具核梭杆菌与结直肠癌关系的研究进展

结直肠癌(colorectal cancer,CRC)是目前世界范围内及国内最常见的恶性肿瘤之一.近十年来其发病率与致死率呈逐年上升趋势.其发生是遗传、环境、微生物等多因素多步骤的过程,越来越多的研究表明具核梭杆菌(Fusobacterium nucleatum,Fn)在结直肠癌的发生、发展过程中起重要作用.研究具核梭...     

具核梭杆菌在结直肠癌发展及诊疗中的作用

结直肠癌(colorectal cancer, CRC)发病率高且难以治愈。越来越多的证据表明肠道微生物群生态失调与CRC发生发展密切相关,具核梭杆菌(Fusobacterium nucleatum, Fn)已经被确定为肠道微生物群中的病原体,有助于结直肠发生癌变。本文综述了Fn诱导CRC发生发展的重要机制,包括毒力因子、慢性炎症、miRNA、免疫调节和肠道代谢物,并描述了Fn在诊断治疗中的临床价值,以期为新型肿瘤生物标志物的筛查与新兴免疫治疗靶点的开发提供参考。     

具核梭杆菌与肠道肿瘤相关性及

摘 要：具核梭杆菌（Fusobacterium nucleatum）是革兰氏阴性专性厌氧菌,与多种感染性疾病密切相关。研究发现,具核梭杆菌在人体肠道内广泛存在,依其黏附和侵袭性产生毒性,并且不同菌株具有不同的毒力。目前,越来越多的实验研究证明,具核梭杆菌与结直肠癌之间存在相关性。具核梭杆菌在结直肠癌发生发展中的作用仍在探索中。     

结肠癌患者口腔具核梭杆菌与结肠癌发生关系的研究

目的：分析口腔具核梭杆菌（Fn）感染与结肠癌发生的关系。方法选取100例结肠癌患者为观察组,100例健康体检者为对照组,对比两组Fn感染率及Fn DNA含量差异。同时根据肿瘤分期将观察组患者分为A期组（39例）,B期组（31例）及C期组（30例）,对比3组间Fn感染率及Fn DNA含量差异。结果观察组Fn感染率及Fn DNA含量均高于对照组（P﹤0.05）;观察组3组间,Fn感染率分别是41.03%、70.97%和93.33%,而Fn DNA含量分别是（55.12±5.79）×108/L、（62.16±6.78）×108/L、（66.23±6.17）×108/L,3组间Fn感染率和Fn DNA含量比较差异均有统计学意义（P﹤0.05）,其中以C期组Fn感染率及Fn DNA含量最高;且经相关性分析发现,肿瘤分期与Fn DNA含量存在相关性（r=0.756,P﹤0.05）。结论 Fn感染在结肠癌的发生发展中可能具有一定作用,临床应对Fn感染引起重视,Fn感染可作为辅助结肠癌患者进行病理分期的一项指标。     

具核梭杆菌在上消化道恶性肿瘤中的作用及其机制

上消化道恶性肿瘤（食管癌和胃癌）的发病率高,生存率低,严重威胁人类生命健康,具核梭杆菌（Fn）是一种常见的革兰氏阴性厌氧菌,被证明与多种疾病相关。近期的研究表明,Fn与上消化道恶性肿瘤具有潜在的相关性,Fn在癌组织中富集,可通过促进上皮间质转化（EMT）、抑制机体抗肿瘤免疫、干扰多胺代谢等多种作用机制增强肿瘤细胞的增殖、迁移能力及耐药性,从而调控肿瘤的发生发展,影响肿瘤的治疗效果及预后,靶向Fn 治疗可以提高治疗肿瘤的疗效和改善患者预后;而应用天青蛋白、噬菌体引导的生物治疗等方法可有效治疗Fn感染;目前,针对Fn的疫苗也正在开发中。阐明Fn在上消化道恶性肿瘤发生发展和治疗中的作用及其可能的机制,以及针对Fn 的治疗策略,将有助于上消化道恶性肿瘤的早期诊断,提供新的有效的预防和治疗策略。     

结直肠癌标志物粪便检测的研究现状

结直肠癌(CRC)标志物粪便检测主要有以下4种方法：粪便隐血试验、粪便DNA检测、粪便微小RNA检测、粪便具核梭杆菌(Fn)检测。免疫法粪便隐血试验已经被国内外专家共识推荐作为CRC筛查的首选方法。由于粪便DNA检测费用偏高,目前国内尚未进行大样本的人群筛查,被推荐为CRC筛查的第二级检查。粪便微小RNA检测逐渐受到学...     

