The Topol Institute For Medical And Biochemical Research

General Aspects of the Institute's Activities

The scope of the institute's actviities is to be free to evolve with changes that will undoubtedly occur with the history of the institute.
However, it is conceived, as the name implies, that the essential and initial phase of the work will be directed towards biomedical and biotechnological problems.
Basic research will be continued, having its origins from studies being presently conducted at the University of Nevada, Reno and is concerned with the biochemistry of cancer. It is planned that from this promising research program, clinical studies will be conducted in conjunction with various area hospitals.

Other experimental work ideas will be generated at the Nevada Institute of Theoetical Medicine which will join The Topol Institute at its conception.

Other programs will include i) adult education, i) waste management and tobbaco plant (human gene) research in conjuction with the agriculture department at UNR, and physical biology projects.

A gret deal of the Institute's activities will include a variety of scientific and public meetings on various timely scientific/health issues.

We also wish to offer scholarships to all levels of local education programs in conjunction with the institute's goals and develop a series of public lectues involving the interpretive center which is still being designed and formulated.
[Note: more specifics are included in the following section of this brief]

Activities of The Topol Institute 

Experimental

I. Basic cancer research. Omega-3 fatty acid effects on apostolic genes and oncogenes that affect human tumor growth.

II. Clinical cancer research. Effect of omega-3 fatty acids and S-adenosyl-L-methionine on humans with various types of cancer.

III. Studies with natural products with potential medical activity with special reference to the creosote bush and other ectopic preparations.

IV. Theoretical medical research. Computer modeling of faty acids and their interaction with specific transcriptional proteins, omega-3 fatty acid mechanisms, biophilosophical aspects of embryonic gene evolution. Steroid mechanisms in carcinogenesis.

V. Adult computer science education

VI. Studies on the development of waste management using botanical methodology.

VII. Studies on tobacco plant plasmids with human genes.

VIII. Physical Biology Projects.

Non-experimental Activities

I Grant development

II International research collaboration

III Formulate the First International Theoretical Medicine conference

IV Staff meetings

V Managing editorship of the Journal of Experimental and  Theoretical Cancer Research and the Topol Institute Journal

VI Formulate a pharmaceutical company sponsored meeting on  "Omega-3 Fatty acids and Cancer'

VII Develop scholarships to UNR and regional high school students in Cancer Research.

Organizational Structure

Board members:

President and Chairman of the board: Mr. P. Topol

Staff

Director: Dr. R. Pardini (Consultant)

Assistant Director: Dr. R.L. Hancock (acting director)

Experimental Cancer Laboratory Head: Dr. R. Pardini

Biophysics Division. Head: Mr. P. Topol

Nevada Institute of Theoretical Medicine Head: Dr. R.L Hancock

Staff Scientists

Secretaries

Laboratory Technitions

Colony Assistants

Animal Dietitian

Financial Officer

Accountant

Business Officer

Maintenance and Grounds Workers

Model Systems

Dog Colony

Nude Mouse Colony

Invertebrate Culture

Tissue Culture

Rooms

Experimental Laboratory A

Experimental Laboratory B

Biophysics Laboratory

Tissue Culture Room

Colony Rooms: A (Vertebrates), B (Nude Mice), C (Nutrition, and  D (Invertebrates)

Offices

Library (electronic)

Main Library

Library/Conference Room of NITM

Interpretive Center

Mini-auditorium

Information office/Telephone Operator

Wash Up Room (Animal Care) Storage/Maintenance/Utiliites Building

Copier/Fax/Mail Room

Equipment

Furniture

Copiers

Centrifuges

Laboratory Equipment and Supplies

Computers/Servers/Network

Fume Hoods

Journal Subscriptions Books

Finanacial Aspects:

 1. UNR interm contract over three year period  1.5 m  (See appendix)

 2. The Topol Institute (initial year) . 55.0 m

 3. The Topol Institute's operating costs . 10.0 m  (for two additional years)

 4. Associated Divisional Developments  8.5 m  (e.g. Agricultural forests research, water  purification schemes, unique energy supply research, industrial park company incentives, etc.)

 Total 75.0 m

Estimated Costs for Institute

Initial Year

Following Nine Years

Staff Salaries  (in thousands per annum)

Finances:

Building (Design, Architectural, Insurance, Maintenance,  Landscaping, Parking area)

Supplies and Equipment

Publication Costs

Staff (Salaries)

Interpretive Center Models and Illustrative Pieces

Legal Consultation/Contracts

Miscellaneous

Money Estimates: (proforma to be developed by an accountant

Goal:

The Institute's main goal will be to develop non-toxic and non-noxious types of therapies and preventative measures that can be applied to a large variety of clinical cancer cases.

Background:

Research on cancer therapy is being concucted at the Ally M. Lee Laboratory for Cancer Research. (Dr. R. Pardini, Director) located at the University of Nevada,Reno in Reno, NV. The research effort there would be transferred to the Experimental Cancer Divsion of the Proposed Topol Institute.

To date we at the Ally M. Lee Laboratory have successfully inhibited over fifty percent of the growth of a variety of human tumors (carcinomas) maintained in nude mice with tfish oil diets rich in omega-3 fatty acids. Furthermore, we have studied the biochemistry of the mechanism and have evidence that omega-3 fatty acids cause regression (apoptosis) of the tumor by changing growth factor related genes. Further investigation of these findings should allow us to accomplish a complete resolution of the growth of a large variety of human tumors including mammary, prostate, colorectal, and ovarian carcinomas presently being researched.

Divisions of the Institute:

The above will act as a nucleus for the Experimental Cancer Research Division.

With regards to the Theoretical Medicine Division, it will simply acquire the incorporated and ongoing Nevada Institute of Theoretical Medicine recently developed by Dr. R.L. Hancock and place it under the Topol Institutes charter. It deals mainly with theories of potential processes. Those that would be deemed of probable importance would then be explored by the Experimental Division. In the future it is hoped that an addition of computer molecular modeling section be added that would greatly facilitate the work in this division.

The Physical Biology Division will explore unique approaches to cancer therapy involving physical systems such as electromagnetic fields, etc.

The Natural Products Laboratory will deal essentially with plant extracts. These will be tested on specific kinds of human tumor models for anti-cancer activity.

The Natural Products Laboratory will deal essentially with plant extracts. These will be tested on specific kinds of human tumor models for anti-cancer activity.

The Purina Pet Tumor Facility will be jointly operated by the Purina pet food company and will explore the development of preventative cancer measures for pets that can be used as pet food additives.

The Senior Learning Center is yet to be formulated.

The Computer Center will deal with program research in super learing and molecular modeling.

Associated Groups (Rental space for interested parties, e.g. T-test, Inc.)

A clinical division is being formulated.

The Biotechnology Park

We envisage the development of an industrial park to be built on the institute's grounds. Such a park will be made available for short and long term leases for biotechnology companies that would be interested in a close association with the institute's scientific research (e.g. Purina, Inc. setting up a dog tumor colony allowing research on the prevention of dog tumors through special dietary suppliments). The infrastructue and in most cases the building would be available and further arrangements would be set up by each company leasing whatever amount of space deemed necessary for their purposes.

Summery:

Thus the overall plan of the Institute will be to

i) develop, in theory, new therapeutic approaches,

ii) explore these ideas in experimental models and eventually

iii) assess these approaches under clinical conditions.

Appendix

PROPOSAL TO THE TOPOL CHARITABLE FOUNDATION FOR CONTRACT RESEARCH AT THE UNIVERSITY OF NEVADA

Title: Medicinal and Cosmetic applications of Naturally Occurring Substances

Principle Investigator. Dr. Ronald S. Pardini Goats: To advance research currently being conducted at the A11ie M. Lee Laboratory for Cancer Research and the Natural Products Laboratory under the direction of Dr. Ronald S. Pardini. More specifically we propose to pursue the following three specific objectives:

1) Evaluate the impact of dietary and parental administration of individual and mixtures of fatty acids  on human tumor growth and response to therapy

2) Evaluate and develop natural product anti-oxidant topical formulations

3) Evaluate and develop natural product derived treatments for cancer Proposal: We propose to conduct research to evaluate the potential medical and cosmetic applications of naturally occurring products employing appropriate laboratory models.

1) Our laboratory has reported that dietary omega-3 (n-3) fatty acids depressed the growth of human  mammary carcinoma MX-1, human colon carcinomas WiDr and COLO, human prostate  carcinoma PC-3, human pancreatic carcinoma AsPC-1 and human ovarian carcinoma NJ8197  grown in athymic mice. We have also reported that dietary n-3 fatty acids increased the  responsiveness of human mammary carcinoma MX-1 to chemotherapy with mitomycin C and  cyclophosphamide. The n-3 fatty acid diets increased the infra-tumor concentration of p53, the  tumor suppresser protein which we believe is the cause of the decreased tumor growth. We now  propose to further characterize the omega-3 response of other tumor suppresser proteins and  oncogenes by employing standard biochemical tests and gene expression an-ay technology. We  will concurrently develop and test fatty acid mixtures for their effect on tumor growth and tumor  suppressorloncogene response. Our objective would be to develop unique fatty acid formulations  that could be taken either orally or parenterally which would inhibit tumor growth and enhance  therapy.

2) Oxidative stress has been implicated as a causative factor in light induced aging of skin, pain and  erythema associated with sunburn, light-induced wrinkling, and light induced skin cancers. We will  evaluate the anti-oxidant properties of potential topical formulations which will provide the rationale  to develop a family of skin care products. We will prepare selected topical formulations from  natural products containing various anti-oxidants. These formulations will be tested in animal  model systems for antioxidant potential and protection against fight-induced oxidative stress. We  will establish a bank of biochemical/physical markers in mouse skin which are associated with  oxidative photodamage and neopiastic transformation. We will identify effective anti-oxidants for  inclusion into marketable topical formulations. Once we have identified an optimum antioxidant  test formulation(s), additional product development, i.e. optimizing consistency, texture, aroma, etc.  will be performed prior to commercialization.

3) Our laboratory has considerable expertise and experience in the development of natural products  for clinical application. We have successfully developed a secondary metabolite isolated from a  desert plant and guided the research through to clinical trials. In addition, I was involved in the  writing and application for several patents on inventions generated during the research. The  research involved conducting the pre-clinical research which included the extraction, isolation and  purification of the potentially active compounds, conducting biochemical, in vitro cell culture and  laboratory animal model screening for appropriate biological activity, pharmaceutical formulation to  optimize activity, and toxicology. These studies demonstrated sufficient purity, efficacy and safety  of the new product to earn an investigative new drug (IND) clearance from the Food and Drug  Administration (FDA). The clinical trials generated sufficient responses to support a New Drug  Application (NDA) which was approved by the FDA. We will similarly evaluate selected new  natural products for clinical application by conducting the pre-clinical screens and testing. Those  new isolates that show promising results will be further evaluated for safety, efficacy and purity, to address the three criteria essential for an IND application with the FDA. We will also help in the preparation of the IND application.

SPECIFIC RESEARCH OBJECTIVES:

Specific research objectives and timelines will be determined by mutual agreement between the Topol Foundation and the University of Nevada Agricultural Experiment Station.

ACCESS TO UNIVERSITY FACILITIES

University policy dictates that only University employees or students are permitted to conduct research in University laboratories.

TIMELINE:

The initial contract will be for three years beginning on 1 July 2000 annual allocations on 1 July 2000, 2001 and 2002. The project will terminate on 30 June 2003 with a provision to extend the project with mutual agreement between the Topol Foundation and the University of Nevada, Agricultural Experiment Station. It is agreed that the principle investigator will prepare an annual report due on 30 June 2001, 2002 and 2003. The project may be terminated by either party with 90 days advance notice.

BUDGET