571.65
AUTORES
/ AUTHORS: - Prabhune KA; Gorantla VS; Perez-Abadia G;
Francois CG; Vossen M; Laurentin-Perez LA; Breidenbach WC; Wang GG; Anderson
GL; Pidwell DJ; Barker JH; Maldonado C
INSTITUCIÓN
/ INSTITUTION: - Division of Plastic and Reconstructive
Surgery, University of Louisville, Louisville, Kentucky, USA.
RESUMEN
/ SUMMARY: - BACKGROUND: We and others have shown that
mixed allogeneic chimerism induces donor-specific tolerance to composite tissue
allografts across major histocompatibility complex barriers without the need
for immunosuppression. However, a delay period between bone marrow
transplantation and limb allotransplantation is required, making such protocols
impractical for clinical application. This study eliminates this delay period
in a rat hind limb allotransplantation model by performing mixed allogeneic
chimerism induction and transplantation “simultaneously.” METHODS: Group 1
included controls in which naive Wistar Furth (WF) hosts received ACI hind
limbs. Group 2 included (ACI-->WF) chimeras that received limbs from
third-party donors (Fisher), and group 3 included chimeras that received irradiated
(1,050 cGy) ACI limbs. In group 4, WF hosts conditioned with 950 cGy received
irradiated (1,050 cGy) ACI limbs followed by infusion of 100 x 10(6) ACI
T-cell-depleted bone marrow cells and immunotherapy (tacrolimus and
mycophenolate mofetil) for 28 days. Group 5 animals received the same treatment
as group 4 animals without immunotherapy. RESULTS: The rats in groups 1 and 2
rejected their limbs within 10 days. Only one rat in group 4 survived to the
end of the study. Groups 3 and 5 demonstrated long-term limb survival without
rejection or graft-versus-host disease. High levels of donor chimerism
(>80%) were achieved and maintained throughout the study. Mixed lymphocyte
reaction assays in both groups revealed donor-specific hyporesponsiveness with
vigorous third-party reactivity. CONCLUSIONS: This study demonstrated that
infusion of donor bone marrow cells into conditioned hosts immediately after
limb transplantation results in stable mixed chimerism, robust tolerance, and
reliable limb allograft survival.
----------------------------------------------------
[17]
TÍTULO / TITLE: - Elucidating TOR
signaling and rapamycin action: lessons from Saccharomyces cerevisiae.
REVISTA
/ JOURNAL: - Microbiol Mol Biol Rev. - Acceso gratuito
al texto completo a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://mmbr.asm.org/
●●
Cita: Microbiology & Molecular Biology Reviews: <> 2002
Dec;66(4):579-91, table of contents.
AUTORES
/ AUTHORS: - Crespo JL; Hall MN
INSTITUCIÓN
/ INSTITUTION: - Division of Biochemistry, Biozentrum,
University of Basel, CH-4056 Basel, Switzerland.
RESUMEN
/ SUMMARY: - TOR (target of rapamycin) is a
phosphatidylinositol kinase-related protein kinase that controls cell growth in
response to nutrients. Rapamycin is an immunosuppressive and anticancer drug
that acts by inhibiting TOR. The modes of action of TOR and rapamycin are
remarkably conserved from S. cerevisiae to humans. The current understanding of
TOR and rapamycin is derived largely from studies with S. cerevisiae. In this
review, we discuss the contributions made by S. cerevisiae to understanding
rapamycin action and TOR function. N.
Ref:: 171
----------------------------------------------------
[18]
TÍTULO / TITLE: - European best practice
guidelines for renal transplantation. Section IV: Long-term management of the
transplant recipient. IV.3.2. Long-term immunosuppression. Therapy conversion.
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: <> 2002;17 Suppl 4:20-1.
RESUMEN
/ SUMMARY: - GUIDELINE: Conversion of immunosuppressive
drug therapy is recommended to avoid or reduce drug-specific adverse effects,
and is generally safe for long-term graft outcome.
----------------------------------------------------
[19]
TÍTULO / TITLE: - Nutrient signaling
through TOR kinases controls gene expression and cellular differentiation in
fungi.
REVISTA
/ JOURNAL: - Curr Top Microbiol Immunol 2004;279:53-72.
AUTORES
/ AUTHORS: - Rohde JR; Cardenas ME
INSTITUCIÓN
/ INSTITUTION: - Department of Molecular Genetics and Microbiology,
Duke University Medical Center, Durham, NC 27710, USA.
