Research Jan Vermorken

Abstract

Colorectal cancer (CRC) remains the third most common form of cancer and cancer related deaths in developed countries. The prognosis of CRC is largely determined by the extent of primary disease at the time of diagnosis. Although the introduction of new chemotherapeutic agents improved the prognosis of CRC over the past decades, the outlook for most patients remains poor and difficult to predict. Tumor recurrence after curative resection continues to be a significant problem in the management of CRC. Since CRC is not uniformly fatal and large differences in survival exist depending on stage of the disease, optimal patient selection for therapeutic intervention mandates strategies to individualize patient treatment using both prognostic and predictive indicators. These robust markers can better quantify the risks and benefits of a particular treatment approach for an individual patient. The TNM staging system is currently the most important determent of prognosis, however it does not allow for an accurate prediction of the postoperative risk of tumor recurrence for individual patients. Therefore, identification of additional prognostic markers to supplement the standard clinical and pathological staging of the tumor is warranted. This study aims at investigating the prognostic value of several immunological parameters, as well as the role of two viral infections in CRC.

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

This is a fundamental research project financed by the Research Foundation - Flanders (FWO). The project was subsidized after selection by the FWO-expert panel.

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan

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Project type(s)

• Research Project

Abstract

The aim of the project is 1) Research on different signal transduction pathways to clarify the mechanism of radiosensitisation under normoxic and hypoxic conditions, and to elucidate the mechanism of resistance under hypoxia; 2) In depth study of the involvement of proteins with altered gene expression using western blot analysis and flow cytometry.

Researcher(s)

• Promoter: Vermorken Jan
• Co-promoter: Lardon Filip
• Fellow: Pauwels Bea

Research team(s)

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• Research Project

Abstract

Researcher(s)

• Promoter: Vermorken Jan
• Co-promoter: Lardon Filip

Research team(s)

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• Research Project

Abstract

Because of promising results in the clinic and a vast interest for in vitro research to the combination of chemotherapy and radiotherapy, an efficient in vitro hypoxia model will be developed to study the interactions between chemotherapy and radiotherapy under hypoxic conditions. This model will be used to investigate the interaction both under normoxic and hypoxic conditions and to study possible regulating factors and signal transduction of the radiosensitizing mechanism.

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Pauwels Bea
• Co-promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan
• Fellow: Simoens Cindy

Research team(s)

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• Research Project

Abstract

It is well established that solid tumours frequently contain regions of hypoxia. Tumour hypoxia may induce resistance or a reduced sensitivity to radiation and chemotherapy. In that respect, it is very important to investigate new therapies in preclinical research under hypoxic conditions. However, an efficient in vitro hypoxia model is not available so far. Therefore, it seems very desirable to develop and optimize an hypoxic model. In this way, it will be possible to study the interaction between cytotoxic agents (for example cisplatin, gemcitabine) and irradiation under normoxic and hypoxic conditions in vitro. In addition, the hypoxia model can be used to analyse factors that contribute to radiosensitization under normoxia and hypoxia.

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan
• Fellow: Wouters An

Research team(s)

Project type(s)

• Research Project

Abstract

Objectives of the project: 1. To study of the influence af gemcitabine and/or radiotherapy on the cell cycle checkpoint-mechanism ta understand the molecular mechanism af cell cycle arrest. 2. To clarify the apoptotic pathway: Is the increased apoptosis observed after treatment with gemcitabine/radiotherapy reached by the mitochondria' ar by the receptor-mediated pathway? 3. To Investigate the influence af gemcitabine on the repair af radiation-induced DNA damage as a possible mechanism for radiosensitisation.

Researcher(s)

• Promoter: Vermorken Jan
• Co-promoter: Lardon Filip
• Fellow: Pauwels Bea

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

There is an urgent need for preclinical research to the interaction between chemo- and radiotherapy, to optimise the clinical application. Gemcitabine is a nucleoside analogue with radiosensitising properties. In this project, the molecular mechanism of this enhancement effect will be investigated. The radiosensitising effect is correlated with the cell cycle effect of gemcitabine. Therefore, the checkpoint mechanism will be studied to determine its responsibility for the enhancement effect. Secondly, the increased apoptotic cell death will be further investigated to clarify the pathway of apoptosis. The interaction between gemcitabine and radiation might be caused bya reduction of the sublethal damage repair. In the third part of the study, the influence of gemcitabine on the repair of radiation-induced DNA damage and the characteristics of the DNA repair mechanism playing a role in the radiosensitising effect will be investigated.

