Ting-Chao Chou

Ting-Chao Chou
Memorial Sloan Kettering Cancer Center | MSKCC · Division of Molecular Pharmacology & Chemistry

Doctor of Philosophy (Ph.D. Yale'70)
MAL-PD theory based Top-Down alternative biomedical R&D, to complement the Conventional Observation based Bottom-Up R&D

About

436
Publications
76,885
Reads
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33,264
Citations
Citations since 2016
48 Research Items
11309 Citations
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201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500
Introduction
Prof. Ting-Chao Chou retired from the Molecular Pharmacology & Chemistry, Memorial Sloan-Kettering Cancer Center in 2013. He is Founder, PD Science LLC (USA). He does research in Theoretical Biology, Pharmacodynamics (PD), Biodynamics (BD) and Bioinformatics (BI) of the Mass-Action Law, Computer Graphics for Econo-Green Drug R&D and Regulations. His 433 publications have 39,392 citations in over 1,469 biomedical journals. He derived the Median-Effect Equation and the Combination Index Theorem.
Additional affiliations
August 1998 - June 2013
Memorial Sloan Kettering Cancer Center
Position
  • Retired
Description
  • Retired from the Director of Preclinical Pharmacology Core, MSKCC (6.1.2013)
August 1972 - August 2000
Cornell University Graduate School of Medical Sciences
Position
  • Professor
Description
  • Affiliated with Memorial Sloan-Kettering Cancer Center, New York, NY
September 1965 -
Yale University
Position
  • PhD Student
Description
  • Equations of bi-mode Patterns, Median-Effect Equation of the Mass-Action Law. Theory leads to Chou’s 273- articles that have been cited 25,926 times in >754 bio-medical journals as of 4.4.2017 (Google-Scholar, Web-of-Science, Wikipedia - Ting-Chao Chou).
Education
August 1965 - January 2000
Yale University
Field of study
  • Pharmacology

Publications

Publications (436)
Article
The conventional bottom-to-up approach of R&D is usually from aims to design, to experimental findings, to fitting empirical curves, formula, or model, to statistical analysis, to drawing conclusion/hypothesis. The alternative nonconventional, top-to-down approach is the mathematical system analysis to derive the unified general pharmacodynamics th...
Article
During the past century, there are over 15 different definitions of "synergism" or methods of its measurement, but none supported the others. These generate tremendous confusions and controversies in biomedical science and biomedical R&D, despite the fact that treatments of the most dreadful diseases such as cancer and AIDS, are mainly using drug c...
Article
The conventional bottom-to-up approach of R&D is usually: aims, design, findings, data analysis, statistics, and conclusions or suggestive hypothesis. The experimental findings need to fitting empirical curves, formula, or model. The alternative nonconventional, top-to-down approach,shown here, is the mathematical system analysis to derive the unif...
Article
Full-text available
Differentiated thyroid cancer (DTC) patients are usually known for their excellent prognoses. However, some patients with DTC develop refractory disease and require novel therapies with different therapeutic mechanisms. Targeting Wee1 with adavosertib has emerged as a novel strategy for cancer therapy. We determined the effects of adavosertib in fo...
Conference Paper
Preclinical animal studies or clinical protocol designs frequently limited by the dose-number or dose-range involved, especial for multiple candidate drugs and their combinations. The unified theory of the Mass-Action Law Pharmacodynamics and Bioinformatics [MAL-PD/BI] and its combination index (CI) theory provide general principle for drug evaluat...
Conference Paper
Full-text available
Biological system-analysis by the mass-action law with biophysical, biochemical and mathematical induction-and-deduction leads to the derivation of >300 reaction rate equations. These derived equations led to general biodynamics/pharmacodynamics and bioinformatics (MAL-BD/PD/BI) general paradigms for “Dose” and “Effect”. 1. Median-Effect Eq. (MEE)...
