Bi8110 Mechanisms of carcinogenesis

Faculty of Science
Spring 2022
Extent and Intensity
2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).
Teacher(s)
prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
doc. Mgr. Karel Souček, Ph.D. (lecturer)
doc. RNDr. Alena Hyršlová Vaculová, Ph.D. (lecturer)
prof. Mgr. Vítězslav Bryja, Ph.D. (lecturer)
Guaranteed by
prof. Mgr. Vítězslav Bryja, Ph.D.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Supplier department: Department of Experimental Biology – Biology Section – Faculty of Science
Timetable
Tue 10:00–11:50 B11/333
Prerequisites
Bi7070 Physiology of Cell Systems
Basic knowledge of biochemistry, cell physiology and molecular biology and passing through lecture of Physiology of cell systems are neccessary.
Course Enrolment Limitations
The course is also offered to the students of the fields other than those the course is directly associated with.
fields of study / plans the course is directly associated with
there are 9 fields of study the course is directly associated with, display
Course objectives
The course gives a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer. Molecular and biological principles of changes in extra-, inter-, and intracellular communication leading to disruption of cellular proliferation, differentiation, and apoptosis and the role of stem cells, specific signalling pathways, and tumour microenvironment in cancer development are explained. The students obtain knowledge of development of frequent cancers such as leukemias, colon, prostate, breast, lung, liver, and skin cancer including specific mechanisms. Next, the role of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis is explained. Finally, possibilities and importance of recent diagnostic and therapeutic approaches including mechanisms of action of specific drugs are described.
Learning outcomes
At the end of the course students should be able to: understand a complex view of the process of carcinogenesis, including mutagenic (genotoxic), epigenetic, and non-genotoxic factors that play a role during the development of cancer; explain and understand basic processes leading to cancer development including metastases on the level of cells and cellular polupations; interpret molecular and biological principles influencing extra-, inter-, and intracellular communication and specific signal transduction leading to disruption of cellular proliferation, differentiation, and apoptosis; explain the role and importance of stem cells, specific signalling pathways and tumour microenvironment in cancer development; describe mechanisms of frequent cancer type development (leukemias, colon, prostate, breast, lung, liver, and skin cancer); understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis; discuss questions of cancer prevention, diagnosis and therapy; use acquired knowledge of new research results from described areas for prevention and new therapeutic strategies.
Syllabus
  • Cancer origin and development; history, terminology, basic concepts. Individual cancer stages (initiation, promotion, progression) and their characteristic; genetic, epigenetic and non-genotoxic aspects; Cell transformation, cell contact inhibition; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, classification according to tissues. Importance of mutations in cancer development; DNA damage and repair; microsatellites, genetic instability; clonal selection and expansion; gene amplification, loss of heterozygosity; cell cycle control, apoptosis and mutated phenotype; genetic vs. environmental factors; human hereditary syndromes. Molecular basis of cancer development; proto-oncogenes and oncogenes, tumour suppressor genes; viral transformation; activation and inactivation mutations; growth stimulation and inhibition; autocrine signalling; feedback regulation. Epigenetic mechanisms of carcinogenesis; DNA methylation, histone acetylation, microRNA. Cell immortalization; telomeres and telomerase, factors affecting immortalization, use in cancer therapy. Cancer promotion; non-genotoxic factors and mechanisms; the role of cellular communication and interaction; stimulatory and inhibitory signals; growth regulators in carcinogenesis; the role and importance of gap junctions (GJ); regulation of GJ and its disturbances in cancer; deregulation of proliferation, differentiation and apoptosis; tissue homeostasis. Hormone-dependent cancers; signal transduction of steroid hormones, intracellular receptors; exogenous hormones. Cancer stem cell theory; the role in cancer development, tumour heterogeneity. The role of tumour microenvironment; specific signalling and cell communication. Metastases and their origin; metastatic cascade, modulation of cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; disturbance