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: It is controversial as to whether the development of gastric cancer is influenced byHelicobacter pylorieradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate.: To investigate the morphological changes in the gastric neoplasm afterH. pylorieradication.: We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication.: Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels.: The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate. [ABSTRACT FROM AUTHOR]

Investigates the relationship between Helicobacter pylori infection and tumor growth of gastric carcinoma. Consideration of H. pylori as a risk factor for gastric carcinoma; Association of H. pylori infection with cell proliferation; Difference found between the H. pylori- positive and H.pylori-eradicated groups.

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3–21% of Helicobacter pylori-associated chronic gastritis ( Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM ( P<0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori has been established as a risk factor for gastric carcinoma (GCa). Since before the discovery of H. pylori, atrophic gastritis and intestinal metaplasia have been linked to GCa, especially the intestinal-type tumor. The prevalence of H. pylori infection and atrophic gastritis increase with age. Thus, analysis of H. pylori infection in young patients with GCa could help clarify the role of this bacterium in the development of GCa. Accordingly, we investigated the relationship between H. pylori infection, GCa, and histologic gastritis in patients less than 30 years old. Methods: Fifty GCa patients less than 30 years (mean, 26.4 years) and 100 sex- and age-matched controls (mean, 26.8 years) were examined for the presence of H. pylori infection and histologic gastritis. Results: The prevalence of H. pylori infection was significantly higher in GCa patients than in controls (94% versus 40%, P < 0.01). Its prevalence was not associated with tumor location, tumor stage, or histologic type. Gastritis, atrophy, and intestinal metaplasia significantly increased the risk of GCa. By means of multiple logistic regression analysis, the odds ratio for the risk of GCa in H. pylori-positive subjects was found to be 23.5 (95% confidence interval, 6.84-80.7). Conclusions: We confirmed a strong association between H. pylori infection and GCa in young patients. Along with H. pylori infection, histologic gastritis might play an important role in the pathogenesis of GCa in these patients. [ABSTRACT FROM AUTHOR]

Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumour progression. The purpose of this study was to investigate the localization of human telomerase RNA (hTR) expression in human oesophageal dysplasia and cancer by using in situ mRNA hybridization (ISH) with avidin-biotin staining. Ki-67 immunoreactivity was also examined. We analysed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of the mRNA in each sample was verified by using a poly d(T)20 probe. Seventy-six samples (63%) showed no mRNA degradation; these included 30 carcinomas, 7 dysplasias and 39 normal mucosae. At the single-cell level, high levels of hTR expression were found in the cytoplasm and especially in the nucleus. Most (>90%) cancer cells demonstrated high levels of hTR expression in 29 (97%) of the 30 tumours. Most dysplastic cells also showed high levels of hTR in all 7 dysplastic cases. In all 39 normal mucosae, most basal cells indicated high levels of hTR expression, which were also seen in infiltrating lymphocytes. The distribution of hTR-expressing cells was similar to that of Ki-67-positive cells. These data suggest that overexpression of hTR may be correlated with the proliferative activity that defined by Ki-67 immunoreactivity and is an early event in carcinogenesis of the oesophagus. [ABSTRACT FROM AUTHOR]

Inhibition of WEE1, a key regulator of the G2/M checkpoint of the cell cycle, induces apoptosis by initiating mitosis without repairing DNA damage. However, the effects of WEE1 inhibitors on the tumor immune microenvironment in colorectal cancer (CRC) remain unclear. Here, we investigated the association between WEE1 expression and CRC clinicopathological features using surgically resected CRC specimens and assessed the antitumor effects of a WEE1 inhibitor using CRC cell lines and orthotopic transplantation mouse models. WEE1 expression was not correlated with the clinicopathological features of CRC. The WEE1 inhibitor suppressed cell proliferation in a concentration-dependent manner in all CRC cell lines. It also increased the percentage of cells in the G2/M phase and apoptotic cells, especially in cell lines with p53 mutations, but did not alter these cell percentages in most p53 wild-type cell lines. In the orthotopic mouse model of CRC, tumor volume was significantly reduced in the WEE1 inhibitor-treated group compared to that in the control group. RNA sequencing and immunohistochemistry analyses of mouse tumors revealed that treatment with the WEE1 inhibitor activated tumor immunity and suppressed stromal reactions. These results demonstrate the potential antitumor effects of WEE1 inhibitors in CRC, particularly in patients with p53 mutations.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.

