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2. Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease

Author

Terrett, Jack A., primary, Ly, Justin Q., additional, Katavolos, Paula, additional, Hasselgren, Catrin, additional, Laing, Steven, additional, Zhong, Fiona, additional, Villemure, Elisia, additional, Déry, Martin, additional, Larouche-Gauthier, Robin, additional, Chen, Huifen, additional, Shore, Daniel G., additional, Lee, Wyne P., additional, Suto, Eric, additional, Johnson, Kevin, additional, Brooks, Marjory, additional, Stablein, Alyssa, additional, Beaumier, Francis, additional, Constantineau-Forget, Léa, additional, Grand-Maître, Chantal, additional, Lépissier, Luce, additional, Ciblat, Stéphane, additional, Sturino, Claudio, additional, Chen, Yong, additional, Hu, Baihua, additional, Elstrott, Justin, additional, Gandham, Vineela, additional, Joseph, Victory, additional, Booler, Helen, additional, Cain, Gary, additional, Chou, Carolina, additional, Fullerton, Aaron, additional, Lepherd, Michelle, additional, Stainton, Shannon, additional, Torres, Elizabeth, additional, Urban, Konnie, additional, Yu, Lanlan, additional, Zhong, Yu, additional, Bao, Linda, additional, Chou, Kang-Jye, additional, Lin, Jessica, additional, Zhang, Wei, additional, La, Hank, additional, Liu, Liling, additional, Mulder, Teresa, additional, Chen, Jun, additional, Chernov-Rogan, Tania, additional, Johnson, Adam R., additional, Hackos, David H., additional, Leahey, Rebecca, additional, Shields, Shannon D., additional, Balestrini, Alessia, additional, Riol-Blanco, Lorena, additional, Safina, Brian S., additional, Volgraf, Matthew, additional, Magnuson, Steven, additional, and Kakiuchi-Kiyota, Satoko, additional

Published
2024
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3. Data from Effects of Anti-VEGF on Pharmacokinetics, Biodistribution, and Tumor Penetration of Trastuzumab in a Preclinical Breast Cancer Model

Author

Pastuskovas, Cinthia V., primary, Mundo, Eduardo E., primary, Williams, Simon P., primary, Nayak, Tapan K., primary, Ho, Jason, primary, Ulufatu, Sheila, primary, Clark, Suzanna, primary, Ross, Sarajane, primary, Cheng, Eric, primary, Parsons-Reponte, Kathryn, primary, Cain, Gary, primary, Van Hoy, Marjie, primary, Majidy, Nicholas, primary, Bheddah, Sheila, primary, dela Cruz Chuh, Josefa, primary, Kozak, Katherine R., primary, Lewin-Koh, Nicholas, primary, Nauka, Peter, primary, Bumbaca, Daniela, primary, Sliwkowski, Mark, primary, Tibbitts, Jay, primary, Theil, Frank-Peter, primary, Fielder, Paul J., primary, Khawli, Leslie A., primary, and Boswell, C. Andrew, primary

Published
2023
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4. Data from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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5. Supplementary Figure 1 from Effects of Anti-VEGF on Pharmacokinetics, Biodistribution, and Tumor Penetration of Trastuzumab in a Preclinical Breast Cancer Model

Author

Pastuskovas, Cinthia V., primary, Mundo, Eduardo E., primary, Williams, Simon P., primary, Nayak, Tapan K., primary, Ho, Jason, primary, Ulufatu, Sheila, primary, Clark, Suzanna, primary, Ross, Sarajane, primary, Cheng, Eric, primary, Parsons-Reponte, Kathryn, primary, Cain, Gary, primary, Van Hoy, Marjie, primary, Majidy, Nicholas, primary, Bheddah, Sheila, primary, dela Cruz Chuh, Josefa, primary, Kozak, Katherine R., primary, Lewin-Koh, Nicholas, primary, Nauka, Peter, primary, Bumbaca, Daniela, primary, Sliwkowski, Mark, primary, Tibbitts, Jay, primary, Theil, Frank-Peter, primary, Fielder, Paul J., primary, Khawli, Leslie A., primary, and Boswell, C. Andrew, primary

Published
2023
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6. Supplementary Table 1-2 from Effects of Anti-VEGF on Pharmacokinetics, Biodistribution, and Tumor Penetration of Trastuzumab in a Preclinical Breast Cancer Model

