Van anus tot kanis

Rede, In verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht Experimentele Gastroenterologie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 29 april 201

Meeting report on the first Sino-Dutch symposium on oncology

On October 31, 2015, the first Sino-Dutch symposium on oncology was organized in Guangzhou (China). The symposium revealed similarities between Chinese and Dutch efforts to improve the care of tumor patients and to create enhanced insight into the nature of cancers. In particular, it became evident for some types of cancer that immunotherapy should focus on counteracting interleukin-17-associated immunity and targeting cancer stroma. Targeting specific cancer microenvironment and stroma also opens new therapeutic options, including the use of radio-active theranostics and live tumor imaging-guided surgeries

Opportunities for conventional and in situ cancer vaccine strategies and combination with immunotherapy for gastrointestinal cancers, a review

Survival of gastrointestinal cancer remains dismal, especially for metastasized disease. For various cancers, especially melanoma and lung cancer, immunotherapy has been proven to confer survival benefits, but results for gastrointestinal cancer have been disappointing. Hence, there is substantial interest in exploring the usefulness of adaptive immune system education with respect to anti-cancer responses though vaccination. Encouragingly, even fairly non-specific approaches to vaccination and immune system stimulation, involving for instance influenza vaccines, have shown promising results, eliciting hopes that selection of specific antigens for vaccination may prove useful for at least a subset of gastrointestinal cancers. It is widely recognized that immune recognition and initiation of responses are hampered by a lack of T cell help, or by suppressive cancer-associated factors. In this review we will discuss the hurdles that limit efficacy of conventional cancer therapeutic vaccination methods (e.g., peptide vaccines, dendritic cell vaccin

Helicobacter pylori pathogenicity factors related to gastric cancer

_Background_. Although the causal relationship between Helicobacter pylori infection and the development of gastric cancer is firmly established, the exact nature of the pathogenicity factors of H. pylori that predispose to gastric oncogenesis remains incompletely characterized. We investigated the association between H. pylori virulence genotypes and disease in a well-characterized cohort consisting of 109 H. pylori isolates from gastric biopsies originating from patients. _Methods_. The prevalence of genotype was assessed by PCR and related to clinical histopathological parameters. _Results_. The relation of babA2 and babB negative and iceA1 positive genotype as a single genotype and the development of cases to GC was statistically significant (P<0.001). The cagE, cagA, and iceA1 were found more commonly in patients with GC as compared with the other groups. The relation of the presence of iceA1 and the development of cases to GC was statistically significant (P=0.008), bu

Bacterial biofilms as a potential contributor to mucinous colorectal cancer formation

A prominent mucinous phenotype is observed in 10–15% of all colorectal cancers (CRCs). They are associated with a proximal location, and more commonly observed among tumors with mismatch repair defects and a promoter CpG methylator phenotype. However, none of these features has been clearly linked mechanistically to this mucinous subtype. Here, we propose that bacterial biofilms could represent a currently unappreciated contributor to mucinous CRC formation. The colonic microbiome and biofilms in particular, are emerging as important factors in tumor initiation and progression. Intriguingly, biofilms preferentially accompany proximal tumors, suggesting that there may be a direct mechanistic link with mucinous CRCs

Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma

Hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide but the mechanistic basis as to how chronic HCV infection furthers the HCC process remains only poorly understood. Accumulating evidence indicates that HCV core and nonstructural proteins provoke activation of the Wnt/β-catenin signaling pathway, and the evidence supporting a role of Wnt/β-catenin signaling in the onset and progression of HCC is compelling. Convincing molecular explanations as to how expression of viral effectors translates into increased activity of the Wnt/β-catenin signaling machinery are still largely lacking, hampering the design of rational strategies aimed at preventing HCC. Furthermore, how such increased signaling is especially associated with HCC oncogenesis in the context of HCV infection remains obscure as well. Here we review the body of contemporary biomedical knowledge on the role of the Wnt/β-catenin pathway in the progression from chronic hepatitis C to cirrhosis and HCC and explore potential hypotheses as to the mechanisms involved

Lipopolysaccharide restricts murine norovirus infection in macrophages mainly through NF-kB and JAK-STAT signaling pathway

