Cancer Research and Treatment

Original Articles

The Roles of Ninjurin1 and Estrogen in Modulating AOM/DSS-Induced Colitis-Associated Colorectal Cancer in Male Mice: Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Eun Shin, Ha-Na Lee, Hoon Choi, Kyu-Won Kim, Sejin Jeon, Goo Taeg Oh; Received October 2, 2024 Accepted January 10, 2025 Published online January 13, 2025; DOI: https://doi.org/10.4143/crt.2024.959 [Accepted]

Abstract PDF: Purpose
Ninjury-induced protein 1 (Ninj1) is associated with inflammation and tumor progression and shows increased expression in various cancers. This study aimed to investigate the role of Ninj1 in colitis-associated colorectal cancer (CRC) by focusing on its interaction with 17β-estradiol (E2).
Materials and Methods
Using an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model of colitis-associated CRC, wild-type (WT) and Ninj1 knockout (KO) male mice were treated with or without E2.
Results
At week 2, Ninj1 KO mice exhibited attenuated colitis symptoms than WT mice following AOM/DSS treatment. E2 administration significantly alleviated these symptoms in both WT and Ninj1 KO mice, with reductions in the disease activity index (DAI), colon length shortening, and histopathological damage. The levels of pro-inflammatory mediators were reduced by E2 treatment in both groups, with the Ninj1 KO group showing a more pronounced response. At week 13, tumor development in Ninj1 KO mice was significantly lower than that in WT mice, particularly in the distal colon. E2 treatment inhibited tumor formation in WT mice and had a stronger inhibitory effect on distal colon tumorigenesis in Ninj1 KO mice. Immune cell populations, including the populations of macrophages and T cells, were also modulated by E2 in WT mice; however, these effects were diminished in Ninj1 KO mice.
Conclusion
These findings suggest that Ninj1 plays a role in modulating colitis and CRC progression, with E2 exerting anti-inflammatory and anti-tumorigenic effects that are influenced by Ninj1 status.

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Sex-specific Molecular Markers NRF2 and PD-L1 in Colon Carcinogenesis: Implications for Right-sided Colon Cancer: Chin-Hee Song, Yonghoon Choi, Nayoung Kim, Ryoung Hee Nam, Jin Won Kim, Jae Young Jang, Eun Hye Kim, Sungchan Ha, Ha-Na Lee; Received August 22, 2024 Accepted December 26, 2024 Published online December 27, 2024; DOI: https://doi.org/10.4143/crt.2024.818 [Accepted]

Abstract PDF: Purpose
This study examined the roles of nuclear factor erythroid 2-related factor 2 (NRF2) and programmed death ligand 1 (PD-L1) in colon carcinogenesis, underscoring on sex and differences in tumor location.
Materials and Methods
A total of 378 participants were enrolled from Seoul National University Bundang Hospital: 88 healthy controls (HC), 139 patients with colorectal adenoma (AD), and 151 patients with colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (PCR), methylation-specific PCR, and immunohistochemistry (IHC) were performed utilizing tumor samples from patients and normal mucosa in the HC group.
Results
NRF2 mRNA expression was higher in the CRC group than in the HC and AD groups, with decreased NRF2 methylation in the AD and CRC groups. NRF2 protein expression, as evaluated by IHC, increased in the AD and CRC groups relative to that in the HC group. PD-L1 protein expression was remarkably higher in the CRC group than in the HC and AD groups. These patterns were consistent in both males and females. In sex- and CRC location-specific analyses, NRF2 methylation was lower in female than in male patients with CRC. NRF2 protein expression was significantly higher in females, particularly in patients with right-sided CRC. Moreover, females exhibited increased PD-L1 mRNA expression compared to males in the AD group, and PD-L1 mRNA levels were higher in females with right-sided CRC than in those with cancer at other locations.
Conclusion
Differences in NRF2 and PD-L1 expression indicate site-specific colon carcinogenesis based on sex, particularly in females with right-sided CRC.

