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3. Impact of race and social determinants of health on outcomes in patients with aggressive B-cell NHL treated with CAR-T therapy

Author

Karmali, Reem, Machhi, Rushad, Epperla, Narendranath, Shouse, Geoffrey, Romancik, Jason, Moyo, Tamara K., Kenkre, Vaishalee, Ollila, Thomas A., Fitzgerald, Lindsey, Hess, Brian, David, Kevin, Roy, Ishan, Zurko, Joanna, Chowdhury, Sayan Mullick, Annunzio, Kaitlin, Ferdman, Robert, Bhansali, Rahul S., Harris, Elyse I., Liu, Jieqi, Nizamuddin, Imran, Ma, Shuo, Moreira, Jonathan, Winter, Jane, Pro, Barbara, Stephens, Deborah M., Danilov, Alexey, Shah, Nirav N., Cohen, Jonathon B., Barta, Stefan K., Torka, Pallawi, and Gordon, Leo I.

Published
2024
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5. Peri–CAR-T practice patterns and survival predictors for all CAR-T patients and post–CAR-T failure in aggressive B-NHL

Author

Zurko, Joanna, Nizamuddin, Imran, Epperla, Narendranath, David, Kevin, Cohen, Jonathon B., Moyo, Tamara K., Ollila, Thomas, Hess, Brian, Roy, Ishan, Ferdman, Robert, Liu, Jieqi, Chowdhury, Sayan Mullick, Romancik, Jason, Bhansali, Rahul S., Harris, Elyse I., Sorrell, Mckenzie, Masel, Rebecca, Kittai, Adam S., Denlinger, Nathan, Sigmund, Audrey M., Fitzgerald, Lindsey, Galvez, Carlos, Ma, Shuo, Winter, Jane, Pro, Barbara, Gordon, Leo I., Danilov, Alexey, Stephens, Deborah, Shah, Nirav N., Kenkre, Vaishalee, Barta, Stefan K., Torka, Pallawi, Shouse, Geoffrey, and Karmali, Reem

Published
2023
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7. Cancer Rehabilitation

Author

Shahpar, Samman, primary, Roy, Ishan, additional, Villanueva, Eric W., additional, and Flores, Madeline, additional

Published
2022
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9. Low-dose orthotopic cancer implantation permits measurement of longitudinal functional changes associated with cachexia.

Author

Roy, Ishan, Binder-Markey, Benjamin, Willbanks, Amber, Sychowski, Danielle, Phipps, Tenisha, Barber, Addison, McAllister, Donna, D'Andrea, Dominic, Franz, Colin K., Pichika, Rajeswari, Dwinell, Michael B., and Lieber, Richard L.

Subjects
WALKING speed, GRIP strength, PHYSICAL mobility, ANIMAL populations, MUSCULAR atrophy
Abstract

Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating preclinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of nonspecific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, to investigate cachexia-related function at the basic science level. Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC)-derived cells. One hundred twenty-eight animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. We extended the survival of the KPC orthotopic model to 8–9 wk postimplantation using a relatively low 100-cell dose of DT10022 KPC cells (P < 0.001). In this low-dose orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 wk postimplantation compared with controls (P < 0.001). Gait speed in LO animals declined as early as 2 wk postimplantation, whereas grip strength change was a late event. Principal component and regression analyses revealed distinct cachectic and noncachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia (P < 0.01), whereas grip strength decline was not (P = 0.19). Gait speed represents an accurate surrogate for cachexia-related physical function as opposed to grip strength. NEW & NOTEWORTHY: Previous studies of cancer-induced cachexia have been confounded by the relatively rapid death of animal subjects. Using a lower dose of cancer cells in combination with a battery of behavioral, structural, histological, and biochemical techniques, we show that gait speed is actually the best indicator of functional decline due to cachexia. Future studies are required to define the underlying physiological basis of these findings. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Immunomodulatory Role of the Stem Cell Circadian Clock in Muscle Repair

