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WAR ON CANCER 1971. USA Kongress, “National Cancer Act” (R. Nixon). “Virus Cancer Program”

WAR ON CANCER 1971. USA Kongress, “National Cancer Act” (R. Nixon). “Virus Cancer Program”. Richard Milhous Nixon (January 9, 1913 – April 22, 1994). ... by the year 1981. Trends in age-standardized lung cancer incidence and death rates by sex, United States, 1975-2005.

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WAR ON CANCER 1971. USA Kongress, “National Cancer Act” (R. Nixon). “Virus Cancer Program”

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  1. WAR ON CANCER 1971. USA Kongress, “National Cancer Act” (R. Nixon). “Virus Cancer Program” Richard Milhous Nixon (January 9, 1913 – April 22, 1994) ... by the year 1981

  2. Trends in age-standardized lung cancer incidence and death rates by sex, United States, 1975-2005 Jemal, A. et al. J. Natl. Cancer Inst. 2008 100:1672-1694; doi:10.1093/jnci/djn389

  3. Transformeerimata Transformeeritud

  4. Oncogenes Normal genes (regulate cell growth) 1st mutation (leads to accelerated cell division) 1 mutation sufficient for role in cancer development

  5. Tumor Suppressor Genes Normal genes (prevent cancer) 1st mutation (susceptible carrier) 2nd mutation or loss (leads to cancer)

  6. Trends in age-standardized lung cancer incidence and death rates by sex, United States, 1975-2005 Jemal, A. et al. J. Natl. Cancer Inst. 2008 100:1672-1694; doi:10.1093/jnci/djn389

  7. “Tüvirakud, kasvajarakud ja kasvaja tüvirakud”

  8. Tüvirakk – pluripotentne rakk, mis annab kahte tüüpi järglasi: endataolisi pluripotentseid rakke ja diferentseerunud rakutüüpe.

  9. Pluripotentne (nt sisemine rakumass, ES rakud) Totipotentne rakk (nt sügoot) Multipotentne (nt hematopoeetilised tüvirakud) Lõpuni diferentseerunud rakud (nt neuronid)

  10. Kasvaja tüvirakkon iseuuenev rakk, mille järglasteks on samasugused tüvirakud ning diferentseerunud rakud, mis moodustavad kasvajate põhimassi. Neid on seni leitud leukeemiatest, rinna, käärsoole, eesnäärme, pankrease, pea ja kaela kasvajatest, melanoomidest... jne.

  11. Kasvaja tüvirakud • Parandavad väga efektiivselt DNA kahjustusi – seega tekitavad resistentsuse kiiritusele • Stimuleerivad angiogeneesi, produtseerides vajalikke faktoreid (näiteks VEGF). • On lihtsalt migreeruvad, seega soodustavad metastaaside teket.

  12. Julius Cohnheim (1839-1884) (1867): Kasvajad ei teki mitte normaalsetest täiskasvanu rakkudest, vaid “embrüonaalsetest” jäänukitest – rakkudest, mis on täiskasvanud organismis oma arengus “maha jäänud” “Onkogenees on blokeeritud ontogenees”

  13. A B C D E F Figure 1 control +nutlin

  14. G2 G1 pThr160 CDK2 CYCLIN E pThr160 CDK2 CYCLIN A s Na-butyrate nutlin DIFFERENTIATION Thr160 CDK2 CYCLIN E p21 p53 Thr160 CDK2 CYCLIN A X Figure 9

  15. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R. The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5856-61

  16. Published online 24 January 2009 | Nature | doi:10.1038/news.2009.56 News Human embryonic stem cell trial wins approval In a milestone for a politically charged field, the US Food and Drug Administration (FDA) has approved the world's first clinical trial of a therapy generated by human embryonic stem cells. Geron, a Menlo Park, California-based company, announced on 23 January that it has won the regulatory agency's approval to launch a small, phase I safety study of a stem cell–derived therapy for spinal cord injury. In the trial, eight to ten paralyzed individuals within 7 to 14 days of their injury will be injected at the point of injury with stem cell–derived precursors to oligodendrocytes, which are key supportive cells in the central nervous system. It is hoped that the cells will lay down sheaths of myelin — an insulator essential for conducting nerve impulses — around injured neurons, as well as stimulating nerve cells to regenerate. The cells have demonstrated both capabilities in animals.1