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Gastrointestinal cancer

The Persistence of Hypertriglyceridemia and the Risk of Early Onset Colorectal Cancer According to Tumor Subsites: A Nationwide Population-Based Study: Young Hoon Chang, Cheol Min Shin, Kyungdo Han, Jin Hyung Jung, Eun Hyo Jin, Joo Hyun Lim, Seung Joo Kang, Yoon Jin Choi, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee; Cancer Res Treat. 2024;56(3):825-837. Published online December 20, 2023; DOI: https://doi.org/10.4143/crt.2023.753

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Purpose
The incidence of early-onset colorectal cancer (EoCRC) is increasing worldwide. The association between hypertriglyceridemia (HTG) and EoCRC risk remains unclear.
Materials and Methods
We conducted a nationwide cohort study of 3,340,635 individuals aged 20-49 years who underwent health checkups between 2009 and 2011 under the Korean National Health Insurance Service. HTG was defined as serum triglyceride (TG) level ≥ 150 mg/dL. According to the change in TG status, participants were categorized into persistent normotriglyceridemia (NTG; group 1), NTG to HTG (group 2), HTG to NTG (group 3), and persistent HTG (group 4) groups. The EoCRC incidence was followed up until 2019.
Results
In total, 7,492 EoCRC cases developed after a mean of 6.05 years of follow-up. Group 4 had the highest risk of EoCRC (adjusted hazard ratio [aHR], 1.097; 95% confidence interval [CI], 1.025 to 1.174). While the risk of rectal cancer was significantly increased in groups 3 and 4 (aHR [95% CI], 1.236 [1.076 to 1.419] and 1.175 [1.042-1.325], respectively), no significant risk differences were observed in right colon cancer. In group 4, male sex and diabetes were associated with a further increased risk of EoCRC (aHR [95% CI], 1.149 [1.082 to 1.221] and 1.409 [1.169 to 1.699], respectively). In addition, there was a dose-response relationship between serum TG levels and the risk of EoCRC (p for trends < 0.0001).
Conclusion
Persistent HTG increased the risk of EoCRC, which was significantly higher only for rectal cancer and marginally higher for other colonic subsites.

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Obesity-Associated Colorectal Cancer
Lucia Gonzalez-Gutierrez, Omar Motiño, Daniel Barriuso, Juan de la Puente-Aldea, Lucia Alvarez-Frutos, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
International Journal of Molecular Sciences.2024; 25(16): 8836. CrossRef

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Development and Validation of Models to Predict Lymph Node Metastasis in Early Gastric Cancer Using Logistic Regression and Gradient Boosting Machine Methods: Hae Dong Lee, Kyung Han Nam, Cheol Min Shin, Hye Seung Lee, Young Hoon Chang, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee, Sang-Hoon Ahn, Hyung-Ho Kim; Cancer Res Treat. 2023;55(4):1240-1249. Published online March 21, 2023; DOI: https://doi.org/10.4143/crt.2022.1330

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Purpose
To identify important features of lymph node metastasis (LNM) and develop a prediction model for early gastric cancer (EGC) using a gradient boosting machine (GBM) method.
Materials and Methods
The clinicopathologic data of 2556 patients with EGC who underwent gastrectomy were used as training set and the internal validation set (set 1) at a ratio of 8:2. Additionally, 548 patients with EGC who underwent endoscopic submucosal dissection (ESD) as the initial treatment were included in the external validation set (set 2). The GBM model was constructed, and its performance was compared with that of the Japanese guidelines.
Results
LNM was identified in 12.6% (321/2556) of the gastrectomy group (training set & set 1) and 4.3% (24/548) of the ESD group (set 2). In the GBM analysis, the top five features that most affected LNM were lymphovascular invasion, depth, differentiation, size, and location. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristics of set 1 were 0.566, 0.922, 0.516, and 0.867, while those of set 2 were 0.810, 0.958, 0.803, and 0.944, respectively. When the sensitivity of GBM was adjusted to that of Japanese guidelines (beyond the expanded criteria in set 1 [0.922] and eCuraC-2 in set 2 [0.958]), the specificities of GBM in sets 1 and 2 were 0.516 (95% confidence interval, 0.502-0.523) and 0.803 (0.795-0.805), while those of the Japanese guidelines were 0.502 (0.488-0.509) and 0.788 (0.780-0.790), respectively.
Conclusion
The GBM model showed good performance comparable with the eCura system in predicting LNM risk in EGCs.