肠道菌群微生态与结直肠癌的研究进展

近年来中国结直肠癌的发病率逐年升高,已成为最常见的消化道恶性肿瘤之一。随着分子生物学及宏基因组学的深入研究,发现肠道菌群微生态及其代谢模式的改变可通过破坏正常组织细胞DNA、激活致癌信号传导途径,产生促肿瘤代谢物和抑制抗肿瘤免疫反应等多因素来影响结直肠癌的发生和发展。因此,研究者们尝试利用微生态制剂治疗和预防肿瘤。目前,以益生菌和排泄物移植技术为代表的微生态制剂可调节肠道菌群微生态,诱导结直肠癌细胞凋亡和细胞周期阻滞,分泌抗肿瘤细胞因子及调节免疫系统来抗肿瘤。微生态制剂为结直肠癌患者带来了希望,但目前肠道菌群微生态在结直肠癌中的具体作用机制仍不明确,仍需进一步的大样本研究深入探讨。本文就肠道菌群微生态与结直肠癌的研究进展进行综述,以期为结直肠癌的诊治探索新的方法。      

传统与快速肠道准备方法对结直肠癌术后肠道微生态的影响

目的 探讨传统与快速肠道准备方法对结直肠癌术后肠道微生态的影响.方法 选取2008年2月至2016年3月进行结直肠癌手术的62例患者的临床资料进行回顾性分析,根据入院时间先后顺序分组,将2008年2月至2013年5月间进行传统肠道准备的患者30例作为对照组,2013年6月至2016年3月间进行快速肠道准备的患者32例作为观察组.对2组患者术中肠道清洁度、手术前后菌群计数及菌群失调情况、术后并发症进行观察与比较.结果 2组患者肠道清洁度比较,差异无统计学意义(P＞0.05).手术后2组患者双歧杆菌及乳酸杆菌数量均显著下降,大肠杆菌及粪肠球菌数量均显著升高.观察组变化幅度明显低于对照组,差异有统计学意义(P＜0.05).观察组手术后肠道菌群失调情况与术前差异无统计学意义,对照组肠道菌群失调情况明显加重,观察组与对照组比较有统计学差异(P＜0.05).观察组患者术后并发症发生率为9.38％,远低于对照组的40.00％,差异有统计学意义(P＜0.05).结论 对拟行结直肠癌手术的患者进行快速肠道准备安全有效,对肠道菌群影响小于传统肠道准备,值得临床推广.     

结直肠癌组织中核因子κB的表达及其意义

大肠癌为常见的消化系统恶性肿瘤之一 ,许多基因及细胞因子在大肠癌的发生发展过程中发挥重要作用。近年来 ,核因子ＮＦ -κＢ在炎症、应激反应等方面的研究有一定进展 ,但是ＮＦ -κＢ与肿瘤尤其是与大肠癌的关系尚未见报道。我们应用免疫组化Ｓ -Ｐ法检测 5 2例结直肠癌组织中ＮＦ -κＢｐ6 5蛋白的表达 ,现报告如下。1　材料和方法1.1　材料材料为我院 1998年～ 1999年经手术切除的结直肠癌标本5 2例。男性患者 32例 ,女性 2 0例 ,年龄 2 7～ 81岁 ,平均 5 5岁 ,术前均未行放疗、化疗。Ｄｕｋｅｓ分期 :Ａ期 13例 ,Ｂ期 2 1例 ,Ｃ期 18例…     

Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis

Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8⁺ T cells, CD33⁺ cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163⁺ cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8⁺ T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8⁺ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.     

