The role of FKBP51 in the prognosis of ulcerative colitis-associated colorectal cancer

PurposeUlcerative colitis (UC) carries a high risk of developing colorectal cancer (CRC). FK506-binding protein 51 (FKBP51) is a key regulator of glucocorticoid resistance and inflammatory tumor microenvironment. This study aimed to investigate the role of FKBP51 in UC-CRC prognosis.Materials and methodsThe FKBP51 expression was measured by immunohistochemistry, qRT-PCR and western blot in control and tumor-containing tissues from UC-CRC patients. H&E staining was used to analyze the inflammatory status of each sample. The relationship between FKBP51 expression and UC-CRC prognosis was assessed by Kaplan–Meier curves and Mann-Whitney U test, and receiver-operating characteristic curves were generated to clarify the role of FKBP51 in predicting survival period and recurrence of UC-CRC patients.ResultsThe FKBP51 expression was significantly (p ​< ​0.01) increased by 36.3% in tumor-containing tissues compared to control tissues in UC-CRC patients. Nuclear enrichment of FKBP51 in tumor-containing tissues was significantly (p ​< ​0.001) increased by 78.5%. The UC-CRC patients with higher levels of FKBP51 expression ratio between tumor-containing tissues and control tissues had shorter survival periods, but greater neutrophil invasion and neutrophils to lymphocytes ratio (NLR) in peripheral blood. Moreover, the FKBP51 expression ratio was more helpful in predicting the survival periods and recurrence in the UC-CRC patients than the NLR in peripheral blood.ConclusionsThe FKBP51 expression ratio between tumor-containing tissue and control tissue may be an important biomarker of inflammatory tumor microenvironment and more helpful for the UC-CRC prognosis.     

The effect of appendectomy on the course of ulcerative colitis: a systematic review

Aim Previous studies have shown significantly lower appendectomy rates in ulcerative colitis (UC) patients compared with healthy controls. Evidence indicating that the appendix has an immunomodulatory role in UC has been accumulating. To examine the latest evidence on the effect of appendectomy on the disease course of UC. Method PubMed, The Cochrane Library and EMBASE were searched. Primary end‐points were number of relapses, use of steroids, number of hospital admissions and number of colectomies. Results The search resulted in six observational studies (five case–control studies and one cohort study) totalling 2532 patients. Owing to clinical heterogeneity, no meta‐analysis could be conducted. One study found lower relapse rates in patients appendectomized before the onset of UC [absolute risk reduction (ARR) = 21.5%; 95% CI: 1.71–45.92%]. Another two studies found a reduced requirement for immunosuppression in appendectomized patients (ARR = 20.2%; 95% CI: 9.67–30.46% in the first study and ARR = 21.4%; 95% CI: 10.32–32.97% in the second study). In addition, one study found lower colectomy rates in nonappendectomized patients (ARR = 8.7%; 95% CI: 1.29–18.66%) and two studies found lower colectomy rates in appendectomized patients (ARR = 21.4%; 95% CI: 13.17–28.79% in the first study and ARR = 18.7%; 95% CI: 7.50–29.97% in the second study). Conclusion There are limited and conflicting data available regarding the effect of appendectomy on the disease course of UC. Most studies suggest a beneficial effect and the minority find no, or a negative, effect.     

Association between microRNA polymorphisms and chronic pancreatitis

BackgroudMicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1β, IL-6, TNF-α, NF-κB and chemokine MCP-1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk.MethodsThe rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP).ResultsThe frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076–1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233–10.916, p = 0.019; OR = 5.667, 95%CI = 1.852–17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a.ConclusionThese findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development.     

TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice

Tumor necrosis factor like cytokine 1A (TL1A) is a member of the TNF superfamily. Accumulating evidence demonstrated the importance of TL1A in the pathogenesis of inflammatory bowel disease (IBD) and suggested a potential role of TL1A blocking in IBD therapy. Here we aimed to explore whether the anti-TL1A antibody could ameliorate intestinal inflammation and fibrosis in IBD. A T cell transfer model of chronic colitis was induced by intraperitoneal injection of CD4⁺CD45RB^high naive T cells isolated from either C57BL/6 wild type (WT) mice or LCK-CD2-Tl1a-GFP transgenic (L-Tg) mice into recombinase activating gene-1-deficient (RAG^?/?) mice. The colitis model mice were treated prophylactically or therapeutically with anti-Tl1a antibody or IgG isotype control. Haematoxylin and eosin staining (H&E staining), Masson's trichrome staining (MT staining) and sirius red staining were used to detect histopathological changes in colonic tissue; immunohistochemical staining was used to detect the expressions of collagen I, collagen III, TIMP1, vimentin, α-SMA and TGF-β1/Smad3. Results showed that anti-Tl1a antibody could reduce intestinal inflammation and fibrosis by inhibiting the activation of intestinal fibroblasts and reducing the collagen synthesis in the T cell transfer model of chronic colitis. The mechanism may be related to the inhibition of TGF-1/Smad3 signaling pathway.     