Author

Pastuskovas, Cinthia V., primary, Mundo, Eduardo E., primary, Williams, Simon P., primary, Nayak, Tapan K., primary, Ho, Jason, primary, Ulufatu, Sheila, primary, Clark, Suzanna, primary, Ross, Sarajane, primary, Cheng, Eric, primary, Parsons-Reponte, Kathryn, primary, Cain, Gary, primary, Van Hoy, Marjie, primary, Majidy, Nicholas, primary, Bheddah, Sheila, primary, dela Cruz Chuh, Josefa, primary, Kozak, Katherine R., primary, Lewin-Koh, Nicholas, primary, Nauka, Peter, primary, Bumbaca, Daniela, primary, Sliwkowski, Mark, primary, Tibbitts, Jay, primary, Theil, Frank-Peter, primary, Fielder, Paul J., primary, Khawli, Leslie A., primary, and Boswell, C. Andrew, primary

Published
2023
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7. Supplemental Figure 5 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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8. Supplemental Figure 8 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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9. Supplemental Figure 6 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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10. Supplemental Figure 3 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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11. Supplemental Figure 7 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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12. Supplemental Figure 4 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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13. Supplemental Figure 2 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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14. Supplemental Figure 1 from Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, primary, Yen, Ivana, primary, Flagella, Michael, primary, O'Brien, Tom, primary, Evangelista, Marie, primary, Schmidt, Stephen, primary, Xiao, Yang, primary, Choi, Jonathan, primary, Kowanetz, Kaska, primary, Ramiscal, Judi, primary, Wong, Kenton, primary, Jakubiak, Diana, primary, Yee, Sharon, primary, Cain, Gary, primary, Gazzard, Lewis, primary, Williams, Karen, primary, Halladay, Jason, primary, Jackson, Peter K., primary, and Malek, Shiva, primary

Published
2023
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15. Supplementary information from Balancing Efficacy and Safety of an Anti-DLL4 Antibody through Pharmacokinetic Modulation

Author

Couch, Jessica A., primary, Zhang, Gu, primary, Beyer, Joseph C., primary, de Zafra, Christina L. Zuch, primary, Gupta, Priyanka, primary, Kamath, Amrita V., primary, Lewin-Koh, Nicholas, primary, Tarrant, Jacqueline, primary, Allamneni, Krishna P., primary, Cain, Gary, primary, Yee, Sharon, primary, Ross, Sarajane, primary, Cook, Ryan, primary, Tsai, Siao Ping, primary, Ruppel, Jane, primary, Ridgway, John Brady, primary, Paluch, Maciej, primary, Hass, Philip E., primary, Franklin, Jayme, primary, and Yan, Minhong, primary

Published
2023
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18. Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

Author

Schnegelsberg, Birthe, Sun, Tung-Tien, Cain, Gary, Bhattacharya, Anindya, Nunn, Philip A., Ford, Anthony P.D.W., Vizzard, Margaret A., and Cockayne, Debra A.

Subjects
Neurons -- Analysis, Nerve growth factor -- Research, Nerve growth factor -- Health aspects, Bladder diseases -- Research, Bladder diseases -- Risk factors, Biological sciences
Abstract

NGF has been suggested to play a role in urinary bladder dysfunction by mediating inflammation, as well as morphological and functional changes, in sensory and sympathetic neurons innervating the urinary bladder. To further explore the role of NGF in bladder sensory function, we generated a transgenic mouse model of chronic NGF overexpression in the bladder using the urothelium-specific uroplakin II (UPII) promoter. NGF mRNA and protein were expressed at higher levels in the bladders of NGF-overexpressing (NGF-OE) transgenic mice compared with wild-type littermate controls from postnatal day 7 through 12-16 wk of age. Overexpression of NGF led to urinary bladder enlargement characterized by marked nerve fiber hyperplasia in the submucosa and detrusor smooth muscle and elevated numbers of tissue mast cells. There was a marked increase in the density of CGRP- and substance P-positive C-fiber sensory afferents, neurofilament 200-positive myelinated sensory afferents, and tyrosine hydroxylase-positive sympathetic nerve fibers in the suburothelial nerve plexus. CGRP-positive ganglia were also present in the urinary bladders of transgenic mice. Transgenic mice had reduced urinary bladder capacity and an increase in the number and amplitude of nonvoiding bladder contractions under baseline conditions in conscious open-voiding cystometry. These changes in urinary bladder function were further associated with an increased referred somatic pelvic hypersensitivity. Thus, chronic urothelial NGF overexpression in transgenic mice leads to neuronal proliferation, focal increases in urinary bladder mast cells, increased urinary bladder reflex activity, and pelvic hypersensitivity. NGF-overexpressing mice may, therefore, provide a useful transgenic model for exploring the role of NGF in urinary bladder dysfunction. nerve growth factor; urothelium; transgenic mouse; bladder hypersensitivity; inflammation; afferent innervation doi:10.1152/ajpregu.00367.2009

