Characterization of leukocytes infiltrating colorectal tumors

This thesis describes six studies which characterized tumor-infiltrating leukocytes (TIL) in colorectal cancer. TIL have shown to be of importance in the natural anti-tumor immunity of cancer patients. Chapter 1 gives an introductory overview of tumor immunology, TIL and colorectal cancer. In chapter 2 we describe the presence, location, and phenotype of tumor-infiltrating dendritic cells in colorectal cancer. With special attention to their association with other tumor-infiltrating immune cells, i.e. lymphocytes. Chapter 3 elaborates further on the role of tumor-infiltrating DC by evaluating whether there is an association between the presence and maturation status of tumor-infiltrating DC, T lymphocytes and clinical prognosis in patients with colorectal cancer. In chapter 4 NK cell infiltration in colorectal cancer is studied in relationship with loss of tumor MHC class I expression. In chapter 5 TIL were characterized in a case-control design, with tumors showing complete absence or normal expression of HLA class I. We further characterized TIL in a group of colorectal tumors displaying systemic P53 reactivity in chapter 6. Chapter 7 describes the technique of the multi-color immunohistochemical analysis, which we used to characterize the phenotype of TIL in the two preceding chapters. Chapter 8 Summary and Discussion.KWF KankerbestrijdingUBL - phd migration 201

Complaints and Diagnoses of Emergency Department Patients in the Netherlands: A Comparative Study of Integrated Primary and Emergency Care

Contains fulltext : 154853.PDF (publisher's version ) (Open Access)OBJECTIVE: In the Netherlands, an increasing number of emergency departments (EDs) and general practitioner cooperatives collaborate by creating one Emergency-Care-Access-Point (ECAP). This has resulted in fewer patients at ECAP EDs. The objective of this study was to explore differences in patient characteristics, presented complaints and ED discharge diagnoses between EDs with an ECAP and EDs without an ECAP. METHODS: A retrospective observational study was performed with 1800 consecutive patient records sampled from six EDs spread over the Netherlands in 2013. We extracted data on time and date of presentation, sex, age, presenting complaint, discharge diagnosis, origin and follow up. RESULTS: At ECAP EDs, the mean age was 47.8 years (95%CI 46.1-49.4) compared to 41.3 (95%CI 39.7-42.9). Compared to non-ECAP EDs, more patients were referred by medical professionals (74.7% versus 46.8%), more patients received hospital admission (45.2% versus 29.0%) and fewer patients received GP follow-up (4.1% versus 16.9%). There was no significant difference in presenting complaints between ECAP and non-ECAP EDs. Most prevalent complaints were trauma (25.7% versus 29.7%), abdominal pain (12.1% versus 10.9%) and general symptoms (7.8% versus 4.8%). The most prevalent ED diagnoses significantly differed with fractures and dislocations (10.8%), sprains and strains (10.4%) and respiratory infections (6.8%) at ECAP EDs versus fractures and dislocations (10.7%), wounds (9.3%) and sprains and strains (8.9%) at non-ECAP EDs. CONCLUSION: Compared to non-ECAP EDs, patients at ECAP EDs were older, medical professionals referred more patients and more patients received a hospital admission. We found some small differences in discharge diagnoses between ECAP EDs compared to non-ECAP EDs, but no difference in presented complaints

A cellular automata model to investigate immune cell-tumor cell interactions in growing tumors in two spatial dimensions

We develop a hybrid cellular automata model to describe the effect of the immune system and chemokines on a growing tumor. The hybrid cellular automata model consists of partial differential equations to model chemokine concentrations, and discrete cellular automata to model cell–cell interactions and changes. The computational implementation overlays these two components on the same spatial region. We present representative simulations of the model and show that increasing the number of immature dendritic cells (DCs) in the domain causes a decrease in the number of tumor cells. This result strongly supports the hypothesis that DCs can be used as a cancer treatment. Furthermore, we also use the hybrid cellular automata model to investigate the growth of a tumor in a number of computational “cancer patients.” Using these virtual patients, the model can explain that increasing the number of DCs in the domain causes longer “survival.” Not surprisingly, the model also reflects the fact that the parameter related to tumor division rate plays an important role in tumor metastasis

ROLE OF CD1A AND HSP60 IN THE ANTITUMORAL RESPONSE OF OESOPHAGEAL CANCER.

Oesophageal cancer (OC) is one of the most common and severe forms of tumor. A wider knowledge of molecular mechanisms which lead to a normal epithelium becoming a neoplasm may reveal new strategies to improve treatment and outcome of this disease. In this review, we report recent findings concerning molecular events which take place during carcinogenesis of the oesophagus. In particular, we focus on the role of two molecules, CD1a and Hsp60, which are overexpressed in oesophageal and many other types of tumor. Both molecules may present tumor antigens and promote in situ the stimulation of an antitumoral immune activity. We suggest there is a synergistic action between these molecules. Further knowledge about their intracellular pathways and extracellular roles may help develop new antitumoral tools for OC