1. komponenta

Lecture type	Total
Lectures	30
Practicum	30

* Load is given in academic hour (1 academic hour = 45 minutes)

LEARNING OUTCOMES:
Students will be able to:
1. Understanding the main steps in the process of carcinogenesis
2. Precise knowledge about mechanisms by which oncogenes, tumor suppressor genes and others factors induced cancer
3. learn the major signaling pathways that lead to tumor progression
4. learn the mechanisms of tumor resistance to apoptosis and apoptosis interact with other forms of cell death
5. understand the importance of epigenetic factors in the modification of oncogenes and tumor suppressor genes
6. understand the process of metastasis, the relationship of the tumor and host during the metastatic cascade
7. Learned the main factors which influence metastatic spread of cancer cells to diferent target tissue
8. gain insight into the molecular pathways of metastasis
9. learn more about the process of creating blood vessels (angiogenesis) in the tumor and the importance and roles of metalloproteinases and other enzymes in cancer
10. learn how to identify key molecular markers of cancer and detection method

COURSE CONTENTS:
1. Causes of cancer, Characteristic Properties of Cancers and Cancer Cells, Characterization and Classification of Cancers
2. Cancer as a genetic disease, Genetic alterations in cancer cells, Inherited predisposition to cancer, Cancer genes, Accumulation of genetic and epigenetic changes in human cancers
3. Oncogenes, Tumor Suppressor Genes, activation, oncogenic potential and mechanism of actionof some individual oncogens, propertis of individual tumor suppresor genes
4. Alterations Intrinsic to the Tumor Cells, Cell Division and Survival, Cell Cycle Control, Growth Factors and their Receptors, Proto-Oncogenic Transcription Factors, Control of Cell Death, Receptors and Ligands Modulating Cell Death, Cancer-Associated Gene Mutations
5. Alterations of Signaling to Cell Division and Survival in Cancer, Cancer pathways, Signal Transduction Mechanisms , Overview of Some Signal Transduction Pathways Important in Cancer, The RAS Pathway and other Small G-Proteins, MAPK signaling as a cancer pathway , The PI3K pathway, Regulation of the cell cycle by the MAPK and PI3K pathways, mTOR, Tyrosine kinase pathways , The TP53 network, Signaling by TGF-betta factors, The NF-kappa B pathway
6. Apoptosis in Cancer, Limits to cell proliferation, Mechanisms of apoptosis, Mechanisms of diminished apoptosis in cancer, Resistance to Apoptosis in Cancer and Potential Targets for Therapy
7. Replicative senescence and its disturbances in human cancers, Pathways to Senescence, Telomerase, Regulation of Telomerase Activity. Signalling pathways that regulate autophagy, Autophagy and Apoptosis, Autophagy and senescence, Autophagy and Cancer, Autophagy and immunity, mitotic catastophe
8. Cancer Epigenetics, Mechanisms of epigenetic inheritance, DNA methylation, Histon modification, miRNA
9. Invasion and metastasis, Invasion and metastasis as multistep processes, Genes and proteins involved in cell-to-cell and cell-matrix adhesion, Genes and proteins involved in extracellular matrix remodeling during tumor invasion, Identification of the Metastatic Genes and Metastasis Suppressor Genes, Homing Receptors and their Ligands, Signal Transduction Leading to Invasion, Host-tumor interactions: Tumor effects on the host
10. Angiogenesis,angiogenic and antiangiogenic factors, Matrix Metalloproteinases, Proteinases of the Fibrinolytic System, Other Enzymes Interactions of invasive tumors with the immune system, The importance of tumor-stroma interactions, Tissue Inhibitors of Metalloproteinases.

EXERCISES:
For students of the Molecular oncology course, practice include microscopy of histological slides of various tumors. Students will have the opportunity to examine samples of tumor tissue colored by immunohistochemistry which will give them a deeper information on the expression of certain proteins within the tumor cells.
On samples of breast cancer we will observe expression of the estrogen receptor, expression of the epidermal growth factor receptor 2 (HER-2), proliferation of cells through expression of Ki-67, the expression of markers of apoptosis, Bcl-2 and Bax and expression of mutated p53 protein. For comparison they will observe two subtypes of breast cancer of varying degrees of aggressiveness and metastatic potential. They will also look at lymph nodes occupied with metastasis of breast cancer.
Samples of melanoma will serve as an example of breakthrough basement membrane by loss of laminin and collagen at the site of penetration and the expression of matrix metalloproteinase-2 and 9 (MMP2, MMP).
They will also look at histology of colon cancer and cervix (CIN III) cancer.

1. Knowles M, Selby P. Introduction to the cellular and molecular biology of cancer, Oxford Univ Press, Oxford, 2010
2. Georg F. Weber, Molecular Mechanisms of Cancer Hardcover, Springer, Dordrecht, The Netherlands, 2007
3. Wolfgang Arthur Schulz, Molecular Biology of Human Cancers, Springer, Dordrecht, The Netherlands, 2005
4. Boranić M. i sur. Karcinogeneza suvremena gledišta o podrijetlu malignih tumora. Medicinska naklada, Zagreb, 2000

Izborni predmeti - Regular module - Physiology and Immunobiology