Article
Wee1 is a kinase that regulates the G2/M progression by inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease. The therapeutic effects of adavosertib, a Wee1 inhibitor for anaplastic...
Article
Full-text available
Polo‐like kinases (PLKs) are potent regulators of cell proliferation and cell survival. PLKs are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease. The therapeutic effects of volasertib, a PLK inhibitor, was evaluated for the treatment of ATC either alone or in combination with sorafenib. Volasertib de...
Conference Paper
p>The Median-Effect Equation (MEE) for single drug, and the Combination Index Equation (CIE) for multiple drug combinations, are basis for general Pharmacodynamics (PD), and Biodynamics (BD). Both, MEE and CIE are derived from system analysis of the Mass-Action Law (MAL). The MAL-PD/BD theory, equations and algorithms allow automated computer simul...
Conference Paper
Full-text available
The mass-action law (MAL) based Median-Effect Equation (MEE) for single- drug, and the Combination Index Equation (CIE) for drug-combinations, are the basis for unified Pharmacodynamics (PD) and Biodynamics (BD). To date, the MAL-PD/BD theory, in 3 articles alone, have 12,577 citations in 1,248 biomedical journals (Google Scholar Citation-Ting-Chao...
Article
Full-text available
Pharmacology Mass‐Action Law Based Pharmacodynamics General Theory, Equation, Algorithm, and Computer Simulation for Econo‐Green Biomedical R&D and for Quantitative/indexed Drug Evaluation Guidance Ting-Chao Chou First published: 20 April 2020 https://doi.org/10.1096/fasebj.2020.34.s1.00298 Abstract The Mass‐Action Law (MAL) based Median‐Effect Equ...
Article
Full-text available
Abs. R301 ASBMB. EB-2020 San Diego [4.5.2020 Sun. 1:25 to 2:00 PM]. [Cancelled due to COVID-19 Pandemic]. Biophysical, Biochemical and Mathematical Doctrine of the Median: The Algorithms of the Unified Bio-Dynamics Theory for Basic Biomedical R&D and Regulatory Guidance Ting-Chao Chou*, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 [*P...
Article
Full-text available
Polo-like kinases (PLKs) are pivotal regulators of cell proliferation and cell survival; therefore, PLKs may be potential targets in the treatment of malignancy. The therapeutic effects of volasertib, a PLKs inhibitor for papillary and follicular thyroid cancer (known as well-differentiated thyroid cancer) were evaluated in this study. Volasertib i...
Article
Full-text available
Altered cyclin-dependent kinase activity is observed in many human malignancies. Cyclin-dependent kinases that promote cell cycle progression may be promising targets in the treatment of cancer. The therapeutic effects of roniciclib, a cyclindependent kinase inhibitor for medullary thyroid cancer were investigated in the present study. Roniciclib i...
Article
Full-text available
Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular th...
Article
Full-text available
The unified theory of the median-effect equation (MEE) of the mass-action law (MAL) indicates that dose and effect are interchangeable, and all dose-effect curves can be transformed into straight-lines by the median-effect plot. Therefore, it allows pharmacodynamics (PD) analysis using small size experimentation for in vitro and in vivo studies. Fu...
Article
Full-text available
Type B trichothecene mycotoxins (TCT B) are secondary metabolites produced by Fusarium fungi. Deoxynivalenol (DON), nivalenol (NIV) and their acetylated derivatives (3-acetyldeoxynivalenol: 3-ADON, 15-acetyldeoxynivalenol: 15-ADON, and 4-acetylnivalenol or fusarenon-X: FX) frequently co-occur in cereals following fungal infection by Fusarium specie...
Article
Full-text available
Many human cancers have altered cyclin-dependent kinase activity. Inhibition of cyclin-dependent kinases may arrest cell cycle progression and represents an important strategy in the treatment of malignancies. We evaluated the therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor, as a treatment for anaplastic thyroid cancer. Ronic...
