Review of  "Biophysics of Cancer".

Jeannette A. Hovsepian, M.D.
Editor: "Embryoma Gene Networks".
frensasc@ix.netcom.com



Biophysics of Cancer:  http://www.cancerbiophysics.net

KeyWords: Euchromatin, Embryomas, Entropy, Enhancers, EMT.

John H. Frenster, M.D., Division of Medical Oncology, Department of Medicine,
Stanford University School of Medicine, 94027-5446, frensterjh@aol.com

Science: Biophysical Society; Am. Assoc. Cancer Research; Am. Soc. Clin. Oncology;
RNA Society; Am. Soc. Cell Biology, Am. College Physicians;

Born: Chicago Illinois, USA. October 14, 1928.
Married: Jeannette A. Hovsepian, M.D. June 15, 1958
Specialty; Cancer Research, 1956-2011.



Early Experiments on the Cell Nucleus:

1. Frenster JH, Allfrey VC, and Mirsky AE,
"Metabolism and Morphology of Ribonucleoprotein Particles from the Cell Nucleus of Lymphocytes".   Proc. Natl. Acad. Science U.S.A. vol. 46, pp. 432-444 (April, 1960).

2. Frenster JH, Allfrey VG,  Mirsky AE,
"In Vitro Incorporation of Amino Acids into the Proteins of Isolated Nuclear Ribosomes".
Biochimica et Biophysica Acta vol. 47: pp. 130-137 (1961).

3. Frenster JH, Allfrey VC, and Mirsky AE,
"Repressed and Active Chromatin Isolated from Interphase Lymphocytes."
Proc. Natl. Acad. Science., U.S.A, vol. 50, no. 6, pp. 1026-1032 (Dec. 1963):


The Miracle Year:    1965,   ( 9 papers ),   8 as the sole author:

1. Frenster JH,
"Ultrastructural Continuity Between Active and Repressed Chromatin",
Nature vol. 205, no. 4978, pp. 1341-1342 (March 27, 1965).

2. Frenster JH,
"Nuclear Polyanions as De-Repressors of Synthesis of Ribonucleic Acid.",
Nature, vol. 206, no. 4985, pp. 680-683, (May 15, 1965).

3. Frenster JH,
"A Model of Specific De-repression within Interphase Chromatin".
Nature vol. 206, no. 4990, pp. 1269-1270 (June 19, 1965).

4. Frenster JH,
"Analysis of Queueing and Renewal within Human Systems."
Nature, vol. 207, no. 5002, pp. 1139-1140 (September 11, 1965).

5. Frenster JH,
"Localized Strand Separations within Deoxyribonucleic Acid during Selective Transcription".
Nature, vol. 208: no. 5013, pp. 894-896 (November 27,  (1965).

6. Frenster JH,
"Correlation of the Binding to DNA Loops or to DNA Helices with the Effect on RNA Synthesis".
Nature vol. 208, no. 5015, p. 1093 (December 11, 1965).

7. Frenster JH,
"Mechanisms of Repression and De-Repression within Interphase Chromatin".
In-Vitro, vol. 1, pp. 78-101, (1965).

8. Frenster JH,
“Human Ecology and Clinical Medicine”,
New England Journal of Medicine, vol. 273, pp. 339-340 (1965).

9. Rose HG, and Frenster JH,
"Composition and Metabolism of Lipids within Repressed and Active Chromatin of Interphase Lymphocytes".Biochimica et Biophysica Acta, vol. 106, no. 3: pp. 577-591 (December 2, 1965).


Follow-up Experiments on the Cell Nucleus:

1. Frenster JH,  and Rogoway WM,
"In-Vitro Activation and Re-infusion of Autologous Human Lymphocytes".
Lancet Vol. 2, pp. 979-980 (November 2, 1968).

2. Meisner LF,  and Frenster JH,
"In Vivo Evolution within Radiation-Induced Clones of Human Lymphocytes".

3. Keshgegian AA, Meisner LF, and Frenster JH,
"Thymidine Reversal of Ribothymidine Inhibition of Lymphocyte Mitosis",

4. Stanley DA, Frenster JH, and Rigas DA,
"Localization of 3H-Phytohemagglutinin within Human Lymphocytes and Monocytes",

5. Frenster JH,
"Electron Microscopic Localization of Acridine Orange Binding to DNA within Human Leukemic Bone Marrow Cells". Cancer Research  Vol. 31, 1128-1133 (August, 1971).

6. Frenster JH,
"Ultrastructural Probes of  Chromatin within Living Human Lymphocytes".
Nature Vol. 236, No. 67, pp. 175-176, (April 12, 1972).