Background: Non-Helicobacter pylori Helicobacter (NHPH) has recently been linked to various gastric diseases. However, the relationship between NHPH infection and gastric cancer remains controversial. This study aimed to identify the effect of NHPH infection on gastritis and gastric cancer development., Materials and Methods: Formalin-fixed paraffin-embedded tissues were obtained from 73 patients with gastric cancer, of whom 21 cases were Helicobacter pylori (Hp) current infection, 37 cases were Hp previous infection, and 15 cases were Hp naïve infection, and were screened for NPHPs using polymerase chain reaction. The results were compared with NHPH infection rates in the patients with gastritis-related diseases reported in the previous study. We evaluated the association of NHPH infection with gastritis and clinicopathological features of gastric cancer., Results: NHPH infection rates were 4/21 (19%) in "Hp current" patients, 4/37 (11%) in "Hp previous" infection patients, and 1/15 (7%) in "Hp naïve" patients, showing no significant difference in infection rates based on Hp infection status. NHPH infection rates in gastric cancer patients were similar to those in the patients with gastritis-related diseases reported in the previous study. A comparison of NHPH-positive and negative patients showed no significant differences in atrophic gastritis status, serum gastritis markers, or clinicopathological characteristics of gastric cancer, such as localization, size, gross type, differentiation, or depth., Conclusions: The association between gastric cancer and NHPH infection would have important implications for gastric cancer prevention, diagnostics, and treatment, however, no significant association was found in this particular population., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to be declared for any of the authors., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

The role of tumor-infiltrating T cells (TILs) in colorectal cancer (CRC) and their significance in early-stage CRC remain unknown. We investigated the role of TILs in early-stage CRC, particularly in deep submucosal invasive (T1b) CRC. Sixty patients with CRC (20 each with intramucosal [IM group], submucosal invasive [SM group], and advanced cancer [AD group]) were randomly selected. We examined changes in TILs with tumor invasion and the relationship between TILs and LN metastasis risk. Eighty-four patients with T1b CRC who underwent initial surgical resection with LN dissection or additional surgical resection with LN dissection after endoscopic resection were then selected. TIL phenotype and number were evaluated using triple immunofluorescence for CD4, CD8, and Foxp3. All subtypes were more numerous according to the degree of CRC invasion and more abundant at the invasive front of the tumor (IF) than in the center of the tumor (CT) in the SM and AD groups. The increased Foxp3 cells at the IF and high ratios of Foxp3/CD4 and Foxp3/CD8 positively correlated with LN metastasis. In conclusion, tumor invasion positively correlated with the number of TILs in CRC. The number and ratio of Foxp3 cells at the IF may predict LN metastasis in T1b CRC.

Purpose: Dental floss clip (DFC) traction-assisted endoscopic submucosal dissection (ESD) is widely performed owing to its simplicity. This study aimed to clarify the appropriate indications for the DFC traction method in early gastric cancer when ESD is performed by less-experienced endoscopists., Methods and Methods: We retrospectively analyzed 1,014 consecutive patients who had undergone gastric ESD performed by less-experienced endoscopists between January 2015 and December 2020. Gastric ESD was performed without DFC in all cases before December 2017 [DFC (-) group, 376 cases], and ESD was performed with DFC in all cases after January 2018 [DFC (+) group, 436 cases]. The procedure time and rates of en bloc resection, complete resection, and adverse events of the groups were compared., Results: The procedure time did not differ significantly between the 2 groups. However, when comparing lesions >20 mm, the procedure time in the DFC (+) group was significantly shorter than that in the DFC (-) group (95±46 vs. 75±31, P<0.01). The procedure time for lesions located in the greater curvature of the upper or middle stomach and lesions >20 mm located in the lesser curvature side of the stomach in the DFC (+) group was significantly shorter than that in the DFC (-) group., Conclusions: The indications for DFC during gastric ESD by less-experienced endoscopists include lesions located in the greater curvature of the upper or middle stomach, and lesions >20 mm located in the lesser curvature of the stomach., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Gastric Cancer Association.)