Author

Peek, Clara B, primary, Zhu, Pei, additional, Pfrender, Eric, additional, Steffeck, Adam, additional, Reczek, Colleen, additional, Zhou, Yalu, additional, Thakkar, Abhishek, additional, Gupta, Neha, additional, Willbanks, Amber, additional, Lieber, Richard, additional, Roy, Ishan, additional, and Chandel, Navdeep S, additional

Published
2024
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11. Subsequent malignant neoplasms in patients previously treated with anti-CD19 CAR T-cell therapy

Author

Melody, Megan, primary, Epperla, Narendranath, additional, Shouse, Geoffrey, additional, Romancik, Jason, additional, Allen, Pamela, additional, Moyo, Tamara K., additional, Kenkre, Vaishalee, additional, Ollila, Thomas, additional, Fitzgerald, Lindsey, additional, Hess, Brian, additional, David, Kevin, additional, Herr, Megan M., additional, Odetola, Oluwatobi, additional, Lin, Adam, additional, Moreira, Jonathan, additional, Ma, Shuo, additional, Winter, Jane N., additional, Roy, Ishan, additional, Stephens, Deborah, additional, Danilov, Alexey, additional, Shah, Nirav N., additional, Barta, Stefan K., additional, Cortese, Matthew, additional, Cohen, Jonathon B., additional, Gordon, Leo I., additional, and Karmali, Reem, additional

Published
2024
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12. Decreased Bed Mobility Function Is Associated With Postdischarge Mortality for Cancer Patients in Inpatient Rehabilitation.

Author

Roy, Ishan, Marks, Julia, Fram, Julia, Jayabalan, Prakash, and Spill, Gayle

Subjects
*PATIENTS, *RECEIVER operating characteristic curves, *SURVIVAL rate, *HOSPITAL care, *LOGISTIC regression analysis, *FUNCTIONAL assessment, *CANCER patients, *RETROSPECTIVE studies, *DESCRIPTIVE statistics, *MANN Whitney U Test, *MULTIVARIATE analysis, *LONGITUDINAL method, *ODDS ratio, *MEDICAL rehabilitation, *MEDICAL records, *ACQUISITION of data, *ELECTRONIC health records, *STATISTICS, *TUMORS, *CONFIDENCE intervals, *PHYSICAL mobility
Abstract

Objective: The establishment of rehabilitation goals for hospitalized cancer patients depends on accurate medical prognosis and matching goals to clinical timelines. Current tools for estimating prognosis are limited. We hypothesized that bed mobility is a predictor of mortality in cancer patients admitted to inpatient rehabilitation. Design: In a retrospective cohort of 187 subjects with nonneurologic cancer admitted to inpatient rehabilitation, Functional Independence Measure scores and 6-mo mortality were analyzed. Results: In the cohort, survival rate was 71% at 6 mos. In univariate analysis, discharge bed mobility score (odds ratio = 0.75, 95% confidence interval = 0.61-0.90, P = 0.003), bed mobility Functional Independence Measure gain (odds ratio = 0.66, 95% confidence interval = 0.51-0.85, P = 0.002), and bed mobility Functional Independence Measure efficiency (odds ratio = 0.011, 95% confidence interval = 0.00032-0.21, P = 0.006) were inversely associated with 6-mo mortality after discharge from inpatient rehabilitation facility. In multivariate analysis with additional motor Functional IndependenceMeasure items, only bed mobility (odds ratio = 0.73, 95% confidence interval = 0.54-0.97, P = 0.029) and grooming (odds ratio = 0.79, 95% confidence interval = 0.63-0.99, P = 0.041) were independently associated with mortality. Conclusions: Lower discharge and lower change in bed mobility Functional Independence Measure scores are associated with mortality in cancer patients in inpatient rehabilitation. Bed mobility could serve as a clinical tool for estimatingmedical prognosis in hospitalized cancer patients and should be validated in prospective studies. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Gait speed is a biomarker of cancer-associated cachexia decline and recovery