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Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach
Y. Zou, Q. Mao, Z. Zhao, X. Zhou, Y. Pan, Z. Zuo, W. Zhang
Clinical Radiology.2024; 79(2): e211. CrossRef
eCura and W-eCura: different scores, different populations, same goal
Rui Morais, Diogo Libanio, João Santos-Antunes
Gut.2024; 73(11): e29. CrossRef
A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria
Minoru Kato, Yoshito Hayashi, Ryotaro Uema, Takashi Kanesaka, Shinjiro Yamaguchi, Akira Maekawa, Takuya Yamada, Masashi Yamamoto, Shinji Kitamura, Takuya Inoue, Shunsuke Yamamoto, Takashi Kizu, Risato Takeda, Hideharu Ogiyama, Katsumi Yamamoto, Kenji Aoi,
Gastric Cancer.2024; 27(5): 1069. CrossRef
The Application of Artificial Intelligence to Cancer Research: A Comprehensive Guide
Amin Zadeh Shirazi, Morteza Tofighi, Alireza Gharavi, Guillermo A. Gomez
Technology in Cancer Research & Treatment.2024;[Epub] CrossRef
Computed Tomography-Based Radiomics Analysis of Different Machine Learning Approaches for Differentiating Pulmonary Sarcomatoid Carcinoma and Pulmonary Inflammatory Pseudotumor
An-Lin Zhang, Yan-Mei Fu, Zhi-Yang He
Iranian Journal of Radiology.2024;[Epub] CrossRef
Screening of gastric cancer diagnostic biomarkers in the homologous recombination signaling pathway and assessment of their clinical and radiomic correlations
Ahao Wu, Tengcheng Hu, Chao Lai, Qingwen Zeng, Lianghua Luo, Xufeng Shu, Pan Huang, Zhonghao Wang, Zongfeng Feng, Yanyan Zhu, Yi Cao, Zhengrong Li
Cancer Medicine.2024;[Epub] 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: 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

Abstract PDF PubReader ePub

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
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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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Aberrant DNA Methylation Maker for Predicting Metachronous Recurrence After Endoscopic Resection of Gastric Neoplasms: Cheol Min Shin, Nayoung Kim, Hyuk Yoon, Yoon Jin Choi, Ji Hyun Park, Young Soo Park, Dong Ho Lee; Cancer Res Treat. 2022;54(4):1157-1166. Published online January 18, 2022; DOI: https://doi.org/10.4143/crt.2021.997

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate whether MOS methylation can be useful for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms.
Materials and Methods
From 2012 to 2017, 294 patients were prospectively enrolled after endoscopic resection of gastric dysplasia (n=171) or early gastric cancer (n=123). When Helicobacter pylori was positive, eradication therapy was performed. Among them, 124 patients completed the study protocol (follow-up duration > 3 years or development of metachronous recurrence during the follow-up). Methylation levels of MOS were measured at baseline using quantitative MethyLight assay from the antrum.
Results
Median follow-up duration was 49.9 months. MOS methylation levels at baseline were not different by age, sex, and current H. pylorii infection, but they showed a weak correlation with operative link on gastritis assessment (OLGA) or operative link on gastric intestinal metaplasia assessment (OLGIM) stages (Spearman’s ρ=0.240 and 0.174, respectively; p < 0.05). During the follow-up, a total of 20 metachronous gastric neoplasms (13 adenomas and 7 adenocarcinomas) were developed. Either OLGA or OLGIM stage was not useful in predicting the risk for metachronous recurrence. In contrast, MOS methylation high group (≥ 34.82%) had a significantly increased risk for metachronous recurrence compared to MOS methylation low group (adjusted hazard ratio, 4.76; 95% confidence interval, 1.54 to 14.79; p=0.007).
Conclusion
MOS methylation can be a promising marker for predicting metachronous recurrence after endoscopic resection of gastric neoplasms. To confirm the usefulness of MOS methylation, validation studies are warranted in the future (ClinicalTrials No. NCT04830618).

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MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population
Catarina Lopes, Tatiana C. Almeida, Catarina Macedo-Silva, João Costa, Sofia Paulino, Carmen Jerónimo, Diogo Libânio, Mário Dinis-Ribeiro, Carina Pereira
Clinical Epigenetics.2024;[Epub] CrossRef
The methylation signature of hepatocellular carcinoma trajectory based on pseudotime and chronological time for predicting precancerous patients
Kang Li, Chaoran Zang, Yanan Zhao, Dandan Guo, Wanting Shi, Tingting Mei, Ang Li, Yonghong Zhang
The Oncologist.2024;[Epub] CrossRef
Risk assessment of metachronous gastric cancer development using OLGA and OLGIM systems after endoscopic submucosal dissection for early gastric cancer: a long-term follow-up study
Yun Suk Na, Sang Gyun Kim, Soo-Jeong Cho
Gastric Cancer.2023; 26(2): 298. CrossRef

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Association between the Persistence of Obesity and the Risk of Gastric Cancer: A Nationwide Population-Based Study: Joo Hyun Lim, Cheol Min Shin, Kyung-Do Han, Seung Woo Lee, Eun Hyo Jin, Yoon Jin Choi, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee; Cancer Res Treat. 2022;54(1):199-207. Published online May 4, 2021; DOI: https://doi.org/10.4143/crt.2021.130

