PMID- 24156349
OWN - NLM
STAT- MEDLINE
DCOM- 20140926
LR  - 20211021
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 11
DP  - 2013 Oct 24
TI  - Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to 
      the patients' bed.
PG  - 268
LID - 10.1186/1479-5876-11-268 [doi]
AB  - BACKGROUND: Major goals in translational oncology are to reduce systemic toxicity 
      of current anticancer strategies and improve effectiveness. An extremely 
      efficient cancer cell mechanism to avoid and/or reduce the effects of highly 
      cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark 
      of all malignant tumors. The H +-rich milieu that anticancer drugs meet once they 
      get inside the tumor leads to their protonation and neutralization, therefore 
      hindering their access into tumor cells. We have previously shown that proton 
      pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading 
      to a consistent chemosensitization of tumors. In this study, we investigated the 
      effects of PPI in chemosensitizing osteosarcoma. METHOD: MG-63 and Saos-2 cell 
      lines were used as human osteosarcoma models. Cell proliferation after 
      pretreatment with PPI and subsequent treatment with cisplatin was evaluated by 
      using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft 
      treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre 
      historically controlled trial, was performed to evaluate the activity of a 
      pre-treatment administration of PPIs as chemosensitizers during neoadjuvant 
      chemotherapy based on methotrexate, cisplatin, and adriamycin. RESULTS: 
      Preclinical experiments showed that PPI sensitize both human osteosarcoma cell 
      lines and xenografts to cisplatin. A clinical study subsequently showed that 
      pretreatment with PPI drug esomeprazole leads to an increase in the local effect 
      of chemotherapy, as expressed by percentage of tumor necrosis. This was 
      particularly evident in chondroblastic osteosarcoma, an histological subtype that 
      normally shows a poor histological response. Notably, no significant increase in 
      toxicity was recorded in PPI treated patients. CONCLUSION: This study provides 
      the first evidence that PPI may be beneficially added to standard regimens in 
      combination to conventional chemotherapy.
FAU - Ferrari, Stefano
AU  - Ferrari S
FAU - Perut, Francesca
AU  - Perut F
FAU - Fagioli, Franca
AU  - Fagioli F
FAU - Brach Del Prever, Adalberto
AU  - Brach Del Prever A
FAU - Meazza, Cristina
AU  - Meazza C
FAU - Parafioriti, Antonina
AU  - Parafioriti A
FAU - Picci, Piero
AU  - Picci P
FAU - Gambarotti, Marco
AU  - Gambarotti M
FAU - Avnet, Sofia
AU  - Avnet S
FAU - Baldini, Nicola
AU  - Baldini N
FAU - Fais, Stefano
AU  - Fais S
AD  - Anti-Tumour Drugs Section Department of Therapeutic Research and Medicines 
      Evaluation, Istituto Superiore di Sanita, Rome, Italy. stefano.fais@iss.it.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20131024
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Proton Pump Inhibitors)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Line, Tumor
MH  - Child
MH  - Drug Evaluation, Preclinical
MH  - Female
MH  - Humans
MH  - Male
MH  - Osteosarcoma/*drug therapy/pathology
MH  - Proton Pump Inhibitors/*therapeutic use
MH  - Young Adult
PMC - PMC3815282
EDAT- 2013/10/26 06:00
MHDA- 2014/09/27 06:00
PMCR- 2013/10/24
CRDT- 2013/10/26 06:00
PHST- 2013/06/24 00:00 [received]
PHST- 2013/09/23 00:00 [accepted]
PHST- 2013/10/26 06:00 [entrez]
PHST- 2013/10/26 06:00 [pubmed]
PHST- 2014/09/27 06:00 [medline]
PHST- 2013/10/24 00:00 [pmc-release]
AID - 1479-5876-11-268 [pii]
AID - 10.1186/1479-5876-11-268 [doi]
PST - epublish
SO  - J Transl Med. 2013 Oct 24;11:268. doi: 10.1186/1479-5876-11-268.