Author

Roy, Ishan, primary, Binder-Markey, Benjamin, additional, Sychowski, Danielle, additional, Willbanks, Amber, additional, Phipps, Tenisha, additional, McAllister, Donna, additional, Bhakta, Akash, additional, Marquez, Emily, additional, D'Andrea, Dominic, additional, Franz, Colin, additional, Pichika, Rajeswari, additional, Dwinell, Michael, additional, Jayabalan, Prakash, additional, and Lieber, Richard L, additional

Published
2023
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17. Sonographic Diaphragm Abnormalities are an Unexpectedly Frequent Feature of Long COVID Outpatients with Unexplained Dyspnea and Fatigue

Author

Deo, Prabhav P., primary, Bailey, Joseph I., additional, Jensen, Alexandra S., additional, Farr, Ellen, additional, Fahey, Meghan, additional, Isherwood, Matthew, additional, Chakka, Keerthana, additional, Wolfe, Lisa F., additional, Roy, Ishan, additional, Sala, Marc A., additional, and Franz, Colin K., additional

Published
2023
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18. Supplemental Figures S1-S5 from Pancreatic Cancer Cell Migration and Metastasis Is Regulated by Chemokine-Biased Agonism and Bioenergetic Signaling

Author

Roy, Ishan, primary, McAllister, Donna M., primary, Gorse, Egal, primary, Dixon, Kate, primary, Piper, Clinton T., primary, Zimmerman, Noah P., primary, Getschman, Anthony E., primary, Tsai, Susan, primary, Engle, Dannielle D., primary, Evans, Douglas B., primary, Volkman, Brian F., primary, Kalyanaraman, Balaraman, primary, and Dwinell, Michael B., primary

Published
2023
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19. Data from Pancreatic Cancer Cell Migration and Metastasis Is Regulated by Chemokine-Biased Agonism and Bioenergetic Signaling

Author

Roy, Ishan, primary, McAllister, Donna M., primary, Gorse, Egal, primary, Dixon, Kate, primary, Piper, Clinton T., primary, Zimmerman, Noah P., primary, Getschman, Anthony E., primary, Tsai, Susan, primary, Engle, Dannielle D., primary, Evans, Douglas B., primary, Volkman, Brian F., primary, Kalyanaraman, Balaraman, primary, and Dwinell, Michael B., primary

Published
2023
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20. Supplementary Methods, Figures 1 - 2, Tables 1 - 3 from CXM: A New Tool for Mapping Breast Cancer Risk in the Tumor Microenvironment

Author

Flister, Michael J., primary, Endres, Bradley T., primary, Rudemiller, Nathan, primary, Sarkis, Allison B., primary, Santarriaga, Stephanie, primary, Roy, Ishan, primary, Lemke, Angela, primary, Geurts, Aron M., primary, Moreno, Carol, primary, Ran, Sophia, primary, Tsaih, Shirng-Wern, primary, De Pons, Jeffery, primary, Carlson, Daniel F., primary, Tan, Wenfang, primary, Fahrenkrug, Scott C., primary, Lazarova, Zelmira, primary, Lazar, Jozef, primary, North, Paula E., primary, LaViolette, Peter S., primary, Dwinell, Michael B., primary, Shull, James D., primary, and Jacob, Howard J., primary

Published
2023
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21. Data from CXM: A New Tool for Mapping Breast Cancer Risk in the Tumor Microenvironment

Author

Flister, Michael J., primary, Endres, Bradley T., primary, Rudemiller, Nathan, primary, Sarkis, Allison B., primary, Santarriaga, Stephanie, primary, Roy, Ishan, primary, Lemke, Angela, primary, Geurts, Aron M., primary, Moreno, Carol, primary, Ran, Sophia, primary, Tsaih, Shirng-Wern, primary, De Pons, Jeffery, primary, Carlson, Daniel F., primary, Tan, Wenfang, primary, Fahrenkrug, Scott C., primary, Lazarova, Zelmira, primary, Lazar, Jozef, primary, North, Paula E., primary, LaViolette, Peter S., primary, Dwinell, Michael B., primary, Shull, James D., primary, and Jacob, Howard J., primary