Published
2010

19. CBPi_manuscript_Supplemental_Data_Table_1_(11-22-19) - Preclinical Safety Assessment of a Highly Selective and Potent Dual Small-Molecule Inhibitor of CBP/P300 in Rats and Dogs

Author

Katavolos, Paula, Cain, Gary, Farman, Cindy, F. Anthony Romero, Magnuson, Steven, Ly, Justin Q., Choo, Edna F., Katakam, Anand Kumar, Andaya, Roxanne, and Maher, Jonathan

Subjects
FOS: Clinical medicine, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

CBPi_manuscript_Supplemental_Data_Table_1_(11-22-19) for Preclinical Safety Assessment of a Highly Selective and Potent Dual Small-Molecule Inhibitor of CBP/P300 in Rats and Dogs by Paula Katavolos, Gary Cain, Cindy Farman, F. Anthony Romero, Steven Magnuson, Justin Q. Ly, Edna F. Choo, Anand Kumar Katakam, Roxanne Andaya and Jonathan Maher in Toxicologic Pathology

Published
2020
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20. Generation and characterization of a unique reagent that recognizes a panel of recombinant human monoclonal antibody therapeutics in the presence of endogenous human IgG

Author

Wang, Xiangdan, Quarmby, Valerie, Ng, Carl, Chuntharapai, Anan, Shek, Theresa, Eigenbrot, Charles, Kelley, Robert F., Shia, Steven, McCutcheon, Krista, Lowe, John, Leddy, Cecilia, Coachman, Kyle, Cain, Gary, Chu, Felix, Hotzel, Isidro, Maia, Mauricio, Wakshull, Eric, and Yang, Jihong

Published
2013
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22. Pharmacokinetic drivers of toxicity for basic molecules: Strategy to lower pKa results in decreased tissue exposure and toxicity for a small molecule Met inhibitor

Author

Diaz, Dolores, Ford, Kevin A., Hartley, Dylan P., Harstad, Eric B., Cain, Gary R., Achilles-Poon, Kirsten, Nguyen, Trung, Peng, Jing, Zheng, Zhong, Merchant, Mark, Sutherlin, Daniel P., Gaudino, John J., Kaus, Robert, Lewin-Koh, Sock C., Choo, Edna F., Liederer, Bianca M., and Dambach, Donna M.

Published
2013
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25. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X 3-deficient mice

Author

Cockayne, Debra A., Hamilton, Sara G., Zhu, Quan-Ming, Dunn, Philip M., Zhong, Yu, Novakovic, Sanja, Malmberg, Annika B., Cain, Gary, Berson, Amy, Kassotakis, Laura, Hedley, Linda, Lachnit, Wilhelm G., Burnstock, Geoffrey, McMahon, Stephen B., and Ford, Anthony P. D. W.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Debra A. Cockayne (corresponding author) [1]; Sara G. Hamilton [2]; Quan-Ming Zhu [1]; Philip M. Dunn [3]; Yu Zhong [3]; Sanja Novakovic [1]; Annika B. Malmberg [1]; Gary Cain [...]

Published
2000
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26. The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase

Author

Davis, June P., Cain, Gary A., Pitts, William J., Magolda, Ronald L., and Copeland, Robert A.

Subjects
Immunosuppressive agents -- Research, Enzyme inhibitors -- Research, Biological sciences, Chemistry
Abstract

The effects of leflunomide and its active metabolite, A771726, on the function of purified recombinant human dihydroorotate dehydrogenase (DHODase) were studied. A771726 effectively prevented DHODase activity but leflunomide was impotent. A771726 was 100 to 1000-times more effective in inhibiting DHODase than for protein tyrosine kinases. Findings indicated that the immunosuppressive capability of A771726 can be explained by the effective prevention of DHODase activity.

