Lectures winter term 2023/2024

PATHOBIOCHEMISTRY 2 - Molecular oncology
5th-8th week

Lectures are held on Monday 16:15 to 17:45 in the Lecture hall 1.26, U nemocnice 4 and Friday from 16:15 to 17:45 in the Cori lecture hall, U nemocnice 5

5th week Monday 30.10.	Physical, chemical and viral carcinogenesis, changes in cancer cell metabolism.	Physical factors involved in the development of cancer: a) the influence of UV radiation b) the influence of ionizing radiation c) the involvement of other physical factors - foreign body chronic mechanical damage etc. Chemical carcinogenesis a) types of chemical carcinogens b) mechanisms of action of chemical carcinogens. Viral carcinogenesis a) DNA oncogenic viruses - mechanism of induction of cancer b) RNA oncogenic viruses * induction of primary hepatoma by HCV * retroviruses and cancer. Metabolic changes in cancer cells, Warburg effect.	doc.MUDr. J. Křemen, CSc.
Friday 3.11.	Biomarkers of cancer diseases	Tumor biomarkers - definition and division; diagnostic, monitoring, screening, prognostic, predictive and pharmacodynamic biomarkers, special cases - oncofetal biomarkers; Examples of use in clinical practice - organ specificity, tumour detection and diagnosis, release into the blood, prediction of tumour risk, differential diagnosis of tumours, cancer staging, monitoring of cancer treatment efficacy, detection of residual cancer and tumour recurrence after treatment, searching for patients at risk in the general population; Sensitivity, specificity, positive and negative predictive value, ROC curves, Kaplan-Meier survival function estimation; prediction of cancer prognosis, decision making on treatment selection, drug dosage adjustments.	MUDr.I.Melezínek, CSc., Mimořádný profesor UK
6th week Monday 6.11.	Principles of cancer development (tumor microenvironment, regulation of neovascularization, metastatic cascade).	Tumor heterogeneity and mechanisms of its origin (clonal evolution, cancer stem cells). Tumour microenvironment and its importance in carcinogenesis. Types and molecular mechanisms of neovascularization (with emphasis on angiogenesis and vasculogenesis), characteristics of tumor vasculature. Regulators of neovascularization, VEGF. Metastatic cascade, EMT, different invasion strategies, infiltration and colonization of target organs. Angiogenesis and metastasis as possible therapeutic targets.	doc. MUDr. P.Bušek, Ph.D
Friday 10.11.	DNA-based Diagnostics in Oncology	Molecular diagnostics of 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 (PCR, HRM, Sanger sequencing, MLPA, next gen sequencing). Sporadic cancers, types of somatic mutations. large-scale mutations, gene amplifications, deletions of large chromosomal regions, chromosomal translocations and their analysis. Microsatellite instability in human tumors and detection. Minimal residual disease and detection.	doc.Mgr.J.Šána,Ph.D.
7th week Monday 13.11.	Biochemical principles of anti-cancer treatment I.	Modalities of anticancer therapy: Hormone therapy, biochemical mechanism of action and therapeutic use, adverse effects; radiotherapy, biochemical mechanism of action and therapeutic use, bystander and abscopal effects, adverse effects; Chemotherapy, biochemical mechanism of action of alkylating agents, antimetabolites, microtubular agents and topoisomerase inhibitors, therapeutic use, adverse effects; Targeted therapy, mechanism of action of tyrosine kinase inhibitors, therapeutic use, classification of antibodies, kinome.	MUDr.I.Melezínek, CSc., Mimořádný profesor UK
Friday 17.11.	Holidays
8th week Monday 20.11.	Biochemical principles of anti-cancer treatment II.	Targeted therapy, mechanism of action of inhibitors of self-renewal signaling cascades Wnt, Notch, Hedgehog, induction of apoptosis, therapy directed against DNA repair mechanisms, CD antigens, cell cycle regulators, proteasomes and epigenetic mechanisms,therapeutic use, adverse effects; Immunotherapy, biochemical mechanisms of action of oncolytic viruses, vaccines, LAK and TIL cells, T-receptors, CAR-T cells, cytokines, checkpoint inhibitors, therapeutic uses, adverse effects.	MUDr. I. Melezínek, CSc., Mimořádný profesor UK
8th week Friday 24.11.	Mechanisms of tumorigenesis (pathobiochemistry of malignant transformation).	What is a malignant tumor, genetics and epigenetics. Disorders of cell development and differentiation, cancer stem cells. Immortalization, role of telomeres. Tumor transformation, signaling disorders leading to tumor transformation, causes of changes in signaling pathways affecting cell proliferation (RTKs, cytokine receptors, Wnt signaling, TGF-beta, Rb), apoptosis (DRs, caspases, role of mitochondria) and DNA repair pathways (HNEJ, HR, MMR).	prof. MUDr. A.Šedo, DrSc

8.9.2023
Prof. MUDr. Aleksi Šedo,DrSc.
Head of the Inst.of Biochemistry and Exp.Oncology