7. Frenster JH,  and Herstein PR,
"RNA in Gene De-Repression".
Proc. AAAS Symposium, December 28-30, 1972,

8. Archibald RB, and Frenster JH,
"Quantitative Ultrastructural Analysis of In-Vivo Lymphocyte-Reed-Sternberg Cell Interactions in Hodgkin's Disease." Natl. Cancer Inst. Monogr. 36: 239-245 (1973).

9. Frenster JH, Nakatsu SL, and Masek MA,
"Ultrastructural Probes of DNA Templates within Human Bone Marrow and Lymph Node Cells".
Advances in Cell and Molecular Biology", vol. 3, pp. 1-19 (1974).

10. Nakatsu SL, Masek MA, Landrum S, and Frenster JH,
"Activity of DNA Templates During Cell Division and Cell Differentiation".
Nature, 248 : 334-335 (1974).

11. Frenster JH,
"Ultrastructural Probes of Chromatin During Cell Differentiation and Cell Division within Living Human Bone Marrow Cells".
Proc. Ninth FEBS Meeting, Volume 33, Pages 419-428, (1974).

12. Frenster JH,
"Ultrastuctural Probes of Gene De-Repression within Human Leukemia and Lymphoma Cells."
11th International Cancer Congress, Florence, Italy, October, 1974.

13. Frenster JH,
"Model of Single-Stranded Integration of Oncogenic Viral Genomes",
Biophys. J. vol. 15: 137a (1975).

14. Frenster JH,
"Phytohemagglutinin-Activated Autochthonous Lymphocytes for Systemic Immunotherapy of  Human Neoplasms", Ann. N.Y. Acad. Sci. 277: 45-51 (1976).

15. Frenster JH, Papalian MM, Masek MA, and Frenster JA,
"Electron Microscopic Analysis of Lymph Node Cellular Activity in Hodgkin's Disease."
Journal of the National Cancer Institute, vol. 63, pp. 331-335, (Aug. 1979).

16. Frenster JH,
"Selective Gene De-Repression by De-Repressor RNA."

17. Frenster JH,
"Single-Cell Analysis of DNase I-Sensitive Sites during Neoplastic and Normal Cell Differentiation within Human Bone Marrow."

18. Masek MA, Rhoades DJ, and Frenster JH, "In-Vivo Macrophage Interactions with Lymphocytes in Hodgkin's Disease", Proc. Am. Assoc. Cancer Res. 14: 8 (1973).

19. Rowan RA, Masek MA, Thompson JM, and Frenster JH, "Electron Microscopic Localization of Acid Phosphatase Activity within Hodgkin's Disease Lymph Nodes", Proc. Am. Assoc. Cancer Res. 16: 10 (1975).

20. Frenster JH, "Analysis of Queueing and Renewal Systems in Hodgkin's Disease", Proc. Am. Assoc. Cancer Res. vol. 16: p. 223 (March, 1975).

21. Frenster JH, Landrum SR, Masek MA, and Wilson LS, "Nuclear Maturation Within Neoplastic Cells In-Vivo", J. Cell Biol. 67: 123a (1975).

22. Frenster JH, Landrum SR, Masek MA, et al, "Comparison of DNA Helix Openings during In-Vivo Mitosis of Normal and Neoplastic Human Cells", Proc. Am. Assoc. Cancer Res. 19, 1-2 (1978).

23. Frenster JA, Papalian MM, Masek MA, et al, "Persistent Euchromatin after DNA Template Inactivation", J. Cell Biol. 79, 110a-111a (1978).

24. Frenster JH, Papalian MM, Masek MA, and Frenster JA, "Asymmetry of Intra-Nuclear Function during Immune Lymphocyte Activation", Biophys. J. vol. 25, no. 2, part 2, p. 228a, Feb. 1979.

25. Frenster JH, "Single-Cell Analysis of DNase I-Sensitive Sites During Neoplastic Cell Differentiation within Hodgkin's Disease Lymph Nodes", Leukemia Reviews International, Rich MA, Editor, Volume 1, pp. 22-23, (Marcel Dekker, Inc. New York/1983).



More Recent Studies of the Cell Nucleus:
 

1. Frenster JH,  and Hovsepian JA,
“Heterochromatin to Euchromatin Transition within Human Interphase T- Lymphocytes”.
in: "Dynamic DNA Packaging Across Kingdoms: Chromatin and Beyond".

2, Frenster JH, "Nuclear RNA Species Activate DNA Transcription Within Chromatin",
FASEB Journal, Vol. 13, No. 7, A1506 (April 23, 1999).

3. Frenster JH, and Hovsepian JA, "RNA Feedback Mechanisms during Eukaryotic Gene Regulation", "Northwest Symposium on Systems Biology", p. 15, Oct. 17-18, 2002.