Article
Full-text available
The global incidence of Fusarium head blight and attendant cereal grains multi-contamination by the trichothecene mycotoxins deoxynivalenol (DON) and nivalenol (NIV) are increasing as a possible result of climate change and inadequate agricultural practices. At the molecular level, these mycotoxins bind to the ribosome, activate the mitogen-activat...
Article
Based on physico-chemical principle of the mass-action law, bio-system analysis (arrangement & combinatorial) several hundred rate equations have been derived and published. Mathematical induction allows the deduction of them into the unified general median-effect equation (MEE) that makes dose & effect “interchangeable” for the 1st order and highe...
Conference Paper
Full-text available
Based on the systematic dynamic rate derivations with the mass-action principle and mathematical induction-deduction, the median-effect equation of Chou, and the combination index (CI) equation and their algorithm allow quantitative determination of synergism (CI<1), additive effect (CI=1) and antagonism (CI>1) (Pharmacol Rev 58:621-681, 2006). Bas...
Article
Full-text available
Background We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer. Materials and methods Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactat...
Data
The effect of dinaciclib on mitosis in thyroid cancer cells. (A) Chromosomal appearance was evaluated in BHP7-13, WRO82-1 and 8505C cells treated with dinaciclib (25 nM) or placebo for 24 h using immunofluorescence confocal microscopy. DNA was stained with DAPI. Placebo-treated cells at metaphase (white arrows), anaphase (yellow arrows) and telopha...
Data
Effects of dinaciclib on the expression of proteins associated with the cell cycle. (A) In BHP7-13 cells, dinaciclib (25 nM) decreased CDK1 and cyclin B1 levels by 8 h and the inhibitory effects persisted for 24 h. Aurora A was transiently increased by 4 h and decreased by 6 h. (B) In WRO82-1 cells, dinaciclib (25 nM) decreased CDK1 by 8 h and the...
Data
Biweekly intraperitoneal injections of paclitaxel (0.4 mg/mouse) over a 21-day treatment period failed to repress 8505C tumor growth. (TIF)
Data
Effects of dinaciclib on the expression of proteins associated with apoptosis. (A) In BHP7-13 cells, dinaciclib (25 nM) decreased Mcl-1 level by 4 h (the effect persisting for 24 h), Bcl-xL level by 16 h, and survivin level by 8 h. (B) In WRO82-1 cells, dinaciclib (25 nM) decreased Mcl-1 level by 4 h (the effect persisting for 24 h), Bcl-xL level b...
Data
Dinaciclib decreased the levels of cyclin B1, Aurora A, Mcl-1, Bcl-xL, and survivin in 8305C cells. (A) The expression of cell-cycle and apoptosis proteins was evaluated by Western blotting in 8305C cells treated with dinaciclib (25 nM) or placebo for the indicated periods. (B) Band density was quantified using Molecular Imager VersaDoc MP 4000 sys...
Data
The association between susceptibility to dinaciclib and baseline expression of Mcl-1 and Bcl-xL and the ratio of Mcl-1:Bcl-xL in seven thyroid cancer cell lines. (A) Immunoblot analysis was performed to evaluate the expression of Mcl-1 and Bcl-xL in seven untreated thyroid cancer cell lines. The sequence of proteins loaded was according to the Dm...
Data
Daily intraperitoneal injections of mice with 30 mg/kg dinaciclib had no significant effect on growth of 8505C tumor xenografts over 12 days. (TIF)
Data
Dinaciclib accumulated 8305C cells in mitosis and inhibited mitotic progression in prophase. (A) The percentage of 8305C cells in mitosis was assessed after treatment with placebo or dinaciclib (25 nM) for 24 h. Cells were stained with DAPI, and chromosome features were evaluated using immunofluorescence confocal microscopy. Mitotic index was asses...
Data
The association between susceptibility to dinaciclib and baseline expression of survivin in seven thyroid cancer cell lines. (A) Immunoblot analysis was performed to evaluate the expression of survivin in seven untreated thyroid cancer cell lines. (B) Band density was quantified. The ratios of survivin to α-tubulin in each cell line were calculated...
