PMID- 17360768
OWN - NLM
STAT- MEDLINE
DCOM- 20070612
LR  - 20211203
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 22 Suppl 1
DP  - 2007 May
TI  - The role of proliferation signal inhibitors in post-transplant malignancies.
PG  - i11-6
AB  - The proliferation signal inhibitors [PSIs; mammalian target of rapamycin (mTOR) 
      inhibitors] are widely used for immunosuppression in transplant recipients. 
      Alongside their immunosuppressive properties, PSIs also have substantial 
      anti-neoplastic activity, as a result of their inhibition of cellular signalling 
      pathways involved in critical functions such as cell division, T-cell activation, 
      invasion and growth factor production. In vitro and in vivo studies have shown 
      that PSIs can prevent the growth of experimentally transformed cells and 
      tumour-derived cell lines, and can also increase the sensitivity of cells to 
      apoptosis-inducing agents. The mechanisms of anti-tumour activities of PSIs 
      identified in pre-clinical studies include up-regulation of adhesion molecules 
      with reversion to less invasive phenotypes, and inhibition of angiogenesis 
      resulting from both decreased vascular endothelial growth factor production and 
      decreased endothelial sensitivity to such growth factors. In clinical trials of 
      PSIs in transplant recipients, results show that the incidence of malignancies is 
      substantially lower in patients receiving PSIs than in those receiving 
      calcineurin inhibitor (CNI)-based immunosuppression, with significantly longer 
      times to the development of malignancy. This protective effect of the PSIs is 
      also present in patients receiving combination therapy with a CNI and a PSI. 
      There is also evidence to suggest a role for PSIs in the management of 
      post-transplantation malignancy, with reports of complete resolution of primary 
      and metastatic tumours after conversion from a CNI to a PSI. These beneficial 
      effects have led to the investigation of everolimus and an analogue of sirolimus 
      as a treatment for patients with advanced solid tumours.
FAU - Gutierrez-Dalmau, Alex
AU  - Gutierrez-Dalmau A
AD  - Department of Nephrology, Hospital Clinic, University of Barcelona, 08036 
      Barcelona, Spain.
FAU - Campistol, Josep M
AU  - Campistol JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20070314
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Calcineurin Inhibitors
MH  - Cyclosporine/therapeutic use
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Kidney Transplantation/*adverse effects
MH  - Lymphoproliferative Disorders/drug therapy
MH  - Neoplasms/*drug therapy/etiology
MH  - PTEN Phosphohydrolase/physiology
MH  - Protein Kinases/*drug effects
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/*therapeutic use
MH  - TOR Serine-Threonine Kinases
RF  - 25
EDAT- 2007/03/16 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/03/16 09:00
PHST- 2007/03/16 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/03/16 09:00 [entrez]
AID - gfm084 [pii]
AID - 10.1093/ndt/gfm084 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2007 May;22 Suppl 1:i11-6. doi: 10.1093/ndt/gfm084. Epub 
      2007 Mar 14.