The inflammasome machinery has recently been recognized as an emerging pillar of innate immunity. However, little is known regarding the interaction between the classical interferon (IFN) response and inflammasome activation in response to norovirus infection. We found that murine norovirus (MNV-1) infection induces the transcription of IL-1β, a hallmark of inflammasome activation, which is further increased by inhibition of IFN response, but fails to trigger the release of mature IL-1β. Interestingly, pharmacological inflammasome inhibitors do not affect viral replication, but slightly reverse the inflammasome activator lipopolysaccharide (LPS)-mediated inhibition of MNV replication. LPS efficiently stimulates the transcription of IFN-β through NF-ĸB, which requires the transcription factors IRF3 and IRF7. This activates downstream antiviral IFN-stimulated genes (ISGs) via the JAK-STAT pathway. Moreover, inhibition of NF-ĸB and JAK-STAT signaling partially reverse LPS-mediated anti-MNV activity, suggesting additional antiviral mechanisms activated by NF-ĸB. This study reveals additional insight in host defense against MNV infection

Serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) predict severity of liver disease in chronic hepatitis B

Background and aim: Caspase-cleaved cytokeratin 18 (CK18-Asp396) is a potential clinically useful biomarker in liver disease as it is released from hepatocytes during apoptosis. In this study, we investigated serum CK18-Asp396 levels in chronic hepatitis B (CHB). Patients and methods: Overall, 163 patients with CHB were included. Serum CK18-Asp396 levels were determined by enzyme-linked immunosorbent assay (ELISA), and results were related to steatosis grade, histological activity index, inflammation score, and METAVIR fibrosis grade as well as to viral load, serum levels of liver enzymes, and albumin. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of serum CK18-Asp396 levels for assessing disease activity. Results: A higher level of serum CK 18 concentrations was found in patients with significant inflammation vs no significant inflammation (378.5 [interquartile range {IQR}: 173.2-629.6] vs 137.3 [87.5-197.7], P < 0.05; approximately threefold increase) and in patients with significant fibrosis vs no significant fibrosis (177.8 [IQR: 120.8-519.1] vs 142.7 [IQR: 88.8-214.4], P < 0.05; 1.25-fold increase). There was no differential CK 18 level by degree of steatosis. CK 18 was an independent predictor of significant inflammation with an 82% specificity and a 94% negative predictive value. We found the strongest correlation of CK 18 with alanine aminotransferase and aspartate aminotransferase (both r = 0.52; P < 0.001), but less with albumin (r = -0.24; P < 0.05) and viral load (log) (r = 0.19; P < 0.05). Conclusion: CHB appears to be accompanied by continuous high levels of hepatocyte apoptosis as judged from serum CK 18, suggesting that elimination of the infected compartment constitutes a defensive strategy against disease. Accordingly, CK 18 works as an independent predictor of significant inflammation with a high specificity

Factors associated with ethnical disparity in overall survival for patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an important cause of cancer-related death worldwide. Ethnical disparity in overall survival has been demonstrated for HCC patients in the United States (U.S.). We aimed to evaluate the contributors to this survival disparity. The SEER database was used to identify HCC patients from 2004 to 2012. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate overall survival by ethnicity and the contributors to ethnical survival disparity. A total of 33 062 patients were included: 15 986 Non-Hispanic Whites, 6535 Hispanic Whites, 4842 African Americans, and 5699 Asians. Compared to Non-Hispanic Whites, African Americans had worse survival (HR, 1.18; 95%CI, 1.14-1.23), while Asians had a better survival (HR, 0.85; 95%CI, 0.82-0.89), and Hispanic Whites had a similar survival (HR, 1.01; 95%CI, 0.97-1.05). Multivariate Cox analysis identified that tumor presentation- and treatment-related factors significantly contributed to the ethnical survival disparity. Especially, tumor size was the most important contributor (HR, 1.11; 95%CI, 1.07-1.16). There is no ethnical survival disparity in patients undergoing liver transplantation and sub-analysis of patients within the Milan criteria for liver transplantation demonstrated no significant survival disparity between African Americans and non-Hispanic Whites in transplantation adjustment analysis (HR, 1.23; 95%CI, 1.11-1.35 in non-adjustment analysis to HR, 1.05; 95%CI, 0.95-1.15 after adjustment). Finally, no important contributor to the superior overall survival in Asians was identified. In conclusion, poor tumor presentation at diagnosis, limited benefit from resection and restricted utilization of liver transplantation are important contributors to poorer survival of African Americans with HCC