PMID- 26048456
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20190221
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 51
IP  - 12
DP  - 2015 Aug
TI  - Baseline caspase activity predicts progression free survival of 
      temsirolimus-treated head neck cancer patients.
PG  - 1596-602
LID - S0959-8049(15)00452-9 [pii]
LID - 10.1016/j.ejca.2015.05.021 [doi]
AB  - Squamous cell cancer of the head and neck (SCCHN) is a frequent aggressive 
      malignancy with limited therapeutic options. Increasing evidence suggests that 
      mammalian target of rapamycin (mTOR)-inhibitors might be effective in advanced 
      SCCHN. However, non-invasive biomarkers for early prediction of treatment 
      efficacy are not established in SCCHN. Highly proliferating tumours are 
      characterised by enhanced cell turnover which is associated with enhanced 
      apoptosis. During apoptosis of epithelial cells caspases cleave cytokeratin 
      (CK)-18 can be detected in the blood. In this study we analysed sera from 
      patients with relapsed or metastatic SCCHN patients who have been treated with 
      temsirolimus for caspase-cleaved and total (caspase-cleaved and uncleaved) CK-18 
      by enzyme-linked immunosorbent assays (ELISAs). In addition, caspase-3 activity 
      was detected by luminometric substrate assay. SCCHN patients revealed higher 
      serum levels of those biomarkers compared to healthy controls. Importantly, 
      patients with short progression-free survival (PFS) showed higher serum levels of 
      caspase-3 activity compared to patients with longer PFS (⩾ 2months). Caspase-3 
      activity is inversely correlated with PFS. A cut-off value for caspase-3 activity 
      was determined that correctly predicted PFS <2months with a sensitivity of 86% 
      and a specificity of 67%. These data demonstrate that detection of serum 
      caspase-3 activity might be a useful non-invasive biomarker for early 
      identification of SCCHN patients not responding to treatment with novel targeted 
      therapies such as mTOR-inhibitors.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - John, Katharina
AU  - John K
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
FAU - Rosner, Imme
AU  - Rosner I
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany.
FAU - Keilholz, Ulrich
AU  - Keilholz U
AD  - Charite Comprehensive Cancer Center, University of Berlin, Berlin, Germany.
FAU - Gauler, Thomas
AU  - Gauler T
AD  - University Hospital Essen, Essen, Germany.
FAU - Bantel, Heike
AU  - Bantel H
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
FAU - Grunwald, Viktor
AU  - Grunwald V
AD  - Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, 
      Hannover Medical School, Hannover, Germany. Electronic address: 
      Gruenwald.Viktor@mh-hannover.de.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20150602
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 3.4.22.- (Caspases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Biomarkers, Tumor/*blood
MH  - Carcinoma, Squamous Cell/blood/*drug therapy/enzymology
MH  - Caspases/*blood
MH  - Disease-Free Survival
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Head and Neck Neoplasms/blood/*drug therapy/enzymology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Sirolimus/*analogs & derivatives/therapeutic use
MH  - Squamous Cell Carcinoma of Head and Neck
OTO - NOTNLM
OT  - Apoptosis
OT  - Biomarker
OT  - Caspase-activity
OT  - Squamous cell cancer of the head and neck
OT  - mTOR-inhibitor
EDAT- 2015/06/07 06:00
MHDA- 2015/09/22 06:00
CRDT- 2015/06/07 06:00
PHST- 2015/05/05 00:00 [received]
PHST- 2015/05/09 00:00 [accepted]
PHST- 2015/06/07 06:00 [entrez]
PHST- 2015/06/07 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
AID - S0959-8049(15)00452-9 [pii]
AID - 10.1016/j.ejca.2015.05.021 [doi]
PST - ppublish
SO  - Eur J Cancer. 2015 Aug;51(12):1596-602. doi: 10.1016/j.ejca.2015.05.021. Epub 
      2015 Jun 2.