Evidence map›Paper›PMID 29642386›Full record

ArticleInternational journal of molecular sciences2018

Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture.

Tatsuya Usui, Masashi Sakurai, Koji Umata, Mohamed Elbadawy, Takashi Ohama, Hideyuki Yamawaki, Shoichi Hazama, Hiroko Takenouchi, Masao Nakajima, Ryouichi Tsunedomi and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
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

62 citing papers in PubMed, 99 citations in OpenAlex.

  1. Review
  2. From mono- to multi-cellularFrontiers in cell and developmental biology · 2026
    Review
  3. Review
  4. Review
  5. PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling.Journal of experimental & clinical cancer research : CR · 2025
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. The Impact of Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024
    Review
  19. Review
  20. Review

2 more citing papers are in PubMed but not listed here.

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

15 authors at 4 institutions in 2 countries.

Tatsuya UsuiLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. fu7085@go.tuat.ac.jp.
Masashi SakuraiLaboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. sakurai@yamaguchi-u.ac.jp.
Koji UmataLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. t007tb@yamaguchi-u.ac.jp.
Mohamed ElbadawyLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. kanedam@cc.tuat.ac.jp.ORCID 0000-0001-9368-1535
Takashi OhamaLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. t.ohama@yamaguchi-u.ac.jp.
Hideyuki YamawakiLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada City, Aomori 034-8628, Japan. yamawaki@vmas.kitasato-u.ac.jp.
Shoichi HazamaDepartment of Translational Research and Developmental Therapeutics against Cancer, School of Medicine, Yamaguchi University, 1-1-1 Ogushi, Ube, Yamaguchi 755-8505, Japan. hazama@yamaguchi-u.ac.jp.
Hiroko TakenouchiDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1-1 Ogushi, Ube, Yamaguchi 755-8505, Japan. h-take@yamaguchi-u.ac.jp.
Masao NakajimaDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1-1 Ogushi, Ube, Yamaguchi 755-8505, Japan. masao-y@yamaguchi-u.ac.jp.
Ryouichi TsunedomiDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1-1 Ogushi, Ube, Yamaguchi 755-8505, Japan. tsune-r@yamaguchi-u.ac.jp.
Nobuaki SuzukiDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1-1 Ogushi, Ube, Yamaguchi 755-8505, Japan. nobusuzu@yamaguchi-u.ac.jp.
Hiroaki NaganoDepartment of Gastroenterological, Breast and Endocrine Surgery, Graduate School of Medicine, Yamaguchi University, 1-1-1 Ogushi, Ube, Yamaguchi 755-8505, Japan. hnagano@yamaguchi-u.ac.jp.
Koichi SatoLaboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. k-sato@yamaguchi-u.ac.jp.ORCID 0000-0001-5265-0775
Masahiro KanedaLaboratory of Veterinary Anatomy, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. kanedam@cc.tuat.ac.jp.ORCID 0000-0003-0660-7156
Kazuaki SasakiLaboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan. skazuaki@cc.tuat.ac.jp.
Yamaguchi University · JPTokyo University of Agriculture and Technology · JPBenha University · EGKitasato University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Colorectal cancer is one of the most common causes of cancer death worldwide. In patients with metastatic colorectal cancer, combination treatment with several anti-cancer drugs is employed and improves overall survival in some patients. Nevertheless, most patients with metastatic disease are not cured owing to the drug resistance. Cancer stem cells are known to regulate resistance to chemotherapy. In the previous study, we established a novel three-dimensional organoid culture model from tumor colorectal tissues of human patients using an air-liquid interface (ALI) method, which contained numerous cancer stem cells and showed resistance to 5-fluorouracil (5-FU) and Irinotecan. Here, we investigate which inhibitor for stem cell-related signal improves the sensitivity for anti-cancer drug treatment in tumor ALI organoids. Treatment with Hedgehog signal inhibitors (AY9944, GANT61) decreases the cell viability of organoids compared with Notch (YO-01027, DAPT) and Wnt (WAV939, Wnt-C59) signal inhibitors. Combination treatment of AY9944 or GANT61 with 5-FU, Irinotecan or Oxaliplatin decreases the cell viability of tumor organoids compared with each anti-cancer drug alone treatment. Treatment with AY9944 or GANT61 inhibits expression of stem cell markers c-Myc, CD44 and Nanog, likely through the decrease of their transcription factor, GLI-1 expression. Combination treatment of AY9944 or GANT61 with 5-FU or Irinotecan also prevents colony formation of colorectal cancer cell lines HCT116 and SW480. These findings suggest that Hedgehog signals mediate anti-cancer drug resistance in colorectal tumor patient-derived ALI organoids and that the inhibitors are useful as a combinational therapeutic strategy against colorectal cancer.

Indexed as

Drug Resistance, NeoplasmCamptothecinColorectal NeoplasmsFluorouracilHCT116 CellsHedgehog ProteinsHumansHyaluronan ReceptorsIrinotecanNeoplastic Stem CellsOrganoidsOrganoplatinum CompoundsOxaliplatinProto-Oncogene Proteins c-mycPyridinesPyrimidinesCamptothecinFluorouracilGANT 61GLI1 protein, humanHedgehog ProteinsHyaluronan ReceptorsIrinotecanOrganoplatinum CompoundsOxaliplatinProto-Oncogene Proteins c-mycPyridinesPyrimidinestrans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane DihydrochlorideZinc Finger Protein GLI1chemoresistancecolorectal cancerHedgehog signalorganoidstem cell

Identifiers

PMID29642386
PMCPMC5979580
OpenAlexW2796200410

What OpenQuestion 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 OpenQuestion graph.