Objectives: Complete en-bloc resection of pedunculated colorectal carcinoma is necessary for a proper pathological diagnosis. However, due to poor visibility, large pedunculated colorectal carcinomas are difficult to snare and resect en-bloc using endoscopic resection or polypectomy. Additionally, the bleeding risk of large pedunculated colorectal carcinomas is relatively high. We aimed to assess the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas., Methods: We conducted a retrospective multicenter cohort study to assess 36 consecutive patients with 36 large pedunculated colorectal carcinomas who underwent endoscopic submucosal dissection and evaluated the outcomes of endoscopic submucosal dissection. Furthermore, patients were divided into two groups according to the procedure time, and the factors related to the procedure time were assessed., Results: The mean tumor size was 34.1 ± 9.9 mm. The en-bloc, complete en-bloc, and curative resection rates were 97% (35/36), 97% (35/36), and 81% (29/36), respectively. The rate of severe bleeding during the procedure was 11% (4/36); however, it could be controlled endoscopically in all patients. The rate of intraoperative perforation and delayed bleeding was 0% (0/36). Delayed perforations occurred in one patient that required surgery. A long procedure time was correlated with the location of the flexure and poor endoscope operability. No recurrence was observed in any patient. None of the patients died of colorectal carcinoma., Conclusions: Our results showed the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas., Competing Interests: The authors declared ST is the president of JGES., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated macrophages. Anti-TNFα mAb acts as an inhibitor of tumor progression in the tumor microenvironment of a colorectal cancer orthotopic transplant mouse model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Takasago et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.

Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein-protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 ( OLFM4 ) and the Nanog homeobox ( NANOG ) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.

Introduction: The effects of low-dose alcohol consumption on colorectal cancer development are not well understood. Epidemiological studies have reported that people who consume small amounts of alcohol have lower mortality rates than both nondrinkers and heavy drinkers. This phenomenon has been labeled the "J-curve effect" of alcohol. This study examined the effects of low-dose alcohol (0.5%, 1%, and 2%) on tumor growth in a transplant colon cancer model., Methods: BALB/c and BALB/c nude mice were used to analyze T-cell immunity. Syngeneic CT26 murine colon cancer cells were implanted into the cecal wall, and the resulting T-cell immune effects were monitored., Results: The growth of orthotopic tumors was markedly inhibited upon ingestion of low-dose (0.5%) alcohol compared with that in the control mice. In contrast, cells from the same line were injected into the cecal wall of nude mice, and tumor growth inhibition was not observed. Histopathological and RNA sequence analyses were performed to elucidate the mechanisms underlying tumor growth inhibition. An increase in tumor CD8+ T lymphocytes and changes in cytokine levels were observed. Microbiome analysis using 16S rRNA gene sequencing of cecal contents was performed and revealed Mucispirillum schaedleri and Clostridium cocleatum showed decreased and increased abundance, respectively, in the alcohol group., Discussion/conclusion: Ingesting a threshold amount of alcohol results in the infiltration of T lymphocytes, which may enhance immune responsiveness in mouse colorectal cancer models., (© 2022 S. Karger AG, Basel.)

In this study, we investigated the in vivo metastasis suppression effects of the platelet-derived growth factor receptor inhibitor dasatinib, which targets cancer-associated fibroblasts (CAFs), in combination with an anti-programmed cell death-1 (PD-1) antibody. We classified clinical CRC cases as inflamed, excluded, or desert using immunohistochemical analysis and evaluated the tumor stroma. The excluded type was the most common, and cases with high-volume stroma in the primary lesions also had a high stromal volume in the liver metastatic lesions. Liver-metastasis mouse models with different stromal volumes were established and treatment-induced changes in the tumor immune microenvironment were evaluated. The anti-PD-1 antibody alone exhibited a therapeutic effect for the liver metastases with low stromal volumes but not for the liver metastases with high stromal volumes. In contrast, antitumor effects were observed with anti-PD-1 antibody/dasatinib combination therapy even in the liver metastases with high stromal volumes. Combination therapy reduced the stromal volume, promoted immune cell infiltration, induced antitumor cytotoxic T-cell responses, activated antitumor immunity, and promoted tumor regression. These results suggest that CAFs play an important role in the immune evasion of CRC and that anti-PD-1 antibody/dasatinib combination therapy has potential as a treatment option for patients with metastatic CRC for whom immunotherapy alone is ineffective.