Published
1996

29. Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma

Author

Dengler, Hart S., primary, Wu, Xiumin, additional, Peng, Ivan, additional, Rinderknecht, Cornelia H., additional, Kwon, Youngsu, additional, Suto, Eric, additional, Kohli, Pawan Bir, additional, Liimatta, Marya, additional, Barrett, Kathy, additional, Lloyd, Julia, additional, Cain, Gary, additional, Briggs, Mike, additional, Addo, Stephanie, additional, Salmon, Gary, additional, Ubhayakar, Savita, additional, Deshmukh, Gauri, additional, Shahidi-Latham, Sheerin K., additional, Quiason-Huynh, Cristine M., additional, Jackman, Janet, additional, Liu, John, additional, Ray, Nicholas C., additional, Goodacre, Simon C., additional, Johnson, Adam, additional, McKenzie, Brent S., additional, Lee, Wyne P., additional, Zak, Mark, additional, Kenny, Jane R., additional, and Ghilardi, Nico, additional

Published
2018
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31. Asbestos: From Beginning to End.

Author

McMullin, Richard C. and Cain, Gary K.

Abstract

In conjunction with a bond proposal for energy related items, the North County Public Schools (Missouri) undertook the task of removing friable asbestos Missouri school district undertook the task of removing friable asbestos from schools. Specifications for asbestos abatement prepared by the district administrative office were reviewed by the Environmental Protection Agency (EPA). A prebidding conference allowed prospective bidders to examine each facility. In addition to requesting the usual costs of the abatement project, bidders were asked to provide previous references; a full financial disclosure; and, since insurance costs could easily be as much as one-third or more of the bid price, an insurance company's verification of insurability. Monitoring the abatement project involved periodic visits by EPA and school district officials. The district became one of four in Missouri to receive federal money, and became the only Missouri district to receive funds for the second year. To promote a positive asbestos abatement project, school districts are advised to (1) allot enough time to obtain funding; (2) prepare plans and specifications that conform to the law; (3) solicit early bids, with prebid conferences mandatory for prospective bidders; (4) have the school attorney review final contract documents; (5) monitor the project themselves in addition to other monitoring agencies or consultants; and (6) actively pursue federal money. Attached is a three-page handout summarizing the guidelines. (MLF)

Published
1987

32. Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer

Author

Jarzabek, Monika A., primary, Proctor, William R., additional, Vogt, Jennifer, additional, Desai, Rupal, additional, Dicker, Patrick, additional, Cain, Gary, additional, Raja, Rajiv, additional, Brodbeck, Jens, additional, Stevens, Dale, additional, van der Stok, Eric P., additional, Martens, John W. M., additional, Verhoef, Cornelis, additional, Hegde, Priti S., additional, Byrne, Annette T., additional, and Tarrant, Jacqueline M., additional

Published
2018
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37. Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window

Author

Rudolph, Joachim, primary, Murray, Lesley J., additional, Ndubaku, Chudi O., additional, O’Brien, Thomas, additional, Blackwood, Elizabeth, additional, Wang, Weiru, additional, Aliagas, Ignacio, additional, Gazzard, Lewis, additional, Crawford, James J., additional, Drobnick, Joy, additional, Lee, Wendy, additional, Zhao, Xianrui, additional, Hoeflich, Klaus P., additional, Favor, David A., additional, Dong, Ping, additional, Zhang, Haiming, additional, Heise, Christopher E., additional, Oh, Angela, additional, Ong, Christy C., additional, La, Hank, additional, Chakravarty, Paroma, additional, Chan, Connie, additional, Jakubiak, Diana, additional, Epler, Jennifer, additional, Ramaswamy, Sreemathy, additional, Vega, Roxanne, additional, Cain, Gary, additional, Diaz, Dolores, additional, and Zhong, Yu, additional

Published
2016
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38. Balancing Efficacy and Safety of an Anti-DLL4 Antibody through Pharmacokinetic Modulation

Author

Couch, Jessica A., primary, Zhang, Gu, additional, Beyer, Joseph C., additional, de Zafra, Christina L. Zuch, additional, Gupta, Priyanka, additional, Kamath, Amrita V., additional, Lewin-Koh, Nicholas, additional, Tarrant, Jacqueline, additional, Allamneni, Krishna P., additional, Cain, Gary, additional, Yee, Sharon, additional, Ross, Sarajane, additional, Cook, Ryan, additional, Tsai, Siao Ping, additional, Ruppel, Jane, additional, Ridgway, John Brady, additional, Paluch, Maciej, additional, Hass, Philip E., additional, Franklin, Jayme, additional, and Yan, Minhong, additional

Published
2016
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39. Proof of Concept for an Automated Image Analysis Method to Quantify Rat Bone Marrow Hematopoietic Lineages on H&E Sections.

