Macrophage involvement in the pathological evolution of ulcerative colitis-associated colon cancer and progress of related traditional Chinese medicine drug interventions

Intestinal macrophages are essential players in intestinal inflammation and intestinal immune homeostasis.Intestinal macrophages have the ability to polarize into two distinct phenotypes based on various environmental signals.These phenotypes include the typically activated pro-inflammatory M1 phenotype and the alternatively activated anti-inflammatory M2 phenotype.Under normal circumstances,intestinal macrophages prevent inflammatory damage to the gut.However,when genetic and environmental factors influence the polarization of intestinal macrophages,it can lead to an imbalance in M1/M2 macrophage activation and subsequently an imbalance in the control of intestinal inflammation.It transforms physiological inflammation into pathological intestinal damage.In patients with ulcerative colitis-associated cancer(UC-CRC),intestinal inflammatory disorders are closely associated with intestinal M1/M2 macrophage polarization imbalance.Consequently,restoring the polarization equilibrium of M1/M2 macrophages might be an evidence of traditional Chinese medicine in the treatment of UC-CRC,the pivotal role o effective measure to prevent and treat UC-CRC.This paper aims to examine the clinicalf macrophage polarization in UC-CRC pathogenesis,and the potential mechanisms of traditional Chinese medicine in regulating macrophage polarization to treat UC-CRC.Our goal is to provide novel insights into the clinical practice,basic research,and drug development of UC-CRC.

Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing

Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.

Study on the mechanism of action of Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil in the treatment of colitis-associated colon cancer

Objective:To investigate the therapeutic effects and mechanisms of Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil administration in mice with colitis-associated colon cancer.Methods:To establish a colitis-associated colon cancer mouse model and observe the behavior and activity of mice after Feng-Liao-Chang-Wei-Kang and 5-fluorouracil administration;HE staining to observe the pathological changes of mouse colonic tissue;Western blot was used to detect the expression of mouse colon tissue in IL-6/STAT3 pathway-related proteins.Results:The survival rate of mice in the co-administered group was significantly increased,and the intestinal wall thickening and interstitial inflammation of mice were significantly reduced.Western blot results showed that the expression levels of P-STAT3 and IL-6 were significantly increased in the colonic tissue of mice after modeling,and the combined administration inhibited the expression of Cyclin D1,CDK4 and Bcl-2 protein in the IL-6/STAT3 pathway and upregulated the expression of Bax(P<0.05).Conclusion:Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil inhibits IL-6/STAT3 pathway to exert inhibition of colitis-associated colon cancer inhibition of colitis-associated colon cancer.

Ulcerative colitis-associated colorectal cancer

The association between ulcerative colitis(UC) and colorectal cancer(CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC(UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, lowgrade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC.

Status of colitis-associated cancer in ulcerative colitis

Surgical therapy for ulcerative colitis(UC) depends on the medical therapy administered for the patient's condition. UC is a benign disease. However, it has been reported that the rare cases of cancer in UC patients are increasing, and such cases have a worse prognosis. Recently, surgical therapy has greatly changed, there has been quite an increase in the number of UC patients with high-grade dysplasia and/or cancer. These lesions are known as colitis-associated cancer(CAC). The relationship between inflammation and tumorigenesis is well-established, and in the last decade, a great deal of supporting evidence has been obtained from genetic, pharmacological, and epidemiological studies. Inflammatory bowel disease, especially UC, is an important risk factor for the development of colon cancer. We should determine the risk factors for UC patients with cancer based on a large body of data, and we should attempt to prevent the increase in the number of such patients using these newly identified risk factors in the near future. Actively introducing the surgical treatment in addition to medical treatment should be considered. Several physicians should analyze UC from their unique perspectives in order to establish new clinically relevant diagnostic and treatment methods in the future. This article discusses CAC, including its etiology, mechanism, diagnosis, and treatment in UC patients.

