Cancer Research and Treatment

Ryoung Hee Nam

3 Articles

Gastrointestinal cancer

Anti–PD-L1 Antibody and/or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Jina Choi, Ha-Na Lee; Cancer Res Treat. 2023;55(3):894-909. Published online January 9, 2023; DOI: https://doi.org/10.4143/crt.2022.1427

Purpose
17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti–PD-L1 and/or estrogen treatment in MC38 colon cancer model.
Materials and Methods
A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti–PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition.
Results
At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti–PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti–PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti–PD-L1 group.
Conclusion
Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti–PD-L1 might contribute to treatment of MC38 colon cancer.

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Distribution and roles of Ligilactobacillus murinus in hosts
Zhou Chuandong, Jicong Hu, Jiawen Li, Yuting Wu, Chan Wu, Guanxi Lai, Han Shen, Fenglin Wu, Changli Tao, Song Liu, Wenfeng Zhang, Hongwei Shao
Microbiological Research.2024; 282: 127648. CrossRef
Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
Zihong Wu, Yuqing Huang, Renyi Zhang, Chuan Zheng, Fengming You, Min Wang, Chong Xiao, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
17β-estradiol in colorectal cancer: friend or foe?
Zihong Wu, Chong Xiao, Jiamei Wang, Min Zhou, Fengming You, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
Sexual dimorphism of gut microbiota in colorectal cancer
Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
Chinese Science Bulletin.2024;[Epub] CrossRef
Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer
Zihong Wu, Yi Sun, Wenbo Huang, Zhenzhen Jin, Fengming You, Xueke Li, Chong Xiao
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes
Zhihui Song, An Yan, Zehui Guo, Yuhang Zhang, Tao Wen, Zhenzhen Li, Zhihua Yang, Rui Chen, Yi Wang
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef

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Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Ha-Na Lee; Cancer Res Treat. 2023;55(1):196-218. Published online July 1, 2022; DOI: https://doi.org/10.4143/crt.2022.080

Abstract PDF Supplementary Material PubReader ePub

Purpose
Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model.
Materials and Methods
Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch.
Results
The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls.
Conclusion
In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis.

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Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
Zihong Wu, Yuqing Huang, Renyi Zhang, Chuan Zheng, Fengming You, Min Wang, Chong Xiao, Xueke Li
Cell Communication and Signaling.2024;[Epub] CrossRef
Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin
Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-mo Hayashi, Gen Watanabe, Kentaro Nagaoka
The Journal of Toxicological Sciences.2024; 49(4): 151. CrossRef
Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics
Vineet Singh, Kanika Mahra, DaRyung Jung, Jae-Ho Shin
Probiotics and Antimicrobial Proteins.2024; 16(5): 1744. CrossRef
Role of sex steroids in colorectal cancer: pathomechanisms and medical applications
Jianglan Wu
American Journal of Cancer Research.2024; 14(7): 3200. CrossRef
Gender-affirming hormonal therapy induces a gender-concordant fecal metagenome transition in transgender individuals
Timur Liwinski, Matthias K. Auer, Johanna Schröder, Ina Pieknik, Christian Casar, Dorothee Schwinge, Lara Henze, Günter K. Stalla, Undine E. Lang, Alina von Klitzing, Peer Briken, Thomas Hildebrandt, Jeanne C. Desbuleux, Sarah V. Biedermann, Paul-Martin H
BMC Medicine.2024;[Epub] CrossRef
N-acyl glycines produced by commensal bacteria potentiate GLP-1 secretion as GPCR ligands
Anna Drzazga, Przemysław Bernat, Adriana Nowak, Marcin Szustak, Eliza Korkus, Edyta Gendaszewska-Darmach, Maria Koziołkiewicz
Biomedicine & Pharmacotherapy.2024; 180: 117467. CrossRef
Role of intestinal testosterone-degrading bacteria and 3/17β-HSD in the pathogenesis of testosterone deficiency-induced hyperlipidemia in males
Jun Tao, Wen Dai, Yongnan Lyu, Hang Liu, Juan Le, Ting Sun, Qian Yao, Zhiming Zhao, Xuejun Jiang, Yan Li
npj Biofilms and Microbiomes.2024;[Epub] CrossRef
Sexual dimorphism of gut microbiota in colorectal cancer
Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
Chinese Science Bulletin.2024;[Epub] CrossRef
Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer
Zihong Wu, Yi Sun, Wenbo Huang, Zhenzhen Jin, Fengming You, Xueke Li, Chong Xiao
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
From-Toilet-to-Freezer: A Review on Requirements for an Automatic Protocol to Collect and Store Human Fecal Samples for Research Purposes
Frances Widjaja, Ivonne M. C. M. Rietjens
Biomedicines.2023; 11(10): 2658. CrossRef
Murine models of colorectal cancer: the azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colitis-associated cancer
Dzhuliia Dzhalilova, Natalia Zolotova, Nikolai Fokichev, Olga Makarova
PeerJ.2023; 11: e16159. CrossRef

