PubTransformer

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PMID- 28739697
OWN - NLM
STAT- MEDLINE
DA  - 20170725
DCOM- 20170810
LR  - 20170810
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 37
IP  - 8
DP  - 2017 Aug
TI  - Z-360 Suppresses Tumor Growth in MIA PaCa-2-bearing Mice via Inhibition of
      Gastrin-induced Anti-Apoptotic Effects.
PG  - 4127-4137
AB  - BACKGROUND/AIM: The aim of the study was to evaluate the anti-tumor mechanism of 
      Z-360, a gastrin/cholecystokinin-2 receptor (CCK2R) antagonist, in MIA PaCa-2
      cells and in a subcutaneous xenograft mice model. MATERIALS AND METHODS: The
      anti-tumor effects of Z-360 and/or gemcitabine were monitored using a MIA PaCa-2 
      xenograft model. The effect of Z-360 on apoptosis in the model was examined by
      TUNEL staining and real-time PCR analysis and the effect in MIA PaCa-2 cells
      stably expressing human CCK2R was also evaluated by caspase-3/7 activity.
      RESULTS: In this xenograft model, Z-360 significantly reduced the tumor weight,
      increased TUNEL-positive cells and suppressed the expression of anti-apoptosis
      factors such as survivin, XIAP and Mcl-1, and these effects of Z-360 combined
      with gemcitabine were more effective. Furthermore, gastrin-17 and gastrin-34
      inhibited apoptosis in vitro and Z-360 dose-dependently abrogated this effect.
      CONCLUSION: These results suggest that Z-360 exerts an anti-tumor effect through 
      a reduction in anti-apoptosis factors by blocking CCK2R.
CI  - Copyright(c) 2017, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Shiomi, Yoshihiro
AU  - Shiomi Y
AD  - Central Research Laboratories, ZERIA Pharmaceutical Co., Ltd., Kumagaya, Japan
      [email protected]
FAU - Yoshimura, Makoto
AU  - Yoshimura M
AD  - Central Research Laboratories, ZERIA Pharmaceutical Co., Ltd., Kumagaya, Japan.
FAU - Kuki, Kazumasa
AU  - Kuki K
AD  - Central Research Laboratories, ZERIA Pharmaceutical Co., Ltd., Kumagaya, Japan.
FAU - Hori, Yuko
AU  - Hori Y
AD  - Central Research Laboratories, ZERIA Pharmaceutical Co., Ltd., Kumagaya, Japan.
FAU - Tanaka, Takao
AU  - Tanaka T
AD  - Central Research Laboratories, ZERIA Pharmaceutical Co., Ltd., Kumagaya, Japan.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Benzodiazepinones)
RN  - 0 (Gastrins)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (MCL1 protein, human)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (Receptor, Cholecystokinin B)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
RN  - 0 (Z-360)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 60748-06-3 (gastrin 17)
RN  - B76N6SBZ8R (gemcitabine)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.99.- (gastrinase)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Benzodiazepinones/*administration & dosage
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - Endopeptidases/administration & dosage
MH  - Gastrins/administration & dosage
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins/biosynthesis
MH  - Mice
MH  - Myeloid Cell Leukemia Sequence 1 Protein/biosynthesis
MH  - Pancreatic Neoplasms/*drug therapy/genetics/pathology
MH  - Receptor, Cholecystokinin B/antagonists & inhibitors/biosynthesis/*genetics
MH  - X-Linked Inhibitor of Apoptosis Protein/biosynthesis
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - MiaPaCa-2
OT  - Pancreatic cancer
OT  - Z-360
OT  - apoptosis
OT  - cholecystokinin-2 receptor
OT  - gastrin
OT  - gemcitabine
OT  - xenograft
EDAT- 2017/07/26 06:00
MHDA- 2017/08/11 06:00
CRDT- 2017/07/26 06:00
PHST- 2017/06/06 [received]
PHST- 2017/06/29 [revised]
PHST- 2017/06/30 [accepted]
AID - 37/8/4127 [pii]
PST - ppublish
SO  - Anticancer Res. 2017 Aug;37(8):4127-4137.