Fifteen-year-old colon cancer patient with a 10-year history of ulcerative colitis

Inflammatory bowel disease (IBD) is regarded as one of the risk factors for colorectal cancer, and early detection of cancer in these patients may be difficult, especially in pediatric patients. Prognosis of pediatric colorectal cancer is known to be poor, because of delayed diagnosis and unfavorable differentiation. We report a case of a pediatric patient with a 10-year history of ulcerative colitis who was diagnosed with sigmoid colon cancer when he was 15 years old. He underwent proctocolectomy with ileal pouch anal anastomosis. Postoperative pathological examination of the tumor revealed adenocarcinoma. The pericolic tissue layer was infiltrated, but metastases were not found in either of the two lymph nodes. Children with a long history of predisposing factors such as IBD need particular attention to the possibility of colorectal cancer. Early diagnosis through regular screening with colonoscopy is one of the most important critical factors for a good prognosis.

Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice

BACKGROUND Although expression of interleukin(IL)-34 is upregulated in active ulcerative colitis(UC),the molecular function and underlying mechanism are largely unclear.AIM To investigate the function of IL-34 in acute colitis,in a wound healing model and in colitis-associated cancer in IL-34-deficient mice.METHODS Colitis was induced by administration of dextran sodium sulfate(DSS),and carcinogenesis was induced by azoxymethane(AOM).Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model.The association between IL-34 expression and epithelial proliferation was studied in patients with active UC.RESULTS IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase.The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization.IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS.No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice.IL-34 was dramatically increased in the active UC patients as previously reported.More importantly,expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC.CONCLUSION IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice.It might be served as a potential therapeutic target in UC.

Surveillance for colitis-associated colon neoplasia

The risk of developing colon cancer is increased in colitis patients, particularly if the disease is extensive and its duration long-standing. Endoscopic guidelines have been developed with the goal of detecting early neoplastic changes prior to development of advanced malignancy. Unfortunately, the natural history of this superimposed neoplastic process in colitis appears to be very heterogeneous and poorly understood. Moreover, there are numerous confounding variables in colitis patients that limit accurate assessment of the surveillance effectiveness of colonoscopy and multi-site biopsy protocols. Although the clinical challenge posed to even the most experienced clinicians remains significant, evolving methods of endoscopic imaging may facilitate better evaluation of this highly select group of patients.

Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis

AIM:To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer(CC)or high grade dysplasia(HGD).METHODS:This is a single center(Lenox Hill Hospital)retrospective cohort and descriptive study of extensive ulcerative colitis(UC)for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis.Data analyzed included:duration of UC,date of diagnosis of(CC)or(HGD),number of surveillance colonoscopies,and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal.Two subgroups of patients were compared:group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD.RESULTS:Of 115 patients with longstanding UC reviewed,68 patients met the inclusion criteria.Twenty patients were in group 1 and 48 in group 2.We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation.Overall,histological disease activity in the absence of gross/endoscopic disease was found in 31.2%(95%CI:28%-35%)of colonoscopies performed on the entire cohort of 68 patients.Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients,88%(95%CI:72%-97%)vs 59%(95%CI:53%-64%).Only 3/20(15%)of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity(i.e.,no endoscopic or histological activity)as compared to 37/48(77%)of patients in group 2,and only 3.3%(95%CI:0.09%-8.3%)of colonoscopies in group 1 had no histological inflammation compared to23%(95%CI:20%-27%)in group 2.CONCLUSION:Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease.Our findings support including the elimination of histological inflammation in the definition of mucosal healing,and support this endpoint as an appropriate goal of therapy because of its risk of increasing dysplasia and colon cancer.

