PMID- 31069565
OWN - NLM
STAT- In-Data-Review
LR  - 20190610
IS  - 1573-7276 (Electronic)
IS  - 0262-0898 (Linking)
VI  - 36
IP  - 3
DP  - 2019 Jun
TI  - Identification of canonical NFkappaB (C-NFkappaB) pathway in uveal melanoma and
      their relation with patient outcome.
PG  - 271-290
LID - 10.1007/s10585-019-09969-y [doi]
AB  - Inflammation in uveal melanoma (UM) is linked to a bad prognosis. It is rare type
      of cancer, of which the metastases are usually fatal within a year. Infiltration 
      with an inflammatory infiltrate increases with disease progression but does not
      seem to inhibit metastasis. The Canonical NFkappaB (C-NFkappaB) pathway is known 
      to play a crucial role in tumor inflammation. We therefore, studied the
      expression of canonical NFkappaB proteins and their prognostic relevance in UM.
      Our study evaluated the expression of C-NFkappaB proteins (p65, p50, and c-Rel)
      by using immunohistochemistry on sections from 75 formalin-fixed UM. Activation
      of the NFkappaB subunit was determined on fresh tumor specimens by measuring the 
      DNA-binding activity in nuclei using an NFkappaB ELISA assay. Real-time PCR was
      performed on frozen material on 58 tumors. The presence of native C-NFkappaB
      heterodimers (p65/p50 and c-Rel/p50) was confirmed by co-immunoprecipitation
      followed by Western blotting. We observed a high nuclear immunoreactivity of p65,
      p50, and c-Rel proteins in 54, 60 and 41% UM cases, respectively. Expression of
      C-NFkappaB proteins significantly correlated with parameters which are related to
      the inflammatory environment of UM. Nuclear immunoreactivity of p65 and p50 was
      associated with lower patient survival (p = 0.041; p = 0.048) while c-Rel was
      not. Our finding reveals that C-NFkappaB proteins expressed are more often in UM 
      with inflammation than those without inflammation. Activation of the canonical
      NFkappaB pathway is more frequent in high risk UM patients. These observations
      might help to understand the behaviour of high risk tumors, with upregulation of 
      C-NFkappaB proteins contributing to tumor aggressiveness.
FAU - Singh, Mithalesh Kumar
AU  - Singh MK
AD  - Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All
      India Institute of Medical Sciences, New Delhi, India.
FAU - Singh, Lata
AU  - Singh L
AD  - Departrment of Biosciences, Jamia Millia Islamia, New Delhi, India.
FAU - Pushker, Neelam
AU  - Pushker N
AD  - Department of Ophthalmology, Dr. R. P. Centre for Ophthalmic Sciences, All India 
      Institute of Medical Sciences, New Delhi, India.
FAU - Saini, Neeru
AU  - Saini N
AD  - Functional Genomics Unit, Institute of Genomics and Integrative Biology, New
      Delhi, India.
FAU - Meel, Rachna
AU  - Meel R
AD  - Department of Ophthalmology, Dr. R. P. Centre for Ophthalmic Sciences, All India 
      Institute of Medical Sciences, New Delhi, India.
FAU - Chosdol, Kunzang
AU  - Chosdol K
AD  - Department of Biochemistry, AIIMS, New Delhi, India.
FAU - Bakhshi, Sameer
AU  - Bakhshi S
AD  - Department of Medical Oncology, IRCH, AIIMS, New Delhi, India.
FAU - Sen, Seema
AU  - Sen S
AD  - Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All
      India Institute of Medical Sciences, New Delhi, India.
FAU - Venkatesh, Pradeep
AU  - Venkatesh P
AD  - Department of Ophthalmology, Dr. R. P. Centre for Ophthalmic Sciences, All India 
      Institute of Medical Sciences, New Delhi, India.
FAU - Chawla, Bhavna
AU  - Chawla B
AD  - Department of Ophthalmology, Dr. R. P. Centre for Ophthalmic Sciences, All India 
      Institute of Medical Sciences, New Delhi, India.
FAU - Kaur, Jasbir
AU  - Kaur J
AD  - Department of Ocular Biochemistry, Dr. R. P. Centre for Ophthalmic Sciences, All 
      India Institute of Medical Sciences, New Delhi, India.
FAU - Kashyap, Seema
AU  - Kashyap S
AUID- ORCID: http://orcid.org/0000-0002-8746-9017
AD  - Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All
      India Institute of Medical Sciences, New Delhi, India. dr_skashyap@hotmail.com.
LA  - eng
GR  - 3/2/2/327/2015-NCD-III/Indian Council of Medical Research (ICMR)
PT  - Journal Article
DEP - 20190508
PL  - Netherlands
TA  - Clin Exp Metastasis
JT  - Clinical & experimental metastasis
JID - 8409970
OTO - NOTNLM
OT  - Immunohistochemistry
OT  - Inflammation
OT  - NFkappaB
OT  - Uveal melanoma
OT  - c-Rel/p50 heterodimer
OT  - p65/p50
EDAT- 2019/05/10 06:00
MHDA- 2019/05/10 06:00
CRDT- 2019/05/10 06:00
PHST- 2019/01/29 00:00 [received]
PHST- 2019/05/03 00:00 [accepted]
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2019/05/10 06:00 [medline]
PHST- 2019/05/10 06:00 [entrez]
AID - 10.1007/s10585-019-09969-y [doi]
AID - 10.1007/s10585-019-09969-y [pii]
PST - ppublish
SO  - Clin Exp Metastasis. 2019 Jun;36(3):271-290. doi: 10.1007/s10585-019-09969-y.
      Epub 2019 May 8.