Prospectus

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Mechanisms of disease 2

Course
2022-2023

Admission requirements

Description

During this 6-week course the student will gain insight into the relation between (epi) genetic alterations in cells and morphologic and functional changes in the affected cells and tissues. Students will learn how genetic alterations (including hereditary ones) cause cancer development. Furthermore, the classification of tumors (tumor types), the cancer cell characteristics that lead to metastatic spread, the interaction between cancer cells and the host immune system, and diagnostic and treatment procedures will be discussed. Based upon these findings the multidisciplinary approach of many aspects of curative treatment options in a variety of malignancies (e.g. breast, endometrial, colorectal, non-small cell lung (NSCL), melanoma and hematological cancers) will be discussed.

The theme “Hemodynamic disorders” (fig. 1) will introduce you to the major clinical symptoms resulting from the disturbance of the maintenance of blood flow and to their underlying mechanisms. Primary and secondary hemostasis, thrombosis and atherosclerosis will be discussed Finally, thrombosis will be presented as a paraneoplastic phenomenon in relation to cancer.

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, hereditary genetic defects, and environmental (lifestyle) factors.
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) .

  1. 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.
  2. Has elementary knowledge about major developments, moments and figures in the history of cancer and oncology
  3. Can describe the ways in which cancer became more visible over the last two centuries and can explain this change with medical-scientific and social-cultural factors.
  4. Can describe and explain how changes over time in medical treatment regimes in changing circumstances affected patients’ experiences of cancer throughout the twentieth century, using the example of breast cancer.
  5. 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.
  6. 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.
  7. Understands the regulation of the normal growth pattern of the hematopoietic system and the physiological responses to endogenous and exogenous stimuli.
  8. Describes the main laboratory findings and imaging modalities in the most important hematological malignancies (e.g. acute and chronic leukemia and lymphomas).
  9. 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.
  10. Understands the role of the vessel wall, endothelium, thrombocytes and plasma factors in hemostasis and the role of pro- and anticoagulant factors.
  11. Understands the principles and mechanism of balance between thrombosis and haemorrhage.
  12. Is able to explain in clinical cases which component of hemostasis is disturbed and knows which clinical tests can be used to identify this.
  13. Can describe the differences between congenital and acquired diseases of thrombotic disorders.
  14. Can explain the principles of pharmacological interventions targeting coagulation.
  15. Relates clinical aspects and epidemiology of thrombosis to cancer and the mechanisms playing a role in thrombosis as a paraneoplastic phenomenon.
  16. 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).

Timetable

All course and group schedules are published on our LUMC scheduling website or on the LUMC scheduling app.

Mode of instruction

Lectures, workgroup meetings, patient demonstrations, response lectures, interactive sessions and self-study exercises.

Assessment method

Testing is done by means of a mid-point exam and a final exam (multiple choice and open questions and an integrated extended matching puzzle).

The exam dates can be found on the schedule website.

Reading list

  • Robbins and Cotran Pathologic Basis of Disease, Kumar, Abbas & Fausto, 9th edition, 2014 (or 10th edition, 2021)

  • Clinical Medicine, Kumar, Clark, 9th edition, 2016 (or 10th edition, 2021)

  • TRC section Pharmacotherapy

Registration

Students are required to register for exams through uSis. The registration for a working group is done by handing in your ‘studieplan’.

Contact

g2md2@lumc.nl

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