L-fucose ameliorates the carcinogenic properties of Fusobacterium nucleatum in colorectal cancer

Fusobacterium nucleatum (Fn) is considered a promoting factor in colorectal cancer (CRC); however, only a few studies have investigated therapies against Fn. L-fucose is a natural monosaccharide that has prebiotic potential. The present study aimed to investigate the effect of L-fucose on the carcinogenic properties of Fn. The HCT116 and SW480 colon cancer cell lines were treated with Fn and Fn+L-fucose (Fnf), respectively. The Cell Counting Kit-8 (CCK-8), colony formation, Transwell migration and invasion and wound healing assays were performed to assess the proliferative, migratory and invasive abilities of the cells, respectively. Western blot was performed to detect the protein levels of jak/stat3 pathway components and EMT. The results of the CCK-8, colony formation, Transwell and wound healing assays demonstrated that treatment with Fn significantly enhanced the proliferative, migratory and invasive abilities of HCT116 and SW480 colon cancer cells. Notably, these effects were significantly reversed following addition of L-fucose. Furthermore, L-fucose inhibited the carcinogenic properties of Fn to activate the stat3 pathway and epithelial-to-mesenchymal transition. Taken together, the results of the present study suggest that L-fucose ameliorates the carcinogenic properties of Fn in vitro, and thus may serve as a novel therapeutic target for flora-related colon cancer.     

Fusobacterium nucleatum and colorectal cancer: A review

Fusobacterium nucleatum (F. nucleatum) is a Gram-negative obligate anaerobe bacterium in the oral cavity and plays a role in several oral diseases, including periodontitis and gingivitis. Recently, several studies have reported that the level of F. nucleatum is significantly elevated in human colorectal adenomas and carcinomas compared to that in adjacent normal tissue. Several researchers have also demonstrated that F. nucleatum is obviously associated with colorectal cancer and promotes the development of colorectal neoplasms. In this review, we have summarized the recent reports on F. nucleatum and its role in colorectal cancer and have highlighted the methods of detecting F. nucleatum in colorectal cancer, the underlying mechanisms of pathogenesis, immunity status, and colorectal cancer prevention strategies that target F. nucleatum.     

Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway

The prevalence of invasive Fusobacterium nucleatum (Fn) within the serrated neoplasia pathway of the proximal colon has seldom been investigated. We examined the invasive Fn and bacterial biofilms in 35 proximal hyperplastic polyps (HPs), 33 sessile serrated adenomas (SSAs), 48 proximal colorectal cancers (CRCs) and 10 matched metastatic lymph nodes using 16S rRNA fluorescence in situ hybridization (FISH). Samples of normal mucosa, traditional adenomas (TAs), distal HPs, distal CRCs and matched lymph nodes with or without metastases were used as controls. The prevalence of invasive Fn within proximal HPs (65.7%) and SSAs (78.8%) were significantly higher than that of proximal TAs (28.9%) and distal TAs (24.4%; p < 0.05). Invasive Fn was detected in markedly more proximal CRCs (89.6%) than in distal CRCs (42.2%; p < 0.05). Moreover, invasive Fn was detected in a significantly higher proportion of matched metastatic lymph nodes (100%) than that within nonmetastatic lymph nodes (40.0%; p < 0.001). Bacterial biofilms were found on 52.1% of proximal CRCs, 55.6% of distal CRCs and 48.5% of SSAs. Biofilms were positive for Fn in 47.9% of proximal CRCs, 48.9% of distal CRCs and 27.3% of SSAs. However, the presence of Fn in biofilms was not related to invasive Fn within colorectal tissues (p = 0.415). Invasive Fn may play a role in the carcinogenesis of proximal colon developing via the serrated neoplasia pathway, but might have a less important role in the TA‐carcinoma sequence. Bacterial biofilms may not contribute to the invasion of Fn into tumor tissues.     