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan
• Fellow: Pauwels Bea

Research team(s)

Project type(s)

• Research Project

Abstract

It is well established that solid tumours frequently contain regions of hypoxia. Tumour hypoxia may induce resistance or a reduced sensitivity to radiation and chemotherapy. In that respect, it is very important to investigate new therapies in preclinical research under hypoxic conditions. However, an efficient in vitro hypoxia model is not available so far. Therefore, it seems very desirable to develop and optimize an hypoxic model. In this way, it will be possible to study the interaction between cytotoxic agents (for example cisplatin, gemcitabine) and irradiation under normoxic and hypoxic conditions in vitro. In addition, the hypoxia model can be used to analyse factors that contribute to radiosensitization under normoxia and hypoxia.

Researcher(s)

• Promoter: Lardon Filip
• Co-promoter: Vermorken Jan
• Fellow: Wouters An

Research team(s)

Project type(s)

• Research Project

Abstract

(part UA) Aim of this study is to investigate differences in biological behaviour between sporadic colorectal tumours and to determine the relation of these differences with clinico-pathological parameters. This way we hope to find markers that can differentiate between patients with a low or a high risk of relapse.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

The role of HPV in the development of cervical cancer has been established beyond doubt. The odds ratio of the presence of HPV for the development of cervical cancer is even higher than that of smoking for lung cancer. In 1999, Walboomers et al. developed guidelines for the optimal detection of HPV in cervical cancer specimens, with which they were able to detect HPV in 99.7% of all cervical cancer cases. The Polish partner in this project has accumulated material of 300 cervical cancer cases. Although they adhered to the guidelines, i.e. use of fresh frozen material, use of multiple PCR methods directed at different parts of the HPV genome, the prevalence of HPV in their material was only 70%. To definitively rule out the unlikely possibility of a methodological flaw, the samples will be tested with a recently developed general HPV PCR that amplifies a short (60 basepairs) region and hence is very sensitive. However, as it is expected that this will not dramatically effect the HPV prevalence in this population, we want to look at differences between the HPV positive and HPV negative populations by studying loss of heterozygosity, single cell electrophoresis and microsatellite instability. These techniques should give us insight into changes in the human genome in the presence or absence of HPV. These data, combined with clinico-pathological parameters, will show whether the two populations are truly different.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

The concurrent use of chemotherapy and radiation has been applied more frequently in the treatment of cancer. Besides the possibility to improve local control and to treat the disease both locally and systemically, some chemotherapeutic agents have the potential to increase the sensitivity for radiation, i.e. radiosensitization. Although the combined-modality therapy may lead to an improved therapeutic outcome, the combination of gemcitabine and radiotherapy also results in increased toxicity of normal tissues. Therefore, this combination has to be applied carefully in the clinic. The use of cytoprotectieve agents, like amifostine, which selectively protects a broad range of normal tissues against a variety of cytotoxic therapies, including several chemotherapeutic agents and radiotherapy, might optimize the combination gemcitabine and radiotherapy. The combination gemcitabine and radiotherapy will be studied in tumor cells and optimized by the use of amifostine. Different treatment schedules will be tested to determine the optimal schedule for the combination gemcitabine and radiotherapy. Besides the cytotoxicity, other parameters will be measured to clarify the mechanism of radiosensitization such as the influence on the cell cycle, the role of apoptosis and p53, intracellular dFdCTP concentration and the influence on cellular nucleotides. Optimization of the combination gemcitabine-radiotherapy and the use of amifostine in vitro, might result in new clinical applications of this combination.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

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• Research Project

Abstract

Researcher(s)

• Promoter: Lambert Julien
• Co-promoter: Vermorken Jan
• Fellow: Nijsten Tamarius

Research team(s)