4. Hovsepian JA, and Frenster JH,
"RNA-Induced Melting of DNA during Selective Gene Transcription".

5, Hovsepian JA, and Frenster JH,
"Euchromatin as an Extensile Force within Mammalian Cell Nuclei".,

6. Hovsepian JA, and Frenster JH,
"Chromosome-Chromosome Contact Points and Paired Sense-Antisense RNA Synthesis".

7. Frenster JH, and Hovsepian JA,
"DNase-I Ultrastructural Probe Sites and Kissing Chromosomes".

8. Frenster JH, and Hovsepian JA,
"DNA-DNA Tetraplex Model of Paired Sense-Antisense RNA Synthesis".

9. Frenster JH, and Hovsepian JA,
"Kissing Chromosomes and Paired Sense-Antisense RNA Synthesis".

10. Frenster JH,
 "Oncogenes as Molecular Targets within Active Chromatin".
  Clinical Cancer Research, vol. 5, suppl. l, p. 3855s, (624), (November, 1999).

11. Frenster JH, and Hovsepian JA,
 “Models of Embryonic Gene-Induced Initiation and Reversion of Adult Neoplasms”.

12. Frenster JH, and Hovsepian JA,
"Embryonic Gene Re-expression May Initiate Adult Neoplasms".

13. Frenster JH, and Hovsepian JA,
"Cellular Dynamics of Embryomas within Adult Neoplasms".
Biophysical J., vol.98, issue 3, supplement 1, pages 1-766, (January, 2010).



Human Systems Integration:

1. Frenster JH, and Hovsepian JA,
"Models of successive levels of resolution during individual gene transcription".

2, Herstein PR, and Frenster JH,
 "Mated Models of Gene Regulation in Eukaryotes".

3. Frenster JH, and Herstein PR,
Review: "Gene De-Repression",
New Eng. J. Med. 288: 1224-1229

4. Frenster JH,
"Selective Control of DNA Helix Openings during Gene Regulation".
Cancer Research 36: 3394-3398.

5. Frenster JH,
"Matrix Cognition and Spiritual Progress".
Presented at CogSci98, (The Twentieth Annual Conference of the Cognitive Science Society) at Madison, WI USA,  August 1-4, 1998, and at ( The 20th World Congress of Philosophy ) at Boston, MA USA, August 10-16, 1998.



Current Cancer Research:
 

1. Frenster JH, and Hovsepian JA,
“Ultrastructural Probes of Clusters of Open Regulatory Elements (CORE) within Chromatin”.



Power-Point Presentation:

1. Frenster JH,
 "Ultrastructural  Probes  of  Active  DNA  Sites,  and  the  RNA  Activators  of  DNA".



Conclusions from Embryoma Genomics:

1. Each cell retains all of its embryonic genes for a lifetime.

2. Controls for embryonic genes are often absent in adults.

3. Uncontrolled embryonic genes can replicate wildly.

4.  Replicating genes participate in  intra-cellular competition.

5.  The basis for gene competition is selective transcription.

6.  MicroRNAs can reprogram embryomic transcription.

7.  Gene reprogramming can produce normal phenotypes.

8.  Normal phenotypes can by-pass chromosomal lesions.

9.  MicroRNA therapy may need to be permanent.

10. Transplantation of microRNAs could be preferred.

http://www.embryomas.net/



Conclusions from Euchromatin Thermodynamic Pathways.

1. Pathways within cell genomes involve a flow of information.

2. Information can flow by direct contact or by third parties.

3. Direct contact within whole genomes is difficult to regulate.

4. DNA-DNA direct contects are influenced by agents.

5. Nuclear agents include hydrophilic ionic and hydrophobic conforming ligands.

6. Third parties within genomes involve RNAs and proteins.

7.  RNAs and proteins are easy to regulate or reverse.

8.  Information can be shared, lost, or transformed.

9. System information can be hidden during system isolation.

10.  Local information can be permanently lost during system entropy.

http://www.cancerbiophysics.net/



Further Topics in:  Euchromatin,  active DNA, and  RNA  ribo-regulators:

Links to Current Research in Euchromatin:
Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:
Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

A Brief History of Activator RNA:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".
(PowerPoint Presentation).

Top of Page - Euchromatin Network -  Euchromatin Research -  Research in Quantitative Radiology

For Further Information and Feedback:

Jeannette A. Hovsepian, M.D.
E-mail: frensasc@ix.netcom.com
Phone:  +1 650 367 6483



Definitions:

euchromatin: "the most active portion of the genome within the cell nucleus".
embryoma:  "adult neoplasm expressing one or more embryo-exclusive genes".
entropy:  "maximum entropy defines the isolated reaction steady-state equilibrium".
EMT: "activated embryonic gene network driving cancer progression".
enhancers: "long noncoding RNAs capable of activating gene transcription".