Author

Kozlowsk, Cleopatra, Fullerton, Aaron, Cain, Gary, Katavolos, Paula, Bravo, Joseph, and Tarrant, Jacqueline M.

Subjects
HEMATOPOIESIS, BONE marrow
Abstract

The bone marrow is an important site for assessment of the hematopoietic toxicity of new drug candidates. Here, we extended our previous work, where we developed a computer algorithm to automatically quantitate overall bone marrow cell density by analyzing digitized images of standard hematoxylin and eosin (H&E) slides of rat bone marrow and further evaluated the capability to quantify myeloid: erythroid + lymphoid (M:EL) ratio and megakaryocyte cell density. We tested the algorithm in a toxicity study, where rats were dosed with two molecules known to affect bone marrow composition, monomethyl auristatin E, and a Bcl-xL inhibitor. The image analysis method detected significant changes in M:EL and megakaryocyte number that were either not found or semiquantitatively described by manual microscopic observation of the same slides. The image analysis results were consistent with other more established but time-consuming methods that measure changes in bone marrow cell composition: smear cytology, flow cytometry, and microscopic assessment. Our work demonstrates the feasibility of a rapid and more quantitative assessment of changes in bone marrow cell lineage composition using a computer algorithm compared to microscopic examination of H&E-stained bone marrow sections. [ABSTRACT FROM AUTHOR]

Published
2018
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40. Exploring Funding Options

Author

Cain, Gary

Subjects
Employee benefits, Health insurance -- Finance, Group insurance -- Finance, Business, Insurance, Company financing, Employee benefits, Finance
Abstract

Alternate ways of funding group medical plans may make sense for employers, if their cash flows are dependable. Professionally underwriting a group medical plan includes designing the plan and matching [...]

Published
2001

41. Keeping Up With Progress

Author

Cain, Gary

Subjects
United States. Department of Labor -- Laws, regulations and rules, Health insurance industry -- Laws, regulations and rules, Drugs -- Laws, regulations and rules, Health insurance -- Laws, regulations and rules, Pharmaceutical industry -- Laws, regulations and rules, Health Insurance Portability and Accountability Act of 1996, Business, Insurance, Government regulation, Laws, regulations and rules
Abstract

Breakthrough drugs and scientific discoveries are great for patients, but they can create headaches for health insurance underwriters. The only constant is change. That's a familiar statement used to describe [...]

Published
2001

42. The Art of Medical Underwriting

Author

Cain, Gary

Subjects
Health insurance industry -- Management, Insurance policies -- Interpretation and construction, Health insurance, Business, Insurance, Company business management, Management, Interpretation and construction
Abstract

Rating employee groups is hardly a science. More often than not, underwriters must choose from a limited number of informational tools available to them. Matching rate to risk: It's the [...]

Published
2001

43. The Online Privacy Maze

Author

Cain, Gary

Subjects
Right of property -- Laws, regulations and rules -- Safety and security measures, Health insurance industry -- Laws, regulations and rules -- Safety and security measures, Confidential communications -- Laws, regulations and rules -- Safety and security measures, Internet -- Safety and security measures, Health insurance -- Laws, regulations and rules -- Safety and security measures, Business, Insurance, Government regulation, Internet security, Safety and security measures, Laws, regulations and rules
Abstract

Keeping up to date on proposed privacy laws and concocting a privacy work plan can help health insurers safely take advantage of online underwriting. Most everyone by now has used [...]

Published
2000

44. Multiple Choice Tests Underwriters

Author

Cain, Gary

Subjects
Health insurance industry -- Services, Insurance policies -- Evaluation -- Usage -- Services, Employee benefits -- Evaluation -- Usage, Health insurance -- Usage -- Evaluation -- Services, Business, Insurance, Employee benefits, Evaluation, Usage, Services
Abstract

As health insurers provide more choices for employees, the tenets of group underwriting face greater strains. The trend in group insurance is toward employees gaining more control of their medical [...]