Published
2023
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22. Impact of Race and Social Determinants of Health on Outcomes in Patients with Aggressive B-Cell Lymphomas Treated with Chimeric Antigen Receptor T-Cell (CART) Therapy

Author

Karmali, Reem, primary, Epperla, Narendranath, additional, Shouse, Geoffrey, additional, Romancik, Jason T., additional, Moyo, Tamara K., additional, Kenkre, Vaishalee P., additional, Ollila, Thomas A., additional, Fitzgerald, Lindsey A., additional, Hess, Brian T., additional, Evens, Andrew M., additional, Roy, Ishan, additional, Zurko, Joanna, additional, Chowdhury, Sayan Mullick, additional, Annunzio, Kaitlin, additional, Ferdman, Robert, additional, Bhansali, Rahul, additional, Harris, Elyse I., additional, Sorrell, McKenzie, additional, Liu, Jieqi, additional, Nizamuddin, Imran A., additional, Ma, Shuo, additional, Moreira, Jonathan, additional, Winter, Jane N., additional, Pro, Barbara, additional, Stephens, Deborah M., additional, Danilov, Alexey V, additional, Shah, Nirav N., additional, Cohen, Jonathon B., additional, Barta, Stefan K., additional, Torka, Pallawi, additional, and Gordon, Leo I., additional

Published
2022
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23. Double Hit/Double Expressor Lymphomas: A Multicenter Analysis of Survival Outcomes with CD19-Directed CAR T-Cell Therapy

Author

Zurko, Joanna, primary, Shouse, Geoffrey, additional, Torka, Pallawi, additional, Moyo, Tamara K., additional, Romancik, Jason T., additional, Nizamuddin, Imran A., additional, Annunzio, Kaitlin, additional, Liu, Jieqi, additional, Barta, Stefan K., additional, Ferdman, Robert, additional, Bhansali, Rahul, additional, Cohen, Jonathon B., additional, Chowdhury, Sayan Mullick, additional, Shah, Nirav N., additional, Harris, Elyse I., additional, Kenkre, Vaishalee P., additional, Sorrell, McKenzie, additional, Hess, Brian T., additional, Stephens, Deborah M., additional, Fitzgerald, Lindsey A., additional, Ollila, Thomas A., additional, Roy, Ishan, additional, Ma, Shuo, additional, Winter, Jane N., additional, Pro, Barbara, additional, Moreira, Jonathan, additional, Gordon, Leo I., additional, Danilov, Alexey V, additional, Evens, Andrew M., additional, Epperla, Narendranath, additional, and Karmali, Reem, additional

Published
2022
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24. Consensus Cachexia Criteria Are Independently Linked to Progression Free and Overall Survival in Multi-Site Analysis of Patients with Aggressive B-Cell Lymphomas Treated with CAR T-Cell Therapy

Author

Roy, Ishan, primary, Epperla, Narendranath, additional, Shouse, Geoffrey, additional, Romancik, Jason T., additional, Moyo, Tamara K., additional, Kenkre, Vaishalee P., additional, Ollila, Thomas A., additional, Fitzgerald, Lindsey A., additional, Hess, Brian T., additional, Evens, Andrew M., additional, Zurko, Joanna, additional, Chowdhury, Sayan Mullick, additional, Annunzio, Kaitlin, additional, Ferdman, Robert, additional, Bhansali, Rahul S., additional, Harris, Elyse I., additional, Sorrell, McKenzie, additional, Liu, Jieqi, additional, Nizamuddin, Imran A., additional, Moreira, Jonathan, additional, Ma, Shuo, additional, Winter, Jane N., additional, Pro, Barbara, additional, Stephens, Deborah M., additional, Danilov, Alexey V, additional, Shah, Nirav N., additional, Cohen, Jonathon B., additional, Barta, Stefan K., additional, Torka, Pallawi, additional, Gordon, Leo I., additional, and Karmali, Reem, additional

