Evidence map›Paper›PMID 39034442›Full record

ArticleJournal of cellular and molecular medicine2024

SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.

Jooyoung Lee, Jiye Kim, Ryunjin Lee, Eunkyeong Lee, Hye-In An, Yong-Jae Kwon, Hana Jin, Chan-Gi Pack, Inki Kim, Young-In Yoon and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular and molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Jooyoung LeeAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.ORCID 0000-0002-7938-8196
Jiye KimAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Ryunjin LeeAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Eunkyeong LeeAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Hye-In AnAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Yong-Jae KwonDepartment of Surgery, Gangneung Asan Hospital, University of Ulsan College of Medicine, Seoul, South Korea.
Hana JinDivision of Vascular Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Chan-Gi PackConvergence Medicine Research Center (CREDIT), Asan Institute for Life Sciences, ASAN Medical Center, Seoul, Republic of Korea.
Inki KimConvergence Medicine Research Center (CREDIT), Asan Institute for Life Sciences, ASAN Medical Center, Seoul, Republic of Korea.
Young-In YoonDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Gil-Chun ParkDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Eun-Kyoung JwaDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Jae Hyun KwonDepartment of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
Jung-Man NamgoongDivision of Pediatric Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Gi-Won SongDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Shin HwangDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Eunyoung TakAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Sung-Gyu LeeDivision of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Funding

CARCINOGENESIST32CA009054 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI EDINGER, AIMEE L, FRUMAN, DAVID ALEXANDER · 1985 to 2025
$8.6M
Asan Institute for Life Sciences, Asan Medical Center 2023IP0028National Research Foundation of Korea 2015K1A4A3046807National Research Foundation of Korea 2017R1D1A1B04032429National Research Foundation of Korea 2021R1G1A1093955National Research Foundation of Korea 2022R1A2C2006141NCI NIH HHS T32 CA009054
6 · The paper itself

Abstract

Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.

Indexed as

Carcinoma, HepatocellularHepatitis B virusLiver NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesSignal TransductionSorafenibSuperoxide Dismutase-1TOR Serine-Threonine KinasesAnimalsApoptosisCell Line, TumorCell ProliferationDitiocarbDrug Resistance, NeoplasmDitiocarbhepatitis B virus X proteinMTOR protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesSOD1 protein, humanSorafenibSuperoxide Dismutase-1TOR Serine-Threonine KinasesTrans-ActivatorsViral Regulatory and Accessory Proteinsdisulfiramhepatitis B virushepatocellular carcinomaSorafenib resistancesuperoxide dismutase

Identifiers

PMID39034442
PMCPMC11260765

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.