Potential of new anti-cancer agents targeting the nuclear translocation signaling of HB-EGF C-terminal fragments during the development of colitis-associated cancer

In inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD), the duration and severity of inflammation are responsible for the development of colorectal cancer. Inflammatory cytokines such as interleukin (IL)-8 and tumor necrotic factor (TNF)-a, which are released by epithelial and immune cells, are involved in the pathogenesis of colitis-associated cancer. Current treatments for advanced colorectal cancers focus primarily on targeting epidermal growth factor receptor (EGFR) signaling. IL-8 (a G-protein coupled receptor (GPCR) agonist), which is involved in neutrophil recruitment and activation in persistent active colitis, also promotes cleavage of theproheparin-binding epidermal growth factor—like growth factor (proHB-EGF) through a disintegrin and metalloproteinase (ADAM), so that the resulting soluble HB-EGF activates EGFR. In parallel, the carboxy-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, where HB-EGF-CTF binds the nuclear promyelocytic leukemia zinc finger (PLZF) protein, resulting in the nuclear export of the PLZF transcriptional repressor and thereby affecting cell proliferation. Screening for potent chemical inhibitors of the interactions between HB-EGF-CTF and PLZF identified telmisartan (and related compounds in corporating a biphenyl tetrazole moiety) as inhibitors of cell proliferation. Here we focus on the inhibitory effects of these compounds on cell proliferation, demonstrating the potential for targeting the nuclear translocation of HB-EGF-CTF in the treatment of colitis-associated cancer.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Rectal hepatoid carcinoma with liver metastases in a patient affected by ulcerative colitis

BACKGROUND:Hepatoid tumors(HTs)are rare extra-hepatic neoplasms with the histological features, biochemical profile and,sometimes,even clinical course of hepatocellular carcinoma.We present a case of rectal hepatoid adenocarcinoma with metachronous liver metastases. METHODS:Four months after total procto-colectomy for a rectal adenocarcinoma(Astler-Coller C2),a 42-year-old man with ulcerative colitis showed hypoechoic masses in the hepatic parenchyma by abdominal ultrasonography. Carcinoembryonic antigen was normal,but alpha- fetoprotein was 32 000μg/L.Fine-needle biopsy revealed that liver masses were positive for hepatocellular carcinoma. The patient underwent left hepatectomy and alcoholisation of a small deep nodule in segment 8. RESULTS:Immunohistochemistry and albumin mRNA in situ hybridization suggested that the nodules were metastases of a HT.The patient was well during the first 6 months and refused any adjuvant chemotherapy.He died from liver failure 19 months after initial diagnosis. CONCLUSIONS:HT is a rare colon cancer.The preoperative diagnosis of this tumor requires a high degree of suspicion,the availability of a panel of immunohistochemical markers,and a certain amount of luck.The prognosis is poor despite an aggressive andmultimodal therapeutic strategy.So far,none of the hypotheses proposed about the origin and the biology of these tumors is convincing.

Depression and anxiety levels in therapy-nave patients with inflammatory bowel disease and cancer of the colon

AIM: To assess whether depression and anxiety are more expressed in patients with the first episode of inflammatory bowel disease (IBD) than in individuals with newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa including 20 males and 10 females, aged 39-78, underwent a structured interview, which comprised Hamilton’s Depression Rating Inventory, Hamilton’s Anxiety Rating Inventory and Paykel’s Stressful Events Rating Scale. RESULTS: Patients of the IBD group expressed both depression and anxiety. Depressive mood, sense of guilt, psychomotor retardation and somatic anxiety were also more pronounced in IBD patients. The discriminant function analysis revealed the total depressive score was of high importance for the classification of a newly diagnosed patient into one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher levels of depression and anxiety. Moreover, a psychiatrist in the treatment team is advisable from the beginning.

Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

Tenascin-C(TNC)is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies,including colon cancer.Although TNC is considered a negative prognostic factor for cancer patients,the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly understood.We previously found that TNC has a cryptic functional site and that a TNC peptide containing this site,termed TNIIIA2,can potently and persistently activate beta1-integrins.In contrast,the peptide FNIII14,which contains a cryptic bioactive site within the fibronectin molecule,can inactivate beta1-integrins.This review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer,particularly the major involvement of its cryptic functional site TNIIIA2.We propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.

