PMID- 21573932
OWN - NLM
STAT- MEDLINE
DCOM- 20120827
LR  - 20211020
IS  - 2211-3436 (Electronic)
IS  - 2211-3428 (Linking)
VI  - 34
IP  - 4
DP  - 2011 Aug
TI  - Tumor necrosis factor-alpha is associated with positive lymph node status in patients 
      with recurrence of colorectal cancer-indications for anti-TNF-alpha agents in cancer 
      treatment.
PG  - 315-26
LID - 10.1007/s13402-011-0027-7 [doi]
AB  - INTRODUCTION: The progressive growth of malignancies is accompanied by a decline 
      in the immune response through mechanisms which are poorly understood. Apoptosis 
      and induction of inflammation by tumor released cytokines as tumor escape 
      mechanisms have been proposed to play an important role in colorectal 
      carcinogenesis. METHODS: Expression of Tumor necrosis factor-alpha (TNF-alpha) was 
      analyzed in colorectal cancer specimen and the cancer cell line HT-29 by 
      immunohistochemistry and RT-PCR. TNF-alpha expression on protein and mRNA level were 
      correlated with clinical characteristics and impact on survival. TNFR-1 was 
      co-labelled with TNF-alpha and CD8+ cytotoxic T cells in immunofluorescence double 
      staining experiments. RESULTS: 94% (n = 98/104) of the patients with CRC 
      expressed TNF-alpha. High TNF-alpha expression was significantly associated with positive 
      lymph node stage and recurrence of the tumor. Multivariate analysis revealed high 
      TNF-alpha expression as an independent prognostic factor. Immunohistochemistry was 
      correlated with RT-PCR results (small te, Cyrillic = 0.794). Immunofluorescence double staining 
      experiments revealed increased TNFR-1 expression by CD8+ cells. CONCLUSIONS: 
      TNF-alpha expression by tumor cells may be an efficient immunological escape 
      mechanism by inflammation-enhanced metastases and probably by induction of 
      apoptosis in tumor-infiltrating CD8+ immune cells resulting in a down regulation 
      of the tumoral immune response. Our data support the role of tumor-derived TNF-alpha 
      expression as an important promoter of tumoral immune escape mechanisms and 
      malignant progression, and suggest that analysis on either protein 
      (immunohistochemistry) or RNA level (RT-PCR) can be used effectively in this 
      respect. Targeting TNF-alpha may be a promising option, especially in cases with high 
      TNF-alpha expression and positive lymph node metastases.
FAU - Grimm, M
AU  - Grimm M
AD  - Department of General-, Visceral-, Vascular and Pediatric Surgery, University of 
      Wuerzburg Hospital, Germany. Grimm_M@chirurgie.uni-wuerzburg.de
FAU - Lazariotou, M
AU  - Lazariotou M
FAU - Kircher, S
AU  - Kircher S
FAU - Hofelmayr, A
AU  - Hofelmayr A
FAU - Germer, C T
AU  - Germer CT
FAU - von Rahden, B H A
AU  - von Rahden BH
FAU - Waaga-Gasser, A M
AU  - Waaga-Gasser AM
FAU - Gasser, M
AU  - Gasser M
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Cell Oncol (Dordr)
JT  - Cellular oncology (Dordrecht)
JID - 101552938
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adenocarcinoma/genetics/pathology
MH  - Aged
MH  - Antineoplastic Agents/*pharmacology/*therapeutic use
MH  - CD8-Positive T-Lymphocytes/drug effects/pathology
MH  - Colorectal Neoplasms/*drug therapy/genetics/*pathology
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymph Nodes/drug effects/metabolism/*pathology
MH  - Lymphatic Metastasis/pathology
MH  - Lymphocytes, Tumor-Infiltrating/drug effects/pathology
MH  - Male
MH  - Middle Aged
MH  - Observer Variation
MH  - Prognosis
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Recurrence
MH  - Survival Analysis
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/genetics/*metabolism
EDAT- 2011/05/17 06:00
MHDA- 2012/08/28 06:00
CRDT- 2011/05/17 06:00
PHST- 2011/05/17 06:00 [entrez]
PHST- 2011/05/17 06:00 [pubmed]
PHST- 2012/08/28 06:00 [medline]
AID - 10.1007/s13402-011-0027-7 [doi]
PST - ppublish
SO  - Cell Oncol (Dordr). 2011 Aug;34(4):315-26. doi: 10.1007/s13402-011-0027-7.