  17. MILLEKS? Table. Potential US Patient Populations for Stem Cell-Based Therapies. Condition Number of patients Cardiovascular disease 58 million Autoimmune diseases 30 million Diabetes 16 million Osteoporosis 10 million Cancers 8.2 million Alzheimer’s disease 5.5 million Parkinson’s disease 5.5 million Burns (severe) 0.3 million Spinal-cord injuries 0.25 million Birth defects 0.15 million/year Source: Derived from Perry (2000)

  18. The Nobel Prize in Physiology or Medicine 2007 Mario R. Capecchi Sir Martin J. Evans Oliver Smithies "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells"

  19. President Bush’s veto on embryonic stem cell development (2001) 2006: Senate approves a Stem Cell Bill, Bush’s veto

  20. Palin has called herself "as pro-life as any candidate can be“ and has called abortion an "atrocity." Palin has stated that abortion should be banned in nearly all cases, including rape and incest, except if the life of the mother is endangered. Palin has stated that she does not support embryonic stem cell research.

  21. 2004 US presidential elections, blue - DEM, red - REP

  22. 2008 US presidential elections, blue - DEM, red - REP

  23. CONGREGATION FOR THE DOCTRINE OF THE FAITH INSTRUCTION DIGNITAS PERSONAE ON CERTAIN BIOETHICAL QUESTIONS Rome, from the Offices of the Congregation for the Doctrine of the Faith, 8 September 2008, Feast of the Nativity of the Blessed Virgin Mary. William Card. LevadaPrefect + Luis F. Ladaria, S.I.Titular Archbishop of ThibicaSecretary   The use of embryonic stem cells or differentiated cells derived from them – even when these are provided by other researchers through the destruction of embryos or when such cells are commercially available – presents serious problems from the standpoint of cooperation in evil and scandal.

  24. She (=the Church) reminds them that the ethical value of biomedical science is gauged in reference to both the unconditional respect owed to every human being at every moment of his or her existence, and the defense of the specific character of the personal act which transmits life.

  25. Maimets T. Millal algab inimese elu? Akadeemia (2008) 8, 1671-1694.

  26. MILLAL ALGAB INIMESE ELU? • Jaapani maapiirkondades tekib inimene hetkel, kui vastsündinu teeb esimese häälitsuse. • Gaana põhjaosas loetakse vastsündinu kui (täisväärtusliku) inimese tekkeks seitsmendat päeva pärast tema sündi. • Ayatali põlisrahva seas (Taivanil) tekib „inimeseks olemine” alles siis, kui lapsele on nimi pandud – see toimub kaks kuni kolm aastat pärast sündi. • Mitmete indiaanisuguharude jaoks Mojave kõrbes algab inimelu siis, kui vastsündinu esimest korda rinda saab (Morowitz ja Trefil 1992). • Antiikses Kreekas uskusid Pythagoras ja tema õpilased, et inimese hing tekib juba tema viljastamise hetkel ja niiviisi on see ka fikseeritud Hippokratese vandes. • Platoni seisukohad lähtus keha ja hinge duaalsusest – need on erinevad asjad. Platoni järgi algab inimese elu hetkel, kui kehasse siseneb hing. Järelikult peab „inimeseks saamine” toimuma mingil kindlal ajahetkel ning see ei saa toimuda paljuastmelise pikaajalise protsessina. Millal siis? • Platon: sünnihetkel • Aristoteles : poisslaps tekib neljakümnendal raseduse päeval, tütarlaps aga üheksakümnendal päeval

  27. *Seisukoht, et lootel ei teki hinge enne raseduse 40. päeva, valitses hiljem Aquino Thomase, Hippo Augustinuse ja Püha Hieronymuse õpetuste kaudu pikalt ametlikku katoliiklikku mõtteviisi. • *1558. aastal sätestas paavst Sixtus V, et karistuseks abordi või rasedusvastaste vahendite kasutamise eest on kirikust väljaheitmine. • *Tema järglane paavst Gregorius IX aga tõi tagasi endise seisukoha, et lõplikult valmimata (hingestamata) loote tapmine ei ole mõrv. • *See positsioon kestis aastani 1869, kui paavst Pius IX sätestas, et abort loote mistahes arengufaasis on inimese tapmine ja selle karistuseks kirikust väljaheitmine. • *G.W. Bush - “don’t fund, don’t ban” poliitika. 09.08.2001. • * Erinevused religioonides