Published
2000

45. MEK and ERK Kinase Inhibitors Increase Circulating Ceruloplasmin and Cause Green Serum in Rats.

Author

Diaz, Dolores, Cain, Gary, La, Nghi, Dambach, Donna, Schwartz, Jacob, Pai, Rama, and Tarrant, Jacqueline M.

Subjects
*MITOGEN-activated protein kinases, *EXTRACELLULAR signal-regulated kinases, *CERULOPLASMIN
Abstract

Inhibition of the mitogen-activated protein kinase/extracellular signal-regulated (MAPK/ERK) pathway is an attractive therapeutic approach for human cancer therapy. In the course of evaluating structurally distinct small molecule inhibitors that target mitogen-activated protein kinase kinase (MEK) and ERK kinases in this pathway, we observed an unusual, dose-related increase in the incidence of green serum in preclinical safety studies in rats. Having ruled out changes in bilirubin metabolism, we demonstrated a 2- to 3-fold increase in serum ceruloplasmin levels, likely accounting for the observed green color. This was not associated with an increase in α-2-macroglobulin, the major acute phase protein in rats, indicating that ceruloplasmin levels increased independently of an inflammatory response. Elevated serum ceruloplasmin was also not correlated with changes in total hepatic copper, adverse clinical signs, or pathology findings indicative of copper toxicity, therefore discounting copper overload as the etiology. Both ERK and MEK inhibitors led to increased ceruloplasmin secretion in rat primary hepatocyte cultures in vitro, and this increase was associated with activation of the Forkhead box, class O1 (FOXO1) transcription factor. In conclusion, increased serum ceruloplasmin induced by MEK and ERK inhibition is due to increased synthesis by hepatocytes from FOXO1 activation and results in the nonadverse development of green serum in rats. [ABSTRACT FROM AUTHOR]

Published
2017
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46. Combination Drug Scheduling Defines a “Window of Opportunity” for Chemopotentiation of Gemcitabine by an Orally Bioavailable, Selective ChK1 Inhibitor, GNE-900

Author

Blackwood, Elizabeth, primary, Epler, Jennifer, additional, Yen, Ivana, additional, Flagella, Michael, additional, O'Brien, Tom, additional, Evangelista, Marie, additional, Schmidt, Stephen, additional, Xiao, Yang, additional, Choi, Jonathan, additional, Kowanetz, Kaska, additional, Ramiscal, Judi, additional, Wong, Kenton, additional, Jakubiak, Diana, additional, Yee, Sharon, additional, Cain, Gary, additional, Gazzard, Lewis, additional, Williams, Karen, additional, Halladay, Jason, additional, Jackson, Peter K., additional, and Malek, Shiva, additional

Published
2013
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47. Toxicity Profile of Small-Molecule IAP Antagonist GDC-0152 Is Linked to TNF-α Pharmacology

Author

Erickson, Rebecca I., primary, Tarrant, Jacqueline, additional, Cain, Gary, additional, Lewin-Koh, Sock-Cheng, additional, Dybdal, Noel, additional, Wong, Harvey, additional, Blackwood, Elizabeth, additional, West, Kristina, additional, Steigerwalt, Ronald, additional, Mamounas, Michael, additional, Flygare, John A., additional, Amemiya, Kenjie, additional, Dambach, Donna, additional, Fairbrother, Wayne J., additional, and Diaz, Dolores, additional

Published
2012
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49. Effects of Anti-VEGF on Pharmacokinetics, Biodistribution, and Tumor Penetration of Trastuzumab in a Preclinical Breast Cancer Model

Author

Pastuskovas, Cinthia V., primary, Mundo, Eduardo E., additional, Williams, Simon P., additional, Nayak, Tapan K., additional, Ho, Jason, additional, Ulufatu, Sheila, additional, Clark, Suzanna, additional, Ross, Sarajane, additional, Cheng, Eric, additional, Parsons-Reponte, Kathryn, additional, Cain, Gary, additional, Van Hoy, Marjie, additional, Majidy, Nicholas, additional, Bheddah, Sheila, additional, dela Cruz Chuh, Josefa, additional, Kozak, Katherine R., additional, Lewin-Koh, Nicholas, additional, Nauka, Peter, additional, Bumbaca, Daniela, additional, Sliwkowski, Mark, additional, Tibbitts, Jay, additional, Theil, Frank-Peter, additional, Fielder, Paul J., additional, Khawli, Leslie A., additional, and Boswell, C. Andrew, additional

Published
2012
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