of proteolytic-antiproteolytic balance, the role of mucins. Epithelial-mesenchymal transition and its regulation. Angiogenesis; its significance; interaction of cancer cell with endothelium; the role of cell adhesion; inducers and inhibitors of angiogenesis. Development of specific cancer types (genetic and epigenetic causes, environmental factors); Haemopoietic disorders - leukemias; chronic myeloid leukemia, myelodysplastic syndrome, acute leukemia, genetic disorders, disturbing of proliferation, differentiation, and apoptosis; diagnosis and therapy; therapeutic use of cytokines. Epithelial tumours; carcinomas of colorectum, breast, prostate and skin; other cancer types; Genetic and non-genetic causes; hereditary syndromes; precancerous stages, ethiology, development, specific signalling pathways; endogenous factors – cytokines, growth factors, eicosanoids; the role of environmental factors. Hormone-dependent cancers; steroid hormone signal transduction; intracellular receptors; exogenous hormones. Environmental factors in carcinogenesis; radiation; chemical carcinogens, viruses, bacteria; Significance of life style; Nutritional aspects of carcinogenesis; Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants). Content and composition of dietary fat; polyunsaturated fatty acids (PUFAs, n-6 and n-3 types) and their metabolites in carcinogenesis; molecular mechanism of their action; modulation of cell membranes and cellular lipidome, oxidative metabolism; fibre and short-chain fatty acids (butyrate). Practical aspects, prevention, clinics. Cancer prevention, diagnostics and therapy; Preventive factors; Tumour diagnosis and specific markers; prognostic vs. predictive factors; cytokinetic parameters, molecular and other markers; Predictive oncology, molecular pathology; Modern detection methods (flow and high resolution cytometry and microscopy, laser scanning, molecular methods, microarrays); Therapy - surgery, radiation, chemotherapy, immunotherapy; supporting factors. Mechanisms of action of chemotherapeutics; mechanisms of drug resistance; New trends in cancer therapy; comparison of methods and interpretation of measured parameters; Data evaluation, bioinformatics, multivariate analyses.
Literature
    required literature
  • Genotoxicita a karcinogeneze. (Genotoxicity and carcinogenesis) https://is.muni.cz/auth/el/1431/jaro2013/Bi6871/um/genotx-a-karcige/index.html . E-learningový učební materiál
  • ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
    recommended literature
  • ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
  • Nutritional oncology. Edited by David Heber. 2nd ed. Amsterdam: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. info
  • Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
  • Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
  • Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
  • Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
  • ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
  • KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
  • KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
  • HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. Oxford: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. info
  • Doporučené speciální reviews a vědecké články ( Recommended reviews and research papers)
  • FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
Teaching methods
Lectures and class discussion. Learning answers for individual lectures in e-learning didacting material.
Assessment methods
Attendance of the lectures is not mandantory but highly recommended for right understanding of the subject matter. During lectures, students are asked about subjects of past lectures. The course is finished first by short written exam. Students must answer about 10 questions which go through all topics discoursed. This is followed by detail oral examination which is evaluated together with written exam by the teacher.
Language of instruction
Czech
Follow-Up Courses
Further comments (probably available only in Czech)
Study Materials
The course is taught annually.
Information on course enrolment limitations: Na předmět se vztahuje povinnost registrace, bez registrace může být znemožněn zápis předmětu!
The course is also listed under the following terms Spring 2008 - for the purpose of the accreditation, Spring 2011 - only for the accreditation, Spring 2003, Spring 2004, Spring 2005, Spring 2006, Spring 2007, Spring 2008, Spring 2009, Spring 2010, Spring 2011, Spring 2012, spring 2012 - acreditation, Spring 2013, Spring 2014, Spring 2015, Spring 2016, Spring 2017, spring 2018, Spring 2019, Spring 2020, Spring 2021, Spring 2023, Spring 2024, Spring 2025.
  • Enrolment Statistics (Spring 2022, recent)
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