  28. Perinatal, Birth Weeks 20-24:EEG Day 14: Gastrulation Day 1: Fertilization WHEN DOES HUMAN LIFE BEGIN? Scientific Considerations

  29. Eesti Kirikute Nõukogu bioeetilised seisukohad (2006): (http://www.ekklesia.ee/parnuimmaanuel/Rubriik/bioeetilised_seisukohad.htm). „...iga inimene on loodud Jumala näo järgi ja Tema sarnaseks - see annab talle asendamatu väärtuse, väärikuse ja pühaduse”. „Juba viljastumisel saab tekkiv inimelu ainulaadse geneetilise koodi”. EKNi liikmekirikud usuvad, et loodutena Jumala näo järgi on kõik inimelud alates viljastumise hetkest võrdselt väärtuslikud ja väärikad

  30. MIS ON GEEN? Maimets T. Kas siniste silmade, valgete õite ja haiguste geenid on olemas? Akadeemia (2005), 11, 2344-2384.

  31. Gregor Johann Mendel (July 20, 1822 – January 6, 1884)

  32. The word gene is completely free of any hypothesis; it expresses only the evident fact that, in any case, many characteristics of the organism are specified in the germ cells by means of special conditions, foundations, and determiners which are present in unique, separate, and thereby independent ways - in short, precisely what we wish to call genes. Wilhelm Johannsen (1909) Wilhelm Ludvig Johannsen born Feb. 3, 1857, Copenhagen, Den.died Nov. 11, 1927, Copenhagen GENOTÜÜP FENOTÜÜP Johansseni jaoks on organismi fenotüüp kogu genotüübi produkt, mis on tekkinud individuaalse arengu käigus reaktsioonina keskkonnatingimustele. Et genotüübi reaktsiooninormid on võimelised plastiliselt kohanema erinevatele keskkonnatingimustele, siis võivad fenotüübid varieeruda kontiinuumina. Genotüübid varieeruvad diskreetsetena, ent nende tulemused fenotüübi tasemel teostuvad reaktsiooninormina terviklikult: „Seega tuleks hoiduda rääkimast „mingi konkreetse tunnuse geenist”, isegi juhtudel, kus ei paista mingit ohtu nende segiajamisele. Näiteks klassikalistes herneste katsetes ei ole korrektne rääkida „kollase värvuse” või „kortsulisuse” geenidest. Kollane värv ja kortsud on vaid reaktsioonid teguritele, millel võib olla hernetaimes veel palju muid tagajärgi” (Johannsen 1911).

  33. James Watson and Francis Crick, crackers of the DNA code, in 1959

  34. GEEN „DNA piirkond (nii kodeerivad DNA järjestused, regulaatorjärjestused kui intronid), mis kontrollib diskreetset pärilikku tunnust, vastates tavaliselt ühele valgule või RNA-le” (Alberts et al 1994). „DNA segment, mis on seotud polüpetiidahela moodustamisega; ta sisaldab DNA järjestusi, mis eelnevad ja järgnevad kodeerivatele järjestustele (eksonitele) ning ka järjestusi viimaste sees (intronid)”. (Lewin 1997) s.t. Geen = nukleotiidide järjestus.

  35. 人类基因组计划1%测序中国实验室

  36. Figure 1 Nuclear-donor cat, and cloned kitten with its surrogate mother. a, Adult female cat that supplied cumulus cells for nuclear transplantation. The cells were cultured in DMEM/F12 medium for 5 days at 37 °C until confluent; micromanipulation was used to enucleate ova obtained after routine ovariohysterectomy and to transfer the donor's cumulus cells into the perivitelline space. Enucleated ova and cumulus cells were fused by electrofusion; a second electropulse was applied to activate the oocytes. b, The surrogate mother, a synchronized recipient of three cloned embryos, produced one cloned kitten, which was delivered by caesarian section 66 days after embryonic transfer. Shin et al, Nature 415, 859 (2002)

  37. EPIGENEETIKA Kas kõik ikka on ära määratud DNA nukleotiidse järjestuse poolt?

  38. “Mendel’s gene is more than just a DNA moiety” (T. Jenuwein and C.D. Allis, Science 293, 1074-1080, 2001)

  39. Scott F. Gilbert “Tänane bioloog peab üheaegselt mõtlema viies dimensioonis: kolmes ruumimõõtmes, evolutsiooni ja individuaalse arengu (development) dimensioonis”.

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