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Mechanisms of disease 2



In this six week course the mechanisms of cancer development and haemodynamic disorders will be discussed in relation to genetics and clinico-pathological aspects. In a multidisciplinary integrated approach students will learn the basic principles of tumor development and metastasis including diagnostics and the different treatment modalities (surgery, radiation, chemo- and hormonal treatment including personalized medicine). In the theme haemodynamic disorders the mechanisms of thrombosis and atherosclerosis will be discussed, partly in relation to cancer development.

Course objectives

The student:
1. defines the role of mutations, epigenetic changes, viruses and environmental factors in the development of malignancies (tumorsuppressor genes (TSG), oncogenes, types of mutations, familial cancers (Knudson), Human Papilloma Virus (HPV), epigenetics, genomic instability).
2. 2. describes the mechanism of differentiation of stem cells to end-stage highly differentiated cells and the regulation of this process by cytokines/growth factors and their receptors and the physiological response to endo- and exogenous factors such as stress responses and infection, respectively.
3. explains the differences between normal and abnormal growth and regulation, dysregulation of the hematopoietic cell system and the approach to the patient with cytopenia or cytosis.
4. understands the regulation of the normal growth pattern of the hematopoietic system and the physiological responses to endogenous and exogenous stimuli.
5. describes the main laboratory findings and imaging modalities in the most important hematological malignancies (e.g. acute and chronic leukemia and lymphomas).
6. denominates the processes that initiate and influence tumor growth and relates these to the morphological changes in a tumor cell.
7. can distinguish (pathologically and clinically) between benign and malignant tumors, and name the differences.
8. can specify the properties of tumors that can serve as guidance for therapeutic purposes (rate of cell proliferation, highly specific mutations, gene expression profiles, protein expression and production).
9. is able to use appropriately the oncologic vocabulary regarding benign and malignant tumors and their pre-malignant stages.
10. is able to explain the difference between grade and stage of malignancies.
11. describes and applies in given cases the principles of staging of cancer (f.i. TNM).
12. is able to describe the principles and differences between the different diagnostic modalities: cytology/histology, immunophenotyping (FACS-analysis), cytogenetics, FISH, and gene-expression profiles and how to apply these tests in clinical cases.
13. provides an overview of the cellular defense mechanisms against cancer (DNA damage, DNA repair, cell cycle checkpoints, apoptosis, immune system).
14. can explain the impact on patient care and the ethical consequences of genomic analysis of tumors and genetic screening of patients (whole genome sequencing, gene expression analysis, exome sequencing, germ line mutations, variants of uncertain significance).
15. identifies (environmental) determinants of malignancies and knows how to deal with these determinants on an individual (patient oriented) and societal level.
16. describes the principles and methods used for appropriate staging of patients with malignancies (CT/MR/Ultrasound/PET-CT).
17. explains the mechanisms by which malignant tumors can metastasize and knows the differences between metastatic spread via lymph nodes, blood vessels or per continuitatem.
18. has knowledge of the principles, benefits and drawbacks of population cancer screening and can use the arguments in a discussion.
19. describes the different aspects and intentions of anti-cancer treatment modalities (curative vs palliative, local control vs systemic control, adjuvant vs neoadjuvant, combination of modalities) • surgery (R0/1/2, organ saving procedures, palliative surgery), • medical oncology (concept of micrometastatic disease, targeted therapies, mechanism of action of chemotherapy, hormonal treatment,) • radiation oncology (primary treatment, elective treatment, chemoradiation, therapeutic window, local treatment, technical issues) • immunotherapy (vaccination and treatment with specific antibodies)
20. understands the role of the vessel wall, endothelium, thrombocytes and plasma factors in hemostasis and the role of pro- and anticoagulant factors. 21. understands the principles and mechanism of balance between thrombosis and hemorrhage.
22. is able to explain in clinical cases which component of hemostasis is disturbed and knows which clinical tests can be used to identify this.
23. can describe the differences between congenital and acquired diseases of thrombotic disorders.
24. can explain the principles of pharmacological interventions targeting coagulation.
25. relates clinical aspects and epidemiology of thrombosis to cancer and the mechanisms playing a role in thrombosis as a paraneoplastic phenomenon. 26. can describe the mechanism by which atherosclerosis develops in vessels and which factors are involved in and predispose for this condition (e.g. dietary factors, hypercholesterolemia, radiotherapy and chemotherapy).

Mode of instruction

Lectures, workgroup meetings, patient demonstrations, self-study exercises

Assessment method

Testing is done by means of a mid-point exam and a final exam. Some open questions will be asked, as well as multiple choice questions.


  • Kumar V., Abbas A.K. and Fausto N., Robbins and Cotran Pathologic basis of disease, Elsevier Saunders, 9th edition, 2015

  • Kumar P., Clark., Clinical Medicine, 9th edition, 2015

  • Turnpenny P. Emery’s elements of medical genetics, 14th edition, 2011

  • Alberts, e.a., Essential Cell Biology, 4th edition, 2015

  • TRC (Teaching Resource Center) Pharmacology Database


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