Hepatoid adenocarcinoma of the colon in a patient with inflammatory bowel disease

A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease(PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon,who was initially treated with a subtotal colectomy with ileostomy.One year later,the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis,as well as a markedly elevated serum level of alpha-fetoprotein(AFP).Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid adenocarcinoma.Subsequent review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic adenocarcinoma.The patient was subsequently treated with a cytotoxic regimen of FOLFOX(oxaliplatin,leucovorin,5-fluorouracil) and bevacizumab,with stable results being achieved after six months.This case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.

白藜芦醇通过调节铁死亡通路抑制小鼠溃疡性结肠炎相关性结肠癌实验研究

目的:观察白藜芦醇(Res)是否可通过调节铁死亡通路抑制小鼠溃疡性结肠炎相关性结肠癌(UCACC)。方法:(1)将28只C57BL/6小鼠随机分为Control组、氧化偶氮甲烷(AOM)组、AOM+葡聚糖硫酸钠盐(DSS)组、AOM+DSS+Res组。造模实验周期为70 d。AOM组、AOM+DSS组和AOM+DSS+Res组第1天注射1次AOM。从造模第2周开始AOM+DSS组和AOM+DSS+Res组饮用含DSS水,第3周更换为无菌水,第4周换为含DSS水,以此循环到造模实验周期结束。Control组和AOM组饮用无菌水,AOM+DSS+Res组每周给予Res灌胃。造模结束后处死小鼠,取小鼠结肠组织,HE染色后观察小鼠结肠组织病理改变。分别采用免疫组织化学法(IHC)和Western blot检测小鼠结肠组织谷胱甘肽过氧化物酶4(GPX4)、长链脂酰辅酶A合成酶4(ACSL4)、铁蛋白重链(FTH)、P53蛋白的表达。(2)将人结肠癌HCT 116细胞分为空白对照组及4、8、16μg/ml Res组。用不同浓度(4、8、16μg/ml)Res处理HCT 116细胞。收集处理的细胞后,采用CCK-8实验检测细胞增殖活性,采用Western blot检测细胞GPX4、ACSL4、FTH蛋白的表达。结果:(1)HE染色结果显示小鼠UCACC模型建模成功,Res可明显抑制AOM+DSS诱导的小鼠UCACC形成。IHC染色结果显示,与Control组比较,AOM组FTH蛋白表达下降;AOM+DSS组GPX4和FTH蛋白表达明显上升,ACSL4和P53蛋白表达明显下降(均P<0.05)。与AOM+DSS组比较,AOM+DSS+Res组GPX4和FTH蛋白表达下降,ACSL4和P53蛋白表达明显上升(均P<0.05)。Western blot检测结果显示,与Control组比较,AOM组GPX4、FTH蛋白表达下降,ACSL4表达上升;AOM+DSS组GPX4和FTH蛋白表达上升,ACSL4和P53蛋白表达下降(均P<0.05)。与AOM+DSS组比较,AOM+DSS+Res组GPX4和FTH蛋白表达下降,ACSL4和P53蛋白表达上升(均P<0.05)。(2)CCK-8实验结果显示,8、16μg/ml Res组细胞存活率低于空白对照组(均P<0.05)。Western blot检测结果显示,与空白对照组比较,4、8、16μg/ml Res组细胞GPX4和FTH蛋白表达下降,ACSL4蛋白表达上升(均P<0.05)。结论:Res可以通过调控细胞铁死亡通路抑制UCACC。

髓样细胞触发受体与溃疡性结肠炎及其相关癌变的研究进展

越来越多研究表明炎症在恶性肿瘤发生发展中有举足轻重的作用。在很大程度上与免疫细胞参与恶性肿瘤有关,其中关键是模式识别受体(PRRs)激活的免疫应答。髓样细胞触发受体(TREMs)作为PRRs的一员,来自于髓样细胞,主要成员为TREM-1和TREM-2。已有研究表明,TREMs广泛参与多种炎症以及恶性肿瘤的生长过程,包括结肠癌。本文主要讨论溃疡性结肠炎及其相关癌变机制以及TREMs在炎症相关结肠癌中的研究进展。