RESUMEN
/ SUMMARY: - The TOR kinases were first identified in
Saccharomyces cerevisiae as the targets of the immunosuppressive drug
rapamycin. Subsequent studies employing rapamycin as a tool in yeast have given
us insight into the structure and function of the TOR kinases, as well as the
biological role of the TOR signaling program in transmitting nutrient signals
to promote cell growth. One of the major advances from this area has been in
defining an unexpected role for TOR signaling in the regulation of
transcription. The identification of target genes subject to regulation by TOR
has provided a platform for the dissection of the signaling events downstream
of the TOR kinases. Studies aimed at understanding TOR-regulated transcription
have begun to shed light on how TOR signaling cooperates with other signaling
programs. In addition, the TOR pathway regulates the developmental program of
pseudohyphal differentiation in concert with highly conserved MAP kinase and
PKA signaling programs. Remarkably, rapamycin also blocks filamentation in a
number of important human and plant pathogens and the mechanism of rapamycin
action is conserved in Candida albicans and Cryptococcus neoformans. The antimicrobial
properties of less immunosuppressive analogs of rapamycin hold promise for the
development of an effective antifungal therapy. N. Ref:: 65
----------------------------------------------------
[20]
TÍTULO / TITLE: - Signaling pathways
involved in translational control of protein synthesis in skeletal muscle by
leucine.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):856S-860S.
AUTORES
/ AUTHORS: - Anthony JC; Anthony TG; Kimball SR;
Jefferson LS
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, P.O. Box 850, The Pennsylvania State University College of
Medicine, Hershey, PA 17033, USA.
RESUMEN
/ SUMMARY: - Numerous reports established that in
skeletal muscle the indispensable branched-chain amino acid leucine is unique
in its ability to initiate signal transduction pathways that modulate
translation initiation. Oral administration of leucine stimulates protein
synthesis in association with hyperphosphorylation of the translational
repressor, eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1),
resulting in enhanced availability of the mRNA cap-binding protein eIF4E, for
binding eIF4G and forming the active eIF4F complex. In addition, leucine
enhances phosphorylation of the 70-kDa ribosomal protein S6 kinase (S6K1).
These results suggest that leucine upregulates protein synthesis in skeletal
muscle by enhancing both the activity and synthesis of proteins involved in
mRNA translation. The stimulatory effects of leucine on translation initiation
are mediated in part through the protein kinase mammalian target of rapamycin
(mTOR), where both insulin signaling and leucine signaling converge to promote
a maximal response. N.
Ref:: 34
----------------------------------------------------
[21]
TÍTULO / TITLE: - A benefit-risk
assessment of basiliximab in renal transplantation.
REVISTA
/ JOURNAL: - Drug Saf. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.csmwm.org/
●●
Cita: Drug Safety: <> 2004;27(2):91-106.
AUTORES
/ AUTHORS: - Boggi U; Danesi R; Vistoli F; Del Chiaro
M; Signori S; Marchetti P; Del Tacca M; Mosca F
INSTITUCIÓN
/ INSTITUTION: - Division of General Surgery and
Transplants, Department of Oncology, Transplants and Advanced Technologies in
Medicine, University of Pisa, Pisa, Italy. uboggi@med.unipi.it
RESUMEN
/ SUMMARY: - Interleukin-2 (IL-2) and its receptor
(IL-2R) play a central role in T lymphocyte activation and immune response
after transplantation. Research on the biology of IL-2R allowed the
identification of key signal transduction pathways involved in the generation
of proliferative and antiapoptotic signals in T cells. The alpha-chain of the
IL-2R is a specific peptide against which monoclonal antibodies have been
raised, with the aim of blunting the immune response by means of inhibiting
proliferation and inducing apoptosis in primed lymphocytes. Indeed,
basiliximab, one of such antibodies, has proved to be effective in reducing the
episodes of acute rejection after kidney and pancreas transplantation. The use
of basiliximab was associated with a significant reduction in the incidence of
any treated rejection episodes after kidney transplantation in the two major
randomised studies (placebo 52.2% vs basiliximab 34.2% at 6 months, European
study; placebo 54.9% vs basiliximab 37.6% at 1 year, US trial). Basiliximab and
equine antithymocyte globulin (ATG) administration resulted in a similar rate
of biopsy-proven acute rejection at 6 months (19% for both) and at 12 months
(19% and 20%, respectively). The use of basiliximab appears not to be
associated with an increased incidence of adverse events as compared with
placebo in immunosuppressive regimens, including calcineurin inhibitors,
mycophenolate mofetil or azathioprine and corticosteroids, and its safety
profile is superior to ATG. Moreover, a similar occurrence of infections is
noted in selected studies (65.5% after basiliximab vs 65.7% of controls),
including cytomegalovirus infection (17.3% vs 14.5%), and cytokine-release
syndrome is not observed. Finally, economic analysis demonstrated lower costs of
overall treatment in patients treated with basiliximab. Therefore, the use of
basiliximab entails a very low risk, allows safe reduction of corticosteroid
dosage and reduces the short- and mid-term rejection rates. However, the
improvement in the long-term survival of kidney grafts in patients treated
according to modern immunosuppressive protocols is still to be demonstrated.
