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Commentary | Clinician's Corner

Hyperthermic Biology and Cancer Therapies:  A Hypothesis for the “Lance Armstrong Effect”

Donald S. Coffey, PhD; Robert H. Getzenberg, PhD; Theodore L. DeWeese, MD
JAMA. 2006;296(4):445-448. doi:10.1001/jama.296.4.445.
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There is perhaps no more important question in cancer research than to understand the molecular basis of how the majority of patients with testicular cancer can be treated so effectively. For instance, how could Lance Armstrong, who was diagnosed with very advanced metastatic testicular cancer, be treated so successfully that he could subsequently win multiple grueling Tours de France? Although such therapeutic success is now common for many patients with this type of advanced testicular cancer, this type of outcome is unattainable for the majority of patients with other types of advanced solid tumors. What accounts for the astounding therapeutic success with testicular cancer, and can this outcome be explained both at the cellular and molecular levels? Understanding the basis for the “Lance Armstrong effect” may provide therapeutic targets to enhance cures of other common advanced solid tumors that remain so refractory to the best systemic treatments.

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Figure. Model of Nuclear Matrix and DNA Loop Domains
Grahic Jump Location

In the intact nucleus (A), the DNA is condensed in length by more than 10 000 fold with many levels of organization. The nuclear matrix (B) is revealed by extracting the lipids and histones, which releases and extends over 50 000 DNA loop domains. The nuclear matrix represents a highly dynamic scaffold that defines nuclear shape and provides the higher-order organization of these DNA loops, with each loop attached at its base to a fixed site for DNA synthesis.The matrix proteins represent only 10% of the total nuclear proteins, yet their protein composition is both tissue and tumor-type specific. A major target for hyperthermia stress is the proteins organizing the nuclear matrix that are exceptionally sensitive to heat-induced unfolding and modifications.1112 The nuclear matrix proteins of testicular germ cells are stressed by normal body temperature.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

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