PMID- 26245309
OWN - NLM
STAT- MEDLINE
DCOM- 20160602
LR  - 20211203
IS  - 1440-1843 (Electronic)
IS  - 1323-7799 (Linking)
VI  - 20
IP  - 8
DP  - 2015 Nov
TI  - Temsirolimus targets multiple hallmarks of cancer to impede mesothelioma growth 
      in vivo.
PG  - 1263-71
LID - 10.1111/resp.12604 [doi]
AB  - BACKGROUND AND OBJECTIVE: The mechanistic target of rapamycin (mTOR) promotes 
      cancer cell proliferation and survival, transduces pro-angiogenic signals and 
      regulates immune cell differentiation and function. We hypothesized that 
      temsirolimus, an mTOR inhibitor, would curtail experimental mesothelioma 
      progression in vivo by limiting tumour cell growth, abrogating tumour 
      angiogenesis and modulating immune/inflammatory tumour milieu. METHODS: We 
      produced flank and pleural syngeneic murine mesotheliomas by delivering AE17 and 
      AB1 murine mesothelioma cells into the right flank or the pleural space of 
      C57BL/6 and BALB/c mice, respectively. Animals were given five times/week 
      intraperitoneal injections of 20 mg/kg temsirolimus or vehicle and were 
      sacrificed on day 26 (flank) or on day 15 (pleural) post-tumour cell propagation. 
      RESULTS: Temsirolimus limited mesothelioma growth in vivo by stimulating tumour 
      cell apoptosis, inhibiting tumour angiogenesis, enhancing tumour lymphocyte 
      abundance and blocking pro-tumour myeloid cell recruitment. Pleural fluid 
      accumulation was significantly mitigated in AE17 but not in AB1 mesotheliomas. In 
      vitro, temsirolimus hindered mesothelioma cell growth, NF-kappaB activation and 
      macrophage migration. CONCLUSIONS: In conclusion, temsirolimus apart from 
      inducing tumour cell apoptosis, targets tumour angiogenesis and influences 
      inflammatory tumour microenvironment to halt experimental mesothelioma growth in 
      vivo.
CI  - (c) 2015 Asian Pacific Society of Respirology.
FAU - Vazakidou, Maria Eleni
AU  - Vazakidou ME
AD  - 'Marianthi Simou Laboratory', 1st Department of Critical Care and Pulmonary 
      Medicine, National and Kapodistrian University of Athens, School of Medicine, 
      Evangelismos Hospital, Athens, Greece.
FAU - Magkouta, Sophia
AU  - Magkouta S
AD  - 'Marianthi Simou Laboratory', 1st Department of Critical Care and Pulmonary 
      Medicine, National and Kapodistrian University of Athens, School of Medicine, 
      Evangelismos Hospital, Athens, Greece.
FAU - Moschos, Charalampos
AU  - Moschos C
AD  - 'Marianthi Simou Laboratory', 1st Department of Critical Care and Pulmonary 
      Medicine, National and Kapodistrian University of Athens, School of Medicine, 
      Evangelismos Hospital, Athens, Greece.
FAU - Psallidas, Ioannis
AU  - Psallidas I
AD  - 'Marianthi Simou Laboratory', 1st Department of Critical Care and Pulmonary 
      Medicine, National and Kapodistrian University of Athens, School of Medicine, 
      Evangelismos Hospital, Athens, Greece.
AD  - Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, UK.
AD  - Oxford Respiratory Trials Unit, Churchill Hospital, Oxford, UK.
FAU - Pappas, Apostolos
AU  - Pappas A
AD  - 'Marianthi Simou Laboratory', 1st Department of Critical Care and Pulmonary 
      Medicine, National and Kapodistrian University of Athens, School of Medicine, 
      Evangelismos Hospital, Athens, Greece.
FAU - Psarra, Katherina
AU  - Psarra K
AD  - Department of Immunology-Histocompatibility, Evangelismos Hospital, Athens, 
      Greece.
FAU - Kalomenidis, Ioannis
AU  - Kalomenidis I
AD  - 'Marianthi Simou Laboratory', 1st Department of Critical Care and Pulmonary 
      Medicine, National and Kapodistrian University of Athens, School of Medicine, 
      Evangelismos Hospital, Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150805
PL  - Australia
TA  - Respirology
JT  - Respirology (Carlton, Vic.)
JID - 9616368
RN  - 0 (Antineoplastic Agents)
RN  - 0 (NF-kappa B)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Lung Neoplasms/*drug therapy
MH  - Mesothelioma/*drug therapy
MH  - Mesothelioma, Malignant
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Neovascularization, Pathologic/prevention & control
MH  - Pleural Neoplasms/*drug therapy
MH  - Signal Transduction
MH  - Sirolimus/*analogs & derivatives/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Tumor Microenvironment/drug effects/immunology
OTO - NOTNLM
OT  - mechanistic target of rapamycin
OT  - mesothelioma
OT  - pleural effusion
OT  - temsirolimus
OT  - tumour
EDAT- 2015/08/08 06:00
MHDA- 2016/06/03 06:00
CRDT- 2015/08/07 06:00
PHST- 2015/02/19 00:00 [received]
PHST- 2015/04/16 00:00 [revised]
PHST- 2015/05/03 00:00 [accepted]
PHST- 2015/08/07 06:00 [entrez]
PHST- 2015/08/08 06:00 [pubmed]
PHST- 2016/06/03 06:00 [medline]
AID - 10.1111/resp.12604 [doi]
PST - ppublish
SO  - Respirology. 2015 Nov;20(8):1263-71. doi: 10.1111/resp.12604. Epub 2015 Aug 5.