Background: Primary small-bowel follicular lymphoma (FL) is mainly diagnosed as a duodenal lesion during esophagogastroduodenoscopy. Recently, with the widespread use of small-bowel endoscopy, FL in the jejunum and ileum has been detected. Most patients with small-bowel FL are diagnosed at the localized stage, and a watch-and-wait policy is used. However, the predictive factors for the progression of small-bowel FL have not been clarified. This study retrospectively examined the predictive factors for the progression of primary localized stage small-bowel FL based on clinicopathological and endoscopic findings., Methods: We enrolled 60 consecutive patients with primary small-bowel FL diagnosed at two tertiary hospitals between January 2005 and December 2020, with localized stage, low grade, and low tumor burden with the watch-and-wait policy. We examined the predictive factors for progression according to the clinicopathological and endoscopic findings. Endoscopic findings were focused on the color tone, circumferential location of follicular lesions (circumference ≥ 1/2 or < 1/2), fusion of follicular lesions (fusion [ +] or [ -]), and protruded lesions (≥ 6 mm or < 6 mm)., Results: Progressive disease was observed in 12 (20%) patients (mean observation period, 76.4 ± 55.4 months). In the multivariate analysis, "circumference ≥ 1/2" and "fusion (+)" were significant predictive factors for progression. According to the Kaplan-Meier analysis, progression-free survival was significantly shorter in the "circumference ≥ 1/2" and/or "fusion (+)" group than in the "circumference < 1/2" and "fusion ( -)" group., Conclusions: Endoscopic findings of "circumference ≥ 1/2" and "fusion (+)" were significant predictive factors for the progression of primary localized stage small-bowel FL., (© 2022. Japanese Society of Gastroenterology.)

Background: We have previously reported that eradication therapy was more effective against Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma in non-Helicobacter pylori Helicobacter (NHPH)-positive cases than in NHPH-negative cases and that the infection status of NHPH could be a predictive marker for the efficacy of eradication therapy for H. pylori negative gastric MALT lymphoma. However, a diagnostic test for NHPH infection has not yet been clinically established. In this study, we investigated the endoscopic findings in cases of H. suis-infected gastritis associated with gastric MALT lymphoma reported at our institution., Materials and Methods: Participants were selected from cases of gastric MALT lymphoma who underwent esophagogastroduodenoscopy at Hiroshima University Hospital, who were negative for the API2-MALT1 gene, and who received eradication therapy as a first-line treatment. We examined the endoscopic findings in nine cases from this group in which H. suis infection was confirmed by polymerase chain reaction., Results: Endoscopic findings, such as cracked mucosa, spotty redness, nodular gastritis-like appearance, and white marbled appearance, which have been reported as characteristics of NHPH gastritis, were observed in multiple cases. The most common endoscopic findings in this study were cracked mucosa (7/9 cases), followed by spotty redness (6/9 cases), nodular gastritis-like appearance (5/9 cases), and white marbled appearance (2/9 cases)., Conclusions: Our study may serve as a reference for re-evaluation of the diagnostic criteria for H. suis infection and indications for eradication therapy, particularly for cases of H. pylori negative gastric MALT lymphoma, where endoscopic findings such as those seen in this study were observed in the background mucosa., (© 2022 John Wiley & Sons Ltd.)

Serum amyloid A (SAA) is an acute phase inflammatory protein that we previously described as a robust biomarker of colorectal inflammation in patients with ulcerative colitis (UC) in clinical remission. However, what induces SAA expression in UC remains unclear. This study demonstrates that SAA is significantly expressed in the intestinal tract of UC mouse models when compared with C-reactive protein, another inflammatory biomarker. Moreover, interleukin-6 and tumor necrosis factor-α were found to promote SAA1 expression, as were Toll-like receptor ligands flagellin and lipopolysaccharide. Furthermore, results suggested that the nuclear factor-kappa B (NF-κB) pathway may be involved in the promotion of SAA1 expression by flagellin, which was inhibited by treatment with 5-aminosalicylic acid (5-ASA). Therefore, the flagellin/NF-κB/SAA1 axis may represent one of the mechanisms by which 5-ASA suppresses intestinal inflammation., Competing Interests: The authors have declared that no competing interests exist.