半夏泻心汤抑制DMH/DSS诱导的结肠炎相关性结肠癌的发生

目的:观察半夏泻心汤对DMH/DSS诱导的结肠炎向结肠癌转变的抑制作用.方法:♂ICR小鼠65只,随机分为正常组、模型组和半夏泻心汤3个剂量(100,200,400 mg/ kg)给药组.采用腹腔注射1,2-二甲肼20 mg/kg及饮用含20 g/L的右旋葡聚糖苷钠复制结肠炎相关的小鼠结肠癌.除模型组20只小鼠,其余30只存活小鼠在出现第二次便血时分别口服给予半夏泻心汤100,200和400 mg/kg进行治疗,1次/d,共11 wk.实验第20周,乙醚麻醉处死小鼠,截取结肠,称重;记录结肠肿瘤数目,取结肠做HE染色:摘取脾脏、胸腺称重.结果:在实验第20周,40%的模型组小鼠出现脱肛,成癌率为85%.半夏泻心汤3个剂量组则未见脱肛小鼠,100 mg/kg组成癌率为20%,200和400 mg/kg成癌率为10%.DMH/DSS诱导的结肠癌小鼠脾脏指数显著升高(6.50±4.08 mg/g vs 4.25±3.39 mg/g,P<0.01),而胸腺指数则明显降低(0.60±0.33 mg/g vs0.71±0.29 mg/g,P<0.05),与对照组相比有显著性差异.半夏泻心汤可明显的对抗结肠癌小鼠胸腺的萎缩(P<0.05),而对脾脏的增大也有明显的治疗作用(P<0.01).病理结果表明,半夏泻心汤成功的将小鼠结肠停留在炎症状态,阻止了结肠炎向结肠癌的转变.结论:半夏泻心汤能够显著地抑制结肠炎向结肠癌的转变,结肠炎的有效治疗是防止结肠癌发生的重要措施.

无痛肠镜单人操作132例临床分析

[目的]探讨无痛结肠镜单人操作方法。[方法]采用丙泊酚注射液静脉麻醉,行无痛结肠镜单人操作单人操作技术。[结果]132例肠镜检查中,有127例插至回盲部,21例进入末段回肠,所有病例均无穿孔、出血等并发症发生,插至回盲部成功率96.21%。[结论]在麻醉睡眠情况下进行结肠镜单人操作,受检病人始终处于放松状态,易于接受,并省时省力,值得临床进一步推广。

溃疡性结肠炎诱发结肠癌小鼠模型中RegⅣ的表达及预测价值

目的通过检测再生基因Ⅳ(Regenerating geneⅣ,RegⅣ)和Ki67在溃疡性结肠炎(ulcerative colitis,UC)诱发结肠癌小鼠模型中的表达,探讨RegⅣ对UC诱发结肠癌早期诊断、判断预后的价值。方法 60只BALB/c小鼠分为正常对照组、模型组,采用偶氮氧甲烷(Azoxymethane,AOM)联合葡聚糖硫酸钠(Dextran sulfate sodium,DSS)的方法建立UC癌变的小鼠模型,HE染色观察小鼠结肠组织病理变化,采用免疫组化检测不同时期肠道组织中Ki67和RegⅣ蛋白的表达,实时荧光定量PCR检测此两项指标mRNA的表达。结果癌变组小鼠结肠黏膜中Ki67的表达水平较其他组明显升高(P<0.05),轻-中度不典型增生组RegⅣ的表达水平较癌变组明显升高(P<0.05),免疫组化法统计学结果与RT-PCR一致。结论 Reg IV在肠黏膜癌变过程中表达过量可能先于Ki67,提示RegⅣ可作为预测UC诱发结肠癌的良好分子标志物。