Published
2022
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25. Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL

Author

Zurko, Joanna C, primary, Nizamuddin, Imran, additional, Epperla, Narendranath, additional, David, Kevin A, additional, Cohen, Jonathon B., additional, Moyo, Tamara, additional, Ollila, Thomas A, additional, Hess, Brian T., additional, Roy, Ishan, additional, Ferdman, Robert, additional, Liu, Jieqi, additional, Chowdhury, Sayan Mullick, additional, Romancik, Jason T., additional, Bhansali, Rahul S, additional, Harris, Elyse I., additional, Sorrell, Mckenzie, additional, Masel, Rebecca, additional, Kittai, Adam S, additional, Denlinger, Nathan, additional, Sigmund, Audrey M, additional, Fitzgerald, Lindsey A., additional, Galvez, Carlos, additional, Ma, Shuo, additional, Winter, Jane N, additional, Pro, Barbara, additional, Gordon, Leo I, additional, Danilov, Alexey V, additional, Stephens, Deborah M., additional, Shah, Nirav N, additional, Kenkre, Vaishalee P, additional, Barta, Stefan K, additional, Torka, Pallawi, additional, Shouse, Geoffrey, additional, and Karmali, Reem, additional

Published
2022
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26. Sonographic Diaphragm Abnormalities are an Unexpectedly Frequent Feature of Long COVID Outpatients with Unexplained Dyspnea and Fatigue

Author

Deo, Prabhav P., primary, Bailey, Joseph I., additional, Jensen, Alexandra S., additional, Farr, Ellen, additional, Fahey, Meghan, additional, Isherwood, Matthew, additional, Chakka, Keerthana, additional, Wolfe, Lisa F., additional, Roy, Ishan, additional, Sala, Marc A., additional, and Franz, Colin K., additional

Published
2022
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27. Blockchain Development for Finance Projects

Author

Roy, Ishan, Roy, Ishan, Roy, Ishan, and Roy, Ishan

Abstract

A practical blockchain handbook designed to take you through implementing and re-engineering banking and financial solutions and workflows using eight step-by-step projects Key Features Implement various end-to-end blockchain projects and learn to enhance present-day financial solutions Use Ethereum, Hyperledger, and Stellar to build public and private decentralized applications Address complex challenges faced in the BFSI domain using different blockchain platform services Book Description Blockchain technology will continue to play an integral role in the banking and finance sector in the coming years. It will enable enterprises to build transparent and secure business processes. Experts estimate annual savings of up to 20 billion dollars from this technology. This book will help you build financial apps using blockchain, guiding you through enhancing popular products and services in the banking and finance sector. The book starts by explaining the essential concepts of blockchain, and the impact of blockchain technology on the BFSI sector. Next, you'll delve into re-designing existing banking processes and building new financial apps using blockchain. To accomplish this, you'll work through eight blockchain projects. By demonstrating the entire process, the book helps you understand everything from setting up the environment and building frontend portals to system integration and testing apps. You will gain hands-on experience with the Ethereum, Hyperledger Fabric, and Stellar to develop private and public decentralized apps. Finally, you'll learn how to use ancillary platforms and frameworks such as IPFS, Truffle OpenZeppelin, and MetaMask. By the end of this blockchain book, you'll have an in-depth understanding of how to leverage distributed ledgers and smart contracts for financial use cases. What you will learn Design and implement blockchain solutions in a BFSI organization Explore common architectures and implementation models for enterprise blockchain Des