These conclusions are based on a systematic review of the scientific
literature, indexed on Medline database, concerning the mechanism of action,
therapeutic activity, safety and pharmacoeconomic evaluation of basiliximab in
renal transplantation. N.
Ref:: 62
----------------------------------------------------
[22]
TÍTULO / TITLE: - Role of leucine in the
regulation of mTOR by amino acids: revelations from structure-activity studies.
REVISTA
/ JOURNAL: - J Nutr. Acceso gratuito al texto completo
a partir de 1 año de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.nutrition.org/
●●
Cita: Journal of Nutrition: <> 2001 Mar;131(3):861S-865S.
AUTORES
/ AUTHORS: - Lynch CJ
INSTITUCIÓN
/ INSTITUTION: - Department of Cellular and Molecular
Physiology, The Pennsylvania State University College of Medicine, 500
University Drive, Hershey, PA 17033, USA. clynch@psu.edu
RESUMEN
/ SUMMARY: - In this study an overview is presented of
the mTOR signaling pathway and its regulation by amino acids, particularly
L-leucine. Our laboratory is studying amino acid regulation of mTOR in
adipocytes. Potential roles for mTOR in adipocytes that were previously posited
include hypertrophic growth, leptin secretion, protein synthesis and adipose
tissue morphogenesis. A current area of interest in the field is how amino
acids regulate mTOR and which amino acids are regulatory. Revelations
concerning mechanism and recognition are emerging from different laboratories
that examined the structural requirements for stimulation and inhibition of the
mTOR signaling pathway by leucine and amino acid analogs. In adipocytes and
some other cell types, leucine appears to be the main regulatory amino acid.
However, this is not uniformly the case. In those cells where mTOR is regulated
by several amino acids, there is evidence that the mechanism of mTOR activation
may be different from cells where mainly leucine is regulatory. Furthermore, in
tissues where leucine regulates mTOR, the possible existence of different
tissue-specific leucine recognition sites may be indicated. N. Ref:: 47
----------------------------------------------------
[23]
- Castellano -
TÍTULO / TITLE:Las inmunofilinas: agentes
neuroprotectores y promotores de la regeneracion neural. Immunophilins:
neuroprotective agents and promoters of neural regeneration.
REVISTA
/ JOURNAL: - Neurologia. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://www.stmeditores.com/Revistas/ffasciculo.php?Mw==&MTk=&MjUy
●●
Cita: Neurologia: <> 2002 Apr;17(4):200-13.
AUTORES
/ AUTHORS: - Udina E; Navarro X
INSTITUCIÓN
/ INSTITUTION: - Grupo de Neuroplasticidad y Regeneracion,
Departamento de Biologia Celular, Fisiologia e Inmunologia, Universitat
Autonoma de Barcelona, Bellaterra, España.
RESUMEN
/ SUMMARY: - Immunophilins are a family of proteins
mainly known because they act as receptors of the immunosuppressant drugs
cyclosporin A (CsA) and FK506. Immunophilins serve several general functions,
including regulation of mitochondrial permeability, modulation of ion channels
stability and acting as chaperones for a variety of proteins. However,
immunophilins are also present at high density in the nervous system. CsA,
FK506 and other derivatives inhibit the function of immunophilins and, through
bloking or activating several intracellular pathways, it has been shown that
they exert neuroprotective effects in different experimental models of
ischemia, Parkinson’s disease and excitotoxic insults. Moreover, FK506 also has
neuroregenerative effects, by enhancing the axonal regeneration rate after
lesions of the peripheral nervous system. The development of new agents that selectively
bind to immunophilins opens new interesting perspectives for the therapy of
degenerative diseases and injuries of the nervous system. N. Ref:: 100
----------------------------------------------------
[24]
TÍTULO / TITLE: - Immunoablation followed
or not by hematopoietic stem cells as an intense therapy for severe autoimmune
diseases. New perspectives, new problems.
REVISTA
/ JOURNAL: - Haematologica. Acceso gratuito al texto
completo.
●●
Enlace a la Editora de la Revista http://db.doyma.es/
●●
Cita: Haematologica: <> 2001 Apr;86(4):337-45.
AUTORES
/ AUTHORS: - Marmont AM N. Ref:: 127
----------------------------------------------------
[25]
TÍTULO / TITLE: - Protein phosphatase 2A
on track for nutrient-induced signalling in yeast.
REVISTA
/ JOURNAL: - Mol Microbiol. Acceso gratuito al texto
completo a partir de los 2 años de la fecha de publicación.
●●
Enlace a la Editora de la Revista http://www.blackwell-synergy.com/
●●
Cita: Molecular Microbiology: <> 2002 Feb;43(4):835-42.
