PMID- 22658458
OWN - NLM
STAT- MEDLINE
DCOM- 20130507
LR  - 20211203
IS  - 1938-0674 (Electronic)
IS  - 1533-0028 (Print)
IS  - 1533-0028 (Linking)
VI  - 11
IP  - 4
DP  - 2012 Dec
TI  - Multiplexed protein signal pathway mapping identifies patients with rectal cancer 
      that responds to neoadjuvant treatment.
PG  - 268-74
LID - S1533-0028(12)00068-0 [pii]
LID - 10.1016/j.clcc.2012.05.003 [doi]
AB  - BACKGROUND: Currently there is no reliable technique for predicting clinical or 
      pathologic complete tumor response after radiochemotherapy (RCT) in patients with 
      rectal cancer. We applied reverse phase protein microarray (RPMA) technology to 
      find a signal pathway that may predict the response to preoperative treatment. 
      PATIENTS AND METHODS: Fifteen rectal cancer samples were collected during 
      preoperative RCT. Seven patients had a good response to preoperative therapy 
      (Mandard grade I-II) and 8 patients had a poor response (Mandard grade III-V). 
      Using laser capture microdissection (LCM) and RPMA analysis, we measured the 
      phosphorylation level of nearly 80 end points and analyzed the signaling 
      pathways. RESULTS: We identified 4 signaling proteins whose phosphorylation 
      levels were significantly different (P < .05) between the good vs. poor 
      responders; CHK2 and beta-catenin were more highly phosphorylated in poor 
      responders, whereas PDK1 and glycogen synthase kinase (GSK)-3alpha/beta had lower 
      phosphorylation levels in poor responders. Interestingly GSK-3alpha/beta, beta-catenin, and 
      PDK1 are all present in the phosphatidylinositol-3-kinase (PI3K)-AKT signaling 
      pathway. CONCLUSIONS: Based on our results, we hypothesize that the activating 
      state of the PI3K-AKT pathway can stratify patients who could benefit most from 
      neoadjuvant treatment. Moreover, identification of theranostic targets has the 
      potential to pinpoint new therapeutic strategies for the nonresponsive 
      population.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Mammano, Enzo
AU  - Mammano E
AD  - Clinica Chirurgica II, Department of Surgical, Oncological and 
      Gastroenterological Sciences, University of Padova, Padova, Italy. 
      texaua@libero.it
FAU - Galdi, Francesca
AU  - Galdi F
FAU - Pierobon, Mariaelena
AU  - Pierobon M
FAU - Tessari, Emanuela
AU  - Tessari E
FAU - Deng, Jianghong
AU  - Deng J
FAU - Pucciarelli, Salvatore
AU  - Pucciarelli S
FAU - Agostini, Marco
AU  - Agostini M
FAU - De Marchi, Francesco
AU  - De Marchi F
FAU - Canzonieri, Vincenzo
AU  - Canzonieri V
FAU - De Paoli, Antonino
AU  - De Paoli A
FAU - Belluco, Claudio
AU  - Belluco C
FAU - Liotta, Lance
AU  - Liotta L
FAU - Petricoin, Emanuel
AU  - Petricoin E
FAU - Pilati, Pierluigi
AU  - Pilati P
FAU - Nitti, Donato
AU  - Nitti D
LA  - eng
GR  - R21 CA125698/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20120602
PL  - United States
TA  - Clin Colorectal Cancer
JT  - Clinical colorectal cancer
JID - 101120693
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (PDK1 protein, human)
RN  - 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
RN  - 0 (beta Catenin)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - EC 2.7.11.1 (CHEK2 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 2.7.11.26 (glycogen synthase kinase 3 alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*metabolism
MH  - Checkpoint Kinase 2
MH  - Female
MH  - Follow-Up Studies
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Neoadjuvant Therapy
MH  - Neoplasm Grading
MH  - Phosphorylation
MH  - Prognosis
MH  - Protein Array Analysis
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyruvate Dehydrogenase Acetyl-Transferring Kinase
MH  - Rectal Neoplasms/drug therapy/*metabolism/pathology
MH  - *Signal Transduction
MH  - beta Catenin/metabolism
PMC - PMC3786114
MID - NIHMS477152
EDAT- 2012/06/05 06:00
MHDA- 2013/05/08 06:00
PMCR- 2013/09/29
CRDT- 2012/06/05 06:00
PHST- 2011/08/02 00:00 [received]
PHST- 2012/03/05 00:00 [revised]
PHST- 2012/05/02 00:00 [accepted]
PHST- 2012/06/05 06:00 [entrez]
PHST- 2012/06/05 06:00 [pubmed]
PHST- 2013/05/08 06:00 [medline]
PHST- 2013/09/29 00:00 [pmc-release]
AID - S1533-0028(12)00068-0 [pii]
AID - 10.1016/j.clcc.2012.05.003 [doi]
PST - ppublish
SO  - Clin Colorectal Cancer. 2012 Dec;11(4):268-74. doi: 10.1016/j.clcc.2012.05.003. 
      Epub 2012 Jun 2.