PMID- 27680682
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20180411
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 76
IP  - 22
DP  - 2016 Nov 15
TI  - Preclinical Validation of a Single-Treatment Infusion Modality That Can Eradicate
      Extremity Melanomas.
PG  - 6620-6630
LID - 10.1158/0008-5472.CAN-15-2764 [doi]
AB  - Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an
      effective treatment option for extremity in-transit melanoma but is toxic and
      technically challenging to deliver locoregionally. CBL0137 is an experimental
      clinical drug with broad anticancer activity in animal models, owing to its
      ability to bind DNA in a nongenotoxic manner and inactivate the FACT chromatin
      modulator essential for tumor cell viability. Here, we report that CBL0137
      delivered by ILP in a murine melanoma model is as efficacious as melphalan,
      displaying antitumor activity at doses corresponding to only a fraction of the
      systemic MTD of CBL0137. The ability to bind DNA quickly combined with a
      favorable safety profile made it possible to substitute CBL0137 in the ILP
      protocol, using an intra-arterial infusion method, to safely achieve effective
      tumor suppression. Our findings of a preclinical proof of concept for CBL0137 and
      its administration via intra-arterial infusion as a superior treatment compared
      with melphalan ILP allows for locoregional treatment anywhere a catheter can be
      placed. Cancer Res; 76(22); 6620-30. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Kim, Minhyung
AU  - Kim M
AD  - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New
      York.
AD  - Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
FAU - Neznanov, Nickolay
AU  - Neznanov N
AD  - Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New
      York.
FAU - Wilfong, Chandler D
AU  - Wilfong CD
AD  - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New
      York.
FAU - Fleyshman, Daria I
AU  - Fleyshman DI
AD  - Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New
      York.
FAU - Purmal, Andrei A
AU  - Purmal AA
AD  - Cleveland BioLabs, Inc., Buffalo, New York.
AD  - Incuron, LLC, Buffalo, New York.
FAU - Haderski, Gary
AU  - Haderski G
AD  - Buffalo BioLabs, LLC, Buffalo, New York.
FAU - Stanhope-Baker, Patricia
AU  - Stanhope-Baker P
AD  - Buffalo BioLabs, LLC, Buffalo, New York.
FAU - Burkhart, Catherine A
AU  - Burkhart CA
AD  - Buffalo BioLabs, LLC, Buffalo, New York.
FAU - Gurova, Katerina V
AU  - Gurova KV
AD  - Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New
      York.
FAU - Gudkov, Andrei V
AU  - Gudkov AV
AD  - Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New
      York.
FAU - Skitzki, Joseph J
AU  - Skitzki JJ
AD  - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New
      York. joseph.skitzki@roswellpark.org.
AD  - Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York.
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
GR  - R01 CA197967/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, N.I.H., Extramural
DEP - 20160928
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Animals
MH  - Extremities/*pathology
MH  - Female
MH  - Humans
MH  - *Infusion Pumps
MH  - Melanoma/*drug therapy/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Treatment Outcome
MH  - Validation Studies as Topic
PMC - PMC5609527
MID - NIHMS827039
EDAT- 2016/11/05 06:00
MHDA- 2017/09/12 06:00
CRDT- 2016/09/30 06:00
PHST- 2015/10/07 00:00 [received]
PHST- 2016/07/17 00:00 [revised]
PHST- 2016/09/01 00:00 [accepted]
PHST- 2016/11/05 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
PHST- 2016/09/30 06:00 [entrez]
AID - 0008-5472.CAN-15-2764 [pii]
AID - 10.1158/0008-5472.CAN-15-2764 [doi]
PST - ppublish
SO  - Cancer Res. 2016 Nov 15;76(22):6620-6630. doi: 10.1158/0008-5472.CAN-15-2764.
      Epub 2016 Sep 28.