Gene Technology

1. The Genetic Basis of Cancer Gene Technology Tabacco consumption and lung cancer are correlated -> Environmental factors are important factor for onset of cancer Cancer is a genetic disease -> Mutations can cause cancer!!!

2. Gene Technology Carcinogenic Substances cause Mutations

3. Gene Technology Carcinogenic Substances cause Mutations Fungal (Aspergillus) toxin -> causes liver cancer

4. Gene Technology Carcinogenic Substances cause Mutations

5. Skin cancer Gene Technology Cancer cells show characteristics of rapid growing cells: ->high nucleus-to-cytoplasm ratio -> high frequency of mitotic cells -> little specialized structure

6. Correlation between age and outbreak of cancer Gene Technology

7. Cancer arises from a single cell -> undergoes one or more mutations in particular genes (responsible for cell growth or control of cell growth) -> these changes in cells cause cancer (funtamental cellular properties are altered) All of them are altered -> most destructive tumor -> cancer Only a few changes -> less dangerous tumor Gene Technology Formation of blood vessels No cell death Cells become immortal No aging of cells

8. Normal cells and cells transformed by an oncogene Gene Technology

9. Cell birth – cell death – cell growth Stem cells Gene Technology More differenciated cells

10. Cell growth – Cell differentiation Gene Technology

11. Cancer induced in dividing cells Cancer inducing mutations occuring in nondividing cells (neurons or muscle) -> normally no cancer induced -> if cancer in skin or leukemia or cancer in the intestine (differentiated cells) -> cells that initiate tumor are not the differentiated cells but the precusor cells (progenitor cells) -> fully differentiated cells normally do not divide -> no replication -> if they have a mutation -> no big effect -> apoptosis initiated Gene Technology

12. Cancer cells are used for making cell lines Gene Technology -> to produce recombinant protein in mammalien cell cultures -> cancer cell lines -> immortal cells -> to study gene function in cells

13. Metastasis: Breaking off of cells from primary tumor -> traveling in blood stream -> leaving blood stream at other places -> formation of secundary tumors (metastasis) Gene Technology ECM -> extracellulare matrix EGM -> epidermal growth factor

14. Cell growth – Reproduction in Eukaryotic cells Eukaryotes have 2 types of cells: -> diploid cells (2n) -> Most of the cells (in mammalians: somatic cells) -> haploid cells (n) -> just the gametes (in mammalians: egg + sperm) Haploid cells (n) are just used for fertilization -> sexual reproduction -> Meiosis Diploid cells (2n) -> somatic cells -> asexual reproduction -> Mitosis Gene Technology Diploid cells -> 2 sets of chromosomes (2n) -> 2 sets of the genes Haploid cells -> 1 set of chromosomes (n) -> 1 set of genes

15. Cell growth – Reproduction in Eukaryotic cells 1 diploid cell (2n) Asexual Reproduction in Eukaryotes-> Mitosis -> Replication +Separation of Chromosomes Gene Technology 2 diploid cells (2n)

16. 1 diploid cell (2n) 4 haploid cells (n) Cell growth – Reproduction in Eukaryotic cells SexualReproduction in Eukaryotes-> Meiosis -> Replication + 2x Separation of Chromosomes -> cells are ready for fertilization Gene Technology

17. Cell growth – Reproduction in Eukaryotic cells Gene Technology

18. Cell growth – Stages of the cell cycle (Mitosis) Gene Technology

19. Regulation of cell growth – Stages of the cell cycle (Mitosis) Gene Technology CDKs -> cyclin dependent kinases

20. Overview of checkpoint controls in the cell cycle (Mitosis) Gene Technology Recognition of Mutations trigger blocking of cell cycle

21. Cell Death - Apoptosis Gene Technology Apoptosis induced by several protein factors -> p53 one of the proteins that play an important role Loss of p53 makes cells resistant to apoptosis -> length of telomere end determine aging of cells

22. Telomere Ends determine age of cell Gene Technology

23. The role of Protein p53 Gene Technology

24. Proteins participating in controlling cell growth and cell death Gene Technology If mutations in these proteins -> cause cancer Viruses (mainly retroviruses – integrative viruses) can also cause cancer 2 type of proteins are (when mutated) responsible for onset of cancer: -> Proto-Oncogenes -> Tumor repressor genes

25. Proteins participating in controlling cell growth and cell death Gene Technology

26. Development of Cancer Gene Technology More than one cancer gene activation necessary to develop cancer

27. Some tumors are activated by chromosomal rearrangements -> Recombination expresses a oncogene (myc is an oncogene -> transforms cells into cancer cells ) -> recombination makes fusion out of bcr gene and abl (bcr-abl oncogene -> modified protein kinase) -> active oncogene causes leukemia Gene Technology

28. Some tumors are activated by chromosomal rearrangements -> recombination makes fusion out of bcr gene and abl (bcr-abl oncogene -> modified protein kinase) -> active oncogene causes leukemia Gene Technology Tumor developes

29. Some drugs (chemotherapy) used for inhibiting kinases -> also bcr-abl Gene Technology Bcr-abl with gleevec

30. Ras oncogene causes bladder carcinoma Gene Technology Ras activates cell division -> normally switched on and off by GTP/GDP -> Mutation can not be switched off any more -> oncogene

31. Combination of Ras oncogene and myc oncogene causes exellerates cancer devepment Gene Technology

32. Cancer can be inherited Gene Technology Retinoblastoma -> eye cancer -> also possible for breast cancer (people with inherited mutation in brca gene in one allele -> will eventially have outbreak of breast cancer)

33. Gene Technology Cloning of a human bladder tumor oncogene

34. Tumor cells require blood vessels Tumor cells produce protein factors that stimulate angiogenesis -> formation of blood vessels -> blocking angiogenesis -> reduction in tumor size Gene Technology

35. Proteins involved in cell growth that are affected by cancer causing mutations Gene Technology

36. Studying Cancer by Microarray Systems Gene Technology All known genes of the cell immobilized

37. Studying Cancer by Microarray Systems -> which genes are affected by particular cancer -> which proteins are up-or down regulated Gene Technology

38. Gene Technology Studying Cancer by Microarray Systems -> which genes are affected by particular cancer -> which proteins are up-or down regulated -> which cells are affected

39. Studying Cancer by Microarray Systems Gene Technology Some cancers are caused by rearrangements in genome -> recombination between different chromosomes or genes -> determine copy number of affected genes

41. Challenges for Cancer detection and treatment Detection: -> now: need to have already a tumor (many cells) -> in the future: detection of single cells would be good -> nanoparticles? (could lead to treatment of stimulation of immune system) Treatment: -> now: chemotherapy effective but also a lot of healthy cells are effected -> development of effective drug delivery systems -> primarily cancer cells affected -> use of magnetic nanoparticles attacking tumor cells -> heating particles up Gene Technology

42. Nanobiotechnology/Nanomedicine Liposomes as drug delivery: