COLIN PAUL SPEARS, MD
CEO and Founder, Fibonacci Phyllotaxis Inc. (dba Fibons)
Professor Emeritus, California Northstate University College of Medicine
Personal Information
Work Address | FPI dba Fibons 3415 American River Dr., Ste. C Sacramento CA 95864-5741 |
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Telephone | (916) 482-4717 home/eve (916) 502-0816 cell/text (916) 692-8480 office | |
Fax | (916) 482-4710 | |
Citizenship | USA |
Education
College | Queens College, City University of New York, Queens, N.Y., B.A., Chemistry-Biology 1966, cum laude | |
Medical School | Downstate Campus, State University of New York, Brooklyn, N.Y., M.D., 1970, cum laude | |
Internship | U.S. Public Health Service Hospital, San Francisco, California, 1970-1971, Straight Medicine | |
Associateship | U.S. Public Health Service Hospital, San Francisco, California, 1971-1973, National Aeronautics and Space Administration (NASA) Research Associate in Cardiology | |
Residency | LAC/USC-MC, Los Angeles, California, 1973-1974, Internal Medicine | |
Fellowships | LAC/USC-MC, Los Angeles, California, 1974-1977, Medical Oncology USC Comprehensive Cancer Center, Los Angeles, California, 1977-1983, Research Scholar (Advisor: Prof. Charles Heidelberger) Hematology, The Hospital of the Good Samaritan, Los Angeles, 1983-1984 |
Honors and Distinction
National Cancer Institute, NIH | Cancer Research Training Grant Award, 1974 | |
National Cancer Institute, NIH | Cancer Clinical Training Grant Award, 1975 | |
Meetings Best Abstracts | American Association for Cancer Research, 1979; American Society of Clinical Oncology, 1986 and 1989 Co-author, 1st Place Award, The Genetic Revolution, San Diego, 1994 | |
Member | International Who’s Who of Professionals Distinguished Leadership Award, International Directory of Distinguished Leadership, 1998 | |
Teaching Awards | Consultant of the Year, Family Practice Residency Program, Mercy General Hospital, Sacramento, CA, 2003, 2008 and 2009 | |
Invited Lectures | Management of Breast Cancer in the U.S., Department of Surgery, Sahlgrenska University Göteborg, Sweden, 1992 Discussant, Clinical Pharmacology Section, American Society of Clinical Oncology, 1993 Keynote Speaker, Nordic Clinical Pharmacology Group, Göteborg, Sweden, 1995 Moderator and Speaker: Trimetrexate/5-FU: Review of Preclinical Rationale and Pharmacodynamics, U.S. BioScience Symposium, St. Petersberg, Fl., 8/1998 |
Achievements
Cancer Drug Development | Pharmacodynamic studies of thymidylate synthase (TS) inhibition in vivo 1979 and in clinical tumor biopsies, 1982 using fluorouracil, firsts for any cancer drug Invention of CoFactor, for improvement of 5-FU therapy, USC, 1982, Patents in 1990s, PI role in Phase IIB trial including at Sierra Hematology & Oncology and Mercy General Hospital in 2003, leading to phase III trials (currently under Isofol with Merck) First Investigator for national trial of breast cancer treatment vaccine, 1994, USC-Norris Cancer Center Addition of folate to Alimta (pemetrexed), a TS inhibitor, with successful Registration Trial in NSCLC, Eli Lilly 1999 |
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Chemistry | Methods for Swain-Scott-Spears Nucleophilic Selectivity (S3NS) of aliphatic alkylating agents using green protic chemistry and physiological conditions (1980-present) Invention of selenium and selenone alkylating agents using physical organic chemical kinetics, 1990’s Demonstration in 2018 that bendamustine is a classical alkylating agent, leading to FDA relabeling Studies of evofosfamide S3NS kinetics under hypoxic conditions, explaining its failure in the clinic Studies of ethylphenyglycidate (Strawberry Aldehyde 2) by S3NS showing potential mutagenicity risk | |
Mathematics | Generalized Fibonacci Number, Definition of, cited in MathWorld.com (Mathematica; and the Encyclopedia of Mathematics, CRC Publishing, 2003-present) Mathematics of volume doubling relationships, 1979, 1984, and the 1-2-3-4 of Volume and Area Doubling Rulers, 2021 Erdős Number 3 Fibonacci biology, sequential slide video-microscopy (SSVM) for phyllotaxic patterns in Cotula sericea, 2017 | |
Licensure
California Physician and Surgeon License G23022 since 1970
DEA AS5295301
NPI 1023084720
Board Certification ABIM Member Number 52779
Medicine, American Board of Internal Medicine, 1982 (Lifetime Certification)
Medical Oncology, ABIM, 1985 (Lifetime Certification)
Professional Appointment
Research Scholar: University of Southern Cancer Center, Los Angeles, 1977 – 1982
Assist Prof of Res Med: USC School of Medicine, 1982 – 1983
Clin Assist Prof of Med: USC School of Medicine, 1985 – 1986
Assoc Prof Medicine: Medical Oncology, USC School of Medicine, 1986 – 1997
Prof Clin Medicine: Medical Oncology, USC School of Medicine, 1997 – 1999
Active Staff, Medical Oncology & Hematology, Huntington Memorial Hospital, Pasadena, California, 1997 – 1999
Member, Huntington Medical Research Institute, Pasadena, California, 1996 -1999
Research Scholar, USC Department of Chemistry, Prof. Charles McKenna,Los Angeles, CA,
1998 – 2001
Senior Clinical Research Physician, Oncology Products, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana. 01/04/1999 – 08/04/1999
Attending Physician, Woodland Clinic, Woodland, CA, 03/2001 – 12/2001
Attending Physician, Sacramento Center for Hematology & Medical Oncology,
2800 L Street, Sutter Cancer Center, Sacramento, CA, 12/1999 – 3/2001
Attending Physician, Sierra Hematology & Oncology,
Suite 360, 3939 J Street, Sacramento, CA 95819, 03/26/2001 – present
Partner, Sierra Hematology & Oncology Medical Centers, 2001 – 2017 Retirement
Chairman, Cancer Committee, Mercy General Hospital, Community Comprehensive Cancer Center, Sacramento, 2008 – 2016
Chairman, Weekly Tumor Conference, Mercy General Hospital, Sacramento, 2008 – 2014
Member, Institutional Review Board, Catholic HealthCare West, Sacramento Region 2001 – 2017.
Graduate & Post–Graduate Teaching
Graduate & Post-Graduate Teaching USC, 1985-1997
1. Sang-Ihn Kang, Ph.D., 1985-9. Synthetic chemist. Won a National Academy of Sciences National Research Council Fellowship to work with Dr. Kurt Kohn at the National Cancer Institute’s Laboratory of Molecular Pharmacology.
2. Jashovam Shani, Ph.D., 1984-5. UICC Eleanor Roosevelt Fellow. Appointed Director of the Food and
Drug Administration of Israel in 1989.
3. Nitya G. Kundu, Ph.D., Summer, 1988. UICC Traveling Fellowship, from his post as Professor of
Chemistry, Indian Association for the Cultivation of Science, Calcutta, India.
4. Andrea H. Hayes, Summer, 1987. Junior, pre-med student. USC research done before entry into
Dartmouth Medical School.
5. Shawn Granger, Summer 1988. West Point graduate, USC School of Medicine.
6. Ph.D. Guidance Committee, Dean of Graduate Studies Representative, Paresh Sanghani, 1996; Elaine
Chen, 1992 (USC School of Pharmacy);Jingwen (Jenny) Zheng, 1994; Jeff Wang, 1994.
7. Helena Gustavsson, premedical student, U. of Göteborg, Sweden, 1992-93.
8. Francisco Bravo H.S. preceptor and Science Fair judge, 1991 -1999.
9. University of Göteborg M.D./Ph.D. graduate USC studies preceptor for: Magnus Berne, M.D., Ph.D.
(1986), Roland Frösing, M.D., Ph.D. (1992), Per-Anders Larsson (1994).
CNUCOM, California Northstate University, College of Medicine 2013–2019
Wrote inaugural Hematology Curriculum (with Eva G. Hess MD) for CNU COM, 2013
Low Nucleophilic Selectivity. CNUCOM May 8, 2017.
Barriers to Care by Paraplegics at the Chemotherapy Infusion Center. CNUCOM May 8, 2017.
Military Service
U.S. Public Health Service, Lt (03), 1970-1973
Presidio, Marine Hospital, San Francisco, California
Society Memberships
Memberships Past and Present
American Medical Association
Sacramento-El Dorado County Medical Association
Sierra Sacramento Valley Medical Society
Los Angeles County Medical Association
Pasadena Medical Society
California Medical Association
American Association for Cancer Research
American Society for Clinical Oncology
Association of Northern California Oncologists
American Society of Hematology
American Chemical Society
American Society for Cell Biology – ASCB
SPIE-The International Society for Optical Engineering
International Union of Pure and Applied Chemistry
International Society for the Study of Xenobiotics
International Society for the Study of Comparative Oncology
Mathematics Association of America
American Mathematics Society
Fibonacci Association
American Statistical Association
South Bay Writers Club (California Writers Club)
Sacramento Writers Club (CW)
Consultantships
Biokeys Corporation: Consultant, Los Angeles, CA, 1997-1999
US Bioscience: Investigator Meetings Faculty, 1997-1999
Rhône-Poulenc-Rorer: Speaker, Area Advisory Board, 1997-1999
NCI: Program Project Reviewer, Division of Cancer Treatment, 1988 (Memorial SKCC), 1991 (Roswell
Park), 1993 (Univ. of Michigan), 1994 (Yale Univ.)
NCI, NIH: Phase I-II Cancer Pharmacokinetics Contracts Review Committee, 1997
NIH, PHS SBIR and STTR: Reviewer, 1994, 1995
NCI: Extramural R13 Reviewer, 1991
NCI: Special Emphasis Panel, Chemopreventive Agent Contracts, 1992
NATO: Referee, Collaborative Research Grants, 1991
SPIE: International Working Group in Electronic Imaging
Regional Cancer Treatment: Member, Editorial Board
Reviewer: J. Med. Chem., Cancer Res., Cancer, J. Biol. Chem., J. Natl. Cancer Inst.,
Biochem. Pharmacol., Eur. J. Oncol., Cancer Chemother. Pharmacol., Fibonacci Quarterly, Oncology Research, Gastroenterology, Int. J. Cancer, Drugs, J. Spinal Cord Med., Cancer Imaging
Hospital Staff Privileges
CURRENT
Mercy General Hospital, Sacramento, CA 2001-2027
PRIOR
Sacramento, CA: Sutter General Hospital and Sutter Memorial Hospital.
Davis, CA: Sutter Davis Hospital, 1999-2001.
Pasadena, CA: Huntington Memorial Hospital and St. Luke Medical Center, 2/97 – 1/99.
Los Angeles, CA: The Hospital of the Good Samaritan, 1984-7, Norris Cancer Hospital, 1987-1997,
USC University Hospital, 1992-1997.
Locum Tenens
Practice of Mark Farbstein,
Hematology/Medical Oncology, Pasadena, CA, 11/96
Practice of Lowell Irwin, M.D. and M. Mercedes Brenneisen, M.D.,
MedicalOncology/Hematology, Los Angeles and San Gabriel Valley, CA, 1990s.
Practice of Mark Turrill, M.D.,
Medical Oncology/Hematology, Lakeport, CA, 1999.
Practice of Herbert A. Hartman, Jr., M.D.,
Methodist Cancer Center, Omaha, NE, 2000.
Research Grants as Principal Investigator
NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH
R01 CA39629-04, Biochemistry of 5-Fluorouracil Effects $185,782 Direct costs awarded; 5-01-88 to 4-30-91; CA39629-06S1, $27,285, 5-1-91 – 11-30-91.
LEDERLE LABORATORIES
Grant #179,000, (l) Leucovorin Addition to Protracted Infusion Fluorouracil, $92,055; 3-31-92.
NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH
CA39629-07, Biochemistry and Pathology of 5-FU/&Folate Therapy, $356,977 Direct costs awarded;
7-1-92-6-30-95.
NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH
CA39629-08S, $15,000 Direct costs awarded; 1/1/94-6/30/94.
NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH
CA39629-09, Biochemistry and Pathology of 5-FU/Folate Therapy, $117,000 Direct costs awarded; 7/1/94-6
/30/95.
THERO2X, INC.
Oxygen supersaturated crystalloids as radiation sensitizers, $10,000, 9/95.
UNIVERSITY OF GÖTEBORG
Pharmacodynamics of TS Inhibition, $15,000, 10/1/95.
BRISTOL MYERS-SQUIBB, ONCOLOGY DIVISION
Sequence Dependency of Hydroxyurea and Fluorouracil, $24,000, 7/1/96-2/1/97.
U.S. BIOSCIENCE
Biochemical Correlates of Neutrexin/5-FU/LV in Colorectal Cancer, $25,000, 1997.
RHÔNE-POULENC RORER/UNIVERSITY OF GÖTEBORG
Image Cytometry of Thymidylate synthase and Ki-67 in Phase 3 Colorectal Cancer Patients Randomised to
5-Fluorouracil vs. Camsar, $25,000, 1997-8.
USC NATIONAL ENVIRONMENTAL HEALTH SCIENCES CENTER (NIEHS)
Alkylating Activities and Mutagenicities of Oxygenated Fuel Additives, $15,000, January, 1997.
Research Grants as Co–Investigator
NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH
RFA CA93-09, Phase II Trials of New Anticancer Agents, $237,048 Direct costs awarded; P.I.: Franco M. Muggia; 5% effort; 6/10/94-6/9/98.
NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH
1-U02 CA62505-01 (RFA CA93-07), Phase I Contract, Phase I Molecular and Clinical Pharmacodynamic
Trials; P.I.: Franco Muggia; 5% effort; 1994-1998.
NATIONAL INSTITUTES OF HEALTH, MEDICAL SCIENCES TRAINING PROGRAM
Training of Medical Scientists in Modern Biology; P.I.: Richard Bergman; 5% effort; 1994.
Publications
Peer–Reviewed Publications
Aerosp. Med., 45:274-278, 1974.
Aviat. Space Environ. Med., 46:11-15, 1975.
Proc. Natl. Acad. Sci. USA, 75:1456-1460, 1979.
Mol. Pharmacol., 19:496-504, 1981.
Cancer Res., 41:3095-3099, 1981.
Cancer Res., 42:450-456, 1982.
Exerpta Med. Int. Congr. Series 647:12-19, 1984.
Med. Pediat. Oncol., 12:212-217, 1984.
Cancer Res., 44:4144-4150, 1984.
Mol. Pharmacol., 27:302-307, 1985.
J Clin Oncol. 3(11):1563, 1985.
Cancer Chemother. Pharmacol., 16:237-242, 1986.
Cancer Chemother. Pharmacol., 20:193-197, 1987.
J. Med. Chem., 30:597-602, 1987.
Synthesis, 133-135, 1988.
Adv. Exp. Med. Biol. 244: 97-106, 1988.
Adv. Exp. Med. Biol. 244: 219-224, 1988.
Cancer Invest., 6:377-384, 1988.
Cancer Res., 48:5894-5900, 1988.
Mut. Res., 203:355-366, 1988.
Invest. New Drugs, 7:27-36, 1989.
Biochem. Pharmacol., 38:2985-2993, 1989.
Cancer Chemother. Pharmacol., 25:124-130, 1989.
J. Pharm Sci., 79:57-62, 1990.
Cancer Chemother. Pharmacol., 26:57-61, 1990.
J. Med. Chem., 33:1544-1547, 1990.
J. Med. Chem., 33:1975-1979, 1990.
Anticancer Res., 10:813-816, 1990.
Eur. J. Cancer, 26:874-876, 1990.
Cancer Res., 52:108-116, 1992.
J. Clin. Oncol., 10:1933-1942, 1992.
J. Natl. Cancer Inst., 85:41-44, 1993.
Acta Crystallogr., 49:520-523, 1993.
Eur. J. Med. Chem., 28:473-479, 1993.
Reg. Cancer Treat., 3:140-143, 1993.
Invest. New Drugs, 12:197-206, 1994.
Hematol./Oncol. Clin. N. Amer., 9:397-413, 1995.
Anticancer Res., 15:433-440, 1995.
Bioorg. Medicinal Chem. Lett., 5:1627-1632, 1995.
Eur. J. Cancer, 31A:1306-1310, 1995.
Reg. Cancer Treat., 8:101-108, 1995.
Cell Growth & Differ., 6:1405-1413, 1995.
Biochem. Pharmacol., 50:1347-1351, 1995.
Bioorg. Med. Chem. Lett. 5:1627-1632, 1995.
Cancer Treat. Res. 78: 115-134, 1995.
Fibonacci Quarterly 34.3:121-128, 1996.
Acta Oncol. 35:469-472,1996.
Bioorg. Med. Chem. Lett. 6:1497-1502, 1996.
Biorg. Med. Chem. Lett. 6: 2477-2480, 1996.
J. Clin. Oncol. 15: 2103-2110, 1997.
Cancer J. 10: 266-273, 1997.
Reg. Cancer Treat., 1997.
Cancer Invest. 16(7):447-455, 1998.
Current Topics Medicinal Chem. 2:85-100, 1997.
Anticancer Res.17(5A):3671-3674, 1997.
Hum. Gene Ther. 9:719-728, 1998.
Fibonacci Numbers and their Applications 7: 377-391, 1998.
Clin. Cancer Res. 4(5):1315-1322, 1998.
Eur. J. Medicinal Chem. 34(5):389-398, 1999.
Mutation Res. 446:15-21, 1999.
Anticancer Drugs 12(6):505-511, 2001.
Clin. Cancer Res. 9(16):6012-6019, 2004.
Congressus Numerantium 201: 257-272, 2009.
Congressus Numerantium 201: 273-275, 2009.
Aportaciones Matimaticas Investigation 20: 61-70, 2011. \
Proceedings of the Fifteenth International Conference on Fibonacci Numbers and their Applications, Eszterhay College, Eger, Hungary, June 26, 2012.
2015 Apr;100(4):479-88.
Miscellaneous Publications
1. Spears, C.P. Thymidylate synthetase inhibition in Peyton adenocarcinoma xenografts following bolus
5–fluorouracil. Exerpta Med. Int. Congr. Series, 647:12–19, 1984.
2. Spears, C.P. Management of the Patient with Paraneoplasia. Hospital of the Good Samaritan Manual, Hematology–Oncology Unit, 1984, pp. 1–118.
3. Spears, C.P., Ray, M., Granger, S., Diasio, R.B., and Gustavsson, B.G. Dual role of serine hydroxymethyltransferase in the synergy of fluorouracil and leucovorin: effects of L–serine and glycine on H4PteGlu/5,10–CH2–H4PteGlu ratios; and H4PteGlu–catalyzed release of fluoride ion from alpha!fluoro!beta–alanine. IN: Pteridines and Folic Acid Derivatives (H.Ch. Curtius, S. Ghisla and N. Blau, eds.), Walter de Gruyter, Berlin, 1990.
4. Alaverdian, A., Spears, C.P., Kang, S–I., and Shahinian, A.H. High nitrogen and low sulfur selectivities of alkyl aryl selenones and activities against drug!resistant tumor cell lines. USC Undergrad. J., 2: (1992).
5. Spears, C.P., and Danenberg, P.V. Thymidylate synthase pharmacodynamics; Minutes of the NCI Phase
I Working Group, NCI, CTEP, DCT. Bethesda, MD, October 27 and 28, pp 87–109, 1993.
6. Spears, C. P., Thyroid Cancer, IN: The Complete Cancer Survival Guide, by P. Teely and P. Bashe, Doubleday Books, May, 2000.
7. Spears, C. P. Writers Block and A Song of Fertility. Poems in: Writers Talk, Monthly Newsletter of South Bay Writers Club. 21(6):10,11, 2014.
8. Spears, C.P. Parallel, and Our. Poems in: Writers Talk, Monthly Newsletter of South Bay Club 22 (4): 11, 2014.
9. Spears, C. P. Photo credit. Dedication to Herta Taussig Freitag, Fibonacci Quarterly 34 (5): 467, 1996.
10. Hyatt, K.H., Sullivan, R.W., Spears, C.P., and Vetter W.R. A Study of ventricular contractility and other parameters possibly related to vasodepressor syncope.
US Public Health Service Hospital, San Francisco. NASA CR T-81035, pp.1-35, 1973.
Patents
1. Spears, C.P. Tumor Growth Measurement Device.
U.S. Patent 4,131,998. Jan 2, 1979.
2. Spears, C.P. Biopsy Retriever.
U.S. Patent 5, 133, 360. July 28, 1992.
3. Spears, C.P., and Gustavsson, B.G. Use of 5,10–Methylene–tetrahydrofolate as a Modulator of a
Chemotherapeutic Agent.
U.S. Patent 5, 376,650. December 27, 1994.
4. Spears, C.P., and Gustavsson, B.G. Use of 5,10–Methylene–tetrahydrofolate as a Modulator of a
Chemotherapeutic Agent (Continuation in Part) U.S. Patent 5,534,519. July 9, 1996.
5. Spears, C.P., and Kang, S!I. 2–Chloroethyl Aryl Selenones against Alkylating Agent Resistant Cancer
Cells.
U.S. Patent 5,614,562. March 25, 1997.
6. Spears, C.P., Gustavsson, G., and Carlsson, G. 5,10–Methylene–tetrahydrofolate as a Modulator of a
Chemotherapeutic Agent,
Canadian Patent Application 2,082,881, Notice of Allowance March 16, 2004.
7. Spears, C.P. and Brower, S.P. System and Method for Evaluating Tumor Stability.
U.S.Patent 11,908,154 issued 02/20/2024.
8. Spears, C.P. and Brower, S.P. Transparent Tumor Size Measuring Ruler. US Design Patent
Application 29833158. April1, 2022.
9. Spears, C.P. and Brower, S.P. System and Method for Evaluating Tumor Stability.
Filed November 17, 2023. Publication US-2024-0138707-A1 May 2, 2024.
Selected Abstracts
1. Heidelberger, C., and Spears, C.P. Determinants of sensitivity to 5–fluorouracil (5–FU): new ultrasensitive assays for 5–fluorodeoxyuridylate (FdUMP), deoxyuridylate (dUMP), and thymidylate synthetase (TS). Proc. Am. Assoc. Cancer Res., 20:63, 1979.
2. Spears, C.P., Shahinian, A.H., and Heidelberger, C. Relationship between 5–fluorouracil (5–FU) chemotherapeutic efficacy and thymidylate synthetase (TS) inhibition in murine colon carcinomas. Proc. Am. Assoc. Cancer Res., 22:206, 1981.
3. Spears, C.P., Gustavsson, B.G., Berne, M., and Heidelberger, C. Thymidylate synthetase inhibition by
5–fluorouracil (5–FU) treatment of human gastrointestinal malignancies: dump/&FdUMP ratio as a determinant.
Proc. Am. Assoc. Cancer Res., 24:133, 1983.
4. Spears, C.P., Gustavsson, B.G., Leissner, K.H. and Danenberg, P.V. Parameters of thymidylate synthetase (TS) inhibition in bladder carcinoma after intravesical 5–fluorouracil (5–FU) combined with systemic allopurinol protection.
Proc. Am. Assoc. Cancer Res., 25:166, 1984.
5. Gustavsson, B.G., Berne, M., Frösing, R., and Spears, C.P. Thymidylate synthetase inhibition in dimethylhydrazine!induced rat colon carcinoma after sequential methotrexate/5–fluorouracil administration.
Proc. Am. Assoc. Cancer Res., 26:241, 1985.
6. Spears, C.P., Danenberg, P.V., and Gustavsson, B. Intracellular biochemical pharmacodynamics as a clinical approach to drug sensitivity testing of solid tumors.
Eur. Conf. Clin. Oncol., 3:43, 1985.
7. Spears, C.P., Berne, M.H., and Gustavsson, B.G. Lack of heterogeneity in pharmacodynamic studies of gastrointestinal tumors treated with 5–fluorouracil.
Int. Cancer Congr. XIV, 1986.
8. Spears, C.P., Frösing, R., and Gustavsson, B.G. Intracellular pharmacodynamics of 5–fluorouracil in tumors and normal tissues.
Proc. Am. Soc. Clin. Oncol., 5:1986.
9. Kang, S-I., and Spears, C.P. Selenium Mustards: reactivity correlations in a new class of cytotoxic alkylating agents.
Proc. Am. Assoc. Cancer Res., 27:1106, 1986.
10. Schwartz, J., Alberts, D., Einspahr, J., Peng, Y-M., and Spears, P. Dipyridamole potentiation of FUDR activity against human colon cancer in vitro and in patients.
Proc. Am. Soc. Clin. Oncol., 6:325, 1987
11. Spears, C.P., and Gustavsson, B.G. Deoxyuridylate!fluorodeoxyuridylate competition for binding to bacterial thymidylate synthase at low folate concentrations.
Proc. Am. Assoc. Cancer Res., 28:321, 1987.
12. Spears, C.P., Gustavsson, B.G., and Frösing, R. Serial tumor biopsy analysis of 5-FU/leucovorin. Int. Conf. Regional Cancer Ther., Ulm & Donau, 1987.
13. Spears, C.P., Gustavsson, B.G., Carlsson, G., and Frösing, R. Fluorouracil& leucovorin pharmacodynamics: determination by serial biopsy.
Proc. Am. Assoc. Cancer Res., 29:186, 1988.
14. Spears, C.P., Gustavsson, B.G., Carlsson, G., Frösing, R., Waugh, W., Leichman, C.G., and Muggia, F.M. Activation of leucovorin to methylenetetrahydrofolate for improving thymidylate synthase inhibition after 5-FU: effects of CF dose, L-serine, L-glutamate, and direct methyl-tetrahydrofolate administration.
Proc. Am. Soc. Clin. Oncol., 8:69, 1989.
15. Kang, S-I., and Spears, C.P. Organoselenones: alkylation by selenium-carbon bond breakage. Proc. Am. Assoc. Cancer Res., 30:459, 1989.
16. Kang, S-I., and Spears, C.P. Linear free energy relationships and cytotoxicities of para!substituted
2!haloethylaryl selenides and bis-(2-chloroethyl) selenides.
Quant. Struct.-Act. Relat., 7:109, 1988.
17. Leichman, G., Leichman, L., Rosen, P., Spears, C.P., et al. Biologic modification of continuous low-dose infusion of 5-fluorouracil by low-dose leucovorin.
Proc. Am. Soc. Clin. Oncol., 8:73, 1989.
18. Spears, C.P. Multiple roles of serine hydroxymethyltransferase (SHMT) in the modulation of fluorouracil by leucovorin: correlation of high H4PteGlu levels with response; and SHMT inhibition and fluoride ion production by alpha-fluoro-beta-alanine (FBAL).
Int. Symp. Pteridines and Folic Acid Derivatives, 9:138, 1989.
19. Spears, C.P., Granger, S., Ray, M., Carlsson, G., Gustavsson, B.G. Tetrahydrofolate (FH4)-mediated fluoride ion (F-) production by serine hydroxymethyltransferase (SHMT) processing of FBAL.
Proc. Am. Assoc. Cancer Res., 31:396, 1990.
20. Spears, C.P., Waugh, W., Leichman, L., Leichman, C.G., Jeffers, S., Gustavsson, B.G., and Muggia, F.M. Salvage therapy of breast cancer with fluorouracil (5-FU) and high!dose leucovorin (LV): response correlations with tumor pharmacodynamics.
Proc. Am. Soc. Clin. Oncol., 9:, 1990.
21. Leichman, L., Silberman, H., Leichman, C., Laine, L., Ramos, H., Spears, P., and Jeffers, S. Neoadjuvant chemotherapy for gastric adenocarcinoma (GA) followed by postoperative intraperitoneal (IP) chemotherapy.
Proc. Am. Soc. Clin. Oncol., 9:109, 1990.
22. Leichman C., Leichman, L., Spears, C.P., Jeffers, S., Chavez, J., Groshen, S., Waugh, W., and Rosen, P. Phase II study of protracted infusion 5!fluorouracil (5-FU) with weekly leucovorin (LV) in disseminated, measurable adenocarcinoma of the large bowel. Proc. Am. Soc. Clin. Oncol., 9:129, 1990.
23. Leichman, C.G., Leichman, L., Spears, C.P., Rosen, P., and Jeffers, S. Phase II study of prolonged infusion 5-fluorouracil (PIFU) with weekly leucovorin (LV) in disseminated colorectal cancer (CRC). Proc. Am. Soc. Clin. Oncol., 10:143, 1991.
24. Spears, C.P., Carlsson, G., Leichman, C.G., Gustavsson, B.G., and Leichman, L. Folated-mediated thymidylate synthase (TS) pharmacodynamics (PD): Effect of modulators of fluoropyrimidine therapy.
Proc. Am. Soc. Clin. Oncol., 10:118, 1991.
25. Spears, C.P. Aqueous, in vitro method for determination of linear free energy relationship (LFER) parameters such as Swain-Scott constants in the kinetics of alkylating agents, in reactions with model nucleophiles.
Proc. Am. Assoc. Cancer Res., 32:434, 1991.
26. Tulpule, A., Chan, K., Muggia, F.M., Spears, C.P., Spicer, D., and Jeffers, S. Uracil (U) + Ftorafur (FT): Pharmacokinetic profile of an orally active 5-fluorouracil (FU) prodrug.
Clin. Res., 1991.
27. Muggia, F.M., Chan, K., Tulpule, A., Shahinian, A., Retzios, A., Spears, C.P., Leichman, L., and Jeffers, S. Intraperitoneal (IP) floxuridine (FUDR)+(d,l)-leucovorin (LV): results of pharmacologic studies with LV dose-escalation.
Clin. Res., 1991.
28. Spicer, D., Muggia, F., Tulpule, A., Chan, K., Leichman, G., Spears, P., and Jeffers, S. Phase I circadian dosing of daily oral uracil (U) plus l-(tetrahydro-2-furanyl)-5-fluorouracil (FT) with leucovorin (LV).
Proc. Am. Soc. Clin. Oncol., 10:118, 1991.
29. Spears, C.P., Carlsson, G., Shahinian, A.H., Gustavsson, B.G., and Frösing, R. Pharmacologic (6R,S)-tetrahydrofolate (FH4): synergy with fluorouracil (FUra) by increased thymidylate synthase (TS) inhibition, decreased methylene units, andpromotion of unbalanced growth.
Proc. Am. Assoc. Cancer Res., 33:264, 1992.
30. Spears, C.P., Leichman, C.G., Muggia, F.M., Retzios, A., Imam, A., Kiyabu, M.Y., and Leichman, L. (l)-Leucovorin (l-LV) plus infusion 5-FU: thymidylate synthase (TS) effects in tumor extracts and digital image analysis quantitation.
Proc. Am. Soc. Clin. Oncol., 11:116, 1992.
31. Muggia, F.M., Jeffers, J., Leichman, C.G., Tulpule, A., Hanisch, R., Fuerst, M., Spears, C.P., Wu, X.Y., Chan, K., Spicer, D., and Leichman, L. Potential for uracil+ftorafur (UFT) to mimic protracted infusions of 5-fluorouracil (FU).
Proc. Am. Soc. Clin. Oncol., 11:135, 1992.
32. Spears, C.P., Su, S., Gustavsson, H., and Stevenson, L.A. Digital image analysis (DIA) of in situ thymidylate synthase (TS) protein and mRNA message using a modular system for RGB image processing.
Proc. Am. Assoc. Cancer Res., 34:417, 1993.
33. Grunberg, S.M., Spears, C.P., Jelliffe, R.W., Zaretsky, S., Shahinian, A.H., Su, S., and Tahani, B. Phase I clinical and pharmacokinetic (PK) study of high-dose edatrexate (EDX) with leucovorin (LV) rescue (Protocol NCI-T91-0077).
Proc. Am. Soc. Clin. Oncol., 12:154, 1993.
34. Carlsson, G., Gustavsson, B.G., Hafström, L.O., and Spears, C.P. 5-Fluorouracil (5-FU) and methylenetetrahydrofolate (CH2FH4) as adjuvant therapy in an experimental colonic adenocarcinoma in rats.
18th Int. Congr. Chemother., Abstract No. 272, p. 168 of Proceedings, Stockholm, 1993.
35. Kundu, N.G., Mahanty, J.S., Dasgupta, S.K., and Spears, C.P. Synthesis and biological activities of 5-(acylethynyl)uracils, 5-(2-acylvinyl)uracils and their corresponding 2-deoxyribonucleosides. Division of Medicinal Chemistry, 206th ACS National Meeting, Chicago, IL, August 22!27, 1993.
36. Grunberg, S.M., Spears, C.P., Natale, R., Zaretsky, S., and Ashigawa, T. Phase I evaluation of high-dose edatrexate (EDX) with leucovorin (LV) rescue.
Proc. Am. Soc. Clin. Oncol., 13:146, 1994.
37. Larsson, P-A., Carlsson, C., Spears, C.P., and Gustavsson, B.G. 5,10-Methylene-tetrahydrofolate (CH2FH4) effects on rat colon tumor growth and biomodulation of 5-fluorouracil (FUra).
Proc. Am. Assoc. Cancer Res., 35:426, 1994.
38. Avramis, V.I., Larson, G.P., Spears, C.P., Kwock, R., Nelson, P., Muthini, S., and Rossi, J.J. Hammerhead ribozymes as anti-oncogene (N-myc) biotherapeutic agents.
Proc. Genet. Revolution, p. 11, 1994.
39. Avramis, V.I., Larson, G.P., Spears, C.P., Kwock, R., Nelson, P., Muthlnl, S., and Rossi, J.J. Hammerhead ribozymes as anti-oncogene (N-myc) biotherapeutic agents.
Clin. Chem., 40:2336, 1994.
40. Muggia, F., Israel, V., Pujari, M., Spears, C.P., Leichman, L., Leichman, C.G., Jeffers, S., Rogers, M., and Koda, R. Intraperitoneal (IP) floxuridine (FUDR) and leucovorin (LV) with simultaneous 72h hydroxyurea (HU) IV infusion: pharmacology and tolerance.
Proc. Am. Assoc. Cancer Res., 36:241, 1995.
41. Periclou, A.P., Spears, C.P., Grunberg, S.M., Lee, W.Y., Koda, R., and Avramis, V.I. Pharmacokinetic analyses of 10-edatrexate following a Phase I short-term continuous infusion in patients with carcinomas.
Proc. Am. Soc. Clin. Oncol., 14:458, 1995.
42. Das, P., Kundu, N.G., Spears, C.P., and Su, S. Synthesis and biological activities of 6-(2-acylvinyl) uracils.
Division of Medicinal Chemistry, 207th ACS National Meeting, Anaheim, CA, April 2-6, 1995.
43. Carlsson, G., Frösing, R., Larsson, P-A., Spears, C.P., and Gustavsson, B.G. Fluorouracil (FU) plus 5,10-methylene-tetrahydrofolate ((d,l)-CH2FH4): Phase I-II trial of weekly i.v. bolus therapy.
Am. Soc. Clin. Oncol., 14:469, 1995.
44. Koda, R., Parimoo, D., Spears, C.P., Israel, V., Jeffers, S., Rogers, M., Leichman, L., Leichman, C.G., Pujari, M., and Muggia, F. Hydroxyurea (HU) IV 72-hour infusion during intraperitoneal (IP) fluxouridine (FUDR) and leucovorin (LV): pharmacologic/clinical correlates.
Proc. Am. Assoc. Cancer Res., 37:181, 1996.
45. Spears, C.P., Vergon, C., Polonsky, M., Masterson, M., Habboubi, N., Carlsson, C., Gustavsson, B.G., and the Nordic Biomodulation Group, Phase I/II sequential trimetrexate/split-dose fluorouracil therapy in advanced colorectal cancer.
Proc. Am. Soc. Clin. Oncol. 17: 1999.
46. Alvarez, E., Menon, K., Bewley, J.R., Spears, C.P., Schultz, R.M., Teicher, B.A., Chen, V.J., and Galbreath, E. Immunohistochemical detection of in vivo alteration of thymidylate synthase levels in a human HCT116 colon carcinoma tumor xenograft induced by the use of MTA (LY231514).
Clin. Cancer Res. 5 (Suppl. S):657, 1999.
47. Yazan, O., Spears, C.P., Carlsson, G. Gustavsson, B., Ingram, M.L., and Gruia, G. Thymidylate synthase (TS) and Ki-67 expression in tumor cells of patients with advanced colon cancer randomized to irinotecan (CPT-11) vs. 5-fluorouracil (5-FU).
Ann. Oncol. 11 (Suppl.4):234P, 2000. (Proceeding of the 25th ESMO Congress, 13-17 October, Hamburg, Germany.
48. Lenz, H, Iqbal, S., Groshen, S., Muggia, F.M., Tsao-Wei, D., Johnson , K., Spears, C.P., Gandara, D.R., Yen, Y., Doroshow, J.H., and Newman, E.M. Phase I study of sequency dependency of iv hydroxyurea (HU) in combination with fluorouracil (5-FU).
Proc. Am. Soc. Clin. Oncol. 20:95b, 2001.
49. Odin, E., Wettergren, Y., Carlsson, G., Larsson, L., Spears, C.P., and Gustavsson, B. Gene Expression Ratios of folylpolyglutamate synthetase (FPGS) and gamma-glutamyl hydrolase (GGH) in colorectal carcinoma and paired normal mucosa.
Proc. Am. Soc. Clin. Oncol. 20: #359, 2001.
50. Gustavsson, B., Xiog, S., Salonga, D., Cooc, J., Danenberg, K., Carlsson, G., Odin, E., Spears, P., Lord, R.V., and Danenberg, P.V. Inverse relation between DPD mRNA expression and response to 5FU/LV therapy versus 5FU/5, 10, methylenetetrahydrofolate therapy for patients with colorectal cancer.
Proc. Am. Soc. Clin. Oncol. 21:115a, 2002.
51. Spears, C.P., Carlsson, G., Odin, E., and Gustavsson, B. More rapid and complete thymidylate synthase (TS) inhibition in tumors after 5-FU by methylene-tetrahydrofolate (CH2FH4) preloading.
EORTC-NCI-AACR Symposium, Frankfurt, Germany, November, 2003. Eur. J. Cancer 38 (Suppl.7):S22, 2002.
52. Cantwell, M.J.,Spears, C.P., Robbins, J.M. Antitumor activity of combination of
5,10-methylenetetrahydrofolate, 5-fluorouracil, and anti-vascular endothelial growth factor against human colorectal HT-29 tumors in nude mice.
Proc. Am. Soc. Clin. Oncol. 22: 311s (Abstract 3768), 2004.
53. Spears, C.P., Pineda, R., Reid, T., Robbins, J., Habita, C., Pharmacodynamics of weekly intravenous methylene-tetrahydrofolate/5-fluorouracil on formic acid, RBC folate, and homocysteine levels in patients with metastatic colon cancer.
Proc. Amer. Assoc. Cancer Res. 2005.
54. Reid, T., Spears, C.P., Quadro, R., Subramanian, L., Pawl, L., Jankovic, S., Jelic., N., Milinic, L., Muzikravic, L., Habita, C. A Simon 2 stage study of 5,10-methylenetetrahydrofolic acid with 5-fluorouracil as first line treatment in metastatic colorectal cancer.
Proc. Amer. Soc. Clin. Oncol. 23: 293s (Abstract 3692), 2005.
55. Reid, T., Spears, C.P., Quadro, R., Subramanian, L., Pawl, L., Jankovic, S., Jelic., N., Milinic, L., Muzikravic, L., Robbins, J. 5,10-methylenetetrahydrofolic Acid with 5-fluorouracil as first line treatment in metastatic colorectal cancer: Phase II study results. (https://www.cpspears.com/publications/42nd-ASCO-annual-meeting.pdf)
Proc. Amer. Soc. Clin. Oncol. 24: 170s (Abstract 3699), 2006.
56. Reid, T., Spears, C.P., Subramanian, M., Pawl, L., Jankovic, G., Jelic, S., Milinic, N., Muzikravic., Stewart, J., Robbins, J.M. Response to second line treatment following 5,10-methylenetetrahydrofolate acid (CoFactor) with 5-fluorouracil as first line treatment in metastatic colorectal cancer.
Proc. 8th World Congress on Colon Cancer, Barcelona, Spain, 2006.
57. Spears, C.P., Yan, J.J., and Bicknell-Johnson, M. Modulo Fibonacci Model of Phyllotaxis. Am. Soc. Cell Biol. 46th Ann Meeting, San Diego, p.62, 529 (B492), 2006.
58. Spears, C.P., Khine, A., Nguyen, M.T. Bendamustine shows low Swain-Scott s–constant, nucleophilic selectivity, a basis for prolonged myelosuppression. EuroSciCon, Dublin, Ireland, June 11-13, 2018. Archives Cancer Res. Vol.6.
59. Spears, C.P., and Nguyen, M. Standardized Approach for Comparison of Therapeutic, Mutagenic, and Environmental Alkylating Agents in Neutral Protic Media. 32nd Euro Congress on Cancer Science & Therapy, March 07-08, 2019, Barcelona, Spain.
J. Cancer Sci. Ther. Vol.11:22-23, 2019.
60. Spears, C.P. and Nguyen, M. Nucleophilic Selectivities of Aliphatic Electrophile Candidates for Swain-Scott Analysis: Fully Protic and Aqueous, Green Media, Including Hypoxia, and Non-Nucleophilic Solvents. 17th Annual Congress of International Drug Discovery Science & Technology, Kyoto Intl. Conf. Center, Japan, July 25-27, 2019, pp.222-223.
61. Spears, C.P., Yan, J., Zimmerman, S., Brower, S., Nguyen, M., Anderson, P.G., and
Bicknell-Johnson, M. Wythoff and Zeckendorf Forms of Fibonacci Phyllotaxis (FP):
Extension to Planar Spiral Golden Angle Sorting of Age,Stem Cell, Cousinship OEIS
Sequences and Cotula discolor Histology with 3D Video Sequential Slide Video Microscopy. Fibonacci Association Conference, Harvey Mudd College, July 8, 2024.
