PMID- 38030210
OWN - NLM
STAT- MEDLINE
DCOM- 20231201
LR  - 20231217
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 43
IP  - 12
DP  - 2023 Dec
TI  - Oxidative Stress-regulating Enzymes and Endometrial Cancer Survival in Relation 
      to Metformin Intake in Diabetic Patients.
PG  - 5545-5554
LID - 10.21873/anticanres.16756 [doi]
AB  - BACKGROUND/AIM: Metformin inhibits tumorigenesis in endometrial carcinoma and 
      interferes with the expression of oxidative stress-regulating proteins, such as 
      nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated 
      protein 1 (Keap1). Although manganese superoxide dismutase (MnSOD) is vital for 
      withstanding mitochondrial oxidative stress, it has also been linked with 
      chemoresistance and poorer outcomes in several cancer types. However, data on 
      endometrial cancers are limited. This study aimed to highlight the relationship 
      between mitochondrial redox regulation and endometrial cancer survival in 
      relation to metformin consumption in women with type 2 diabetes mellitus (T2DM). 
      PATIENTS AND METHODS: Our retrospective hospital-based cohort study included 121 
      patients diagnosed with endometrial carcinoma and T2DM between 2007 and 2014. 
      Fifty-eight patients were using metformin at the time of diagnosis. Nrf2 and 
      Keap1 expression levels in the tumor samples were assessed immunohistochemically, 
      and MnSOD levels were measured both immunohistochemically and from the serum 
      samples. RESULTS: High MnSOD tissue expression was associated with better overall 
      survival among metformin users in the univariate analysis (p=0.03). When adjusted 
      for histology and stage, high serum MnSOD was associated with better overall 
      survival (HR=0.22, 95%CI=0.07-0.71, p=0.01). No association was found between 
      MnSOD, Nrf2, or Keap1 and overall survival among metformin non-users. CONCLUSION: 
      Higher expression of MnSOD in patients with endometrial cancer and T2DM is 
      associated with better overall survival if the patient is consuming metformin.
CI  - Copyright (c) 2023 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Kuusiniemi, Ewelina
AU  - Kuusiniemi E
AD  - Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing 
      Services County of North Ostrobothnia, Oulu, Finland; 
      ewelina.kuusiniemi@gmail.com.
AD  - Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
AD  - Medical Research Center, University of Oulu, Oulu University Hospital, Wellbeing 
      Services County of North Ostrobothnia, Oulu, Finland.
FAU - Karihtala, Peeter
AU  - Karihtala P
AD  - Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center 
      and University of Helsinki, Helsinki, Finland.
FAU - Puistola, Ulla
AU  - Puistola U
AD  - Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing 
      Services County of North Ostrobothnia, Oulu, Finland.
AD  - Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
AD  - Medical Research Center, University of Oulu, Oulu University Hospital, Wellbeing 
      Services County of North Ostrobothnia, Oulu, Finland.
FAU - Ahtikoski, Anne
AU  - Ahtikoski A
AD  - Department of Pathology, Fimlab Laboratories, University of Tampere, Tampere, 
      Finland.
FAU - Urpilainen, Elina
AU  - Urpilainen E
AD  - Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing 
      Services County of North Ostrobothnia, Oulu, Finland.
AD  - Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
AD  - Medical Research Center, University of Oulu, Oulu University Hospital, Wellbeing 
      Services County of North Ostrobothnia, Oulu, Finland.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 9100L32L2N (Metformin)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Metformin/therapeutic use
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Cohort Studies
MH  - Retrospective Studies
MH  - Oxidative Stress/physiology
MH  - *Endometrial Neoplasms/drug therapy
OTO - NOTNLM
OT  - Endometrial carcinoma
OT  - Keap1
OT  - MnSOD
OT  - Nrf2
OT  - metformin
OT  - oxidative stress
OT  - type 2 diabetes
EDAT- 2023/11/30 00:42
MHDA- 2023/12/01 06:44
CRDT- 2023/11/29 20:33
PHST- 2023/10/04 00:00 [received]
PHST- 2023/10/25 00:00 [revised]
PHST- 2023/11/01 00:00 [accepted]
PHST- 2023/12/01 06:44 [medline]
PHST- 2023/11/30 00:42 [pubmed]
PHST- 2023/11/29 20:33 [entrez]
AID - 43/12/5545 [pii]
AID - 10.21873/anticanres.16756 [doi]
PST - ppublish
SO  - Anticancer Res. 2023 Dec;43(12):5545-5554. doi: 10.21873/anticanres.16756.