Abstract PDF Supplementary Material PubReader ePub

Purpose
There remains controversy about relationship between obesity and gastric cancer. We aimed to examine the association using obesity-persistence.
Materials and Methods
We analyzed a nationwide population-based cohort which underwent health check-up between 2009 and 2012. Among them, those who had annual examinations during the last 5 years were selected. Gastric cancer risk was compared between those without obesity during the 5 years (never-obesity group) and those with obesity diagnosis during the 5 years (non-persistent obesity group; persistent obesity group).
Results
Among 2,757,017 individuals, 13,441 developed gastric cancer after median 6.78 years of follow-up. Gastric cancer risk was the highest in persistent obesity group (incidence rate [IR], 0.89/1,000 person-years; hazard ratio [HR], 1.197; 95% confidence interval [CI], 1.117 to 1.284), followed by non-persistent obesity group (IR, 0.83/1,000 person-years; HR, 1.113; 95% CI, 1.056 to 1.172) compared with never-obesity group. In subgroup analysis, this positive relationship was true among those < 65 years old and male. Among heavy-drinkers, the impact of obesity-persistence on the gastric cancer risk far increased (non-persistent obesity: HR, 1.297; 95% CI, 1.094 to 1.538; persistent obesity: HR, 1.351; 95% CI, 1.076 to 1.698).
Conclusion
Obesity-persistence is associated with increased risk of gastric cancer in a dose-response manner, especially among male < 65 years old. The risk raising effect was much stronger among heavy-drinkers.

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Diagnosis of gastric cancer in role of endoscopic imaging techniques in artificial intelligence and machine learning applications: An overview
Pooja K., Kishore Kanna R., G. Li, U. Subramaniam, M. Sekar
E3S Web of Conferences.2024; 491: 03016. CrossRef
Joint association of drinking alcohol and obesity in relation to cancer risk: A systematic review and data synthesis
Graeme A. Macdonald, James A. Thomas, Christine Dalais, Bradley J. Kendall, Aaron P. Thrift
Cancer Epidemiology.2024; 91: 102596. CrossRef
Roles of long non‑coding RNA SNHG16 in human digestive system cancer (Review)
Lujie Zhao, Yuling Kan, Lu Wang, Jiquan Pan, Yun Li, Haiyan Zhu, Zhongfa Yang, Lin Xiao, Xinhua Fu, Fujun Peng, Haipeng Ren
Oncology Reports.2024;[Epub] CrossRef
Adiposity and risks of gastrointestinal cancers: A 10‐year prospective study of 0.5 million Chinese adults
Wing Ching Chan, Iona Millwood, Christiana Kartsonaki, Huaidong Du, Daniel Schmidt, Rebecca Stevens, Junshi Chen, Pei Pei, Canqing Yu, Dianjianyi Sun, Jun Lv, Xianyong Han, Liming Li, Zhengming Chen, Ling Yang
International Journal of Cancer.2024;[Epub] CrossRef
Gastric Cancer Risk in Association with Underweight, Overweight, and Obesity: A Systematic Review and Meta-Analysis
Narges Azizi, Moein Zangiabadian, Golnoosh Seifi, Afshan Davari, Elham Yekekhani, Seyed Amir Ahmad Safavi-Naini, Nathan A. Berger, Mohammad Javad Nasiri, Mohammad-Reza Sohrabi
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Qinli Xie, Yangjun He, Danni Zhou, Yi Jiang, Ying Deng, Ruoqing Li
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Risk of gastric cancer in relation with serum cholesterol profiles: A nationwide population-based cohort study
Mi Jin Oh, Kyungdo Han, Bongseong Kim, Joo Hyun Lim, Bokyung Kim, Sang Gyun Kim, Soo-Jeong Cho
Medicine.2023; 102(48): e36260. CrossRef
Decreasing Incidence of Gastric Cancer with Increasing Time after Helicobacter pylori Treatment: A Nationwide Population-Based Cohort Study
Taewan Kim, Seung In Seo, Kyung Joo Lee, Chan Hyuk Park, Tae Jun Kim, Jinseob Kim, Woon Geon Shin
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Integration of clinical and transcriptomics reveals programming of the lipid metabolism in gastric cancer
Yanyan Li, Jungang Zhao, Renpin Chen, Shengwei Chen, Yilun Xu, Weiyang Cai
BMC Cancer.2022;[Epub] CrossRef
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Susanna C. Larsson, Nikolaos Spyrou, Christos S. Mantzoros
Metabolism.2022; 137: 155326. CrossRef
FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells
Jijun Yan, Juntao Liu, Zhengbin Huang, Wenwei Huang, Jianfa Lv
Human Cell.2021; 34(6): 1755. 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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