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• Research Project

Abstract

The project focuses on the use of antigen-modified human dendritic cells (DC) as a potential cancer vaccine. Human dendritic cells (DC) from cancer patients will be cultured starting from peripheral blood monocytes. The major aim is to transfer tumor proteins from autologous tumor cells towards DC by means of transfection of DC with mRNA encoding defined antigens or with total tumor mRNA, or by pulsing of DC with apoptotic/necrotic tumor cells. Tumor antigen-loaded DC will be used for induction of tumor-specific autologous cytotoxic T cells ex vivo. As a first step, DC from cervix carcinoma patients will be loaded with mRNA encoding a single defined antigen (e.g. human papilloma virus E7 antigen) for ex vivo tumor vaccination against defined antigens. In a later phase, DC will be loaded with unfractionated tumor antigens (total tumor mRNA, apoptotic tumor cells). This approach will be tested using tumor material derived from lymphoma patients.

Researcher(s)

• Promoter: Berneman Zwi
• Co-promoter: Lardon Filip
• Co-promoter: Van Bockstaele Dirk
• Co-promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

The combination of radiotherapy and the new generation cytotoxic agents, like gemcitabine, is very promising for the treatment of several types of tumours. These agents can enhance the radiosensitivity of tumour cells. However, the lack of knowledge on the mechanism of this radiosensitising effect limits the optimal design of clinical trials on these combinations. Therefore, a rapid, semi-automated in vitro model was developed to investigate interactions between radiation and chemotherapy. Besides cell survival, parameters like cell cycle and apoptosis will be studied to elucidate the radiosensitising effect of gemcitabine. Since the radiosensitising effect can also result in an increase in toxicity , the application of the cytoprotective agent amifostine will also be investigated.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

Carcinoma of the uterine cervix is one of the most frequent forms of cancer in women. The association between cervical cancer and the human papillomavirus (HPV) is undisputable. This association presents the possibility to use the presence of HPV as a diagnostic/prognostic indicator. Earlier investigations of the presence of HPV DNA in lymph nodes from women with early stage cervical cancer have shown that there is no prognostic value. Most likely HPV DNA can also be present in lymph nodes internalized ini mmuno competent cells, such as macrophages. Detection of RNA, being extremely sensitive to degradation, excludes the presence of deed tumors cells. Follow-up of patients should give an indication of the prognostic value of RNA detection.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

In (pre)clinical studies the cytoprotective agent amifostine was shown to selectively protect normal tissues against chemo- and radiotherapy without a reduction of the antitumor activity. To investigate the mechanism of action of amifostine and to optimize its clinical use, the combination of amifostine and chemo- and radiotherapy is studied in vitro in normal and (sensitive and resistent) tumor cclls. Several aspects will be studied: cytotoxicity, pharmacodynamics (especially intelaction with DNA) and pharmacokinetics. Also new cytostatic agente win be studied.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

Carcinoma of the uterine cervix is one of the most frequent forms of cancer in women. The association between cervical cancer and the human papillomavirus (HPV) is undisputable. This association presents the possibility to use the presence of HPV as a diagnostic/prognostic indicator. Earlier investigations of the presence of HPV DNA in lymph nodes from women with early stage cervical cancer have shown that there is no prognostic value. Most likely HPV DNA can also be present in lymph nodes internalized in immunocompetent cells, such as macrophages. Detection of RNA, being extremely sensitive to degradation, excludes the presence of dead tumour cells. Follow-up of patients should give an indication of the prognostic value of RNA detection.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project

Abstract

Carcinoma of the uterine cervix is one of the most frequent forms of cancer in women. The association between cervical cancer and the human papillomavirus (HPV) is undisputable. This association presents the possibility to use the presence of HPV as a diagnostic/prognostic indicator. Earlier investigations of the presence of HPV DNA in lymph nodes from women with early stage cervical cancer have shown that there is no prognostic value. Most likely HPV DNA can also be present in lymph nodes internalized in immunocompetent cells, such as macrophages. Detection of RNA, being extremely sensitive to degradation, excludes the presence of dead tumour cells. Follow-up of patients should give an indication of the prognostic value of RNA detection.

Researcher(s)

• Promoter: Vermorken Jan

Research team(s)

Project type(s)

• Research Project