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Effect of Estradiol in an Azoxymethane/Dextran Sulfate Sodium-Treated Mouse Model of Colorectal Cancer: Implication for Sex Difference in Colorectal Cancer Development: Hee Jin Son, Sung Hwa Sohn, Nayoung Kim, Ha-Na Lee, Sun Min Lee, Ryoung Hee Nam, Ji Hyun Park, Chin-Hee Song, Eun Shin, Hee Young Na, Joo Sung Kim, Dong Ho Lee, Young-Joon Surh; Cancer Res Treat. 2019;51(2):632-648. Published online August 1, 2018; DOI: https://doi.org/10.4143/crt.2018.060

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study demonstrates that estradiol downregulates inflammation and inhibits colorectal cancer (CRC) development in azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model.
Materials and Methods
AOM/DSS-treated male and female mice were sacrificed at weeks 2, 10, and 16, to assess estrogen effects on colitis and carcinogenesis. Macroscopic and histologic severity of colitis and Western blot and quantitative real-time polymerase chain reaction were evaluated, to measure inflammatory mediators and cytokines.
Results
Compared with AOM/DSS-treated male mice (M-AOM/DSS group), AOM/DSS-treated male mice with estradiol administration (M-AOM/DSS+estr group) displayed at week 2 significantly decreased severity of colitis. At weeks 10 and 16, AOM/DSS-treated female mice (F-AOM/DSS group) and the M-AOM/DSS+estr group showed significantly lower tumor multiplicity compared with the M-AOM/DSS group. At week 2, F-AOM/DSS group had a lower level of nuclear factor-κB (NF-κB) expression and higher level of nuclear factor erythroid 2-related factor 2 (Nrf2) expression, compared to the M-AOM/DSS group. At week 2, expression levels of NF-κB and its related mediators decreased in the M-AOM/DSS+estr group, while levels of Nrf2 and Nrf2-related anti-oxidant enzymes increased. In addition, estradiol significantly increased Nod-like receptor protein 3 (NLRP3) inflammasome expressions in AOM/DSS-treated male mice. In contrast, at weeks 10 and 16, Nrf2 and its-related anti-oxidant enzymes and NLRP3 inflammasome were highly expressed in M-AOM/DSS group and in F-AOM/DSS group, who developed cancer.
Conclusion
The data suggest that estradiol inhibits the initiation of CRC by regulating Nrf2-related pathways. Moreover, these imply the dual role of Nrf2 and NLRP3 inflammasome, including promotion of tumor progression upon tumor initiation.

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Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model
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Cancer Research and Treatment.2023; 55(1): 196. CrossRef
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Anti–PD-L1 Antibody and/or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model
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Combination treatment with 17β-estradiol and anti-PD-L1 suppresses MC38 tumor growth by reducing PD-L1 expression and enhancing M1 macrophage population in MC38 colon tumor model
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The Enhanced Inhibitory Effect of Estrogen on PD-L1 Expression Following Nrf2 Deficiency in the AOM/DSS Model of Colitis-Associated Cancer
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17β-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice
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17β-Estradiol strongly inhibits azoxymethane/dextran sulfate sodium-induced colorectal cancer development in Nrf2 knockout male mice
Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Joo Hee Son, Jeong Eun Yu, Eun Shin, Ha-Na Lee, Do-Hee Kim, Young-Joon Surh
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Effects of 17β-Estradiol on Colorectal Cancer Development after Azoxymethane/Dextran Sulfate Sodium Treatment of Ovariectomized Mice
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17-β estradiol exerts anti-inflammatory effects through activation of Nrf2 in mouse embryonic fibroblasts
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