Prospectus

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Mechanisms of disease 2

Course
2017-2018

Description

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 biological principles of tumor development and metastasis, diagnostic procedures, and different treatment modalities. In the theme haemodynamic disorders the mechanisms of pathogenesis in thrombosis and atherosclerosis will be discussed, partly in relation to cancer development.

Course objectives

The student:
1. Denominates the processes that initiate and influence tumor development and relates these to phenotypical characteristics of tumor cells.
2. Distinguishes tumor suppressor genes (TSG) from oncogenes, different types of genetic alterations, and explains their role in the hereditary/familial predisposition to cancer.
3. Defines the role of genetic alterations, oncogenic viruses, environmental factors, and their interaction with the cell’s DNA repair machinery, in the onset of cancer.
4. Provides an overview of the cellular defence mechanisms against cancer (DNA damage, DNA repair, cell cycle checkpoints, apoptosis, immune system).
5. Can evaluate the risks of cancer development based on familial history and hereditary genetic defects in tumor suppressor genes.
6. Explains the impact on patient care and the ethical consequences of genomic analysis of tumors and genetic screening of patients (e.g. genome sequencing leading to the discovery of germline mutations).
7. Can distinguish (pathologically and clinically) between benign and malignant tumors, and name the differences.
8. Defines the impact of grade and stage in different malignancies and can explain the differences between these features.
9. Can highlight the importance of population screening, early detection of cancer, and disease monitoring through biomarkers.
10. Explains the concept of clonal evolution and clonal heterogeneity in cancer and understands the difference between intra- and inter-tumor heterogeneity and describes their clinical consequence.
11. Explains the mechanisms by which tumors can metastasize and knows the differences between metastatic spread via lymph nodes, blood vessels or per continuitatem.
12. Denominates mechanisms by which the immune system can recognize and control tumor development.
13. Provides a rationale for application of different immunotherapy modalities in distinct tumor types.
14. Describes the principles and methods used for appropriate staging of patients with malignancies (CT/MR/Ultrasound/PET-CT).
15. 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) .
16. Can specify the properties of tumors that can serve as guidance for therapeutic purposes (rate of cell proliferation, genetic alterations, protein expression) and justify the importance of employing molecular diagnosis for personalized treatment.
17. 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.
18. 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.
19. understands the regulation of the normal growth pattern of the hematopoietic system and the physiological responses to endogenous and exogenous stimuli.
20. describes the main laboratory findings and imaging modalities in the most important hematological malignancies (e.g. acute and chronic leukemia and lymphomas).
21. 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 haemorrhage.
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 (multiple choice questions and an integrated extended matching puzzle).

Literature

  • 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,15th edition, 2017

  • TRC (Teaching Resource Center) Pharmacology Database

Contact

“Secretariat department of Pathology”