AUTORES
/ AUTHORS: - Zabrocki P; Van Hoof C; Goris J; Thevelein
JM; Winderickx J; Wera S
INSTITUCIÓN
/ INSTITUTION: - Laboratorium voor Moleculaire Celbiologie,
K.U.Leuven, Kasteelpark Arenberg 31, B-3001 Leuven-Heverlee, Flanders, Belgium.
RESUMEN
/ SUMMARY: - Early studies identified two bona fide
protein phosphatase 2A (PP2A)-encoding genes in Saccharomyces cerevisiae,
designated PPH21 and PPH22. In addition, three PP2A-related phosphatases,
encoded by PPH3, SIT4 and PPG1, have been identified. All share as much as 86%
sequence similarity at the amino acid level. This review will focus primarily
on Pph21 and Pph22, but some aspects of Sit4 regulation will also be discussed.
Whereas a role for PP2A in yeast morphology and cell cycle has been readily
recognized, uncovering its function in yeast signal transduction is a more
recent breakthrough. Via their interaction with phosphorylated Tap42, PP2A and
Sit4 play a pivotal role in target of rapamycin (TOR) signalling. PPH22
overexpression mimics overactive cAMP-PKA (protein kinase A) signalling and
PP2A and Sit4 might represent ceramide signalling targets. The methylation of
its catalytic subunit stabilizes the heterotrimeric form of PP2A and might
counteract TOR signalling. We will show how these new elements could lead us to
understand the role and regulation of PP2A in nutrient-induced signalling in
baker’s yeast. N.
Ref:: 41
----------------------------------------------------
[26]
TÍTULO / TITLE: - Mitochondrial
permeability transition in acute neurodegeneration.
REVISTA
/ JOURNAL: - Biochimie 2002 Feb-Mar;84(2-3):241-50.
AUTORES
/ AUTHORS: - Friberg H; Wieloch T
INSTITUCIÓN
/ INSTITUTION: - Laboratory for Experimental Brain
Research, Wallenberg Neuroscience Center, BMC A13, 221 84 Lund, Sweden.
RESUMEN
/ SUMMARY: - Acute neurodegeneration in man is
encountered during and following stroke, transient cardiac arrest, brain
trauma, insulin-induced hypoglycemia and status epilepticus. All these severe
clinical conditions are characterized by neuronal calcium overload, aberrant
cell signaling, generation of free radicals and elevation of cellular free
fatty acids, conditions that favor activation of the mitochondrial permeability
transition pore (mtPTP). Cyclosporin A (CsA) and its analog
N-methyl-valine-4-cyclosporin A (MeValCsA) are potent blockers of the mtPTP and
protect against neuronal death following excitotoxicity and oxygen glucose
deprivation. Also, CsA and MeValCsA diminish cell death following cerebral
ischemia, trauma, and hypoglycemia. Here we present data that strongly imply
the mtPT in acute neurodegeneration in vivo. Compounds that readily pass the blood-brain-barrier
(BBB) and block the mtPT may be neuroprotective in stroke. N. Ref:: 100
----------------------------------------------------
[27]
TÍTULO / TITLE: - Measle virus-infected
dendritic cells develop immunosuppressive and cytotoxic activities.
REVISTA
/ JOURNAL: - Immunobiology 2001 Dec;204(5):629-38.
AUTORES
/ AUTHORS: - Vidalain PO; Azocar O; Rabourdin-Combe C;
Servet-Delprat C
INSTITUCIÓN
/ INSTITUTION: - Immunobiologie Fondamentale et Clinique,
CERVI-INSERM, Lyon, France. servet@cervi-lyon.inserm.fr
RESUMEN
/ SUMMARY: - Measle virus (MV) infection induces a
transient but profound immunosuppression characterized by a panlymphopenia
which occasionally results in opportunistic infections responsible for a high
rate of mortality in malnourished children. MV can encounter human dendritic
cells (DC) in the respiratory mucosa or in the secondary lymphoid organs. After
a brief presentation of DCs, we review progress in understanding the immunobiology
of MV-infected DCs that could account for MV-induced immunosuppression. In
addition, we develop the newly described TRAIL-mediated cytotoxic function of
DCs that is turned on by MV infection, but also by interferons or
double-stranded RNA (poly (I:C)). Finally, we propose a model where the
measles-associated lymphopenia could be mediated by TRAIL and the
measles-induced immunosuppression could be transiently prolonged by
Fas-mediated destruction of DCs. N.
Ref:: 38
----------------------------------------------------
[28]
TÍTULO / TITLE: - Antiproliferative
prostaglandins and the MRP/GS-X pump role in cancer immunosuppression and
insight into new strategies in cancer gene therapy.
REVISTA
/ JOURNAL: - Biochem Pharmacol 2001 Oct 1;62(7):811-9.
AUTORES
/ AUTHORS: - Homem de Bittencourt PI Jr; Curi R