Published
2020

29. A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer

Author

Rabin, Erik E., primary, Kim, Miri, additional, Mozny, Andreas, additional, Cardoza, Krislyn, additional, Bell, April C., additional, Zhai, Lijie, additional, Bommi, Prashant, additional, Lauing, Kristen L., additional, King, Amanda L., additional, Armstrong, Terri S., additional, Walunas, Theresa L., additional, Fang, Deyu, additional, Roy, Ishan, additional, Peipert, John D., additional, Sieg, Erica, additional, Mi, Xinlei, additional, Amidei, Christina, additional, Lukas, Rimas V., additional, and Wainwright, Derek A., additional

Published
2022
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31. Cachexia is a risk factor for negative clinical and functional outcomes in patients receiving chimeric antigen receptor T‐cell therapy for B‐cell non‐Hodgkin lymphoma

Author

Roy, Ishan, primary, Smilnak, Gordon, additional, Burkart, Madelyn, additional, Hamilton, Elizabeth, additional, Thorp, Katherine, additional, Miyata, Sarah, additional, Ma, Shuo, additional, Pro, Barbara, additional, Winter, Jane, additional, Gordon, Leo, additional, and Karmali, Reem, additional

Published
2022
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32. Relationship Between Cachexia and the Functional Progress of Patients With Cancer in Inpatient Rehabilitation.

Author

Roy, Ishan, Huang, Kevin, Bhakta, Akash, Marquez, Emily, Spangenberg, Jacqueline, and Jayabalan, Prakash

Subjects
*CANCER patient psychology, *CONFIDENCE intervals, *FUNCTIONAL status, *RETROSPECTIVE studies, *MANN Whitney U Test, *DESCRIPTIVE statistics, *CACHEXIA, *LOGISTIC regression analysis, *LONGITUDINAL method
Abstract

Cachexia is common in cancer patients receiving inpatient rehabilitation, and cachexia severity correlates with capacity for functional recovery and clinical prognosis after rehabilitation. Purpose: Although inpatient rehabilitation can improve functional independence in patients with cancer, the role of cachexia in this population is unknown. Our objectives were to: 1) Establish prevalence of cachexia in a cohort of cancer patients receiving inpatient rehabilitation and its association with demographic and oncological history. 2) Determine the relationship between the presence of cachexia and functional recovery and whether these patients in inpatient rehabilitation have a distinct prognosis. Methods: This is a retrospective cohort study of 250 patients over 330 admissions to an inpatient rehabilitation facility. Body weight loss threshold and Weight Loss Grading Scale identified patients with and without cachexia. Main outcomes were functional independence measure scores, discharge destination, and 6-mo survival. Results: Prevalence of cachexia in inpatient rehabilitation was 59% using consensus body weight loss criteria, and 77% of cancer patients had a Weight Loss Grading Scale score greater than 0. Patients with and without cachexia had similar motor and cognitive gains, although patients with severe cachexia had more limited functional gains (P < 0.05) and increased odds of acute care return (P < 0.01). Patients with a Weight Loss Grading Scale score of 4 had decreased survival at 6 mos (P < 0.05) compared with noncachectic patients. Conclusions: These data suggest that there is a relationship between cachexia and recovery for cancer patients that should be further studied in rehabilitation settings. [ABSTRACT FROM AUTHOR]

Published
2023
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36. Factors associated with unplanned transfers among cancer patients at a freestanding acute rehabilitation facility.

Author

Bhakta, Akash, Roy, Ishan, Huang, Kevin, Spangenberg, Jacqueline, and Jayabalan, Prakash

Abstract

Copyright of PM & R: Journal of Injury, Function & Rehabilitation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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37. Immune Reconstitution and Infection Patterns Following CAR T-Cell Therapy in Patients with Aggressive Lymphoma

Author

Melody, Megan, Epperla, Narendranath, Shouse, Geoffrey P., Romancik, Jason T., Moyo, Tamara K., Kenkre, Vaishalee P, Ollila, Thomas, Fitzgerald, Lindsey, Hess, Brian, David, Kevin A., Annunzio, Kaitlin, Herr, Megan, Bhansali, Rahul S., Harris, Elyse I, Davis, James A, Odetola, Oluwatobi, Lin, Adam Yuh, Moreira, Jonathan, Ma, Shuo, Winter, Jane N., Stephens, Deborah M., Danilov, Alexey, Shah, Nirav N., Roy, Ishan, Barta, Stefan K., Cortese, Matthew J, Torka, Pallawi, Cohen, Jonathon B., Gordon, Leo I., and Karmali, Reem

Published
2023
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41. Cachexia is an independent factor for negative clinical and functional outcomes in lymphoma patients receiving CART therapy.

