Disorders of Growth Proliferations

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Disorders of Growth (Proliferations)
Dr. Venkatesh M. Shashidhar Senior Lecturer in
Pathology Fiji School of Medicine
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Cell Cycle

• G1 - Pre-synthetic growth phase
• S - DNA synthesis phase
• G2 - Premitotic growth phase
• M - Mitotic phase (morphologic division)

G1 S M G2
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Growth Control

• Autocrine signaling - Cytokines
• Paracrine signaling - PDGF
• Endocrine signaling - Pituitary GH

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Molecular control

• Receptors -
• Signal transduction system - MAP kinase
• Transcription factors -
• Alter genes - Proto-oncogenes - gene prod
• initiation of cell division.

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Cell cycle regulation

• Cascade of regulatory protein phosphorylation -
  Cyclins
• Cyclin dependent kinases
• Growth Inhibition - Contact inhibition
• TGF-ß

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Growth Factors

• EGF/TGF-?
• PDGF
• FGF
• VEGF
• Cytokines

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Summary

• Cell growth and differentiation involve its
  integration of multiple signals.
• Interplay of Growth promotors and Inhibitors.

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Cell Population Balance

• Balance (lost in neoplasia)
• Proliferation
• Differentiation
• Apoptosis

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Invasion (Loss of contact inhibition)
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Carcinogenesis (eg. lung ca)
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Carcinogenesis
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Characteristics of neoplastic cell

• Loss of contact inhibition (stroma independ)
• may attain "immortality"
• They are dis-cohesive and transplantable--favoring
  invasion and metastasis.
• Tumor cells can secrete collagenases or
  proteases, and then invade.