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

Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease

Background and aims: Treatment with infliximab induces remission in about 70% of patients with steroid refractory Crohn's disease. Because Crohn's disease is considered to be mediated by uncontrolled activation of mucosal T lymphocytes, we hypothesised that infliximab could induce apoptosis of T lymphocytes. Methods: Induction of apoptosis in vivo was studied in 10 patients with therapy refractory Crohn's disease. In vitro, resting or stimulated Jurkat T cells were incubated with infliximab. Results: Infusion of infliximab (5 mg/kg) in steroid refractory patients with Crohn's disease induced a clinical response in 9/10 patients but did not influence expression of activation markers, homing receptors, memory cells, Fas expression, or Bax/Bcl-2 expression on peripheral blood T lymphocytes. In contrast, a significant increase in CD3 and TUNEL positive cells within colonic biopsies was detected 24 hours after infusion of infliximab, suggesting that infliximab stimulates apoptosis of activated T lymphocytes but not of resting T cells. To test this hypothesis, the effects of infliximab on Jurkat T cells were investigated. We observed that infliximab induced apoptosis and an increase in the Bax/Bcl-2 ratio of CD3/CD28 stimulated Jurkat T cells but not of unstimulated Jurkat cells. Conclusions: Our data indicate that infliximab treatment causes a rapid and specific increase in apoptosis of T lymphocytes in the gut mucosa. These findings may explain the rapid and sustained therapeutic effects of infliximab in Crohn's disease

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