josmart 06.11.2017

Syllabus of lectures - Pathobiochemistry 2


Lectures winter term 2017/2018

PATHOBIOCHEMISTRY 2 - Molecular oncology
5th-8th week

Lectures are held on Mondays and Fridays from 16.15 to 17.45 in Chemistry Lecture Hall (3.073) Kateřinská 32, 3rd floor

5th week



Mechanisms of tumor disease formation (physical, chemical and viral carcinogenesis)


Physical factors participating in tumor induction a) effect of UV radiation b) effect of ionising radiation c) participating of other physical factors - foreign bodies, chronical mechanic injure etc Chemical carcinogenesis a) types of chemical carcinogenes b) mechanisms of chemical carcinogen action Viral carcinogenesis a) DNA oncogenic viruses - mechanisms of tumor disease induction b) RNA oncogenic viruses * induction of primary hepatomas with HCV * retroviruses and tumor diseases

doc.MUDr. J. Křemen, CSc.



Pathobiochemistry of tumorigenesis (pathobiochemistry of malignant transformation)


. What is malignant tumor, genetics and epigenetics. Defects in cellular maturation and differentiation, cancer stem cells. Immortalization, role of telomeres. Malignant transformation, disturbances in signal transduction pathways resulting in malignant transformation, role of failure in signaling pathways regulating cellular proliferation (RTKs, cytokine receptors, Wnt signalization, Rb), apoptosis (DRs, caspases, mitochondria-associated factors), and DNA-repair pathways (HNEJ, HR, MMR).

doc.MUDr. Z. Kleibl, PhD.

6th week



Mechanisms of cancer progression (tumour microenvironment, regulation of neovascularization, metastatic cascade).


Tumor heterogeneity and its origin (clonal evolution, cancer stem cells). Tumour microenvironment and its role in cancerogenesis. Types and molecular mechanisms of neovascularization (with the emphasis on angiogenesis and vasculogenesis), characteristics of tumor vessels. Regulators of neovascularization, VEGF. Metastatic cascade, EMT, invasion strategies, infiltration and colonization of target organs. Angiogenesis and metastasis as possible therapeutic targets

MUDr. P.Bušek, PhD.



DNA-based Diagnostics in Oncology


Molecular diagnostics to hereditary cancer syndromes. Inherited gene mutations, single base-pair substitutions, short gene deletions, small insertions, large genomic rearrangements. The analysis of mutations in inherited predispositions to cancer, prescreening methods (DGGE, DHPLC, PTT, MLPA, aCGH), identification and characterization of mutations (DNA sequencing), analysis of RNA. Minimal residual disease. Sporadic tumors, types of somatic mutations. Large-scale mutations, gene amplifications, deletions of large chromosomal regions, chromosomal translocations. Analysis of gene alterations, fluorescent in situ hybridization, Analysis of microsatellite markers, microsatellite instability in human tumors, loss of heterozygosity. RNDr. J. Soukupová, PhD

7th week



Biomarkers of cancer diseases


Definition of cancer biomarkers; sensitivity and specificity of biomarkers; classification of biomarkers according to their biochemical structure and function, and their site of production and localization: tumour specific and organ specific biomarkers, intracellular and secretory biomarkers; clinical application and interpretation of cancer biomarkers detection and quantitation: risk assessment of tumour development, screening and diagnosis of tumours, differential diagnosis of tumours, decision making on anticancer therapy selection and monitoring of treatment efficacy, detection of residual cancer disease and tumour recurrence after therapy, prognosis prediction of cancer disease.

doc.MUDr.E.Křepela, CSc



No lecture

8th week


Signal transduction ellements as therapeutic targets



Therapeutic concepts in oncology. Targeted therapy. Growth inhibition: inhibitors of tyrosinkinases and Ras mediated signaling. Induction of apoptosis: "Death" receptors, inhibition of antiapoptotic proteins and HSPs. Inhibition of the "self-renewal": Notch. Wnt, Hedgehog. Stroma targeted therapy: inhibition of neovascularization, invasion and metastasizi. Biological therapy

MUDr. I. Melezínek, CSc

8th week



Biochemical principles of anti-cancer treatment



Purpose and types of anti-cancer treatment. Chemotherapy, cytostatics: Alkylating agents, Anti-metabolites, Plant-alkaloides, Topoisomerase inhibitors, Antitumour antibiotics, Miscellanous agents. Hormonal therapy. Immunotherapy. Targeted therapy. Radiation therapy MUDr. I. Melezínek, CSc

    Prof. MUDr. Aleksi Šedo,DrSc.
    Head of the Inst.of Biochemistry and Exp.Oncology


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