Feeding associated neonatal necrotizing enterocolitis (Primary NEC) is an inflammatory bowel disease

Neonatal necrotizing enterocolitis which develops after feeding preterm infants is characterized by severe intestinal inflammation and profound systemic metabolic acidosis. The fermentation of undigested dietary carbohydrate by colonic flora yields gases (CO₂ and H₂) and short chain organic acids. These organic acids can disrupt the intestinal mucosa and initiate inflammation driven predominantly by resident mast cells and by granulocytes which are recruited from blood. A systemic acidosis ensues derived from intestinal acids, not classic lactic acidosis produced from anaerobic metabolism. The systemic acidosis further compromises inflamed bowel leading to bowel necrosis.     

Genomic profiling of inflammatory breast cancer: A review

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite efforts in the past decade to delineate the molecular biology of IBC by applying high-throughput molecular profiling technologies to clinical samples, IBC remains insufficiently characterized. The reasons for that include limited sizes of the study population, heterogeneity with respect to the composition of the IBC and non-IBC control groups and technological differences across studies. In 2008, the World IBC Consortium was founded to foster collaboration between research groups focusing on IBC. One of the initial projects was to redefine the molecular profile of IBC using an unprecedented number of samples and search for gene signatures associated with survival and response to neo-adjuvant chemotherapy. Here, we provide an overview of all the molecular profiling studies that have been performed on IBC clinical samples to date.     

上颌窦炎性肌纤维母细胞瘤病例报告及文献回顾

摘要：目的探讨上颌窦炎性肌纤维母细胞瘤的临床表现，病理学特征、诊断、治疗及预后，旨在提高耳鼻咽喉科医生对该病的认识和治疗水平，并减少漏诊误诊。方法报告1例上颌窦炎性肌纤维母细胞瘤，并复习相关的国内外文献。结果CT扫描示窦腔可见低密度肿块影且突入眼眶，邻近窦壁明显受压、变薄，增强明显不均匀强化。MRI示类圆形稍高/等T2、T1信号肿块影，边界不清。病理示瘤组织主要由梭形肌纤维母细胞及大量炎性细胞组成。免疫组化中SMA、VIM等呈阳性，CK呈阴性。术后随访9个月，复查CT示左上颌窦窦腔未见明显新生物，呈术后改变。结论上颌窦炎性肌纤维母细胞瘤是非常罕见的，其诊断主要依靠病理及免疫组化检测。根治性手术切除仍为目前首选治疗方法，对于体积过大的血供占位病变，术前可辅助介入栓塞治疗。     

干细胞疗法治疗炎症性肠病的应用

炎症性肠病是一种慢性炎症性疾病,主要包括克罗恩病和溃疡性结肠炎,其发病原因尚不清楚。干细胞疗法在治疗炎症性肠病方面可能是非常有价值的,近年来,干细胞疗法的研究也更加突出而显著,本文就干细胞疗法治疗炎症性肠病的应用作一概述。     

Tofacitinib for the treatment of ulcerative colitis

ABSTRACT

Introduction: New generations of small molecules are being developed for the treatment of ulcerative colitis. Among them, tofatinib (a Janus kinase (JAK) inhibitor) has demonstrated efficacy for inducing and maintaining remission and achieving mucosal healing with a reasonable safety profile. Oral administration is attractive for patients and lack of immunogenicity represents an advantage over biologic drugs.

Areas covered: This review discusses the molecular aspects of the JAK-STAT pathway; the mechanism of action of tofacitinib pertinent to ulcerative colitis and the evidence on the efficacy of tofacitinib for achieving clinically relevant outcomes, including clinical remission, mucosal healing, and normalization of quality of life, as well as safety aspects with special attention to adverse events related to the mode of action of the drug.

Expert commentary: Tofacitinib will be the first drug on the class of JAK inhibitors to be available for treatment of ulcerative colitis. The efficacy of the drug, with a rapid onset of action even in cases of severe colitis, oral administration, and possibility to use the drug intermittently without generating immunogenicity, will bring about a redesign of current treatment paradigms for ulcerative colitis.