Author

Roy, Ishan, primary, Smilnak, Gordon John, additional, Burkart, Madelyn, additional, Williams, Corinne, additional, Hamilton, Elizabeth, additional, Miyata, Sarah, additional, Thorp, Katherine, additional, Ma, Shuo, additional, Winter, Jane N., additional, Pro, Barbara, additional, Gordon, Leo I., additional, and Karmali, Reem, additional

Published
2021
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45. Structural basis for chemokine recognition by a G protein–coupled receptor and implications for receptor activation

Author

Ziarek, Joshua J., primary, Kleist, Andrew B., additional, London, Nir, additional, Raveh, Barak, additional, Montpas, Nicolas, additional, Bonneterre, Julien, additional, St-Onge, Geneviève, additional, DiCosmo-Ponticello, Crystal J., additional, Koplinski, Chad A., additional, Roy, Ishan, additional, Stephens, Bryan, additional, Thelen, Sylvia, additional, Veldkamp, Christopher T., additional, Coffman, Frederick D., additional, Cohen, Marion C., additional, Dwinell, Michael B., additional, Thelen, Marcus, additional, Peterson, Francis C., additional, Heveker, Nikolaus, additional, and Volkman, Brian F., additional

Published
2017
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48. Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells

Author

Zimmerman, Noah P., Roy, Ishan, Hauser, Andrew D., Wilson, Jessica M., Williams, Carol L., and Dwinell, Michael B.

Subjects
rho GTP-Binding Proteins, Phosphodiesterase Inhibitors, Pyridines, Vasodilator Agents, Colforsin, Apoptosis, Quinolones, Amides, Cyclic AMP-Dependent Protein Kinases, Deoxycytidine, Gemcitabine, Article, Pancreatic Neoplasms, Cell Movement, rhoC GTP-Binding Protein, 1-Methyl-3-isobutylxanthine, Cell Line, Tumor, Cyclic AMP, Humans, Neoplasm Invasiveness, Enzyme Inhibitors, rhoA GTP-Binding Protein, Carcinoma, Pancreatic Ductal, Cell Proliferation
Abstract

Aggressive dissemination and metastasis of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis and marked lethality. Rho monomeric G protein levels are increased in pancreatic cancer tissue. As the mechanisms underlying PDAC malignancy are little understood, we investigated the role for cAMP in regulating monomeric G protein regulated invasion and migration of pancreatic cancer cells. Treatment of PDAC cells with cAMP elevating agents that activate adenylyl cyclases, forskolin, protein kinase A, 6-Bnz-cAMP, or the cyclic nucleotide phosphodiesterase inhibitor cilostamide significantly decreased migration and Matrigel invasion of PDAC cell lines. Inhibition was dose-dependent and not significantly different between forskolin or cilostamide treatment. cAMP elevating drugs not only blocked basal migration, but similarly abrogated transforming-growth factor-β-directed PDAC cell migration and invasion. The inhibitory effects of cAMP were prevented by the pharmacological blockade of protein kinase A. Drugs that increase cellular cAMP levels decreased levels of active RhoA or RhoC, with a concomitant increase in phosphorylated RhoA. Diminished Rho signaling was correlated with the appearance of thickened cortical actin bands along the perimeter of non-motile forskolin or cilostamide-treated cells. Decreased migration did not reflect alterations in cell growth or programmed cell death. Collectively these data support the notion that increased levels of cAMP specifically hinder PDAC cell motility through F-actin remodeling.

Published
2013

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