Intratumor Fusobacterium nucleatum promotes the progression of pancreatic cancer via the CXCL1-CXCR2 axis

Intratumor bacteria modify the tumor immune microenvironment and influence outcomes of various tumors. Periodontal pathogen Fusobacterium nucleatum has been detected in pancreatic cancer tissues and is associated with poor prognosis. However, it remains unclear how F. nucleatum affects pancreatic cancer. Here, we compared clinical features with F. nucleatum colonization in pancreatic cancer tissues. F. nucleatum was detected in 15.5% (13/84) of pancreatic cancer patients. The tumor size was significantly larger in the F. nucleatum-positive group than in the negative group. To clarify the biological effect of intratumor F. nucleatum on pancreatic cancer progression, we performed migration/invasion assays and cytokine array analysis of cancer cells cocultured with F. nucleatum. F. nucleatum promoted CXCL1 secretion from pancreatic cancer cells, leading to cancer progression through autocrine signaling. Intratumor F. nucleatum suppressed tumor-infiltrating CD8⁺ T cells by recruiting myeloid-derived suppressor cells (MDSCs) to the tumor in an F. nucleatum-injected subcutaneous pancreatic cancer mouse model, resulting in tumor progression. Furthermore, tumor growth accelerated by F. nucleatum was suppressed by MDSC depletion or cytokine inhibitors. Intratumor F. nucleatum promoted pancreatic cancer progression through autocrine and paracrine mechanisms of the CXCL1-CXCR2 axis. Blockade of the CXCL1-CXCR2 axis may be a novel therapeutic approach for patients with intratumor F. nucleatum-positive pancreatic cancer.     

Mediation effect of intestinal microbiota on the relationship between fiber intake and colorectal cancer

Higher fiber intake has been associated with a lower risk of colorectal cancer (CRC) and has been shown to protect against CRC based on probable evidence. Recent studies revealed a possible mechanism whereby the interaction between intestinal microbiota and fiber intake mediates CRC risk. However, the specific intestinal bacteria and the amount of these bacteria involved in this mechanism are not fully known. Therefore, this single-center study aimed to determine whether specific intestinal bacteria mediated the relationship between fiber intake and CRC risk. We enrolled patients who received colonoscopy at National Cancer Center Hospital. This cross-sectional study included 180 patients with clinically diagnosed CRC and 242 controls. We conducted a causal mediation analysis to assess the natural indirect effect and natural direct effect of specific intestinal bacteria on association between fiber intake and CRC risk. The median age was 64 (interquartile range, 54-70) years, and 58% of the participants were males. We used metagenomics for profiling gut microbiomes. The relative abundance of each species in each sample was calculated. Among the candidate, Fusobacterium nucleatum and Gemella morbillorum had a significant natural indirect effect based on their highest fiber intake compared to the lowest fiber intake, with a risk difference (95% confidence interval, proportion of mediation effect) of −0.06 [−0.09 to −0.03, 23%] and −0.03 [−0.06 to −0.01, 10.5%], respectively. Other bacteria did not display natural indirect effects. In conclusion, Fusobacterium nucleatum and Gemella morbillorum were found to mediate the relationship between fiber intake and CRC risk.     

AQPs在结直肠癌缺氧微环境中的表达及临床意义研究现状

结直肠癌（colorectal cancer,CRC）的发病率和死亡率逐年上升,水通道蛋白是一类存在于细胞膜上的膜转运蛋白,参与缺氧肿瘤微环境中肿瘤细胞的增殖、侵袭和转移等过程,甚至与肿瘤耐药性相关。结直肠癌患者中存在多种水通道蛋白的表达失调,在肿瘤的发生和发展过程中发挥关键作用。随着精准治疗的开展,将水通道蛋白作为新靶点可能为结直肠癌的治疗提供新途径。本文就水通道蛋白(aquaporins,AQPs)在结直肠癌缺氧微环境中的表达及其临床意义作一综述。     

结直肠癌与自然杀伤细胞的相关性探讨北大核心

目的:研究结直肠癌及其配对的癌旁组织的自然杀伤(nature killer,NK)细胞数量及分布情况。方法:结直肠癌及其配对的癌旁组织各40例,以SP免疫组化法检测NK细胞。结果:结直肠癌及其配对的癌旁组织中均未检测到NK细胞的浸润。结论:结直肠癌及其配对的癌旁组织中缺乏NK细胞浸润可能与肿瘤微环境、生理微环境、未知的NK细胞亚型相关,结直肠癌患者可能不适用NK细胞进行免疫治疗。