PMID- 28765947
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20181113
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 38
IP  - 4
DP  - 2017 Oct
TI  - Acid ceramidase confers radioresistance to glioblastoma cells.
PG  - 1932-1940
LID - 10.3892/or.2017.5855 [doi]
AB  - Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy 
      of the central nervous system. The standard treatment protocol, which involves 
      surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), 
      still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or 
      progression, developing resistance to standard treatment. This study demonstrates 
      that GBMs acquire resistance to radiation via upregulation of acid ceramidase 
      (ASAH1) and sphingosine‑1-phosphate (Sph-1P). Moreover, inhibition of ASAH1 and 
      Sph-1P, either with humanized monoclonal antibodies, small molecule drugs (i.e. 
      carmofur), or a combination of both, led to suppression of GBM cell growth. These 
      results suggest that ASAH1 and Sph-1P may be excellent targets for the treatment 
      of new GBMs and recurrent GBMs, especially since the latter overexpresses ASAH1.
FAU - Doan, Ninh B
AU  - Doan NB
AD  - Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, 
      WI 53226, USA.
FAU - Nguyen, Ha S
AU  - Nguyen HS
AD  - Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, 
      USA.
FAU - Al-Gizawiy, Mona M
AU  - Al-Gizawiy MM
AD  - Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Mueller, Wade M
AU  - Mueller WM
AD  - Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, 
      USA.
FAU - Sabbadini, Roger A
AU  - Sabbadini RA
AD  - Department of Biology, San Diego State University, and Lpath Inc., San Diego, CA 
      92121, USA.
FAU - Rand, Scott D
AU  - Rand SD
AD  - Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Connelly, Jennifer M
AU  - Connelly JM
AD  - Department of Neurology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Chitambar, Christopher R
AU  - Chitambar CR
AD  - Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Schmainda, Kathleen M
AU  - Schmainda KM
AD  - Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Mirza, Shama P
AU  - Mirza SP
AD  - Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, 
      WI 53226, USA.
LA  - eng
GR  - R01 CA082500/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170728
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Lysophospholipids)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 3.5.1.23 (ASAH1 protein, human)
RN  - EC 3.5.1.23 (Acid Ceramidase)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Acid Ceramidase/biosynthesis/*metabolism
MH  - Brain Neoplasms/*enzymology/metabolism/pathology/*radiotherapy
MH  - Cell Line, Tumor
MH  - Glioblastoma/*enzymology/metabolism/pathology/*radiotherapy
MH  - Humans
MH  - Immunohistochemistry
MH  - Lysophospholipids/metabolism
MH  - Neoplasm Recurrence, Local/enzymology/pathology
MH  - Radiation Tolerance
MH  - Sphingosine/analogs & derivatives/metabolism
MH  - Up-Regulation
PMC - PMC5652937
EDAT- 2017/08/03 06:00
MHDA- 2018/05/01 06:00
PMCR- 2017/07/28
CRDT- 2017/08/03 06:00
PHST- 2017/01/02 00:00 [received]
PHST- 2017/06/19 00:00 [accepted]
PHST- 2017/08/03 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2017/08/03 06:00 [entrez]
PHST- 2017/07/28 00:00 [pmc-release]
AID - or-38-04-1932 [pii]
AID - 10.3892/or.2017.5855 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Oct;38(4):1932-1940. doi: 10.3892/or.2017.5855. Epub 2017 Jul 28.