Bad news with a side of good news
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Bad News with a side of Good news. Genetic Syndromes Teratogens Endocrine disruption Cancer Anti-angiogenesis treatment Induced Pluripotent Stem Cells Regenerative Biology. A New Hope. Phantom Menace. Attack of the Clones. Lucky to be here!. 17.1. Better to be lucky than good?.

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Bad News with a side of Good news

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Bad news with a side of good news

Bad News with a side of Good news

  • Genetic Syndromes

  • Teratogens

  • Endocrine disruption

  • Cancer

  • Anti-angiogenesis treatment

  • Induced Pluripotent Stem Cells

  • Regenerative Biology

A New Hope

Phantom Menace

Attack of the Clones


Lucky to be here

Lucky to be here!

17.1


Better to be lucky than good

Better to be lucky than good?

occasionally live

a short time


Nondisjunction

Nondisjunction

Fig 16.4


Human syndromes

Human Syndromes

  • Mosaic pleiotropy

  • Relational pleiotropy

  • Genetic and Phenotypic heterogeneity.


Teratogenesis

Teratogenesis

  • DDT- pesticide

  • Thalidomide- sedative during pregnancies

  • Rubella- 1964 epidemic leading to 20,000 blind, deaf, or both fetuses.

DDT

Thalidomide


Timing is everything

Timing is everything

Fig. 17.5


Teratogens

Teratogens

  • Table 17.2


Alcohol

Alcohol

  • Fetal Alcohol Syndrome (FAS)

    • 1 out of 650 children

  • Fetal alcohol Spectrum Disorder (FASD)

    • 3 times as many kids with FASD than FAS


Retinoic acid

Retinoic Acid

  • Accutane: 13-cis-retinoic acid

  • Hox gene expression

  • Pharyngeal Arches


Endocrine disruptors

Endocrine disruptors

  • Hormonal Agonists/Antagonists

  • Block Synthesis, elimination and transportation of hormones

  • Prime organism to be more sensitive to hormones

PCBs

Bisphenol A (BPA)

Diethylstibestrol (DES)


Diethylstibestrol des

Diethylstibestrol (DES)

  • Gonad Development

  • Hoxa10 regulation

  • Guess who? BMP or Wnt?

17.9 then 17.11, then 17.12


Plastic bottles a source of teratogens

Plastic bottles a source of teratogens?

  • Nonylphenol

  • Bisphenol A

Fig. 16.22 and 16.25


Nonylphenol

Nonylphenol

  • Tufts University- estrogen responsive tumor cells

  • Plastic containers that held water and serum were culprit.


Bisphenol a bpa

Bisphenol A (BPA)

  • Developed as a synthetic estrogen

  • 2 Billion Pounds still produced yearly

  • Used for:

    • Resin lining in most cans

    • Polycarbonate plastic in baby bottles, childrens toys

    • Dental sealant.

    • Brightly colored polycarbonate bottles

  • Water in Polycarbonate bottles for week at Room Temp.

    • 300 mg per liter of BPA


Bisphenol a bpa1

Bisphenol A (BPA)

Figure 17.13 and 17.14

  • Low dose exposure

    • Meiotic defects

  • Predispostion to breast cancer

  • 95% of individuals tested in U.S. and Japan have measurable amounts of BPA in urine

  • Plastics industry claims “evidence is meager”

  • Nalgene and Wal-Mart no longer make or sell BPA containing bottles.


Other teratogens

Other teratogens

  • Heavy Metals

  • Pathogens

    • Rubella- within first 6 weeks

    • Toxoplasmagondii


Cancer a disease of development

Cancer: a disease of development

  • Context dependent tumors

    • Cell-cell communication

    • Paracrine pathways

  • Cancer Stem cell hypothesis

    • MITF and melanocytes

  • Embryonic migration pathways

  • Epigenetic reprogramming


Cancer stem cell hypothesis

Cancer Stem Cell Hypothesis


Cancer a disease of development1

Cancer: a disease of development

  • Context dependent tumors

    • Cell-cell communication

    • Paracrine pathways

  • Cancer Stem cell hypothesis

    • MITF and melanocytes

  • Embryonic migration pathways

  • Epigenetic reprogramming


Cancer epigenetic reprogramming

Cancer: Epigenetic reprogramming


Cancer epigenetic reprogramming1

Cancer: Epigenetic reprogramming


Light at end of tunnel

Light at end of tunnel..

  • Anti-Angiogenesis

  • Stem cells and tissue regeneration


Anti angiogenesis

Anti-Angiogenesis

  • VEGFs

  • Fgfs

17.22


Embryonic stem cells

Embryonic Stem Cells

  • Embryonic stem cells

  • Embryonic germ cells

17.23


Induced pluripotent stem cells

Induced Pluripotent stem cells

  • Fbx15 enhancer

  • OCT4, SOX2, c-MYC, and KLF4

17.25


Induced pluripotent stem cells1

Induced Pluripotent stem cells

  • Use of viral vectors

  • Inject fibroblasts transduced with OCT4, SOX2, KLF4, and c-MYC.

17.26


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