Article
Full-text available
This brief article focuses on two aims: i) To investigate the in vitro pharmaco-dynamic interactions of combining synthetic potent microtubule targeting anticancer agent, Fludelone (FD) with cyto-protective agent, Panaxytriol (PXT) derived from Panax ginseng, and ii) To illustrate step-by-step operation for conducting two-drug combination in vitro...
Patent
Full-text available
The present invention provides compounds of Formula (I), compositions comprising an effective amount of a compound of Formula (I), optionally with chemotherapeutic drugs such as a tubulin-binding drug, and methods of their use for reducing the toxicity of cytotoxic agents, treating or preventing cancer or a neuropathic disorder, inducing a chemopro...
Article
Full-text available
Drug combinations have been widely used in the treatment of the most dreadful diseases, such as cancer and AIDS. In the search for synergistic combinations for therapy, numerous articles have been published during the past century. However, the term “synergy” has at least 20 different definitions in literature but none supports others. The confusio...
Article
Triple-negative breast cancers (TNBCs) have poor clinical outcomes owing to a lack of targeted therapies. Activation of the MEK/MAPK pathway in TNBC has been associated with resistance to conventional chemotherapy and biologic agents and has a significant role in poor clinical outcomes. NV1066, a replication-competent herpes virus, infected, replic...
Patent
The present invention provides a series of 2,3-bis(hydroxymethyl)-4H-benzo[d]pyrrolo-[1,2-a]thiazoles and 1,2-bis(hydroxymethyl)indolizino[6,7-b]indole derivatives and their bis(alkylcarbamates) derivatives. These derivatives were designed as bi-functional DNA cross-linking agents. The in vitro cytotoxicity study of these compounds revealed that th...
Research Proposal
Full-text available
It is a Graphic Review file based on my published articles as indicated in Google Scholar Citations - Ting-Chao Chou (h-index: 70; Total citations as of 1.21.2019: 30,814) or in Web of Science: "www.researcherid.com/rid/B-4111-2009" (total citations: 21,541, as of 1.21.2019; Among 273 articles, average citations per article is: 78.8). Main article:...
Article
Combining oncolytic viruses with conventional therapy such as radiation is an innovative option for pancreatic cancer. We demonstrated that combination of GLV-1h151 and radiation yielded a synergistic cytotoxic effect, with the greatest effect achieved in the AsPC-1cell line. Combination treatment significantly increased apoptosis compared with eit...
Article
Full-text available
We evaluated the therapeutic effects of the histone deacetylase inhibitor PXD101 alone and in combination with conventional chemotherapy in treating thyroid cancer. We studied eight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic and medullary). The cytotoxicity of PXD101 alone and in combination with three conventio...
Article
Physico-chemical principle of the mass-action law algorithm (MALA) is the basis for systematic pharmacodynamics (PD) that leads to general median-effect equation (MEE) for single entity effect and the combination index equation (CIE) for multiple entity interactions (Chou TC, Pharmacol. Rev. 58: 621-681, 2006; Free web access: http://pharmrev.aspet...
Article
Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Drug combination is widely used in therapy against the most dreadful diseases such as cancer and AIDS. The combination index (CI) theorem based on the general median-effect equation (MEE) of the mass-action law (MAL) has been broadly used in combination of drug-drug, drug-...
Patent
The present invention provides convergent processes for preparing epothilone A and B, desoxyepothilones A and B, and analogues thereof. Also provided are analogues related to epothilone A and B and intermediates useful for preparing same. The present invention further provides novel compositions based on analogues of the epothilones and methods for...
Patent
Full-text available
The present disclosure relates to a series of bis(hydroxymethyl) and its bis(carbamate) of 8H-3a-azacyclopenta[a]indene-1-yl and 5,10-dihydropyrrolo-[1,2-b]isoquinolines derivatives (Formula I-Formula IV) as DNA di-alkylating agents. The preliminary antitumor studies indicated that compounds disclosed herein could exhibit potent cytotoxicity in vit...
Article
A series of bis(hydroxymethyl)indolizino[6,7-b]indoles and their bis(alkylcarbamates) were synthesized for antitumor studies. These agents were designed as hybrid molecules of β-carboline (topoisomerase inhibition moiety) and bis(hydroxymethyl)pyrrole (DNA cross-linking moiety). The preliminary antitumor studies indicated that these agents exhibite...
Article
Full-text available
We assessed the utility of the dual PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235) as single agent therapy and in combination with conventional chemotherapy for thyroid cancer. Eight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic, medullary) were studied. The cytotoxicity of BEZ235 and five conventional chemotherapeutic ag...
Data
Reported data of genetic alterations in thyroid cancer cell lines and Dm of BEZ235. (TIF)
Data
BEZ235 degrades caspase-3 in vitro. Quantification of immunoblot showed caspase-3 was decreased in KAT4C and KAT18 at 72 hours at doses ranged from 6.25 to 100 nmol/L. (TIF)
Data
Five chemotherapeutic agents induce dose and time dependent cytotoxicity in 4 anaplastic thyroid cancer cell lines. Dose-response curves were obtained on day 3 and 4 from cells treated with serial dilutions of chemotherapeutic agents (paclitaxel, irinotecan, etoposide, 5-FU, doxorubicin) for a 4-day course on ATC cell lines using LDH assays. All dr...
Data
Basal expression of p27 in thyroid cancer cell lines. (TIF)
Data
BEZ235 consistently inhibits mTORC1 signaling and activates p-ERK1/2. A, p-AKT (Thr308) was transient reduced by 2 hours in TT and BHP7-13 and increased by 4 hours in 8505C and KAT4C. B, p-AKT (Ser473) was reduced by 2 and 8 hours in TT and BHP7-13 and increased by 2 hours in 8505C and KAT4C. C, p-4E-BP1 (Thr70) was consistently reduced by 2 hours...
Data
BEZ235 represses the expression of p-AKT, p-S6 ribosomal protein and capase-3 in vivo. The effects of BEZ235 on p-AKT, p-S6 ribosomal protein, PCNA and capase-3 in vivo. Quantification of immunoblot showed BEZ235 greatly repressed p-AKT (Thr308), p-S6 ribosomal protein (Ser235/236) and caspase-3 by 2 to 4 hours with durable effects. PCNA was slight...
Data
BEZ235 inhibits p-S6 ribosomal protein (Ser235/236) and activates p-ERK1/2 and p27 in KAT4C. A, p-AKT (Thr308), p-AKT (Ser473) and p-ERK1/2 (Thr202/Tyr204) was increased by 4 hours and persisted for more than 24 hours. p-S6 ribosomal protein (Ser235/236) was reduced from 8 hours through over 24 hours. B, p27 was increased by 24 hours. p53, p21 and...
Data
BEZ235 activates p27 expression in thyroid cancer cell lines. A, p53was decreased by 2 to 4 hours in 8505C and TT and increased in KAT4C by 8 hours. B, p21 was repressed in TT and BHP7-13 and increased in KAT4C by 8 hour. C, p27 was increased in all cell lines. The elevation of p27 achieved statistical significance at 8 hour in TT. There was no det...
Conference Paper
Our previously studies demonstrated that bis(hydroxymethyl)cyclopenta[a]indenes, which bear a bis(hydroxymethyl)pyrrolidine pharmacophore, exhibited potent antitumor activity in inhibiting various human tumor xenografts. We also demonstrated that these agents showed strong synergistic therapeutic efficacy in combination with arsenic trioxide (ATO)...
Article
s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA Most anticancer agents have poor water-solubility and thus, have a higher risk of failure during the period of new drug discovery and development. Our previous exploration of water-soluble N-mustard-benzene conjugates has led t...